Preparation of Radiolabeled Zolbetuximab Targeting CLDN18.2 and Its Preliminary Evaluation for Potential Clinical Applications.

Claudin18.2 (CLDN18.2), due to its high expression in various gastric cancer tissues, is considered an optimal target for antitumor drug molecules. In this study, we obtained the labeled compounds of [125I]I-zolbetuximab using the Iodogen method. Under the optimum labeling conditions, the molar activity of [125I]I-zolbetuximab was 1.75 × 102 GBq/µmol, and the labeling efficiency was more than 99%. The labeled compounds exhibited excellent in vitro stability in both phosphate buffer saline (PBS, pH = 7.4) and fetal bovine serum systems (FBS) (radiochemical purity >90% at 72 h). The uptake percentage of [125I]I-zolbetuximab in MKN45-CLDN18.2 cells is 24.69 ± 0.84% after 6 h. The saturation binding assay and specificity assay further demonstrated the high specificity of [125I]I-zolbetuximab for CLDN18.2. The long retention at the tumor site and rapid metabolic clearance at other organ sites of [125I]I-zolbetuximab were observed in small-animal SPECT-CT imaging. The same trend was also observed in the biodistribution study. Due to the excellent targeting ability of zolbetuximab for CLDN18.2, [125I]I-zolbetuximab exhibits strong specific binding and retention with cells and tumors highly expressing CLDN18.2. However, the balance between mAb's longer cycle time in vivo and targeting binding and retention ability should be intensively considered for using this kind of radiopharmaceutical in the diagnosis and treatment of CLDN18.2-positive gastric cancer.

Control and surveillance of redox potential for 233Pa dissolution in 2LiF-BeF2 molten salt.

233Pa, the precursor nuclide of 233U in the thorium-uranium conversion is prone to reductive deposition in 2LiF-BeF2 (66 : 34 mol%, FLiBe) molten salt. We explored the adjustment and control of the redox potential of the FLiBe melt to avoid the 233Pa reduction deposition. The experimental data indicated that the deposited 233Pa can be completely dissolved and reentered into the molten salt with the addition of oxidant NiF2, and the distribution and behaviour of uranium, thorium, neptunium, and most fission products did not have any significant change in the NiF2-oxidised FLiBe molten salt, showing the feasibility of this manner to make 233Pa exist stably in the melt. The effects of NiF2-addition on the behaviour of the fission products 95Nb and 131I in the FLiBe molten salt were also investigated. It was found that 131I could be used as a redox indicator to monitor the redox potential of the oxidation-enhanced FLiBe molten salt. All the information drawn from this study could provide significant support for the control and surveillance of the redox potential of the FLiBe molten salt in the upcoming thorium molten salt reactor (TMSR).

Effect of oxide impurities on the dissolution behavior of Th4+, Be2+ and U4+ in fluoride salts.

Oxides are one of the most important impurities in the fuel salt of molten salt reactors (MSRs), and excessive oxide impurities pose a risk to the safe operation of MSRs. This study focused on investigating the precipitation behavior between Th4+, U4+, and Be2+ with O2- in the 2LiF-BeF2 (FLiBe) eutectic salt system. The results showed that the solubility of UO2 was 5.52 × 10-3 mol kg-1, and the solubility product (Ksp) of UO2 was 6.14 × 10-7 mol3 kg-3 in FLiBe salt at 650 °C. It was also found that the O2- ion would firstly react with U4+ to form UO2, and then the excessive O2- would react with Be2+ to generate BeO in the FLiBe system. Despite conducting the solubility experiment of ThO2 and titration experiment of FLiBe-ThF4, the system failed to achieve the solubility and the Ksp of ThO2. The main reason for this was that O2- preferentially reacted with Be2+ over Th4+ to form precipitates, in other words, Be2+ exerted a protective effect against Th4+. Above all, this work experimentally demonstrated that in the FLiBe system, O2- preferentially combines with U4+ to form a precipitate, followed by Be2+, while Th4+ is relatively inert.

Recovery of FLiBe from ThF4-FLiBe salt using precipitation-distillation coupled method.

The low-pressure distillation of FLiBe salt containing ThF4 was carried out at 1223 K and <10 Pa using thermogravimetric equipment. The weight loss curve indicated a rapid distillation stage at the beginning of distillation, followed by a slow stage. The composition and structure analyses showed that the rapid distillation process originated from the evaporation of LiF and BeF2, while the slow distillation process was mainly attributed to the evaporation of ThF4 and LiF complexes. Precipitation-distillation coupled method was employed for the recovery of FLiBe carrier salt. XRD analysis indicated that ThO2 was formed and remained in the residue with the addition of BeO. Our results showed that the combination of precipitation and distillation treatment was an effective way to recover carrier salt.

Activity Measurement of Iodine Fission Products in 2LiF-BeF2 Salt and Its Application in Redox Potential Surveillance for a Thorium Molten Salt Reactor.

The activities of 131I, 132I, 133I, and 135I produced by neutron-induced fission of 235U in 2LiF-BeF2 (FLiBe) eutectic salt and their dependence on the redox potential were studied. The dependence observed experimentally suggested that the activity ratio for 131I to 132I could be used as an indicator of the redox potential for FLiBe salt. Relying on the selective adsorption of iodine ions on the activated silver probe by ion exchange, a novel method for activity distribution measurement of the iodine isotopes in FLiBe salt was founded. The method is simple, fast, and easy to operate and would be suitable particularly to in situ monitor the redox potential of a thorium molten salt reactor, where the redox potential should keep at a high level to avoid possible safety risk induced by 233Pa deposition in the reactor.

UiO-66-NH-(AO) MOFs with a New Ligand BDC-NH-(CN) for Efficient Extraction of Uranium from Seawater.

Metal-organic frameworks (MOFs) with a high surface area and excellent stability are potential candidates for uranium (U) adsorption. Amidoxime (AO) is the most widely used functional group to extract U, which is usually introduced into MOFs by two-step post-synthetic methods (PSMs). Herein, MOF UiO-66-NH-(AO) was obtained by a one-step PSM with amidoximation from UiO-66-NH-(CN), which was synthesized by a new organic ligand of 2-cyano-terephthalic acid and whose morphology was octahedron and could be well controlled with the new ligand. The one-step PSM can greatly maintain the octahedron of the MOFs. What is more, UiO-66-NH-(AO) showed good adsorption performance for U, the adsorption equilibrium was obtained within 1500 min, and the adsorption capacity of U was calculated to be 134.1 mg/g according to the Langmuir model. It also had excellent selectivity for U in the presence of high concentrations of vanadium (V), ferrum (Fe), magnesium (Mg), calcium (Ca), and zirconium (Zr). The adsorption capacity of U in natural seawater was determined to be 5.2 mg/g within 8 days. The recyclability of UiO-66-NH-(AO) in simulated seawater was demonstrated for at least four adsorption/desorption cycles. The binding mechanism was investigated by the extended X-ray absorption fine structure spectroscopy, revealing that U binding occurs in a fashion η2 motif. This study provides a reliable idea for the modification of MOFs and the potential for MOF-based materials to extract U from seawater.

Transient release of radioactive iodine from the fission of UF4 in 2LiF-BeF2 salt.

In this study, the behavior of fission product iodine released from the melting process of a mixture consisting of UF4 irradiated with neutrons and 2LiF-BeF2 (FLiBe) salt was studied. The experiment showed that a large amount of iodine was released immediately during melting and captured by Ni metal foils. The transient release of iodine observed in this experiment is attributed to the redox reaction between the hot atoms of the fission product iodine that cumulated due to long-time irradiation. The effect of the redox status of the molten salt on the transient release of iodine was also investigated. Based on this investigation, it was proposed that the activity ratios of 131I to salt-seeking fission products in the fuel salt, as an effective diagnostic criterion, may be used for the surveillance of the redox potential of fuel salts in a molten salt reactor.

Distribution and behaviour of 233Pa in 2LiF-BeF2 molten salt.

Distribution and behavior of 233Pa, essential in the thorium-uranium nuclear fuel cycle, were studied in 2LiF-BeF2 (66 : 34 mole%, FLiBe) molten salt by γ-ray spectrometry. The experiments showed that 233Pa deposited slightly on the surface of graphite crucible. The addition of Hastelloy and metallic lithium decreased the 233Pa specific activity in the salt by 1 to 2 orders of magnitude rapidly. Analysis indicated that reductive deposition of 233Pa was responsible for the rapid decrease of 233Pa specific activity in the salt. Additional experiments strongly supported the mechanism of reductive deposition of 233Pa induced by Hastelloy and metallic lithium. In view of the large deposition of 233Pa on Hastelloy, the possible influence of fissile nuclide 233U produced from 233Pa decay on the operation of thorium-based molten salt reactor was discussed.

Evaporation behavior of 2LiF-BeF2-ZrF4 molten salt with irradiated nuclear fuel.

The evaporation behaviours of various components were investigated by using a low pressure distillation method in a 2LiF-BeF2-ZrF4 mixture containing irradiated ThF4 and UF4. The experiment showed that BeF2 and ZrF4 were found to mainly condensate at the outer cover, the coolest zone, and their relative volatilities vs. LiF were 9.8 and 32.2, respectively, while for ThF4 and UF4, at four different temperature zones the values were almost constant, at 0.1 and 0.3. The radioactivity of various nuclides was further detected using gamma spectrometer analysis. 137Cs was hardly observed due to long half-time decay. 233Pa was found to co-evaporate with the carrier salt, while 239Np mainly remained in the residual salt as 237U. In different temperature zones, the decontamination factors of rare earth in receiver salts ranged from 10 to 103. On the basis of the investigation, it was proposed that the distribution of various nuclides after distillation, may be helpful to design the feasible condensate system to recover the carried salt in a molten salt reactor.

Reusable fibrous adsorbent prepared via Co-radiation induced graft polymerization for iodine adsorption.

Volatile iodine released from nuclear power plant reactors is radiological hazard to environment and human's health because of their high fission yield and environmental mobility. The complexity of nuclear waste management motivated the development of solid-phase adsorbents. Herein, co-radiation induced graft polymerization (CRIGP) was employed in the graft polymerization of N-vinyl-2-pyrrolidone (NVP) onto polyethylene-coated polypropylene skin-core (PE/PP) fibers using electron beam (EB) irradiation. This work provides a one-step green synthetic approach to prepare iodine fibrous adsorbents without any chemical initiators or large amount of organic solvent. The original and modified PE/PP fibers were characterized by fourier transform infrared spectrometry (FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric (TG) and scanning electron microscopy (SEM) to demonstrate the grafting of NVP onto the PE/PP fibers. The capacity of iodine absorbed by the PE/PP-g-PNVP fibers was 1237.8 mg/g after 180 min. Meanwhile, absorbents can be regenerated efficiently by two different means of ethanol elution and heating at 120 °C, respectively. Within 10 min, 94.17% and 90.12% of the iodine can be released from the PE/PP-g-PNVP fibers with these two methods, respectively. The adsorbent exhibited a long service life of at least ten adsorption-desorption cycles, suggesting that PE/PP-g-PNVP fibers might be a promising adsorbent for volatile iodine adsorption from fission products in nuclear power plant reactors.

Autophagy changes in lung tissues of mice at 30 days after carbon black-metal ion co-exposure.

OBJECTIVES: Accumulating studies have investigated the PM2.5-induced pulmonary toxicity, while gaps still remain in understanding its toxic mechanism. Due to its high specific surface area and adsorption capacity similar to nanoparticles, PM2.5 acts as a significant carrier of metals in air and then leads to altered toxic effects. In this study, we aimed to use CBs and Ni as model materials to investigate the autophagy changes and pulmonary toxic effects at 30 days following intratracheal instillation of CBs-Ni mixture. MATERIALS AND METHODS: Groups of mice were instilled with 100 µL normal saline (NS), 20 µg CBs, and 4 µg Ni or CBs-Ni mixture, respectively. At 7 and 30 days post-instillation, all the mice were weighed and then sacrificed. The evaluation system was composed of the following: (a) autophagy and lysosomal function assessment, (b) trace element biodistribution observation in lungs, (c) pulmonary lavage biomedical analysis, (d) lung histopathological evaluation, (e) coefficient analysis of major organs and (f) CBs-Ni interaction and cell proliferation assessment. RESULTS: We found that after CBs-Ni co-exposure, no obvious autophagy and lysosomal dysfunction or pulmonary toxicity was detected, along with complete clearance of Ni from lung tissues as well as recovery of biochemical indexes to normal range. CONCLUSIONS: We conclude that the damaged autophagy and lysosomal function, as well as physiological function, was repaired at 30 days after exposure of CBs-Ni. Our findings provide a new idea for scientific assessment of the impact of fine particles on environment and human health, and useful information for the comprehensive treatment of air pollution.

Study on the Thermal Stability of the Na2UF8 Complex in the Argon Atmosphere.

The Na2UF8 complex is an important intermediate compound in the purification of UF6 by the adsorption-desorption process during fluoride volatility of the spent nuclear fuel, and its decomposition is seriously affected by temperature and atmosphere. In this study, the thermal stability of Na2UF8 in the argon atmosphere was investigated by the in situ Raman spectroscopy. The decomposition products of Na2UF8 at different temperatures were systematically determined by X-ray diffraction spectroscopy and X-ray absorption fine structure spectroscopy. The results indicated that Na2UF8 on the NaF sorbent was stable under 300 °C in the argon atmosphere, and it started to decompose into UF6 and NaF rapidly when the temperature was above 300 °C. Meanwhile, a small amount of Na2UF8 was converted to Na3UF7, and it was stable in the temperature range from 350 to 450 °C. The decomposition mechanism of the Na2UF8 and the formation mechanism of Na3UF7 on the NaF sorbent were speculated according to the experimental results.

One-Dimensional Synergistic Core-Shell Nanozymes with Superior Peroxidase-like Activity for Ultrasensitive Colorimetric Detection of Blood Cholesterol.

In this paper, a simple and green strategy was proposed to fabricate one-dimensional core-shell Fe3O4@C/Ni nanocomposites. The rationally designed hybrid nanostructures notably exhibited an extremely excellent peroxidase-mimicking property, arising from the synergetic effects of Fe3O4, carbon, and Ni nanoparticles, along with the hollow and hierarchically porous nanostructures. Based upon the outstanding peroxidase-like activity and cholesterol oxidase cascade reaction, a label-free, ultrasensitive, and highly selective colorimetric assay for cholesterol determination has been developed. Under the optimized conditions, the colorimetric biosensor demonstrated a linear response to cholesterol ranging from 5 to 200 µM, with a relatively low detection limit of 0.17 µM. More importantly, cholesterol determination as low as 5 µM could be directly distinguished with the naked eye. In addition, we successfully determined the total cholesterol content in human serum samples with satisfactory accuracy and good precision. The Fe3O4@C/Ni nanocatalyst-based colorimetric biosensor provides great potential in point-of-care testing in disease diagnosis.

Silver nanoparticles exert concentration-dependent influences on biofilm development and architecture.

OBJECTIVES: To investigate the impact of silver nanoparticles (AgNPs) on the biofilm growth and architecture. MATERIALS AND METHODS: Silver nitrate was reduced by d-maltose to prepare AgNPs in the presence of ammonia and sodium hydroxide. The physicochemical properties of AgNPs were characterized by transmission electron microscopy, ultraviolet-visible spectroscopy and inductively coupled plasma mass spectrometry. The development of biofilm with and without AgNPs was explored by crystal violet stain. The structures of mature biofilm were visually studied by confocal laser scanning microscopy and scanning electron microscopy. Bacterial cell, polysaccharide and protein within biofilm were assessed quantitatively by colony-counting method, phenol-sulphuric acid method and Bradford assay, respectively. RESULTS: The spherical AgNPs (about 30 nm) were successfully synthesized. The effect of AgNPs on Pseudomonas aeruginosa biofilm development was concentration-dependent. Biofilm was more resistant to AgNPs than planktonic cells. Low doses of AgNPs exposure remarkably delayed the growth cycle of biofilm, whereas high concentration (18 µg/mL) of AgNPs fully prevented biofilm development. The analysis of biofilm architecture at the mature stage demonstrated that AgNPs exposure at all concentration led to significant decrease of cell viability within treated biofilms. However, sublethal doses of AgNPs increased the production of both polysaccharide and protein compared to control, which significantly changed the biofilm structure. CONCLUSIONS: AgNPs exert concentration-dependent influences on biofilm development and structure, which provides new insight into the role of concentration played in the interaction between antibacterial nanoparticles and biofilm, especially, an ignored sublethal concentration associated with potential unintended consequences.

Coordination Structures of the Uranyl(VI)-Diamide Complexes: A Combined Mass Spectrometric, EXAFS Spectroscopic, and Theoretical Study.

The coordination structures of a series of uranyl-diamide complexes, namely UO2(TMGA)22+, UO2(TMTDA)22+, and UO2(TMPDA)22+ (TMGA: N, N, N', N'-tetramethylglutaramide; TMTDA: N, N, N', N'-tetramethyl-3-thiodiglycolamide; TMPDA: N, N, N', N'-tetramethylpyridine-2,6-dicarboxamide), in the gas phase and solution were studied by electrospray ionization (ESI) mass spectrometry, density functional theory (DFT) calculations, and extended X-ray absorption fine structure (EXAFS) spectroscopy. ESI of UO2Cl2-TMGA, UO2Cl2-TMTDA, and UO2Cl2-TMPDA solutions produced UO2(TMGA)22+, UO2(TMTDA)22+, and UO2(TMPDA)22+ as the major complexes in the gas phase. The gas-phase fragmentation patterns of these three complexes upon collision-induced dissociation (CID) are quite similar, and the products arising from (CH3)2N-COcarbonyl, CH2-COcarbonyl, Cpyridine-COcarbonyl, and CH2-CH2/S bond cleavages were identified, which agree with the degradation patterns of diamides upon γ irradiation in solution. DFT calculations revealed similar bidentate coordination modes of TMGA and TMTDA in the UO2(TMGA)22+ and UO2(TMTDA)22+ complexes in the gas phase. For UO2(TMPDA)22+, UO22+ is coordinated by two Ocarbonyl and one Npyridine from each TMPDA, which acts as a tridentate ligand. The results from EXAFS analysis indicate that the coordination structures of UO2(TMGA)22+, UO2(TMTDA)22+, and UO2(TMPDA)22+ in solution are similar to those in the gas phase.

A novel ion-imprinted amidoxime-functionalized UHMWPE fiber based on radiation-induced crosslinking for selective adsorption of uranium.

A novel uranium-imprinted adsorbent (AO-Imp fiber) was prepared by radiation-induced crosslinking of amidoxime-functionalized ultra-high molecular weight polyethylene fiber (AO fiber). The porous structure was characterized by scanning electron microscopy (SEM) and positron annihilation lifetime (PAL) spectroscopy after ion imprinting. This ion-imprinted fiber exhibited enhanced adsorption selectivity for uranium in the form of both UO2 2- and [UO2(CO3)3]4- in batch experiments. Compared with AO fiber, the adsorption capacity of the AO-Imp(250) fiber for uranium increased from 0.36 mg g-1 to 1.00 mg g-1 in simulated seawater and from 5.02 mg g-1 to 12.03 mg g-1 in simulated acid effluent, while its adsorption capacities for other co-existing metal ions were particularly low. This study provides an approach to prepare ion-imprinted adsorbents without introducing crosslinking reagents, which may be a promising method for uranium extraction.

Serum protein corona-responsive autophagy tuning in cells.

Autophagy represents an important cellular response to nanoparticles (NPs), whose modulation holds great promise for developing nanomedicine. Here, we systematically studied cell autophagy responses elicited by the NP-protein corona with diverse protein corona types surrounding NPs with different sizes, shapes, and compositions. We demonstrated that these physicochemical properties of NP-protein coronas exerted a remarkable influence on cell autophagy responses. Particularly, for surface protein type-associated modulation of cell autophagy, we correlated the autophagy level to adsorbed protein type on Fe3O4 NPs. Accordingly, we could modulate cell autophagy in response to various levels of protein adsorption. Our work provides new clues to modulate cell autophagy by rational designing NP-protein complexes, which could aid in further biological and therapeutic applications.

Infrared Spectroscopic and Theoretical Studies of Group 3 Metal Isocyanide Molecules.

A series of group 3 metal isocyanide complexes were prepared via the reactions of laser ablated scandium, yttrium, and lanthanum atoms with (CN)2 in an argon matrix. The product structures were identified on the basis of their characteristic infrared absorptions from isotopically labeled (CN)2 samples as well as the calculated frequencies and isotopic frequency ratios. Group 3 metal atoms reacted with (CN)2 to form M(NC)2 (M = Sc, Y, La) when the samples were subjected to λ > 220 nm irradiation. Other products such as M(NC)3 and MNC were produced together with M(NC)2 through either the reactions of M(NC)2 and (CN)2 or the loss of one CN ligand from M(NC)2. CCSD(T)//B3LYP calculations reveal that ScNC possesses a 3Δ ground state, while 1Σ+ is most stable for YNC and LaNC. All of the M(NC)2 and M(NC)3 complexes were predicted to have doublet and singlet ground states, respectively. Group 3 metal cyanides are less stable than the isocyanides by at least 4 kcal/mol at the CCSD(T) level, and their C-N stretches are much weaker than the N-C stretches of the isocyanides. No absorption can be assigned to the M(CN) x complex, which would appear between 2100 and 2250 cm-1.

Formation and Characterization of Zr4+ Stabilized by Neutral Tridentate Ligands in the Gas Phase.

Ligated tetrapositive metal ions are rare gas-phase species which tend to form complexes with lower charges due to the high 4th ionization energies of metals. We report the observation of tetrapositive Zr(TMPDA)34+ and Zr(TMOGA)34+ complexes in the gas phase by electrospray ionization of Zr(ClO4)4/TMPDA and Zr(ClO4)4/TMOGA mixtures. The Zr4+ center in both complexes is coordinated by nine atoms from three neutral diamide ligands forming nine-coordinate twisted tricapped trigonal prismatic geometry on the basis of DFT calculations. Collision-induced dissociation of both complexes resulted in the loss of protonated ligands to form tripositive Zr(TMPDA)(TMPDA-H)3+ and Zr(TMOGA)(TMOGA-H)3+ products which retain the IV oxidation state of zirconium at the cost of charge reduction from 4+ to 3+ of the whole complexes. The very high 4th ionization energy of zirconium (34.34 eV) makes tetrapositive zirconium complex the most challenging tetracation to be stabilized against charge reduction in the gas phase to date. Graphical abstract ᅟ.

Systematic Study in Mammalian Cells Showing No Adverse Response to Tetrahedral DNA Nanostructure.

The advent of DNA technology has demonstrated great potential in a wide range of applications, especially in the field of biology and biomedicine. However, current understanding of the toxicological effects and cellular responses of DNA nanostructures remains to be improved. Here, we chose tetrahedral DNA nanostructures (TDNs), a type of nanocarriers for delivering molecular drugs, as a model for systematic live-cell analysis of the biocompatibility of TDNs to normal bronchial epithelial cells, carcinoma cells, and macrophage. We found that the interaction behaviors of TDNs in different cell lines were very different, whereas after internalization, most of the TDNs in diverse cell lines were positioned to lysosomes. By a systematic assessment of cell responses after TDN exposure to various cells, we demonstrate that internalized TDNs have good innate biocompatibility. Interestingly, we found that TDN-bearing cells would not affect the cell cycle progression and accompany cell division and that TDNs were separated equally into two daughter cells. This study improves our understanding of the interaction of DNA nanostructures with living systems and their biocompatibility, which will be helpful for further designing DNA nanostructures for biomedical applications.