Delta-like ligand 3-targeted radioimmunotherapy for neuroendocrine prostate cancer.

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer with limited meaningful treatment options. NEPC lesions uniquely express delta-like ligand 3 (DLL3) on their cell surface. Taking advantage of DLL3 overexpression, we developed and evaluated lutetium-177 (177Lu)-labeled DLL3-targeting antibody SC16 (177Lu-DTPA-SC16) as a treatment for NEPC. SC16 was functionalized with DTPA-CHX-A" chelator and radiolabeled with 177Lu to produce 177Lu-DTPA-SC16. Specificity and selectivity of 177Lu-DTPA-SC16 were evaluated in vitro and in vivo using NCI-H660 (NEPC, DLL3-positive) and DU145 (adenocarcinoma, DLL3-negative) cells and xenografts. Dose-dependent treatment efficacy and specificity of 177Lu-DTPA-SC16 radionuclide therapy were evaluated in H660 and DU145 xenograft-bearing mice. Safety of the agent was assessed by monitoring hematologic parameters. 177Lu-DTPA-SC16 showed high tumor uptake and specificity in H660 xenografts, with minimal uptake in DU145 xenografts. At all three tested doses of 177Lu-DTPA-SC16 (4.63, 9.25, and 27.75 MBq/mouse), complete responses were observed in H660-bearing mice; 9.25 and 27.75 MBq/mouse doses were curative. Even the lowest tested dose proved curative in five (63%) of eight mice, and recurring tumors could be successfully re-treated at the same dose to achieve complete responses. In DU145 xenografts, 177Lu-DTPA-SC16 therapy did not inhibit tumor growth. Platelets and hematocrit transiently dropped, reaching nadir at 2 to 3 wk. This was out of range only in the highest-dose cohort and quickly recovered to normal range by week 4. Weight loss was observed only in the highest-dose cohort. Therefore, our data demonstrate that 177Lu-DTPA-SC16 is a potent and safe radioimmunotherapeutic agent for testing in humans with NEPC.

MRI-Based Interstitial Fluid Velocity Analysis for Drug Delivery Efficiency Evaluation in Tumor.

There are many flow behaviors in solid tumors, including intravascular, bloodstream, and interstitial convection. Studies have shown that tumor interstitial fluid (TIF) is an important part of tumor microenvironment regulation and affects drug delivery and metabolism between tumor cells. Magnetic resonance imaging (MRI) is suitable for detecting the flow rates of liquids in tissues. Clinical phase contrast PC-MRI technology has been designed to observe the blood flow in large vessels such as arteries and veins; however, it is not sensitive enough to deal with slow flow velocity. Our previously developed vertical plane echo PC-MRI technology, the Velocity Mapping sequence, improved the signal-to-noise ratio (SNR) for measuring slow interstitial fluid rate. In this study, this sequence was used to determine the TIF flow rate in MDA-MB-231 human breast tumor cells used in BALB/c nude male mice. Two different sizes of contrast agents were intravenously injected, and the relationship between their distribution and the TIF flow rate was studied for the first time. Combining the results of clinical scanning showed that small-molecule DTPA-Gd (diethylenetriaminepentaacetic acid-gadolinium) was distributed immediately around the tumor margin after the injection. This distribution was positively correlated to the high flow rate area of the TIF before administration. In contrast, nanoparticles NaGdF4-PEG (polyethylene glycol) entered the tumor and reached their peak at 3 h. Drug distribution was negatively correlated with the high-flow-rate region of the TIF. Investigation of the TIF velocity can help better understand the fluid behavior in tumors and its role in drug delivery.

Design, development and bio-evaluation of a novel radio-ligand 99mTc-THQ-DTPA as a sigma 2 receptor specific breast tumor imaging agent.

Over-expression of sigma-2 receptor in cancer cells provides an opportunity to develop molecular probes for diagnosis, even for non-receptor specific malignancies like triple negative breast cancers. In this work, a novel sigma-2 receptor ligand [THQ-DTPA] has been synthesized and characterized using 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (THQ) and diethylenetriaminepentaacetic acid (DTPA). The ligand is further chelated with 99mTc for application as metal based radiotracer [99mTc-THQ-DTPA]. Radiolabelling with 99mTc was achieved in an excellent yield of 98.0 ± 0.5% using stannous chloride as a reducing agent. The radioligand was found to be stable in human serum up-to 24 h, bio-compatible with less than 4% hemolysis, and exhibited high binding with sigma receptors isolated from rat liver membrane (Kd of 16.32 ± 4.93 nM and Bmax of 0.5232 ± 0.06 pmol/mg). Bio-distribution studies in triple-negative breast tumor bearing nude mice showed high tumor uptake after 30 min of injection with tumor/muscle (T/M) ratio of 3.58 ± 0.09. At 240 min, the T/M ratio (2.84 ± 0.20) decreased by 35% when administered in sigma blocked tumor bearing mice (1.81 ± 0.16) suggesting the selectivity of the ligand. Tumor imaging in gamma camera indicated a contrast of 3.56 at 30 min p.i. The above findings indicate that the ligand 99mTc-THQ-DTPA binds to sigma-2 receptors with high affinity and has potential for triple-negative breast tumor imaging.

Zinc deficiency induced by the chelating agent DTPA and its regulatory interpretation for developmental toxicity classification.

Aminocarboxylic acid (ethylenediamine-based) chelating agents such as DTPA are widely used in a variety of products and processes. Recently, DTPA was classified in the European Union as a developmental toxicant CLP Category 1B. However, according to the CLP regulation (CLP, 2008) classification as a developmental toxicant requires a chemical to possess an intrinsic, specific property to do so. This paper provides overwhelming evidence that shows the developmental toxicity only seen at a sustained high dose of 1000 mg DTPA/kg bw/day in rats during pregnancy is mediated by zinc depletion which leads to non-specific secondary effects associated with zinc deficiency. Therefore, based on the CLP regulation itself, viz. the lack of a specific, intrinsic property, supported by significant differences in zinc kinetics and physiology between pregnant rats and pregnant women, DTPA should not be classified as a developmental toxicant. Moreover, classification for developmental toxicity resulting from zinc deficiency, and only observed at high doses, would not increase protection of human health; instead, it will only lead to onerous and disproportionate restrictions being placed on the use of this substance.

Enhancing oral bioavailability of Ca-DTPA by self double emulsifying drug delivery system (SDEDDS).

OBJECTIVE: BCS class III drug (highly soluble, poorly permeable) possesses low oral bioavailability. The research work highlights the utility of self-double emulsifying drug delivery system (SDEDDS) which are stable isotropic mixture of w/o primary emulsion and hydrophilic surfactants for improving oral bioavailability of Ca-DTPA (Calcium diethylenetriamine pentaacetate). Upon oral administration, SDEDDS rapidly emulsifies into w/o/w double emulsions in the aqueous gastrointestinal environment, with hydrophilic drugs entrapped inside oil reservoirs. METHODS: SDEDDS formulation was successfully developed using excipients, that is, medium chain triglycerides, oleic acid, phospholipids, Span 80, Tween 80 using double emulsification technique. RESULTS: The optimized formulation F4 (Aq. phase: 11.6%w,w; MCT & oleic acid: 70.9%w/w; Span 80:17.5%w/w; Lecithin:16%w/w and Tween 80 (10%w/w)) appeared bright yellow liquid which upon dilution appeared milky white within 2 min, droplet size (501.7 nm), pdi value (0.044), zeta potential (-52 mV), entrapment efficiency (79.6 ± 1.63), viscosity (72.2 ± 1.8 mpA.s), significant high cumulative in vitro drug permeation (CDP) and 2.17-fold increase in apparent permeability coefficient. Pharmacokinetic studies in rats showed 1.17-fold increases in AUC of F4 and comparatively higher plasma levels (Cmax) compared with pure drug administered orally. The Absolute (OF4, OD) and Relative bioavailability was found to be 14.52%, 12.35%, and 117.47%, respectively. CONCLUSION: The present studies have clearly demonstrated that SDEDDS could readily form w/o/w double emulsions in vivo with enhanced in vitro and in vivo oral bioavailability. Therefore, considerable augmentation in the rate and extent of oral drug absorption ratified the better performance of the SDEDDS in enhancing the bioavailability of Ca-DTPA.

Potential of combined reactor and static composting applications for the removal of heavy metals and antibiotic resistance genes from chicken manure.

Chicken manure (CM) can pose a serious threat to environmental and human health, and need to be managed properly. The compost can effectively treat CM. However, there is limited research on the heavy metals and antibiotic resistance genes (ARGs) during compost CM. In this study, the combined application of reactor and static composting (RSC) was used to produce organic fertilizer of CM (OCM), and heavy metals, ARGs and bacterial community structure was investigated. The results show that RSC could be used to produce OCM, and OCM meet the National organic fertilizer standard (NY/T525-2021). Compared to the initial CM, DTPA-Cu, DTPA-Zn, DTPA-Pb, DTPA-Cr, DTPA-Ni and DTPA-As in OCM decreased by 40.83%, 23.73%, 34.27%, 38.62%, 16.26%, and 43.35%, respectively. RSC decreased the relative abundance of ARGs in CM by 84.06%, while the relative abundance of sul1 and ermC increased. In addition, the relative abundance and diversity of ARGs were mainly influenced by the bacterial community, with Actinobacteria, Firmicutes, and Proteobacteria becoming the dominant phyla during composting, and probably being the main carriers and dispersers of most of the ARGs. Network analyses confirmed that Gracilibacillus, Lactobacillus, Nocardiopsis, Mesorhizobium and Salinicoccus were the main potential hosts of ARGs, with the main potential hosts of sul1 and ermC being Mesorhizobium and Salinicoccus. The passivation and physicochemical properties of heavy metals contribute to the removal of ARGs, with sul1 and ermC being affected by the toal heavy metals. Application of RSC allows CM to produce mature, safe organic fertilizer after 32 d and reduces the risk of rebound from ARGs, but the issues of sul1 and ermC gene removal cannot be ignored.

Bioavailability and Toxicity of nano Copper Oxide to Pakchoi (Brassica Campestris L.) as Compared with bulk Copper Oxide and Ionic Copper.

The increasing use of copper oxide nano particles (nCuO) as nano-fertilizers and pesticides have raised concerns over their impact on soil environment and agricultural products. In this study, two nCuO with different shapes, namely spherical nCuO (CuO NPs) and tubular nCuO (CuO NTs), were selected to investigate their bioavailability and toxicity to pakchoi in two soils with different properties. At the meantime, CuO bulk particles (CuO BPs) and Cu(NO3)2 were used for comparison. Results showed that all the Cu treatments increased the DTPA extractable (DTPA-Cu) concentrations in GD soil (acidic) more than in HN soil (alkaline). The DTPA-Cu concentrations increased in the order of Cu(NO3)2 ≈ CuO NPs > CuO BPs ≈ CuO NTs in GD soil and Cu(NO3)2 > CuO NPs > CuO BPs ≈ CuO NTs in HN soil. While for the contents of Cu in the aerial parts of pakchoi, the order is CuO NPs > Cu(NO3)2 > CuO NTs ≈ CuO BPs in GD soil and CuO NPs ≈ Cu(NO3)2 > CuO BPs ≈ CuO NTs in HN soil. Only CuO NPs reduced pakchoi biomass in GD soil. There are no significant difference among CuO NPs, CuO BPs, and Cu(NO3)2 in reducing the chlorophyll contents in pakchoi in HN soil, whereas in GD soil, CuO NPs and CuO BPs led to significantly lower chlorophyll contents in pakchoi compared to Cu(NO3)2. Additionally, CuO NPs and Cu(NO3)2 increased Mn and Mo in pakchoi leaf in HN soil, while increased Zn in pakchoi leaf in GD soil. These results indicated that CuO NPs showed higher or comparable toxicity and bioavailability to pakchoi compared with Cu(NO3)2 depending on soil properties, and nCuO are more easily to be transferred from roots to the aerial parts than CuO BPs and Cu(NO3)2.

Does livestock-Manure-Derived Biochar Suitable for the Stabilization of Cadmium and Zinc in Contaminated Soil?

Both livestock-manure and livestock-manure-derived biochar have been used to remediate heavy metal-contaminated soil. However, direct comparisons of the heavy metal stabilization efficiency of livestock-manure and EQC-manure-biochar (derived from an equal quantity of corresponding livestock-manure) are limited. In the present study, the effect of livestock-manures and EQC-manure-biochars on soil properties and heavy metal bioavailability and leachability were compared using two contrasting soils (Ferralsols and Fluvisols). The results showed that both the livestock-manures and EQC-manure-biochars significantly changed soil pH, available phosphorus, available potassium, alkaline nitrogen and organic matter content (p < 0.05), but the trends were variable. In Ferralsols, the DTPA-extractable Cd and Zn decreased by -0.38%~5.70% and - 3.79%~9.98% with livestock-manure application and by -7.99%~7.23% and - 5.67%~7.17% with EQC-manure-biochars application. In Fluvisols, the DTPA-extractable Cd and Zn decreased by 13.39%~17.41% and - 45.26%~14.24% with livestock-manure application and by 10.76%~16.90% and - 36.38%~16.37% with EQC-manure-biochar application. Furthermore, the change in TCLP-extractable Cd and Zn in both soils was similar to that of DTPA-extractable Cd and Zn. Notably, the Cd and Zn stabilization efficiency of the EQC-manure-biochars was no better than that of the corresponding livestock-manures. These results suggest that the use of livestock-manure-derived biochar is not cost-effective for the remediation of heavy metal-contaminated soil.

Bi-DTPA, a potential CT-guided radiation sensitizer.

The therapeutic effects and application of radiotherapy are restricted to some extent due to low radiosensitivity of tumor tissues and adverse effects by excess dosage. Current radiosensitizers are confronted with problems in clinical translation because of complicated manufacture technique and high cost. In this research, we have synthesized a radiosensitizer with advantages in low cost and mass production, which could be applied to CT imaging and enhanced radiotherapy in breast cancer, namely Bi-DTPA. It not only enhanced tumor CT imaging which resulted in better therapeutic accuracy, but also realized radiotherapy sensitization by producing massive ROS and inhibit tumor proliferation, providing a sound perspective in the clinical translation of the radiosensitizer.

RUNX3 regulates the susceptibility against EGFR-targeted non-small cell lung cancer therapy using 47Sc-conjugated cetuximab.

BACKGROUND: Radioimmunotherapy with cetuximab and conjugates with various radioisotopes is a feasible treatment option for different tumor models. Scandium-47 (47Sc), one of several ß--particle-emitting radioisotopes, displays favorable physical and chemical properties for conjugation to monoclonal antibodies. However, the therapeutic efficacy of 47Sc in preclinical and clinical studies is largely unknown. Given that intrinsic alterations in tumors greatly contribute to resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy, research on overcoming resistance to radioimmunotherapy using cetuximab is required. METHODS: 47Sc was produced by irradiation of a CaCO3 target at the HANARO research reactor in KAERI (Korea Atomic Energy Research Institute) and prepared by chromatographic separation of the irradiated target. Cetuximab was conjugated with 47Sc using the bifunctional chelating agent DTPA. Radiochemical purity was determined using instant thin-layer chromatography. The immunoreactivity of 47Sc-DTPA-cetuximab was evaluated using the Lindmo method and an in vitro cell-binding assay. The inhibitory effects of cetuximab and 47Sc-DTPA-cetuximab were confirmed using cell growth inhibition and BrdU cell proliferation assays. Differences in protein expression levels between cetuximab- and 47Sc-DTPA-cetuximab-treated cells were confirmed using western blotting. Complex formation between RUNX3 and DNA repair components was confirmed using immunoprecipitation and western blotting. RESULTS: Cetuximab induces cell cycle arrest and cell death in EGFR-overexpressing NSCLC cells. Radiolabeling of cetuximab with 47Sc led to increased therapeutic efficacy relative to cetuximab alone. Application of 47Sc-DTPA-cetuximab induced DNA damage responses, and activation of RUNX3 significantly enhanced the therapeutic efficacy of 47Sc-DTPA-cetuximab. RUNX3 mediated susceptibility to EGFR-targeted NSCLC therapy using 47Sc-DTPA-cetuximab via interaction with components of the DNA damage and repair machinery. CONCLUSIONS: 47Sc-DTPA-cetuximab promoted cell death in EGFR-overexpressing NSCLC cells by targeting EGFR and inducing DNA damage as a result of ß irradiation emitted from the conjugated 47Sc. Activation of RUNX3 played a key role in DNA damage and repair processes in response to the ionizing radiation and inhibited cell growth, thus leading to more effective tumor suppression. RUNX3 can potentially moderate susceptibility to 47Sc-conjugated cetuximab by modulating DNA damage and repair process mechanisms.

Investigation of Chelating Agents for the Removal of Thorium from Human Teeth upon Nuclear Contamination.

Thorium-232 (232Th) is a radioactive heavy metal that is of increasing interest as a source of nuclear energy. However, upon nuclear incidents, the ingestion or inhalation of Th in major quantities can contribute to chemical and radiological health problems, including accumulation in the bone tissue and an increased risk of developing pancreatic, lung, and hematopoietic cancers. The major mineral component of the bone is hydroxyapatite (HAP)─also the major mineral component of the teeth. As such, the teeth are the first site of exposure upon oral ingestion of Th-contaminated materials, and Th can pose a potential risk to teeth development. In essence, in the case of human contamination, it is critical to identify effective chelating agents capable of removing Th. Using a batch study methodology, this present work investigates the uptake and the removal of Th from synthetic HAP and from teeth samples by diethylenetriamine pentaacetate (DTPA), ethylenediaminetetraacetic acid (EDTA), and other promising chelating agents. Th uptake over synthetic HAP exceeds 98% at physiological pH with <1 min of contact time and uptake exceeds 90% across the entire pH range. Regarding teeth, over 1 mg Th uptaken per gram of tooth is observed after 24 h. The overall effectiveness of chelating agents for the removal of Th from is as follows: DTPA > EDTA > NaF/mouthwash/3,4,3-LI(1,2-HOPO); this trend was observed both in synthetic HAP and Th-impregnated teeth samples.

Leveraging a Dual Variable Domain Immunoglobulin to Create a Site-Specifically Modified Radioimmunoconjugate.

Site-specifically modified radioimmunoconjugates exhibit superior in vitro and in vivo behavior compared to analogues synthesized via traditional stochastic methods. However, the development of approaches to site-specific bioconjugation that combine high levels of selectivity, simple reaction conditions, and clinical translatability remains a challenge. Herein, we describe a novel solution to this problem: the use of dual-variable domain immunoglobulins (DVD-IgG). More specifically, we report the synthesis, in vitro evaluation, and in vivo validation of a 177Lu-labeled radioimmunoconjugate based on HER2DVD, a DVD-IgG containing the HER2-targeting variable domains of trastuzumab and the catalytic variable domains of IgG h38C2. To this end, we first modified HER2DVD with a phenyloxadiazolyl methlysulfone-modified variant of the chelator CHX-A″-DTPA (PODS-CHX-A''-DTPA) and verified the site-specificity of the conjugation for the reactive lysines within the catalytic domains via chemical assay, MALDI-ToF mass spectrometry, and SDS-PAGE. The chelator-bearing immunoconjugate was subsequently labeled with [177Lu]Lu3+ to produce the completed radioimmunoconjugate, [177Lu]Lu-CHX-A″-DTPAPODS-HER2DVD, in >80% radiochemical conversion and a specific activity of 29.5 ± 7.1 GBq/µmol. [177Lu]Lu-CHX-A″-DTPAPODS-HER2DVD did not form aggregates upon prolonged incubation in human serum, displayed 87% stability to demetalation over a 7 days of incubation in serum, and exhibited an immunoreactive fraction of 0.95 with HER2-coated beads. Finally, we compared the pharmacokinetic profile of [177Lu]Lu-CHX-A″-DTPAPODS-HER2DVD to that of a 177Lu-labeled variant of trastuzumab in mice bearing subcutaneous HER2-expressing BT-474 human breast cancer xenografts. The in vivo performance of [177Lu]Lu-CHX-A″-DTPAPODS-HER2DVD matched that of 177Lu-labeled trastuzumab, with the former producing a tumoral activity concentration of 34.1 ± 12.1 %ID/g at 168 h and tumor-to-blood, tumor-to-liver, and tumor-to-kidney activity concentration ratios of 10.5, 9.6, and 21.8, respectively, at the same time point. Importantly, the DVD-IgG did not exhibit a substantially longer serum half-life than the traditional IgG despite its significantly larger size (202 kDa for the former vs 148 kDa for the latter). Taken together, these data suggest that DVD-IgGs represent a viable platform for the future development of highly effective site-specifically labeled radioimmunoconjugates for diagnostic imaging, theranostic imaging, and radioimmunotherapy.

Effect of soil texture and zinc oxide nanoparticles on growth and accumulation of cadmium by wheat: a life cycle study.

Cadmium (Cd) is getting worldwide attention due to its continuous accumulation in agricultural soils which is due to anthropogenic activities and finally Cd enters in food chain mainly through edible plants. Cadmium free food production on contaminated soils is great challenge which requires some innovative measures for crop production on such soils. The current study evaluated the efficiency of zinc oxide nanoparticles (ZnONPs) (0, 150 and 300 mg/kg) on the growth of wheat in texturally different soils including clay loam (CL), sandy clay loam (SCL), and sandy loam (SL) which were contaminated with were contaminated with 25 mg/kg of Cd before crop growth. Results depicted that doses of ZnONPs and soil textures significantly affected the biological yields, Zn and Cd uptake in wheat plants. The application of 300 mg/kg ZnONPs caused maximum increase in dry weights of shoot (66.6%), roots (58.5%), husk (137.8%) and grains (137.8%) in CL soil. The AB-DTPA extractable Zn was increased while Cd was decreased with doses of NPs depending upon soil textures. The maximum decrease in AB-DTPA extractable Cd was recorded in 300 mg/kg of ZnONPs treatment which was 58.7% in CL, 33.2% in SCL and 12.1% in SL soil as compared to respective controls. Minimum Cd concentrations in roots, shoots, husk and grain were found in 300 mg/kg ZnONPs amended CL soil which was 58%, 76.7%, 58%, and 82.6%, respectively. The minimum bioaccumulation factor (0.14), translocation index (2.46) and health risk index (0.05) was found in CL soil with the highest dose of NPs. The results concluded that use of ZnONPs significantly decreased Cd concentration while increased Zn concentrations in plants depending upon doses of NPs and soil textures.

Effects of mercapto-palygorskite application on cadmium accumulation of soil aggregates at different depths in Cd-contaminated alkaline farmland.

Mercapto-palygorskite (MP) is a novel immobilization material for cadmium (Cd) pollution, but the immobilization mechanism on alkaline Cd contaminated soil is not completely clear. In this paper, field experiment was carried out to study the effect of MP on the transfer of Cd in aggregates at different depth, the contribution of soil aggregates to the reduction of Cd in bulk soil and the immobilization mechanism of MP. The results showed that MP had no significant influence on the total Cd content, soil aggregates distribution, pH value, CEC value and enzyme activities no matter at any depth. At the depth of 0-20 cm, MP significantly reduced the DTPA-Cd in bulk soil by 60.7%, and increased the GWD and R0.25 value. Similarly, the content of DTPA-Cd in the soil aggregates was deceased by 40.2-63.6%, the OM, DOC, available Fe, Mn and S in soil aggregates were significantly increased by 15.0-19.1%, 19.2-41.7%, 24.7-41.2% and 12.5-35.1% respectively. The Cd fraction of aggregates, especially exchangeable Cd (EXE-Cd) and bound to Fe/Mn oxide Cd (OX-Cd), was reduced by 5.4-28.1% and increased by 22.3-50.4%. In addition, MP had different effects on the GSF value of soil aggregates, but there was a downward trend for AFX value at 0-20 cm soil depth. MP almost had no significant influence on the above indexes at the depth of 20-40 cm and 40-60 cm, but except the Cd fraction, the GSF and AFX value in individual aggregates. Small aggregates (<1 mm) and large aggregates (>1 mm) contributed 59.1% and 22% to the reduction of Cd in bulk soil. Partial Least Structural Equation Model (PL-SEM) revealed that S promoted the production of available Fe, Mn, OM and DOC, while the content of DOC inhibited the formation of EXE-Cd and the available Fe and Mn boosted the production of OX-Cd.

Functionalized maghemite nanoparticles for enhanced adsorption of uranium from simulated wastewater and magnetic harvesting.

Maghemite (γ-Fe2O3) nanoparticles (MNPs) were functionalized with 3-aminopropyltriethoxysilane (APTES) to give APTES@Fe2O3 (AMNP) which was then reacted with diethylenetriamine-pentaacetic acid (DTPA) to give a nanohybrid DTPA-APTES@Fe2O3 (DAMNP). Nano-isothermal titration calorimetry shows that DTPA complexation with uranyl ions in water is exothermic and has a stoichiometry of two DTPA to three uranyl ions. Density functional theory calculations indicate the possibility of several complexes between DTPA and UO22+ with different stoichiometries. Interactions between uranyl ions and DAMNP functional groups are revealed by X-photoelectron and Fourier transform infrared spectroscopies. Spherical aberration-corrected Scanning Transmission Electron Microscopy visualizes uranium on the particle surface. Adsorbent performance metrics were evaluated by batch adsorption studies under different conditions of pH, initial uranium concentration and contact time, and the results expressed in terms of equilibrium adsorption capacities (qe) and partition coefficients (PC). By either criterion, performance increases from MNP to AMNP to DAMNP, with the maximum uptake at pH 5.5 in all cases: MNP, qe = 63 mg g-1, PC = 127 mg g-1 mM-1; AMNP, qe = 165 mg g-1, PC = 584 mg g-1 mM-1; DAMNP, qe = 249 mg g-1, PC = 2318 mg g-1 mM-1 (at 25 °C; initial U concentration 0.63 mM; 5 mg adsorbent in 10 mL of solution; contact time, 3 h). The pH maximum is related to the predominance of mono- and di-cationic uranium species. Uptake by DAMNPs follows a pseudo-first-order or pseudo-second-order kinetic model and fits a variety of adsorption models. The maximum adsorption capacity for DAMNPs is higher than for other functionalized magnetic nanohybrids. This adsorbent can be regenerated and recycled for at least 10 cycles with less than 10% loss in activity, and shows high selectivity. These findings suggest that DAMNP could be a promising adsorbent for the recovery of uranium from nuclear wastewaters.

A back propagation neural network approach to estimate the glomerular filtration rate in an older population.

BACKGROUND: The use of creatinine-based glomerular filtration rate (GFR)-estimating equations to evaluate kidney function in elderly individuals does not appear to offer any performance advantages. We therefore aimed to develop an accurate GFR-estimating tool for this age group. METHODS: Adults aged ≥ 65 years who underwent GFR measurement by technetium-99 m-diethylene triamine pentaacetic acid (99mTc-DTPA) renal dynamic imaging were included. Data were randomly split into a training set containing 80% of the participants and a test set containing the remaining 20% of the subjects. The Back propagation neural network (BPNN) approach was used to derive a novel GFR estimation tool; then we compared the performance of the BPNN tool with six creatinine-based equations (Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI], European Kidney Function Consortium [EKFC], Berlin Initiative Study-1 [BIS1], Lund-Malmö Revised [LMR], Asian modified CKD-EPI, and Modification of Diet in Renal Disease [MDRD]) in the test cohort. Three equation performance criteria were considered: bias (difference between measured GFR and estimated GFR), precision (interquartile range [IQR] of the median difference), and accuracy P30 (percentage of GFR estimates that are within 30% of measured GFR). RESULTS: The study included 1,222 older adults. The mean age of both the training cohort (n = 978) and the test cohort (n = 244) was 72 ± 6 years, with 544 (55.6%) and 129 (52.9%) males, respectively. The median bias of BPNN was 2.06 ml/min/1.73 m2, which was smaller than that of LMR (4.59 ml/min/1.73 m2; p = 0.03), and higher than that of the Asian modified CKD-EPI (-1.43 ml/min/1.73 m2; p = 0.02). The median bias between BPNN and each of CKD-EPI (2.19 ml/min/1.73 m2; p = 0.31), EKFC (-1.41 ml/min/1.73 m2; p = 0.26), BIS1 (0.64 ml/min/1.73 m2; p = 0.99), and MDRD (1.11 ml/min/1.73 m2; p = 0.45) was not significant. However, the BPNN had the highest precision IQR (14.31 ml/min/1.73 m2) and the greatest accuracy P30 among all equations (78.28%). At measured GFR < 45 ml/min/1.73 m2, the BPNN has highest accuracy P30 (70.69%), and highest precision IQR (12.46 ml/min/1.73 m2). The biases of BPNN and BIS1 equations were similar (0.74 [-1.55-2.78] and 0.24 [-2.58-1.61], respectively), smaller than any other equation. CONCLUSIONS: The novel BPNN tool is more accurate than the currently available creatinine-based GFR estimation equations in an older population and could be recommended for routine clinical use.

Modelling DTPA therapy following Am contamination in rats.

A major challenge in modelling the decorporation of actinides (An), such as americium (Am), with DTPA (diethylenetriaminepentaacetic acid) is the fact that standard biokinetic models become inadequate for assessing radionuclide intake and estimating the resulting dose, as DTPA perturbs the regular biokinetics of the radionuclide. At present, most attempts existing in the literature are empirical and developed mainly for the interpretation of one or a limited number of specific incorporation cases. Recently, several approaches have been presented with the aim of developing a generic model, one of which reported the unperturbed biokinetics of plutonium (Pu), the chelation process and the behaviour of the chelated compound An-DTPA with a single model structure. The aim of the approach described in this present work is the development of a generic model that is able to describe the biokinetics of Am, DTPA and the chelate Am-DTPA simultaneously. Since accidental intakes in humans present many unknowns and large uncertainties, data from controlled studies in animals were used. In these studies, different amounts of DTPA were administered at different times after contamination with known quantities of Am. To account for the enhancement of faecal excretion and reduction in liver retention, DTPA is assumed to chelate Am not only in extracellular fluids, but also in hepatocytes. A good agreement was found between the predictions of the proposed model and the experimental results for urinary and faecal excretion and accumulation and retention in the liver. However, the decorporation from the skeletal compartment could not be reproduced satisfactorily under these simple assumptions.

Application of ferromanganese functionalized biochar simultaneously reduces Cd and Pb uptake of wheat in contaminated alkaline soils.

The reduction of Cd and Pb accumulation in wheat grains grown on Cd and Pb contaminated alkaline soils is a pressing issue that needs to be solved. In this study, ferromanganese functionalized biochar (FM-BC) was used to remediate Cd and Pb contaminated alkaline soils and mitigate Cd and Pb accumulation in wheat grains. The immobilization capacity and mechanism of FM-BC were investigated by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) characterization and chemical analysis. Fe and Mn loaded on FM-BC improved the removal efficiencies of DTPA-Cd and DTPA-Pb in soil with DTPA-Cd removal of 22.99%- 52.04% (JM22) and 25.54%- 53.32 (AK58) and DTPA-Pb removal of 11.39%- 22.36% (JM22) and 5.38%- 13.00% (AK58). The FT-IR and XRD results indicated that the complexation and precipitation of Cd and Pb with the Fe-Mn oxides and the oxygen-containing functional groups on biochar surface stabilized the Cd and Pb in soil for the observation of Cd2Mn3O8, PbHPO4, CdCO3, and PbO2 on FM-BC isolated from contaminated soils. FM-BC with excellent adsorption capacity reduced the available Cd and Pb in the soil, therefore, thereby inhibiting the Cd and Pb accumulation in wheat. In the 3% FM-BC treatment, Cd and Pb contents in wheat grains were lower than 0.10 mg/kg and 0.20 mg/kg, respectively, reaching the national safety standards. And FM-BC increased the Fe, Mn, Na and Zn contents in wheat grains, and improved the growth and yield of wheat. These findings suggest that FM-BC can be considered a prospective and effective material for remediation of alkaline soils contaminated with Cd and Pb.

Efficacy of pentasodium diethylenetriamine pentaacetate in ameliorating anosmia post COVID-19.

BACKGROUND: COVID-19 has been frequently demonstrated to be associated with anosmia. Calcium cations are a mainstay in the transmission of odor. One of their documented effects is feedback inhibition. Thus, it has been advocated that reducing the free intranasal calcium cations using topical chelators such as pentasodium diethylenetriamine pentaacetate (DTPA) could lead to restoration of the olfactory function in patients with post-COVID-19 anosmia. METHODOLOGY: This is a randomized controlled trial that investigated the effect of DTPA on post-COVID-19 anosmia. A total of 66 adult patients who had confirmed COVID-19 with associated anosmia that continued beyond three months of being negative for SARS-CoV-2 infection. The included patients were randomly allocated to the control group that received 0.9 % sodium chloride-containing nasal spray or the interventional group that received 2 % DTPA-containing nasal spray at a 1:1 ratio. Before treatment and 30 days post-treatment, the patients' olfactory function was evaluated using Sniffin' Sticks, and quantitative estimation of the calcium cations in the nasal mucus was done using a carbon paste ion-selective electrode test. RESULTS: Patients in the DTPA-treated group significantly improved compared to the control group in recovery from functional anosmia to hyposmia. Additionally, they showed a significant post-treatment reduction in the calcium concentration compared to the control group. CONCLUSION: This study confirmed the efficacy of DTPA in treating post-COVID-19 anosmia.

Date palm-magnetized biochar for in-situ stabilization of toxic metals in mining-polluted soil: evaluation using single-step extraction methods and phytoavailability.

Mining activities provide a pathway for the entry and accumulation of various heavy metals in soil, which ultimately leads to severe environmental pollution. Utilization of various immobilizing agents could restore such contaminated soils. Therefore, in this study, date palm-derived biochars (BCs: produced at 300 °C, 500 °C and 700 °C) and magnetized biochars (MBCs) were employed to stabilize heavy metals (Cd, Pb, Cu and Zn) in mining polluted soil. Metal polluted soil was amended with BCs and MBCs at w/w ratio of 2% and cultivated with wheat (Triticum aestivum L.) in a greenhouse. After harvesting, dry and fresh biomass of plants were recorded. The soil and plant samples were collected, and the concentrations of heavy metals were measured after extracting with water, DTPA (diethylenetriaminepentaacetic acid), EDTA (ethylenediaminetetraacetic acid), and acetic acid. BCs and MBCs resulted in reduced metal availability and uptake, with higher fresh and dry biomass (>36%). MBCs showed maximum decrease (>70%) in uptake and shoot concentration of metals, as these reductions for Cd and Pb reached below the detection limits. Among all single-step extractions, the DTPA-extractable metals showed a significant positive correlation with shoot concentrations of tested metals. Thus, the synthesized BCs and MBCs could effectively be used for stabilizing heavy metals and improve plant productivity in multi-contaminated soils. However, future studies should focus on long term field trials to restore contaminated mining soils using modified biochars.

This study has demonstrated the performance of magnetized biochars for in-situ stabilization of toxic metals (Cd, Pb, Cu and Zn) in mining polluted soil by single extraction method. All the produced BCs and magnetized BCs showed great potential in immobilizing the metals and reducing their availability in soil, consequently decreasing their shoot concentration and plant uptake. Significant negative correlations were observed between soil pH and metal extraction from applied extraction methods such as water soluble, DTPA, and EDTA extractions. We found DTPA as a suitable extractant for investigating metal uptake in plant in multi-contaminated soils. Treatments with MBCs showed maximum decrease in plant uptake and concentration of studied metals. Thus, application of MBCs could efficiently immobilize soil heavy metals.