Biodistribution Analysis of Peptide-Coated Magnetic Iron Nanoparticles: A Simple and Quantitative Method.

Biodistribution tracks compounds or molecules of interest in vivo to understand a compound's anticipated efficacy and safety. Nanoparticles deliver nucleic acid and drug payloads and enhance tumor permeability due to multiple properties such as high surface area to volume ratio, surface functionalization, and modifications. Studying the in vivo biodistribution of nanoparticles documents the effectiveness and safety of nanoparticles and facilitates a more application-driven approach for nanoparticle development that allows for more successful translation into clinical use. In this study, we present a relatively simple method to determine the biodistribution of magnetic iron nanoparticles in mice. In vitro, cells take up branched amphiphilic peptide-coated magnetic nanobeads (BAPc-MNBs) like their counterparts, i.e., branched amphiphilic peptide capsules (BAPCs) with a hollow water-filled core. Both BAPc-MNBs and BAPCs have widespread applications as a nanodelivery system. We evaluated the BAPc-MNBs tissue distribution in wild-type mice injected intravenously (i.v.), intraperitoneally (i.p.), or orally gavaged to understand the biological interactions and to further the development of branched amphiphilic peptide-based nanoparticles. The magnetic nanoparticles allowed collection of the BAPc-MNBs from multiple organs by magnetic bead sorting, followed by a high-throughput screening for iron content. When injected i.v., nanoparticles were distributed widely to various organs before elimination from the system via the intestines in feces. The spleen accumulated the highest amount of BAPc-MNBs in mice administered NPs via i.v. and i.p. but not via oral gavage. Taken together, these data demonstrate that the magnetic sorting not only allowed quantification of the BAPc-MNBs but also identified the distribution of BAPc-MNBs after distinct administration methods.

Targeting FLT3-TAZ signaling to suppress drug resistance in blast phase chronic myeloid leukemia.

BACKGROUND: Although the development of BCR::ABL1 tyrosine kinase inhibitors (TKIs) rendered chronic myeloid leukemia (CML) a manageable condition, acquisition of drug resistance during blast phase (BP) progression remains a critical challenge. Here, we reposition FLT3, one of the most frequently mutated drivers of acute myeloid leukemia (AML), as a prognostic marker and therapeutic target of BP-CML. METHODS: We generated FLT3 expressing BCR::ABL1 TKI-resistant CML cells and enrolled phase-specific CML patient cohort to obtain unpaired and paired serial specimens and verify the role of FLT3 signaling in BP-CML patients. We performed multi-omics approaches in animal and patient studies to demonstrate the clinical feasibility of FLT3 as a viable target of BP-CML by establishing the (1) molecular mechanisms of FLT3-driven drug resistance, (2) diagnostic methods of FLT3 protein expression and localization, (3) association between FLT3 signaling and CML prognosis, and (4) therapeutic strategies to tackle FLT3+ CML patients. RESULTS: We reposition the significance of FLT3 in the acquisition of drug resistance in BP-CML, thereby, newly classify a FLT3+ BP-CML subgroup. Mechanistically, FLT3 expression in CML cells activated the FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway, which conferred resistance to a wide range of BCR::ABL1 TKIs that was independent of recurrent BCR::ABL1 mutations. Notably, FLT3+ BP-CML patients had significantly less favorable prognosis than FLT3- patients. Remarkably, we demonstrate that repurposing FLT3 inhibitors combined with BCR::ABL1 targeted therapies or the single treatment with ponatinib alone can overcome drug resistance and promote BP-CML cell death in patient-derived FLT3+ BCR::ABL1 cells and mouse xenograft models. CONCLUSION: Here, we reposition FLT3 as a critical determinant of CML progression via FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway that promotes TKI resistance and predicts worse prognosis in BP-CML patients. Our findings open novel therapeutic opportunities that exploit the undescribed link between distinct types of malignancies.

Efficiency Enhancement of Electro-Adsorption Desalination Using Iron Oxide Nanoparticle-Incorporated Activated Carbon Nanocomposite.

Capacitive deionization (CDI) technology is currently considered a potential candidate for brackish water desalination. In this study, we designed iron oxide nanoparticle-incorporated activated carbon (AC/Fe2O3) via a facile and cost-effective hydrothermal process. The as-synthesized material was characterized using several techniques and tested as electrodes in CDI applications. We found that the distinctive properties of the AC/Fe2O3 electrode, i.e., high wettability, high surface area, unique structural morphology, and high conductivity, resulted in promising CDI performance. The electrosorptive capacity of the AC/Fe2O3 nanocomposite reached 6.76 mg g-1 in the CDI process, with a high specific capacitance of 1157.5 F g-1 at 10 mV s-1 in a 1 M NaCl electrolyte. This study confirms the potential use of AC/Fe2O3 nanocomposites as viable electrode materials in CDI and other electrochemical applications.

A Personalized 3D-Printed Model for Obtaining Informed Consent Process for Thyroid Surgery: A Randomized Clinical Study Using a Deep Learning Approach with Mesh-Type 3D Modeling.

The aim of this study was to evaluate the usefulness of a personalized 3D-printed thyroid model that characterizes a patient's individual thyroid lesion. The randomized controlled prospective clinical trial (KCT0005069) was designed. Fifty-three of these patients undergoing thyroid surgery were randomly assigned to two groups: with or without a 3D-printed model of their thyroid lesion when obtaining informed consent. We used a U-Net-based deep learning architecture and a mesh-type 3D modeling technique to fabricate the personalized 3D model. The mean 3D printing time was 258.9 min, and the mean price for production was USD 4.23 for each patient. The size, location, and anatomical relationship of the tumor and thyroid gland could be effectively presented using the mesh-type 3D modeling technique. The group provided with personalized 3D-printed models showed significant improvement in all four categories (general knowledge, benefits and risks of surgery, and satisfaction; all p < 0.05). All patients received a personalized 3D model after surgery and found it helpful to understand the disease, operation, and possible complications and their overall satisfaction (all p < 0.05). In conclusion, the personalized 3D-printed thyroid model may be an effective tool for improving a patient's understanding and satisfaction during the informed consent process.

Nonvolatile memory thin-film transistors using biodegradable chicken albumen gate insulator and oxide semiconductor channel on eco-friendly paper substrate.

Nonvolatile memory thin-film transistors (TFTs) fabricated on paper substrates were proposed as one of the eco-friendly electronic devices. The gate stack was composed of chicken albumen gate insulator and In-Ga-Zn-O semiconducting channel layers. All the fabrication processes were performed below 120 °C. To improve the process compatibility of the synthethic paper substrate, an Al2O3 thin film was introduced as adhesion and barrier layers by atomic layer deposition. The dielectric properties of biomaterial albumen gate insulator were also enhanced by the preparation of Al2O3 capping layer. The nonvolatile bistabilities were realized by the switching phenomena of residual polarization within the albumen thin film. The fabricated device exhibited a counterclockwise hysteresis with a memory window of 11.8 V, high on/off ratio of approximately 1.1 × 10(6), and high saturation mobility (µsat) of 11.5 cm(2)/(V s). Furthermore, these device characteristics were not markedly degraded even after the delamination and under the bending situration. When the curvature radius was set as 5.3 cm, the ION/IOFF ratio and µsat were obtained to be 5.9 × 10(6) and 7.9 cm(2)/(V s), respectively.

Potential consolidation-induced NAPL migration from coal tar impacted river sediment under a remedial sand cap.

Subaqueous sediment, if capped for remediation purposes, may undergo consolidation due to the increased effective weight of the capping material. The standard Atterberg limits test and a modified drained three-dimensional consolidation test (DTCT) were performed on sediment collected from a river adjacent to a former manufactured gas plant site that contains high concentrations of coal tar. The plastic limit of five sediment samples ranged between 72 and 89%, and the liquid limit ranged between 123 and 194%. The plasticity index ranged from 51 to 122%, with the values among the sediments correlating with the coal tar content (r(2)=0.93). DTCT experiment was performed on 5 cm sediment overlain with 5 cm sand to a maximum applied effective cell pressure of 41.4 kPa. Consolidation increased almost linearly at lower pressures (<13.8 kPa); however, as higher pressures were imposed, the ratio of consolidation per applied pressure decreased. The results of this study suggest that porewater advection, resulting from sediment consolidation, will occur from the sediment to the capping material. Because this water will contain numerous polycyclic aromatic hydrocarbons, measures, such as adding sorptive materials, should be taken to reduce the flux of these compounds.