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To selectively target and treat murine melanoma B16BL6 tumors expressing αvβ3 integrin receptors, we engineered tumor-specific functional extracellular vesicles (EVs) tailored for the targeted delivery of antitumor drugs. This objective was achieved through the incorporation of a pH-responsive adjuvant, cyclic arginine-glycine-aspartic acid peptide (cRGD, serving as a tumor-targeting ligand), and 5-fluorouracil (5-FU, employed as a model antitumor drug). The pH-responsive adjuvant, essential for modulating drug release, was synthesized by chemically conjugating 3-(diethylamino)propylamine (DEAP) to deoxycholic acid (DOCA, a lipophilic substance capable of integrating into EVs' membranes), denoted as DEAP-DOCA. The DOCA, preactivated using N-(2-aminoethyl)maleimide (AEM), was chemically coupled with the thiol group of the cRGD-DOCA through the thiol–maleimide click reaction, resulting in the formation of cRGD-DOCA. Subsequently, DEAP-DOCA, cRGD-DOCA, and 5-FU were efficiently incorporated into EVs using a sonication method. The resulting tumor-targeting EVs, expressing cRGD ligands, demonstrated enhanced in vitro/in vivo cellular uptake specifically for B16BL6 tumors expressing αvβ3 integrin receptors. The ionization characteristics of the DEAP in DEAP-DOCA induced destabilization of the EVs membrane at pH 6.5 through protonation of the DEAP substance, thereby expediting 5-FU release. Consequently, an improvement in the in vivo antitumor efficacy was observed for B16BL6 tumors. Based on these comprehensive in vitro/in vivo findings, we anticipate that this EV system holds substantial promise as an exceptionally effective platform for antitumor therapeutic delivery. [ABSTRACT FROM AUTHOR]

In this study, we fabricated γ-cyclodextrin (γCD)-based nanoparticles (NPs) for dual antitumor therapy. First, γCD (the backbone biopolymer) was chemically conjugated with low-molecular-weight hyaluronic acid (HA; a tumoral CD44 receptor-targeting molecule) and 3-(diethylamino)propylamine (DEAP; a pH-responsive molecule), termed as γCD-(DEAP/HA). The obtained γCD-(DEAP/HA) self-assembled in aqueous solution, producing the γCD-(DEAP/HA) NPs. These NPs efficiently entrapped paclitaxel (PTX; an antitumor drug) and triiron dodecacarbonyl (FeCO; an endogenous cytotoxic gas molecule) via hydrophobic interactions between PTX and FeCO with the unprotonated DEAP molecules in γCD-(DEAP/HA) and a possible host–guest interaction in the γCD rings. The release of PTX and FeCO from the NPs resulted from particle destabilization at endosomal pH, probably owing to the protonation of DEAP in the NPs. In vitro studies using MCF-7 tumor cells demonstrated that these NPs were efficiently internalized by the cells expressing CD44 receptors and enhanced PTX/FeCO-mediated tumor cell apoptosis. Importantly, local light irradiation of FeCO stimulated the generation of cytotoxic CO, resulting in highly improved tumor cell death. We expect that these NPs have potential as dual-modal therapeutic candidates with enhanced antitumor activity in response to acidic pH and local light irradiation. [ABSTRACT FROM AUTHOR]

Background: It is necessary to develop a mechanism to estimate and analyze cumulative radiation risks from multiple CT exams in various clinical scenarios in children. Objective: To identify major contributors to high cumulative CT dose estimates using actual dose-length product values collected for 5 years in children. Materials and methods: Between August 2006 and July 2011 we reviewed 26,937 CT exams in 13,803 children. Among them, we included 931 children (median age 3.5 years, age range 0 days-15 years; M:F = 533:398) who had 5,339 CT exams. Each child underwent at least three CT scans and had accessible radiation dose reports. Dose-length product values were automatically extracted from DICOM files and we used recently updated conversion factors for age, gender, anatomical region and tube voltage to estimate CT radiation dose. We tracked the calculated CT dose estimates to obtain a 5-year cumulative value for each child. The study population was divided into three groups according to the cumulative CT dose estimates: high, ≥30 mSv; moderate, 10-30 mSv; and low, <10 mSv. We reviewed clinical data and CT protocols to identify major contributors to high and moderate cumulative CT dose estimates. Results: Median cumulative CT dose estimate was 5.4 mSv (range 0.5-71.1 mSv), and median number of CT scans was 4 (range 3-36). High cumulative CT dose estimates were most common in children with malignant tumors (57.9%, 11/19). High frequency of CT scans was attributed to high cumulative CT dose estimates in children with ventriculoperitoneal shunt (35 in 1 child) and malignant tumors (range 18-49). Moreover, high-dose CT protocols, such as multiphase abdomen CT (median 4.7 mSv) contributed to high cumulative CT dose estimates even in children with a low number of CT scans. Conclusion: Disease group, number of CT scans, and high-dose CT protocols are major contributors to higher cumulative CT dose estimates in children. [ABSTRACT FROM AUTHOR]

Background: Although the use of polytetrafluoroethylene (PTFE)-covered biliary stents has proven to be feasible for the treatment of benign and malignant biliary disease, less is known regarding the outcomes of percutaneous placement of a covered stent in patients with malignant duodenobiliary obstruction. Purpose: To investigate the technical and clinical efficacy of the percutaneous placement of a PTFE-covered biliary stent in patients with malignant duodenobiliary obstruction. Material and Methods: From April 2007 to September 2012, the medical records of 45 consecutive patients with malignant duodenobiliary obstruction were retrospectively reviewed. All percutaneous biliary stent deployment was performed using PTFE-covered stents, whereas duodenal stent insertion was performed either fluoroscopically or endoscopically using covered or uncovered stents. Results: Biliary stent deployment was technically successful in all patients. None of the stents migrated after deployment. Procedure-related minor complications, including self-limiting hemobilia, occurred in three (7%) patients. Successful internal drainage was achieved in 39 (87%) of the 45 patients. The median survival time after biliary stent placement was 62 days (95% confidence interval, 8-116 days), and the cumulative stent patency rates at 1, 3, 6, and 12 months were 96%, 92%, 75%, and 38%, respectively. The causes of biliary stent dysfunction included stent occlusion caused by a subsequently inserted duodenal stent (n = 7), food impaction (n = 3), and sludge incrustation (n = 1). One patient developed acute cholecystitis 131 days after biliary stent placement and underwent percutaneous transhepatic gallbladder drainage. Conclusion: Percutaneous insertion of a PTFE-covered stent is a safe and effective method for palliative treatment of patients with malignant duodenobiliary obstruction. If possible, subsequent biliary stent insertion is preferable in order to prevent possible biliary stent dysfunction caused by subsequent insertion of a duodenal stent. [ABSTRACT FROM AUTHOR]

In this study, bio-based thermoplastic polyurethane (TPU) for use in soft actuators is bio-based poly(ether-urethane) made using fermented corn, along with bio-derived compounds such as propane-1,3-diol (PDO) as a chain extender. Bio-based TPUs were obtained through a solvent-free one-shot synthesis method, and the effects of varying the [NCO]/[OH] molar ratio and type of isocyanates on chemical structure, thermal stability, and mechanical properties were investigated. The degree of phase separation (DPS) and state of hard segment (HS) / soft segment (SS) of TPU are important factors affecting the thermal and physical properties of the prepared film. These properties depend on the [NCO]/[OH] molar ratio and the type of isocyanates used for polymerization. The results showed that, when aromatic isocyanate was used, the degree of separation of the HS/SS was improved as the molar ratio increased. The average molecular weight and DPS as well as thermal and mechanical properties of 1-isocyanato-4-[(4-isocyanatophenyl)methyl]benzene (MDI)-based TPU samples are all higher than those of 1,1'-methylenebis(4-isocyanatocyclohexane) (H12MDI)-based TPU samples in spite of the lower HS content. These findings of this study are expected to contribute to the preparation of fused deposition modeling (FDM) 3D printing or 4D printing for shape memory polymer from bio-based TPU filaments for use in soft actuators with a shore hardness range of 59~84A. [ABSTRACT FROM AUTHOR]

[Display omitted] Under hydrostatic pressure, α-quartz (α-SiO 2) undergoes solid-state mechanical amorphization wherein the interpenetration of [SiO 4 ]2− tetrahedra occurs and the material loses crystallinity. This phase transformation requires a high hydrostatic pressure of 14 GPa because the repulsive forces resulting from the ionic nature of the Si–O bonds prevent the severe distortion of the atomic configuration. Herein, we experimentally and computationally demonstrate that e-beam irradiation changes the nature of the interatomic bonds in α-quartz and enhances the solid-state mechanical amorphization at nanoscale. Specifically, during in situ uniaxial compression, a larger permanent deformation occurs in α-quartz submicron pillars compressed during e-beam irradiation than in those without e-beam irradiation. Microstructural analysis reveals that the large permanent deformation under e-beam irradiation originates from the enhanced mechanical amorphization of α-quartz and the subsequent viscoplastic deformation of the amorphized region. Further, atomic-scale simulations suggest that the delocalized excess electrons introduced by e-beam irradiation move to highly distorted atomic configurations and alleviate the repulsive force, thus reducing the barrier to the solid-state mechanical amorphization. These findings deepen our understanding of electron–matter interactions and can be extended to new glass forming and processing technologies at nano- and microscale. [ABSTRACT FROM AUTHOR]

[Display omitted] • Conceptual 3D-printed NIR-responsive bullet was designed for synergistic cancer therapy. • Ti in PLA enhances radiopacity which enable image-guided therapy. • High photothermal efficiency of 3D-printed nBts allows synergistic chemo-photothermal therapy. • Structural customization of the nanodrug delivery platform was possible with 3D printing process. • This strategy serves to demonstrate the great potential for multimodal tumor therapies. Multimodal cancer treatment that combines anticancer drug delivery with other therapeutic strategies, such as photothermal therapy, has shown enormous potential for biomedical applications. However, traditional nanoscale photothermal conversion agents require complicated synthesis processes and lack biosafety, detectability, and mechanical reinforcement ability in the hyperthermia platform. Here, we engineered near-infrared laser (NIR)-responsive bullets as multifunctional nanodrug platforms via a three-dimensional (3D) printing process as an image-guided versatile chemo-photothermal cancer treatment platform. This customizable platform not only serves as a container for anticancer nanodrugs but also possesses excellent radiopacity and high photothermal conversion efficiency, merging on-demand anticancer nanodrug release and hyperthermia effect. Benefiting from the combined chemo-photothermal therapy, the 3D-printed platform showed enhanced cytotoxicity to cancer cells in vitro. Furthermore, in vivo results confirmed effective on-demand nanodrug release and synergistic inhibition of tumor growth upon NIR laser irradiation. 3D-printed NIR-responsive bullets can synergistically enhance anticancer efficiency while evading potential clinical application risks, offering great potential for multimodal cancer therapies. [ABSTRACT FROM AUTHOR]

Objectives: One objective was to evaluate the air trapping index (ATI), measured by inspiration/expiration CT, in COPD patients and nonsmokers. Another objective was to assess the association between the pulmonary function test (PFT) and CT parameters such as ATI or other indices, separately in the whole lung, in emphysema, and in hyperinflated and normal lung areas. Methods: One hundred and thirty-eight COPD patients and 29 nonsmokers were included in our study. The ATI, the emphysema index (EI), the gas trapping index (Exp -856) and expiration/inspiration ratio of mean lung density (E/Iratio of MLD) were measured on CT. The values of the whole lung, of emphysema, and of hyperinflated and normal lung areas were compared and then correlated with various PFT parameters. Results: Compared with nonsmokers, COPD patients showed a higher ATI in the whole lung and in each lung lesion (all P < 0.05). The ATI showed a higher correlation than EI with FEF, RV and RV/TLC, and was comparable to Exp -856 and the E/I ratio of MLD. The ATI of emphysema and hyperinflated areas on CT showed better correlation than the normal lung area with PFT parameters. Conclusions: Detailed analysis of density change at inspiration and expiration CT of COPD can provide new insights into pulmonary functional impairment in each lung area. Key Points: • COPD patients show significant air trapping in the lung. • The air trapping index is a comparable parameter to other CT indices. • Air trapping of emphysema and hyperinflated lung areas relates to functional loss. • The emphysema area changes more, with less air trapping than other areas. [ABSTRACT FROM AUTHOR]

Background: Imaging findings of bilateral pulmonary vein atresia have not been described. Objective: To describe cardiac CT findings and clinical outcomes of bilateral pulmonary vein atresia. Materials and methods: Three newborns with bilateral pulmonary vein atresia were encountered at our institution during a period of 8 years. We evaluated prenatal echocardiographic findings, clinical presentations, postnatal echocardiographic findings, chest radiographic findings, cardiac CT findings and clinical outcomes. Results: All newborns presented immediately after birth with severe cyanosis, respiratory distress and acidosis that were unresponsive to medical management. Prenatal and postnatal echocardiographic studies and chest radiography were misleading, inconclusive or nonspecific in making the diagnosis in these children; however cardiac CT clearly demonstrated atresia of the bilateral pulmonary veins with multiple small mediastinal collateral veins and pulmonary edema. Surgical treatments were not feasible for this anomaly. Their clinical outcomes were universally dismal and all infants died within 3 days. Conclusion: Cardiac CT provides an accurate diagnosis of bilateral pulmonary vein atresia and leads to prompt treatment decision in these children. [ABSTRACT FROM AUTHOR]