Intratumoral Cancer Chemotherapy with a Carrier-Based Immunogenic Cell-Death Eliciting Platinum (IV) Agent

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see doi.org/10.1021/acs.molpharmaceut.0c00781.A carrier-based, immunogenic cell death (ICD)-eliciting platinum(IV) chemotherapeutic agent was synthesized via complexation between an axially derivatized Pt(IV)-tocopherol and hyaluronan (HA)–tocopherol nanocarrier. The resultant HA-Pt(IV) complex demonstrated antiproliferative activity and induced calreticulin translocation, an indicator of ICD, in murine and human head and neck cancer (HNC) cells. The intratumorally administered HA-Pt(IV) treatments were tolerable and efficacious in both immunocompetent and immunodeficient mice with HNC, partially because of the direct cytotoxicity. Superior efficacy and survival were observed in the immunocompetent group, suggesting a possible Pt(IV)-induced immunological response, which would only manifest in animals with an intact immune system. Subsequent imaging of tumor tissues demonstrated increased macrophage infiltration in the HA-Pt(IV)-treated tumors compared to the nontreated controls and the cisplatin-treated tumors, suggesting favorable inflammatory activation. RNA sequencing of HA-Pt(IV)-treated tumors indicated that carbohydrate and vitamin metabolisms were the most important Kyoto Encyclopedia of Genes and Genomes pathways, and molecular function, biological process, and cellular component were highly enriched gene ontology categories

OC6 project phase III : validation of the aerodynamic loading on a wind turbine rotor undergoing large motion caused by a floating support structure

This paper provides a summary of the work done within Phase III of the Offshore Code Comparison, Collaboration, Continued, with Correlation and unCertainty project (OC6), under International Energy Agency Wind Task 30. This phase focused on validating the aerodynamic loading on a wind turbine rotor undergoing large motion caused by a floating support structure. Numerical models of the Danish Technical University 10-MW reference wind turbine were validated using measurement data from a 1:75 scale test performed during the UNsteady Aerodynamics for FLOating Wind (UNAFLOW) project and a follow-on experimental campaign, both performed at the Politecnico di Milano wind tunnel. Validation of the models was performed by comparing the loads for steady (fixed platform) and unsteady wind conditions (harmonic motion of the platform). For the unsteady wind conditions, the platform was forced to oscillate in the surge and pitch directions under several frequencies and amplitudes. These oscillations result in a wind variation that impacts the rotor loads (e.g., thrust and torque). For the conditions studied in these tests, the system mainly described a quasi-steady aerodynamic behavior. Only a small hysteresis in airfoil performance undergoing angle of attack variations in attached flow was observed. During the experiments, the rotor speed and blade pitch angle were held constant. However, in real wind turbine operating conditions, the surge and pitch variations would result in rotor speed variations and/or blade pitch actuations depending on the wind turbine controller region that the system is operating. Additional simulations with these control parameters were conducted to verify the fidelity between different models. Participant results showed in general a good agreement with the experimental measurements and the need to account for dynamic inflow when there are changes in the flow conditions due to the rotor speed variations or blade pitch actuations in response to surge and pitch motion. Numerical models not accounting for dynamic inflow effects predicted rotor loads that were 9 % lower in amplitude during rotor speed variations and 18 % higher in amplitude during blade pitch actuations

Two-Dimensional Numerical Modeling and Design Optimization of a Moored Buoy Under Ice Load

A single point mooring (SPM) system is one of the possible mooring systems in the field of Arctic floating production. It consists of a moored buoy to provide its anchoring unit with the capacity of mooring and ice sheltering. In the preliminary design phase, the performance of the mooring buoy must be assessed. This can be done by numerical modeling. This thesis provides a model for the two-dimensional numerical simulation of a moored buoy under ice loading, and it optimizes the buoy design based on the results of the numerical simulation.The model is constructed based on the discrete element method (DEM), where the elements consist of the elements describing the level ice, and one element describing the buoy. The numerical model is capable of simulating several ice-structure interaction mechanisms, including the ice compressive failure, the ice bending failure, and friction.The model consists of three parts. A compliant contact formulation describes the behavior of contacts between elements. Contact forces are solved implicitly using a Lagrange multiplier formulation. Lastly, the mooring system is described using the catenary equation. The model is validated against a number of analytical solutions, demonstrating that the model is capable of simulating the buoy-ice interaction. An example of the buoy design optimization process is demonstrated. The optimization aims to obtain a concept design of a satisfactorily performing moored buoy with minimized dimensions under a specific ice condition. Design criteria were determined for the maximum pitch angle and the maximum horizontal displacement of the buoy. Given the desired design criteria, one can obtain the most optimized buoy design after several phases of selection.Offshore and Dredging Engineerin

Potential Application of Luteolin as an Active Antibacterial Composition in the Development of Hand Sanitizer Products

Antibacterial hand sanitizers could play a prominent role in slowing down the spread and infection of hand bacterial pathogens; luteolin (LUT) is potentially useful as an antibacterial component. Therefore, this study elucidated the antibacterial mechanism of LUT against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) and developed an antibacterial hand sanitizer. The results showed that LUT had excellent antibacterial activity against both E. coli (minimum inhibitory concentration (MIC) = 312.5 μg/mL, minimal bactericidal concentration (MBC) = 625 μg/mL), and S. aureus (MIC = 312.5 μg/mL, MBC = 625 μg/mL). Furthermore, LUT induced cell dysfunction in E. coli and S. aureus, changed membrane permeability, and promoted the leakage of cellular contents. Confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) analysis showed that LUT treatment affected cell structure and disrupted cell membrane integrity. The Fourier transform infrared analysis (FTIR) also confirmed that the LUT acted on the cell membranes of both E. coli and S. aureus. Overall, the application of LUT in hand sanitizer had better inhibition effects. Therefore, this study could provide insight into expanding the application of LUT in the hand sanitizer markets

High-Temperature-Sensing Smart Bolt Based on Indium Tin Oxide/In₂O₃ Thin-Film Thermocouples with Nickel-Based Single-Crystal Superalloy via Screen Printing

In this study, thin-film thermocouples (TFTCs) were combined with a smart bolt to design a smart bolt that can directly test high temperature in service monitoring and parameter calculation for gas turbine structure design. The first-principles calculation was used to analyze the design of the surface properties of nickel-based alloys and insulating layers, and finite element analysis was used to optimize dimension parameters by controlling the thermal stress matching of insulating layers and sensitive layers. The effect of the glass powder with different particle sizes on the microstructure of the ITO and In2O3 films was studied via SEM. The preferred particle size of the additive glass powder is 400 nm. The XRD pattern shows the (222) peak has the highest intensity. The intensities of the (222) and (622) peaks increase after the heat treatment. The calibration results show that the average Seebeck coefficient of the TFTCs can reach 64.9 μV/°C at 1100 °C with a maximum voltage of 71.4 mV. The repeatability error of the cycles of the sensor after heat treatment is ±1.05%. The repeatability of the sensor is up to 98.95%. The smart bolts were tested for application in small aero engines. It can be seen that under the impact of 1000 °C, the thermal response of the prepared smart bolt is better than that of the K-type armored thermocouple, and the thermal balance is achieved faster. The intelligent bolt sensor proposed in this work has better engineering application prospects owing to its convenience of installation in harsh environments

Dynamic changes of D-dimer and neutrophil-lymphocyte count ratio as prognostic biomarkers in COVID-19

BACKGROUND: Since December 2019, the outbreak of COVID-19 caused a large number of hospital admissions in China. Many patients with COVID-19 have symptoms of acute respiratory distress syndrome, even are in danger of death. This is the first study to evaluate dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio (NLR) as a prognostic utility in patients with COVID-19 for clinical use. MEHTODS: In a retrospective study, we collected data from 349 hospitalized patients who diagnosed as the infection of the COVID-19 in Wuhan Pulmonary Hospital. We used ROC curves and Cox regression analysis to explore critical value (optimal cut-off point associated with Youden index) and prognostic role of dynamic changes of D-Dimer and NLR. RESULTS: Three hundred forty-nine participants were enrolled in this study and the mortality rate of the patients with laboratory diagnosed COVID-19 was 14.9%. The initial and peak value of D-Dimer and NLR in deceased patients were higher statistically compared with survivors (P < 0.001). There was a more significant upward trend of D-Dimer and NLR during hospitalization in the deceased patients, initial D-Dimer and NLR were lower than the peak tests (MD) -25.23, 95% CI: − 31.81- -18.64, P < 0.001; (MD) -43.73, 95% CI:-59.28- -31.17, P < 0.001. The test showed a stronger correlation between hospitalization days, PCT and peak D-Dimer than initial D-Dimer. The areas under the ROC curves of peak D-Dimer and peak NLR tests were higher than the initial tests (0.94(95%CI: 0.90–0.98) vs. 0.80 (95% CI: 0.73–0.87); 0.93 (95%CI:0.90–0.96) vs. 0.86 (95%CI:0.82–0.91). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR was 0.73 mg/L, 3.78 mg/L,7.13 and 14.31 respectively. 35 (10.03%) patients were intubated. In the intubated patients, initial and peak D-Dimer and NLR were much higher than non-intubated patients (P < 0.001). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR in prognosticate of intubation was 0.73 mg/L, 12.75 mg/L,7.28 and 27.55. The multivariable Cox regression analysis showed that age (HR 1.04, 95% CI 1.00–1.07, P = 0.01), the peak D-Dimer (HR 1.03, 95% CI 1.01–1.04, P < 0.001) were prognostic factors for COVID-19 patients’ death. CONCLUSIONS: To dynamically observe the ratio of D-Dimer and NLR was more valuable during the prognosis of COVID-19. The rising trend in D-Dimer and NLR, or the test results higher than the critical values may indicate a risk of death for participants with COVID-19

NSC-derived exosomes enhance therapeutic effects of NSC transplantation on cerebral ischemia in mice

Transplantation of neural stem cells (NSCs) has been proved to promote functional rehabilitation of brain lesions including ischemic stroke. However, the therapeutic effects of NSC transplantation are limited by the low survival and differentiation rates of NSCs due to the harsh environment in the brain after ischemic stroke. Here, we employed NSCs derived from human induced pluripotent stem cells together with exosomes extracted from NSCs to treat cerebral ischemia induced by middle cerebral artery occlusion/reperfusion in mice. The results showed that NSC-derived exosomes significantly reduced the inflammatory response, alleviated oxidative stress after NSC transplantation, and facilitated NSCs differentiation in vivo. The combination of NSCs with exosomes ameliorated the injury of brain tissue including cerebral infarction, neuronal death, and glial scarring, and promoted the recovery of motor function. To explore the underlying mechanisms, we analyzed the miRNA profiles of NSC-derived exosomes and the potential downstream genes. Our study provided the rationale for the clinical application of NSC-derived exosomes as a supportive adjuvant for NSC transplantation after stroke