CFD simulation of cannabidiol delivery through microneedle patches.

This study investigates the efficiency and influence of microneedle parameters, specifically Needle Point Angle (a) and Needle Height (h), on the diffusion of Cannabidiol (CBD) across varying skin depths. Utilizing the Latin Hypercube Sampling method, twelve distinct cases were analyzed. Observations reveal a consistent high concentration of CBD delivered via the microneedle patch, with a notable decrease in concentration as the depth increases, displaying a non-linear trend. Multivariate polynomial regression offers a quantitative relationship between the variables, with the third-order bivariate fitting providing the most accurate representation. Compared to other CBD delivery mechanisms, microneedle patches present enhanced CBD concentrations, circumventing challenges faced by other methods such as dosage inaccuracy, systemic absorption issues, and CBD degradation. The results highlight the potential of microneedle patches as a promising avenue for optimized transdermal drug delivery.

A ternary model of proton therapy based on boron medium radiosensitization and enhancement paths: a Monte Carlo simulation.

Background: To overcome proton therapy limitations [low linear energy transfer (LET) radiation with a relative biological effectiveness (RBE) typically ranging from 1.1 to 1.2], radiosensitization techniques can be employed to increase the radiosensitivity of tumor cells and improve the effectiveness of radiation therapy. In this study, we suggest using a boron-based medium to overcome the biological limitations of proton therapy. By inducing the hydrogen-boron fusion reaction (p + 11B → 3α) of incident protons and capturing thermal neutrons [10B + n → 7Li3+ (0.84 MeV) + 4He2+ (1.47 MeV) + γ (0.477 MeV)], high LET α particles can be released. We propose a "ternary" radiotherapy model to enhance the biological effect of proton therapy. Methods: Using Monte Carlo simulation, the possibility of interacting low-energy proton beams with 11B and thermal neutrons with 10B to produce α particles with higher RBE to enhance the biological effect of proton radiotherapy were investigated. And the number and location of α particles and thermal neutrons produced by the interaction of protons with natural boron had also been studied. Results: Under the basic principle of the "ternary" radiotherapy model, comparative analyses of neutrons and α particles produced by proton beams of different energies incident on the phantoms, which were composed of boron isotopes of different concentrations in proportion to the phantoms, have shown that the α particle yield decreased with decreasing boron doping concentration, whereas the neutron yield increased with decreasing boron doping concentration. The distribution of thermal neutrons and α particles in the longitudinal direction of the proton beam were also studied, and it was found that the number of α particles produced was high at high boron concentrations, and the locations of α and thermal neutrons were close to the treatment target. Conclusions: The proton therapy ternary model is theoretically feasible from the perspective of mathematical analysis and Monte Carlo simulation experiments.

Equation of state of Iridium: from insight of ensemble theory.

The equations of state (EOS) of Iridium are, for the first time, obtained by solving the high-dimension integral of partition function based on a recently developed approach of ultrahigh efficiency and precision without any artificial parameter, and the deviation of 0.25% and 1.52% from the experiments was achieved respectively for the isobaric EOS in a temperature range of 300 K-2500 K and the isothermal EOS at 300 K up to 300 GPa. Specific comparisons show that the deviation of EOS based on harmonic approximation even including anharmonic effect, manifests worse than ours by several times or even one order of magnitude, indicating that ensemble theory is the very approach to understand the thermodynamic properties of condensed matter.

Enhancing the phase stability of ceramics under radiation via multilayer engineering.

In metallic systems, increasing the density of interfaces has been shown to be a promising strategy for annealing defects introduced during irradiation. The role of interfaces during irradiation of ceramics is more unclear because of the complex defect energy landscape that exists in these materials. Here, we report the effects of interfaces on radiation-induced phase transformation and chemical composition changes in SiC-Ti3SiC2-TiC x multilayer materials based on combined transmission electron microscopy (TEM) analysis and first-principles calculations. We found that the undesirable phase transformation of Ti3SiC2 is substantially enhanced near the SiC/Ti3SiC2 interface, and it is suppressed near the Ti3SiC2/TiC interface. The results have been explained by ab initio calculations of trends in defect segregation to the above interfaces. Our finding suggests that the phase stability of Ti3SiC2 under irradiation can be improved by adding TiC x , and it demonstrates that, in ceramics, interfaces are not necessarily beneficial to radiation resistance.

Removal Mechanism of Oxide Layer on the Surface of Sn-0.4Ti Alloy for Quartz Glass Sealing.

The oxide layer on the surface of Sn-0.4Ti alloy and its removal mechanism were investigated by coalitional analyses, using XPS and TEM technologies. The results show that a compact SnO1.65 oxide layer of less than 4 nm in thickness exists on the surface of Sn-0.4Ti alloy. A large number of TiO2 nanoparticles with scale of several to tens of nanometers were grown in Sn-0.4Ti matrix by depleting SnO1.65 while welding at 800 °C. These nanoparticles were adhered to the interfacial layer between Sn-0.4Ti alloy and quartz glass, which was formed by the reaction of Sn-0.4Ti and SiO2 after SnO1.65 removal from the Sn-0.4Ti. This work may promote further works on Sn-Ti design to further improve the welding quality between Sn-Ti alloy and quartz glass, and also provide a feasible research idea to remove the oxide layer on the surfaces of solders.

Effect of fluoride on osteocyte-driven osteoclastic differentiation.

Excessive systemic uptake of inorganic fluorides causes disturbances of bone homeostasis. The mechanism of skeletal fluorosis is still uncertain. This study aimed to study the effect of fluoride on osteocyte-driven osteoclastogenesis and probe into the role of PTH in this process. IDG-SW3 cells seeded in collagen-coated constructs were developed into osteocyte-like cells through induction of mineral agents. Then, osteocyte-like cells were exposed to fluoride in the presence or absence of parathyroid hormone (PTH). Cell viability and their capacity to produce receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and sclerostin (SOST) were detected by MTT and Western blot assays, respectively. Finally, a transwell coculture system using osteocyte-like cells seeded in the low compartment, and osteoclast precursors added in the inserts was developed to observe the osteocyte-driven osteoclasogenesis response to fluoride with or without PTH, and the expression of molecules involved in this mechanism were measure by real time RT-PCR. Results showed that osteocytes withstood a toxic dose of fluoride, and yet PTH administration significantly reduced osteocytes viability. PTH amplified the effect of fluoride on the expression of osteoclastogenesis-related molecules in osteocyte, but did not enlarged the stimulating effect of fluoride on osteoclastogenesis drove by osteocyte coculture. Gene expression levels of TRAP, RANK, JNK and NFAtc1 significantly increased in fluoride affected osteoclast precursor cocultured with osteocyte-like cells. The impact of fluoride on osteocyte-driven osteoclast differentiation was stronger than that of PTH. In conclusion, osteocyte played a pivotal role on the mechanism underlying fluoride-affected osteoclastogenesis in which RANK-JNK-NFATc1 signaling pathway was involved, and PTH had a significant impact in this process.

Establishment and validation of a nomogram with intratumoral heterogeneity derived from 18F-FDG PET/CT for predicting individual conditional risk of 5-year recurrence before initial treatment of nasopharyngeal carcinoma.

BACKGROUND: Intratumoral heterogeneity has an enormous effect on patient treatment and outcome. The purpose of the current study was to establish and validate a nomogram with intratumoral heterogeneity derived from 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for prognosis of 5-Year progression-free survival (PFS) of patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 171 NPC patients who underwent pretreatment 18F-FDG PET/CT were retrospectively enrolled. Data was randomly divided into training cohort (n = 101) and validation cohort (n = 70). The clinicopathologic parameters and the following PET parameters were analyzed: maximum and mean standardized uptake value (SUVmax, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity index (HI, SUVmax/SUVmean) for primary tumor and maximal neck lymph node. Cox analyses were performed on PFS in the training cohort. A prognostic nomogram based on this model was developed and validated. RESULTS: For the primary tumor, MTV-2.5, TLG-2.5, MTV-70%, and TLG-70% were significantly correlated with PFS. For the maximal neck lymph node, short diameter and HI were significantly correlated with PFS. Among the clinicopathologic parameters, M stage was a significant prognostic factor for recurrence. In multivariate analysis, M stage (P = 0.006), TLG-T-70% (P = 0.002), and HI-N (P = 0.018) were independent predictors. Based on this prognostic model, a nomogram was generated. The C-index of this model was 0.74 (95% CI: 0.63-0.85). For the cross validation, the C-index for the model was 0.73 (95% CI: 0.62-0.83) with the validation cohort. Patients with a risk score of ≥111 had poorer survival outcomes than those with a risk score of 0-76 and 77-110. CONCLUSIONS: Intratumoral heterogeneity derived from 18F-FDG PET/CT could predict long-term outcome in patients with primary NPC. A combination of PET parameters and the TNM stage enables better stratification of patients into subgroups with different PFS rates.

Effects of Embedded Helium on the Microstructure and Mechanical Properties of Erbium Films.

A series of helium (He) charged nanograin-sized erbium (Er) films were deposited by direct current (DC)-magnetron sputtering with different He/Ar mixture gases. The microstructure and mechanical properties of He-charged Er films were investigated by X-ray diffraction (XRD), transmission electron microscopy (TEM), and nanoindentation. The helium concentrations in Er films, determined by elastic recoil detection analysis (ERDA), ranged from 0 to 49.6%, with the increase in He:Ar flow ratio up to 18:1. The XRD results show that the grain sizes of Er films decreased with and increase in He content. The embedded He atoms induced the formation of spherical nanometer He bubbles, and the diameter of the He bubbles increased with the He content. The hardness and Young's modulus increased and decreased with the decreasing grain sizes of polycrystalline Er-He films. The mechanisms of mechanical properties with respect to the grain size and He content were discussed based on the Hall-Petch formula and composite spheres model.

Does capitation prepayment based Integrated County Healthcare Consortium affect inpatient distribution and benefits in Anhui Province, China? An interrupted time series analysis.

OBJECTIVE: This study aims to compare the level and trend changes of inpatient and funds distribution, as well as inpatient benefits before and after the official operation of the ICHC in Anhui. METHODS: A total of 1,013,815 inpatient cases were collected from the hospitalisation database in two counties in Anhui Province, China, during the course of the study from January 2014 to June 2017. The effect of the reform was assessed beginning with its formal operation in February 2016. Longitudinal time series data were analysed using segmented linear regression of an interrupted time series analysis. RESULTS: The average hospitalisation expenses showed a decreasing trend and the actual compensation ratio increased significantly (p-value < 0.01). Most of the indicators in the two counties performed well, and the effect of ICHC policy was better in Funan County than in Dingyuan County. The distribution of inpatients and NRCMS funds outside the county after the reform in Dingyuan showed an increasing trend (0.27, 95%CI: 0.12 to 0.42, p-value < 0.01; 0.70, 95%CI: 0.32 to 1.09, p-value < 0.01) and the distribution of inpatients and NRCMS funds in THs showed a more obvious upward trend after the reform in Funan (0.44, 95%CI: 0.22 to 0.67, p-value < 0.001; 0.34, 95%CI: 0.23 to 0.45, p-value < 0.001). CONCLUSIONS: This study suggests that the ICHC policy provides effective strategies in promoting the integration of the healthcare delivery system in China. These strategies include strengthening family doctor signing service system and health management, developing telemedicine technology, reducing the weak points of the healthcare services, and introducing private hospitals to form new ICHCs.

Charged particle radiobiology beamline using tandem accelerator-based MeV protons and carbon ions: a pilot study on the track-end radiation quality, variable biological effectiveness and Bayesian beam dosimetry.

For in vitro cell irradiation using tandem accelerator-based MeV protons and carbon ions, by TOPAS simulation, a pilot study of performance evaluation is presented on a collimation beamline for 3 MeV protons and 10 MeV carbon ions from a 2 × 3 MV tandem accelerator. Based on the elements and source parameters, a collimated beam of 2.8 MeV protons or 2.5 MeV carbon ions, with 5.175 mm or 5.166 mm full width tenth maximum (FWTM), respectively, can be delivered to the target cell dish. TOPAS simulations and/or deterministic algorithms present a Bragg curve of linear energy transfer (LET) (10-70 keV µm-1) along a 138 µm range of the proton beam, and a declining LET of the carbon beam (900-100 keV µm-1) within 4 µm range. Based on the biophysical models for relative biological effectiveness (RBE) of protons, TOPAS RBE scorers presents a set of depth-variation curves of the proton RBE (for V79 and DU145 cells), linearly related to the Bragg curve of the proton LET. Based on the microdosimetric-kinetic (MK) theory, in the 4 µm range for a monolayer cell thickness, the mean RBEα (V79 cells) of the carbon ion beam is estimated as 3.612 (late S phase) and 1.737 (G 1/S phase) for the mean LET of 492 keV µm-1. For practical irradiations, a tunable proton RBE can be acquired by changing the thickness of the cell dish. For the low-energy high-fluence (rate) beams, indirect beam measurements are proposed to detect the proton-beam induced scattering/recoil protons from a beam-intercepting Mylar film, and the carbon-beam induced backscattered electrons from a gold-deposited Havar-foil beam window. Statistical dosimetry for the indirect measurement is established, using a Bayesian model based on the preset number of detection counts, by which the mean value of the whole-dish dose can be prescribed and the uncertainty introduced in the survival data can be corrected.

Enhanced Photoelectrochemical Activity of ZnO-Coated TiO2 Nanotubes and Its Dependence on ZnO Coating Thickness.

One-dimensional heterogeneous nanostructures in the form of ZnO-coated TiO2 nanotubes (ZnO/TiO2 NTs) were fabricated by atomic layer deposition of an ultrathin ZnO coating on electrochemical anodization-formed TiO2 nanotubes (NTs) with the thickness of ZnO coating being precisely controlled at atomic scale, and the photoelectrochemical activity of the fabricated ZnO/TiO2 NTs and the influence of ZnO coating and its thickness were studied. The structures of TiO2 NTs and ZnO coatings were characterized by X-ray diffraction, Raman backscattering spectroscopy, and transmission electron microscopy. The photoelectrochemical activity was studied through the measurements of electrochemical impendence, flat-band potential, and transient photocurrent density. The TiO2 NTs exhibit anatase structure, and the ZnO coatings are structured with hexagonal wurtzite. The photoelectrochemical activity of the ZnO/TiO2 NTs is strongly dependent on the thickness of ZnO coating. ZnO/TiO2 NTs with a thinner rather than a thicker ZnO coating exhibit better photoelectrochemical activity with reduced charge transfer resistance, increased negative flat-band potentials, and enhanced photocurrent densities. Under visible illumination, an increase of about 60 % in the photoelectrochemical activity is obtained for ZnO/TiO2 NTs with an about 2-nm-thick ZnO coating.

Evolution Law of Helium Bubbles in Hastelloy N Alloy on Post-Irradiation Annealing Conditions.

This work reports on the evolution law of helium bubbles in Hastelloy N alloy on post-irradiation annealing conditions. After helium ion irradiation at room temperature and subsequent annealing at 600 °C (1 h), the transmission electron microscopy (TEM) micrograph indicates the presence of helium bubbles with size of 2 nm in the depth range of 0-300 nm. As for the sample further annealed at 850 °C (5 h), on one hand, a "Denuded Zone" (0-38 nm) with rare helium bubbles forms due to the decreased helium concentration. On the other hand, the "Ripening Zone" (38-108 nm) and "Coalescence Zone" (108-350 nm) with huge differences in size and separation of helium bubbles, caused by different coarsening rates, are observed. The mechanisms of "Ostwald ripening" and "migration and coalescence", experimentally proved in this work, may explain these observations.