Mesenchymal stem cells (MSCs) have attracted increasing attention as vehicles for cancer treatment. Herein, MSC-based synergistic oncotherapy strategy is presented for the first time. To achieve this ...goal, yolk–shell structured gold nanorod embedded hollow periodic mesoporous organosilica nanospheres (GNR@HPMOs) with high paclitaxel (PTX) loading capability and excellent photothermal transfer ability upon near-infrared (NIR) light irradiation are first prepared. Cytotoxicity and migration assays show that the viability and tumor-homing capability of MSCs are well-retained after internalization of high content of PTX loaded GNR@HPMOs (denoted as GNR@HPMOs-PTX). In vitro experiments show the GNR@HPMOs-PTX loaded MSCs (GNR@HPMOs-PTX@MSCs) possess synergistic chemo–photothermal killing effects for breast cancer cells. Also, photoacoustic imaging shows that the MSCs can improve dispersion and distribution in tumor tissue for GNR@HPMOs-PTX after intratumoral injection. In vivo experiments in breast cancer model of nude mice further demonstrate that the GNR@HPMOs-PTX@MSCs significantly inhibit tumor growth, suggesting their great potential for synergistic therapy of cancer.
Objective Selenium is an essential micronutrient and a type of dietary antioxidant. This study aimed to investigate the associations of dietary selenium intake with the risk of human chronic disease ...cardiovascular disease (CVD), diabetes mellitus (DM), and cancer and mortality among US general adults. Methods The dietary and demographic data in this study were collected from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Death outcomes were determined by associating with the National Death Index (NDI) records as of December 31, 2019. Logistic regression analyses were used to investigate the relationship of selenium intake with the risk of CVD, DM, and cancer. The effect of dietary selenium on all-cause and disease-specific mortality was estimated with restricted cubic spline (RCS) curves based on the univariate and multivariate Cox proportional hazard models. Results Among the 25,801 participants, dietary selenium intake was divided into quintiles (Q1–Q5). After covariate adjustment, the results showed that the participants with higher quintiles (Q4 and Q5) of selenium intake tended to have a low risk of CVD (OR = 0.97, 95% CI: 0.96, 0.99; OR = 0.98, 95% CI: 0.97, 1.00, respectively). Moreover, the RCS curves showed a significant nonlinear association between selenium intake and the risk of all-cause (with a HR of 0.82, 95% CI: 0.68, 0.99) and DM-specific mortality (with the lowest HR of 0.30; 95% CI, 0.12–0.75). Furthermore, we conducted a subgroup analysis and found a negative correlation between the highest quartile of selenium intake and all-cause mortality among participants aged 50 and above (HR = 0.75, 95% CI: 0.60–0.93, p = 0.009). Conclusion Our results indicated that a moderate dietary selenium supplement decreased the risk of CVD and displayed a nonlinear trend in association with the risk of all-cause and DM-specific mortality among US adults. In addition, we found that participants aged 50 and older may benefit from higher selenium intake. However, these findings still need to be confirmed through further mechanism exploration.
In view of the problems existing in the field application of eddy current tools, the research on eddy current tools drainage gas recovery was carried out.Based on Fluent software and ground ...experiments, the optimal structure size of the eddy current drainage gas production tool is determined as follows: the wing height of the helix is 1.5mm, the diameter of the helix is 50mm, the wing width of the helix is 2mm, and the helix Angle is 55°, which provides reference for field application.
In order to investigate the evolution of oxide film on T91 steel, oxidation tests were conducted in water vapor atmosphere at 750 °C. The phase compositions and microstructures of the oxide scales ...for early stage oxidation were investigated by using glancing angle XRD and SEM equipped with EDS. The results showed that during the initial oxidation stage Cr-rich oxide film formed and then it covered the sample surface rapidly. The initial Cr-rich oxide film was mainly composed of FeCr
2
O
4
, (Fe,Cr)
2
O
3
and Fe
2
O
3
. This oxide film acted as a barrier against outward diffusion of iron and inward diffusion of oxygen. During the initial oxidation stage, chromium in the sample surface was consumed gradually, and then a large amount of iron ions penetrated the oxide film and diffused rapidly to the sample surface, resulting in forming an outer “non-protective” Fe
2
O
3
layer.
Abstract With a focus on the issue of drill pipe failure brought on by the interaction of tension and torsion in deep and ultra-deep wells, the yield limit curve of the pipe body and joints under the ...combination of tension and torsion was drawn. According to the practice of DNV-RP-F201, it was investigated how temperature affected drill pipe strength. The findings demonstrate that as temperature increases, both yield and tensile strength decrease linearly, and the decreasing range gradually decreases when temperature exceeds 140°C, and yield strength decreases by 31.91% in 140°C. Under the conditions of the same yield strength and outer diameter, the larger the thickness of the drill pipe body is, the higher its tensile strength and torsional strength are. The resulting yield limit curve covers a wider range. As the temperature increases, the yield limit elliptic curves of titanium alloy drill pipes with various wall thicknesses gradually shrink. This work presents the foundation for the strength research of titanium alloy drill pipe under tension and torsion load.
A novel cerium-tannic acid passivation treatment was performed on galvanized steel. The corrosion resistance of cerium-tannic passivated samples was tested by dropping test with 0.5 wt.% CuSO
4
...aqueous solution. The mass loss per unit area of passivated samples was measured after the corrosion in 0.5 mol/L NaCl + 0.005 mol/L H
2
SO
4
at room temperature for 96 h. The electrochemical behaviors of cerium, tannic acid, and cerium-tannic acid passivated samples on galvanized steel in 0.5 mol/L NaCl solution were investigated by polarization curves and electrochemical impendence spectra. The corrosion equivalent circuit was established according to the impedance characteristics. The results show that cerium-tannic acid treated samples exhibit better corrosion resistance than the sole cerium or tannic acid treated samples under the same condition. The mechanism of synergistic effect for cerium-tannic acid passivation on galvanized steel was discussed.
Purpose
18
F-Alfatide II has been translated into clinical use and been proven to have good performance in identifying breast cancer. In this study, we investigated
18
F-Alfatide II for evaluation of ...axillary lymph nodes (ALN) in breast cancer patients and compared the performance with
18
F-FDG.
Methods
A total of 44 female patients with clinically suspected breast cancer were enrolled and underwent
18
F-Alfatide II and
18
F-FDG PET/CT within a week. Tracer uptakes in ALN were evaluated by visual analysis, semi-quantitative analysis with maximum standardized uptake value (SUV
max
), mean standardized uptake value (SUV
mean
), and SUV
max
ratio of target/non-target (T/NT).
Results
Among 44 patients, 37 patients were pathologically diagnosed with breast cancer with metastatic (17 cases) or non-metastatic (20 cases) ALN. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of visual analysis were 70.6%, 90%, 81.1%, 85.7%, and 78.3% for
18
F-Alfatide II, 64.7%, 90%, 78.4%, 84.6%, and 75% for
18
F-FDG, respectively. By combining
18
F-Alfatide II and
18
F-FDG, the sensitivity significantly increased to 82.4%, the specificity was 85%, the accuracy increased to 83.8%, the PPV was 82.4%, and the NPV significantly increased to 85.0%. Three cases of luminal B subtype were false negative for both
18
F-Alfatide II and
18
F-FDG. The other 2 false negative cases of
18
F-Alfatide II were triple-negative subtype and 3 false negative cases of
18
F-FDG were luminal B subtype too. The AUCs of three semi-quantitative parameters (SUV
max
, SUV
mean
, T/NT) for
18
F-Alfatide II were between 0.8 and 0.9, whereas those for
18
F-FDG were more than 0.9.
18
F-Alfatide II T/NT had the highest Youden index (76.5%), specificity (100%), accuracy (89.2%), and PPV (100%) among these semi-quantitative parameters.
18
F-Alfatide II uptake as well as
18
F-FDG uptake in metastatic axillary lymph nodes (MALN) was significantly higher than that in benign axillary lymph nodes (BALN). Both
18
F-Alfatide II and
18
F-FDG did not show difference in primary tumor uptake irrespective of ALN status.
Conclusion
18
F-Alfatide II can be used in breast cancer patients to detect metastatic ALN, however, like
18
F-FDG, with high specificity but relatively low sensitivity. The combination of
18
F-Alfatide II and
18
F-FDG can significantly improve sensitivity and NPV.
18
F-Alfatide II T/NT may serve as the most important semi-quantitative parameter to evaluate ALN.
The hot-deformation behavior of the as-cast Mn18Cr18N high-nitrogen austenitic stainless steel, produced with the electroslag-remelting metallurgical technology, was studied using ...isothermal-compression tests in a temperature range of 1223–1473 K) and a strain-rate range of 0.001–1 s–1). The flow-stress curves of the Mn18Cr18N steel were obtained under different hot-deformation conditions. By establishing the hyperbolic sine-law Zener-Hollomon equation, the hot-deformation activation energy of the Mn18Cr18N steel was obtained. Based on the mechanism of dislocation evolution, a physically-based constitutive model was established. In addition, the expression of the dynamic-recovery coefficient of the model was modified. Compared with the model before the modification, the modified constitutive model could effectively improve the prediction accuracy of the flow stress for the as-cast Mn18Cr18N austenitic stainless steel.
Chinfloxacin hydrochloride is a novel tricyclic fluorinated quinolone in development for treatment of conventional and biothreat infections. This first-in-human randomized study in Chinese healthy ...subjects was divided into 5 parts. Part A was a single-ascending-dose study to assess safety and tolerability of chinfloxacin. The single-dose pharmacokinetic study, a food effect study, and a multiple-dose pharmacokinetics study were conducted in parts B, C, and D, respectively. Part E was a randomized, placebo-controlled and positive-control single-dose, crossover study to evaluate the effect of chinfloxacin on thorough electrocardiographic QT/corrected QT (QTc) interval. The results suggest that single and multiple oral administrations of chinfloxacin were well tolerated. The observed adverse events (AEs) were dizziness, nausea, weakness, photosensitive dermatitis, and increased frequency of defecation. All AEs were mild and were resolved spontaneously without any treatment. The time to peak plasma concentration (
and
, respectively) was about 2 h, and the half-life was 14 to 16 h. Food slightly affected the drug's rate and extent of absorption, increasing the
from 1.60 to 2.59 h and reducing the
by 13.6% and area under the concentration-time curve by 8.95%. Chinfloxacin at 400 mg had no effect on prolongation of QT/QTc intervals. Although 600 mg chinfloxacin had a mild effect on the prolongation of the QT/QTc interval, the effect was less pronounced than that of the positive control, 400 mg moxifloxacin. The pharmacokinetics and safety profiles of chinfloxacin in healthy Chinese volunteers support its once-daily dosing in future clinical investigations. (This study has been registered at www.ChiCTR.org.cn under identifiers ChiCTR-TRC-10001619 for parts A to D and ChiCTR1800015906 for part E.).
Nemonoxacin, a nonfluorinated quinolone, has been approved in Taiwan and mainland China for the treatment of bacterial infection. Whether nemonoxacin is associated with the adverse events of other ...quinolones, such as the risk for QT-interval prolongation, which has led to the withdrawal of several fluoroquinolones from the market, needs to be elucidated.
The effects of nemonoxacin on thorough QT/QTc interval was investigated in this randomized, placebo- and positive-controlled crossover study conducted according to the International Conference on Harmonisation E14 guideline. Forty-eight healthy adults received a single oral dose of nemonoxacin 500 mg (therapeutic dose), nemonoxacin 750 mg (supratherapeutic dose), moxifloxacin 400 mg (positive control), or placebo in 1 of 4 cohorts (Williams Latin square design) in the fasted condition. After a 7-day washout, 6 male and 6 female subjects were orally administered a 500-mg dose of nemonoxacin after high-fat food intake. The primary end point was the change in QT interval corrected for heart rate using the Fridericia formula (QTcF). The secondary end point was the change in QT interval corrected for heart rate using the Bazett formula (QTcB).
The study revealed that nemonoxacin was classified as not likely dangerous at the therapeutic dose (500 mg) and as potentially dangerous at the supratherapeutic dose (750 mg). The Tmax of nemonoxacin was 1 to 2 hours after administration, and the elimination half-life was 5 to 7 hours, in the fasted conditions. High-fat food intake had significant effects on the Tmax, Cmax, AUC0–∞, and QT/QTc interval of nemonoxacin compared with these values in the fasted condition. A correlation between QTcF and the plasma drug concentration of nemonoxacin was not observed.
Nemonoxacin at the clinically therapeutic and supratherapeutic doses had a prolongation effect on QT/QTc. ClinicalTrials.gov identifier: NCT03362853.
PDF
