The multidrug resistance in tumor (MDR) is a major barrier to efficient cancer therapy. Modern pharmacological studies have proven that tetrandrine (TET) has great potential in reversing MDR. ...However, it has a series of medication problems in clinic such as poor water solubility, low oral bioavailability and short half-life in vivo. Aiming at the above problems, red blood cell membrane-camouflaged TET-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (RPTNs) had been developed. The RPTNs had spherical shell-core double layer structure with average particle size of 164.1 ± 1.65 nm and encapsulation efficiency of 84.1% ± 0.41%. Compared with TET-PLGA nanoparticles (PTNs), the RPTNs reduced RAW 264.7 macrophages' swallowing by 32% due to its retention of natural membrane proteins. The cumulative drug release of RPTNs was 81.88% within 120 h. And pharmacokinetic study showed that the blood half-life of RPTNs was 19.38 h, which was 2.95 times of free drug. When RPTNs of 2 μg/mL TET were administered in combination with adriamycin (ADR), significant MDR reversal effect was observed in drug-resistant cells MCF-7/ADR. In a word, the RPTNs hold potential to improve its efficacy and broaden its clinical application.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The accurate identification of the gas-liquid two-phase flow pattern within the impeller of a centrifugal pump is critical to develop a reliable model for predicting the gas-liquid two-phase ...performance of the centrifugal pump. The influences of the inlet gas volume fraction, the liquid phase flow rate and the pump rotational speed on the flow characteristics of the centrifugal pump were investigated experimentally. Four typical flow patterns in the impeller of the centrifugal pump, i.e., the bubble flow, the agglomerated bubble flow, the gas pocket flow and the segregated flow, were obtained, and the corresponding flow pattern maps were drawn. After oversampling based on the SMOTE algorithm, a four-layer artificial neural network model with two hidden layers was constructed. By selecting the appropriate network super parameters, including the neuron numbers in the hidden layer, the learning rate and the activation function, the different flow patterns in the centrifugal pump impeller were identified. The identification rate of the model increased from 89.91% to 94.88% when the original data was oversampled by the SMOTE algorithm. It is demonstrated that the SMOTE algorithm is an effective method to improve the accuracy of the artificial neural network model. In addition, the Kappa coefficient, the Macro-F1 and the Micro-F1 were 0.93, 0.95 and 0.95, respectively, indicating that the model established in this paper can well identify the flow pattern in the impeller of a centrifugal pump.
Curcumin (Cur) is a promising drug for neurological diseases. Nevertheless, the application of Cur has been limited due to its difficulty in penetrating blood-brain barrier (BBB). Intranasal drug ...delivery, a noninvasive alternative delivery of Cur, can effectively help Cur cross BBB and inert into central nervous system directly. Odorranalectin (OL) which is the smallest lectin can prolong the residence time of Cur in the nasal mucosa and promote cellular uptake. In this work, a nasal delivery system incorporating OL modified Cur-loaded nanoparticles (Cur-OL-NPs) was developed and expected to bypass BBB and promote the absorption of Cur. We conjugated OL to polyethylene glycol-poly (lactic-co-glycolic acid) (PEG-PLGA), and combined polyethylene glycol-poly (γ-benzyl-L-glutamate) (PEG-PBLG) and OL-PEG-PLGA to prepare nanoparticles to improve the stability, bioavailability and targeting of Cur. Compared with unmodified NPs, increased efficiency of Cur-OL-NPs cellular uptake by Calu-3 cells had been obtained with no severe toxicity. Furthermore, in vivo pharmacokinetic studies also showed that Cur-OL-NPs had higher relative bioavailability. Thus, it is concluded that the results indicated that OL-NPs as carriers of Cur had a promising future in nasal drug delivery system.
The torsional vibration characteristics of the hydro-generator set considering the electromagnetic and hydraulic vibration resources coupling are studied. The moment of rotation consists of water ...flow driving and magnetic torques caused by the air gap magnetic field in the generator rotor in the case of ignoring the mechanical friction. A coupling torque vibration model of hydro-generator shaft system was established. The model considered the coupling action of hydraulic and electromagnetic excitations, as well as the elastic effect of rotor spiders. The influences of the rotor moment inertia, rotor stiffness, and mass of turbine water added into the torsional natural vibration of the unit shaft system were studied. The effect of hydraulic excitation frequency on torsional vibration response was also investigated. The frequency response curves of shaft torque, torsional vibration angle, and electromagnetic torque were presented. The electromagnetic and hydraulic coupling resonance was studied when hydraulic excitation frequency was equal to zero and first-order frequencies. The excitation electric current and internal active power angle on torsional vibration was further analyzed. This study provides an analysis model and method considering the coupling of electromagnetic and hydraulic vibration resources for design and stable operation of water turbine generator sets.
The purpose of the paper is to clarify the serrated flow behavior and to explore the grain-size and strain-rate effects on serrations in coarse- and fine-grained FeMnC twin-induced plasticity (TWIP) ...steels at room temperature. Tensile tests were performed under extensometer-measured strain control, rather than under conventional cross-head displacement control, at strain rates ranging from 6 × 10
−6
to 6 × 10
−3
s
−1
. The results indicate that both the coarse- and fine-grained steels show different types of serrations, which depend on strain rate, and demonstrate a nonmonotonic strain-rate sensitivity of the critical strain for the onset of serrations, i.e., a positive strain-rate sensitivity of the critical strain in the high strain-rate region typified by type A serrations, and a negative strain-rate sensitivity in the low strain-rate region typified by type C ones. As compared to the coarse-grained steel, the fine-grained steel increases the critical strains, showing an inverse grain-size effect. The findings suggest that the fine-grained FeMnC TWIP steel suppresses the serrated flow, possibly due to the enhanced dynamic recovery associated with the decreased planar slip length in the fine-grained low stacking-fault-energy steel.
Background The aim of this study is to investigate the expression levels of ephrinB2 in patients with lower extremity peripheral arterial disease (PAD) and explore its association with the severity ...of the disease and the risk of amputation after endovascular revascularization. Methods During the period from March 2021 to March 2023, this study collected blood samples and clinical data from 133 patients diagnosed with lower extremity PAD and 51 healthy volunteer donors. The severity of lower extremity PAD patients was classified using the Rutherford categories. The expression of ephrin-B2 in plasma samples was detected using the Western Blotting. Results Compared to the control group, the levels of serum ephrinB2 in patients were significantly elevated ( p < 0.001). Moreover, the plasma EphrinB2 levels were positively correlated with white blood cell counts (r = 0.204, p = 0.018), neutrophil counts (r = 0.174, p = 0.045), and neutrophil-to-lymphocyte ratio (NLR) (r = 0.223, p = 0.009). Furthermore, the AUCs of plasma ephrinB2 level, NLR, and their combination as predictors for amputation events within 30 months after lower extremity PAD endovascular revascularization were 0.659, 0.730 and 0.811. In the high-ephrinB2 group, the incidence of amputation events within 30 months after endovascular revascularization was higher. Conclusions Plasma EphrinB2 levels may be linked to lower extremity PAD development, inflammation, and postoperative amputation. Combining EphrinB2 and NLR can improve amputation prediction accuracy after endovascular revascularization in lower extremity PAD patients.
Commercial virtual power plants (CVPP) connect the form of renewable energy resource portfolio to the power market and reduce the risk of the unstable operation of a single renewable energy. ...Combining different kinds of large-scale renewable energy in CVPP to provide capacity services like base load, peak shaving, and valley-filling, etc., for the system loads is an urgent problem to be solved. Therefore, it is valuable to analyze the capacity allocation ratio of the CVPP to maximize the utilization of all kinds of energy, especially for the large-scale multi-energy base. This paper proposed a multi-energy coordinated operation framework by considering various load demands, including base load and peak shaving for the capacity allocation of CVPP based on the world’s largest renewable energy resource base on the upstream area of the Yellow River. The main procedures of this framework are as follows: (1) A paratactic model satisfying base load and peak shaving is proposed to determine the ability of the CVPP operation model’s capacity services to meet the different demands of the power system load. (2) A hybrid dimension reduction algorithm with a better convergence rate and optimization effect solves the proposed paratactic model based on the ReliefF and the Adaptive Particle Swarm Optimization (APSO). The results show that the large-scale CVPP with different compositions can achieve both of the goals of a stable base load output and stable residual load under different weather conditions. Compared with the operation on sunny days, the base load fluctuation and residual load fluctuation of CVPP on rainy days are reduced by 14.5% and 21.9%, respectively, proving that CVPP can alleviate renewable energy’s dependence on weather and improve energy utilization.