In this project, a novel ultrasound-mediated synthesis route was firstly developed to prepare carbon dots (CDs) decorated hydroxyapatite (HAp) targeted fluorescent nanocomposites (HAp-CDs) under low concentration of folic acid. Folic acid not only served as carbon source to form fluorescent CDs but also as targeted molecules to specifically recognize HeLa human cervical cancer cells. Furthermore, the HAp surface of HAp-CDs nanocomposites was successfully grafted with hyperbranched polyglycerol (HAp-CDs-PG) through surface-initiated ring-opening polymerization of glycidol. The grafted PG layer not only tremendously enhanced the aqueous dispersibility and stability of HAp-CDs nanocomposites, but also effectively inhibited non-specific cellular uptake of HAp-CDs-PG. Finally, the folate residues on HAp-CDs-PG achieved targeted uptake by recognizing folate receptors on Hela cells, while HAp-CDs-PG was mainly located in the cytosol of HeLa cells after being uptaken. Due to its good biocompatibility as determined by Cell Counting Kit-8 (CCK-8), HAp-CDs-PG was used to load anticancer drug doxorubicin (Dox) and efficiently delivered into targeted cells by folate receptor-mediated endocytosis, leading to an enhanced therapeutic efficacy of Dox. Thus, the HAp-CDs-PG nanocomposites could potentially be used for simultaneous cancer-targeted drug delivery and self-targeted cell imaging.
Eukaryotic initiation translation factor 3 subunit h (EIF3H) plays critical roles in regulating translational initiation and predicts poor cancer prognosis, but the mechanism underlying EIF3H tumorigenesis remains to be further elucidated. Here, we report that EIF3H is overexpressed in colorectal cancer (CRC) and correlates with poor prognosis. Conditional Eif3h deletion suppresses colorectal tumorigenesis in AOM/DSS model. Mechanistically, EIF3H functions as a deubiquitinase for HAX1 and stabilizes HAX1 via antagonizing βTrCP-mediated ubiquitination, which enhances the interaction between RAF1, MEK1 and ERK1, thereby potentiating phosphorylation of ERK1/2. In addition, activation of Wnt/β-catenin signaling induces EIF3H expression. EIF3H/HAX1 axis promotes CRC tumorigenesis and metastasis in mouse orthotopic cancer model. Significantly, combined targeting Wnt and RAF1-ERK1/2 signaling synergistically inhibits tumor growth in EIF3H-high patient-derived xenografts. These results uncover the important roles of EIF3H in mediating CRC progression through regulating HAX1 and RAF1-ERK1/2 signaling. EIF3H represents a promising therapeutic target and prognostic marker in CRC.
Epithelium-specific ETS transcription factor 1 (ESE1) has been implicated in epithelial homeostasis, inflammation, as well as tumorigenesis, and cancer progression. However, numerous studies have reported contradictory roles-as an oncogene or a tumor suppressor of ESE1 in different cancers, and its function in the development and progression of pancreatic ductal adenocarcinoma (PDAC) has remained largely unexplored. Herein, we report that ESE1 was found upregulated in primary PDAC compared to normal pancreatic tissue, but high expression of ESE1 correlated to better relapse-free survival in patients with PDAC. Interestingly, ESE1 was found to exhibit dual roles in regulation of malignant properties of PDAC cells in that its overexpression promoted cell proliferation, whereas its downregulation enhanced epithelial-mesenchymal transition (EMT) phenotype. In the context of TGF-β-induced EMT, ESE1 is markedly downregulated at post-transcriptional level, and reconstituted ESE1 expression partially reversed TGF-β-induced EMT marker expression. Furthermore, we identify AGR2 as a novel transcriptional target of ESE1 that participates in TGF-β-induced EMT in PDAC. Collectively, our findings reveal an ESE1/AGR2 axis that interacts with TGF-β signaling to modulate EMT phenotype in PDAC.
Atomic magnetometry based on longitudinal field modulation allows transverse x-and y-components measurement of a magnetic field simultaneously. In this paper, cross-axis isolation between these two-axis components is derived and investigated mathematically. An analytical model is established to optimize the cross-axis isolation during the transversal components measurement. By manipulating the amplitude and the frequency of the longitudinal field modulation, two transverse magnetic field components could be divided completely. The proposed technique plays significant role in optimization of vectoral atomic magnetometry.
Chaotic fiber ring lasers (CFRLs) can be regarded as a type of complex multi-longitudinal-mode (MLM) lasers in optical frequency domain. However, most experimental investigations on laser chaos generation are only restricted to measurements of total intensity dynamics, with frequency-domain longitudinal mode information neglected. In this work, we experimentally study the longitudinal mode dynamics of a CFRL with pump modulation by utilizing a heterodyne detection scheme, in which a beat signal between the chaotic laser and a reference laser is generated. High-resolution instantaneous emission spectra reflecting the fine longitudinal-mode structure of the CFRL in overall are measured through heterodyne detection. Besides, longitudinal mode frequency and intensity dynamics of the CFRL are monitored simultaneously via time-frequency analysis and discussed in detail. Experimental results show that the CFRL exhibits dense and irregular MLM oscillation all the time when operating at intensity chaos state. Meanwhile, each oscillating longitudinal mode in the CFRL is broadened in spectral line due to pump modulation, and can perform chaotic or random-like behaviors in mode intensity. This work will play a significant role in the further analysis, understanding and application of chaotic fiber ring lasers.
As an important technique for developing high-precision gyroscopes, atom interferometry with continuous atomic beams has exhibited advantages of high short-term sensitivity and dynamic response relative to that with periodically launched atom clouds. This article reanalyzes the characteristics of an atomic beam interferometric gyroscope from perspectives including the continuous operation mode and the modified sensitivity dependence on laser and atomic sources. Specific requirements on certain experimental parameters are explored including the Raman beam diameter, detection beam diameter, atomic flux, laser power, laser phase noise, atomic longitudinal and transverse velocity distributions. The parameter determining strategy is discussed to achieve target sensitivity with controlled conditions such as system volume and operating bandwidth. The results would provide strong support on analytical method and data reference for further improvement of atomic beam interferometric gyroscopes.
The primal cohomology K-Q of the theta divisor Theta of a principally polarized abelian fivefold (ppav) is the direct sum of its invariant and anti-invariant parts K-Q(+1), resp. K-Q(-1) under the action of -1. For smooth Theta. these have dimension 6 and 72 respectively. We show that K(Q)(+1 )consists of Hodge classes and, for a very general K-Q(+1) is a simple Hodge structure of level 2.
Tungsten oxide (WOx) is an important n-type semiconductor, which has attracted wide attention in the fields of gas sensing materials, photocatalysis, photoluminescence and electrochemistry due to its excellent electro-optical properties. However, the application potential of WOx-based nanomaterials in biomedicine has been neglected. In this paper, we firstly synthesized tungsten oxide nanowires (WOx) by one-step method using tungsten chloride and triethylene glycol as raw materials, and reported an effective surface engineering strategy for polyglycerol-functionalized tungsten oxide nanowires (WOx-PG) to enhance their colloidal stability, biocompatibility, and selective toxicity to specific cancer cells in dispersion media. The WOx-PG was further derivatized and covalently combined with FA (WOx-PG-FA) as a drug targeting vector to deliver doxorubicin (DOX) to cancer cells. Compared with WOx NWs, WOx-PG exhibits smaller size (30 - 90 nm), more uniform distribution, better solubility and biocompatibility. The hemolysis rate of PG-modified WOx NWs was significantly reduced, being only 1.35 % at 200 mu g/ml. The in vitro drug release percentage of WOx-PG-FA/DOX reached 80.78 % within 48 h at pH 5.2. In vitro toxicity assays and confocal laser scanning microscope (CLSM) results indicated that PG-functionalized WOx NWs were not cytotoxic, and WOx PG-FA/DOX had highly selective cytotoxicity on HeLa cells. These results indicate that WOx -PG-FA is a potential drug carrier for effective targeting of cancer therapy.
In this study, a novel control scheme for the discontinuous conduction mode (DCM) operation boost power factor correction (PFC) converter is proposed. Instead of adopting constant duty cycle (CDC) control, variable duty cycle control or frequency control, the magnetic control or variable inductor control is adopted to regulate the output voltage, so CDC and switching frequency can be implemented for the switch. The operation principles of the proposed control scheme are discussed in details, and the analysis of the input current, power factor, boundary condition and design considerations are presented. In addition, the modelling of the variable inductor and the DCM operation boost PFC converter with variable inductor are derived in detail, by linearising the non-linear components, the model of the DCM operation boost PFC converter with the proposed control scheme can be obtained, and the design procedures of the PI controller are presented. Finally, a 70 W experimental prototype is built to verify the theoretical analysis and the effectiveness of the proposed control scheme.
The reliability and service life of power cables is closely related to the cable ampacity and temperature rise. Therefore, studying the temperature field distribution and the cable ampacity is helpful to improve the construction guidelines of cable manufacturers. Taking a 8.7/15 kV YJV 1 × 400 XLPE three-loop power cable as the research object, cable temperature is calculated by IEC-60287 thermal circuit method and numerical simulation method, respectively. The results show that the numerical simulation method is more in line with the actual measured temperature, and the relative error is only 0.32% compared with the actual measured temperature. The temperature field and air velocity field of cluster cables with different laying methods are analyzed by finite element method. The corresponding cable ampacity are calculated by secant method. The results show that when the cable is laid at the bottom of the cable trench, the cable current is 420 A, which is 87.5% of the regular laying. Under irregular laying mode, the temperature of cable is higher than that of regular laying mode and the cable ampacity is lower than that of regular laying mode. At the same time, a multiparameter online monitoring system is developed to online monitor the temperature, water level and smoke concentration of the cable.
In this work, a carbon dots (CDs)-coated CuFe2O4 (CuFe2O4-CDs) nanocomposite consisting of magnetic CuFe2O4 core and CDs shell was synthesized via a facile one-pot solvothermal strategy. The CuFe2O4-CDs nanocomposite was characterized by TEM, XRD, XPS, TGA and VSM. Due to the protection of the CDs layer, the CuFe2O4-CDs exhibits excellent reusability and outstanding catalytic activity which is far superior to similar materials in catalytic reduction of 4-nitrophenol (4-NP), Methylene blue (MB) and Rhodamine B (RhB). The results suggested that the CuFe2O4-CDs nanocomposites have promising potential as an efficient and reusable catalyst for water environment treatment.
In this paper, we synthesized a polyglycerol(PG)-mediated superparamagnetic graphene oxide nanocomposite called MGON, consisting of PG-modified superparamagnetic iron oxide nanoparticles (SPION) covalently bonded to PG-functionalized graphene oxide (GO). MGON exhibits better dispersibility and colloidal stability in aqueous solution than the magnetic graphene oxide reported in the literature. The physicochemical properties of MGON were analyzed by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), and UV-vis spectroscopy. Applied to the adsorption of tetracycline (TC) in aqueous solution as an adsorbent, the MGON showed excellent adsorption performance with the maximum adsorption capacity of 684.93 mg/g at 298 K. Adsorption kinetics and isotherm results indicate that the adsorption process conforms to the pseudo-second-order kinetics and Langmuir isotherm models. Adsorption thermodynamics has confirmed that the adsorption process of TC on MGON is spontaneous and endothermic. With the increase of temperature, the adsorption capacity of MGON increases continuously, and the adsorption capacity of MGON is the largest when the pH value is 7. Furthermore, the π-π and cation-π interaction, amidation reaction, and hydrogen bonding can be used to explain the adsorption mechanism of TC on MGON. Desorption and regeneration experiments showed that MGON still had 67.65% regenerative performance after five cycles. Hence, MGON is a promising adsorbent in the removal of tetracycline from wastewater.
In this work, a numerical method combining conduction and radiation is used to study the stagnant effective thermal conductivity of a simple cubic packed bed with high solid to fluid thermal conductivity ratios. The experiment is designed to verify the numerical model and the numerical results agree well with the experimental results. It is found that the effective thermal conductivity accounting for conduction and radiation declines first until 690 K as the temperature rises and then increases. This trend is a result of the interactions between different heat transfer components. Compared with the numerical values and experimental values, the ZBS correlation with a proper value for the empirical parameter phi selected is capable of predicting the stagnant effective thermal conductivity in the bulk region. Lastly the different heat transfer components caused by the solid/fluid conduction, contact conduction and radiation are extracted from the total effective thermal conductivity and their individual contributions are analyzed. The contact conduction makes a major contribution to the effective thermal conductivity but gets weaker as temperature rises. The radiation overtakes contact conduction after 920 K. The solid/fluid conduction has little influence on the effective thermal conductivity.
In this paper, analysis and design of the LLC resonant converter with magnetic control for light electric vehicles (LEVs) application are presented. The magnetic control instead of the widely used frequency control or phase shift control is adopted for the LLC resonant converter to achieve a better performance. The magnetic components and electromagnetic interference (EMI) filter design are simplified due to the fixed frequency operation, and the constant switching frequency and duty cycle operation for the primary switches are achieved. Meanwhile, a design methodology for the LLC resonant converter with magnetic control for battery charger application is proposed; by carefully designing the resonant tank, zero voltage switching (ZVS) and zero current switching (ZCS) operation for semiconductors are guaranteed. An experimental prototype is built to verify the theoretical analysis.
Up to date, few attentions have been given to the special characterization of water-soluble inorganic ions (WSIs) in the submicron atmospheric particles. In this study, to implement a highly size-resolved characterization of WSIs in the submicron atmospheric particles, ten sets of size-segregated submicron atmospheric particles were collected in Hangzhou (China) from November to December 2015, with cut-off diameters of 0.060, 0.108, 0.170, 0.260, 0.400, 0.650, and 1.000 μm. The particulate WSIs, including Cl−, NO3−, SO42−, Na+, NH4+, K+, and Ca2+ were analyzed by ion chromatography, and their mode distributions and potential sources were assessed. It was found that the particulate WSIs constituted a substantial part (40.4~70.9%) in each fraction of submicron particles, of which the secondary inorganic ions (SO42−, NO3−, and NH4+) were the dominant species. The sulfur oxidation rate (SOR) and nitrogen oxidation rate (NOR) were increased when the submicron particles became coarser, indicating the enhanced secondary formation processes of SO42− and NO3− in the coarser submicron particles, thus resulting in the higher fractional contribution of secondary inorganic aerosols in the coarser submicron atmospheric particles. The correlation coefficients between K+ and Cl−, NO3−, and SO42− were 0.9293 (P = 0.002), 0.9702 (P < 0.001), and 0.9723 (P < 0.001), suggesting their dominant contribution from the biomass burning. Furthermore, it was found that PM0.4–1 (aerodynamic diameter of 0.400–1.000 μm) was a substantial part (66.6%) of submicron atmospheric particles. Compared to PM0.4 (aerodynamic diameter ≤ 0.400 μm), the concentration of WSIs in PM0.4–1 was prominently higher, and the secondary formation processes of SO42− and NO3− in PM0.4–1 were significantly enhanced.
Capacitive current feedback active damping is widely used in the LCL-type grid-connected inverter, which can effectively suppress the resonance peak of the system. However, the control delay in digital control system can change the characteristic of capacitive current feedback active damping and make the positive and negative boundary frequency of equivalent resistance is f(s)/6, which affects the stability of the grid-connected inverter and the robustness to grid impedance. At the same time, the control delay would introduce phase lag and limit the bandwidth of the control loop. Therefore, a delay compensation method considering both active damping characteristics and loop bandwidth is proposed, which can expand the boundary frequency to 0.43f(s) and greatly improve the robustness and dynamic performance of the system. Moreover, the sampling method is synchronous sampling, which strong switching-noise immunity. Simulation results verify the validity of the proposed method.
In the field of modern nanomedicine, ZnO nanoparticles were considered as an emerging candidate for drug delivery because of their inherent biocompatibility and stability. However, the poor dispersibility in a physiological medium obstructed their clinic applications. In this paper, the red fluorescence ZnO nanoparticles were synthesized, using a facile chemical method of polyol in boiling trimethylene glycol (TREG) with zinc acetate. The as-synthesized ZnO nanoparticles were first time grafted with PG layer through ring-opening polymerization of glycidol (ZnO-PG). As calculated from the TGA data, the weight ratio of the grafted PG was about 68 wt%. Then, the ZnO-PG engineered to conjugate with arginine-glycine-aspartate (RGD) peptide by stepwise organic reactions. Finally, anticancer drugs Doxorubicin hydrochloride (DOX) was immobilized on ZnO-PG-RGD (approximately 21.8 ± 0.9 nm) to form ZnO-PG-RGD/DOX. The drug release percentage reaches 70.6% within 48 h under pH 5.2, which was more than 3-fold higher than that pH 7.4. The properties of ZnO nanoparticles and its derivatives were detected by power XRD, TEM, EDS, FTIR, TGA, DLS, Zeta potential and UV. The grafted PG layer not only largely enhanced the dispersibility, but also inhibited ZnO nanoparticles from the uptake by U87MG and Hela cells. In contrast, ZnO-PG-RGD was selectively taken up by U87MG, not Hela cells, demonstrating an obvious targeting property. When ZnO-PG-RGD/DOX was used, U87MG cells showed specificity damaged compared with Hela cells. Thus, functionalized ZnO nanoparticle was a promising nanomaterial in cancer theranostics.
In this study, a core-satellite nanocomposite, termed Ag@Fe3O4 consisting of Ag particles as the inner core and many superparamagnetism Fe3O4 nanoparticles (NPs) as the outer surface, synthesized by a facile and efficient polyol method. The Ag@Fe3O4 nanocomposites were characterized using X-ray diffraction, X-ray photoelectron spectroscopy and Transmission electron microscopy measurements. The results indicated that Ag particles were successfully coated with Fe3O4 NPs aDnd showed excellent conversion efficiency of more than 99% within 8 min in the catalytic reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP). Furthermore, the magnetically functionalized Ag nanocomposites could be easily recovered with an external magnet, which retained good activity and stability after five cycles. (C) 2018 Elsevier B.V. All rights reserved.
TGF-beta plays a central role in prostate cancer (PCa) bone metastasis, and it is crucial to understand the bone cell specific role of TGF-beta signaling in this process. Thus, we used knockout (KO) mouse models having deletion of the Tgfbr2 gene specifically in osteoblasts (Tgfbr2(Col1CreERT) KO) or in osteoclasts (Tgfbr2(LysMCre) KO). We found that PCa-induced bone lesion development was promoted in the Tgfbr2(Col1CreERT) KO mice, but was inhibited in the Tgfbr2(LysMCre) KO mice, relative to their respective control Tgfbr2(FloxE2) littermates. Since metastatic PCa cells attach to osteoblasts when colonized in the bone microenvironment, we focused on the mechanistic studies using the Tgfbr2(Col1CreERT) KO mouse model. We found that bFGF was upregulated in osteoblasts from PO-injected tibiae of Tgfbr2(Col1CreERT) KO mice and correlated with increased tumor cell proliferation, angiogenesis, amounts of cancer-associated fibroblasts and osteoclasts. In vitro studies showed that osteoblastogenesis was inhibited, osteoclastogenesis was stimulated, but PC3 viability was not affected, by bFGF treatments. Lastly, the increased PO-induced bone lesions in Tgfbr2(Col1CreERT) KO mice were significantly attenuated by blocking bFGF using neutralizing antibody, suggesting bFGF is a promising target inhibiting bone metastasis. (C) 2018 Elsevier B.V. All rights reserved.
In the system of multi-inverters connected with the gird, the impedance of the grid will cause a coupling between inverters. The coupling effect of the inverters makes it complex to analyze the resonant characteristics of the multiple grid-tied inverters, especially between inverters of the different type. An increasing number of parallel converters makes the coupling effect more serious. Based on this, a method of decoupling and simplifying the coupling effect of multi inverters is proposed. First, the output current of the inverter is separated and the resonance characteristics of each part are analyzed. Then, the relationship between the interaction current resonance of the multiple grid-tied inverters and the overall current harmonic oscillation of the network is obtained. Finally, a simulation model is built on the Matlab/Simulink platform, and the correctness of the conclusion is verified by simulation.