Abstract To investigate the role of miR-223-3p in the modulatory effect of paeonol (Pae) on high glucose (HG)-induced endothelial cell apoptosis. HG (25 mmol/L) was used to induce cellular damage and ...apoptosis in the mouse cardiac microvascular endothelial cells (MCMECs). Various concentration of Pae was tested and 60 μmol/L Pae was selected for the subsequent studies. MCMECs were transfected with exogenous miR-223-3p mimics or anti-miR-223-3p inhibitors. Cell viability was assessed by MTT assay and apoptosis was quantified by flow cytometry. The expression of miR-223-3p and NLRP3 mRNA was measured using real-time quantitative RT-PCR, and protein level of NLRP3 and apoptosis-related proteins was detected by immunoblotting. Pae significantly attenuated HG-induced apoptosis of MCMECs in a concentration-dependent manner. In addition, Pae (60 µmol/L) significantly reversed HG-induced down-regulation of miR-223-3p and up-regulation of NLRP3. Pae (60 µmol/L) also significantly blocked HG-induced up-regulation of Bax and Caspase-3 as well as down-regulation of Bcl-2. Moreover, exogenous miR-223-3p mimics not only significantly attenuated HG-induced apoptosis, but also significantly suppressed NRLP-3 and pro-apoptotic proteins in the MCMECs. In contrast, transfection of exogenous miR-223-3p inhibitors into the MCMECs resulted in not only significantly increased apoptosis of the cells, but also significant suppression of NLRP3 and pro-apoptotic proteins in the cells. Pae attenuated HG-induced apoptosis of MCMECs in a concentration-dependent manner. MiR-223-3p may mediate the modulatory effects of Pae on MCMEC survival or apoptosis through targeting NLRP3 and regulating apoptosis-associated proteins.
We reported a novel and effective strategy to achieve higher continuity at a lower volume fraction of interphase by using compatibilizers in ternary blend consisting of PVDF, PS and HDPE. PVDF-g-PS ...was synthesized by electron beam radiation induced free radical graft copolymerization reaction and PVDF-g-PS was characterized by FTIR, DSC and 1H NMR. PVDF-g-PS showed effective compatibilization in PVDF/PS binary blend. The phase size of PVDF/PS binary blend was decreased at addition of PVDF-g-PS. For phase morphology development, morphology of uncompatibilized PVDF/PS/HDPE (52/6/42 vol%) ternary blend revealed a part of PS droplets situated in PVDF/HDPE interface, the other part was located inside HDPE phase. Whereas, compatibilized blend showed more and more PS migrate to PVDF/HDPE interface. When adding 7% PVDF-g-PS, PS droplets formed into uniform layer self-assembly arrayed at interface, then tri-continuous morphology was formed and continuity of PS phase increased by 32%, ultralow percolation threshold ternary blend was successfully achieved.
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•PVDF-g-PS is synthesized by electron beam radiation induced free radical graft copolymerization reaction.•PS droplets migrate to interface of PVDF/HDPE self-assembly when adding PVDF-g-PS.•Tri-continuous morphology in PVDF/PS/HDPE ternary blend is achieved at effect of PVDF-g-PS when PS phase is as low as 6%.
•Tensile performance of UHPC can be significantly improved by tailoring fiber parameters and matrix toughness.•Crumb rubber demonstrates the most predominant effect in enhancing tensile strain ...capacity.
Ultra-high performance concrete (UHPC) features high strength but a relatively low tensile strain capacity. Matrix, fiber parameters and their interaction are the controlling factors, which need careful designation to enhance the tensile performance of UHPC. In this research, different fiber parameters, e.g., fiber shapes, fiber aspect ratios, fiber hybridization and crumb rubber are utilized to tailor fiber parameters and matrix toughness to improve the tensile properties of UHPC. Systematic investigations were carried out to obtain the uniaxial tensile, compressive, fracture toughness and single-crack tension properties of UHPC. Results show that the tensile properties of UHPC could be largely improved by adjusting the fiber parameters and matrix toughness, in which the incorporation of crumb rubber demonstrates the most predominant effect in enhancing both tensile strength and strain capacity. The tensile strain capacity and crack number of developed UHPC reach 5585 με and 18, respectively, which are almost twice as the values of referred UHPC. The fracture toughness of developed UHPC ranges from 4.01 to 6.17 MPa·m1/2, approaching that of metals and alloys. The methods used in this work provide potential methods for more efficient improvement of the tensile performance of UHPC.
Background
Afatinib is the only currently approved EGFR‐tyrosine kinase inhibitors for advanced non–small cell lung cancer (NSCLC) patients with EGFR G719X/L861Q/S768I. However, there are limited ...real‐world data concerning the benefits and resistance mechanisms of afatinib in patients with these nonclassical mutations. To fill this gap, the present study was conducted.
Methods
All NSCLC patients treated with afatinib were screened, and patients with EGFR G719X/L861Q/S768I were enrolled into the analysis. Either tumor tissue or blood specimens were detected by the commercial next‐generation sequencing (NGS) panels or amplification‐refractory mutation system (ARMS)‐polymerase chain reaction (PCR) to figure out the mutation genotype.
Results
A total of 106 advanced NSCLC patients with EGFR G719X/L861Q/S768I received afatinib treatment. The benefits of afatinib exhibited heterogeneity in different mutation genotypes. Notably, at baseline, NGS testing was performed in 59 patients, and TP53 was the most frequently coexisting mutation. Patients with TP53 mutations obtained fewer survival benefits than those with TP53 wild‐type. A total of 68 patients ultimately experienced progression, and 27 patients received NGS testing to clarify the potential resistance mechanisms. EGFR‐T790M, CDK4 amplification, FGFR1 amplification, PIK3CA, MET amplification, RET fusions, HER2, and BRAF mutations were identified in three (11.1%), three (11.1%), three (11.1%), three (11.1%), three (11.1%), one (3.7%), one (3.7%), and one (3.7%) of the cases, respectively. Five patients underwent ARMS‐PCR testing for detecting EGFR‐T790M mutation, and only one patient was T790M‐positive.
Conclusions
The present study elucidated the differential benefits of afatinib within different mutation genotypes and first revealed the spectrum of potential resistance mechanisms in patients with EGFR G719X/L861Q/S768I. The results of this study may provide practical clinical information that can guide optimal treatment in this setting.
The present study was the first to be designed specifically for advanced non–small cell lung cancer patients with EGFR G719X/L861Q/S768I, and the authors have elucidated the potential resistance mechanisms of afatinib for the first time. After progression on afatinib treatment, lower incidences of EGFR‐T790M was indicated in EGFR uncommon mutations, whereas resistance mechanisms remained unclear in 39% of these patients with nonclassical EGFR mutation.
To design a variable recursive digital filter whose stability is always guaranteed, it is necessary to ensure that the stability conditions are always satisfied in the tuning process. Furthermore, it ...is also necessary to keep a certain margin for the stability (stability margin) in such a way that some unpredictable environmental changes and coefficient-value deviations will not cause instability. To add a stability margin to the stability of the second-order (2nd-order) recursive filter, this paper first introduces a stability trapezoid by trimming the well-known stability triangle of the 2nd-order recursive digital filter. Then, we quantitatively analyze the upper bound for the stability margin by using a stability-margin parameter. This theoretical stability-margin analysis is fundamental to the design of a variable recursive filter with an expected stability margin. Finally, we utilize a demonstrative example to verify the consistence between the theoretical upper bound of the stability margin and the computer simulation results.
•We propose a stability trapezoid for guaranteeing a specified stability-margin.•We analyze the relation between stability margin and stability-margin parameter.•We use a demonstrative example to verify the stability margin.•We have verified the consistence between stability margin and simulation results.
Colloidal quantum dots (QDs) as photocatalysts enable catalysis of CO2-to-CO conversion in the presence of electron donors. The surface and/or interfacial chemical environment of the QDs is essential ...for the activity and selectivity of the CO2 photoreduction. Various strategies, including exposing active metal sites or anchoring functional organic ligands, have been applied to tune the QDs’ surface chemical environment and thus to improve both activity and selectivity of CO2 photoreduction, which occurs at surface of the QDs. However, the efficient and selective photocatalytic CO2 reduction with QD photocatalysts in water is still a challenging task due to low CO2 solubility and robust competing reaction of proton reduction in water. Different from state-of-the-art QDs’ surface manipulation, we proposed to ameliorate the interfacial chemical environment of CdSe QDs via assembling the QDs into functional polymeric micelles in water. Herein, CdSe@PEI-LA assemblies were constructed by loading CdSe QDs into polymeric micelles formed by PEI-LA, a polyethylenimine (PEI)-based functional amphiphilic polymer. Due to self-assembly and high CO2 adsorption capacity of PEI-LA in water, the photocatalytic CO2-to-CO conversion efficiency and selectivity of the CdSe@PEI-LA assemblies in water were dramatically improved to 28.0 mmol g–1 and 87.5%, respectively. These two values increased 57 times and 1.5 times, respectively, compared with those of the pristine CdSe QDs. Mechanism studies revealed that CdSe QDs locate in polymeric micelles of high CO2 local concentration and the photoinduced electron transfer from the conduction band of CdSe QDs to Cd–CO2* species is thermodynamically and kinetically improved in the presence of PEI-LA. The CdSe@PEI-LA system represents a successful example of using a functionalized amphiphilic polymer to ameliorate interfacial microenvironments of nanocrystal photocatalysts and realizing efficient and selective CO2 photoreduction in water.
Magnesium alloys show broad application prospects as biodegradable implanting materials due to their good biocompatibility, mechanical compatibility, and degradability. However, the influence ...mechanism of microstructure evolution during forming on the mechanical properties and corrosion resistance of the magnesium alloy process is not clear. Here, the effects of rolling deformation, such as cold rolling, warm rolling, and hot rolling, on the microstructure, mechanical properties, and corrosion resistance of the WE43 magnesium alloy were systematically studied. After rolling treatment, the grains of the alloy were significantly refined. Moreover, the crystal plane texture strength and basal plane density decreased first and then increased with the increase in rolling temperature. Compared with the as-cast alloy, the strength of the alloy after rolling was significantly improved. Among them, the warm-rolled alloy exhibited the best mechanical properties, with a tensile strength of 346.7 MPa and an elongation of 8.9%. The electrochemical experiments and immersion test showed that the hot working process can greatly improve the corrosion resistance of the WE43 alloy. The hot-rolled alloy had the best corrosion resistance, and its corrosion resistance rate was 0.1556 ± 0.18 mm/year.
One of the biggest challenges in clonal propagation of grapevine (
) is difficulty of rooting. Adventitious root initiation and development are the critical steps in the cutting and layering process ...of grapevine, but the molecular mechanism of these processes remains unclear. Previous reports have found that microRNA (miRNA)-encoded peptides (miPEPs) can regulate plant root development by increasing the transcription of their corresponding primary miRNA. Here, we report the role of a miPEP in increasing adventitious root formation in grapevine. In this study, we performed a global analysis of miPEPs in grapevine and characterized the function of vvi-miPEP171d1, a functional, small peptide encoded by primary-miR171d. There were three small open reading frames in the 500-bp upstream sequence of pre-miR171d. One of them encoded a small peptide, vvi-miPEP171d1, which could increase the transcription of
Exogenous application of vvi-miPEP171d1 to grape tissue culture plantlets promoted adventitious root development by activating the expression of vvi-
Interestingly, neither exogenous application of the vvi-miPEP171d1 peptide nor overexpression of the vvi-miPEP171d1 coding sequence resulted in phenotypic changes in Arabidopsis (
). Similarly, application of synthetic ath-miPEP171c, the small peptide encoded by the Arabidopsis ortholog of
, inhibited the growth of primary roots and induced the early initiation of lateral and adventitious roots in Arabidopsis, while it had no effect on grape root development. Our findings reveal that miPEP171d1 regulates root development by promoting
expression in a species-specific manner, further enriching the theoretical research into miPEPs.
Background Hyperaccumulator plants are unusual plants that accumulate particular metals or metalloids, such as nickel, zinc, cadmium and arsenic, in their living tissues to concentrations that are ...hundreds to thousands of times greater than what is normal for most plants. The hyperaccumulation phenomenon is rare (exhibited by less than 0.2% of all angiosperms), with most of the ~500 hyperaccumulator species known globally for nickel. Scope This review highlights the contemporary understanding of nickel hyperaccumulation processes, which include root uptake and sequestration, xylem loading and transport, leaf compartmentation and phloem translocation processes. Conclusions Hyperaccumulator plants have evolved highly efficient physiological mechanisms for taking up nickel in their roots followed by rapid translocation and sequestration into the aerial shoots. The uptake of nickel is mainly involved with low affinity transport systems, presumably from the ZIP family. The presence of high concentrations of histidine prevents nickel sequestration in roots. Nickel is efficiently loaded into the xylem, where it mainly presents as Ni2+. The leaf is the main storage organ, which sequestrates nickel in non-active sites, e.g. vacuoles and apoplast. Recent studies show that phloem translocates high levels of nickel, which has a strong impact on nickel accumulation in young growing tissues.
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