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Aims Both gefitinib and afatinib are epidermal growth factor tyrosine kinase inhibitors (EGFR-TKI) in the treatment of non-small cell lung cancer (NSCLC). It has been reported that gefitinib and afatinib could cause hepatotoxicity during the clinic treatment, therefore it is critical to investigate their hepatotoxicity systematically. In this study, zebrafish (Danio rerio) were used as model animals to compare the hepatotoxicity and their toxic mechanism. Main methods The zebrafish transgenic line [Tg (fabp10a: dsRed; ela3l:EGFP) was used in this study. After larvae developed at 3 days post fertilization (dpf), they were put into different concentrations of gefitinib and afatinib. At 6 dpf, the viability, liver area, fluorescence intensity, histopathology, apoptosis, transaminase reflecting liver function, the absorption of yolk sac, and the expression of relative genes were observed and analyzed respectively. Key findings Both gefitinib and afatinib could induce the larvae hepatotoxicity dose-dependently. Based on the liver morphology, histopathology, apoptosis and function assessments, gefitinib showed higher toxicity, causing more serious liver damage. Both gefitinib and afatinib caused abnormal expressions of genes related to endoplasmic reticulum stress (ERS) pathway and apoptosis. For example, jnk, perk, bip, chop, ire1, bid, caspase3 and caspase9 were up-regulated, while xbp1s, grp78, bcl-2/bax, and caspase8 were down-regulated. The hepatotoxicity difference of gefitinib and afatinib might be due to the different expression level of related genes.

Despite the relatively low emissions in fluidized-bed combustion, NOx emission for biomass combustion is still a major concern because of increasingly stricter regulations. To realize NOx emission behavior in fluidized beds comprehensively, the effects of bed temperature, excess oxygen, staged combustion, and flue gas recirculation (FGR) are investigated in this study. In particular, three different types of operation are applied in staged combustion to find out the key parameter. The results indicate that NOx emissions increase with both bed temperature and excess oxygen, in which the influence of excess oxygen is greater than the other. Lowering bed temperature by water addition seems to be able to simultaneously reduce NOx emission and agglomerate formation, especially for fuels with high nitrogen content, but the pros and cons should be considered. The results in staged combustion infer that the residence time is much more critical than the stoichiometry in the bed. As for FGR, its impact appears to depend on the type of fuel. The correlation between NOx emission behavior and fuel characteristics is also scrutinized; it is concluded that the fuel-N conversion to NOx is essentially related to some features of fuels.

Lung cancer is one of the most common cancers worldwide and is by far the leading cause of cancer death attributed to its rapid metastasis and poor prognosis. Given that hypoxia-inducible factors (HIFs) are associated with cancer metastasis, discovering agents to inhibit HIF-mediated invasive cancer is highly desired.This study aimed to investigate the natural acridone compounds isolated from Severinia buxifolia for the potential to delay hypoxia-induced lung cancer invasiveness by HIF inhibition.Using a hypoxia-responsive element (HRE) luciferase reporter, cell migration and invasion assays, real-time PCR, Western blot, and DNA recombinant clones, compound effect on HIF activity, cancer metastasis, HIF-1α mRNA transcription, HIFs protein stability, and HIF-1α translation were observed under hypoxia conditions.Atalaphyllidine (Sbs-A) and atalaphyllinine (Sbs-B) were found to show the most potent effects on HIF transcriptional activity and HIF-1α protein expression in NSCLC cell line A549, although Sbs-A and Sbs-B might not attribute decreasing HIF-1α mRNA expression to potent inhibition of HIF activity. HIF-1α protein stability was not affected by Sbs-A; also, prolyl hydroxylase and proteasome inhibitors could not reverse the inhibitory effect from compounds. Furthermore, 3 - 10 μM low concentrations of Sbs-A inhibited HIF target gene expression, gelatin zymography activity, and A549 cancer invasion. Ultimately, Sbs-A inhibited HIF-1α 5'UTR-mediated translation independent of oxygen concentration, underlying the mechanism of compounds inhibiting HIF-1α protein expression.Our study proposed Severinia buxifolia-isolated acridone compounds inhibited 5'-mRNA HIFA-mediated translation and provided evidence supporting the ability of acridone compounds in targeting HIFα for delayed lung cancer metastasis.

The relative importance of char-N and volatile-N on NOx emissions is examined in a pilot-scale fluidized-bed combustor. Coke and toluene are used as the base fuels, and nitrogenous compounds (nitrobenzene, pyridine, and pyrrole) are mixed with them alternatively to study the effect of nitrogen origin on NOx formation and reduction. The results show that NOx evolution would be greatly changed if the nitrogenous species are present in the volatile, and NOx reduction inside the combustor may be the key factor that determines the final emissions. When nitrobenzene is employed, the conversion of volatile-N to NOx is 13.17–15.42%, while that of char-N is 4.49–7.59% in the bed temperature of 750–900 °C, indicating that nitrogen present in volatiles may be much more prone to elicit higher NOx. Moreover, the volatile-N conversion to NOx is always greater than that of char-N, regardless of the nitrogen functionality. However, the degree of formation and reduction of NOx would depend firmly on the functional groups of nitrogen, which are nitro, pyridine, and pyrrole in this case. NOx reduction mainly occurs in the splash zone, and NOx generated from char-N is reduced in a manner dissimilar to that of volatile-N.

Since the introduction of the first expounded triboelectric nanogenerator (TENG) in 2012, the theoretical and practical aspects of the TENG have been researched as an alternative energy harvesting technology to convert mechanical energy into electricity efficiently. Numerous self-powered sensing systems have adopted the TENG as a power source to further explore its versatile applications toward different targets. In this study, we employed a TENG to replace a traditional power supply for synthesizing different metallic nanoparticles using an electrochemical approach. Carbon fibers were adopted as the conductive substrates to grow the metallic nanoparticles, where the size and density of the nanoparticles on carbon fibers can be controlled by the electric output of the TENG. Additionally, we demonstrated that the as-prepared carbon modified and integrated with the TENG to construct a wearable self-powered sensing system exhibited significant selectivity and sensitivity toward lactate detection. Furthermore, the design of the sensing unit was favorable regarding its adaptability and flexibility to fit human body shapes and postures. As demonstrated in this study, the as-prepared self-powered sensing system could detect the lactate concentration in human perspiration, which can be an ideal wearable device for end users who seek real-time monitoring of their physical condition. This study concludes with a proposal for noninvasive biosensors, which provide boundless potential for future cross-field applications.

In a rectangular fluidized bed combustor, the tracer gas is injected continuously into the bed from a point source at the center of the distributor plate. In this study, a general governing equation is formulated for tracer gas dispersion in the bed. An analytical solution is derived to estimate the dispersion coefficients, D x and D y , in a horizontal plane. The concentration profiles at different sampling heights with various gas velocities are plotted. Subsequently, to estimate the dispersion coefficients, surface fitting of the obtained analytical solution to the experimental data is performed. The dispersion coefficients obtained from this model are compared with those of a conventional model. Additionally, the effect of walls, bed height and gas injection rate on the dispersion coefficients in a horizontal plane is investigated, and the effect of distributor design on the dispersion coefficients in a horizontal plane is investigated with different tracer positions. It is found that D x and D y are nearly equivalent at a lower tracer gas ratio of the injected gas to the total gas flow rate. It is also demonstrated that the effect of bed height on D x is minor. This model is also able to estimate the dispersion coefficients in the case of a multi-horizontal nozzle distributor.

An ultrasensitive electrochemiluminescence (ECL) biosensor for the detection of microRNA was developed based on nicking enzymes Nb.BbvCI mediated signal amplification (NESA). First, the hairpin probe1-N-CQDs with assistant probe and microRNA (miRNA) formed Y junction structure which was cleaved with the addition of nicking enzymes Nb.BbvCI to release miRNA and assistant probe. Subsequently, the released miRNA and assistant probe can initiate the next recycling process. The generation of numerous intermediate sequences nitrogen doped carbon quantum dots-DNA (N-CQDs-DNA) can further hybridize with hairpin probe2 immobilized on GO/Au composite modified electrode surface, the initial ECL intensity was enhanced. The ECL intensity would increase with increasing concentration of the target miRNA, and the sensitivity of biosensor would be promoted because of the efficient signal amplification of the target induced cycling reaction. The novel designed biosensor provided a highly sensitive and selective detection of miRNA-21 from 10 aM to104 fM with a relatively low detection limit of 10 aM. Thus, our strategy has a potential application in the clinical diagnosis.

Staged combustion significantly affects the complete combustion of biomass and reduces pollutant emissions. This study primarily aimed to compare the thermal behaviors and pollutant emissions of different secondary gas injection modes in a pilot-scale fluidized bed combustor (FBC). Pelletized thorny bamboo was used as the fuel, and silica sand was used as the bed material. Flue gas recirculation (FGR) was employed. The experimental results demonstrate that the secondary gas injection modes in the FBC affected the combustion characteristics. The temperature of pelletized bamboo combustion with tangential injection mode (T mode) was lower than that of centripetal injection mode (C mode); however, T mode produced lower CO and NOx emissions than C mode because of the well-swirling effect. The secondary gas velocity and airflow distribution uniformity in the secondary gas layers jointly affect combustion, while T mode with four nozzles or C mode with two nozzles is optimal to reduce emissions. Furthermore, increasing the elevation of secondary air further reduces NOx emissions in C mode but does not significantly affect emissions in T mode.

We investigate whether the funding liquidity risk to institutional investors influences the negative relation between expected returns and variance (the ‘‘Low-volatility anomaly’’). With the Taiwan stock market as a setting, we implement a multivariate Markov switching model and use the funding liquidity risk to model the time-varying transition probabilities of the regime-switching process to capture changes in the funding liquidity risk regime. Our evidence documents that the low-volatility anomaly is most pronounced when there is high funding liquidity risk. When there is low funding liquidity risk, however, the low-volatility anomaly has a significant reversal. These results imply that the increased funding liquidity risk due to financial shock transmitted from parent banks is associated with higher selling pressure on institutional investors’ high-volatility stocks, leading to the low-volatility anomaly.

We present an approach for synchronizing hyperthermia and thermal-responsive local drug release. The targeting probe has a magnetite nanocrystal (Fe₃O₄@PSMA) core and a polynucleotide shell that carries 5-fluorouracil (5-FU) and anti-human epidermal growth factor receptor 2 (anti-HER2) antibody for cancer cell-specific targeting. The targeting nanocrystals play as an important role to relay the externally delivered radiofrequency energy for tumor hyperthermia. Locoregional heat then triggers a drug release from the oligonucleotide carrier as it directly damages tumor cells. Cell viability assays and pathological examinations show that this synchronization is significantly more efficacious in both in vitro and in vivo models than hyperthermia or chemotherapy alone. Prominent tumor remission in vivo was achieved through radiofrequency synchronization of hyperthermia and chemotherapy after the nanoparticle had been intravenously injected.

In this paper, the technique of image noise cancellation is presented by employing cellular neural networks (CNN) and linear matrix inequality (LMI). The main objective is to obtain the templates of CNN by using a corrupted image and a corresponding desired image. A criterion for the uniqueness and global asymptotic stability of the equilibrium point of CNN is presented based on the Lyapunov stability theorem (i.e., the feedback template "A" of CNN is solved at this step), and the input template "B" of CNN is designed to achieve desirable output by using the property of saturation nonlinearity of CNN. It is shown that the problem of image noise cancellation can be characterized in terms of LMIs. The simulation results indicate that the proposed method is useful for practical application.

This study tested the hypothesis that patients with mild and severe medial knee osteoarthritis (OA) adopt different compensatory gait patterns to unload the deseased knee, in not only the frontal plane but also the sagittal plane. Fifteen patients with mild and 15 with severe bilateral medial knee OA, and 15 normal controls walked while the kinematic and kinetic data were measured. Compared to the normal group, both OA groups had significantly greater pelvic anterior tilt, swing-pelvis list, smaller standing knee abduction, as well as smaller standing hip flexor and knee extensor moments during stance. The severe group also had greater hip abduction, knee extension and ankle plantarflexion. The mild group successfully reduced the extensor moment and maintained normal abductor moment at the diseased knee mainly through listing and anterior tilting the pelvis. With extra compensatory changes at other joints and increased hip abductor moment, the severe group successfully reduced the knee extensor moment but failed to reduce the abductor moment. These results suggest that, apart from training of the knee muscles, training of the hip muscles and pelvic control are essential in the rehabilitative intervention of patients with knee OA, especially for more severe patients.

Tunable (Pb0.5Ba0.5)(Zr1−xTix)O3 (PBZT) films were grown on Pt/Ti/SiO2/Si substrates using chemical solution deposition method. PBZT films contained bimodal distribution of grains and pores. The size of large grains, the amount of small grains, and the porosity all increased with the content of titanium oxide. The microstructural characteristics of PBZT films influenced dielectric properties. Increasing the content of TiO2 in PBZT films increased dielectric constant, tunability, and figure of merit (FOM), while it kept loss tangent relatively unchanged. The composition (x = 0.2) locating near the paraelectric–ferroelectric boundary exhibited optimal dielectric tunability and FOM. The tunability and FOM were improved remarkably from 12% and 6 to 34% and 26, respectively, when 20% of titanium oxide was added to PBZ films.

In this study, we examine how a firm’s advertising and R&D affects the firm’s β-risk and idiosyncratic risk, which are metrics of interest to both finance executives and senior management. Due to the existence of non-normal finance data and heteroscedasticity, this study uses quantile regression to analyze the sample in order to avoid estimation bias. We generate six empirical generalizations. (1) Advertising is significantly associated with lower β-risk for firms with lower, median and higher β-risk. (2) R&D significantly increases β-risk for firms with median and higher β-risk firms. (3) Advertising is significantly associated with lower idiosyncratic risk for firms with higher idiosyncratic risk. (4) R&D is significantly associated with higher idiosyncratic risk for firms with median and higher idiosyncratic risk. (5) Our evidence shows that both advertising and R&D have a stronger effect on firms with higher β- and idiosyncratic risk than on those with lower β- and idiosyncratic risk, respectively. (6) Moreover, our evidence suggests that advertising and R&D tests resoundingly support our hypothesis that the coefficients vary across the quantiles