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Although zinc oxide nanoparticles (ZnO NPs) have demonstrated promising anticancer activity, their therapeutic performances are frequently influenced by the synthesis routes and associated distinct physicochemical characteristics. Herein, ZnO NPs were synthesized through a cost-effective flame spray pyrolysis-assisted approach and their selective anticancer effects and underlying intrinsic apoptosis signaling pathway in human gastric carcinoma cell line (AGS) were examined. Transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and dynamic light scattering (DLS) investigations were used to characterize the synthesized ZnO NPs. Afterwards, AGS and normal fibroblast cells (L-929) were treated with various concentrations of ZnO NPs, and cell proliferation was examined by the MTT assay to determine the IC50 concentration of NPs. Furthermore, the quantification of ROS and apoptosis was done by fluorometer and flow cytometry assays. Additionally, superoxide dismutase (SOD) and catalase (CAT) activity assays were performed to evaluate the oxidative stress-induced cytotoxicity mediated by ZnO NPs against AGS cells. Moreover, caspase-3/-8/-9 activity and mitochondrial membrane potential (MMP) assays were done. Finally, the expression levels of p53, Bax, Bcl-2, caspase-9/-8/-3, and cytochrome c were assessed by quantitative real time PCR and western blot analyses to explore the probable mitochondrial apoptosis signaling pathway induced by ZnO NPs in AGS cells. The results showed that ZnO NPs with an absorption maximum at 350 nm, an average size of 70 nm, a hydrodynamic radius of 92.89 nm, and a zeta potential of −43.13 mV potentially and selectively inhibited the proliferation of AGS cells in comparison with L-929 cells through a remarkable increase in the production of ROS, induction of apoptosis, reduction of SOD and CAT activity, activation of caspase-9/-3, and MMP disruption. Moreover, ZnO NPs triggered up-regulation of p53, Bax, caspase-9/-3, cytochrome c and down-regulation of Bcl-2 at mRNA and protein levels. This study suggests that synthesized ZnO NPs through flame spray pyrolysis can induce selective anticancer effects against gastric cancer cells via intrinsic apoptosis signaling pathway.

For ultrasonic welding (USW) of fiber reinforced thermoplastic composites without energy director (ED), the special contact surface and interphase structures due to the addition of fibers have strong relation to the weld quality. In this study, through the servo-driven USW experiments and the corresponding mini-anisotropy modeling for PA6 and CF/PA6 composites welding without ED, the fusion phenomena and weldability of the materials are addressed. The results show that as compared to pure PA6, CF/PA6 has the higher loss modulus and lower specific capacity, leading to more viscoelastic heat generation during USW. As the CF/PA6 surface has the higher roughness, the more significant local stress and energy concentrations occur around the initial contact area, leading to the increased welding area; while more pores are observed within the joints of composites due to the poor liquidity and air trap from larger contact gap. Due to the interphase structure between CF and PA6, the high strain and high temperature occur around the fibers, where pores form due to thermal decomposition.

ABSTRACT: Objectives: Proteus mirabilis is an important opportunistic Gram-negative pathogen. This study reports the whole genome sequence of multidrug-resistant (MDR) P. mirabilis PM1162 and explores its antibiotic resistance genes (ARGs) and their genetic environments. Methods: P. mirabilis PM1162 was isolated from a urinary tract infection in China. Antimicrobial susceptibility was determined, and whole genome sequencing (WGS) was performed. ARGs, insertion sequence (IS) elements, and prophages were identified using ResFinder, ISfinder, and PHASTER software, respectively. Sequence comparisons and map generation were performed using BLAST and Easyfig, respectively. Results: On its chromosome, P. mirabilis PM1162 harboured 15 ARGs, including cat, tet(J), blaCTX-M-14 (three copies), aph(3′)-Ia, qnrB4, blaDHA-1, qacE, sul1, armA, msr(E), mph(E), aadA1, and dfrA1. We focused our analysis on the four related MDR regions: (1) genetic contexts associated with blaCTX-M-14; (2) the prophage containing blaDHA-1, qnrB4, and aph(3′)-Ia; (3) genetic environments associated with mph(E), msr(E), armA, sul, and qacE; and (4) the class II integron harbouring dfrA1, sat2, and aadA1. Conclusion: This study reported the whole genome sequence of MDR P. mirabilis PM1162 and the genetic context of its ARGs. This comprehensive genomic analysis of MDR P. mirabilis PM1162 provides a deeper understanding of its MDR mechanism and elucidates the horizontal spread of its ARGs, thus providing a basis for the containment and treatment of the bacteria.

Summary: Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors. Funding: Wellcome Trust.

Penthiopyrad (PO), a succinate dehydrogenase inhibitor (SDHI) fungicide, poses a potential risk to fish. Here, we investigated the adverse effects of PO on endocrine regulation and reproductive capacity in zebrafish during a 21-d sublethal exposure to PO concentrations ranging from 0.02 to 2.00 mg/L. Following exposure to PO (0.20 and 2.00 mg/L), female-specific effects including follicle necrosis, structural disturbance of the yolk follicle, fusion of cortical follicles appeared in ovarian tissue of adult females, which led to a significant reduction in fertility. Correspondingly, 0.20 and 2.00 mg/L PO led to a marked reduction in the GSI values of females, and 2.00 mg/L PO caused a 31% decline in the proportion of perinucleolar oocytes (PCO) in oocytes. In addition, testosterone (T) level was obviously suppressed and 17β-estradiol (E2) level was increased in females after exposure to 2.00 mg/L PO. Male zebrafish treated with 0.20 and 2.00 mg/L of PO exhibited significant interstitial enlargement, edema in the testes, and reduced diameter of seminiferous tubules, along with a thinner basement membrane. The effects of PO on males were associated with significant increase in E2 level, suggesting that PO has an estrogenic effect on male fish. Greater E2 levels in serum were further supported by increased transcription levels of genes linked to the hypothalamic-pituitary-gonad-liver (HPGL) axis. Notably, transcription levels of cyp19a, er2b, era, and cyp19b was remarkably increased, exhibiting a clear link with variations in E2 levels. Overall, the present study demonstrates that PO induces reproductive impairment in zebrafish by promoting steroidogenesis.

Implementing a high-efficiency hybrid energy generation system requires to comprehensively analyze the influences of multiple factors on the overall performance, including system layout, design parameters, energy resource endowments. For this purpose, this study developed a thermal-economic model for a 300 kW ORC-based hybrid solar-geothermal power generation system at four sites in China, which represents different solar and geothermal energy resources. The optimal configurations of the hybrid system have been obtained for the minimal levelized cost of energy (LCOE) under a certain annual electricity generation (E). The results show that the solar resources continue to play a dominant role in the proposed hybrid system, especially in optimizing the configuration of the system design parameters for the minimum LCOE. Comparing to the individual solar system, the hybrid power generation system significantly enhances its thermal-economic efficiency across the four selected sites, with a maximum increase of 25.34% in E and a maximum decrease of 16.28% in LCOE. Especially in regions with abundant shallow hydrothermal geothermal reservoirs but average solar resources, utilizing shallow geothermal water to preheat Organic Rankine Cycle (ORC) working fluids is a relatively simple yet efficient application of geothermal energy for power generation, worthy of further promotion and implementation.

A servo-driven ultrasonic welding (USW) offers a good control for joining carbon fiber reinforced thermoplastic composites (CFRTP) with a constant plunging speed, a dynamic applied force and adjusting power in real time. This study focuses on the process and strength analysis during servo-driven USW of CF/PA6 composites without energy director (ED) to obtain the correlation between the operation parameters and joint strength. The results show that a servo-driven welder benefits in USW without ED due to the initial intimate contact between workpieces without horn retraction. It is also found that a typical vibration process can be divided into four stages following the heat evolution and characteristic temperature of CFRTP, i.e., “initial stage”, “soften stage”, “melting stage” and “steady stage”. High energy and amplitude bring enough total energy and high power to melt materials; while a low trigger force and a slow plunging speed can mitigate the excessive squeeze-out with a result of the increase in weld strength. Thus, as the melted material remained in the weld region decides the bonding efficiency, the desired joints can be obtained under the enough welding energy (≥400 J) and amplitude (≥80%), not too high welding force (≤800 N) and plunging speed (≤0.8 mm/s). Meanwhile, weld quality can be online inspected and judged based on welding force evolution, and the measured displacement relative to the set value. This work contributes to the optimal parametric selection for USW of CFRTP plates without ED applying a servo-driven welder.

Background: Accumulating evidence indicated the crucial role for interleukin 6 (IL-6) signaling in the development of allergic asthma. Yet, the role of IL-6 signaling in toluene diisocyanate (TDI)-induced mixed granulocytic airway inflammation still remains unclear. Thus, the aims of this study were to dissect the role of IL-6 signaling and to evaluate the effect of tocilizumab on TDI-induced steroid-resistant asthma. Methods: TDI-induced asthma model was prepared and asthmatic mice were respectively given IL-6 monoclonal antibody, IL-6R monoclonal antibody (tocilizumab, 5 mg/kg, i.p. after each challenge) for therapeutic purposes or isotype IgG as control. Results: TDI exposure just elevated IL-6R expression in the infiltrated inflammatory cells around the airway, but increased glycoprotein 130 expression in the whole lung, especially in bronchial epithelium. Moreover, TDI inhalation increased airway hyperresponsiveness (AHR) to methacholine, coupled with mixed granulocytic inflammation, exaggerated epithelial denudation, airway smooth muscle thickening, goblet cell metaplasia, extensive submucosal collagen deposition, dysregulated Th2/Th17 responses, as well as innate immune responses and raised serum IgE. And almost all these responses except for raised serum IgE were markedly ameliorated by the administration of IL-6 neutralizing antibody or tocilizumab, but exhibited poor response to systemic steroid treatment. Also, TDI challenge induced nucleocytoplasm translocation of HMGB1 and promoted its release in the BALF, as well as elevated lung level of STAT3 phosphorylation, which were inhibited by anti-IL-6 and anti-IL-6R treatment. Conclusions: Our data suggested that IL-6 monoclonal antibody and tocilizumab might effectively abrogate TDI-induced airway inflammation and remodeling, which could be used as a clinical potential therapy for patients with severe asthma.

Although many models have been proposed to estimate the effective thermal conductivity (ETC) of nanofluids, the thermal conduction mechanisms need to be further addressed to improve the prediction accuracy of ETC model. In this paper, by fully considering the effects of particle clustering, Brownian motion, Kapitza resistance and nanolayer of particle, Hamilton-Crosser model is reconstructed to establish an improved model for the ETC of nanofluids. To develop this model, the particle clustering is characterized by the particle size distribution analysis, and the thermal conductivity distribution in the nanolayer is represented as a specific function of the distance from the nanoparticle. The influences of temperature, viscosity, particle size and other factors on the ETC of nanofluids are also included in this model. The results show that the accuracy of this model can be improved as compared to those considering only several of these factors, and the maximum error is 3% against the available experimental data. With this model, the inconsistency phenomena in ETC data of nanofluids can be explained in the view of the agglomeration and Brownian motion with the system conditions.