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Emphysema, myofibroblast accumulation and airway remodeling can occur in the lungs due to exposure to atmospheric pollution, especially fine particulate matter (PM2.5), leading to chronic obstructive pulmonary disease (COPD). Specifically, bronchial epithelium-fibroblast communication participates in airway remodeling, which results in COPD. An increasing number of studies are now being conducted on the role of exosome-mediated cell-cell communication in disease pathogenesis. Here, we investigated whether exosomes generated from bronchial epithelial cells could deliver information to normal stromal fibroblasts and provoke cellular responses, resulting in airway obstruction in COPD. We studied the mechanism of exosome-mediated intercellular communication between human bronchial epithelial (HBE) cells and primary lung fibroblasts (pLFs). We found that PM2.5-induced HBE-derived exosomes promoted myofibroblast differentiation in pLFs. Then, the exosomal lncRNA expression profiles derived from PM2.5-treated HBE cells and nontreated HBE cells were investigated using an Agilent Human LncRNA Array. Combining coculture assays and direct exosome treatment, we found that HBE cell-derived exosomal HOTAIRM1 facilitated the myofibroblast differentiation of pLFs. Surprisingly, we discovered that exosomal HOTAIRM1 enhanced pLF proliferation to secrete excessive collagen secretion, leading to airway obstruction by stimulating the TGF-β/SMAD3 signaling pathway. Significantly, PM2.5 reduced FEV1/FVC and FEV1 and increased the level of serum exosomal HOTAIRM1 in healthy people; moreover, serum exosomal HOTAIRM1 was associated with PM2.5-related reductions in FEV1/FVC and FVC. These findings show that PM2.5 triggers alterations in exosome components and clarify that one of the paracrine mediators of myofibroblast differentiation is bronchial epithelial cell-derived HOTAIRM1, which has the potential to be an effective prevention and therapeutic target for PM2.5-induced COPD. [ABSTRACT FROM AUTHOR]

In this study, we employed classic electrochemical techniques including cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) to perform electrochemical characterization on atomic-level single-crystal TiO2 electrodes and extract capacitive and resistive properties of single-crystal TiO2 electrode/solution interface in KCl and KCl/K3PO4 at various pH levels. The lattice structure and crystal appearance were characterized using X-ray diffractometry (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy to facilitate the in-depth exploration of heterogeneous reaction dynamics and theory. Furthermore, this study aimed to verify and improve the theory and application of capacitance at the single-crystal TiO2 electrode/solution interface. The electrochemical measurements indicate that, in the same pH, the presence of PO43− significantly increases the total capacitance (CT), outer capacitance (CO), electrical double-layer capacitance (Cdl), and diffusion layer capacitance (Cdiff) at single-crystal TiO2 electrode/solution interface. This enhancement is attributed to the direct interaction between PO43− and the single-crystal TiO2 electrode surface, leading to the specific adsorption of PO43− on the electrode surface, revealing higher current and stronger electrochemical activity in the interaction between TiO2 and PO43−. Additionally, our XPS results indicate the adsorption of PO43− on the single-crystal TiO2 electrode surface. The interaction of PO43− with the TiO2 surface demonstrates increased hydrophilicity and enhanced adsorption capacity through mechanisms such as ligand exchange or cation bridging, thereby augmenting the Cdl at the single-crystal TiO2 electrode/solution interface. [ABSTRACT FROM AUTHOR]

Hollow microspheres Bi2WO6 (HBWO) were prepared by the solvothermal method for the adsorption of U(VI) from aqueous solutions. Batch experiments and characterization analysis investigated the adsorption performance and mechanism. The results showed that the adsorption equilibrium could be reached in 30 min at T = 303 K, pH = 6, CU(VI) = 10 mg/L, m/V = 0.1 g/L. The removal efficiency of HBWO for U(VI) in solution was 95.53%, which was about 20% higher than Bi2WO6 nanosheets. The maximum Langmuir adsorption capacity could reach 523.13 mg/g. FTIR and XPS analysis indicated that the interaction mechanism of U(VI) with HBWO is mainly surface complexation of strong ionic bond (M–O) and hydroxyl (–OH) groups. In addition, HBWO has strong ion selectivity for U(VI) and good regeneration and reuse performance. These results demonstrated that HBWO might potentially remediate actual uranium-containing wastewater. [ABSTRACT FROM AUTHOR]

Epilepsy is one of the most prevalent neurological conditions and antiepileptic drugs are the mainstay of epilepsy treatment. High variation in pharmacokinetic profiles of several antiepileptic drugs highlights the importance of therapeutic drug monitoring to estimate pharmacokinetic properties and consequently individualize drug posology. In this work, a simple, rapid and robust liquid chromatography-tandem mass spectrometry method was developed for simultaneous quantification of carbamazepine and its metabolite carbamazepine-10,11-epoxide, gabapentin, levetiracetam, lamotrigine, oxcarbazepine and its metabolite mono-hydroxy-derivative metabolite, phenytoin, topiramate, and valproic acid in human plasma for therapeutic drug monitoring. d6-Levetiracetam, d4-gabapentin and d6-valproic acid were used as internal standards. After addition of internal standards along with two-step protein precipitation and dilution sample preparation, plasma samples were analyzed on a C18 column using a gradient elution in 5 min without interference. The calibration curves were linear over a 100-fold concentration range, with determination coefficients (r2) greater than 0.99 for all analytes. The limit of quantification was 0.5 μg mL−1 (0.1 μg mL−1 for oxcarbazepine, 2 μg mL−1 for levetiracetam, and 10 μg mL−1 for valproic acid) with precision and accuracy ranging from 3% to 9% and from 94% to 112%, respectively. Intra- and inter-day precision and accuracy values were within 15% at low, medium and high quality control levels. No significant matrix effect was observed in the normal, hemolyzed, lipemic, and hyperbilirubin blood samples. This method was successfully used in the identification and quantitation of antiepileptic drugs in patients undergoing mono- or polytherapy for epilepsy. [ABSTRACT FROM AUTHOR]

Fine particulate matter organic extract (Po) was reported to promote inflammation in the lung. Sex differences were reported in many inflammatory diseases. In this study, we investigated the effects of Po exposure on pulmonary inflammatory response and evaluated the role of sex in this process. While mice were exposed to 100 µg/m3 Po for 12 weeks by an inhalation exposure system, the lung histopathological analysis shown obvious inflammation, the cell numbers in bronchoalveolar lavage fluid (BALF) were significantly increased, and most inflammatory cytokines in BALF were upregulated. The results of factorial analysis of variance shown that there was an interaction between sex and Po exposure in the inflammatory cell numbers and the levels of tumor necrosis factor-α (TNF-α), interleukin-5 (IL-5), and growth-related oncogene/keratinocyte chemoattractant (GRO/KC). Notably, these changes and interactions were diminished while Po-exposed mice were administered with the estrogen receptor β (ERβ) antagonist. We speculated that sex might affect the levels of inflammatory indicators in BALF of Po-exposed mice and female mice were more prone to inflammation while exposed to Po. Moreover, ERβ was involved in these processes. To our knowledge, this is the first investigation about the role of sex in Po-induced adverse effects. [ABSTRACT FROM AUTHOR]

This bioequivalence study was conducted to determine the pharmacokinetics and safety profiles of an originator and a generic avanafil formulation in Chinese male subjects under fed and fasting conditions. Each eligible subject was initially randomly given avanafil (200 mg) in a test‐reference or reference‐test order, before being switched to another study drug sequence after 7 drug‐free days. The bioequivalence of test and reference avanafil were determined if the 90%CIs of the geometric mean ratio (GMR) for the area under plasma concentration‐time curve (AUC) from time 0 to infinity (AUC0‐∞), AUC from time 0 to the last detectable concentration (AUC0‐t), and the maximum plasma concentration (Cmax) fell within the range 80%‐125%. Under fasting/fed conditions, the 90%CIs of GMR for AUC0‐∞, AUC0‐t, and Cmax were 98.9% to 109.5%/96.0% to 101.2%, 99.6% to 110.3%/96.6% to 102.4%, and 99.3% to 116.8%/94.3% to 106.7%, respectively, which were all within the 80%‐125% range. Adverse events (AEs) occurred in 20.8% of subjects under fasting conditions and 20.7% of subjects under fed conditions, with a severity of grade 1. No significant difference was found in the rate of occurrence of AEs and drug‐related AEs in the test and reference‐avanafil groups (all P >.05). We concluded that the test and reference avanafil were bioequivalent in healthy Chinese male subjects under fasting and fed conditions. [ABSTRACT FROM AUTHOR]

Background: Currently, SARS-CoV-2 liver invasion, inflammatory cytokines, and antiviral drugs are widely thought to be associated with liver dysfunction in COVID-19 patients. Besides, previous studies indicated that ACEI/ARB drugs can increase the expression of hepatic ACE2, a cell entry receptor for SARS-CoV-2. This study aims to investigate whether ACEI/ARB aggravates liver injury and the association of inflammatory cytokines and antiviral drugs with liver dysfunction in patients with hypertension and COVID-19.Method: This retrospective study included 127 hypertensive patients with long-term use or nonuse of ACEI/ARBs hospitalized for COVID-19 from January 30 to April 7, 2020, in Tongji hospital of Wuhan, China. Demographic, clinical, laboratory, treatment, and outcome data were collected.Results: Of the 127 patients with COVID-19 and hypertension, 43 taking long-term of ACEI/ARBs and 84 without using ACEI/ARBs. Abnormal liver function was observed in part of ACEI/ARB and non-ACEI/ARB users but without significant differences between these two groups. Serum inflammatory cytokines, IL-6, IL-8, and TNFα, as well as inflammation-related markers, ferritin, procalcitonin, and C-reactive protein, were significantly elevated in patients with liver dysfunction. IL-6 level was positively correlated with liver function tests on admission and highly consistent with the changes of abnormal ALT, AST, and GGT during hospitalization, but the correlations of other inflammatory cytokines were low. There was no significant association between the use of antiviral drugs and liver dysfunction in these patients.Conclusion: The elevation of inflammatory cytokine, IL-6, but not ACEI/ARB and antiviral drugs, is closely associated with liver dysfunction in patients with hypertension and COVID-19. [ABSTRACT FROM AUTHOR]

Hollow microspheres Bi2WO6 (HBWO) were prepared by the solvothermal method for the adsorption of U(VI) from aqueous solutions. Batch experiments and characterization analysis investigated the adsorption performance and mechanism. The results showed that the adsorption equilibrium could be reached in 30 min at T = 303 K, pH = 6, CU(VI) = 10 mg/L, m/V = 0.1 g/L. The removal efficiency of HBWO for U(VI) in solution was 95.53%, which was about 20% higher than Bi2WO6 nanosheets. The maximum Langmuir adsorption capacity could reach 523.13 mg/g. FTIR and XPS analysis indicated that the interaction mechanism of U(VI) with HBWO is mainly surface complexation of strong ionic bond (M–O) and hydroxyl (–OH) groups. In addition, HBWO has strong ion selectivity for U(VI) and good regeneration and reuse performance. These results demonstrated that HBWO might potentially remediate actual uranium-containing wastewater. [ABSTRACT FROM AUTHOR]

PM2.5 pollution is an important and urgent problem in China that can increase mortality and hospital admissions. Traffic-originated PM2.5 organic component (tPo) mainly contains polycyclic aromatic hydrocarbons (PAHs). Research has shown that PAHs can promote invasion, metastasis, and cancer stem cell properties in lung adenocarcinoma cells, but the exact toxicological mechanism is unknown. In the present study, we investigated the effect of lncRNAs on the progression of lung adenocarcinoma induced by tPo and the underlying mechanisms mediated by lncRNA-signaling pathway interactions. We found that chronic tPo treatment upregulated the expression of loc107985872, which further promoted cell invasion and migration, EMT and cancer stem cell properties via notch1 pathway in lung adenocarcinoma cells. Meanwhile, activation of the notch1 signaling pathway through loc107985872 might be associated with abnormally high expression of its upstream proteins, such as ADAM17, PSEN1 and DLL1. Moreover, tPo exposure induced EMT and the acquisition of cancer stem cell-like properties via the notch1 signaling pathway in vivo. In summary, loc107985872 upregulated by tPo promoted lung adenocarcinoma progression via the notch1 signaling pathway. Image 1 • Chronic tPo treatment upregulated loc107985872 in lung adenocarcinoma cells. • Loc107985872 promotes lung adenocarcinoma progression via notch1 pathway in vitro. • Activation of notch1 pathway might be associated with ADAM17, PSEN1 and DLL1. • tPo exposure induced EMT via notch1 pathway in female and male mice. • tPo exposure promoted cancer stem cell properties via notch1 pathway in female mice. [ABSTRACT FROM AUTHOR]

This study was conducted to elucidate the neuroprotective effect of caffeic acid phenethyl ester (CAPE), ( R )-2-Hydroxy-3-(3,4-dihydroxyphenyl) propionic acid (Danshensu) and Curcumin, three caffeic acid derivatives which are contained in fruits, grains and certain dietary supplements. Our results showed that these compounds significantly attenuated H 2 O 2 -induced toxicity in PC12 cells in a dose-dependent manner. Furthermore, these compounds significantly improved the behavioral performance of d -gal-treated mice in both step-down avoidance test and Morris water maze test. Biochemical examination and western blot analysis showed that these compounds could ameliorate oxidative stress and facilitate activation of the protein kinase A (PKA)-cyclic AMP response element-binding protein (CREB) pathway. Its beneficial effects may partly relate to enhancing the activity of endogenous antioxidant enzymes and modulating the PKA/CREB signaling pathway. Furthermore, our results also indicated that the presence of 3, 4-dihydroxyphenyl groups in A ring may enhance their neuroprotective activity. [ABSTRACT FROM AUTHOR]

The associations between particulate matter (PM) exposure, psychosocial stress and blood cell parameters are bringing novel insights to characterize the early damage of multiple diseases. Based on two studies conducted in three Chinses cities using cross-sectional (Beijing, 425 participants) and panel study (Tianjin and Shanghai, 92 participants with 361 repeated measurements) designs, this study explored the associations between short-term exposure to ambient PM and blood cell parameters, and the effect modification by psychosocial stress. Increasing PM 2.5 exposure was significantly associated with decreases in red blood cell (RBC) count and mean corpuscular hemoglobin concentration (MCHC), and increases in mean corpuscular volume (MCV), platelets count (PLT) and platelet hematocrit (PCT) in both studies. For instance, a 10 μg/m3 increment in PM 2.5 concentration was associated with a 1.04% (95%CI: 0.16%, 1.92%) increase in PLT (4-d) and a 1.09% (95%CI: 0.31%, 1.87%) increase in PCT (4-d) in the cross-sectional study, and a 0.64% (95%CI: 0.06%, 1.22%) increase in PLT (1-d) and a 0.72% (95%CI: 0.33%, 1.11%) increase in PCT (1-d) in the panel study, respectively. In addition, stronger increases in MCV, PLT, and PCT associated with PM 2.5 exposure were found in higher psychosocial stress group compared to lower psychosocial stress group (p for interaction <0.10), indicating that blood cell parameters of individuals with higher psychosocial stress might be more susceptible to the early damages of PM 2.5 exposure. • We evaluated the association of PM2.5 and blood cell parameters in two studies. • Short-term PM2.5 exposure was associated with altered blood cell parameters. • Higher psychosocial stress potentiates the effect of PM2.5 on blood cell parameters. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that exposures to ambient particulate matter with aerodynamic diameter <2.5 μm (PM2.5) and stress are associated with adverse cardiovascular health effects.Objectives: To investigate the potential modifying effect of trait anxiety on the association between short-term exposures to PM2.5 and HRV variables.Methods: A panel of 92 middle-aged and elderly adults in Tianjin and Shanghai were recruited for repeated follow-ups with measurements of 24-h personal exposures to air pollutants and Holter ECG monitoring. Heart rate variability (HRV) variables calculated over 5-minute segments during the 24 h, including low frequency power (LF), high frequency power (HF), standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (rMSSD), were included in the analysis. The Trait Anxiety Inventory was used to investigate the long-term general anxiety level of the participants. Generalized linear mixed-effects model was used to analyze the association between exposure factors and HRV variables, and potential effect modification by trait anxiety.Results: Data on 87 participants were included in final analysis after exclusions. Higher exposure to PM2.5 was associated with lower levels of LF, HF, SDNN and rMSSD, and the largest decreases in LF, HF, SDNN and rMSSD were found at 3-h moving average. Trait anxiety significantly modified the associations of PM2.5 with LF, HF, SDNN and rMSSD, with stronger inverse associations found in high trait anxiety group than in low trait anxiety group. For an IQR (27.3 μg/m³) increase in PM2.5 at 3-h moving average, there were decreases of 3.50% (95% CI: -4.46%, -2.54%) and 3.50% (95% CI: -4.49%, -2.50%) in the high trait anxiety group, and decreases of 0.81% (95% CI: -1.22%, -0.40%) and 0.65% (95% CI: -1.07%, -0.23%) in the low trait anxiety group in HF and rMSSD, respectively (both p for interaction<0.01).Conclusion: Our study suggests that trait anxiety could modify the association of short-term exposure to PM2.5 with HRV variables, indicating that higher trait anxiety may increase the cardiac susceptibility to air pollution in the study participants. [ABSTRACT FROM AUTHOR]