Distribution characteristics, source attribution, and health risk assessment of organophosphate esters in indoor and outdoor dust from various microenvironments in Beijing.

The occurrence and profiles of organophosphate esters (OPEs) were studied in indoor and outdoor dusts from various microenvironments, including forty-seven outdoor dusts from green belts, roads, parks and residence areas, seventy-seven indoor dusts from private cars, print shops, taxis, furniture shops, offices, dormitories, shopping malls and residences house in different districts in Beijing. The total concentrations (Σ12OPEs) were eighteen times higher in indoor dusts (7.14 ×102 to 2.24 ×104 ng/g) than in outdoor dusts (36.0-1.56 ×103 ng/g). OPEs concentrations in samples from taxi and private cars were obviously higher than other indoor microenvironments. Both indoor and outdoor microenvironments also showed different compositional profiles of OPEs, indicating that polyurethane foam/building materials and hydraulic fluids/plastics were the greatest contributions in different microenvironments, with chlorinated alkyl phosphates (Cl-OPEs) being the predominant compound in both indoor dust (52.1-86.5%) and outdoor dust samples (42.6-81.3%). The uncertainty was reduced by Monte Carlo simulation, and the pollution levels of 50th and 95th percentiles were employed to calculate the average daily dosage, which was then used to calculate hazard quotient (HQ) for assessing the health risks to adults and children. Results showed that OPEs were safe even at extremely consumed concentration percentile (95th) in all groups.

Estimating the prevalence of depression using wastewater-based epidemiology: A case study in Qinghai Province, West China.

Wastewater-based epidemiology (WBE) is considered a cost-effective alternative approach capable of determining the consumption and prevalence of drug use in communities, however, the application of WBE for estimating the prevalence of depression has seldom been reported. In this study, the prevalence of antidepressants was estimated in five cities in Qinghai Province, west China to examine the feasibility of using WBE to estimate the depression prevalence. Residual concentrations of the drugs varied from different wastewater treatment plants (WWTPs) in five cities. Venlafaxine (0.06-720 ng/L), O-desmethylvenlafaxine (1.31-1659 ng/L), paroxetine (

Comprehensive investigation and risk assessment of organic contaminants in Yellow River Estuary using suspect and nontarget screening strategies.

Contaminants of emerging concerns (CECs) include numerous chemicals that may pose known and unknown risks to the ecosystem, and identification and risk ranking of these compounds is essential for the environmental management. In this study, liquid and gas chromatography time-of-flight mass spectrometry (LC-QTOF-MS and GC-QTOF-MS) were used to characterize the occurrence of CECs in the surface water of the Yellow River Estuary (YRE). A total of 295 and 315 chemicals were identified by LC-QTOF-MS and GC-QTOF-MS, respectively. The occurrence of two compounds, erucamide and 2-phenylquinoline, was for the first time reported in the aquatic environment in YRE. The concentrations of 121 CECs, including 35 antibiotics, 49 pesticides and veterinary, 16 polycyclic aromatic hydrocarbons and 21 phthalic acid esters were further quantified by target analysis, which showed the detection of 99 compounds in the surface water in the range of 7.07-4611.26 ng/L. Ecological risks of pollutants based on the risk quotient (RQ) method revealed that 13 pollutants posed ecological risks to the aquatic ecosystem (RQ > 1), and pesticides (n = 12) were the main risk contributors. Here, all CECs data sets were finally transformed and ranked in the framework of the toxicological priority index (ToxPi), and a total of 81 priority control pollutants were identified in the surface water of YRE. This study highlighted the necessity of suspect and nontarget screening for CECs in estuaries, and revealed the importance of localized contamination sources in urban and agricultural environment.

Effect of thiamethoxam on the behavioral profile alteration and toxicity of adult zebrafish at environmentally relevant concentrations.

Thiamethoxam (THM) is a commercial neonicotinoid insecticide with broad-spectrum insecticidal activity. It has been widely detected in the aquatic environment, but its behavioral toxicity on aquatic organisms received limited attention. In this study, adult zebrafish were exposed to THM at three levels (0.1, 10, and 1000 µg/L) for 45 days to investigate its effect on their ecological behavior, histopathology, bioaccumulation, and stress response. The bioconcentration factor in zebrafish brain was significantly higher (p < 0.05) at low concentration of THM (0.1 µg/L) than in other treatment groups. In terms of individual behavior, the locomotor activity, aggregation, and social activity of fish were enhanced after THM exposure, but the memory of the food zone was disturbed and abnormal swimming behavior was observed. THM exposure caused brain tissue necrosis, erythrocyte infiltration, cloudy swelling, and other pathological changes in brain tissue and affected the concentrations of acetylcholinesterase and cortisol related to neurotoxicity. The condition factor and organ coefficients (brain, heart, and intestine) of zebrafish were markedly impacted by THM treatment at 0.1 and 1000 µg/L, respectively. This finding showed that THM was more harmful to fish behavior than lethality, reproduction, and growth, and a behavioral study can be a useful tool for ecological risk assessment.

Cancer Stem Cell Biomarkers in the Nervous System.

Cancer stem cells (CSCs) have been increasingly recognized in recent years. CSCs from human neural tumors are one of the root causes of metastatic tumor progression, therapeutic resistance and recurrence. However, there is a lack of comprehensive literature that systematically consolidates the biomarkers specific to CSCs in neurological cancers. Therefore, this review provides a comprehensive summary of cancer stem cell (CSC) biomarkers for neurological tumors such as glioma, meningioma, medulloblastoma and neurofibroma. It also points out the possible functions of these biomarkers in diagnosis, treatment and prognosis, providing a broader perspective. First, we quantitatively screened key words such as CSCs, biomarkers, and expression by bibliometric analysis and clarified the intrinsic connections between the key words. Then, we describe the CSC biomarkers of major neurological tumors and their pathway mechanisms, and provide an in-depth analysis of the commonalities and differences with the biomarkers of non-CSCs. In addition, many studies have shown that antipsychotic drugs can inhibit tumor growth and reduce the expression of CSC biomarkers, which facilitates targeted therapy against tumors in the nervous system. Therefore, this study will focus on the biomarkers of CSCs in the nervous system, hoping to provide guidance for future in-depth exploration and monitoring of neurological tumors for clinical applications.

[Comparison of Health Risk from Sources of Perfluoroalkyl Substances in Taihu Lake for Different Years].

Pollution characteristics and spatial distributions of perfluoroalkyl substances (PFASs) in surface water samples were investigated in Taihu Lake in 2010 and 2019, respectively. A hybrid model based on the positive matrix factorization (PMF) and the health risk assessment model were employed for quantifying the contributions of sources to PFASs concentrations and the source risks. The method contained two stages:1 the sources of PFASs were apportioned using the PMF model, and 2 the contribution of health risks from each source was quantitively estimated. Three factors (source categories) were extracted using PMF, including:coating industry sources, textile and electroplating sources, and fluoride-processing industry sources. Their contributions to PFASs concentration were 29.59%, 25.68%, and 44.72% for 2010 and 67.69%, 10.26%, 22.05%, for 2019, respectively. The health risk of PFASs in the water assessed by the health risk assessment (HRA) model was 4.56E-07 for 2010 and 2.69E-07 for 2019, which was lower than 1E-06. The source contributions to health risks estimated by the PMF-HRA hybrid model were:64.86% (2010) and 92.48% (2019) for textile and electroplating sources, 31.30% (2010) and 5.04% (2019) for coating industry sources, and 3.84% (2010) and 2.48% (2019) for fluoride-processing industry sources. For the two years, the concentrations of PFOA and PFOS were reduced significantly, indicating the effective control of their emissions during the past ten years in Taihu Lake. However, it was also shown that the concentrations of PFBS and PFHxS were increased. These findings suggest that the above short chain-PFCs species should be the focus for further control and management, and their health risks should be studied in future research.

Association between air pollution and outpatient visits for allergic rhinitis: Effect modification by ambient temperature and relative humidity.

Mounting evidence indicated the associations between air pollution and outpatient visits for allergic rhinitis (AR), while few studies assessed the effect modification of these associations by ambient temperature and relative humidity (RH). In this study, dataset of AR outpatients was obtained from Chinese People's Liberation Army Strategic Support Force Characteristic Medical Center in Beijing during 2014 to 2019, and the average concentrations of air pollutants including particulate matter ≤2.5 µm in diameter (PM2.5) and ≤10 µm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and meteorological factors (temperature and RH) at the same period were collected from one nearby air monitoring station. We performed a time-series study with Poisson regression model to examine the effects of air pollutants on AR outpatients after adjustment for potential confounders. And the effects modification analysis was further conducted by stratifying temperature and RH by tertiles into three groups of low, middle and high. In total of 33,599 outpatient visits for AR were recorded during the study period. Results found that a 10 µg/m3 increase in PM2.5, PM10, NO2 and SO2 was associated with significant increases in AR outpatients of 1.24% (95% confidence interval (CI): 0.69%, 1.78%), 0.79% (95% CI: 0.43%, 1.15%), 3.05% (95% CI: 1.72%, 4.40%) and 5.01% (95% CI: 1.18%, 8.96%), respectively. Stronger associations were observed in males than those in females, as well as in young adults (18-44 years) than those in other age groups. Air pollution effects on AR outpatients increased markedly at low temperature (<33.3th percentile) and high RH (>66.7th percentile). Findings in this study indicate that air pollution is associated with increased risk of AR outpatients, and the effects of air pollution on AR could be enhanced at low temperature and high RH.

Multi-walled carbon nanotubes induce IL-1ß secretion by activating hemichannels-mediated ATP release in THP-1 macrophages.

Multi-walled carbon nanotubes (MWCNTs) are known to induce pulmonary inflammatory effects through stimulating pro-inflammatory cytokine secretion from alveolar macrophages. Despite extensive studies on MWCNTs' pro-inflammatory reactivity, the understanding of molecular mechanisms involved is still incomplete. In this study, we investigated hemichannel's involvement in MWCNTs-induced macrophage IL-1ß release. Our results showed that the unmodified and COOH MWCNTs could induce ATP release and ATP-P2X7R axis-dependent IL-1ß secretion from THP-1 macrophages. By using various inhibitors, we confirmed that the MWCNTs-induced ATP release was primarily through hemichannels. EtBr dye uptake assay detected significant hemichannels opening in MWCNTs exposed THP-1 macrophages. Inhibition of hemichannels by CBX, 43Gap27, or 10Panx1 pretreatment results in decreased ATP and IL-1ß release. The addition of ATP restored the reduced IL-1ß secretion level from hemichannel inhibition. We also confirmed with five other types of MWCNTs that the induction of hemichannels by MWCNTs strongly correlates with their capacity to induce IL-1ß secretion. Taken together, we conclude that hemichannels-mediated ATP release and subsequent NLRP3 inflammasome activation through P2X7R may be one mechanism by which MWCNTs induce macrophage IL-1ß secretion. Our findings may provide a novel molecular mechanism for MWCNTs induced IL-1ß secretion.

Paracellular permeability changes induced by multi-walled carbon nanotubes in brain endothelial cells and associated roles of hemichannels.

Multi-walled carbon nanotubes (MWCNTs) have promising applications in neurology depending on their unique physicochemical properties. However, there is limited understanding of their impacts on brain microvascular endothelial cells, the cells lining the vessels and maintaining the low and selective permeability of the blood-brain barrier. In this study, we examined the influence of pristine MWCNT (p-MWCNT) and carboxylated MWCNT (c-MWCNT) on permeability and tight junction tightness of murine brain microvascular endothelial cells, and investigated the potential mechanisms in the sight of hemichannel activity. Treatment with p-MWCNT for 24 h at subtoxic concentration (20 µg/mL) decreased the protein expression of occludin, disrupted zonula occludens-1 continuity, and elevated monolayer permeability as quantified by transendothelial electrical resistance and paracellular flux of 4000 Da fluorescein isothiocyanate-dextran conjugates. Moreover, p-MWCNT exposure also increased hemichannel activity with upregulated protein expression and altered subcellular localization of connexin (Cx)43 and pannexin (Panx)1. p-MWCNT-induced elevation in endothelial permeability could be prevented by hemichannel inhibitor carbenoxolone and peptide blocker of Cx43 and Panx1, indicating the crucial role of activated Cx43 and Panx1 hemichannels. Furthermore, Cx43 and Panx1 hemichannel-mediated ATP release might be involved in p-MWCNT-induced rise in endothelial permeability. In contrast, the above effects caused by p-MWCNT were not observed in cells treated with c-MWCNT, the functionalized form with more stable dispersion and a lower tendency to aggregate. Our study contributes further understanding of the impact of MWCNTs on brain endothelial tightness and permeability, which may have important implications for the safety application of MWCNTs in nanomedicine.

Enoxaparin sensitizes human non-small-cell lung carcinomas to gefitinib by inhibiting DOCK1 expression, vimentin phosphorylation, and Akt activation.

Gefitinib is widely used for the treatment of lung cancer in patients with sensitizing epidermal growth factor receptor mutations, but patients tend to develop resistance after an average of 10 months. Low molecular weight heparins, such as enoxaparin, potently inhibit experimental metastasis. This study aimed to determine the potential of combined enoxaparin and gefitinib (enoxaparin + gefitinib) treatment to inhibit tumor resistance to gefitinib both in vitro and in vivo. A549 and H1975 cell migration was analyzed in wound closure and Transwell assays. Akt and extracellular signal-related kinase 1/2 signaling pathways were identified, and a proteomics analysis was conducted using SDS-PAGE/liquid chromatography-tandem mass spectrometry analysis. Molecular interaction networks were visualized using the Cytoscape bioinformatics platform. Protein expression of dedicator of cytokinesis 1 (DOCK1) and cytoskeleton intermediate filament vimentin were identified using an enzyme-linked immunosorbent assay, Western blot, and small interfering RNA transfection of A549 cells. In xenograft A549-luc-C8 tumors in nude mice, enoxaparin + gefitinib inhibited tumor growth and reduced lung colony formation compared with gefitinib alone. Furthermore, the combination had stronger inhibitory effects on cell migration than either agent used individually. Additional enoxaparin administration resulted in better effective inhibition of Akt activity compared with gefitinib alone. Proteomics and network analysis implicated DOCK1 as the key node molecule. Western blot verified the effective inhibition of the expression of DOCK1 and vimentin phosphorylation by enoxaparin + gefitinib compared with gefitinib alone. DOCK1 knockdown confirmed its role in cell migration, Akt expression, and vimentin phosphorylation. Our data indicate that enoxaparin sensitizes gefitinib antitumor and antimigration activity in lung cancer by suppressing DOCK1 expression, Akt activity, and vimentin phosphorylation.