o-Semiquinone Radical and o-Benzoquinone Selectively Degrade Aniline Contaminants in the Periodate-Mediated Advanced Oxidation Process.

Advanced oxidation processes (AOPs) often employ strong oxidizing inorganic radicals (e.g., hydroxyl and sulfate radicals) to oxidize contaminants in water treatment. However, the water matrix could scavenge the strong oxidizing radicals, significantly deteriorating the treatment efficiency. Here, we report a periodate/catechol process in which reactive quinone species (RQS) including the o-semiquinone radical (o-SQ•-) and o-benzoquinone (o-Q) were dominant to effectively degrade anilines within 60 s. The second-order reaction rate constants of o-SQ•- and o-Q with aniline were determined to be 1.0 × 108 and 4.0 × 103 M-1 s-1, respectively, at pH 7.0, which accounted for 21% and 79% of the degradation of aniline with a periodate-to-catechol molar ratio of 1:1. The major byproducts were generated via addition or polymerization. The RQS-based process exhibited excellent anti-interference performance in the degradation of aniline-containing contaminants in real water samples in the presence of diverse inorganic ions and organics. Subsequently, we extended the RQS-based process by employing tea extract and dissolved organic matter as catechol replacements as well as metal ions [e.g., Fe(III) or Cu(II)] as periodate replacements, which also exhibited good performance in aniline degradation. This study provides a novel strategy to develop RQS-based AOPs for the highly selective degradation of aniline-containing emerging contaminants.

Molecularly imprinted polymer sheathed mesoporous silica tube as SPME fiber coating for determination of tobacco-specific nitrosamines in water.

Tobacco-specific nitrosamines (TSNAs) are probably carcinogenic disinfection byproducts eliciting health risk concerns. The determination and surveillance of TSNAs in water is still cumbersome due to the lack of advanced sample preparation methods. Herein, we prepared a solid phase microextraction (SPME) fiber coated with the molecularly imprinted polymer (MIP) sheathed mesoporous silica tube (MST) composite material, and developed a highly efficient, selective, and sensitive method for the determination of five TSNAs in water. Benefiting from the TSNAs-specific recognition of MIP and the increased specific surface area derived from MST, the MIP@MST fiber exhibited excellent extraction performance for TSNAs, which was much superior to the commercially available SPME fibers. By coupling to high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), the outstanding analytical merits such as low method detection limits (ranging 0.1-6.7 ng L-1) and good reproducibility (intra-fiber and inter-fiber relative standard deviations ranging 4.1 %-11.6 % and 3.5 %-12.2 %, respectively) were achieved with the consumption of 8 mL water sample and 100 µL methanol solvent in 50 min. The feasibility of the SPME-HPLC-MS/MS method was demonstrated in tap water and chloraminated source water, with relative recoveries for the five TSNAs ranging from 85.2 % to 108.5 %. In result, none of the TSNAs were found in the tap water samples, while 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-Butanol (NNAL) were detected in the chloraminated source water samples. The rapid and convenient SPME-HPLC-MS/MS method developed in this study offers a powerful tool for monitoring TSNAs in water.

Complement factor H inhibits endothelial cell migration through suppression of STAT3 signaling.

Complement factor H (CFH), a major soluble inhibitor of complement, is a plasma protein that directly interacts with the endothelium of blood vessels. Mutations in the CFH gene lead to diseases associated with excessive angiogenesis; however, the underlying mechanisms are unknown. The present study aimed to determine the effects of CFH on endothelial cells and to explore the underlying mechanisms. The adenoviral plasmid expressing CFH was transduced into HepG2 cells, and the culture medium supernatant was collected and co-cultured with human umbilical vein endothelial cells (HUVECs). Cell proliferation was measured by CCK8 and MTT assays, and cell migration was measured by wound healing and Transwell assays. Reverse transcription-quantitative PCR was performed to detect gene transcription. Western blotting was used to determine protein levels. The results revealed that CFH can inhibit migration, but not viability, of HUVECs. In addition, CFH did not significantly alter MAPK or TGF-ß signaling, whereas it decreased STAT3 phosphorylation in HUVECs. Furthermore, CFH failed to reduce migration of HUVECs, with inhibition of STAT3 signaling by STATTIC or activation of STAT3 signaling by overexpression of STAT3 (Y705D) compromising CFH-inhibited HUVEC migration. CFH also decreased the expression levels of vascular endothelial growth factor receptor 2, a downstream effector of STAT3 mediating endothelial cell migration. In conclusion, the present study suggested that CFH may be a potential therapeutic target for angiogenesis-related diseases.

Synergistic cytotoxicity of binary combinations of inorganic and organic disinfection byproducts assessed by real-time cell analysis.

Chlorine, chlorine dioxide, and ozone are widely used as disinfectants in drinking water treatments. However, the combined use of different disinfectants can result in the formation of various organic and inorganic disinfection byproducts (DBPs). The toxic interactions, including synergism, addition, and antagonism, among the complex DBPs are still unclear. In this study, we established and verified a real-time cell analysis (RTCA) method for cytotoxicity measurement on Chinese hamster ovary (CHO) cell. Using this convenient and accurate method, we assessed the cytotoxicity of a series of binary combinations consisting of one of the 3 inorganic DBPs (chlorite, chlorate, and bromate) and one of the 32 regulated and emerging organic DBPs. The combination index (CI) of each combination was calculated and evaluated by isobolographic analysis to reflect the toxic interactions. The results confirmed the synergistic effect on cytotoxicity in the binary combinations consisting of chlorite and one of the 5 organic DBPs (2 iodinated DBPs (I-DBPs) and 3 brominated DBPs (Br-DBPs)), chlorate and one of the 4 organic DBPs (3 aromatic DBPs and dibromoacetonitrile), and bromate and one of the 3 organic DBPs (2 I-DBPs and dibromoacetic acid). The possible synergism mechanism of organic DBPs on the inorganic ones may be attributed to the influence of organic DBPs on cell membrane and cell antioxidant system. This study revealed the toxic interactions among organic and inorganic DBPs, and emphasized the latent adverse outcomes in the combined use of different disinfectants.

ClO2 pre-oxidation changes dissolved organic matter at the molecular level and reduces chloro-organic byproducts and toxicity of water treated by the UV/chlorine process.

The formation of undesirable chloro-organic byproducts is of great concern in the UV/chlorine process. In this study, chlorine dioxide (ClO2) pre-oxidation was applied to control the formation of chloro-organic byproducts and the toxicity in UV/chlorine-treated water. The molecular-level changes in dissolved organic matter (DOM) were tracked by using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and ClO2 pre-oxidation was found to preferentially react with DOM moieties with high aromaticity level and with a carbon number of > 18, producing compounds with a higher degree of oxidation and lower aromaticity. The ClO2-treated DOM was found to be less susceptible to attack by radicals and free chlorine in the UV/chlorine process compared to the raw DOM. ClO2 pre-oxidation resulted in a significant decrease in the number of unknown chloro-organic byproducts (i.e., -17%) and the total intensity of organic chlorine detected by FT-ICR-MS (i.e., -31%). The molecular characteristics, such as O/C, aromaticity index, and the average number of chlorine atoms, of these unknown chloro-organic byproducts generated in the scenarios with and without ClO2 pre-oxidation were also different. Additionally, ClO2 pre-oxidation reduced the genotoxicity (SOS/umu test) and cytotoxicity (Hep G2 cytotoxicity assay) of UV/chlorine-treated water by 26% and 20%, respectively. The findings in this study highlight the merits of ClO2 pre-oxidation for controlling chloro-organic byproducts and reducing the toxicity of water treated by the UV/chlorine process in actual practice.

Multi-angle comparison of UV/chlorine, UV/monochloramine, and UV/chlorine dioxide processes for water treatment and reuse.

Advanced oxidation processes (AOPs) have been increasingly studied and practiced for micropollutant abatement in drinking water treatment and potable water reuse. This study conducted the multi-angle comparison of the UV/chlorine, UV/monochloramine (UV/NH2Cl), and UV/chlorine dioxide (UV/ClO2) AOPs with respect to reactive species generation, micropollutant degradation, byproduct formation, and toxicity change. The concentrations of radicals (HO·, Cl·, and ClO·) generated in the three AOPs followed the order of UV/chlorine > UV/NH2Cl > UV/ClO2 at an oxidant dose of 70 µM, an irradiation wavelength of 254 nm, and a pH of 7.5. The concentration of ozone generated in the UV/ClO2 AOP was higher than that in the UV/chlorine AOP, while ozone was not generated in the UV/NH2Cl AOP. The effects of pH (pH 6.0, 7.5, and 9.0) and UV wavelength (254 nm, 285 nm, and 300 nm) on the three AOPs were evaluated and compared. Using the radical and ozone concentrations determined in this study, the pseudo-first-order degradation rate constants of 24 micropollutants by the three AOPs were predicted and compared. When the three AOPs were used to treat the water containing the same concentration of natural organic matter, the formation of total organic chlorine (TOCl) and the organic byproduct-associated toxicity followed the same order of UV/chlorine > UV/NH2Cl > UV/ClO2. On the contrary, the inorganic byproduct-associated toxicity followed the order of UV/ClO2 > UV/chlorine > UV/NH2Cl, due to the high concentrations of chlorite and chlorate formed in the UV/ClO2 AOP. Findings in this study offer fundamental information useful for the selection and operation of AOPs for micropollutant abatement in drinking water treatment and potable water reuse.

Sequential ClO2-UV/chlorine process for micropollutant removal and disinfection byproduct control.

This study systematically revealed the feasibility of the sequential ClO2-UV/chlorine process for micropollutant removal and disinfection byproduct (DBP) control. The results demonstrated that the sequential ClO2-UV/chlorine process was effective for the removal of 12 micropollutants. ClO2 pre-treatment reduced the formation of disinfect byproducts (DBPs) in the UV/chlorine process. Compared to the UV/chlorine process, ClO2 pre-treatment (1.0 mg L-1) decreased the formation of the 6 DBPs by 25.1-72.2%; and decreased the formation potential of the 6 DBPs by 13.9-51.8%. Moreover, ClO2 pre-treatment reduced the concentration of total organic chlorine by 19.8%. ClO2 pre-treatment affected the UV/chlorine process in different ways. Firstly, ClO2 pre-treatment generated chlorite, which dominantly served as a scavenger of chlorine radical (Cl) and hydroxyl radical (HO). Secondly, ClO2 pre-treatment decreased the reactivity of natural organic matter (NOM) towards radicals. Finally, ClO2 pre-treatment altered the properties of NOM, in terms of reducing the electron-donating capacity and aromaticity of NOM (SUVA254), and slightly reducing the average molecular weight of NOM. Overall, ClO2 pre-treatment effectively controlled the formation of DBPs in the UV/chlorine process. This study confirmed the sequential ClO2-UV/chlorine process was an alternative strategy to balancing the micropollutant removal and DBP control.

Hypoxia Inhibits Proliferation of Human Dermal Lymphatic Endothelial Cells via Downregulation of Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 Expression.

OBJECTIVE: Lymphatic endothelial cell (LEC) proliferation is essential for lymphangiogenesis. Hypoxia induces lymphangiogenesis, but it directly inhibits LEC proliferation and the underlying mechanisms have not been fully understood. The aim of this study was to investigate the role of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in hypoxia-repressed LEC proliferation. METHODS: Human dermal lymphatic endothelial cells (HDLECs) were cultured under normoxic or hypoxic conditions, and cell proliferation was determined using MTT or CCK-8 assays. CEACAM1 expression was silenced by siRNA transfection. Activation of mitogen-activated protein kinases (MAPKs) was examined by Western blotting and blocked by specific inhibitors. RESULTS: Under hypoxia, HDLECs proliferation was suppressed and CEACAM1 expression was downregulated. Silence of CEACAM1 in normoxia inhibited HDLECs proliferation and did not further decrease proliferation in HDLECs in response to hypoxia, suggesting that CEACAM1 may mediate hypoxia-induced inhibition of HDLECs proliferation. In addition, silence of CEACAM1 increased phosphorylation of MAPK molecules: extracellular signal-regulated kinase (ERK), p38 MAPK and Jun N-terminal kinase (JNK) in HDLECs. However, only inhibition of the JNK pathway rescued the reduction of HDLEC proliferation induced by CEACAM1 silence. CONCLUSION: Our results suggested that hypoxia downregulates CEACAM1 expression by activation of the JNK pathway, leading to inhibition of HDLEC proliferation. These findings may help to understand the mechanisms of LEC-specific response to hypoxia and develop novel therapies for pathological lymphangiogenesis.

Micropollutant abatement and byproduct formation during the co-exposure of chlorine dioxide (ClO2) and UVC radiation.

Photolysis of ClO2 by UVC radiation occurs in several drinking water treatment scenarios (e.g., pre-oxidation by ClO2 with post-UVC disinfection or a multi-barrier disinfection system comprising ClO2 and UVC disinfection in sequence). However, whether micropollutants are degraded and undesired byproducts are formed during the co-exposure of ClO2 and UVC radiation remain unclear. This study demonstrated that four micropollutants (trimethoprim, iopromide, caffeine, and ciprofloxacin) were degraded by 14.4-100.0% during the co-exposure of ClO2 and UVC radiation in the synthetic drinking water under the environmentally relevant conditions (UV dose of 207 mJ cm-2, ClO2 dose of 1.35 mg L-1, and pH of 7.0). Trimethoprim and iopromide were predominantly degraded by ClO2 oxidation and direct UVC photolysis, respectively. Caffeine and ciprofloxacin were predominantly degraded by the radicals (HO• and Cl•) and the in-situ formed free chlorine from ClO2 photolysis, respectively. The yields of total organic chlorine (12.5 µg L-1 from 1.0 mg C L-1 of NOM) and chlorate (0.14 mg L-1 From 1.35 mg L-1 of ClO2) during the co-exposure were low. However, the yield of chlorite was high (0.76 mg L-1 from 1.35 mg L-1 of ClO2), which requires attention and control.

Dihydroartemisinin inhibits the expression of von Willebrand factor by downregulation of transcription factor ERG in endothelial cells.

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has effective antitumor and anti-inflammatory actions. von Willebrand factor (vWF), a large multifunctional glycoprotein, has a prominent function in hemostasis and is a key factor in thrombus formation. In addition, vWF has been regarded as a prospective biomarker for the diagnosis of endothelial dysfunction. In our experiment, we observed that 25 µM DHA specifically downregulated the expression of vWF mRNA and protein in human umbilical vein endothelial cells (HUVECs). Further investigations demonstrated that this DHA-decreased vWF expression was mediated by the transcription factor ERG and not GATA3. Luciferase activity assay confirmed that DHA regulated the ERG binding with the -56 ETS-binding motif on the human vWF promoter. Thus, the -56 ETS motif on the vWF promoter region regulates the expression of vWF gene which is induced by DHA. Taken together, we proved that DHA decreased the vWF transcription through the downregulation of ERG in HUVECs. As vWF plays a key role in vascular homeostasis, our findings suggest a new role of DHA in vascular diseases.

Prognostic value of plasma von Willebrand factor levels in major adverse cardiovascular events: a systematic review and meta-analysis.

BACKGROUND: Prediction of major adverse cardiovascular events (MACEs) may offer great benefits for patients with coronary artery disease (CAD). Von Willebrand factor (vWF) is stored in endothelial cells and released into blood plasma upon vascular dysfunction. This meta-analysis was performed to evaluate the prognostic value of plasma vWF levels in CAD patients with MACEs. METHODS: A total of 15 studies were included in this meta-analysis through the search in PubMed, Embase and CNKI. Data were collected from 960 patients who had MACEs after CAD and 3224 controls nested without the adverse events. The standard mean difference (SMD) and 95% confidence intervals (95% CI) were calculated using random-effects model. RESULTS: The plasma vWF levels examined at 24 h and 48 h after admission were significantly higher in CAD patients with MACEs than those without. The pooled SMD among the MACEs group and the non-MACEs group was 0.55 (95% CI = 0.30-0.80, P < 0.0001) and 0.70 (95% CI = 0.27-1.13, P = 0.001), respectively. However, no significant difference was found in plasma vWF levels on admission between the two groups. CONCLUSION: Plasma vWF level in CAD patients examined at 24 h and 48 h after admission might be an independent prognostic factor for MACE.

Plasma levels of von Willebrand factor in type 2 diabetes patients with and without cardiovascular diseases: A meta-analysis.

Chronic vascular complications are the major causes of death and disability of type 2 diabetes mellitus (T2DM) patients. von Willebrand factor (vWF) is involved in pathogenesis of cardiovascular diseases (CVD). Previous studies showed elevated plasma levels of vWF in T2DM patients with CVD, but the association has not been validated. The aim of this meta-analysis was to compare plasma levels of vWF in T2DM patients with and without CVD. We performed a meta-analysis based on published case-control studies of vWF in T2DM patients with and without CVD indexed in PubMed and other databases updated to April 2018. After independently assessing methodological quality and extracting data, 9 eligible studies were obtained including 576 cases and 632 controls. The standard mean difference (SMD) and 95% confidence intervals (95% CI) were calculated using random-effects model. Meta-analysis showed that plasma level of vWF was significantly higher in T2DM patients with CVD than T2DM patients without CVD (SMD = 0.61; 95% CI, 0.32-0.90; P < .00001). Subgroup and sensitivity analyses confirmed the robustness of the results. Plasma levels of vWF are significantly elevated in patients with T2DM complicated by CVD. This study helps further characterize the prognostic value of vWF for cardiovascular complications in T2DM patients.