Pleiotropic modifiers of age-related diabetes and neonatal intestinal obstruction in cystic fibrosis.

Individuals with cystic fibrosis (CF) develop complications of the gastrointestinal tract influenced by genetic variants outside of CFTR. Cystic fibrosis-related diabetes (CFRD) is a distinct form of diabetes with a variable age of onset that occurs frequently in individuals with CF, while meconium ileus (MI) is a severe neonatal intestinal obstruction affecting ∼20% of newborns with CF. CFRD and MI are slightly correlated traits with previous evidence of overlap in their genetic architectures. To better understand the genetic commonality between CFRD and MI, we used whole-genome-sequencing data from the CF Genome Project to perform genome-wide association. These analyses revealed variants at 11 loci (6 not previously identified) that associated with MI and at 12 loci (5 not previously identified) that associated with CFRD. Of these, variants at SLC26A9, CEBPB, and PRSS1 associated with both traits; variants at SLC26A9 and CEBPB increased risk for both traits, while variants at PRSS1, the higher-risk alleles for CFRD, conferred lower risk for MI. Furthermore, common and rare variants within the SLC26A9 locus associated with MI only or CFRD only. As expected, different loci modify risk of CFRD and MI; however, a subset exhibit pleiotropic effects indicating etiologic and mechanistic overlap between these two otherwise distinct complications of CF.

MagicalRsq: Machine-learning-based genotype imputation quality calibration.

Whole-genome sequencing (WGS) is the gold standard for fully characterizing genetic variation but is still prohibitively expensive for large samples. To reduce costs, many studies sequence only a subset of individuals or genomic regions, and genotype imputation is used to infer genotypes for the remaining individuals or regions without sequencing data. However, not all variants can be well imputed, and the current state-of-the-art imputation quality metric, denoted as standard Rsq, is poorly calibrated for lower-frequency variants. Here, we propose MagicalRsq, a machine-learning-based method that integrates variant-level imputation and population genetics statistics, to provide a better calibrated imputation quality metric. Leveraging WGS data from the Cystic Fibrosis Genome Project (CFGP), and whole-exome sequence data from UK BioBank (UKB), we performed comprehensive experiments to evaluate the performance of MagicalRsq compared to standard Rsq for partially sequenced studies. We found that MagicalRsq aligns better with true R2 than standard Rsq in almost every situation evaluated, for both European and African ancestry samples. For example, when applying models trained from 1,992 CFGP sequenced samples to an independent 3,103 samples with no sequencing but TOPMed imputation from array genotypes, MagicalRsq, compared to standard Rsq, achieved net gains of 1.4 million rare, 117k low-frequency, and 18k common variants, where net gains were gained numbers of correctly distinguished variants by MagicalRsq over standard Rsq. MagicalRsq can serve as an improved post-imputation quality metric and will benefit downstream analysis by better distinguishing well-imputed variants from those poorly imputed. MagicalRsq is freely available on GitHub.

Identification and single-base gene-editing functional validation of a cis-EPO variant as a genetic predictor for EPO-increasing therapies.

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are currently under clinical development for treating anemia in chronic kidney disease (CKD), but it is important to monitor their cardiovascular safety. Genetic variants can be used as predictors to help inform the potential risk of adverse effects associated with drug treatments. We therefore aimed to use human genetics to help assess the risk of adverse cardiovascular events associated with therapeutically altered EPO levels to help inform clinical trials studying the safety of HIF-PHIs. By performing a genome-wide association meta-analysis of EPO (n = 6,127), we identified a cis-EPO variant (rs1617640) lying in the EPO promoter region. We validated this variant as most likely causal in controlling EPO levels by using genetic and functional approaches, including single-base gene editing. Using this variant as a partial predictor for therapeutic modulation of EPO and large genome-wide association data in Mendelian randomization tests, we found no evidence (at p < 0.05) that genetically predicted long-term rises in endogenous EPO, equivalent to a 2.2-unit increase, increased risk of coronary artery disease (CAD, OR [95% CI] = 1.01 [0.93, 1.07]), myocardial infarction (MI, OR [95% CI] = 0.99 [0.87, 1.15]), or stroke (OR [95% CI] = 0.97 [0.87, 1.07]). We could exclude increased odds of 1.15 for cardiovascular disease for a 2.2-unit EPO increase. A combination of genetic and functional studies provides a powerful approach to investigate the potential therapeutic profile of EPO-increasing therapies for treating anemia in CKD.

Genetic variation in severe cystic fibrosis liver disease is associated with novel mechanisms for disease pathogenesis.

BACKGROUND AND AIMS: It is not known why severe cystic fibrosis (CF) liver disease (CFLD) with portal hypertension occurs in only ~7% of people with CF. We aimed to identify genetic modifiers for severe CFLD to improve understanding of disease mechanisms. APPROACH AND RESULTS: Whole-genome sequencing was available in 4082 people with CF with pancreatic insufficiency (n = 516 with severe CFLD; n = 3566 without CFLD). We tested ~15.9 million single nucleotide polymorphisms (SNPs) for association with severe CFLD versus no-CFLD, using pre-modulator clinical phenotypes including (1) genetic variant ( SERPINA1 ; Z allele) previously associated with severe CFLD; (2) candidate SNPs (n = 205) associated with non-CF liver diseases; (3) genome-wide association study of common/rare SNPs; (4) transcriptome-wide association; and (5) gene-level and pathway analyses. The Z allele was significantly associated with severe CFLD ( p = 1.1 × 10 -4 ). No significant candidate SNPs were identified. A genome-wide association study identified genome-wide significant SNPs in 2 loci and 2 suggestive loci. These 4 loci contained genes [significant, PKD1 ( p = 8.05 × 10 -10 ) and FNBP1 ( p = 4.74 × 10 -9 ); suggestive, DUSP6 ( p = 1.51 × 10 -7 ) and ANKUB1 ( p = 4.69 × 10 -7 )] relevant to severe CFLD pathophysiology. The transcriptome-wide association identified 3 genes [ CXCR1 ( p = 1.01 × 10 -6 ) , AAMP ( p = 1.07 × 10 -6 ), and TRBV24 ( p = 1.23 × 10 -5 )] involved in hepatic inflammation and innate immunity. Gene-ranked analyses identified pathways enriched in genes linked to multiple liver pathologies. CONCLUSION: These results identify loci/genes associated with severe CFLD that point to disease mechanisms involving hepatic fibrosis, inflammation, innate immune function, vascular pathology, intracellular signaling, actin cytoskeleton and tight junction integrity and mechanisms of hepatic steatosis and insulin resistance. These discoveries will facilitate mechanistic studies and the development of therapeutics for severe CFLD.

Control of false discoveries in grouped hypothesis testing for eQTL data.

BACKGROUND: Expression quantitative trait locus (eQTL) analysis aims to detect the genetic variants that influence the expression of one or more genes. Gene-level eQTL testing forms a natural grouped-hypothesis testing strategy with clear biological importance. Methods to control family-wise error rate or false discovery rate for group testing have been proposed earlier, but may not be powerful or easily apply to eQTL data, for which certain structured alternatives may be defensible and may enable the researcher to avoid overly conservative approaches. RESULTS: In an empirical Bayesian setting, we propose a new method to control the false discovery rate (FDR) for grouped hypotheses. Here, each gene forms a group, with SNPs annotated to the gene corresponding to individual hypotheses. The heterogeneity of effect sizes in different groups is considered by the introduction of a random effects component. Our method, entitled Random Effects model and testing procedure for Group-level FDR control (REG-FDR), assumes a model for alternative hypotheses for the eQTL data and controls the FDR by adaptive thresholding. As a convenient alternate approach, we also propose Z-REG-FDR, an approximate version of REG-FDR, that uses only Z-statistics of association between genotype and expression for each gene-SNP pair. The performance of Z-REG-FDR is evaluated using both simulated and real data. Simulations demonstrate that Z-REG-FDR performs similarly to REG-FDR, but with much improved computational speed. CONCLUSION: Our results demonstrate that the Z-REG-FDR method performs favorably compared to other methods in terms of statistical power and control of FDR. It can be of great practical use for grouped hypothesis testing for eQTL analysis or similar problems in statistical genomics due to its fast computation and ability to be fit using only summary data.

WRKY transcription factors modulate flowering time in four Arachis species: a bioinformatics analysis.

BACKGROUND: WRKY proteins are important transcription factors (TFs) in plants, involved in growth and development and responses to environmental changes. Although WRKY TFs have been studied at the genome level in Arachis genus, including oil crop and turfgrass, their regulatory networks in controlling flowering time remain unclear. The aim of this study was to predict the molecular mechanisms of WRKY TFs regulation flowering time in Arachis genus at the genome level using bioinformatics approaches. RESULTS: The flowering-time genes of Arachis genus were retrieved from the flowering-time gene database. The regulatory networks between WRKY TFs and downstream genes in Arachis genus were predicted using bioinformatics tools. The results showed that WRKY TFs were involved in aging, autonomous, circadian clock, hormone, photoperiod, sugar, temperature, and vernalization pathways to modulate flowering time in Arachis duranensis, Arachis ipaensis, Arachis monticola, and Arachis hypogaea cv. Tifrunner. The WRKY TF binding sites in homologous flowering-time genes exhibited asymmetric evolutionary pattern, indicating that the WRKY TFs interact with other transcription factors to modulate flowering time in the four Arachis species. Protein interaction network analysis showed that WRKY TFs interacted with FRUITFULL and APETALA2 to modulate flowering time in the four Arachis species. WRKY TFs implicated in regulating flowering time had low expression levels, whereas their interaction proteins had varying expression patterns in 22 tissues of A. hypogaea cv. Tifrunner. These results indicate that WRKY TFs exhibit antagonistic or synergistic interactions with the associated proteins. CONCLUSIONS: This study reveals complex regulatory networks through which WRKY TFs modulate flowering time in the four Arachis species using bioinformatics approaches.

Genetic Modifiers of Cystic Fibrosis Lung Disease Severity: Whole-Genome Analysis of 7,840 Patients.

Rationale: Lung disease is the major cause of morbidity and mortality in persons with cystic fibrosis (pwCF). Variability in CF lung disease has substantial non-CFTR (CF transmembrane conductance regulator) genetic influence. Identification of genetic modifiers has prognostic and therapeutic importance. Objectives: Identify genetic modifier loci and genes/pathways associated with pulmonary disease severity. Methods: Whole-genome sequencing data on 4,248 unique pwCF with pancreatic insufficiency and lung function measures were combined with imputed genotypes from an additional 3,592 patients with pancreatic insufficiency from the United States, Canada, and France. This report describes association of approximately 15.9 million SNPs using the quantitative Kulich normal residual mortality-adjusted (KNoRMA) lung disease phenotype in 7,840 pwCF using premodulator lung function data. Measurements and Main Results: Testing included common and rare SNPs, transcriptome-wide association, gene-level, and pathway analyses. Pathway analyses identified novel associations with genes that have key roles in organ development, and we hypothesize that these genes may relate to dysanapsis and/or variability in lung repair. Results confirmed and extended previous genome-wide association study findings. These whole-genome sequencing data provide finely mapped genetic information to support mechanistic studies. No novel primary associations with common single variants or rare variants were found. Multilocus effects at chr5p13 (SLC9A3/CEP72) and chr11p13 (EHF/APIP) were identified. Variant effect size estimates at associated loci were consistently ordered across the cohorts, indicating possible age or birth cohort effects. Conclusions: This premodulator genomic, transcriptomic, and pathway association study of 7,840 pwCF will facilitate mechanistic and postmodulator genetic studies and the development of novel therapeutics for CF lung disease.

Ag-CeO2 Based on Electrochemical Sensor for High-Efficient On-Site Detection of Nitrite in Aquaculture Water and Beverages.

Nitrite is one of the most common nitrogenous compounds, which is not only an important indicator of aquaculture water but also widely used as a food additive. Its potential toxicity poses a huge threat to aquatic products and human health. Therefore, it is important to develop a convenient and rapid sensor for the high-efficient onsite detection of nitrite. In this work, a novel electrochemical sensor was developed for the qualitative and quantitative analysis of nitrite. The developed nitrite electrochemical detection system is easily applied in onsite detection. The electrochemical working electrode was constructed based on the combination of Ag-CeO2 and conductive carbon paste (CPE) with excellent electrocatalysis activity and rapid electron transfer ability. By the application of the developed system and under the optimal conditions, the linear range was from 40.0 µM to 500.0 µM, and the detection limit was reduced to 4.3 µM. The recovery was between 92.1% and 108.1%, and the relative standard deviations (RSDs) were 0.49%~9.31%. The sensor exhibited superior reproducibility, high stability sensitivity, and anti-interference ability, confirming its effectiveness for nitrite analysis. Finally, the developed electrochemical sensor was successfully applied to detect nitrite in beverages and aquaculture water samples, indicating that this approach has great potential in onsite food testing and environmental monitoring.

Facile Recycling of Waste Biomass for Preparation of Hierarchical Porous Carbon with High-Performance Electromagnetic Wave Absorption.

Hierarchical-porous-structured materials have been widely used in the field of electromagnetic wave (EMW) absorption, playing a critical role in minimizing EMW interference and pollution. High-quality EMW absorbers, characterized by a lower thickness, lighter weight, wider absorption band, and stronger absorption capacity, have been instrumental in reducing damage and preventing malfunctions in the automotive and aviation industries. The utilization of discarded nut shells through recycling can not only alleviate environmental problems but relieve resource constraints. Herein, a facile method for the preparation of hierarchical porous biomass carbon derived from abandoned Xanthoceras Sorbifolium Bunge Shell (XSS) biomass was developed for high-performance EMW absorption. The porous structures of XSS biochar were studied by using different levels of the K2CO3 activator and simple carbonization. The effect of K2CO3 on the EMW parameters, including the complex permittivity, complex permeability, polarization relaxation, and impedance matching, was analyzed. The best EMW absorption performance of the XSS biochar was observed at a mass ratio of activator-to-biomass of 2:1. A minimum reflection loss (RLmin) of -38.9 dB was achieved at 9.12 GHz, and a maximum effective absorption bandwidth (EABmax) of up to 3.28 GHz (14.72~18.0 GHz) could be obtained at a 1.8 mm thickness. These results demonstrated that hierarchical porous XSS carbon was prepared successfully. Simultaneously, the prepared XSS biochar was confirmed as a potential and powerfully attractive EMW-absorbing material. The proposal also provided a simple strategy for the development of a green, low-cost, and sustainable biochar as a lightweight high-performance absorbing material.

Transforming municipal cotton waste into a multilayer fibre biocomposite with high strength.

We analyzed the problematic textile fiber waste as potential precursor material to produce multilayer cotton fiber biocomposite. The properties of the products were better than the current dry bearing type particleboards and ordinary dry medium-density fiberboard in terms of the static bending strength (67.86 MPa), internal bonding strength (1.52 MPa) and water expansion rate (9.57%). The three-layer, four-layer and five-layer waste cotton fiber composite (WCFC) were tried in the experiment, the mechanical properties of the three-layer WCFC are insufficient, the five-layer WCFC is too thick and the four-layer WCFC had the best comprehensive performance. The cross-section morphology of the four-layer WCFC shows a dense structure with a high number of adhesives attached to the fiber. The hardness and stiffness of the four-layer cotton fiber composite enhanced by the high crystallinity of cellulose content, and several chemical bondings were presence in the composites. Minimum mass loss (30%) and thermal weight loss rate (0.70%/°C) was found for the four-layer WCFC. Overall, our findings suggested that the use of waste cotton fiber (WCF) to prepare biocomposite with desirable physical and chemical properties is feasible, and which can potentially be used as building material, furniture and automotive applications.

Simultaneous modeling of multivariate heterogeneous responses and heteroskedasticity via a two-stage composite likelihood.

Multivariate heterogeneous responses and heteroskedasticity have attracted increasing attention in recent years. In genome-wide association studies, effective simultaneous modeling of multiple phenotypes would improve statistical power and interpretability. However, a flexible common modeling system for heterogeneous data types can pose computational difficulties. Here we build upon a previous method for multivariate probit estimation using a two-stage composite likelihood that exhibits favorable computational time while retaining attractive parameter estimation properties. We extend this approach to incorporate multivariate responses of heterogeneous data types (binary and continuous), and possible heteroskedasticity. Although the approach has wide applications, it would be particularly useful for genomics, precision medicine, or individual biomedical prediction. Using a genomics example, we explore statistical power and confirm that the approach performs well for hypothesis testing and coverage percentages under a wide variety of settings. The approach has the potential to better leverage genomics data and provide interpretable inference for pleiotropy, in which a locus is associated with multiple traits.

Degradation of levofloxacin from antibiotic wastewater by pulse electrochemical oxidation with BDD electrode.

Antibiotic-containing wastewater is a typical biochemical refractory organic wastewater and general treatment methods cannot effectively and quickly degrade the antibiotic molecules. In this study, a novel boron-doped diamond (BDD) pulse electrochemical oxidation (PEO) technology was proposed for the efficient removal of levofloxacin (LFXN) from wastewater. The effects of current density (j), initial pH (pH0), frequency (f), electrolyte types and initial concentration (c0(LFXN)) on the degradation of LFXN were systematically investigated. The degradation kinetics under four different processes have also been studied. The possible degradation mechanism of LFXN was proposed by Density functional theory calculation and analysis of degradation intermediates. The results showed that under the optimal parameters, the COD removal efficiency (η(COD)) was 94.4% and the energy consumption (EEC) was 81.43 kWh·m-3 at t = 120 min. The degradation of LFXN at pH = 2.8/c(H2O2) followed pseudo-first-order kinetics. The apparent rate constant was 1.33 × 10-2 min-1, which was much higher than other processes. The degradation rate of LFXN was as follows: pH = 2.8/c(H2O2) > pH = 2.8 > pH = 7/c(H2O2) > pH = 7. Ten aromatic intermediates were formed during the degradation of LFXN, which were further degraded to F-, NH4+, NO3-, CO2 and H2O. This study provides a promising approach for efficiently treating LFXN antibiotic wastewater by pulsed electrochemical oxidation with a BDD electrode without adding H2O2.

Effect of iron ion configurations on Ni2+ removal in electrocoagulation.

Electrocoagulation (EC) has been widely used to treat the heavy metal wastewater in industry. A novel process of sinusoidal alternating current electrocoagulation (SACC) is adopted to remove Ni2+ in wastewater in this study. The morphology of precipitates and the distribution of the main functional iron configurations were investigated. Ferron timed complex spectroscopy can identify the monomeric iron configurations [Fe(a)], oligomeric iron configurations [Fe(b)] and polymeric iron configurations [Fe(c)]. The optimal operating conditions of SACC process were determined through single-factor experiments. The maximum Ni2+ removal efficiency [Re(Ni2+)] was achieved under the conditions of pH0=7, current density (j) = 7 A/m2, electrolysis time (t) = 25 min, c0(Ni2+) = 100 mg/L. At pH=7, the proportion of Fe(b) and Fe(c) in the system was 50.4 at.% and 23.1 at.%, respectively. In the SACC process, Fe(b) and Fe(c) are the main iron configurations in solution, while Fe(c) are the vast majority of the iron configurations in the direct current electrocoagulation (DCC) process. Re(Ni2+) is 99.56% for SACC and 98.75% for DCC under the same optimum conditions, respectively. The precipitates produced by SACC have a high proportion of Fe(b) configurations with spherical α-FeOOH and γ-FeOOH structures which contain abundant hydroxyl groups. Moreover, it is demonstrated that Fe(b) has better adsorption capacity than Fe(c) through adsorption experiments of methyl orange (MO) dye. Fe(a) configurations in the homogeneous solution had no effect on the removal of nickel.

C3NA: correlation and consensus-based cross-taxonomy network analysis for compositional microbial data.

BACKGROUND: Studying the co-occurrence network structure of microbial samples is one of the critical approaches to understanding the perplexing and delicate relationship between the microbe, host, and diseases. It is also critical to develop a tool for investigating co-occurrence networks and differential abundance analyses to reveal the disease-related taxa-taxa relationship. In addition, it is also necessary to tighten the co-occurrence network into smaller modules to increase the ability for functional annotation and interpretability of  these taxa-taxa relationships.  Also, it is critical to retain the phylogenetic relationship among the taxa to identify differential abundance patterns, which can be used to resolve contradicting functions reported by different studies. RESULTS: In this article, we present Correlation and Consensus-based Cross-taxonomy Network Analysis (C3NA), a user-friendly R package for investigating compositional microbial sequencing data to identify and compare co-occurrence patterns across different taxonomic levels. C3NA contains two interactive graphic user interfaces (Shiny applications), one of them dedicated to the comparison between two diagnoses, e.g., disease versus control. We used C3NA to analyze two well-studied diseases, colorectal cancer, and Crohn's disease. We discovered clusters of study and disease-dependent taxa that overlap with known functional taxa studied by other discovery studies and differential abundance analyses. CONCLUSION: C3NA offers a new microbial data analyses pipeline for refined and enriched taxa-taxa co-occurrence network analyses, and the usability was further expanded via the built-in Shiny applications for interactive investigation.

Chlorinated Paraffins in Two Snake Species from the Yangtze River Delta: Tissue Distribution and Biomagnification.

Very-short, short-, medium-, and long-chain chlorinated paraffins (vSCCPs, SCCPs, MCCPs, and LCCPs, respectively) were analyzed in different tissues of the terrestrial short-tailed mamushi (Gloydius brevicaudus) and the semi-aquatic red-backed rat snake (Elaphe rufodorsata) from the Yangtze River Delta, China. The total CP concentrations in liver, muscle, and adipose tissues in the two snake species were in the range of 2500-24 000, 4900-48 000, and 12-630 ng/g lw, respectively. Tissue burdens indicated that vSCCPs (C6-9) and SCCPs (C10-13) preferentially distributed to snake liver, while adipose was an important storage site and sink of MCCPs (C14-17) and LCCPs (C>18). On a lipid weight basis, vSCCPs and SCCPs were found in highest concentrations in red-backed rat snake liver and MCCPs and LCCPs in muscle, whereas for short-tailed mamushi, all CP groups were predominant in muscle, probably reflecting ecosystem/food web differences. Moreover, vSCCPs, SCCPs, MCCPs, and LCCPs were found to be biomagnified from black-spotted frogs to red-backed rat snakes with mean (maximum) biomagnification factors of 2.2 (3.4), 1.9 (3.7), 1.8 (2.8), and 1.7 (4.5), respectively. This is the first field study of biomagnification potential involving vSCCPs and LCCPs and highlights the need to include all CPs in studies.

Chlorinated Paraffins in Human Milk from Urban Sites in China, Sweden, and Norway.

Short-, medium-, and long-chain chlorinated paraffins (SCCPs, MCCPs, and LCCPs) were analyzed in human milk from the Yangtze River Delta (YRD) and Scandinavia. Individual samples were collected from Shanghai, Jiaxing, and Shaoxing (China), Stockholm (Sweden), and Bodø (Norway) between 2010 and 2016. Mean concentrations (range) of SCCPs, MCCPs, and LCCPs in samples from the YRD were 124 [

High-Intensity Focused Ultrasound in the Treatment of Abdominal Wall Endometriosis.

STUDY OBJECTIVE: To evaluate high-intensity focused ultrasound (HIFU) ablation therapy for abdominal wall endometriosis (AWE). DESIGN: A retrospective study. SETTING: Gynecologic department of a teaching hospital in China. PATIENTS: Thirty patients with AWE were treated from May 2013 to December 2015. INTERVENTIONS: Thirteen patients were treated with HIFU ablation and 17 patients with surgical resection. MEASUREMENTS AND MAIN RESULTS: Color Doppler ultrasonography and magnetic resonance imaging were used to observe the lesions before and after treatment. In addition, recovery time, complications, and adverse reactions of the 2 groups were compared. Menstrual pain was relieved after treatment in all 30 patients. After treatment, the lesions in patients who underwent HIFU ablation decreased gradually, and there was no recurrence. Symptoms recurred in 1 patient in the surgery group 12 months after surgery. The post-treatment hospital length of stay of the HIFU ablation group (1.00 ± 0 days) was significantly shorter than that of the surgical group (5.23 ± 1.24 days; p <.001). The incidence of fever (0% vs 11.8%; p = .049) and complications of the urinary system (7.7% vs 17.6%; p = .043) in the HIFU ablation group were significantly lower than that of the surgical group. CONCLUSIONS: HIFU ablation therapy is a promising treatment for AWE, and further study is warranted.

Comparison between sinusoidal AC coagulation and conventional DC coagulation in removing Cu2+ from printed circuit board wastewater.

A new Electrocoagulation (EC) technique, sinusoidal AC coagulation (SACC), is creatively put forward for Cu2+ removal in the wastewater from the printed circuit board (PCB) production in this paper. The removal efficiency of Cu2+ from PCB wastewater and energy consumption are compared by SACC and conventional direct current coagulation (DCC). The optimal process parameters were established through analysis of response surface methodology (RSM). The coagulations containing Cu2+ was characterized by SEM, EDS, TEM，BET, XRD and FTIR. The nano-ferrum collosol, mainly composed of goethite (α-FeOOH) and magnetite (γ-Fe2O3), absorbs the Cu2+ and coagulates to remove Cu2+. The results show that the removal rates of Cu2+ by SACC and DCC are 99.86％ and 98.21％, respectively, and the energy consumption is 2.76 × 10-2 kWh⋅m-3 for SACC and 4.42 × 10-2 kWh⋅m-3 for DCC under the optimal process conditions of c0 (Cu2+) = 41.99 mg⋅dm-3, pH = 7.14, j = 0.293 A⋅m-2, t = 16.7 min. The pilot tests indicate that the SACC technique is feasible in industrial application. Cu2+ removal were completed through electrodeposition of Cu2+ on iron electrode, the deposition of Cu(OH)2 and the adsorption of Cu2+ by ferrum collosol. The adsorption follows the pseudo-second order kinetics model well. The maximum saturated adsorption capacity (qmax) of Cu2+ on ferrum collosol produced by SACC is larger than that by DCC. The adsorption of Cu2+ on the ferrum collosol prepared by SACC and DCC are in accordance with Langmuir's adsorption isotherms. The novel SACC technique is a promising technique for the highly-efficient treatment of Cu2+ from PCB wastewater.

Treatment of Zn2+ in wastewater by sinusoidal alternating current coagulation: response surface methodology and removal mechanism.

A novel sinusoidal alternating current coagulation (SACC) technique was used to remove the Zn2+ from wastewater in the present study. The response surface methodology was used to analyze the effect of current density, time, initial pH and initial Zn2+ concentration in order to obtain the optimum removal efficiency and to lower energy consumption. The results show that SACC with a current density of 0.31 A·m-2 applied to treat wastewater containing 120 mg·dm-3 Zn2+ at pH = 9 for 21.3 min can achieve a removal efficiency of Zn2+ of 98.80%, and the energy consumption is 1.147 kWh·m-3. The main component of flocs produced in SACC process is Fe5O7OH·4H2O (HFO). Large specific surface area and good adsorption performance of HFO are demonstrated. There is strong interaction between Zn2+ and HFO. Zn2+ is adsorbed and trapped by HFO and then co-precipitated. Freundlich adsorption isotherm model and pseudo-second order kinetics model explained the Zn2+ adsorption behavior well. The Zn2+ adsorption on HFO is an endothermic and spontaneous process.

LL202 ameliorates colitis against oxidative stress of macrophage by activation of the Nrf2/HO-1 pathway.

LL202, a newly synthesized flavonoid derivative, has been confirmed to inhibit the mitogen-activated protein kinase pathway and activation protein-1 activation in monocytes; however, the anti-inflammatory mechanism has not been clearly studied. Uncontrolled overproduction of reactive oxygen species (ROS) has involved in oxidative damage of inflammatory bowel disease. In this study, we investigated that LL202 reduced lipopolysaccharide (LPS)-induced ROS production and malondialdehyde levels and increased superoxide dismutase, glutathione, and total antioxidant capacity in RAW264.7 cells. Mechanically, LL202 could upregulate heme oxygenase-1 (HO-1) via promoting nuclear translocation of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) to regulate LPS-induced oxidative stress in macrophages. In vivo, we validated the role of LL202 in dextran sulfate sodium- and TNBS-induced colitis models, respectively. The results showed that LL202 decreased the proinflammatory cytokine expression and regulated colonic oxidative stress by activating the Nrf2/HO-1 pathway. In conclusion, our study showed that LL202 exerts an anti-inflammatory effect by enhancing the antioxidant capacity of the Nrf2/HO-1 pathway to macrophages.