Synergistic and efficient degradation of acid red 73 by UV/O3/PDS: Kinetic studies, free radical contributions and degradation pathways.

Acid red 73 (AR73) is a representative dye pollutant that poses a threat to the environment and human health. Effectively removing this type of pollutant by conventional processes is difficult. However, this study found that compared with UV/PDS, UV/O3, and PDS/O3, UV/O3/PDS composite system had the highest degradation effect on AR73. The degradation efficiency in the composite system reached 97.61% within 30 min, and the synergistic coefficients in the composite system were all greater than 1. In the UV/O3/PDS system, ·OH was the main free radical that mainly degrades AR73. The increase of PDS dosage promoted the degradation of AR73, but the increase of O3 dosage was difficult to greatly improve the degradation of AR73 effect. The kinetic model of the apparent reaction rate was determined. The UV/O3/PDS system can efficiently degrade AR73 in a wide range of substrate concentrations and pH levels, and at the same time showed good adaptability to various concentrations of anions (Cl-, CO32-, SO32-, and C2O42-). Under raw water quality, the degradation effect of AR73 was still as high as approximately 90%. The theoretical attack site was obtained by DFT calculation, and the possible degradation pathway of AR73 was proposed based on the GC-MS spectrum and UV-Vis absorption spectrum. The attack of -NN- by ·OH, SO4-, and O3 was proposed to be the main possible degradation pathway for AR73. Therefore, this study further improves the understanding of the UV/O3/PDS system and shows the potential applicability of this system in the treatment of dye wastewater.

Boosting the Performance of Nanofiltration Membranes in Removing Organic Micropollutants: Trade-Off Effect, Strategy Evaluation, and Prospective Development.

In view of the high risks brought about by organic micropollutants (OMPs), nanofiltration (NF) processes have been playing a vital role in advanced water and wastewater treatment, owing to the high membrane performance in rejection of OMPs, permeation of water, and passage of mineral salts. Though numerous studies have been devoted to evaluating and technically enhancing membrane performance in removing various OMPs, the trade-off effect between water permeance and water/OMP selectivity for state-of-the-art membranes remains far from being understood. Knowledge of this effect is significant for comparing and guiding membrane development works toward cost-efficient OMP removal. In this work, we comprehensively assessed the performance of 88 NF membranes, commercialized or newly developed, based on their water permeance and OMP rejection data published in the literature. The effectiveness and underlying mechanisms of various modification methods in tailoring properties and in turn performance of the mainstream polyamide (PA) thin-film composite (TFC) membranes were quantitatively analyzed. The trade-off effect was demonstrated by the abundant data from both experimental measurements and machine learning-based prediction. On this basis, the advancement of novel membranes was benchmarked by the performance upper-bound revealed by commercial membranes and lab-made PA membranes. We also assessed the potentials of current NF membranes in selectively separating OMPs from inorganic salts and identified the future research perspectives to achieve further enhancement in OMP removal and salt/OMP selectivity of NF membranes.

Tetrahydroxystilbene glucoside alleviates angiotensin II induced HUVEC senescence via SIRT1.

Tetrahydroxystilbene glucoside (TSG), an active ingredient of Polygonum multiflorum, has been known for certain anti-aging effects. In this study, the possible protective mechanism of TSG on human umbilical vein endothelial cell (HUVEC) senescence induced by angiotensin II (Ang II) was investigated. The results revealed that TSG pretreatment could reduce the percentage of senescence-associated ß-galactosidase (SA-ß-gal) positive cells and decrease the expression levels of the cellular senescence biomarker proteins p53 and PAI-1. At the same time, the expression of SIRT1 in senescent cells showed an upward trend due to TSG treatment. When inhibiting the expression of SIRT1 by EX527, our results showed that TSG reversed the effect of EX527 by promoting the expression level of SIRT1, reducing the expression of SA-ß-gal positive cells and the expression level of p53 and PAI-1 proteins. The present study demonstrated that TSG could protect against HUVEC senescence induced by Ang II, potentially through modulation of SIRT1 activity.

A Facile and Scalable Fabrication Procedure for Thin-Film Composite Membranes: Integration of Phase Inversion and Interfacial Polymerization.

Conventional dense thin-film composite (TFC) membranes evince a universally low water permeability, the increase of which typically relies on introducing additional transport channels based on intricate steps within a membrane preparation process. In this study, we reported a novel and simplified procedure for the fabrication of high-performance TFC membranes. Specifically, the dissolution of aqueous monomers in the casting solution was utilized for the following interfacial polymerization (IP). Since the monomers diffused to the water bath during phase inversion, the control of precipitation time enabled an effective regulation of the monomer concentration in the formed polymeric substrates, where the IP reaction was initiated by the addition of the organic phase. The entire and uniform embedment of aqueous monomers inside the substrates contributed to the formation of ultrathin and smooth selective layers. An excellent separation performance (i.e., water permeability: 34.7 L m-2 h-1 bar-1; Na2SO4 rejection: ∼96%) could be attained using two types of aqueous monomers (i.e., piperazine and ß-cyclodextrin), demonstrating the effectiveness and universality of this method. Compared to the conventional immersion-based process, this novel procedure shows distinct advantages in reducing monomer usage, shortening the production cycle, and achieving a more superior membrane performance, which is highly promising for large-scale membrane manufacture.

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-Glucoside modulated human umbilical vein endothelial cells injury under oxidative stress.

Endothelial cell injury is a major contributor to cardiovascular diseases. The 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-Glucoside (TSG) contributes to alleviate human umbilical vein endothelial cells (HUVECs) injury through mechanisms still know a little. This study aims to clarify the TSG effects on gene expression (mRNA and microRNA) related to oxidative stress and endoplasmic reticulum stress induced by H2O2 in HUVECs. We found that TSG significantly reduced the death rate of cells and increased intracellular superoxide dismutase activity. At qRT-PCR, experimental data showed that TSG significantly counteracted the expressions of miR-9-5p, miR-16, miR-21, miR-29b, miR-145-5p, and miR-204-5p. Besides, TSG prevented the expression of ATF6 and CHOP increasing. In contrast, TSG promoted the expression of E2F1. In conclusion, our results point to the obvious protective effect of TSG on HUVECs injury induced by H2O2, and the mechanism may through miR16/ATF6/ E2F1 signaling pathway.

Formation potential of disinfection byproducts during chlorination of petroleum hydrocarbon-contaminated drinking water.

Recent leaks of underground fuel storage tanks in the Pearl Harbor region have led to direct release of un-weathered petroleum hydrocarbons (PHCs) into drinking water sources, which then directly underwent chlorination disinfection treatment. Since the control of disinfection byproducts (DBPs) traditionally focuses natural organic matters (NOM) from source water and little is known about the interactions between free chlorine and un-weathered PHCs, laboratory chlorination experiments in batch reactors were conducted to determine the formation potential of DBPs during chlorination of PHC-contaminated drinking water. Quantitative analysis of regulated DBPs showed that significant quantities of THM4 (average 3,498 µg/L) and HAA5 (average 355.4 µg/L) compounds were formed as the result of chlorination of un-weathered PHCs. Amongst the regulated DBPs, THM4, which were comprised primarily of chloroform and bromodichloromethane, were more abundant than HAA5. Numerous unregulated DBPs and a large diversity of unidentified potentially halogenated organic compounds were also produced, with the most abundant being 1,1-dichloroacetone, 1,2-dibromo-3-chloropropane, chloropicrin, dichloroacetonitrile, and trichloracetonitrile. Together, the results demonstrated the DBP formation potential when PHC-contaminated water undergoes chlorination treatment. Further studies are needed to confirm the regulated DBP production and health risks under field relevant conditions.

Analysis of rainwater storage and use recommendations: From the perspective of DBPs generation and their risks.

As a vital freshwater resource, rainwater is usually stored in water cellars in arid regions to solve the daily drinking water problems of the population. However, the status of disinfection by-products (DBPs) generation in cellar water under intermittent disinfection conditions is unclear. Therefore, we investigated the formation and distribution characteristics of DBPs in cellar water under intermittent disinfection conditions for the first time. The results demonstrated that six categories of DBPs were selected for detection after chlorination, including trihalomethanes (THMs), haloacetic acids (HAAs), haloketones (HKs), haloacetonitriles (HANs), halonitromethanes (HNMs), and nitrosamines (NAs), among which HAAs, HKs, and HANs were the major DBPs. Only bromoacetic acid (MBAA), dichloroacetic acid (DCAA), and trichloroacetic acid (TCAA) showed an increasing trend of accumulation as the number of disinfections increased. Meanwhile, the precursor composition was gradually transformed from humic substances to amino acids, and both organic substances were the main precursors of HAAs. The health risk assessment showed that the main carcinogenic and non-carcinogenic risks of cellar water were contributed by NAs and HAAs, respectively, and children are more susceptible to the risks than adults. The best time to drink cellar water is after approximately 12 days of storage, when the total carcinogenic risk is the minimum.

Disinfection by-product formation potentials in wastewater effluents and their reductions in a wastewater treatment plant.

Disinfection by-product formation potentials (DBPFPs) in wastewater effluents from eight wastewater treatment plants (WWTPs) were investigated. In addition, a WWTP with one primary effluent and two different biological treatment processes was selected for a comparative study. Formation potential tests were carried out to determine the levels of DBP precursors in wastewater. WWTPs that achieved better organic matter removal and nitrification tended to result in lower DBPFPs in effluents. For the WWTP with two processes, haloacetic acid, trihalomethane, and chloral hydrate precursors were predominant DBP precursors in the primary and secondary effluents. The percent reductions of haloacetonitrile and haloketone formation potentials averaged at 96% which was high in comparison to the reductions of other classes of DBPFPs. In addition, biological treatment changed the DBPFP speciation profile by lowering the HAAFP/THMFP ratio. The eight plant survey and the comparative analysis of the WWTP with two processes implied that besides nitrification, there may be other confounding factors impacting DBPFPs. Oxic and anoxic conditions, formation and degradation of soluble microbial products had impacts on the DBPFP reductions. This information can be used by water and wastewater professionals to better control wastewater-derived DBPs in downstream potable water supplies.

Detection of pediatric drug-induced kidney injury signals using a hospital electronic medical record database.

Background: Drug-induced kidney injury (DIKI) is one of the most common complications in clinical practice. Detection signals through post-marketing approaches are of great value in preventing DIKI in pediatric patients. This study aimed to propose a quantitative algorithm to detect DIKI signals in children using an electronic health record (EHR) database. Methods: In this study, 12 years of medical data collected from a constructed data warehouse were analyzed, which contained 575,965 records of inpatients from 1 January 2009 to 31 December 2020. Eligible participants included inpatients aged 28 days to 18 years old. A two-stage procedure was adopted to detect DIKI signals: 1) stage 1: the suspected drugs potentially associated with DIKI were screened by calculating the crude incidence of DIKI events; and 2) stage 2: the associations between suspected drugs and DIKI were identified in the propensity score-matched retrospective cohorts. Unconditional logistic regression was used to analyze the difference in the incidence of DIKI events and to estimate the odds ratio (OR) and 95% confidence interval (CI). Potentially new signals were distinguished from already known associations concerning DIKI by manually reviewing the published literature and drug instructions. Results: Nine suspected drugs were initially screened from a total of 652 drugs. Six drugs, including diazepam (OR = 1.61, 95%CI: 1.43-1.80), omeprazole (OR = 1.35, 95%CI: 1.17-1.54), ondansetron (OR = 1.49, 95%CI: 1.36-1.63), methotrexate (OR = 1.36, 95%CI: 1.25-1.47), creatine phosphate sodium (OR = 1.13, 95%CI: 1.05-1.22), and cytarabine (OR = 1.17, 95%CI: 1.06-1.28), were demonstrated to be associated with DIKI as positive signals. The remaining three drugs, including vitamin K1 (OR = 1.06, 95%CI: 0.89-1.27), cefamandole (OR = 1.07, 95%CI: 0.94-1.21), and ibuprofen (OR = 1.01, 95%CI: 0.94-1.09), were found not to be associated with DIKI. Of these, creatine phosphate sodium was considered to be a possible new DIKI signal as it had not been reported in both adults and children previously. Moreover, three other drugs, namely, diazepam, omeprazole, and ondansetron, were shown to be new potential signals in pediatrics. Conclusion: A two-step quantitative procedure to actively explore DIKI signals using real-world data (RWD) was developed. Our findings highlight the potential of EHRs to complement traditional spontaneous reporting systems (SRS) for drug safety signal detection in a pediatric setting.

Mining Severe Drug Hypersensitivity Reaction Cases in Pediatric Electronic Health Records: Methodology Development and Applications.

BACKGROUND: Severe drug hypersensitivity reactions (DHRs) refer to allergic reactions caused by drugs and usually present with severe skin rashes and internal damage as the main symptoms. Reporting of severe DHRs in hospitals now solely occurs through spontaneous reporting systems (SRSs), which clinicians in charge operate. An automatic identification system scrutinizes clinical notes and reports potential severe DHR cases. OBJECTIVE: The goal of the research was to develop an automatic identification system for mining severe DHR cases and discover more DHR cases for further study. The proposed method was applied to 9 years of data in pediatrics electronic health records (EHRs) of Beijing Children's Hospital. METHODS: The phenotyping task was approached as a document classification problem. A DHR dataset containing tagged documents for training was prepared. Each document contains all the clinical notes generated during 1 inpatient visit in this data set. Document-level tags correspond to DHR types and a negative category. Strategies were evaluated for long document classification on the openly available National NLP Clinical Challenges 2016 smoking task. Four strategies were evaluated in this work: document truncation, hierarchy representation, efficient self-attention, and key sentence selection. In-domain and open-domain pretrained embeddings were evaluated on the DHR dataset. An automatic grid search was performed to tune statistical classifiers for the best performance over the transformed data. Inference efficiency and memory requirements of the best performing models were analyzed. The most efficient model for mining DHR cases from millions of documents in the EHR system was run. RESULTS: For long document classification, key sentence selection with guideline keywords achieved the best performance and was 9 times faster than hierarchy representation models for inference. The best model discovered 1155 DHR cases in Beijing Children's Hospital EHR system. After double-checking by clinician experts, 357 cases of severe DHRs were finally identified. For the smoking challenge, our model reached the record of state-of-the-art performance (94.1% vs 94.2%). CONCLUSIONS: The proposed method discovered 357 positive DHR cases from a large archive of EHR records, about 90% of which were missed by SRSs. SRSs reported only 36 cases during the same period. The case analysis also found more suspected drugs associated with severe DHRs in pediatrics.

Derivatization-free multi-step extraction for trace haloacetic acids analysis with ion chromatography: Performance and mechanisms.

Haloacetic acids (HAAs) are a type of disinfection byproducts commonly found in drinking water with carcinogenic, mutagenic, or teratogenic risks to humans. Currently, the analytical methods of trace HAAs are either labor-intensive or very expensive. We herein propose a facile multiple-step extraction strategy for HAAs analysis with common ion chromatography (IC). This study is based on a fundamental water chemistry principle that HAAs become protonated featuring positive logKow values (> 0.34) under pH < pKa but deprotonated featuring negative logKow values (< -2.37) under pH > pKa. By taking advantage of the species and property switches, HAAs can be extracted and enriched into methyl tert-butyl ether first at pH < 0.5 and then back-extracted into neutral water and enriched again. Equally important, interfering anions in IC chromatogram are eliminated because they have negative logKow values. Verification results show that HAAs were enriched by 11.4 times in average while interfering anions were almost eliminated (> 99%). Although similar to USEPA Method 552.3 in method detection limits (0.033-0.246 µg/L), recoveries (70%~110%), and relative standard deviations (< 9.91%), this method took ≤ 70 min to run a batch of samples without derivatization, which takes over 2 h. The methodology may be applicable to other pollutants that also have contrasting Kow values at different pH.

Optimization of ozone dosage in an ozone contact tank using a numerical model.

Ozone has been widely applied in drinking water and wastewater treatment plants, and it is essential to determine the ozone dosage and its ratio in ozone contact tank to increase the ozone absorption and utilization rates. Batch experiments were performed to determine the first-order reaction rate coefficient of ozone (k1) in different raw water qualities. Results showed that k1 had an exponential decaying relationship with the ozone consumption amount (ΔO3). Based on the ozone mass transfer and decomposition kinetics, a numerical model was developed to optimize the total ozone dosage and its ratio in three aeration parts by calculating the ozone absorption and utilization rates in an ozone contact tank. The ozone absorption rate was little affected by the water quality, and an even distribution of ozone could greatly increase the ozone absorption rate. However, the ozone utilization rate was tightly related with the water quality. For waters that consumed ozone quickly, ozone should be dosed equally in three aeration parts to increase the ozone utilization rate up to 94.3%. Otherwise, more ozone should be dosed in the first aeration part. An increase in ozone utilization rate would induce an increase in the degree of water purification. This model could give theoretical support for the determination of ozone dosage and its ratio in water treatment plants rather than experience.

Kinetics and mechanism of haloacetaldehyde formation from the reaction of acetaldehyde and chlorine.

Haloacetaldehydes (HALs) are the third prevalent group of disinfection by-products (DBPs) by weight in drinking water, and their cytotoxicity and genotoxicity are higher than regulated DBPs. In order to understand their formation mechanism during chlorination and ozonation-chlorination, this study examined the reaction kinetics of chloral hydrate (CH), dichloroacetaldehyde (DCA), chloroacetaldehyde (CA) and acetaldehyde by chlorine at different pH values and chlorine doses. The results showed that the reaction rate constants increased with pH and chlorine dose, except that the degradation of CH would not be affected by the presence of free chlorine. At the same pH and chlorine dose, the half-lives of CH, DCA, CA and acetaldehyde were in the order of CH > acetaldehyde â‰« DCA > CA. A kinetic model used to predict the formation of HALs and chloroform during chlorination of acetaldehyde was developed, and the predicted data fitted well with the measured data. As pre-ozonation could oxidize natural organic matter to acetaldehydes, the concentration of acetaldehyde formed after pre-ozonation was used to calculate the HAL yields during ozonation-chlorination by the kinetic model, which fitted the experimental results well. The kinetic model elucidated that the formation mechanism of HALs was a stepwise substitution process on the α-hydrogen of acetaldehyde during chlorination.

Study on the influence of operational and management processes of a water reclamation plant since COVID-19 situation.

Reusing treated wastewater can effectively alleviate water shortages and water contamination problems but depends on ensuring the safety of the reclaimed water that is produced. The operating and management conditions for water reclamation plants in China have been changed since the outbreak of the COVID-19 epidemic in China at the end of 2019 to prevent emerging viruses being spread through wastewater treatment processes and the reclaimed water that is produced. Removal of pathogens and trace organic compounds (e.g., pharmaceuticals and personal care products and endocrine disrupting chemicals) in a real water reclamation plant after the start of COVID-19 epidemic was studied. Disinfection byproduct formation caused by chlorine being added to meet disinfection requirements was also assessed. The pathogenic microorganism concentrations in effluent were <2 (most probable number)/L, and the removal rates for most trace organic compounds were >80% when advanced treatments were performed using ozone, ultraviolet light, and chlorine doses of 2 mg/L, 20.5 mJ/cm2, and 2-3 mg/L, respectively. The main disinfection byproduct produced at a chlorine dose of 2 mg/L and a residence time of 1 h was chloroform (at concentrations <15 µg/L). The results indicated that the water reclamation processes with modified conditions gave high pathogen and trace organic compound removal rates and reasonably well-controlled disinfection byproduct concentrations.

The haloacetic acid leap in effluent of a biologically active carbon filter experiencing a disinfectant switch.

Water utilities must disinfect their water despite the formation of carcinogenic disinfection byproducts (DBPs) such as haloacetic acids (HAAs) upon chlorination. Although employment of a biologically active carbon (BAC) filtration process is able to reduce the HAA level preventively by removing the HAA precursors and correctively by removing the already-formed HAAs, this research reported an HAA leap in a bench-scale BAC filter effluent upon a disinfectant switch from chlorine to chloramine, posing a pressure of meeting the stringent HAA regulations. The HAA6 (sum of six HAAs) tripled from a 5 µg/L base level to a maximum of 17 µg/L during progressive switches with 3 chloramine doses at 5, 25, and 50 mg/L. Dichloroacetic acid (DCAA) accounted for the majority of the leap, which also influenced the bromine substitution factor during the HAA formation. Filtration of distilled water using heat-deactivated media evidenced slight HAA desorption and suggested potential roles of soluble microbial products from biofilms as new HAA precursors for a real BAC filter experiencing a disinfectant switch.

Hydroxysafflor Yellow A Attenuates Hydrogen Peroxide-Induced Oxidative Damage on Human Umbilical Vein Endothelial Cells.

Oxidative stress of endothelial cells is thought to be a principal cause that induces many cardiovascular diseases. Hydroxysafflor yellow A (HSYA) is a major active component in traditional Chinese medicine safflower and has been used to cure ischemic cardiovascular diseases in China for many years. This study aims to investigate whether HSYA has a repairing effect on oxidative damage of human umbilical vein endothelial cells (HUVECs) induced by H2O2 and to provide a theoretical basis for the clinical treatment of cardiovascular diseases related to traditional Chinese medicine. Based on the establishment of an H2O2-induced HUVEC oxidative injury model, the cell viability and proliferation rate were measured by the MTT assay and EdU staining. The intracellular GSH/GSSG ratio and SOD activity were determined by kits. The ROS level was detected by flow cytometry. And the BAX, Bcl-2, PTEN, and AKT expressions were evaluated with western blotting methods. The results showed that HSYA treatment significantly attenuated the H2O2-induced HUVEC cell damage, increased the intracellular GSH/GSSG ratio and unit SOD activity also, and decreased the intracellular ROS levels. Furthermore, HSYA increased the expressions of AKT and Bcl-2 proteins and inhibited the expressions of BAX and PTEN proteins. These suggest that HSYA exerts repair effects on H2O2-induced oxidative damage in HUVECs, and the mechanisms may be related to the influence of BAX/Bcl-2 expression and AKT/PTEN signal pathway expression.

SIRT1 Is the Target Gene for 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-Glucoside Alleviating the HUVEC Senescence.

This study aimed to explore the effects of 2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-d-glucoside (TSG) on the senescence of human umbilical vein cells (HUVEC) induced by hydrogen peroxide (H2O2) and to identify the potential targets mediating its protective action. HUVEC cells pre-treated with TSG for 24 h were exposed to H2O2 treatment. TSG significantly decreased H2O2-induced cellular senescence, as indicated by reduced senescence-associated ß-galactosidase (SA-ß-gal) positive staining, the proportion of cells in the G1 phase, cell apoptosis, p21, and plasminogen activator inhibitor-1 (PAI-1) expression. Moreover, TSG promoted Sirtuin 1 (SIRT1) expression. When SIRT1 was inhibited by EX527 or SIRT1 siRNA, the effect of TSG is diminished according to the increased proportion of cells in the G1 phase, cell apoptosis, p21, and PAI-1 expression. Overall, our study established TSG as an anti-senescence compound that exerts its protective action by regulating SIRT1 expression.

Synergistic effects of combining ozonation, ceramic membrane filtration and biologically active carbon filtration for wastewater reclamation.

In this study, we proposed to apply an integrated process which is comprised of in situ ozonation, ceramic membrane filtration (CMF) and biologically active carbon (BAC) filtration to wastewater reclamation for indirect potable reuse purpose. A pilot-scale (20 m3/d) experiment had been run for ten months to validate the prospect of the process in terms of treatment performance and operational stability. Results showed that the in situ O3 + CMF + BAC process performed well in pollutant removal, with chemical oxygen demand, ammonia, nitrate nitrogen, total phosphorus and turbidity levels in the treated water being 5.1 ±â€¯0.9, 0.05 ±â€¯0.01, 10.5 ±â€¯0.8, <0.06 mg/L, and <0.10 NTU, respectively. Most detected trace organic compounds were degraded by>96%. This study demonstrated that synergistic effects existed in the in situ O3 + CMF + BAC process. Compared to pre-ozonation, in situ ozonation in the membrane tank was more effective in controlling membrane fouling (maintaining operational stability) and in degrading organic pollutants, which could be attributed to the higher residual ozone concentration in the tank. Because of the removal of particulate matter by CMF, water head loss of the BAC filter increased slowly and prolonged the backwashing interval to 30 days. BAC filtration was also effective in removing ammonia and N-nitrosodimethylamine from the ozonated water.

Signal Detection of Potentially Drug-Induced Liver Injury in Children Using Electronic Health Records.

Background: This study proposes a quantitative 2-stage procedure to detect potential drug-induced liver injury (DILI) signals in pediatric inpatients using an data warehouse of electronic health records (EHRs). Methods: Eight years of medical data from a constructed database were used. A two-stage procedure was adopted: (i) stage 1: the drugs suspected of inducing DILI were selected and (ii) stage 2: the associations between the drugs and DILI were identified in a retrospective cohort study. Results: 1,196 drugs were filtered initially and 12 drugs were further potentially identified as suspect drugs inducing DILI. Eleven drugs (fluconazole, omeprazole, sulfamethoxazole, vancomycin, granulocyte colony-stimulating factor (G-CSF), acetaminophen, nifedipine, fusidine, oseltamivir, nystatin and meropenem) were showed to be associated with DILI. Of these, two drugs, nystatin [odds ratio[OR]=1.39, 95%CI:1.10-1.75] and G-CSF (OR = 1.91, 95%CI:1.55-2.35), were found to be new potential signals in adults and children. Three drugs [nifedipine [OR = 1.77, 95%CI:1.26-2.46], fusidine [OR = 1.43, 95%CI:1.08-1.86], and oseltamivi r [OR = 1.64, 95%CI:1.23-2.18]] were demonstrated to be new signals in pediatrics. The other drug-DILI associations had been confirmed in previous studies. Conclusions: A quantitative algorithm to detect potential signals of DILI has been described. Our work promotes the application of EHR data in pharmacovigilance and provides candidate drugs for further causality assessment studies.

PM2.5 promotes replication of VSV by ubiquitination degradation of phospho-IRF3 in A549 cells.

Both PM2.5 and respiratory viruses are part of the atmospheric constituents. Respiratory viruses are often associated with PM2.5 exposure, but the mechanism of toxicity remains to be explored. The vitro models that adequately reproduce healthy cells or diseased cells exposing to PM2.5 and infecting VSV can provide a useful tool for studying innate immune mechanisms and investigating new therapeutic focus. In the environment of PM2.5, an infection model in which VSV infected A549 cells was established, that mimics the state in which the antiviral innate immune pathways are activated after the respiratory system is infected with RNA viruses. Subsequently, the model was exposed to PM2.5 for 24 h. PM2.5 could be ingested by A549 cells and synergize with VSV to inhibit cell viability and promote apoptosis. The expression of VSV-G were more abundant after VSV-infected A549 cells were exposed to PM2.5. Furthermore, PM2.5 inhibits VSV-induced IFN-ß expression in A549 cells. ISG15, CCL-5, and CXCL-10 had the same expression tendency with IFN-ß mRNA, consistently. Interestingly, when MG132 was applied, the expression of p-IRF-3 and IFN-ß proteins reduced by PM2.5 were refreshed. Conversely, the expression of VSV-G proteins were decreased. PM2.5 could degrade p-IRF-3 proteins by ubiquitination pathway to inhibit VSV-induced IFN-ß expression in A549 cells. Therefore, replication of the VSV viruses was promoted.