Epidemiology of human papillomavirus infection in women from Xiamen, China, 2013 to 2023.

Background: Cervical cancer is primarily caused by HPV infection. The epidemiology of HPV infection in specific areas is of great meaning of guide cervical cancer screening and formulating HPV vaccination strategies. Here, we evaluated the epidemiological characteristics of HPV infection in Xiamen population. Methods: In total, 159,049 cervical exfoliated cell samples collected from female outpatients in Women and Children's Hospital, School of Medicine, Xiamen between January 2013 and July 2023 were analyzed. HPV DNA detection was performed using HPV genotyping kits (Hybribio Limited Corp, China). An analysis was conducted on the prevalence of HPV infection, taking into account factors such as age, year, and multiple patterns of HPV infection. The differences in prevalence among age groups and years were compared using χ2 test. Results: The overall prevalence of any 21 HPV genotypes was 18.4%, of which the high-risk HPV (HR-HPV) positive rate was 14.6%. The age-specific prevalence of HPV infection showed a bimodal distribution, with two distinct peaks, one at <25 years (31.2%) and the other at 60-64 years (32.9%). There was a downward trend in the prevalence of HPV infection over time, decreasing from 26.2% in 2013 to 14.5% in 2021, and then increasing to 19.0% in 2023. The five most prevent HR-HPV genotypes were HPV52 (4.0%), 58 (2.6%), 16 (2.5%), 51 (1.8%), and 39 (1.7%). Among the positive cases, 76.7% were detected with only one genotype and 23.3% with multiple genotypes. The most common co-infection was HPV52 + HPV58 (0.24%), followed by HPV16 + HPV52 (0.24%), HPV52 + HPV53 (0.21%), HPV52 + HPV81 (0.21%), HPV51 + HPV52 (0.19%), HPV16 + HPV58 (0.18%), and HPV39 + HPV52 (0.17%). Conclusion: The study provided the largest scale information on the recent epidemiological characteristics of HPV infection in Xiamen, and even in Fujian Province, China, which would support making the prevention and control strategies for cervical cancer in the region.

Thermal and electrostatic tuning of surface phonon-polaritons in LaAlO3/SrTiO3 heterostructures.

Phonon polaritons are promising for infrared applications due to a strong light-matter coupling and subwavelength energy confinement they offer. Yet, the spectral narrowness of the phonon bands and difficulty to tune the phonon polariton properties hinder further progress in this field. SrTiO3 - a prototype perovskite oxide - has recently attracted attention due to two prominent far-infrared phonon polaritons bands, albeit without any tuning reported so far. Here we show, using cryogenic infrared near-field microscopy, that long-propagating surface phonon polaritons are present both in bare SrTiO3 and in LaAlO3/SrTiO3 heterostructures hosting a two-dimensional electron gas. The presence of the two-dimensional electron gas increases dramatically the thermal variation of the upper limit of the surface phonon polariton band due to temperature dependent polaronic screening of the surface charge carriers. Furthermore, we demonstrate a tunability of the upper surface phonon polariton frequency in LaAlO3/SrTiO3 via electrostatic gating. Our results suggest that oxide interfaces are a new platform bridging unconventional electronics and long-wavelength nanophotonics.

Effects of non-pharmacological interventions on patients with sarcopenic obesity: A meta-analysis.

OBJECTIVE: Systematic evaluation of the improvement effect of non-pharmacological intervention on patients with sarcopenic obesity. METHODS: Wanfang, VIP, China National Knowledge Infrastructure (CNKI), SinoMed, Web of Science, Cochrane Library, PubMed, and Embase databases were searched systematically for randomized controlled trials (RCTS) and experimental studies of non-pharmacological interventions on patients with sarcopenic obesity. The retrieval period was from the establishment of the databases to October 31, 2022. Meta-analysis was conducted using RevMan 5.4. RESULTS: A total of 18 studies involving 1,109 patients were included. Meta-analysis results showed that non-pharmacological interventions improved patients' body weight [mean difference, MD = -2.74, 95% CI (-4.79, -0.70), P = 0.009], body fat percentage [MD = -0.67, 95% CI (-0.96, -0.38), P<0.00001], grip strength [MD = 1.29, 95% CI (0.81, 1.77), P<0.00001], gait speed [MD = 0.05, 95% CI (0.03, 0.07), P<0.00001], and knee extension strength [MD = 2.56, 95% CI (1.30, 3.82), P<0.0001]. CONCLUSIONS: Non-pharmacological interventions can effectively improve the clinical symptoms and signs of patients with sarcopenic obesity. Dissemination of this information will be therapeutically useful. TRIAL REGISTRATION: Registration. The PROSPERO No. is CRD42023403341.

Chronic diflubenzuron exposure causes reproductive toxic effects in female marine medaka (Oryzias melastigma).

Diflubenzuron, an insecticide commonly used in marine fish farming, has been detected in various marine environments. However, its potential impact on marine fish remains largely unknown. This study investigated the reproductive toxicity of chronic diflubenzuron exposure in female marine medaka (Oryzias melastigma). Marine medaka were exposed continuously to environmentally relevant concentrations of diflubenzuron (0.1, 1, and 10 µg/L) or a solvent control from the fertilized egg to adulthood. In exposed female marine medaka, the gonadosomatic index (GSI) and the number of laid eggs were significantly reduced. Moreover, diflubenzuron-exposed female marine medaka showed altered ovarian histopathology, with an increased relative proportion of immature oocytes and atretic follicles and a decreased relative proportion of mature oocytes. Maternal exposure to diflubenzuron also inhibited the development of the F1 generation, significantly reducing the hatching rate of F1 embryos and significantly increasing the malformation rate of F1 larvae. Furthermore, changes in hormone levels and expression of genes along the hypothalamus-pituitary-gonad-liver (HPGL) axis were observed, which may be the fundamental reason for all the reproductive toxic effects mentioned above. These results provide new insights into the impact of diflubenzuron on the female marine medaka reproductive system and underscore the importance of investigating the potential environmental risks of diflubenzuron in the marine environment.

Leveraging integrated data for program evaluation: Recommendations from the field.

Use of administrative data to inform decision making is now commonplace throughout the public sector, including program and policy evaluation. While reuse of these data can reduce costs, improve methodologies, and shorten timelines, challenges remain. This article informs evaluators about the growing field of Integrated Data Systems (IDS), and how to leverage cross-sector administrative data in evaluation work. This article is informed by three sources: a survey of current data integration efforts in the United States (U.S.) (N=63), informational interviews with experts, and internal knowledge cultivated through Actionable Intelligence for Social Policy's (AISP) 12+ years of work in the field. A brief discussion of the U.S. data integration context and history is provided, followed by discussion of tangible recommendations for evaluators, examples of evaluations relying on integrated data, and a list of U.S. IDS sites with publicly available processes for external data requests. Despite the challenges associated with reusing administrative data for program evaluation, IDS offer evaluators a new set of tools for leveraging data across institutional silos.

Acute and Subacute Safety Evaluation of Black Tea Extract (Herbt Tea Essences) in Mice.

Theabrownin (TB) is a heterogeneous biomacromolecule, extracted from tea, with many functional groups. Importantly, TB possesses diverse health benefits, such as antitumor activity and blood lipid-lowering effects. Presently, the content of TB in tea extract is relatively low. Here, we obtained a deep-processed black tea extract with a high content of TB (close to 80%), which was named Herbt Tea Essences (HTE). Currently, this study was designed to evaluate the biosafety of high-content TB products on mice. We implemented acute and subacute toxic experiments to assess its safety on organs, the serum biochemical and molecular levels. In the acute exposure study, we found that the median lethal dose (LD50) value of HTE was 21.68 g/kg (21.06-24.70 g/kg, greater than 5 g/kg), suggesting that HTE had a low acute toxicity. In the 28-day subacute exposure study, our results showed that no abnormal effects were observed in the 40 and 400 mg/kg/day HTE-treated groups. However, we observed slight nephrotoxicity in the 4000 mg/kg/day HTE-treated group. The HTE-induced nephrotoxic effect might involve the inflammatory response activation mediated by the nuclear transcription factor kappa-B (NF-κB) signaling pathway. This study would provide valuable data for the TB safety assessment and promote this natural biomacromolecule application in daily drinking.

Aryl hydrocarbon receptor agonist diuron and its metabolites cause reproductive disorders in male marine medaka (Oryzias melastigma).

Diuron, a widely used phenylurea herbicide, has been frequently detected in marine organism and seawater all over the world. But the understanding of potential damage of diuron on reproduction in marine fish is currently not enough. Herein, marine medaka (Oryzias melastigma) were continuously exposed to 0, 5, 50, 500, and 5000 ng/L diuron from embryo (0 dpf) to adult (180 dpf) stage. The results suggested that diuron had an adverse influence on male reproduction for marine medaka, including decreased gonado somatic index, histological changes of testes, decreased mobility of sperm, and reduced fecundity through disrupting the balance of sex hormone and genes expression related to hypothalamus-pituitary-gonadal-liver (HPGL) axis. The reduced fecundity was reflected in abnormal sexual behaviors, further inhibited growth and development of F1 embryo and larvae. Moreover, the proportion of diuron metabolites (DCPMU and DCPU) was increased in fish, but the proportion of diuron was decreased with the increasing of exposure concentration. Diuron, DCPMU, and DCPU was identified as aryl hydrocarbon receptor agonist (AhR) agonist using in silico and in vivo models. DCPMU and DCPU induced the gene expression of AhR signaling and metabolizing enzymes (such as cyp1a1) in the livers. A great deal of major metabolites affected various organs related to HPGL axis of male marine medaka and led to serious reproductive disorders. Consequently, it reveals that long-term exposure to environmentally relevant concentrations of diuron and even AhR agonist pesticides pose a potential ecological risk for marine fish.

Role of sanguinarine in regulating immunosuppression in a Lewis lung cancer mouse model.

Myeloid-derived suppressor cells (MDSCs) play an important role in the tumor-induced immunosuppressive microenvironment and have been linked with tumor development, proliferation, and resistance to treatment. Therefore, therapies that target MDSCs, such as sanguinarine (SNG), are now being considered potential treatments for lung cancer. However, the role of SNG in regulating the immune response in lung cancer is still not clear. In view of this, we evaluated the mechanism involved in the antitumor and immunoregulatory response to SNG therapy in a Lewis lung cancer (LLC) mouse model. The tumor mass and volume in the SNG treated LLC mouse model were significantly lower when compared with the control group (p < 0.05), indicating a good response to SNG. SNG also reduced the damage to the spleen, decreased the proportion of MDSCs, and increased the production of T helper 1 (Th1), T helper 2 (Th2), cytotoxic T-lymphocyte (CTL), macrophages, dendritic cells (DC) within the spleen. However, it did not affect the proportion of T helper 17 (Th17) and regulatory T cells (Treg). SNG also down-regulated the proportion of MDSCs in vitro and promoted their apoptosis, differentiation, and maturation. SNG was found to induce the differentiation of MDSCs into macrophages and DC through the nuclear factor kappa-B (NF-κB) pathway in vitro, while it also decreased the expression of arginase-1 (Arg-1) anti-inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) in MDSCs.SNG also reduced the inhibitory effect on the proliferation of CD8+T cells. SNG may reduce the immunosuppressive state induced by lung cancer by promoting cell differentiation and by inhibiting the immunosuppressive activity of MDSCs.

Parental diuron exposure causes lower hatchability and abnormal ovarian development in offspring of medaka (Oryzias melastigma).

Diuron is one of the most widely used herbicides worldwide. It has been widely detected in various aquatic environments, especially in marine ecosystems. Although direct effects of diuron exposure on various organisms have been reported, little is known about its effects on marine fishes including multigenerational effects. Herein, the filial generation (F1) of diuron-exposed marine medaka (Oryzias melastigma) (F0) was raised in clean seawater from fertilized eggs to adulthood and used as a marine fish model to study the potential multigenerational effects of diuron. We found that the successful hatching of F1 larvae was significantly reduced and that ovarian development in F1 females was retarded. A significant increase in the percentage of previtellogenic oocytes, along with a visual decrease in the percentage of vitellogenic and mature oocytes in the F1 ovary, were observed. The hormone levels of the hypothalamus-pituitary-gonad-liver axis and vitellogenin-related transcription were downregulated. In addition, the mRNA levels of DNA methyltransferase in the brain, ovary and liver of F1 adult fish exhibited significant upregulation, suggesting that the probable underlying multigenerational mechanism might be associated with epigenetic modifications. Taken together, these results demonstrated that chronic environmental diuron exposure in F0 marine medaka can inhibit F1 ovary development and suggested that diuron may affect marine fish thriving in the ocean.

Chronic exposure to environmentally realistic levels of diuron impacts the behaviour of adult marine medaka (Oryzias melastigma).

Diuron, a commonly used herbicide and antifouling biocide, has been frequently detected in seawater. The effects of diuron on fish behaviour are currently poorly understood. Herein, the marine medaka (Oryzias melastigma) was continuously exposed to environmentally realistic levels of diuron from the fertilised egg stage to the adult stage. Behavioural evaluation of adult marine medaka indicated that exposure to diuron increased anxiety in the light-dark test and increased predator avoidance. In addition, diuron exposure significantly reduced aggression, social interaction, shoaling, and learning and memory ability. However, only negligible variations in foraging behaviour and in behaviour in the novel tank test were observed. Marine medaka chronically exposed to diuron also showed decreased levels of dopamine in the brain, and changes were observed in the transcription of genes related to dopamine synthesis, degradation and receptors. Exposure to 5000 ng/L diuron caused significant downregulation of the expression of the genes of tyrosine hydroxylase and monoamine oxidase and significantly upregulated the expression of the genes of the D5 dopaminergic receptor. The relative expression of the D4 dopaminergic receptor was significantly upregulated in the 50, 500 and 5000 ng/L diuron-treated groups. These findings highlight the significant neurotoxic effects of diuron and the extent to which this may involve the dopaminergic system of the brain. More broadly, this study reveals the ecological risk associated with environmentally realistic levels of diuron in marine animals.

Acute and subacute oral toxicity of propylene glycol enantiomers in mice and the underlying nephrotoxic mechanism.

Propylene glycol (PG; 1,2-propanediol) has been commonly used as a food additive and vehicle in pharmaceutical preparations. PG can form rectus (R-) enantiomers and sinister (S-) enantiomers. Herein, Kunming mice were used as the animal model to evaluate the acute and subacute oral toxicity of R-PG, S-PG and RS-PG (1:1 racemic mixture of R-PG and S-PG). The median lethal doses of R-PG, S-PG and RS-PG administered by oral gavage to mice were 22.81 g/kg, 26.62 g/kg and 24.92 g/kg, respectively. In the 28-day oral subacute toxicity study, the body weight, organ weights, serum biochemical, and renal histology were examined. There was no difference in subacute toxicity among R-PG, S-PG and RS-PG. The administration of 1 and 5 g/kg/day PG for 28 days caused nephrotoxicity. The kidney somatic index and levels of blood urea nitrogen exhibited a significant increase. Moreover, the activities of superoxide dismutase, catalase, and glutathione peroxidase significantly decreased after the treatment with PG. The levels of malondialdehyde, tumor necrosis factor α, interleukin 1ß, and interleukin 6 significantly increased in the kidney. The results show that the nephrotoxic effects of PG are induced by oxidative stress, and the activation of the inflammatory response is mediated by the NF-κB signaling pathway. Together, these findings provide information on R-PG, S-PG and RS-PG treatments for the risk assessment of toxicity and effects on human health.

Reducing particulates in indoor air can improve the circulation and cardiorespiratory health of old people: A randomized, double-blind crossover trial of air filtration.

Exposure to indoor air particulate pollution increases respiratory and cardiovascular morbidity and mortality, especially in the elderly. To assess a short-term, indoor air filtration's potential benefit on circulatory and cardiopulmonary health among healthy older people, a randomized, double-blind crossover trial was conducted with 24 healthy residents of an aged-care center in Chongqing, China in 2020. Each room received a high-efficiency particulate air filter air purifier and a placebo air purifier for two days. Fifteen circulatory system biomarkers of inflammation, coagulation, and oxidative stress; lung function; blood pressure (BP); heart rate (HR) and fractional exhaled nitric oxide (FeNO) were measured end of each two days. Indoor air particulate pollution was monitored throughout the study period. Linear mixed-effect models were used to associate health outcome variables with indoor particles. This intervention study demonstrated that air filtration was associated with significantly decreased concentrations of inflammatory and coagulation biomarkers, but not of biomarkers of oxidative stress and lung function. Just 48 h of air filtration can improve the cardiopulmonary health of the elderly. Air purifiers may be a public health measure that can be taken to improve circulatory and cardiopulmonary health among older people.

Improvement in the screening performance of potential aryl hydrocarbon receptor ligands by using supervised machine learning.

The aryl hydrocarbon receptor (AhR), which is a ligand-dependent transcription factor, plays a crucial role in the regulation of xenobiotic metabolism. There are a large number of artificial or natural molecules in the environment that can activate AhR. In this study, we developed a virtual screening procedure to identify potential ligands of AhR. One structure-based method and two ligand-based methods were used for the virtual screening procedure. The results showed that the precision rate (0.96) and recall rate (0.64) of our procedure were significantly higher than those of a procedure used in a previous study, which suggests that supervised machine learning techniques can greatly improve the performance of virtual screening. Moreover, a pesticide dataset including 777 frequently used pesticides was screened. Seventy-seven pesticides were identified as potential AhR ligands by all three screening methods, among which 12 have never been previously reported as AhR agonists. Two non-agonist AhR ligands and 14 of the 77 pesticides were randomly selected for testing by in vitro and in vivo assays. All 14 pesticides showed different degrees of AhR agonistic activity, and none of the two non-agonist AhR ligand pesticides showed AhR agonistic activity, which suggests that our procedure had good robustness. Four of the pesticides were reported as AhR agonists for the first time, suggesting that these pesticides may need further toxicity assessment. In general, our procedure is a rapid, powerful and computationally inexpensive tool for predicting chemicals with AhR agonistic activity, which could be useful for environmental risk prediction and management.

Exposure to the AhR agonist cyprodinil impacts the cardiac development and function of zebrafish larvae.

Cyprodinil is a broad-spectrum pyrimidine amine fungicide that has been reportedly used worldwide. However, toxicity studies of cyprodinil on aquatic organisms, specifically zebrafish (Danio rerio), are lacking. In our present study, we predicted cyprodinil binding to the aryl hydrocarbon receptor (AhR) by using molecular docking simulation. Then, we used recombinant HepG2 cells and Tg(cyp1a1-12DRE:egfp) transgenic zebrafish to further assess the AhR agonistic activity of cyprodinil. Besides, the significant upregulation of cyp1a1 further verified that statement. Moreover, we found that zebrafish exposure to cyprodinil induced developmental toxicity in the larvae, particularly during cardiac development. The expression levels of cardiac development-related genes, namely tbx5, nkx2.5, gata4, and tnnt2, were markedly altered, which might cause the adverse effects of cyprodinil on cardiac function and development. In summary, we found that cyprodinil, as an AhR agonist, induced development toxicity in zebrafish larvae, especially on cardiac. Data here can assess the potential effects on organisms in the aquatic environment and promote the regulation and safe use of cyprodinil.

Developmental exposure to mepanipyrim induces locomotor hyperactivity in zebrafish (Danio rerio) larvae.

Mepanipyrim is a widely used fungicide, and residues of mepanipyrim are frequently detected in commodities. However, the neurotoxicity and underlying mechanisms of mepanipyrim are still insufficiently understood. In this study, zebrafish embryos at 0.5-1.0 post-fertilization hours (hpf) were exposed to 0.1, 1, 10 and 100 µg/L mepanipyrim for 7 days. Our results showed that mepanipyrim could cause the locomotor hyperactivity and increase the concentration of γ-amino butyric acid (GABA) and the Na+/K+- and Ca2+-ATPase activities in zebrafish larvae. We have conducted the RNA-sequence and RT-qPCR to analyze the gene expressions. The mRNA expression levels of calcium/sodium ion conduction associated genes were observably up-regulated, demonstrating that mepanipyrim could enhance the cell energy metabolism, the synaptic transmission and skeletal muscle contraction, which were consistent with the locomotor hyperactivity. Meanwhile, exposure to mepanipyrim could significantly change the gene expression levels of gad1, bdnf, nlgn1, and type A and B GABA receptors in zebrafish larvae. This is the first study focusing on the underlying mechanisms of the neurotoxic effects that are induced by mepanipyrim.

Generation and application of a Tg(cyp1a:egfp) transgenic marine medaka (Oryzias melastigma) line as an in vivo assay to sensitively detect dioxin-like compounds in the environment.

Large-range environmental pollution by dioxin and dioxin-like compounds (DLCs) is becoming a serious problem. To establish an in vivo method for the detection of DLCs in seawater, a Tg(cyp1a-12DRE:egfp) transgenic marine medaka (Oryzias melastigma) line was first developed with the modified cyp1a-12DRE promoter driving enhanced green fluorescent protein (EGFP) expression using Tol2 transgenesis technology. With increasing concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), the EGFP fluorescence intensity increased significantly. The Tg(cyp1a-12DRE:egfp) medaka possessed high sensitivity (limit of detection of 1 ng/L TCDD) and specificity and low background. This transgenic line is capable of detecting DLCs in environmental seawater in which the concentration of DLCs is at least 0.12207 ng/L TCDD after sample enrichment. The fluorescence-toxic equivalency (TEQ) values from EGFP intensity were closely correlated with the chemical-TEQ values obtained from chemical analyses. Furthermore, the Tg(cyp1a-12DRE:egfp) medaka can directly detect DLCs in seawater samples after a serious pollution accident and screen unknown aryl hydrocarbon receptor (AhR) agonists for risk assessment. For the first time, a convenient method has been established that sensitively and specifically responds to DLCs using the Tg(cyp1a-12DRE:egfp) marine medaka, which could be a highly efficient tool for detecting seawater DLCs in the future.

AhR Agonist Activity Confirmation of Polyhalogenated Carbazoles (PHCZs) Using an Integration of in Vitro, in Vivo, and in Silico Models.

Polyhalogenated carbazoles (PHCZs) are a kind of rising environmental pollutant that has been reported to pose high risk to human beings and the natural environment. PHCZs are of a similar molecular structure with of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and exhibited some dioxin-like toxicity. Dioxin-like compounds (DLCs) are banned by the Stockholm Convention due to their potential adverse impacts to the environment and public health. However, a few efforts have been made toward the regulation of PHCZs. Herein, we initiated multimodels to systematically determine and validate the dioxin-like effects of PHCZs on a large scale. Transgenic zebrafish line-Tg(cyp1a-12DRE:EGFP) and stably transfected HepG2 cell line with luciferase reporter plasmids were used to screen and evaluate the aryl hydrocarbon receptor (AhR) agonist effects of the target PHCZs, which were then verified by application of molecular docking and expression levels of AhR downstream genes. Results of the two bioassays showed that most of the tested PHCZs could pose dioxin-like AhR agonist effects, change the expression levels of AhR downstream genes, and interact with AhR in accordance with TCDD. In summary, data presented here can help to guide the safe use and regulation of PHCZs.

Driving anger among motor vehicle drivers in China: A cross-sectional survey.

Objective: Driving anger is a common emotion while driving and has been associated with traffic crashes. This study aimed to investigate situations that increase driving anger among Chinese drivers. Methods: A cross-sectional study was conducted among 3,101 drivers in southern China. The translated version of the 33-item Driving Anger Scale (DAS) was used to measure driving anger. Data were collected by face-to-face interviews between June 2016 and September 2016. Results: Confirmatory factor analysis showed that the fit of the original 6-factor model (discourtesy, traffic obstacles, hostile gestures, slow driving, illegal driving, and police presence) was satisfactory, after removing 2 items and allowing 5 error pairs to covary. The model showed satisfactory fit: goodness of fit index (GFI) = 0.90, incremental fit index (IFI) = 0.90, root mean square error of approximation (RMSEA) = 0.06, 90% confidence interval (CI) = 0.061-0.064. Driving anger among Chinese drivers was lower than that in some Western countries. Compared to older and experienced drivers, younger and new drivers were more likely to report driving anger. There was no difference in total reported driving anger between males and females. Additionally, the higher the driver's anger level was, the more likely he or she was to have had a traffic crash. Conclusion: Driving anger is a common emotion among Chinese drivers and has a strong correlation with aggressive driving behavior and traffic crashes.

Bioassay system for the detection of aryl hydrocarbon receptor agonists in waterborne pesticides using zebrafish cyp1a1 promoter-luciferase recombinant hepatic cells.

Currently used pesticides are widely distributed in surface water. Most of them are harmful to aquatic animals. In the present study, a novel recombinant hepatic cell line was developed for detecting the activity of aryl hydrocarbon receptor (AhR) agonists, and their potential bio-toxicity to aquatic animals was evaluated. First, HepG2 cells were stably transfected with a luciferase reporter plasmid containing a zebrafish (Danio rerio) cyp1a1 promoter with twelve copies of dioxin-responsive elements. The minimal detection limit was a 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentration of 0.3 ng/L (equivalent to 0.93 pM). The AhR agonist activity of thirty-seven pesticides was screened by measuring luciferase expression in the recombinant cells. Four pesticides (ipconazole, mepanipyrim, quinoxyfen and pencycuron) significantly induced luciferase expression. Additionally, cells treated with these four pesticides increased the cyp1a1 mRNA expression level, which further confirmed that they are AhR agonists. In conclusion, for the first time, we developed recombinant hepatic cells with a luciferase reporter plasmid containing a modified zebrafish cyp1a1 promoter. The cyp1a1 promoter luciferase reporter cells can be used as a sensitive and specific model to screen AhR agonists among currently used pesticides in water, which could be beneficial for risk assessment in aquatic environments.

Generation of a Tg(cyp1a-12DRE:EGFP) transgenic zebrafish line as a rapid in vivo model for detecting dioxin-like compounds.

Dioxin-like compounds (DLCs) are extremely stable toxic organic compounds and can cause serious health risks. To develop a convenient biomonitoring tool for the detection of DLCs in the environment, we generated a transgenic line-Tg(cyp1a-12DRE:EGFP)-with a zebrafish cyp1a promoter recombined with multiple dioxin-responsive elements (DREs) that drive EGFP expression. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced EGFP expression was observed in the head cartilage (most sensitive), gut, otic vesicle, pectoral fin bud and eye of larvae. The lowest observed effect concentration of TCDD was estimated to be approximately 1 ng/L. Compared with existing zebrafish lines, our transgenic fish displayed comparable or even higher detection sensitivity to DLCs and could serve as an improved and rapid assay in an in vivo context. The Tg(cyp1a-12DRE:EGFP) transgenic zebrafish line also had higher stability for inducing EGFP expression (nearly 100% of our zebrafish induced EGFP at approximately 1 ng/L TCDD) than other lines. In addition, Tg(cyp1a-12DRE:EGFP) zebrafish could serve as a convenient and straightforward tool to assess potential cranial malformations and related health effects.