Case Report: Assessment of primary myxofibrosarcoma in the left atrium using multimodal ultrasonography.

Primary myxofibrosarcoma of the heart, a rare cardiac malignancy, was diagnosed in a middle-aged female patient exhibiting progressive dyspnea following transthoracic echocardiography and pathological analysis. Postoperatively, the patient underwent chemotherapy and Lenvatinib mesylate therapy, with regular check-ups confirming her survival. After 10 months the patient is still alive and well.

Assessing the evolution of hypertension management in Gansu, China: A comparative study of prevalence, awareness, treatment, and control in 2012 and 2022.

The aim of this study is to evaluate the developments in the treatment and prevalence of hypertension by demographic subgroups in least developed area of China in 2012 and 2022. This population-based cross-sectional study was conducted in 2012 and 2022, we applied stratified multistage random sampling to investigate residents aged 18 years or older in Gansu, the least developed province in the northwest of China. Questionnaires and anthropometric measurements were given to all respondents. The standardized prevalence of hypertension in adults in Gansu increased from 26.1% in 2012 to 28.8% in 2022. Compared with 2012, the control rate remains decreased despite the significantly improved awareness and treatment rates of hypertension in 2022. Apart from the reversal of the control rate, the trend of higher prevalence in men and higher awareness and treatment rates in women has not changed. There was an obviously increase in the proportion of participants who had received health education and hypertension management services from medical workers. The treatment was still primarily monotherapy, and there was no significant improvement in the prescription of medication. The prevalence of hypertension has increased mildly in the least developed region of China over the past decade, and the challenge of hypertension management has shifted from increasing awareness and treatment rates to increasing control rates. The onset and control of hypertension are affected by education methods, BMI, local economic conditions and other factors, and targeted strategies can be adopted to strengthen the management of hypertension in economically underdeveloped areas of China.

Bioactivity assessment of organophosphate flame retardants via a dose-dependent yeast functional genomics approach.

Organophosphate flame retardants (OPFRs) have been widely detected in multiple environment media and have many adverse effects with complex toxicity mechanisms. However, the early molecular responses to OPFRs have not been fully elucidated, thereby making it difficult to assess their risks accurately. In this work, we systematically explored the point of departure (POD) of biological pathways at genome-wide level perturbed by 14 OPFRs with three substituents (alkyl, halogen, and aryl) using a dose-dependent functional genomics approach in Saccharomyces cerevisiae at 24 h exposure. Firstly, our results demonstrated that the overall biological potency at gene level (PODDRG20) ranged from 0.013 to 35.079 µM for 14 OPFRs, especially the tributyl phosphate (TnBP) exhibited the strongest biological potency with the least PODDRG20. Secondly, we found that structural characteristics of carbon number and logKow were significantly negatively correlated with POD, and carbon number and logKow also significantly affected lipid metabolism associated processes. Thirdly, these early biological pathways of OPFRs toxification were found to be involved in lipid metabolism, oxidative stress, DNA damage, MAPK signaling pathway, and amino acid and carbohydrate metabolism, among which the lipid metabolism was the most sensitive molecular response perturbed by most OPFRs. More importantly, we identified one resistant mutant strain with knockout of ERG2 (YMR202W) gene participated in steroid biosynthesis pathway, which can serve as a key yeast strain of OPFRs toxification. Overall, our study demonstrated an effective platform for accurately assessing OPFRs risks and provided a basis for further green OPFRs development.

Long-term trends in incidence, mortality and burden of liver cancer due to specific etiologies in Hubei Province.

Liver cancer, a chronic non-communicable disease, represents a serious public health problem. Long-term trends in the burden of liver cancer disease are heterogeneous across regions. Incidence and mortality of liver cancer, based on the Global Burden of Disease, were collected from the Chinese Centre for Disease Control and Prevention. Age-period-cohort model was utilized to reveal the secular trends and estimate the age, period and cohort effects on primary liver cancer due to specific etiologies. Both the age-standardized incidence and mortality rate of liver cancer in Hubei province were on the rise, although there were discrepancies between gender groups. From age-period-cohort analysis, both incidence and mortality of liver cancer due to Hepatitis B virus were the highest in all age groups. The incidence of all liver cancer groups increased with time period in males, while this upward trend was observed in females only in liver cancer due to alcohol use group. Cohort effects indicated the disease burden of liver cancer decreased with birth cohorts. Local drifts showed that the incidence of liver cancer due to specific etiologies was increasing in the age group of males between 40 and 75 years old. The impact of an aging population will continue in Hubei Province. the disease burden of liver cancer will continue to increase, and personalized prevention policies must be adopted to address these changes.

Individualized threshold of the involuntary weight loss in prognostic assessment of cancer.

BACKGROUND: Involuntary weight loss (WL) is a common symptom in cancer patients and is associated with poor outcomes. However, there is no standardized definition of WL, and it is unclear what magnitude of weight loss should be considered significant for prognostic purposes. This study aimed to determine an individualized threshold for WL that can be used for prognostic assessment in cancer patients. METHODS: Univariate and multivariate analyses of overall survival (OS) were performed using Cox proportional hazard models. The Kaplan-Meier method was performed to estimate the survival distribution of different WL levels. Logistic regression analysis was used to determine the relationship between WL and 90-day outcomes. Restricted cubic splines with three knots were used to examine the effects of WL on survival under different body mass index (BMI) conditions. RESULTS: Among the 8806 enrolled patients with cancer, median survival time declined as WL increased, from 25.1 to 20.1, 17.8 and 16.4 months at <2%, 2-5%, 5-10% and ≥10% WL, respectively (P < 0.001). Multivariate adjusted Cox regression analysis showed that the risk of adverse prognosis increased by 18.1% based on the SD of WL (5.45 U) (HR: 1.181, 95% CI: 1.144-1.219, P < 0.001). Similarly, categorical WL was independently associated with OS in patients with cancer. With the worsening of WL, the risk of a poor prognosis in patients increases stepwise. Compared with <2% WL, all-cause mortalities were 15.1%, 37% and 64.2% higher in 2-5%, 5-10%, and ≥10% WL, respectively. WL can effectively stratify the prognosis of both overall and site-specific cancers. The clinical prognostic thresholds for WL based on different BMI levels were 4.21% (underweight), 5.03% (normal), 6.33% (overweight), and 7.60% (obese). Multivariate logistic regression analysis showed that WL was independently associated with 90-day outcomes in patients with cancer. Compared with patients with <2% WL, those with ≥10% WL had more than twice the risk of 90-day outcomes (OR: 3.277, 95% CI: 2.287-4.694, P < 0.001). Systemic inflammation was a cause of WL deterioration. WL mediates 6.3-10.3% of the overall association between systemic inflammation and poor prognoses in patients with cancer. CONCLUSIONS: An individualized threshold for WL based on baseline BMI can be used for prognostic assessment in cancer patients. WL and BMI should be evaluated simultaneously in treatment decision-making, nutritional intervention, and prognosis discussions of patients with cancer.

Improving the assessment of malnutrition in cancer: Using systemic inflammation markers as a supplement to the inflammation items of the GLIM criteria.

BACKGROUND & AIMS: Systemic inflammation is a key pathogenic criterion for diagnosing malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Although cancer is commonly considered as a chronic inflammation-related disease, the inflammatory burden may vary depending on the type and stage of cancer. Therefore, a more precise definition of inflammation criteria could facilitate the identification of malnutrition in cancer. METHODS: This prospective multicenter study included 1683 cancer patients screened via NRS2002 for malnutrition risk. The inflammatory burden index (IBI), C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), and albumin (ALB) level were used to assess the inflammatory burden. Kaplan-Meier and Cox regression analyses were used to determine the relationship between the GLIM criteria and overall survival. Harrell's concordance index (C-index) was used to compare the discriminative performance of the original, IBI-based, CRP-based, NLR-based, and ALB-based GLIM criteria for survival. Logistic regression models were used to assess the association between GLIM criteria and short-term outcomes, length of hospital stay, and hospitalization costs. RESULTS: Compared to the original GLIM criteria, the IBI/CRP/NLR/ALB-based GLIM criteria better predicted the long-term outcomes of patients with cancer (chi-square: 1.316 vs. 78.321 vs. 74.740 vs. 88.719 vs. 100.921). The C-index revealed that the inflammation marker-based GLIM criteria showed significantly better prognostic accuracy than the original GLIM criteria. The ALB-based GLIM criteria exhibited the best prognostic accuracy. The inflammation marker-based GLIM criteria were independent predictive factors for the long-term prognosis of cancer. Patients with malnutrition had a 45% higher risk of adverse long-term prognoses than those without malnutrition. The inflammation marker-based GLIM criteria had good prognostic ability to predict outcomes at 3, 6, and 12 months. The stepwise effect of the grading of severity via the IBI-based GLIM criteria and CRP-based GLIM criteria was notable. The inflammation marker-based GLIM criteria are useful for predicting short-term outcomes, length of hospitalization, and hospitalization costs. CONCLUSION: The inflammation marker-based GLIM criteria have a stronger predictive value than the original GLIM criteria in evaluating both the short- and long-term prognoses of cancer patients. It is recommended to use the inflammation marker-based GLIM criteria for nutritional evaluation of cancer patients.

Deep mining of reported emerging contaminants in China's surface water in the past decade: Exposure, ecological effects and risk assessment.

The identification and management of high-risk contaminants have raised great concern from governments. Facing the growing amount of data on the occurrence of emerging contaminants (ECs) in surface water, a deep mining and quality control strategy was developed to integrate data on all reported ECs in Chinese surface water over the past decade, and an exposure and effect database was further built. In addition, multilevel risk characterization was carried out to prioritize high-risk areas, contaminants and endpoints. A total of 1038 ECs, mainly pharmaceutical and personal care products (PPCPs) and industrial chemicals, were curated, with concentrations ranging from 0.02 pg/L to 533 µg/L. For individual risk, all the provinces had acceptable risks except for Henan, which was characterized with a medium chronic risk. Nine ECs, including 4-nonylphenol and estrone, dominated individual risks. Conversely, for multisubstance risk, 76.20% and 73.87% of aquatic organisms were affected acutely and chronically at the national level, with acute and chronic risks exceeding the safety threshold of 5% in 11 and 19 provinces, respectively. Nineteen ECs, including sitosterol and chyfluthrin, dominated the multisubstance risk. In addition, 9 MoAs mainly inducing electron transfer inhibition, neurotoxicity and narcosis toxicity are high-risk endpoints. The study revealed the ecological risk status and key risk entities of Chinese surface waters, which provided the latest data to support the control of ECs in China.

Unsupervised biological integrity assessment by eDNA biomonitoring of multi-trophic aquatic taxa.

The biological integrity of global freshwater ecosystems is threatened by ever-increasing environmental stressors due to increased human activities, such as land-use change, eutrophication, toxic pollutants, overfishing, and exploitation. Traditional ecological assessments of lake or riverine ecosystems often require human supervision of a pre-selected reference area, using the current state of the reference area as the expected state. However, selecting an appropriate reference area has become increasingly difficult with the expansion of human activities. Here, an unsupervised biological integrity assessment framework based on environmental DNA metabarcoding without a prior reference area is proposed. Taxon richness, species dominance, co-occurrence network density, and phylogenetic distance were used to assess the aquatic communities in the Taihu Lake basin. Multi-gene metabarcoding revealed comprehensive biodiversity at multiple trophic levels including algae, protists, zooplankton, and fish. Fish sequences were mainly derived from 12S, zooplankton mainly from mitochondrial cytochrome C oxidase subunit I, and algae and protists mainly from 18S. There were significant differences in community composition among lakes, rivers, and reservoirs but no significant differences in the four fundamental biological indicators. The algal and zooplankton integrities were positively correlated with protist and fish integrities, respectively. Additionally, the algal integrity of lakes was found to be significantly lower than that of rivers. The unsupervised assessment framework proposed in this study allows different ecosystems, including the same ecosystem in different seasons, to adopt the same indicators and assessment methods, which is more convenient for environmental management and decision-making.

Synergic effects of PM1 and thermal inversion on the incidence of small for gestational age infants: a weekly-based assessment.

BACKGROUND: The synergic effects of thermal inversion (TI) and particulate matter with an aerodynamic diameter ≤1 µm (PM1) exposure and incidence of small for gestational age (SGA) was not clear. OBJECTIVE: We aimed to explore the independent effects of prenatal TI and PM1 exposure on incidence of SGA and their potential interactive effects. METHODS: A total of 27,990 pregnant women who delivered in Wuhan Children's Hospital from 2017 to 2020 were included. The daily mean concentration of PM1 was obtained from ChinaHighAirPollutants (CHAP) and matched with the residential address of each woman. Data on TI was derived from National Aeronautics and Space Administration (NASA). The independent effects of PM1 and TI exposures on SGA in each gestational week were estimated by the distributed lag model (DLM) nested in Cox regression model, and the potential interactive effects of PM1 and TI on SGA were investigated by adapting the relative excess risk due to interaction (RERI) index. RESULTS: Per 10 µg/m3 increase in PM1 was associated with an increase in the risk of SGA at 1-3 and 17-23 gestational weeks, with the strongest effect at the first gestational week (HR = 1.043, 95%CI: 1.008, 1.078). Significant links between one day increase of TI and SGA were found at the 1-4 and 13-23 gestational weeks and the largest effects were observed at the 17th gestational week (HR = 1.018, 95%CI: 1.009, 1.027). Synergistic effects of PM1 and TI on SGA were detected in the 20th gestational week, with RERI of 0.208 (95%CI: 0.033,0.383). IMPACT STATEMENT: Both prebirth PM1 and TI exposure were significantly associated with SGA. Simultaneous exposure to PM1 and TI might have synergistic effect on SGA. The second trimester seems to be a sensitive window of environmental and air pollution exposure.

Global Burden of osteoarthritis associated with high body mass index in 204 countries and territories, 1990-2019: findings from the Global Burden of Disease Study 2019.

OBJECTIVE: To quantify the burden of osteoarthritis (OA) associated with high body mass index (BMI) across 204 countries and territories from 1990 to 2019. METHODS: This study extracted global, regional, and national data on years lived with disability (YLD) of OA associated with high BMI from GBD 2019. The YLD burden of OA associated with high BMI was systematically analyzed by age, SDI, sex, and EAPC. RESULTS: At the global level, ~2.67 million (95% UI: 1.04, 5.75) YLD were attributable to OA associated with high BMI, with an age-standardized rate of 31.9 (95% UI: 12.4, 68.75) YLD per 100,000 population in 2019. There was a 0.5 increase (95% UI: 0.35, 0.79) over the 30 years with an EAPC of 1.45. In 2019, Australasia {57.49 (95% UI: 23.62, 125.38)}, high-income North America {56.2 (95% UI: 23.32, 121.97)}, and Andean Latin America {49.77 (95% UI: 19.73, 111.73)} had the highest age-standardized YLD rates. The population aged at 60-74 group had a higher YLD rate for both males and females. Females tended to be more sensitive to the OA associated with high BMI than male in any region. CONCLUSIONS: In summary, the YLD rate of OA associated with high BMI presented a continuous upward trend in most countries. Women and older people are more sensitive to OA due to physiological and psychological factors. Controlling modifiable risk factors such as maintaining an appropriate BMI is needed for disease prevention.

Trends in the global burden of oral cancer joint with attributable risk factors: Results from the global burden of disease study 2019.

OBJECTIVES: To investigate the characteristics of risk factors for oral cancer and the disease burden they caused. MATERIALS AND METHODS: Data from GBD2019, where the EAPC was calculated to understand mortality trends and the APC model was used for the analysis of age characteristics. RESULTS: Overall oral cancer mortality showed a promising downward trend [EAPC = -0.05 (-0.08 to -0.02)]. Oral cancer mortality attributable to tobacco chewing alone showed a significant upward trend [EAPC = 0.44 (0.36-0.52)]. Males are the majority of oral cancer deaths, while the disease burden of oral cancer in females could be largely attributable to chewing tobacco. The age of death attributable to each risk factor for oral cancer is concentrated between 45 and 74 years. Mortality for oral cancer caused by alcohol and smokeless tobacco was increasing in younger age groups (age < 45), and this trend was more pronounced in middle and middle-high SDI areas. The disease burden of oral cancer in high SDI regions was mainly attributed to alcohol consumption, while in middle and lower SDI regions it was mainly attributed to tobacco. CONCLUSION: Smokeless tobacco proved a critical factor in the significant regional distribution of oral cancer. Oral cancer is on the increase in younger age groups. According to the characteristics of the distribution of risk factors, in traditionally high-incidence regions, such as India and Pakistan, oral cancer kept the highest ASDR, but was not experiencing the fastest growth rate. Additionally, it was oral cancer in middle SDI regions that needs more attention.

Efficacy and safety assessment of glandular augmentation with hyaluronic acid for premature ejaculation.

Glandular augmentation (GA) with hyaluronic acid (HA) is a newly developed, minimally invasive therapy for patients with premature ejaculation (PE); however, evidence supporting its efficacy is scarce. To provide a comprehensive profile of GA with HA gel in managing PE, 184 patients with PE who received GA with HA gel therapy from October 2017 to November 2019 were included and followed up for 1 year. The Fan technique was applied. Intravaginal Ejaculation Latency Time (IELT), Chinese Index of Premature Ejaculation-5(CIPE-5) and Visualised Satisfaction Index (VSI) of sexual experience were assessed at initial and 1-, 3-, 6- and 12-month post injection. A total of 71 patients with primary PE (pPE, 38.6%) and 113 patients with acquired PE (aPE, 61.4%) were enrolled. The mean IELT increased to 100.7 ± 43.2 s(p < .05) for pPE patients and 359.2 ± 87.1 s (p < .05) for aPE patients 1-month post injection and remained significantly higher at the end point with acceptable attenuation. The mean CIPE-5 score increased to 17.6 ± 6.4 (p < .05) in the 1st month and remained steady. The VSI scores increased to 6.6 ± 1.0 (p < .05) for patients with pPE and 7.7 ± 1.2 (p < .01) for patients with aPE. Increments in VSI in patients with aPE were significantly higher than those in patients with pPE (p < .01). No severe complications were noted. GA with HA may be an effective and safe method to treat PE. Patients with acquired PE were also more satisfied post treatment.

Assessment of genotoxic chemicals using chemogenomic profiling based on gene-knockout library in Saccharomyces cerevisiae.

Understanding the adverse effects of genotoxic chemicals and identifying them effectively from non-genotoxic chemicals are of great worldwide concerns. Here, Saccharomyces cerevisiae (yeast) genome-wide single-gene knockout screening approach was conducted to assess two genotoxic chemicals (4-nitroquinoline-1-oxide (4-NQO) and formaldehyde (FA)) and environmental pollutant dichloroacetic acid (DCA, genotoxicity is controversial). DNA repair was significant enriched in the gene ontology (GO) biology process (BP) terms and KEGG pathways when exposed to low concentrations of 4-NQO and FA. Higher concentrations of 4-NQO and FA influenced some RNA metabolic and biosynthesis pathways. Moreover, replication and repair associated pathways were top ranked KEGG pathways with high fold-change for low concentrations of 4-NQO and FA. The similar gene profiles perturbed by DCA with three test concentrations identified, the common GO BP terms associated with aromatic amino acid family biosynthetic process and ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. DCA has no obvious genotoxicity as there was no enriched DNA damage and repair pathways and fold-change of replication and repair KEGG pathways were very low. Five genes (RAD18, RAD59, MUS81, MMS4, and BEM4) could serve as candidate genes for genotoxic chemicals. Overall, the yeast functional genomic profiling showed great performance for assessing the signatures and potential molecular mechanisms of genotoxic chemicals.

Assessment of fibrotic pathways induced by environmental chemicals using 3D-human liver microtissue model.

Exposure to environmental chemicals, particularly those with persistent and bioaccumulative properties have been linked to liver diseases. Induction of fibrotic pathways is considered as a pre-requirement of chemical induced liver fibrosis. Here, we applied 3D in vitro human liver microtissues (MTs) composed of HepaRG, THP-1 and hTERT-HSC that express relevant hepatic pathways (bile acid, sterol, and xenobiotic metabolism) and can recapitulate key events of liver fibrosis (e.g. extracellular matrix-deposition). The liver MTs were exposed to a known profibrotic chemical, thioacetamide (TAA) and three representative environmental chemicals (TCDD, benzo [a] pyrene (BaP) and PCB126). Both TAA and BaP triggered fibrotic pathway related events such as hepatocellular damage (cytotoxicity and decreased albumin release), hepatic stellate cell activation (transcriptional upregulation of α-SMA and Col1α1) and extracellular matrix remodelling. TCDD or PCB126 at measured concentrations did not elicit these responses in the 3D liver MTs system, though they caused cytotoxicity in HepaRG monoculture at high concentrations. Reduced human transcriptome (RHT) analysis captured molecular responses involved in liver fibrosis when MTs were treated with TAA and BaP. The results suggest that 3D, multicellular, human liver microtissues represent an alternative, human-relevant, in vitro liver model for assessing fibrotic pathways induced by environmental chemicals.

Evidence-based assessment on environmental mixture using a concentration-dependent transcriptomics approach.

Development of new approach methodologies is urgently needed to characterize the likelihood that complex mixtures of chemicals affect water quality. Omics advances in ecotoxicology allow assessment on a broadest coverage of disrupted biological pathway by mixtures. Here the usefulness of transcriptomic analyses for evaluation of combined effects and identification of main effect components are explored. Two artificial mixtures (Mix 1 and Mix 2) were tested by a concentration-dependent reduced zebrafish transcriptome (CRZT) approach and toxicity bioassays using zebrafish embryos. Then, the toxicities and transcriptomic effects of 12 component chemicals on embryos were incorporated into additivity models to characterize the combined effects of chemicals in mixtures and to identify the main bioactive compounds. Mix 1 and Mix 2 displayed similar embryo toxicities (LD50: 6.6 µM and 8.7 µM, respectively), however, Mix 2 elicited broader biological process perturbations and 5-fold higher transcriptome potency (point of departure eliciting a 20% pathway response, PODpath20) than Mix 1. The predicted mixture toxicities derived from additivity expectations deviated by 2-fold or less from the measured embryo toxicities except for the Jaw defect endpoint; most biological processes deviated by 3-fold or less. Finally, diclofenac (DFC) and propiconazole (PCZ) were identified as the main contributing components (≥80% explanation) to the embryo toxicity and biological process perturbations by Mix 1. While DFC and chlorophene (CLP) explained up to 80% of the embryo toxicities and biological effects of Mix 2 associated with development and Metabolism processes. The CRZT approach provides a powerful tool for assessment of biological pathways perturbed by chemicals in mixtures and for identification of main bioactive compounds.

Toward Sustainable Environmental Quality: Priority Research Questions for Asia.

Environmental and human health challenges are pronounced in Asia, an exceptionally diverse and complex region where influences of global megatrends are extensive and numerous stresses to environmental quality exist. Identifying priorities necessary to engage grand challenges can be facilitated through horizon scanning exercises, and to this end we identified and examined 23 priority research questions needed to advance toward more sustainable environmental quality in Asia, as part of the Global Horizon Scanning Project. Advances in environmental toxicology, environmental chemistry, biological monitoring, and risk-assessment methodologies are necessary to address the adverse impacts of environmental stressors on ecosystem services and biodiversity, with Asia being home to numerous biodiversity hotspots. Intersections of the food-energy-water nexus are profound in Asia; innovative and aggressive technologies are necessary to provide clean water, ensure food safety, and stimulate energy efficiency, while improving ecological integrity and addressing legacy and emerging threats to public health and the environment, particularly with increased aquaculture production. Asia is the largest chemical-producing continent globally. Accordingly, sustainable and green chemistry and engineering present decided opportunities to stimulate innovation and realize a number of the United Nations Sustainable Development Goals. Engaging the priority research questions identified herein will require transdisciplinary coordination through existing and nontraditional partnerships within and among countries and sectors. Answering these questions will not be easy but is necessary to achieve more sustainable environmental quality in Asia. Environ Toxicol Chem 2020;39:1485-1505. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

A Tiered Approach for Screening and Assessment of Environmental Mixtures by Omics and In Vitro Assays.

New methodology approaches with a broad coverage of the biological effects are urgently needed to evaluate the safety of the universe of environmentally relevant chemicals. Here, we propose a tiered approach incorporating transcriptomics and in vitro bioassays to assess environmental mixtures. The mixture samples and the perturbed biological pathways are prioritized by concentration-dependent transcriptome (CDT) and then used to guide the selection of in vitro bioassays for toxicant identification. To evaluate omics' screening capability, we first applied a CDT technique to test mixture samples by HepG2 and MCF7 cells. The effect recoveries of large-volume solid-phase extraction on the overall bioactivity of the mixture were 48.9% in HepG2 and 58.3% in MCF7. The overall bioactivity potencies obtained by transcriptomics were positively correlated with the panel of 8 bioassays among 14 mixture samples combined with the previous data. Transcriptomics could predict their activation status (AUC = 0.783) and the relative potency (p < 0.05) of bioassays for four of the eight receptors (AhR, ER, AR, and Nrf2). Furthermore, the CDT identified other biological pathways perturbated by mixture samples, such as the pathway related to TP53, CAR, FXR, HIF, THRA, etc. Overall, this study demonstrates the potential of concentration-dependent omics for effect-based water quality assessment.

Integrated assessment of west coast of South Korea by use of benthic bacterial community structure as determined by eDNA, concentrations of contaminants, and in vitro bioassays.

During the past few decades, contamination of sediments by persistent toxic substances (PTSs) has been observed in estuarine and coastal areas on the west coast of South Korea. The contaminants are suspected to cause toxicities in aquatic biota, but little is known about their ecological effects, particularly on benthic microbial communities. In this study, an eDNA-based assessment was applied along with classic assessments of exposure, such as chemistry and in vitro bioassays, to evaluate condition of benthic bacterial communities subjected to PTSs. Two strategies were adopted for the study. One was to conduct a comprehensive assessment in space (by comparing seawater and freshwater sites at five coastal regions) and in time (by following change over a 5-y period). Although we found that bacterial composition varied among and within years, some phyla, such as Proteobacteria (28.7%), Actinobacteria (13.1%), Firmicutes (12.7%), and Chloroflexi (12.5%) were consistently dominated across the study regions. Certain bacterial groups, such as Firmicutes and Verrucomicrobia have been linked to contamination at some sites in the study area and at specific points in time. Bacterial communities were not significantly correlated with salinity or AhR- and ER-mediated potencies, whereas concentrations of PAHs, APs, and certain metals (Cd and Hg) exhibited significant associations to the structure of bacterial communities at the phylum level. In fact, the relative abundance of microbes in the phylum Planctomycetes was significantly and negatively correlated with concentrations of PAHs and metals. Thus, the relative abundance of Planctomycetes could be used as an indicator of sedimentary contamination by PAHs and/or metals. Based on our correlation analyses, Cd and ER-mediated potencies were associated more with bacterial abundances at the class taxonomic level than were other PTSs and metals. Overall, the eDNA-based assessment was useful by augmenting more traditional measures of exposure and responses in a sediment triad approach and has potential as a more rapid screening tool.

Pathway-based assessment of single chemicals and mixtures by a high-throughput transcriptomics approach.

The ever-increasing number of chemicals and complex mixtures demands a high-throughput and cost-effective approach for chemical safety assessment. High-throughput transcriptomics (HTT) is promising in investigating genome-scale perturbation of chemical exposure in concentration-dependent manner. However, the application of HTT has been limited due to lack of methodology for single chemicals and mixture assessment. This study aimed to evaluate the ability of a newly-developed human reduced transcriptomics (RHT) approach to assess pathway-based profiles of single chemicals, and to develop a biological pathway-based approach for benchmarking mixture potency using single chemical-based prediction model. First, concentration-dependent RHT were used to qualitatively and quantitatively differentiate pathway-based patterns of different chemicals, using three model toxicants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), triclosan (TCS) and 5-Chloro-6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (5-Cl-6-OH-BDE-47). AHR-regulated genes and pathways were most sensitively induced by TCDD, while TCS and 5-Cl-6-OH-BDE-47 were much less potent in AHR-associated activation, which was concordant with known MoA of each single chemical. Second, two artificial mixtures and their components of twelve individual chemicals were performed with concentration-dependent RHT. Concentration addition (CA) and independent action (IA) models were used to predict transcriptional potency of mixtures from transcriptomics of individual chemicals. For overall bioactivity, CA and IA models can both predict potency of observed responses within 95% confidence interval. For specific biological processes, multiple biological processes such as hormone signaling and DNA damage can be predicted using CA models for mixtures. The concentration-dependent RHT can provide a powerful approach for qualitative and quantitative assessment of biological pathway perturbated by environment chemical and mixtures.

Assessment of a developed HPLC-MS/MS approach for determining plasma eupatorin in rats and its application in pharmacokinetics analysis.

Eupatorin, a bioactive compound extracted from Java tea (Orthosiphon stamineus), possesses potent anti-cancer, anti-inflammatory and vasodilation activities. To date, no pharmacokinetics studies on eupatorin have yet been performed. Here, we established and validated a sensitive and selective LC-MS/MS (liquid chromatography-tandem mass spectrometry) approach for determining plasma eupatorin in rats. Chromatographic fractionation was conducted on a Wonda Cract ODS-2 C18 Column (4.6 mm × 150 mm, 5 µm) with a mobile phase containing aqueous 0.1% formic acid and acetonitrile using a flow rate of 0.8 ml min-1. In multiple reaction monitoring mode, precursor-to-product ion transitions for quantification of eupatorin and the internal standard were set at 343.1 → 328.1 and 252.0 → 155.9, respectively. The intra- and inter-day precision and accuracy were found to be below 6.72% and within ±8.26% in rat plasma, respectively. Meanwhile, all values of the matrix effect, recovery and stability were within the accepted ranges. Furthermore, we carried out the pharmacokinetic analysis using the developed method. The pharmacokinetic study revealed that while the C max (maximum plasma concentration) of eupatorin and time for reaching the C max (T max) were 974.886 ± 293.898 µg L-1 and 0.25 h, respectively, the half-life was 0.353 ± 0.026 h. This study will be of great significance to the research on the pharmacology, clinical pharmacy and drug action mechanism of eupatorin.