Publications by authors named "Hongxia Yu"

195 Publications

Cost Effectiveness of Different Initial Antimicrobial Regimens for Elderly Community-Acquired Pneumonia Patients in General Ward.

Infect Drug Resist 2021 18;14:1845-1853. Epub 2021 May 18.

National Clinical Research Center of Respiratory Diseases, Center for Respiratory Diseases, China-Japan Friendship Hospital, Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, People's Republic of China.

Purpose: The cost-effectiveness of different guideline-concordant antimicrobial regimens for elderly patients with community-acquired pneumonia (CAP) was rarely discussed. This study attempts to explore the most appropriate cost-effectiveness of guideline-concordant antimicrobial regimen for elderly patients with CAP in general wards.

Patients And Methods: This was a multicenter, retrospective, 4:2:1 matched study enrolling 511 elderly patients with CAP hospitalized in general wards. Two hundred ninety-two patients prescribed with β-lactam monotherapy (group A), 146 patients prescribed with fluoroquinolone monotherapy (group B) and 73 patients prescribed with β-lactam/macrolide combination therapy (group C). Clinical outcomes and medical costs were analyzed by test for categorical variables or Kruskal-Wallis -test for continuous variables.

Results: There were no statistical differences in imaging features, etiology and complications during hospitalization among these three groups. The rates of clinical failure occurrence, in-hospital mortality, 30-day mortality and 60-day mortality also had no significant differences among group A, B and C patients; however, the median length of stay (LOS) in group A patients was 12.0 days, which was significantly higher than that in group B and C patients (both 10.0 days, p<0.02). The median total, drug, and antibiotic costs for one elderly CAP episode in group B patients were RMB 10368.4, RMB 3874.8, and RMB 1796.3, respectively, which were significantly lower than those in group A and C patients (p<0.01).

Conclusion: Non-inferiority of clinical failure occurrence and short-term mortality was observed in different guideline-concordant antimicrobial regimens for elderly patients with CAP in general wards; however, the median LOS and hospitalization-associated costs for one elderly CAP episode with fluoroquinolone monotherapy were significantly lowest, and this strategy was considered to be the most cost-effective strategy in general wards.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IDR.S302852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140887PMC
May 2021

Exposure to legacy and novel perfluoroalkyl substance disturbs the metabolic homeostasis in pregnant women and fetuses: A metabolome-wide association study.

Environ Int 2021 May 13;156:106627. Epub 2021 May 13.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China.

Background: Perfluoroalkyl substances (PFASs) exist extensively and several of these have been verified to be toxic. Prenatal exposure to PFASs has attracted much attention. Metabolome-wide association analyses can be used to explore the toxicity mechanisms of PFASs by identifying associated biomarkers.

Objectives: To evaluate associations between the metabolites in maternal and cord serum and internal exposure to several common PFASs.

Methods: Paired maternal and cord serum samples were collected from 84 pregnant women who gave birth between 2015 and 2016. Seven legacy and two novel PFASs were measured. A nontarget metabolomic method and an iterative metabolite annotation based on metabolic pathways were applied to characterize the metabolic profiles. Linear regression adjusted with the false discovery rate and covariates was used to indicate the associations.

Results: A total of 279 features in maternal serum and 338 features in cord serum were identified as metabolites associated with PFAS exposure. Perfluorooctanoic acid (PFOA) and perfluorohexane sulfonic acid (PFHxS) were two PFASs associated with more metabolites, while the two novel chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs) showed less relevance to the metabolome. With pathway enrichment analysis, we found that three fatty acid metabolisms and retinol metabolism were correlated with PFAS exposure in maternal blood, and that sterol metabolism showed the correlation in both maternal serum and cord serum.

Conclusions: We identified metabolites and pathways in pregnant women and fetuses associated with the exposure to several PFAS, indicating a promising application for metabolome-wide association studies. Additional research is needed to confirm causation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2021.106627DOI Listing
May 2021

The role of Piezo1 in conventional aqueous humor outflow dynamics.

iScience 2021 Feb 7;24(2):102042. Epub 2021 Jan 7.

Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao University Medical College, 38 Dengzhou Road, Qingdao 266021, Shandong, China.

Controlling intraocular pressure (IOP) remains the mainstay of glaucoma therapy. The trabecular meshwork (TM), the key tissue responsible for aqueous humor (AH) outflow and IOP maintenance, is very sensitive to mechanical forces. However, it is not understood whether Piezo channels, very sensitive mechanosensors, functionally influence AH outflow. Here, we characterize the role of Piezo1 in conventional AH outflow. Immunostaining and western blot analysis showed that Piezo1 is widely expressed by TM. Patch-clamp recordings in TM cells confirmed the activation of Piezo1-derived mechanosensitive currents. Importantly, the antagonist GsMTx4 for mechanosensitive channels significantly decreased steady-state facility, yet activation of Piezo1 by the specific agonist Yoda1 did not lead to a facility change. Furthermore, GsMTx4, but not Yoda1, caused a significant increase in ocular compliance, a measure of the eye's transient response to IOP perturbation. Our findings demonstrate a potential role for Piezo1 in conventional outflow, likely under pathological and rapid transient conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.isci.2021.102042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829208PMC
February 2021

Identification of (anti-)androgenic activities and risks of sludges from industrial and domestic wastewater treatment plants.

Environ Pollut 2021 Jan 24;268(Pt B):115716. Epub 2020 Sep 24.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, China.

The annual production of sludges is significant all over the world, and large amounts of sludges have been improperly disposed by random dumping. The contaminants in these sludges may leak into the surrounding soils, surface and groundwater, or be blown into the atmosphere, thereby causing adverse effects to human health. In this study, the (anti-)androgenic activities in organic extracts of sludges produced from both industrial and domestic wastewater treatment plants (WWTPs) were examined using reporter gene assay based on MDA-kb2 cell lines and the potential (anti-)androgenic risks were assessed using hazard index (HI) based on bioassays. Twelve of the 18 samples exhibited androgen receptor (AR) antagonistic activities, with AR antagonistic equivalents ranging from 1.2 × 10 μg flutamide/g sludge to 1.8 × 10 μg flutamide/g sludge; however, no AR agonistic activity was detected in any of the tested samples. These 12 sludges were all from chemical WWTPs; no sludges from domestic WWTPs displayed AR antagonistic activity. Aside from wastewater source, treatment scale and technology could also influence AR antagonistic potencies. The HI values of all the 12 sludges exceeded 1.0, and the highest HI value was above 3.0 × 10 for children; this indicates that these sludges might cause adverse effects to human health and that children are at a greater risk than adults. The anti-androgenic potencies and risks of the subdivided fractions were also determined, and medium-polar and polar fractions were found to have relatively high detection rates and contribution rates to the AR antagonistic potencies and risks of the raw sample extracts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2020.115716DOI Listing
January 2021

Disease burden and prognostic factors for clinical failure in elderly community acquired pneumonia patients.

BMC Infect Dis 2020 Sep 12;20(1):668. Epub 2020 Sep 12.

National Clinical Research Center of Respiratory Diseases,Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.

Background: The study was to evaluate initial antimicrobial regimen and clinical outcomes and to explore risk factors for clinical failure (CF) in elderly patients with community-acquired pneumonia (CAP).

Methods: 3011 hospitalized elderly patients were enrolled from 13 national teaching hospitals between January 1, 2014 and December 31, 2014 initiated by the CAP-China network. Risk factors for CF were screened by multivariable logistic regression analysis.

Results: The incidence of CF in elderly CAP patients was 13.1%. CF patients were older, longer hospital stays and higher treatment costs than clinical success (CS) patients. The CF patients were more prone to present hyperglycemia, hyponatremia, hypoproteinemia, pleural effusion, respiratory failure and cardiovascular events. Inappropriate initial antimicrobial regimens in CF group were significantly higher than CS group. Undertreatment, CURB-65, PH < 7.3, PaO/FiO < 200 mmHg, sodium < 130 mmol/L, healthcare-associated pneumonia, white blood cells > 10,000/mm, pleural effusion and congestive heart failure were independent risk factors for CF in multivariable logistic regression analysis. Male and bronchiectasis were protective factors.

Conclusions: Discordant therapy was a cause of CF. Early accurate detection and management of prevention to potential causes is likely to improve clinical outcomes in elderly patients CAP.

Trial Registration: A Retrospective Study on Hospitalized Patients With Community-acquired Pneumonia in China (CAP-China) (RSCAP-China), NCT02489578. Registered 16 March 2015, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0005E5S&selectaction=Edit&uid=U0000GWC&ts=2&cx=1bnotb.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-020-05362-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486582PMC
September 2020

Structures of Endocrine-Disrupting Chemicals Determine Binding to and Activation of the Estrogen Receptor α and Androgen Receptor.

Environ Sci Technol 2020 09 13;54(18):11424-11433. Epub 2020 Aug 13.

State Key Laboratory of Pollution Control and Resources Reuse, School of the Environment, Nanjing University, Nanjing 210023, Jiangsu, China.

Endocrine-disrupting chemicals (EDCs) can interact with nuclear receptors, including estrogen receptor α (ERα) and androgen receptor (AR), to affect the normal endocrine system function, causing severe symptoms. Limited studies queried the EDC mechanisms, focusing on limited chemicals or a set of structurally similar compounds. It remained uncertain how hundreds of diverse EDCs could bind to ERα and AR and cause distinct functional consequences. Here, we employed a series of computational methodologies to investigate the structural features of EDCs that bind to and activate ERα and AR based on more than 4000 compounds. We used molecular docking and molecular dynamics simulations to elucidate the functional consequences and validated structure-function correlations experimentally using a time-resolved fluorescence resonance energy-transfer assay. We found that EDCs share three levels of key fragments. Primary (20 for ERα and 18 for AR) and secondary fragments (38 for ERα and 29 for AR) are responsible for the binding to receptors, and tertiary fragments determine the activity type (agonist, antagonist, or mixed). In summary, our study provides a general mechanism for the EDC function. Discovering the three levels of key fragments may drive fast screening and evaluation of potential EDCs from large sets of commercially used synthetic compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.0c02639DOI Listing
September 2020

Non-target and suspect screening of per- and polyfluoroalkyl substances in Chinese municipal wastewater treatment plants.

Water Res 2020 Sep 19;183:115989. Epub 2020 Jun 19.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China. Electronic address:

Wastewater treatment plant (WWTP) is one of the major sources of per- and polyfluoroalkyl substances (PFASs) to the aquatic environment. In this study, wastewater samples were collected from 17 WWTPs in 17 cities of China to investigate emerging PFASs in WWTPs. To comprehensively identify PFASs in the wastewater samples, an integrated suspect screening, homologue-based and fragment-based non-target screening method is proposed. Sixty-three PFASs from 13 classes (25 subclasses) were identified, including 14 legacy and 49 emerging PFASs, and this study is the first to report on 12 of these PFASs. We found that emerging PFASs concentration had a significantly positive correlation with the gross domestic product, indicating more substitution of legacy PFASs in the developed area of China. We also analyzed the removal of the 13 PFAS classes, and found that all discovered PFAS classes were not completely removed after the treatment process, whereas the class of perfluoroalkyl ether alcohols significantly increased. All of these results imply that the release of emerging or unknown PFASs from WWTPs is a universal but not negligible problem in China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.watres.2020.115989DOI Listing
September 2020

Mechanistic in silico modeling of bisphenols to predict estrogen and glucocorticoid disrupting potentials.

Sci Total Environ 2020 Aug 23;728:138854. Epub 2020 Apr 23.

State Key Laboratory of Pollution Control and Resources Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, People's Republic of China; Jiangsu Environmental Monitoring Center, Nanjing University, Nanjing, Jiangsu 210023, People's Republic of China; Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, Nanjing University, Nanjing, Jiangsu 210023, People's Republic of China.

Endocrine disrupting chemicals (EDCs) can act as agonists, antagonists or mixed agonists/antagonists toward estrogen receptor α (ERα) and glucocorticoid receptor (GR) in a tissue- and cell-specific manner. However, the activation/inhibition mechanism by which structurally different chemicals induce various types of disruption remain ambiguous. This unrevealed theory limited the in silico modeling of EDCs and the prioritization of potential EDCs for experimental testing. As a kind of chemical widely used in manufacture, bisphenols (BPs) have attracted great attentions on their potential endocrine disrupting effects. BPs used in this study exhibited pure agonistic, pure antagonistic or mixed agonistic/antagonistic activities toward ERα and/or GR. According to the mechanistic modeling, the pure agonistic and pure antagonistic activities were attributed to a single type of protein conformation induced by BPs-ERα and/or BPs-GR interactions, whereas the mixed agonistic/antagonistic activities were attributed to multiple conformations that concomitantly exist. After interacting with BPs, the active conformation recruits coactivator to induce agonistic activity and the blocked conformation inhibits coactivator to induce antagonistic activity, whereas the concomitantly-existing multiple conformations (active, blocked and competing conformations) recruit coactivator, recruit corepressor and/or inhibit coactivator to dually induce the agonistic and antagonistic activities. Therefore, the in silico modeling in this study can not only predict ERα and GR disrupting activities but also, especially, identify the potential mechanisms. This mechanistic study breaks the current bottleneck of computational toxicology and can be widely used to prioritize potential estrogen/glucocorticoid disruptor for experimental testing in both pre-clinic and clinic studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.138854DOI Listing
August 2020

Metabolomic insights into the lasting impacts of early-life exposure to BDE-47 in mice.

Environ Pollut 2020 Aug 4;263(Pt B):114524. Epub 2020 Apr 4.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China. Electronic address:

Early-life exposure to toxicants may have lasting effects that adversely impact later development. Thus, although the production and use of a toxicant have been banned, the risk to previously exposed individuals may continue. BDE-47, a component of commercial penta-BDEs, is a persistent organic pollutant with demonstrated neurotoxicity. To investigate the persistent effects of BDE-47 and the mechanisms thereof, we employed a metabolomics approach to analyze the brain, blood and urine of mice exposed to BDE-47 for 28 days and then 3 months post-exposure. In the brain, BDE-47 was detectable just after exposure but was below the limit of detection (LOD) 3 months later. However, the metabolomic alterations caused by early-life exposure to BDE-47 persisted. Potential biomarkers related to these alterations included phosphatidylcholine, lysophosphatidylcholine, sphingomyelin and several amino acids and biogenic amines. The metabolic pathways involved in the response to BDE-47 in the brain were mainly those related to glycerophospholipid metabolism, sphingomyelin metabolism and neurotransmitter regulation. Thus, our study demonstrates the utility of metabolomics, as the omics most closely reflecting the phenotype, in exploring the mechanisms underlying the lasting effects induced by early-life BDE-47 exposure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2020.114524DOI Listing
August 2020

Nontarget Discovery of Per- and Polyfluoroalkyl Substances in Atmospheric Particulate Matter and Gaseous Phase Using Cryogenic Air Sampler.

Environ Sci Technol 2020 03 6;54(6):3103-3113. Epub 2020 Mar 6.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, People's Republic of China.

Novel per- and polyfluoroalkyl substances (PFASs) have become a key issue in global environmental studies. Although several novel PFASs have been discovered in atmospheric particulate matter through nontarget analysis, information on the environmental occurrence of novel PFASs in atmospheric gaseous phases and conventional sampling techniques is somewhat deficient. Therefore, this Article describes a new type of air sampler, the cryogenic air sampler (CAS), which was used to collect all atmospheric components simultaneously. Nontarget analysis then was performed through PFASs homologue analysis. A total of 117 PFAS homologues (38 classes) were discovered, 48 of which (13 classes) were identified with confidence Level 4 or above. Eleven chlorinated perfluoropolyether alcohols (3 classes) and four chlorinated perfluoropolyether carboxylic acids (2 classes) have been reported for the first time in this Article. This Article is also the first report of 12 hydrosubstituted perfluoroalkyl carboxylates (H-PFCAs) in the atmosphere. H-PFCAs and chlorinated perfluoropolyether carboxylic acids were mainly distributed in the particular phase. These results are evidence that novel chlorinated polyether PFASs should be the focus of future study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.9b05457DOI Listing
March 2020

Suspect and non-target screening of pesticides and pharmaceuticals transformation products in wastewater using QTOF-MS.

Environ Int 2020 04 25;137:105599. Epub 2020 Feb 25.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China. Electronic address:

Pesticides and pharmaceuticals are widely used in modern life and are discharged into wastewater after usage. However, a large number of transformation products (TPs) are formed through abiotic (hydrolysis/photolysis, etc.) and biotic (aerobic/anaerobic degradation by micro-organisms) wastewater treatment processes, and the structure and potential risk of TPs are still unclear. In this study, a suspect and non-target screening was performed to monitor these chemicals with HPLC-QTOF-MS. We identified 60 parent compounds by suspect screening in three Chinese wastewater treatment plants with the commercial database of pesticides and pharmaceuticals, and they were confirmed by authentic standards. Then, suspect and non-target screening strategies based on the predicted diagnostic fragment ions were used to screen TPs of the 60 parent compounds. We tentatively identified 50 TPs and confirmed thirteen of them with authentic standards. Among 13 quantified TPs, about 40% of them showed higher concentration than their parent compounds in effluent. Especially, cloquintocet, as a TP of cloquintocet-mexyl, had a concentration ratio TP/parent = 14,809 in effluent. Twenty-five TPs had higher predicted toxicity than the corresponding parent compounds by calculating their LC values towards aquatic organisms using toxicity prediction software. Twenty identified TPs were firstly reported in this study. These results indicate the importance of TP analysis in environmental monitoring in wastewater.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2020.105599DOI Listing
April 2020

Construction and application of a 1-liter upflow-stacked microbial desalination cell.

Chemosphere 2020 Jun 27;248:126028. Epub 2020 Jan 27.

Key Laboratory of Jiangsu Province for Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, 210094, China. Electronic address:

As increasing demand of global reuse water, microbial desalination cell (MDC) is developed as a potential desalination approach to drive ion migration and separation through biodegradation without any additional energy. A novel, efficient, stable reactor coupled stacked MDC with upflow MDC was constructed, which was named as upflow-stacked MDC (USMDC). Compared with the traditional stacked MDC and upflow MDC, the desalination and generation performance of the USMDC was evaluated. Results showed that, after 24 h, the desalination ratio of USMDC can reach 91.9% when the external resistance was 1.5 Ω, which was 1.18 and 1.48 times higher than SMDC and UMDC, respectively. The long-term performance of the desalination efficiency was tested, which was maintained at 87.2-96.0% and stable for consecutive 120 days. Then, it was also the investigated that the relationship between desalination rate and external resistance during every period. The USMDC produced a maximum power density of 32.91 W m. In addition, the difference of current density between USMDC and SMDC indicates the turbulence generated by cylindrical structure could effectively decrease the internal resistance. It was also corroborated that salt concentration gradient and bipolar electrodialysis would decline the charge transfer efficiency. Accordingly, USMDC was verified having the superior desalination performance thus providing the possibility for application in wastewater reuse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2020.126028DOI Listing
June 2020

Transplacental Transfer of Per- and Polyfluoroalkyl Substances Identified in Paired Maternal and Cord Sera Using Suspect and Nontarget Screening.

Environ Sci Technol 2020 03 25;54(6):3407-3416. Epub 2020 Feb 25.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China.

Novel per- and polyfluoroalkyl substances (PFASs) in various environmental media have attracted increasing attention; however, the information regarding PFASs exposure in pregnant women and fetuses is insufficient. In this study, we built and applied suspect and nontarget screening strategies based on the mass difference of the CF, CFO, and CHCF units to select potential novel PFASs from 117 paired maternal and cord sera. In total, 10 legacy PFASs and 19 novel PFASs from 10 classes were identified to be above confidence levels 3, among which 14 were not previously reported in human serum. Novel PFASs accounted for a considerable percentage of total PFASs in pregnant women and can be transferred to fetuses at non-negligible concentrations (i.e., 27.9% and 30.3% of total PFAS intensities in maternal and cord sera, respectively). The transplacental transfer efficiency (TTE) of PFASs showed a U-shape trend in the series of perfluoroalkyl carboxylic acids, perfluoroalkyl sulfonic acids, and unsaturated perfluorinated alcohols. The TTE of novel PFASs is suggested to be structure-dependent, based on a flexible docking experiment. This study provides comprehensive TTE information on legacy and novel PFASs for the first time, and additional toxicity studies are needed to evaluate the risk of novel PFASs further.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.9b06505DOI Listing
March 2020

Triclosan Affects Ca Regulatory Module and Musculature Development in Skeletal Myocyte during Early Life Stages of Zebrafish ().

Environ Sci Technol 2019 Oct 30;53(20):11988-11998. Epub 2019 Sep 30.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment , Nanjing University , Nanjing 210023 , China.

Advanced technologies for toxicity tests are designed to identify biomarkers with superior predictive power or end points of the complex web of biological pathways. However, the data obtained need to be fully characterized for dose-response, physiological systems, and relevance to a system or (sub) population before biological interpretation and decision making. In this study, the toxicity of triclosan (TCS) on zebrafish was selected as a case study to correlate the observed morphological effects with existing data and identify the critical events by receptor activity sensitivity analysis. Triclosan exhibited weak acute toxicity against zebrafish and significantly affected the development of trunk muscles at 0.52, 1.04, and 1.73 μM. Through receptor-mediated screening, we found that the adverse effects of TCS induce Ryanodine receptor 1 (RyR1) activity and distort Ca signaling. The trunk skeletal muscle abnormalities occurred only when the dihydropyridine receptor (DHPR) was blocked, demonstrating that TCS mainly influenced the Ca regulatory module associated with signaling between DHPRs and RyR1; DHPRs mainly regulated the orthograde and retrograde signaling in skeletal muscles. This unexpected result could integrate the mode of action of TCS and provide insight for high-throughput screening and toxicity prediction using zebrafish.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.9b03231DOI Listing
October 2019

Expressional and functional involvement of gap junctions in aqueous humor outflow into the ocular trabecular meshwork of the anterior chamber.

Mol Vis 2019 26;25:255-265. Epub 2019 Apr 26.

Department of Pharmacology, Qingdao University School of Pharmacy, Qingdao, China.

Purpose: The ocular trabecular meshwork (TM) responsible for aqueous humor (AH) drainage is crucial for regulating intraocular pressure (IOP) of the eye. An IOP elevation that causes distended TM is involved in the pathogenesis of glaucoma, suggesting intercellular connections important for the TM pathophysiology. The goal of this study was to examine whether gap junction proteins between endothelial cells in the TM are expressional and functional.

Methods: The expression levels of the gap junction channels in normal human TM cells were determined with real-time PCR and western blot assays. Immunohistochemistry (IHC) staining was performed to examine the localization of gap junction proteins in normal human TM cells and tissues. IOP and the outflow of AH were measured after intercameral injection of gap junction blockers in C57/BL6 mice.

Results: Gap junction proteins GJA1, GJA8, GJB6, and GJC1 were robustly expressed in human TM cells from three individuals. Among the four gap junction channels, GJA1 and GJA8 exhibited the most abundance in the TM. The IHC analysis further confirmed that these proteins were expressed on the membrane between adjacent cells. In the human TM tissues, GJA1, GJA8, GJB6, and GJC1 were also observed along the trabecular beams. Inhibition of gap junctions with intracameral injection of blockers resulted in a statistically significant increase in aqueous humor outflow resistance and IOP elevation in mice.

Conclusions: The GJA1 and GJA8 gap junction proteins, in particular, are robustly expressed in human TM cells and tissues. Pharmacological inhibition of gap junction channels causes an increased resistance of AH outflow and an elevation of IOP in mice. The present findings suggest the functional role of gap junction channels for regulation of AH outflow in the TM, and activation of gap junctions might represent a therapeutic strategy for treatment of glaucoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545340PMC
April 2020

Polychlorinated diphenyl sulfides can induce ROS and genotoxicity via the AhR-CYP1A1 pathway.

Chemosphere 2019 May 1;223:165-170. Epub 2019 Feb 1.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China.

Polychlorinated diphenyl sulfides (PCDPSs) are a group of chemicals that can interact and activate the aryl hydrocarbon receptor (AhR). Previous studies have shown that PCDPSs can cause oxidative stress in livers. However, information on genotoxicity of PCDPSs is limited. In this study, it is hypothesized that PCDPSs can produce reactive oxygen species (ROS) by activating the AhR and inducing expression of CYP1A1, which subsequently causes genotoxicity. HepG2 cells (transfected with AhR and CYP1A1 siRNA or not) were exposed to six PCDPSs. ROS and expression of five genes were measured to confirm relationships between genotoxicity and signaling along AhR pathway. After 24 h, a significant concentration-dependent ROS was observed. Production of ROS varied with the number of Cl atoms. And the formation of ROS decreases with the increase of the number of Cl atoms, which was consistent with results observed for polychlorinated biphenyls (PCBs). Most of the tested PCDPSs up-regulated expression of CYP1A1 enzyme via signaling AhR pathways. The exposure to 2,3',4,5-tetra-CDPS at 10 μM up-regulated the CYP1A1 mRNA in HepG2 cells to 29-fold. Expression of CYP1A1 mRNA was related to the number of substituted Cl, probably due to the stronger ability of more chlorinated PCDPSs to bind to and activate the AhR. However, there was no significant quantitative relationship between expression of CYP1A1 and concentrations of ROS, probably due to other oxidases' influence. Furthermore, PCDPSs also caused induction of OGG1 and XRS2 more than 2 times, indicates oxidation of bases and breaks of strands. The transfection of cells with siRNA to silence expression of the CYP1A1 gene results in ROS at background levels, further supporting the proposed mechanism PCDPSs inducing ROS and DNA damage via the AhR-mediated pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2019.01.169DOI Listing
May 2019

Acid mine drainage affects the diversity and metal resistance gene profile of sediment bacterial community along a river.

Chemosphere 2019 Feb 1;217:790-799. Epub 2018 Nov 1.

School of Environment and Sustainability, University of Saskatchewan, Saskatoon, SK S7N 5C3, Canada; Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada.

Acid mine drainage (AMD) is one of the most hazardous byproducts of some types of mining. However, research on how AMD affects the bacterial community structure of downstream riverine ecosystems and the distribution of metal resistance genes (MRGs) along pollution gradient is limited. Comprehensive geochemical and high-throughput next-generation sequencing analyses can be integrated to characterize spatial distributions and MRG profiles of sediment bacteria communities along the AMD-contaminated Hengshi River. We found that (1) diversities of bacterial communities significantly and gradually increased along the river with decreasing contamination, suggesting community composition reflected changes in geochemical conditions; (2) relative abundances of phyla Proteobacteria and genus Halomonas and Planococcaceae that function in metal reduction decreased along the AMD gradient; (3) low levels of sediment salinity, sulfate, aquatic lead (Pb), and cadmium (Cd) were negatively correlated with bacterial diversity despite pH was in a positive manner with diversity; and (4) arsenic (As) and copper (Cu) resistance genes corresponded to sediment concentrations of As and Cu, respectively. Altogether, our findings offer initial insight into the distribution patterns of sediment bacterial community structure, diversity and MRGs along a lotic ecosystem contaminated by AMD, and the factors that affect them.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2018.10.210DOI Listing
February 2019

Novel ultra-small micelles based on rebaudioside A: A potential nanoplatform for ocular drug delivery.

Int J Pharm 2018 Dec 3;552(1-2):265-276. Epub 2018 Oct 3.

Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. Electronic address:

We investigated if the self-assembled micelles of rebaudioside A (RA) could potentially be utilized as an ocular drug-delivery system in this investigation. RA self-assembled into micelles with ultra-small particle sizes (<4 nm) in a homogeneous distribution state (polydispersity index < 0.3). RA had good cellular tolerance and no cytotoxicity was observed at concentrations ≤ 18.5 mg/ml at 72 h of incubation. RA also did not cause cell apoptosis at concentration ≤ 12 mg/ml. Coumarin-6 (Cou6)-loaded RA micelles had good cellular tolerance and in vivo non-irritants to the rabbit eyes. RA micelles dramatically improved the cellular uptake of Cou6 (compared to free-Cou6 P < 0.05); an energy-independent, active, intracellular endocytosis pathway was apparently involved, and cellular organelles such as lysosomes, endoplasmic reticuli, and mitochondria were observed with a high distribution of Cou6, while a much more sophisticated endocytosis pathway was apparently involved in the ex vivo corneal endocytosis mechanism tests. The use of RA micelles significantly improved in vivo corneal permeation of the encapsulated Cou6 when compared to free-Cou6 eye drops (P < 0.05). These findings indicate that RA micelle formulations have great potential as a novel ocular drug-delivery system to improve the bioavailability of hydrophobic drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2018.10.006DOI Listing
December 2018

Suspect and Nontarget Screening of Per- and Polyfluoroalkyl Substances in Wastewater from a Fluorochemical Manufacturing Park.

Environ Sci Technol 2018 10 24;52(19):11007-11016. Epub 2018 Sep 24.

State Key Laboratory of Pollution Control and Resource Reuse , Nanjing University , Nanjing 210008 , P. R. China.

Although per- and polyfluoroalkyl substances (PFASs) have always been a key issue in the global environmental field, there are still a lot of undiscovered PFASs in the environment due to new PFAS alternatives developed by manufacturers. Wastewater treatment plants (WWTPs), as one of the sources for PFASs, are an important part of the process of releasing new PFASs into the environment. In this study, suspect screening and PFAS homologue analysis with quadrupole time-of-flight tandem mass spectrometry were used to discover PFASs in wastewater from a WWTP near Yangtze River. Fifteen classes with 90 PFASs were identified, including 12 legacy PFASs (2 classes), 41 previously reported PFASs (7 classes), and 37 new PFASs (6 classes), and 18 of these PFASs were also detected in the nearby Yangtze River. Only 1 PFAS class was removed through the treatment processes (fold change < 1/6). Conversely, 4 PFAS classes increased through the treatment processes (fold change > 6), which could be the transformation products of PFAS precursors. These results implied that most discovered PFASs were not effectively removed in the WWTP. Chlorine-substituted perfluoroalkyl carboxylates (Cl-PFCAs) as the main component of wastewater were detected only in downstream, meaning that Cl-PFCAs in downstream possibly originated from the WWTP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.8b03030DOI Listing
October 2018

Extended suspect screening strategy to identify characteristic toxicants in the discharge of a chemical industrial park based on toxicity to Daphnia magna.

Sci Total Environ 2019 Feb 18;650(Pt 1):10-17. Epub 2018 Aug 18.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China; Jiangsu Environmental Monitoring Center, Nanjing University, Nanjing, Jiangsu 210023, China; Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, Nanjing University, Nanjing 210023, China. Electronic address:

With an increasing amount of industrial wastewater being discharged and the numerous chemicals existed in, methods to identify toxicants in such complex matrices are urgently needed for source control and quality management. In vivo toxicity to Daphnia magna was evaluated in the effluent of a wastewater treatment plant (WWTP). An extended suspect screening strategy was performed by bioassay-directed fractionation, accompanied with suspect screening of 228 suspect chemicals in toxic fractions based on their mass characteristics and chromatography characteristics. A toxicity evaluation of the original samples, organic components extracted by solid-phase extraction (SPE) and the filtered samples showed that organic compounds extracted by SPE were the main toxic components. Four of the 26 fractions of the organic extracts exhibited a toxic unit (TU) > 1.0, with hydrophobic organic compounds contributing most to the toxicity. Twenty-eight of the 228 suspects were identified in four toxic fractions, with 53.6% of the suspects elucidated by spectrum interpretation based on mass characteristics and 53.8% more false positive suspects removed based on chromatography characteristics. Finally, 6 pollutants, including imazalil, prometryn, propiconazole, tebuconazole, buprofezin and diazinon, were further confirmed and explained 48.79% of the observed toxicity. With 2.48 times more of the toxicity explained and 90% of the labor saved, the extended suspect screening strategy enabled more efficient and reliable identification compared to traditional quantitative analysis and non-target screening, especially for identification of characteristic toxicants in complex environmental matrices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2018.08.215DOI Listing
February 2019

Factors associated with blooms of cyanobacteria in a large shallow lake, China.

Environ Sci Eur 2018 28;30(1):27. Epub 2018 Jul 28.

1State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210046 China.

Background: Eutrophication of freshwater systems can result in blooms of phytoplankton, in many cases cyanobacteria. This can lead to shifts in structure and functions of phytoplankton communities adversely affecting the quality of drinking water sources, which in turn impairs public health. Relationships between structures of phytoplankton communities and concentrations of the toxicant, microcystin-leucine-arginine (MC-LR), have not been well examined in large shallow lakes. The present study investigated phytoplankton communities at seven locations from January to December of 2015 in Tai Lake, and relationships between structures and diversities of phytoplankton communities and water quality parameters, including concentrations of MC-LR and metals, were analyzed.

Results: A total of 124 taxa of phytoplankton were observed, and the predominant taxa were sp. and - of and sp. of . The greatest diversities of phytoplankton communities, as indicated by species richness, Simpson, Shannon-Wiener, the Berger and Parker, and the Pielou evenness indices, were observed in spring. Furthermore, productivity of phytoplankton was significantly and negatively correlated with diversities. These results demonstrated that Simpson, Shannon-Wiener, the Berger and Parker, and the Pielou evenness indices of phytoplankton communities were significantly related to trophic status and overall primary productivity in Tai Lake. In addition, temperature of surface water, pH, permanganate index, biochemical oxygen demand, total phosphorus, arsenic, total nitrogen/total phosphorous ratio, and MC-LR were the main factors associated with structures of phytoplankton communities in Tai Lake.

Conclusion: The present study provided helpful information on phytoplankton community structure and diversity in Tai Lake from January to December of 2015. Our findings demonstrated that Simpson, Shannon-Wiener, the Berger and Parker, and the Pielou evenness indices could be used to assess and monitor for status and trends in water quality of Tai Lake. In addition, MC-LR was one of the main factors associated with structures of phytoplankton communities in Tai Lake. The findings may help to address important ecological questions about the impact of a changing environment on biodiversity of lake ecosystems and the control of algae bloom. Further studies are needed to explore the relationship between MC-LR and phytoplankton communities in the laboratory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12302-018-0152-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096964PMC
July 2018

Non-Target and Suspect Screening of Per- and Polyfluoroalkyl Substances in Airborne Particulate Matter in China.

Environ Sci Technol 2018 08 30;52(15):8205-8214. Epub 2018 Jul 30.

State Key Laboratory of Pollution Control and Resource Reuse , School of the Environment, Nanjing University , Nanjing , People's Republic of China.

Airborne particulate matter (APM) has an important role in inhalation exposure, especially in China. The environmental occurrence of conventional and unknown per- and polyfluoroalkyl substances (PFASs) in APM remains unclear. Therefore, in this study, a two-stage experiment was designed to identify potential PFASs and to investigate their distribution in APM. Indoor and outdoor APM samples were collected from five selected cities in China. Through PFAS homologue analysis and suspect screening, 50 peaks were identified with different confidence levels (levels 1-3). Among the identified PFASs, 34 emerging PFASs including p-perfluorous nonenoxybenzenesulfonate, 6:2 polyfluoroalkyl phosphate diester, n:2 fluorotelomer sulfonates, n:2 fluorinated telomer acids, n:2 chlorinated polyfluoroalkyl ether sulfonic acids, 1:n polyfluoroalkyl ether carboxylic acids (1:n PFECAs), perfluoroalkyl dioic acids (PFdiOAs), hydro-substituted perfluoroalkyl dioic acids (H-PFdiOAs), and unsaturated perfluorinated alcohols (UPFAs) were identified in APM. In particular, 1:n PFECAs, PFdiOAs, H-PFdiOAs, and UPFAs were first detected in APM. Although human exposure to perfluorooctanoic acid via inhaled APM was noted to not be a risk (hazard quotient <0.1) in this study, the expansion of the PFASs screened in APM implies that human exposure to PFASs might be much more serious and should be considered in future risk assessments in China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.8b02492DOI Listing
August 2018

Multigenerational Effects and Demographic Responses of Zebrafish ( Danio rerio) Exposed to Organo-Bromine Compounds.

Environ Sci Technol 2018 08 20;52(15):8764-8773. Epub 2018 Jul 20.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment , Nanjing University , Nanjing 210023 , China.

Long-term exposure to toxic chemicals often has deleterious effects on aquatic organisms. In order to support appropriate environmental management of chemicals, a mathematical model was developed to characterize the effects of chemicals on multigenerational population dynamics in aquatic animals. To parametrize the model, we conducted a multigenerational laboratory toxicity test in zebrafish ( Danio rerio) exposed to 2-bromo-4,6-dinitroaniline (BDNA). Long-term exposure to BDNA considerably reduced the fecundity of adult zebrafish (F and F) and caused deformities in the offspring (F). Life history data, including changes in fecundity and population growth, were then integrated into the model to predict population dynamics of zebrafish exposed to two novel brominated flame retardants, bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) and 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB). The model predicted that the fecundity of adult zebrafish would be significantly impaired after exposure to 90.36 μM TBPH and 99.16 μM TBB. Thus, prolonged exposure to such levels over multiple generations could result in population extinction within 20 years. Our results provide an intensive temporal perspective to investigate a keystone that connects with individual response to chemicals, population dynamics, and ultimately ecosystem influences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.8b00569DOI Listing
August 2018

Effects of age, comorbidity and adherence to current antimicrobial guidelines on mortality in hospitalized elderly patients with community-acquired pneumonia.

BMC Infect Dis 2018 04 24;18(1):192. Epub 2018 Apr 24.

National Clinical Research Center of Respiratory Diseases, Center for Respiratory Diseases, China-Japan Friendship Hospital, Yinghuayuan East Street, Chao-yang District, Beijing, China.

Background: Limited information exists on the clinical characteristics predictive of mortality in patients aged ≥65 years in many countries. The impact of adherence to current antimicrobial guidelines on the mortality of hospitalized elderly patients with community-acquired pneumonia (CAP) has never been assessed.

Methods: A total of 3131 patients aged ≥65 years were enrolled from a multi-center, retrospective, observational study initiated by the CAP-China network. Risk factors for death were screened with multivariable logistic regression analysis, with emphasis on the evaluation of age, comorbidities and antimicrobial treatment regimen with regard to the current Chinese CAP guidelines.

Results: The mean age of the study population was 77.4 ± 7.4 years. Overall in-hospital and 60-day mortality were 5.7% and 7.6%, respectively; these rates were three-fold higher in those aged ≥85 years than in the 65-74 group (11.9% versus 3.2% for in-hospital mortality and 14.1% versus 4.7% for 60-day mortality, respectively). The mortality was significantly higher among patients with comorbidities compared with those who were otherwise healthy. According to the 2016 Chinese CAP guidelines, 62.1% of patients (1907/3073) received non-adherent treatment. For general-ward patients without risk factors for Pseudomonas aeruginosa (PA) infection (n = 2258), 52.3% (1094/2090) were over-treated, characterized by monotherapy with an anti-pseudomonal β-lactam or combination with fluoroquinolone + β-lactam; while 71.4% of intensive care unit (ICU) patients (120/168) were undertreated, without coverage of atypical bacteria. Among patients with risk factors for PA infection (n = 815), 22.9% (165/722) of those in the general ward and 74.2% of those in the ICU (69/93) were undertreated, using regimens without anti-pseudomonal activity. The independent predictors of 60-day mortality were age, long-term bedridden status, congestive heart failure, CURB-65, glucose, heart rate, arterial oxygen saturation (SaO) and albumin levels.

Conclusions: Overtreatment in general-ward patients and undertreatment in ICU patients were critical problems. Compliance with Chinese guidelines will require fundamental changes in standard-of-care treatment patterns. The data included herein may facilitate early identification of patients at increased risk of mortality.

Trial Registration: The study was registered at ClinicalTrials.gov ( NCT02489578 ).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-018-3098-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922029PMC
April 2018

eDNA-based bioassessment of coastal sediments impacted by an oil spill.

Environ Pollut 2018 Jul 3;238:739-748. Epub 2018 Apr 3.

School of Earth and Environmental Sciences & Research Institute of Oceanography, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address:

Oil spills offshore can cause long-term ecological effects on coastal marine ecosystems. Despite their important ecological roles in the cycling of energy and nutrients in food webs, effects on bacteria, protists or arthropods are often neglected. Environmental DNA (eDNA) metabarcoding was applied to characterize changes in the structure of micro- and macro-biota communities of surface sediments over a 7-year period since the occurrence of Hebei Spirit oil spill on December 7, 2007. Alterations in diversities and structures of micro- and macro-biota were observed in the contaminated area where concentrations of polycyclic aromatic hydrocarbons were greater. Successions of bacterial, protists and metazoan communities revealed long-term ecological effects of residual oil. Residual oil dominated the largest cluster of the community-environment association network. Presence of bacterial families (Aerococcaceae and Carnobacteriaceae) and the protozoan family (Platyophryidae) might have conferred sensitivity of communities to oil pollution. Hydrocarbon-degrading bacterial families (Anaerolinaceae, Desulfobacteraceae, Helicobacteraceae and Piscirickettsiaceae) and algal family (Araphid pennate) were resistant to adverse effects of spilt oil. The protistan family (Subulatomonas) and arthropod families (Folsomia, Sarcophagidae Opomyzoidea, and Anomura) appeared to be positively associated with residual oil pollution. eDNA metabarcoding can provide a powerful tool for assessing effects of anthropogenic pollution, such as oil spills on sediment communities and its long-term trends in coastal marine environments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2018.02.081DOI Listing
July 2018

Activation of steroid hormone receptors: Shed light on the in silico evaluation of endocrine disrupting chemicals.

Sci Total Environ 2018 Aug 6;631-632:27-39. Epub 2018 Mar 6.

State Key Laboratory of Pollution Control and Resources Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, People's Republic of China; Jiangsu Environmental Monitoring Center, Nanjing University, Nanjing, Jiangsu 210023, People's Republic of China; Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, Nanjing University, Nanjing, Jiangsu 210023, People's Republic of China. Electronic address:

Endocrine disrupting chemicals (EDCs) are of great concern given their potential influence on the endocrine system. In silico methods for the evaluation of EDCs have been widely recognized. However, subcellular molecular mechanisms of action, such as ligand-receptor interactions, receptor conformational switch and protein-protein interactions, are needed for the development of mechanism-based in silico models. Here, molecular mechanisms of action for steroid hormone receptors (SHRs), the important targets of EDCs, are systematically reviewed. Ligand binding and ligand-receptor interactions are required for SHR activation, and facilitate the nuclear translocation and the dimerization of SHRs. Coregulator recruitment results from conformational switch of SHR, which regulates the transcription and results in either an agonistic or an antagonistic effect. EDCs potentially interfere with SHRs by influencing ligand-receptor interactions, nuclear translocation, dimerization and coregulator recruitment. These new findings shed light on the development of mechanism-based computational models for the evaluation of EDCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2018.03.003DOI Listing
August 2018

Disease characteristics and management of hospitalised adolescents and adults with community-acquired pneumonia in China: a retrospective multicentre survey.

BMJ Open 2018 02 15;8(2):e018709. Epub 2018 Feb 15.

Department of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, National Clinical Research Center of Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.

Objectives: To describe the clinical characteristics and management of patients hospitalised with community-acquired pneumonia (CAP) in China.

Design: This was a multicentre, retrospective, observational study.

Setting: 13 teaching hospitals in northern, central and southern China from 1 January 2014 to 31 December 2014 PARTICIPANTS: Information on hospitalised patients aged ≥14 years with radiographically confirmed pneumonia with illness onset in the community was collected using standard case report forms.

Primary And Secondary Outcome Measures: Resource use for CAP management.

Results: Of 14 793 patients screened, 5828 with radiographically confirmed CAP were included in the final analysis. Low mortality risk patients with a CURB-65 score 0-1 and Pneumonia Severity Index risk class I-II accounted for 81.2% (4434/5594) and 56.4% (2034/3609) patients, respectively. 21.7% (1111/5130) patients had already achieved clinical stability on admission. A definite or probable pathogen was identified only in 12.7% (738/5828) patients. 40.9% (1575/3852) patients without pseudomonal infection risk factors received antimicrobial overtreatment regimens. The median duration between clinical stability to discharge was 5.0 days with 30-day mortality of 4.2%.

Conclusions: These data demonstrated the overuse of health resources in CAP management, indicating that there is potential for improvement and substantial savings to healthcare systems in China.

Trial Registration Number: NCT02489578; Results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2017-018709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829872PMC
February 2018

A Reduced Transcriptome Approach to Assess Environmental Toxicants Using Zebrafish Embryo Test.

Environ Sci Technol 2018 01 2;52(2):821-830. Epub 2018 Jan 2.

State Key Laboratory of Pollution Control & Resource Reuse, School of the Environment, Nanjing University , Nanjing, P. R. China , 210023.

Omics approaches can monitor responses and alterations of biological pathways at genome-scale, which are useful to predict potential adverse effects by environmental toxicants. However, high throughput application of transcriptomics in chemical assessment is limited due to the high cost and lack of "standardized" toxicogenomic methods. Here, a reduced zebrafish transcriptome (RZT) approach was developed to represent the whole transcriptome and to profile bioactivity of chemical and environmental mixtures in zebrafish embryo. RZT gene set of 1637 zebrafish Entrez genes was designed to cover a wide range of biological processes, and to faithfully capture gene-level and pathway-level changes by toxicants compared with the whole transcriptome. Concentration-response modeling was used to calculate the effect concentrations (ECs) of DEGs and corresponding molecular pathways. To validate the RZT approach, quantitative analysis of gene expression by RNA-ampliseq technology was used to identify differentially expressed genes (DEGs) at 32 hpf following exposure to seven serial dilutions of reference chemical BPA (10-10EμM) or each of four water samples ranging from wastewater to drinking water (relative enrichment factors 10-6.4 × 10). The RZT-ampliseq-embryo approach was both sensitive and able to identify a wide spectrum of biological activities associated with BPA exposure. Water quality was benchmarked based on the sensitivity distribution curve of biological pathways detected using RZT-ampliseq-embryo. Finally, the most sensitive biological pathways were identified, including those linked with adverse reproductive outcomes, genotoxicity and development outcomes. RZT-ampliseq-embryo approach provides an efficient and cost-effective tool to prioritize toxicants based on responsiveness of biological pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.7b04073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839301PMC
January 2018

Integrated in silico and in vivo approaches to investigate effects of BDE-99 mediated by the nuclear receptors on developing zebrafish.

Environ Toxicol Chem 2018 03 13;37(3):780-787. Epub 2017 Dec 13.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu, China.

One of the most abundant polybrominated diphenyl ethers (PBDEs) is 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), which persists and potentially bioaccumulates in aquatic wildlife. Previous studies in mammals have shown that BDE-99 affects development and disrupts certain endocrine functions through signaling pathways mediated by nuclear receptors. However, fewer studies have investigated the potential of BDE-99 to interact with nuclear receptors in aquatic vertebrates such as fish. In the present study, interactions between BDE-99 and nuclear receptors were investigated by in silico and in vivo approaches. This PBDE was able to dock into the ligand-binding domain of zebrafish aryl hydrocarbon receptor 2 (AhR2) and pregnane X receptor (PXR). It had a significant effect on the transcriptional profiles of genes associated with AhR or PXR. Based on the developed cytoscape of all zebrafish genes, it was also inferred that AhR and PXR could interact via cross-talk. In addition, both the in silico and in vivo approaches found that BDE-99 affected peroxisome proliferator-activated receptor alpha (PPARα), glucocorticoid receptor, and thyroid receptor. Collectively, our results demonstrate for the first time detailed in silico evidence that BDE-99 can bind to and interact with zebrafish AhR and PXR. These findings can be used to elaborate the molecular mechanism of BDE-99 and guide more objective environmental risk assessments. Environ Toxicol Chem 2018;37:780-787. © 2017 SETAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/etc.4000DOI Listing
March 2018

Pharmacokinetics and effects of tetrabromobisphenol a (TBBPA) to early life stages of zebrafish (Danio rerio).

Chemosphere 2018 Jan 29;190:243-252. Epub 2017 Sep 29.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China. Electronic address:

In silico and in vivo approaches were combined in an aggregate exposure pathway (AEP) to assess accumulation and effects of waterborne exposures of early life stages of zebrafish (Danio rerio) to tetrabromobisphenol A (TBBPA). Three metabolites, two of which were isomers, were detected in fish. Two additional metabolites were detected in the exposure solution. Based on kinetics modeling, proportions of TBBPA that were bioaccumulated and metabolized were 19.33% and 8.88%, respectively. Effects of TBBPA and its metabolites were predicted by use of in silico, surflex-Dock simulations that they were capable of interacting with ThRα and activating associated signaling pathways. TBBPA had a greater toxic contribution than its metabolites did when we evaluated the toxicity of these substances based on the toxicity unit method. The half of the internal lethal dose (ILD) was 18.33 μg TBBPA/g at 74 hpf. This finding was further confirmed by changes in expressions of ThRα and other NRs as well as associated genes in their signal pathways. Specifically, exposure to 1.6 × 10, 3.3 × 10 or 6.5 × 10 μg TBBPA/L significantly down-regulated expression of ThRα and associated genes, ncor, c1d, ncoa2, ncoa3, and ncoa4, in the AR pathway and of er2a and er2b genes in the ER pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2017.09.137DOI Listing
January 2018