Bioaccumulation Behavior of Pharmaceuticals and Personal Care Products in Adult Zebrafish (<i>Danio rerio</i>): Influence of Physical-Chemical Properties and Biotransformation

The factors influencing bioaccumulation of pharmaceuticals and personal care products (PPCPs) in aquatic organisms are not well understood. The present study involved a comprehensive laboratory investigation to assess the bioaccumulation behavior of several PPCPs in adult zebrafish (<i>Danio rerio</i>). The studied PPCPs included several ionogenic organic compounds (IOCs) such as weak acids and weak bases. Experiments involved two exposure groups (high and low) and a control group, with a 6 day aqueous exposure, followed by a 7 day depuration phase under flow-through conditions. Uptake rate constants (<i>k</i>_u) ranged between 0.19 and 8610 L·kg^–1·d^–1, while depuration rate constants (<i>k</i>_d) ranged between 0.14 and 5.14 d^–1 in different fish tissues. Steady-state bioconcentration factor (BCF_ss) values varied widely among the studied PPCPs, ranging from 0.09 to 6,460. In many cases, BCF_ss values of individual PPCPs differed substantially among different fish tissues. Positive linear relationships were observed between log BCF_ss values and physical-chemical properties such as octanol–water distribution coefficients (log <i>D</i>_ow), membrane–water distribution coefficients (log <i>D</i>_mw), albumin–water distribution coefficients (log <i>D</i>_BSAw), and muscle protein–water distribution coefficients (log <i>D</i>_mpw), indicating the importance of lipid–, phospholipid–, and protein–water partitioning. The results also showed that for many PPCPs, the estimated whole-body metabolism rate constant (<i>k</i>_m) values were comparable to the observed depuration rate (<i>k</i>_d), indicating that metabolism plays a major role in the overall elimination of these compounds in zebrafish. An exception was sertraline, which exhibited a <i>k</i>_d value (0.4–0.5 d^–1) that was much higher than the estimated whole-body <i>k</i>_m (0.03 d^–1). Overall, the results help to better understand the influence of physical-chemical properties and biotransformation on bioaccumulation behavior of these contaminants of concern in aquatic organisms

Dynamic Heterogeneity and Ionic Conduction in an Organic Ionic Plastic Crystal and the Role of Vacancies

Dynamic heterogeneity was investigated for the first time in a conductive organic ionic plastic crystal by molecular dynamics simulation. A minority fraction of ions that possess above-average dynamics were identified in the plastic crystal phase. The signature of this unusual motional behavior is found in the significant increase in the non-Gaussian parameter α­(<i>t</i>). A study by incorporation of vacancies into the crystal structure shows explicit evidence of coexistence of mobile species with an otherwise rigid matrix, which particularly supports the previous explanation on heterogeneous motional narrowing in nuclear magnetic resonance. It is also found that the origin of dynamic heterogeneity here is inseparable from the inherent structural characteristics of organic ions. This work reveals the profound effect brought by heterogeneous dynamics on the conduction mechanism of this material, as well as the important role of defects on ions dynamics

Dynamic Heterogeneity and Ionic Conduction in an Organic Ionic Plastic Crystal and the Role of Vacancies

Dynamic heterogeneity was investigated for the first time in a conductive organic ionic plastic crystal by molecular dynamics simulation. A minority fraction of ions that possess above-average dynamics were identified in the plastic crystal phase. The signature of this unusual motional behavior is found in the significant increase in the non-Gaussian parameter α­(<i>t</i>). A study by incorporation of vacancies into the crystal structure shows explicit evidence of coexistence of mobile species with an otherwise rigid matrix, which particularly supports the previous explanation on heterogeneous motional narrowing in nuclear magnetic resonance. It is also found that the origin of dynamic heterogeneity here is inseparable from the inherent structural characteristics of organic ions. This work reveals the profound effect brought by heterogeneous dynamics on the conduction mechanism of this material, as well as the important role of defects on ions dynamics

MetDIA: Targeted Metabolite Extraction of Multiplexed MS/MS Spectra Generated by Data-Independent Acquisition

With recent advances in mass spectrometry, there is an increased interest in data-independent acquisition (DIA) techniques for metabolomics. With DIA technique, all metabolite ions are sequentially selected and isolated using a wide window to generate multiplexed MS/MS spectra. Therefore, DIA strategy enables a continuous and unbiased acquisition of all metabolites and increases the data dimensionality, but presents a challenge to data analysis due to the loss of the direct link between precursor ion and fragment ions. However, very few DIA data processing methods are developed for metabolomics application. Here, we developed a new DIA data analysis approach, namely, MetDIA, for targeted extraction of metabolites from multiplexed MS/MS spectra generated using DIA technique. MetDIA approach considers each metabolite in the spectral library as an analysis target. Ion chromatograms for each metabolite (both precursor ion and fragment ions) and MS² spectra are readily detected, extracted, and scored for metabolite identification, referred as metabolite-centric identification. A minimum metabolite-centric identification score responsible for 1% false positive rate of identification is determined as 0.8 using fully ¹³C labeled biological extracts. Finally, the comparisons of our MetDIA method with data-dependent acquisition (DDA) method demonstrated that MetDIA could significantly detect more metabolites in biological samples, and is more accurate and sensitive for metabolite identifications. The MetDIA program and the metabolite spectral library is freely available on the Internet

Expression of <i>IL-25</i>, <i>IL-5</i> and <i>IL-13</i> by ELISA.

<p>Expression of <i>IL-25</i>, <i>IL-5</i> and <i>IL-13</i> by ELISA.</p

Inflammation Responses in the Airway.

<p>Inflammation Responses in the Airway.</p

The expression of <i>IL-25</i> protein in lungs by means of western blot analysis.

<p>The tracheal explants of mice extracted to perform western blot analysis. A. <i>IL-25</i> and <i>GAPDH</i> mRNA expression profile. B. Results of A were quantified and graphed by densitometry using the Image-Pro Plus software. Results are expressed as mean±SD. * indicates <i>P</i> value of less than 0.05; ** indicates <i>P</i> value of more than 0.05, compared with control group.</p

Lung histology.

<p>Pathological sections of lung tissues were harvested after 24h, fixed with buffered formalin, and then 5-micrometer sections were analyzed by HE staining. Original magnification, ×40. A. Asthma group. B.Anti-<i>IL-25</i> group. C. Control group.</p