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The current hazard assessment of the emerging chemical contaminant, zinc oxide nanoparticles (ZnO-NPs), seldom considers the influence of environmental factors. However, under seasonal variation and global climate change, marine organisms are exposed to a changing environment with different regimes of temperature and salinity. This study, therefore, investigated the toxicity of ZnO-NPs, zinc oxide bulk-particles and zinc ions, to the marine copepod Tigriopus japonicusunder the combined influence of temperature and salinity. The toxicity of ZnO-NPs generally increased with increasing temperature. At 15 °C, ZnO-NPs were less toxic because they generated fewer reactive oxygen species (ROS) and the copepods entered dormancy. At 35 °C, ZnO-NPs became more toxic because of their increased ROS production and potential physical impairments associated with the agglomerated particles, in addition to the thermal stress faced by the copepods. Their toxicity generally increased with decreasing salinity, due to their enhanced ion dissolution and osmotic pressure faced by the copepods at low salinity. Hence, ZnO-NPs were most toxic to the copepods at high temperature and low salinity, though temperature was a more influential factor than salinity. Based on the effect thresholds generated from the response surface model with consideration of the joint effect of temperature and salinity, the current marine water quality criteria may not provide adequate protection to marine organisms against ZnO-NPs. Our results provide new insights into the toxicity and modes of action of ZnO-NPs, and highlight the current deficiency of regulations under different regimes of temperature and salinity.

Historical geological and climatic events are the most important drivers of population expansions/contractions, range shifts, and interspecific divergence in plants. However, the species divergence and spatiotemporal population dynamics of alpine cold-tolerant herbal plants in the high-altitude Qinghai-Tibetan Plateau (QTP) and adjacent areas remain poorly understood. In this study, we investigated population evolutionary history of four endangered Notopterygiumherb species in the QTP and adjacent regions. We sequenced 10 nuclear loci, 2 mitochondrial DNA regions, and 4 chloroplast DNA regions in a total of 72 natural populations from the 4 species, and tested the hypothesis that the population history of these alpine herbs was markedly affected by the Miocene–Pliocene QTP uplifts and Quaternary climatic oscillations. We found that the four Notopterygiumspecies had generally low levels of nucleotide variability within populations. Molecular dating and isolation-with-migration analyses suggested that Notopterygiumspecies diverged ~1.74–7.82 million years ago and their differentiation was significantly associated with recent uplifts of the eastern margin of the QTP. In addition, ecological niche modeling and population history analysis showed that N. incisumand N. franchetiiunderwent considerable demographic expansions during the last glacial period of the Pleistocene, whereas a demographic contraction and a expansion occurred for N. forrestiiand N. oviformeduring the antepenultimate interglacial period and penultimate glacial period, respectively. These findings highlight the importance of geological and climatic changes during the Miocene–Pliocene and Pleistocene as causes of species divergence and changes in population structure within cold-tolerant herbs in the QTP biodiversity hotspot.

Supplemental Digital Content is available in the text.A new self-rating functional scale (SRFS) was developed to assess the functionality of patients with schizophrenia, referred to the structure of Personal and Social Performance Scale (PSP). The main aim of this study was to evaluate the reliability and validity of the SRFS. A total of 210 patients with schizophrenia were recruited from outpatient clinics in six sites in China. Demographic information, SRFS, PSP, World Health Organization Disability Assessment Schedule II, and Positive and Negative Syndrome Scale were assessed. Spearman’s correlation coefficient and path analysis were used to assess the reliability and validity of the SRFS. Cronbach’s αcoefficient was used to assess the internal consistency reliability. Cronbach’s αwas 0.83, and ranged from 0.80 to 0.82 stably, indicating that the scale was reliable in internal consistency. Spearman’s correlation coefficient between split two parts was 0.68 (P<0.01), suggesting a moderate to strong split-half reliability. The standardized regression coefficients ranged from 0.48 to 0.79, indicating moderate construct validity. Spearman’s correlation coefficients between SRFS and PSP, World Health Organization Disability Assessment Schedule II, and Positive and Negative Syndrome Scale are 0.59, 0.65, and 0.47 (all P<0.01), respectively, indicating moderate criteria validities. The SRFS is a reliable and valid instrument for assessing personal and social functionality in patients with schizophrenia.

Supplemental digital content is available in the text.In this study, we sought to examine factors associated with dosing of antidepressants (ADs) in Asia. Based on reported data and clinical experience, we hypothesized that doses of ADs would be associated with demographic and clinical factors and would increase over time. This cross-sectional, pharmacoepidemiological study analyzed data collected within the Research Study on Asian Psychotropic Prescription Pattern for Antidepressantsfrom 4164 participants in 10 Asian countries, using univariate and multivariate methods. The AD doses varied by twofold among countries (highest in PR China and RO Korea, lowest in Singapore and Indonesia), and averaged 124 (120–129) mg/d imipramine-equivalents. Average daily doses increased by 12% between 2004 and 2013. Doses were significantly higher among hospitalized patients and ranked by diagnosis: major depression > anxiety disorders > bipolar disorder, but were not associated with private/public or psychiatric/general-medical settings, nor with age, sex, or cotreatment with a mood stabilizer. In multivariate modeling, AD-dose remained significantly associated with major depressive disorder and being hospitalized. Doses of ADs have increased somewhat in Asia and were higher when used for major depression or anxiety disorders than for bipolar depression and for hospitalized psychiatric patients.

In the present study, the SDA (specific denitrification activity) and SMA (specific methanogenic activity) in Start up of mixotrophic anammox reactor was optimized by applying the response surface method (RSM). The purpose of this work was to find the optimal combination of C/N ratio, influent ammonium (NH4+-N) and volatile suspended solid (VSS) with respect to minmum the SDA and SMA. Based on the RSM results, the quadratic model developed for the responses indicated that optimal conditions were C/N ratio of 0.5, influent NH4+-N content of 200mg L-1, and VSS content of 59.31g L-1. Under this conditions, the SDA and SMA were minimize and found to be 0.05 mmol N2 (g VSS d)-1, 0.017 mmol N2 (g VSS d)-1, respectively

Combined with sewage disposal characteristics and content networking technology, Constructing the relatively flexible structure, the price is relatively cheap,reliable performance of sewage treatment monitoring system. Improve the sewage disposal automation and informationization level and the ability of the key sources of pollution monitoring and environmental incident coping,The environmental protection,energy saving and emission reduction is of great significance.

The aim of this study was to survey the use of antipsychotic polypharmacy (APP) in older Asian patients with schizophrenia and examine its demographic and clinical correlates.

Based on the measurement of train speed, this paper briefly describes the basic principle of Doppler speed measurement and the design of speed measurement system. By the analysis of test signal which simulates the actual speed signal and comparison of the simulation results, the AR power spectrum estimation algorithm is selected as the model of speed measurement system, and the Burg method is selected to evaluate the Doppler frequency. Then the effect of parameters such as sampling frequency, length of the input vector, FFT length and estimation order on power spectrum estimation are analyzed, the optimization principles of the parameters are defined. Finally, the determined method is simulated with a high-noise, multi-jamming signal and has good results. The accuracy, stability and immunity are proved by the simulation.

Aims: Previous pharmacoepidemiological studies have highlighted considerable rates of adjunctive psychotropic medication prescriptions in patients with schizophrenia, including the use of adjunctive antidepressants, but this has not previously been studied in East Asia. This study examined the frequency of adjunctive antidepressant prescriptions in patients with schizophrenia and their clinical correlates in six East Asian countries and territories.

To compare impairments in role functioning and treatment rate of mental disorders and chronic physical disorders in the general population of metropolitan China.

Purpose. This study was undertaken to examine the structural determinants of oral bioavailability in the rat of a set of oligopeptides comprising D-amino acids, which were taken to be absorbed paracellularly based on a pronounced sensitivity of permeability to electrical resistance in Caco-2 cell monolayers.

Purpose. To compare the permeability characteristics of HT29-18-C1 colonic epithelial cell line with Caco-2, an established model of intestinal drug transport.

□ Animal models are frequently used to aid prediction of intestinal absorption in humans. However, there is little comparative quantitative information on species differences in paracellular permeation, which is an important route for oral absorption of small to medium-sized hydrophilic drug molecules. This study addresses this issue by comparing the molecular mass (MM) dependency in oral bioavailability between rat and dog of poly(ethylene glycol) (PEG), a polydispersed model mixture commonly used to characterize paracellular absorption, and of a series of eight d-peptides (based on d-phenylalanine). Fasted rats and dogs received PEG (400/900) and the d-peptides (MM 236–406Da), orally and intravenously, with total 24–48h urine collection to estimate oral bioavailability. After HPLC separation, the individual PEG oligomers and d-peptides were determined using radiometric detection, for radiolabeled material, and LC–MS, for unlabeled (PEG) material. All compounds were predominantly excreted unchanged following intravenous administration. After oral administration, the predominant peak in the radiochromatogram was unchanged material, indicating stability of the compounds in the gastrointestinal tract. A clear molecular mass dependency in oral bioavailability was seen with both series, but with absorption much greater in dog than rat. Thus, for PEG in rat, bioavailability decreased sharply from 79 to around 2% with increasing MM between 282 and 591Da, and then tapered to around 1.5% up to 1295Da. Whereas in dog, bioavailability remained around 100% for oligomers up to 600Da and then decreased quite sharply with increasing MM, tending to plateau around 13% beyond 900Da. Likewise, for the d-peptides in rat, bioavailability decreased from 30 to 1% with increasing MM between 236 and 406Da, whereas in dog it was 100%, declining to 16% over the same molecular range. This species difference appears to be due to a larger pore size and greater frequency of pores in the paracellular pathway of dog compared to rat. Furthermore, on the basis of comparison with literature data for PEG and selected drugs, rat would appear to be a better predictor than dog of absorption of hydrophilic compounds in human.

This paper describes a novel method to assess the antiluminal membrane (ALM) and luminal membrane (LM) transport in vivo across renal tubular epithelial cells. The method is based upon a noncompartmental moment analysis of the plasma concentration and urinary excretion rate curves following renal artery injection. Quantitative relationships are represented between the noncompartmental parameters (clearance, volume of distribution, and the mean transit time) and the first-order rate constants associated with transmembrane transport processes. The in vivo transepithelial transport of [14C]p -aminohippurate (PAH) was examined using the rat kidney in the absence or presence of various plasma concentrations of unlabeled PAH, cefazolin, and methotrexate. The tubular secretion intrinsic clearance was reduced with an increase in the plasma concentration of concurrent unlabeled organic onions. The distribution volume of PAH in the kidney decreased in association with a decrease in the amount of PAH secreted, whereas the mean transepithelial (artery-to-lumen) transit time (¯Tcell) remained constant. These findings indicate that ALM transport is a capacity-limited process determining the amount of tubular secretion, and that LM transport is linear over the concentration range examined and independent of the amount of secretion. The contribution of ALM and LM transport to transcellular transport was first clarified in vivo. The present method will be useful for analyzing the transmembrane transport processes in vivo for highly diffusible substances in the kidney.

A new method that can assess the kinetics ofin vivotransepithelial transport in rat kidney has been established. The method is based upon a multiple-indicator dilution experiment and the moment analysis theory. After simultaneous bolus injections ofp-aminohippurate (PAH) and inulin into the right renal artery, blood samples were taken from the carotid artery and urine was separately collected from right and left ureters. The characteristic response for the first passage of drugs through the right kidney was evaluated by taking blood circulation into consideration. To determine the mean artery-tovein transit time and the extraction ratio in the kidney, an intravenous injection was also performed as a reference experiment for deconvolution. The urinary excretion curve corresponding to the first passage was obtained as the difference between both kidneys. The mean artery-tolumen transit time (mean transepithelial transit time, ¯Tcell)was computed by subtracting the mean urinary transit time of inulin from that of secreted PAH. Sinc transport across the luminal membrane into the lumen from tubular epithelial cells can influence the cellular residence time of drugs, ¯Tcelland the single-pass mean residence time in epithelial cells(¯Tcell.sp)can be thought of describing luminal membrane transport. The value of¯Tcellobtained for 0. t mM PAH was 22 sec and it was prolonged to 61 sec in the presence of probenecid, suggesting an inhibitory effect on transport across the luminal membrane. On the other hand, antiluminal membrane transport into cells from blood is characterized by the volume of distribution in the kidney(VdPAH). VdPAHwas remarkably decreased by treatment with probenecid, indicating an inhibitory effect on antiluminal membrane transport. The effects of probenecid on both sides of epithelial cell membrane transport were first demonstratedin vivo.The present method is useful for the analysis ofin vivotransepithelial transport including antiluminal and luminal membrane transport for drugs excreted via tubular secretion.

Animal models are frequently used to aid prediction of intestinal absorption in humans. However, there is little comparative quantitative information on species differences in paracellular permeation, which is an important route for oral absorption of small to medium-sized hydrophilic drug molecules. This study addresses this issue by comparing the molecular mass (MM) dependency in oral bioavailability between rat and dog of poly(ethylene glycol) (PEG), a polydispersed model mixture commonly used to characterize para-cellular absorption, and of a series of eight D-Peptides (based on D-phenylalanine). Fasted rats and dogs received PEG (400/900) and the D-Peptides (MM 236–406 Da), orally and intravenously, with total 24–48 h urine collection to estimate oral bioavailability. After HPLC separation, the individual PEG oligomers and D-Peptides were determined using radiometric detection, for radiolabeled material, and LC–MS, for unlabeled (PEG) material. All compounds were predominantly excreted unchanged following intravenous administration. After oral administration, the predominant peak in the radiochromato-gram was unchanged material, indicating stability of the compounds in the gastrointestinal tract. A clear molecular mass dependency in oral bioavailability was seen with both series, but with absorption much greater in dog than rat. Thus, for PEG in rat, bioavailability decreased sharply from 79 to around 2% with increasing MM between 282 and 591 Da, and then tapered to around 1.5% up to 1295 Da. Whereas in dog, bioavailability remained around 100% for oligomers up to 600 Da and then decreased quite sharply with increasing MM, tending to plateau around 13% beyond 900 Da. Likewise, for the D-Peptides in rat, bioavailability decreased from 30 to 1% with increasing MM between 236 and 406 Da, whereas in dog it was 100%, declining to 16% over the same molecular range. This species difference appears to be due to a larger pore size and greater frequency of pores in the paracellular pathway of dog compared to rat. Furthermore, on the basis of comparison with literature data for PEG and selected drugs, rat would appear to be a better predictor than dog of absorption of hydrophilic compounds in human.

Purpose. The relative contribution of the small and large intestine to paracellular absorption is a subject of some controversy. Direct comparison of paracellular permeability in different epithelia is complicated by variations in junctional density and/or the absorptive surface area. Methods. This study used a combination of morphometric analyses and in vitroabsorption studies to define permeability characteristics in relation to the amount of paracellular pathway present in rat ileum, colon and the model epithelium, Caco-2. Results. Mucosal to serosal amplification was higher in ileum (3.9) than colon (1.9) or Caco-2 (1). Tight junctional density (1p) of ileal crypts was ≈3 fold greater (91 m/cm2) than that measured in ileal villi, colonic surface and crypt cells or Caco-2 monolayers (34−37 m/ cm2). However, when the relative contributions of the crypts and villi was taken into account there was no significant difference in the mean 1p per mucosal area for the three epithelia studied. Using these data to correct for morphometric differences the permeabilities of a range of small hydrophilic molecules (atenolol, D-PheAsp and PEG oligomers MW 282-634) was measured. Permeability of rat ileum and colon were virtually identical for all compounds studied. In contrast, Caco-2 monolayers showed a significantly lower permeability than intestinal tissues with the difference increasing markedly with molecular size. Conclusions. These studies suggest the importance of accounting for morphological variation when comparing the permeability characteristics of different epithelial systems.

Coated zinc oxide nanoparticles (ZnO-NPs) are more commonly applied in commercial products but current risk assessments mostly focus on bare ZnO-NPs. To investigate the impacts of surface coatings, this study examined acute and chronic toxicities of six chemicals, including bare ZnO-NPs, ZnO-NPs with three silane coatings of different hydrophobicity, zinc oxide bulk particles (ZnO-BKs), and zinc ions (Zn-IONs), toward a marine copepod, Tigriopus japonicus. In acute tests, bare ZnO-NPs and hydrophobic ZnO-NPs were less toxic than hydrophilic ZnO-NPs. Analyses of the copepod’s antioxidant gene expression suggested that such differences were governed by hydrodynamic size and ion dissolution of the particles, which affected zinc bioaccumulation in copepods. Conversely, all test particles, except the least toxic hydrophobic ZnO-NPs, shared similar chronic toxicity as Zn-IONs because they mostly dissolved into zinc ions at low test concentrations. The metadata analysis, together with our test results, further suggested that the toxicity of coated metal-associated nanoparticles could be predicted by the hydrophobicity and density of their surface coatings. This study evidenced the influence of surface coatings on the physicochemical properties, toxicity, and toxic mechanisms of ZnO-NPs and provided insights into the toxicity prediction of coated nanoparticles from their coating properties to improve their future risk assessment and management.