The different toxic effects of metalaxyl and metalaxyl-M on Tubifex tubifex.

Metalaxyl and Metalaxyl-M are the fungicides that widely used in many countries. In this study, the environmental behaviors between metalaxyl and metalaxyl-M in Tubifex tubifex (T. tubifex) were quantitative analyzed by using a high performance liquid chromatography with photo-diode-array-detector (HPLC-DAD). Results demonstrated that there was no significant difference (p > 0.05) in the concentration of metalaxyl and metalaxyl-M in T. tubifex during the exposure process. However, the dissipation behaviors of metalaxyl and metalaxyl-M in T. tubifex were different (p < 0.05) during the non-exposure culture process. Meanwhile, the toxic effects were also evaluated by comparing the different influences of these two compounds on related physiological indicators, and functional enzyme activities. The survival rates of T. tubifex were 63.33 ± 15.28% (20 mg L-1), 63.33 ± 5.77% (200 mg L-1) treated with metalaxyl and were 50.00 ± 10.00% (20 mg L-1), 46.67 ± 11.55 (200 mg L-1) treated with metalaxyl-M at the non-exposure culture process. The autotomy rates were increased significantly compared with the initial in all treatments. Besides, the activities of CAT, SOD, and GST in T. tubifex were also inhibited by metalaxyl and metalaxyl-M treatments. Finally, the high-throughput transcriptome sequencing technology was applied to investigate the metabolic pathways of target analytes in T. tubifex, and results proved that the metabolic pathways associated with human diseases (such as viral myocarditis) were up-regulated expression for metalaxyl and metalaxyl-M treatments, and metalaxyl-M up-regulated more significantly. All the results demonstrated that metalaxyl-M had a higher toxicity than metalaxyl on T. tubifex.

The efficacy and safety of a ketogenic diet for children with refractory epilepsy in China: a retrospective single-center cohort study.

BACKGROUND: The ketogenic diet (KD) has been implemented in many different counties. However, in China, study concerning the efficacy of the KD is still at an early-stage of evaluation. Furthermore, the KD is thought to be incompatible with Chinese children because of its lack of palatability, especially for the Asian population. In addition, its substantial antiepileptic effect remains to be confirmed. METHODS: To evaluate the efficacy and safety of the KD treatment of refractory childhood epilepsy in China, we prospectively enrolled 147 children with refractory epilepsy for KD treatment in Guangdong 999 Brain Hospital and followed up the children for 6 months. Outcome was measured by seizure frequencies before and after the KD diet and adverse effects. We also evaluated influences of different variables (starting age, duration of epilepsy, and others) on the outcome. RESULTS: We found after 1 month, 3 months, and 6 months of KD treatment, 28.0%, 55%, and 67.9% of the subjects remained on diet with a >50% seizure reduction and seizure-free rates of 6.5%, 13.2%, and 23.3%, respectively. Gender, starting age, duration, etiology, classification, and seizure type of epilepsy showed no significant influence on efficacy. Anorexia, diarrhea, and gravel were the main side-effects of the KD treatment. CONCLUSIONS: In conclusion, the KD is a safe and efficacious method for childhood refractory epilepsy treatment.

Magnetic solid-phase extraction based on nano-zeolite imidazolate framework-8-functionalized magnetic graphene oxide for the quantification of residual fungicides in water, honey and fruit juices.

In this work, zeolite imidazolate framework-8 (ZIF-8) functionalized magnetic graphene oxide (Fe3O4@APTES-GO/ZIF-8) was successfully synthesized and used as a novel adsorbent in magnetic solid-phase extraction (MSPE) for the determination of four triazole fungicides in water, honey and fruit juices. The main parameters such as extraction time, amount of adsorbent, the pH value of the sample, ionic strength, and desorption solvent which could affect the experiment results were optimization. Under the optimum condition, the obtained linearity of this method ranged from 1 to 1000 µg L-1 for all analytes, with correlation coefficients (R2) ≥ 0.9914. Limit of detections (LODs) and limit of qualifications (LOQs) of four triazole fungicides were ranged from 0.014 to 0.109 µg L-1 and from 0.047 to 0.365 µg L-1, respectively. Based on comparison with outcomes from other studies, Fe3O4@APTES-GO/ZIF-8-MSPE could provide high performance and achieve satisfied results for the analysis of trace triazole fungicides in complicated matrices.

[Distribution Characteristics and Influencing Factors of Phosphorus in the Dongting Lake at Different Water Periods].

To study the distribution characteristics and influencing factors of phosphorus in the Dongting Lake at different water periods, water samples were collected from 18 representative monitoring sections located in the Dongting Lake and its upper rivers from January to December 2016. Various forms of phosphorus concentration in the samples were analyzed. The results showed that, overall, the average concentrations (range) of total phosphorus (TP), total dissolved phosphorus (DTP), and phosphate (DPO) in the Dongting Lake were 0.085 mg·L-1(0.030-0.176 mg·L-1), 0.062 mg·L-1(0.017-0.151 mg·L-1), and 0.053 mg·L-1(0.007-0.144 mg·L-1), respectively. These forms of phosphorus concentrations were all characterized by the intermediate season (IS) > the dry season (DS) > the wet season (WS), with obvious seasonal variation characteristics. In the spatial distribution, the phosphorus concentration increased from west to east in DS and IS and decreased from the west to east in WS. In terms of time distribution, various forms of phosphorus were characterized by obvious seasonal distribution in the east, west, and outlet of the Dongting Lake. The phosphorus concentration in WS was higher than that in DS and IS in the West Dongting Lake. However, the concentration was higher during DS and IS than that in WS for the east and outlet of lake. Various forms of phosphorus concentrations in the west were highest in the Dongting Lake during WS, while those in the outlet and east were relatively highest in DS and IS. Therefore, the phosphorus pollution in the West Dongting Lake should receive more attention during WS, and the pollution in the east and outlet requires higher attention during DS and IS. In terms of form composition, according to the monthly data of the sections, the values of ρ(TPO)/ρ(TP) and ρ(DPO)/ρ(TPO) were mainly above 60% in the water body of the Dongting Lake and its upper rivers. DTP was the main form of TP, and DPO was the main form of DTP. It indicated that the phosphorus in the Dongting Lake and its upper rivers was mainly soluble, which is different from that before the impoundment of the Three Gorges Reservoir. The spatio-temporal distribution of suspended particles (SS) and phosphorus in the Dongting Lake had a certain synergistic effect. The concentration of SS and phosphorus in each water period showed a significant or extremely significant correlation. Therefore, SS was considered as an important factor affecting the seasonal variation of phosphorus in the Dongting Lake. In this study, it was concluded that the Nanzui section, the Daxiaoxihu section, and the East Dongting Lake area were clearly affected by surrounding human activities, respectively including domestic, agricultural, and sand mining sources of phosphorus pollution. The water in the West Dongting Lake has even been affected by mild and moderate eutrophication in 2016. These phenomena should be paid more attention.

[Value of S100A8 in evaluating the prognosis of children with acute lymphoblastic leukemia].

OBJECTIVE: To study the association between S100A8 expression and prognosis in children with acute lymphoblastic leukemia (ALL). METHODS: The clinical data of 377 children with ALL who were treated with the CCLG-2008-ALL regimen were retrospectively reviewed. ELISA and PCR were used to measure serum protein levels and mRNA expression of S100A8. The Kaplan-Meier method was used for survival analysis and a Cox regression analysis was also performed. RESULTS: The children were followed up for 56 months, and the overall survival rate of the 377 children was 89.1%. The prednisone good response group had significantly lower S100A8 protein and mRNA levels than the prednisone poor response group (P<0.01). In the children with standard or median risk, both S100A8 protein and mRNA levels were associated with event-free survival rate (P<0.05). There were significant differences in S100A8 protein and mRNA levels between the children with different risk stratifications (P<0.01). The children who experienced events had significantly higher S100A8 protein and mRNA levels than those who did not (P<0.01). The Kaplan-Meier survival analysis and the Cox regression model suggested that S100A8 overexpression was an independent risk factor for the prognosis of children with ALL. CONCLUSIONS: High S100A8 expression may be associated with the poor prognosis of children with ALL and is promising as a new marker for individualized precise treatment of children with ALL.

[Clinical and genetic characteristics of patients with dentatorubro-pallidoluysian atrophy].

OBJECTIVE: To explore the clinical and genetic characteristics of patients with dentatorubro-pallidoluysian atrophy (DRPLA). METHODS: DNA analysis for DRPLA gene was performed in two patients. Clinical features and genetic testing of Chinese DRPLA patients reported in the literature were reviewed in terms of initial symptoms, CAG repeat and age of onset. RESULTS: Both families were confirmed by genetic analysis. In family 1, the number of CAG repeat in the proband, his brother and his mother was determined respectively as 8/65, 8/53 and 8/18. In family 2, the number of CAG repeat was respectively 13/63, 13/18, 18/52 and 13/13 in the proband, his brother, his father and his mother. The size of the expanded CAG repeats has inversely correlated with the age at onset (P<0.05, r=- 0.555). The age at onset of epilepsy was 10 and that for the onset of ataxia is forty years in initial symptom. CONCLUSION: The clinical characteristics of DRPLA include epilepsy, ataxia and cognitive impairment. The initial symptoms are epilepsy in adolescence and ataxia in adults. The size of expanded CAG repeats inversely correlates with the age at onset. The initial symptoms are different with different age of onset. It is difficult to diagnose DRPLA at an early stage.

Functional connectivity among spikes in low dimensional space during working memory task in rat.

Working memory (WM) is critically important in cognitive tasks. The functional connectivity has been a powerful tool for understanding the mechanism underlying the information processing during WM tasks. The aim of this study is to investigate how to effectively characterize the dynamic variations of the functional connectivity in low dimensional space among the principal components (PCs) which were extracted from the instantaneous firing rate series. Spikes were obtained from medial prefrontal cortex (mPFC) of rats with implanted microelectrode array and then transformed into continuous series via instantaneous firing rate method. Granger causality method is proposed to study the functional connectivity. Then three scalar metrics were applied to identify the changes of the reduced dimensionality functional network during working memory tasks: functional connectivity (GC), global efficiency (E) and casual density (CD). As a comparison, GC, E and CD were also calculated to describe the functional connectivity in the original space. The results showed that these network characteristics dynamically changed during the correct WM tasks. The measure values increased to maximum, and then decreased both in the original and in the reduced dimensionality. Besides, the feature values of the reduced dimensionality were significantly higher during the WM tasks than they were in the original space. These findings suggested that functional connectivity among the spikes varied dynamically during the WM tasks and could be described effectively in the low dimensional space.

Increase of spike-LFP coordination in rat prefrontal cortex during working memory.

Working memory (WM) refers to the short-term maintenance of information with higher cognitive functions. Recent researches show that local field potentials (LFPs) and spikes, as different modes of neural signals, encode WM, respectively. There is a growing interest in how these two signals encode WM in coordination. The aim of this study is to investigate spike-LFP coupling coding of WM via the joint entropy analysis. The experimental data were multi-channel spikes and LFPs obtained from SD rat prefrontal cortex through the implanted microelectrode array during the WM tasks in Y-maze. The short-time Fourier transform (STFT) was applied to analyze the power changes of WM related frequency bands in the LFPs. The joint entropy indexes (JEIs) between spikes and the principle components of LFPs were calculated for each pair of the spike and the LFP series during WM. The results showed that the power of theta (4-12 Hz), low gamma (LG, 30-60 Hz) and high gamma band (HG, 60-100 Hz) in LFPs increased during the WM tasks. In addition, the JEIs between spikes and LFPs components (theta, LG and HG) significantly increased in the correct trials. Besides, the coupling levels were low when the rats waiting in the starting area. These results suggest that the JEIs between spikes and LFPs components (theta, LG and HG) encode WM effectively. These findings could lead to improved understanding of the WM mechanism from the view of spike-LFP joint encoding.

Correlation and prediction of partition coefficient using nonrandom two-liquid segment activity coefficient model for solvent system selection in counter-current chromatography separation.

Selection of a suitable solvent system is the first and foremost step for a successful counter-current chromatography (CCC) separation. In this paper, a thermodynamic model, nonrandom two-liquid segment activity coefficient model (NRTL-SAC) which uses four types of conceptual segments to describe the effective surface interactions for each solvent and solute molecule, was employed to correlate and predict the partition coefficients (K) of a given compound in a specific solvent system. Then a suitable solvent system was selected according to the predicted partition coefficients. Three solvent system families, heptane/methanol/water, heptane/ethyl acetate/methanol/water (Arizona) and hexane/ethyl acetate/methanol/water, and several solutes were selected to investigate the effectiveness of the NRTL-SAC model for predicting the partition coefficients. Comparison between experimental results and predicted results showed that the NRTL-SAC model is of potential for estimating the K value of a given compound. Also a practical separation case on magnolol and honokiol suggests the NRTL-SAC model is effective, reliable and practical for the purpose of predicting partition coefficients and selecting a suitable solvent system for CCC separation.

Polymer-mediated anti-solvent crystallization of nitrendipine: monodispersed spherical crystals and growth mechanism.

PURPOSE: To investigate anti-solvent crystallization and growth mechanism of nitrendipine spherical crystals in an aqueous solution containing polymeric additives. METHODS: Size and shape of crystals were investigated using laser diffractometry, optical microscopy and scanning electron microscopy (SEM). Crystalline form was determined by X-ray powder diffractometer (XRPD). During crystal growth, morphological changes at different time points were observed using SEM. RESULTS: Morphology of nitrendipine crystals was affected by polymers and temperature. Monodispersed micro-spherical crystals were obtained when polyvinyl alcohol (PVA) and PEG 200 were present in crystallization medium at 2°C. During crystallization, large number of amorphous nanoparticles was first observed, followed by aggregation into a core for spherical crystals. Once crystalline state was achieved, rapid growth on core surface was observed with amorphous particles acting as a reservoir allowing formation of star-like particles with needle-like subunits. Spherical crystals were formed by filling the gap between needle-like distinct crystalline units of star-like templates with molecules from dissolved amorphous particles. CONCLUSIONS: Monodispersed nitrendipine spherical crystals were obtained using carefully controlled conditions. A mechanism for the nitrendipine spherical crystal growth is suggested. These findings provide a new insight into spherulitic crystallization of active pharmaceutical ingredients.

In vitro-in vivo study of CoQ10-loaded lipid nanoparticles in comparison with nanocrystals.

The present work described the effect of CoQ10 dissolution characteristics in nanocrystals and lipid nanoparticles (LNs) on its oral absorption in rats. Nanocrystals and LNs were prepared by melt-high pressure homogenization and sucrose monolaurate was used as a stabilizer in all formulations. Witepsol(®)W35 and medium-chain triglycerides (MCT) were selected as lipid additives to form LN(CoQ10+W35) and LN(CoQ10+MCT), respectively. From the results obtained, the particle size of CoQ10 nanocrystals was 285 nm, while it was reduced to 150 nm by mixture with an equal amount of lipid additives due to their lower melting points. In vitro dissolution results indicated that the drug release from two LNs was delayed compared with that from nanocrystals, and LN(CoQ10+W35) exhibited the highest drug release over 4h. Finally, in vivo evaluation demonstrated that the oral absorption of CoQ10 was markedly increased by using nanocrystals and LNs compared with a coarse suspension. A good relationship was found between the in vitro dissolution and in vivo evaluation. The enhanced oral absorption of CoQ10 by nanocrystals and LNs was due to improved dissolution. In conclusion, Witepsol(®)W35 was shown to be a better lipid additive for the preparation of LNs to increase the oral absorption of CoQ10.

Effect of crystal size on the in vitro dissolution and oral absorption of nitrendipine in rats.

PURPOSE: To investigate the effect of crystal size on the dissolution and oral absorption of nitrendipine, a poorly soluble drug, in rats. METHODS: Five types of nitrendipine crystal suspensions with different particle sizes (200 nm, 620 nm, 2.7 microm, 4.1 microm, 20.2 microm) were prepared either by the precipitation-ultrasonication or the anti-solvent precipitation method. The simulated intestinal fluid in the fasted state (FaSSIF) was selected as the dissolution medium, and the dissolution behaviors of different nitrendipine crystals were simulated based on a Noyes-Whitney type equation. The in vivo absorption and the absolute bioavailability of the different nitrendipine crystals were evaluated in Wistar rats. RESULTS: The dissolution rate of nitrendipine was significantly increased by a reduction in particle size. The dissolution test in FaSSIF could discriminate between the differences in the dissolution rates of the different particle sizes, and the simulated results were in agreement with the observed dissolution curves. From the simulated T(50%) values (50% dissolution time), the dissolution rates of crystals with particle sizes of 200 nm, 620 nm, 2.7 microm, 4.1 microm and 20.2 microm were calculated to be 5.1 x 10(4), 1.0 x 10(4), 237, 64 and 11-fold greater than that of the raw crystals and resulted in absolute bioavailability of 61.4% 51.5%, 29.4%, 26.7%, 24.7%, respectively. The reduction in the drug particle size correlated well with incremental improvements in oral absorption. A good linear relationship was observed between the Log (T(50%)) and the absolute bioavailability of nitrendipine. CONCLUSIONS: The dissolution rate and the oral bioavailability of nitrendipine were significantly affected by the crystal size, and the oral bioavailability could be improved significantly by preparing it as nanocrystals. FaSSIF can be used to predict differences in oral absorption of crystals with different particle sizes.