Solution-Processable Route for Large-Area Uniform 2D Semiconductor Nanofilms.

The semiconductor thin film engineering technique plays a key role in the development of advanced electronics. Printing uniform nanofilms on freeform surfaces with high efficiency and low cost is significant for actual industrialization in electronics. Herein, a high-throughput colloidal printing (HTCP) strategy is reported for fabricating large-area and uniform semiconductor nanofilms on freeform surfaces. High-throughput and uniform printing rely on the balance of atomization and evaporation, as well as the introduced thermal Marangoni flows of colloidal dispersion, that suppresses outward capillary flows. Colloidal printing with in situ heating enables the fast fabrication of large-area semiconductor nanofilms on freeform surfaces, such as SiO2/Si, Al2O3, quartz glass, poly(ethylene terephthalate) (PET), Al foil, plastic tube, and Ni foam, expanding their technological applications where substrates are essential. The printed SnS2 nanofilms are integrated into thin-film semiconductor gas sensors with one of the fastest responses (8 s) while maintaining the highest sensitivity (Rg/Ra = 21) (toward 10 ppm NO2), as well as an ultralow limit of detection (LOD) of 46 ppt. The ability to print uniform semiconductor nanofilms on freeform surfaces with high-throughput promises the development of next-generation electronics with low cost and high efficiency.

The effect of novel aromatic heterocycle substituted aminamidine derivatives on Necator americanus.

BACKGROUND: The efficacy of current drugs against hookworms at a single dose is highly variable across regions, age groups and infection intensity. Extensive and repeated use of these drugs also leads to potential drug resistance. Therefore, novel drugs are required for sustained disease control. OBJECTIVES: Novel aromatic heterocycle substituted aminamidine derivatives (AADs) were synthesized based on tribendimine (TBD), and their in vivo potency against Necator americanus was tested. METHODS: The efficacy of the AADs was tested in male hamsters. Oral and IV pharmacokinetic parameters were determined in male Sprague-Dawley rats. The proteomic profiles of N. americanus samples treated with AADs were compared using tandem mass tag-based quantitative proteomic analyses. RESULTS: Most AADs exhibited better anthelmintic activity than TBD at a single oral dose. Compound 3c exhibited improved solubility (>50×), and the curative dose was as low as 25 mg/kg. Similar to TBD, 3c was rapidly metabolized after oral administration and transformed into p-(1-dimethylamino ethylimino)aniline (dADT), an active metabolite against intestinal nematodes. dADT from 3c had better pharmacokinetic profiles than that from TBD and achieved an oral bioavailability of 99.5%. Compound 3c possessed rapid anthelmintic activity, clearing all worms within 24 h after an oral dose of 50 mg/kg. Quantitative proteomic analysis indicated that it might be related to ATP metabolism and cuticle protein synthesis. CONCLUSIONS: Compound 3c is a novel and promising compound against N. americanus in vivo.

Self-Assembly of Metal-Organic Frameworks on Graphene Oxide Nanosheets and In Situ Conversion into a Nickel Hydroxide/Graphene Oxide Battery-Type Electrode.

Graphene oxide (GO) has been widely reported as a supercapacitor electrode. Especially, GO is usually utilized to composite with electrochemical active materials, such as transition-metal oxide/hydroxide/sulfide, due to its considerable conductivity and mechanical strength. However, the ideal design and treatment for compositing GO with active materials are still challenging. Herein, an Ni-metal-organic framework (MOF) was self-assembled on GO nanosheets via the solvothermal method and was subsequently etched into the Ni(OH)2-GO composite electrode material through a gentle hydrolysis strategy. The GO support enables fast electron transport within the composite material, and the nickel hydroxide growth on GO nanosheets can prevent their aggregation, guaranteeing rapid ion migration. The improved Ni(OH)2-GO battery-type electrode features outstanding stability (capacity retention of 108% at 8000 cycles) and a considerable specific capacity (SC) of 1007.5 C g-1 at a current density of 0.5 A g-1. Compared with MOF-derived Ni(OH)2 obtained through hydrolysis, Ni(OH)2-GO only contains 7.41% wt GO, while its SC is almost 50% higher. An asymmetric supercapacitor has an energy density of 65.22 W h kg-1 and a power density of 395.27 W kg-1 utilizing p-phenylenediamine-functional reduced GO as the negative electrode, and it can maintain 73.08% capacity during 8000 cycles at a current density of 5 A g-1.

Profiling of Transcriptome-Wide N6-Methyladenosine (m6A) Modifications and Identifying m6A Associated Regulation in Sperm Tail Formation in Anopheles sinensis.

Recent discoveries of reversible N6-methyladenosine (m6A) methylation on messenger RNA (mRNA) and mapping of m6A methylomes in many species have revealed potential regulatory functions of this RNA modification by m6A players-writers, readers, and erasers. Here, we first profile transcriptome-wide m6A in female and male Anopheles sinensis and reveal that m6A is also a highly conserved modification of mRNA in mosquitoes. Distinct from mammals and yeast but similar to Arabidopsis thaliana, m6A in An. sinensis is enriched not only around the stop codon and within 3'-untranslated regions but also around the start codon and 5'-UTR. Gene ontology analysis indicates the unique distribution pattern of m6A in An. sinensis is associated with mosquito sex-specific pathways such as tRNA wobble uridine modification and phospholipid-binding in females, and peptidoglycan catabolic process, exosome and signal recognition particle, endoplasmic reticulum targeting, and RNA helicase activity in males. The positive correlation between m6A deposition and mRNA abundance indicates that m6A can play a role in regulating gene expression in mosquitoes. Furthermore, many spermatogenesis-associated genes, especially those related to mature sperm flagellum formation, are positively modulated by m6A methylation. A transcriptional regulatory network of m6A in An. sinensis is first profiled in the present study, especially in spermatogenesis, which may provide a new clue for the control of this disease-transmitting vector.

Conversion of Amorphous MOF Microspheres into a Nickel Phosphate Battery-Type Electrode Using the "Anticollapse" Two-Step Strategy.

Metal-organic frameworks (MOFs) have attracted great attention as templates for preparation of functional porous materials owing to their adjustable structures, rich porosity, and controllable components. However, collapsed templates during the conversion process hinder their application and synthesis of derivatives. In this study, we demonstrate a novel two-step etching strategy during which amorphous MOF microspheres are initially transformed into nickel hydroxide and then subsequently transformed into microspherical nickel phosphates. Through this strategy, the prepared nickel phosphates maintain the microspherical morphology of MOFs but with no MOF residuals, exhibiting ultrahigh specific surface area, uniform pore size, and good structural robustness. Examined as a supercapacitor electrode, they show an outstanding specific capacity of 820 C g-1 at 0.5 A g-1 and remarkable cycling stability of 88% capacity retention after 10 000 cycles. Moreover, an asymmetric supercapacitor constructed utilizing reduced graphene cross-linked with p-phenylenediamine oxide (PPD-rGO) as the cathode displays a preeminent energy density of 64.56 Wh kg-1 at a power density of 507 W kg-1. This strategy has important significance in guiding the preparation of high-performance MOF-derived electrodes.

Accurately Regulating the Electronic Structure of Nix Sey @NC Core-Shell Nanohybrids through Controllable Selenization of a Ni-MOF for pH-Universal Hydrogen Evolution Reaction.

N-doped carbon-encapsulated transition metal selenides (TMSs) have garnered increasing attention as promising electrocatalysts for hydrogen evolution reaction (HER). Accurately regulating the electronic structure of these nanohybrids to reveal the underlying mechanism for enhanced HER performances is still challenging and thus requires deep excavation. Herein, a series of pomegranate-like Nix Sey @NC core-shell nanohybrids (including Ni0.85 Se @ NC, NiSe2 @NC, and NiSe@NC) through controllable selenization of a Ni-MOF precursor is reported. The component of the nanohybrids can be fine-tuned by tailoring the selenization temperature and feed ratio, through which the electronic structure can be synchronously regulated. Among these nanohybrids, the Ni0.85 Se @ NC exhibits the optimum pH-universal HER performance with overpotentials of 131, 135, and 183 mV in 0.5 m H2 SO4 , 1.0 m KOH, and 1.0 m PBS, respectively, at 10 mA cm-2 , which are attributed to the increased partial density of state at the Fermi level and effective van der Waals interactions between Ni0.85 Se and NC matrix explained by density functional theory calculations.

"HOT" Alkaline Hydrolysis of Amorphous MOF Microspheres to Produce Ultrastable Bimetal Hydroxide Electrode with Boosted Cycling Stability.

Nickel/cobalt hydroxide is a promising battery-type electrode material for supercapacitors. However, its low cycle stability hinders further applications. Herein, Ni0.7 Co0.3 (OH)2 core-shell microspheres exhibiting extreme-prolonged cycling life are successfully synthesized, employing Ni-Co-metal-organic framework (MOF) as the precursor/template and a specific hydrolysis strategy. The Ni-Co-MOF and KOH aqueous solution are separated and heated to 120 °C before mixing, rather than mixing before heating. Through this hydrolysis strategy, no MOF residual exists in the product, contributing to close stacking of the hydroxide nanoflakes to generate Ni0.7 Co0.3 (OH)2 microspheres with a robust core-shell structure. The electrode material exhibits high specific capacity (945 C g-1 at 0.5 A g-1 ) and unprecedented cycling performance (100% after 10 000 cycles). The fabricated asymmetric supercapacitor delivers an energy density of 40.14 Wh kg-1 at a power density of 400.56 W kg-1 and excellent cycling stability (100% after 20 000 cycles). As far as is known, it is the best cycling performance for pure Ni/Co(OH)2 .

In vitro efficacies of solubility-improved mebendazole derivatives against Echinococcus multilocularis.

Recently, we introduced an epoxy group to mebendazole by a reaction with epichlorohydrin and obtained two isoforms, mebendazole C1 (M-C1) and mebendazole C2 (M-C2). The in vitro effects of mebendazole derivatives at different concentrations on Echinococcus multilocularis protoscoleces and metacestodes as well as cytotoxicity in rat hepatoma (RH) cells were examined. The results demonstrated that the solubility of the two derivatives was greatly improved compared to mebendazole. The mortality of protoscoleces in vitro reached to 70-80% after 7 days of exposure to mebendazole or M-C2, and M-C2 showed higher parasiticidal effects than mebendazole (P > 0.05). The parasiticidal effect of M-C1 was low, even at a concentration of 30 µm. The percentage of damaged metacestodes that were treated with mebendazole and M-C2 in vitro at different concentrations were similar, and M-C1 exhibited insignificant effects on metacestodes. Significant morphological changes on protoscoleces and metacestodes were observed after treatment with mebendazole and M-C2. In addition, the introduction of an epoxy group to mebendazole also reduced its cytotoxicity in RH cells. Our results demonstrate that the introduction of an epoxy group not only improved the solubility of mebendazole, but also increased its parasiticidal effects on E. multilocularis and reduced its cytotoxicity in RH cells.

Bimetallic-MOF Derived Accordion-like Ternary Composite for High-Performance Supercapacitors.

Supercapacitors are regarded to be highly probable candidates for next-generation energy storage devices. Herein, a bimetallic Co/Ni MOF is used as a sacrificial template through an alkaline hydrolysis and selective oxidation process to prepare an accordion-like ternary NiCo2O4/ß-Ni xCo1- x(OH)2/α-Ni xCo1- x(OH)2 composite, which is composed of Co/Ni(OH)2 nanosheets with large specific surface as the frame and NiCo2O4 nanoparticles with high conductivity as the insertion, for supercapacitor application. This material exhibits both high specific capacitance (1315 F·g-1 at 5 A·g-1) and excellent cycle performance (retained 90.7% after 10 000 cycles). This hydrolysis-oxidation process, alkali hydrolysis followed by oxidation with H2O2, offers a novel approach to fabricate the Ni/Co-based electrode materials with enhanced supercapacitor performance.

[Antiprotozoal Activities of Eucalyptus Extracts and Their Chemical Components].

Eucalyptus is a fast-growing plant with rich activities. The roots, stems and leaves of Eucalyptus all have medicinal values. Extracts from different parts of various kinds of Eucalyptus show antiparasitic effects, not only the repelling and killing effects on ectoparasites such as ticks and mites, but also the antiparasitic activities against endoparasites such as helminth and protozoa. This paper reviews the effects of Eucalyptus extracts and their chemical componets on protozoa including flagellates, sporozoan and ciliates.

[In vitro Killing Effect of Eucalyptus robusta Leaves Extract on Echinococcus granulosus Protoscolices].

Objective: To investigate the effect of Eucalyptus robusta leaves extract against Echinococcus granulosus protoscolices in vitro. Methods: Mature leaves of Eucalyptus robusta were collected on 24th day in each month from January to December 2012, and air-dried in the room. Ultrasonic extraction of the leaves was done with 4 solvents with different polarity, petroleum ether, dichloromethane, ethyl acetate and anhydrous ethanol. Protoscolices were incubated with the extract at various concentrations for 72 h, and mortality and median lethal dose（LC50） was calculated. Results: The extracts were different in characteristics and yield. The petroleum ether extract was in the form of black oil, while dichloromethane, ethyl acetate and anhydrous ethanol extracts were in the form of dark green, pink and white powder respectively. The average yields by petroleum ether, dichloromethane, ethyl acetate, and anhydrous ethanol were 4.4%, 2.1%, 2.3% and 2.3%, respectively. The extract yield was highest for petroleum ether, with a yield of 5.4% in May. The mortality of protoscoleces in all monthly groups of petroleum ether and dichloromethane extracts reached 100% with the concentration of 100 µg/ml and the same mortality reached in most groups of petroleum ether extracts with the concentration of 50 µg/ml. The effects of dichloromethane extracts were less than petroleum ether extracts, but significantly stronger than those of ethyl acetate and ehanol extracts. Further studies conducted on petroleum ether and dichloromethane extracts showed, the lethal effect of petroleum ether extract ranked in month of preparation from strong to weak as June>March>November>April>February>May>October>August>December>July>January>September. In June, the LC50 was 2.577 µg/ml and 95% confidence interval was 0.85-6.22 µg/ml. The lethal effect of dichlorom ethane extract ranked in month of preparation from strong to weak as November>May>October>April>July>December>June>September>August>February>March>January. In November, the LC50 was 21.85 µg/ml, and 95% confidence interval was 12.38-36.28 µg/ml. Conclusion: The Eucalyptus robusta leaves contain potential compounds against Echinococcus granulosus. Further experiments of isolation, analysis and identification are needed.

[In Vitro Effects of Aminoalcohol-carbazole Compound BTB3 against Echinococcus granulosus].

Objective: To evaluate the effects of a aminoalcohol-carbazole compound BTB3 against Echinococcus granulosus in vitro. Methods: The protoscoleces from sheep and germinal cells from secondary-infected mice were cultured and treated with 1, 2, 4, 8, 10 and 20 µg/ml BTB3 for 3 days. The viability of protoscoleces and cells was determined by the methylene blue exclusion method and CCK-8 assay. Meanwhile, the effect of 10 µg/ml BTB3 on germinal cells was assessed by scanning electron microscopy（SEM）. The metacestodes were treated with 1, 5 and 10 µg/ml BTB3 for two weeks, and the integrity of the metacestodes was evaluated by SEM. Results: The 10 µg/ml and 20 µg/ml BTB3 caused a death rate of （100.0±0.0）% and （85.2±7.2）% respectively for protoscoleces. As the concentration decreased, the death rate remained below 10%. Moreover, the activity inhibition rate on germinal cells was about 100% for 8, 10 and 20 µg/ml BTB3, and was reduced with the decrease of BTB3 concentration other than the afore-mentioned three. SEM revealed detachment, shrinkage, and cavitation of germinal cells after BTB3 treatment. And the metacestodes all showed the loss of turgidity after BTB3 treatment for 14 days, which indicated cell detachment and uneven distribution of cells in internal cyst of metacestodes. Conclusion: BTB3 has strong effects against Echinococcu granulosus protoscoleces, germinal cells and metacestodes in vitro, which make it a potential drug against hydatid diseases.

In vivo and in vitro efficacies of mebendazole, mefloquine and nitazoxanide against cyst echinococcosis.

Echinococcus granulosus is a cestode parasite. The metacestode stage causes cystic echinococcosis (CE) mainly in the human liver and lung. Current chemotherapy against CE is based on mebendazole and albendazole. However, benzimidazoles result in a low cure rate or are ineffective in many patients; therefore, novel compounds for the treatment of this disease have been studied. Mefloquine was reported to be dramatically effective on cultured Echinococcus multilocularis metacestodes in vitro. And, nitazoxanide has a prominent protoscolicidal effect. However, these compounds have no impact on the growth of cysts harbored in mice. In this study, we investigated the in vitro and in vivo efficacy of mebendazole, mefloquine, and nitazoxanide against E. granulosus protoscoleces, germinal cells, and infected mice. The effect of mebendazole on protoscoleces and germinal cell was proved to be dose-dependent in vitro. And, a reduction of the cyst weight was also the found after oral application of mebendazole to infected mice. Mefloquine (5 and 10 µg/ml) caused death within 24 h of protoscoleces and germinal cells in vitro, whereas a lower concentration of 1 µg/ml was ineffective. In mice infected with E. granulosus, oral mefloquine (200 and 400 mg/kg twice weekly for 2 weeks) showed no reduction in parasite weight. Without affecting the viability of germinal cells and the growth of hydatid cysts, nitazoxanide only showed protoscolicidal effects in infected mice. In conclusion, mebendazole, mefloquine, and nitazoxanide showed various effects on E. granulosus under different conditions. These drugs could be useful to some extent in the treatment of CE.

Significance of higher drug concentration in erythrocytes of mice infected with Schistosoma japonicum and treated orally with mefloquine at single doses.

The purpose of the present study is to understand the pharmacokinetic feature of mefloquine measured by erythrocytes and plasma in Schistosoma japonicum (S. j.)-infected mice and non-infected mice after oral administration of the drug at single doses. A high-performance liquid chromatography (HPLC) method was used to measure the plasma and erythrocyte concentrations of mefloquine at varying intervals posttreatment. Our results demonstrated that in non-infected mice treated orally with mefloquine at an ineffective dose of 50 mg/kg or effective dose of 200 mg/kg for 2-72 h, the erythrocyte-to-plasma ratios of mefloquine were 5.8-11.2 or 2-14.2. On the other hand, in S. j.-infected mice treated with the same single doses of the drug, the erythrocyte and plasma drug concentration ratios were 3.1-4.6 or 2.9-8.5, manifesting that either in infected mice or in non-infected mice that received oral mefloquine resulted in higher concentration of mefloquine in erythrocytes than that in plasma. Unexpectedly, under oral administration of mefloquine at a higher single dose of 200 mg/kg, the pharmacokinetic parameter C max values for plasma from S. j.-infected and non-infected mice were 1.6 ± 0.3 and 2.0 ± 0.4 µg/mL, respectively, which were below the determined in vitro LC50 (50 % lethal concentration) value of 4.93 µg/mL. Therefore, the plasma concentration of mefloquine may display a little effect against schistosomes during the treatment. Although the values of T 1/2 and AUC0-∞ for erythrocytes were significantly longer and higher in infected mice than those of corresponding non-infect mice that received the same single mefloqine dose of 50 mg/kg, the C max value was only 2.6 ± 0.4 µg/mL lower than the determined in vitro LC50, which may explain why this low single dose is ineffective against schistosomes in vivo. After administration of higher mefloquine dose of 200 mg/kg, the C max value for erythrocytes in infected mice was 30 % (7.4 ± 0.7 versus 10.7 ± 2.7 µg/mL) lower than that in the corresponding non-infected mice, but its level was above the determined in vitro LC95 (95 % lethal concentration) value of 6.12 µg/mL. Meanwhile, longer T 1/2 value of 159.2 ± 129.3 h in infected mice led to significant increase in AUC0-∞ value (1969.3 ± 1057.7 vs 486.4 ± 53.0 µg/mL·h), relative to corresponding non-infected mice. In addition, the mean residence time (MRT0-∞) in infected mice was also significantly longer than that in non-infected mice. All these results may beneficial for the treatment. According to the results, we suggest that higher ratios of mefloquine concentration in erythrocytes to plasma may offer a way to transport mefloquine to the worm gut through ingestion of erythrocytes by the worms, where the gut is the site for displaying the effect by mefloquine.

[Controlled Veterinary Drug Delivery Systems against Parasitic Infection].

Parasitic infections, especially the gastrointestinal and lung nematode infections, are most common in livestock in temperate areas, and it is the major constraints affecting livestock production. In grazing season, outdoor activities of animals cause inconvenience to the application of antiparasitic drugs. Therefore, controlled drug delivery systems can prolong the effect time and reduce the difficulty of drug administration. This review summarizes several types of long-term delivery devices and dosage forms including intraruminal devices, long-acting injectables, in-situ forming implants, novel microparticles and nanoparticles. Their advantages and drawbacks are dicussed.

[Plasma Metabolism and Protective Effect of Oral Administration of Niclosamide on Schistosoma japonicum Cercarial Invasion in Mice].

OBJECTIVE: To study the metabolism of niclosamide in plasma, and the protective effect of its oral administration on Schistosoma japonicum cercarial invasion in mice. METHODS: Twenty-four female Kunming mice were randomly divided into 8 groups, each with 3 mice. Each mouse was treated orally with 120 mg niclosamide per kilogram of body weight (120 mg/kg). The plasma samples were collected at 0.25, 0.5, 1, 2, 4, 8, 16, and 24 h after treatment by retro-orbital blood sampling. The blood drug concentration was determined by HPLC. The pharmacokinetics parameters were calculated such as peak concentration (Cmax), peak time (Tmax), mean residence time (MRT), and elimination half life (T½). Thirty Kunming mice were randomly divided into 6 groups. Among them, 5 groups were treated orally with 40, 80, 120, 160, and 200 mg/kg niclosamide, respectively. The remaining untreated group served as control. One hour post-treatment, each mouse was infected with 40 ± 2 Schistosoma japonicum cercariae. Another 35 mice treated with 200 mg/kg niclosamide were randomly divided into 7 groups. Mice in each group were infected with 40 ± 2 S. japonicum cercariae on 0.25, 1, 4, 8, 12, and 24 h after treatment, named as group A, B, C, D, E, and F. Five untreated mice served as control (group G). All mice were sacrificed 35 days post-infection. Mean worm burden and worm reduction were calculated. RESULTS: At a dose of 120 mg/kg niclosamide, the blood drug concentration was (0.40 ± 0.28) µg/ml at 0.25 h post-treatment, reached a peak of (0.91 ± 0.34) µg/ml at 1 h, and decreased to (0.49 ± 0.38) µg/ml at 2 h, and got close to 0 at 16 h. The mean residence time (MRT) in mice was (6.78 ± 1.47) h, and the elimination half time was (6.80 ± 7.05) h. No significant difference was found in worm burden between different dose groups and control group (P > 0.05). The mean worm burden in group A was significantly lower than that of the control (P < 0.05) with a mean worm reduction of 79.1%. And there was no significant difference in worm burden between other groups and the control (P > 0.05). CONCLUSIONS: The blood drug concentration increases rapidly by gavage administration of 120 mg/kg niclosamide, reaching to the maximum concentration at 1 h post-treatment. It shows a certain potective effect of oral administration of 200 mg/kg niclosamide on Schistosoma japonicum cercarial invasion at 0.25 h after treatment.

Interfacial Self-Assembly of Oriented Semiconductor Monolayer for Chemiresistive Sensing.

Semiconductor nanofilm fabrication with advanced technology is of great importance for next-generation electronics/optoelectronics. Fabrication of high-quality and perfectly oriented semiconductor thin films and integration into high-performance electronic devices with low cost and high efficiency are huge challenges. Here we exquisitely utilized the Marangoni effect to perfectly guide tin disulfide (SnS2) nanocoins into an ordered assembly in milliseconds, resulting in an uniaxial-oriented monolayer semiconductor film. Further exploration revealed that the formed "crumple zone" at the interface caused by the Marangoni force endows the nanofilm with a rapid healable capability, which can be easily transferred to arbitrary substrates. As a proof of concept, the nanocoin-monolayer was transferred onto a micro-interdigitated electrode substrate to form a high-performance chemiresistive sensor that can effectively monitor the trace amounts of toxic gases. In addition, the assembled monolayer nanofilms can be conformally printed on freeform surfaces: both flat and nonflat substrates. This efficient and low-cost Marangoni force-assisted surface self-assembly (MFA-SSA) strategy is promising for advanced microelectronics and real industrial applications.

[Effect of long-term use of albendazole on mice liver].

OBJECTIVE: To observe the change in serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), direct bilirubin (DBL), indirect bilirubin (IBIL), albumin (ALB) and globulin (GLB), and mouse liver ultrastructure during 1-16 weeks of albendazole treatment. METHODS: 180 female Kunming mice were divided randomly into albendazole treatment group and negative control group. Each mouse of albendazole treatment group was treated with 136.3 mg/(kg x d) albendazole. The mice in control group were given same amount of physiological saline. After 1, 2, 4, 6, 8, 10, 12, 14 and 16 weeks of treatment, 10 mice from each group were randomly selected, serum samples were collected and analyzed for the above seven liver function indices. Pathological changes of liver were observed by transmission electron microscopy. Linear regression analysis was conducted for the relationship between liver function indices(dependent variable) and pathological scores (independent variable). RESULTS: During 1-16 weeks of albendazole treatment, there was no significant difference in serum levels of DBL, IBIL, ALB and GLB between albendazole treatment group and control group. Compared with other treatment period, after 12 weeks of treatment the serum levels of ALT (55.2 +/- 23.7), AST(176.4 +/- 49.2) and ALP(141.1 +/- 19.4) in albendazole treatment group were higher than that of the control (35.5 +/- 8.6, 108.2 +/- 21.9, 84.0 +/- 24.8) (P < 0.05). After 2, 8, 10, 12 and 14 weeks of treatment, the pathological score of albendazole treatment group was 11.8 +/- 4.8, 10.6 +/- 4.8, 13.6 +/- 3.5, 29.8 +/- 10.7, and 5.6 +/- 2.5, respectively, which was higher than that of the control (0.8 +/- 0.4, 1.2 +/- 0.8, 2.4 +/- 2.0, 1.2 +/- 0.4, 1.4 +/- 1.1) (P < 0.05). Among the three liver function indices AST, ALT and ALP, AST was the best fit index for linear regression. The regression formula was Y = -17.616 + 0.188X. CONCLUSION: Long-term treatment with albendazole at a dosage of 136.3 mg/(kg x d) for mice can cause significant elevation of serum levels of ALT, AST and ALP, and result in mild pathological changes in the liver.

Ultrastructural alterations of adult Schistosoma japonicum harbored in mice treated with a single oral dose of OZ78.

OBJECTIVE: To observe the ultrastructural alterations of adult Schistosoma japonicum induced by synthetic trioxolane OZ78. METHODS: Eight out of ten mice infected with 40-60 S. japonicum cercariae for 35 d were treated orally with OZ78 at a single dose of 400 mg/kg. Four groups of two mice were killed at 24 h, 3 d, 7 d, and 14 d post treatment, and schistosomes were recovered by perfusion technique, fixed, and examined by transmission electron microscopy. Schistosomes obtained from the remaining two untreated mice served as control. RESULTS: After infected mice were treated with OZ78 for 24 h, the prominent alterations in tegument of both male and female worms were observed, which revealed in flattened surface due to swelling of cytoplasmic processes, irregular expansion in distal end of cytoplasmic processes accompanied by decrease in rod-like and discoid-like secretory bodies, focal lysis of tegumental matrix; fusion of some cytoplasmic processes to form a large piece, disruption or disappearance of basal membrane, and destruction of internal structures in sensory organelles. In the subtegument, no or slight swelling and focal lysis of muscle bundles were seen, while the syncytium beneath the muscle showed enlargement of nucleus with indistinction of partial nuclear membrane, formation of small vacuoles due to focal lysis of chromatin, and emergence of degenerated mitochondria in perinuclear cytoplasm. As to parenchymal tissues, the major alterations included degeneration of mitochondria, formation of some small vacuoles and myelin-like structures. In gut epithelial cells, the prominent alterations were irregular enlargement of nucleus with light lysis of nucleoli and fusion of partial bi-layer nuclear membrane, degeneration of mitochondria in cytoplasm and collapse of microvilli. At this time point, in the vitelline cells of female worms, the most significant alteration was the collapse of many vitelline droplets, which led to release of the vitelline balls, followed by their lysis and fusion. Three to 7 d post treatment, the damage to the worms aggravated either in extent or in severity along with time. The significant damages to male and female worms were fusion of cytoplasmic processes, peeling or collapse of damaged cytoplasmic processes resulting in exposure of muscle bundles, severe destruction of sensory organelles and syncytium, focal or extensive swelling and lysis of muscle bundles, emergence of some larger piece of degenerated parenchymal tissues and severe damage to the gut epithelial cell. While in the vitelline cells of female worms, decrease in the number of vitelline droplet, focal lysis of nucleus and extensive lysis of parenchymal tissues among the vitelline cells were also observed. Fourteen days post OZ78 dosing, male and female worms which survived the treatment showed some renovation in damaged tegument and subtegument, while most gut epithelial cells and vitelline cells still revealed in prominent injury. CONCLUSION: The results demonstrate that OZ78 possesses an extensive damage to the ultrastructure in tegument and subtegument tissues including syncytium, parenchymal tissues, gut epithelial cells, and vitelline cells of adult S. japonicum.

[In vitro metabolism of fenbendazole prodrug].

Synthesized fenbendazole prodrug N-methoxycarbonyl-N'-(2-nitro-4-phenylthiophenyl) thiourea (MPT) was analyzed in vitro in artificial gastric juice, intestinal juice and mouse liver homogenate model by using HPLC method, and metabolic curve was then generated. MPT was tested against Echinococcus granulosus protoscolices in vitro. The result showed that MPT could be metabolized in the three biological media, and to the active compound fenbendazole in liver homogenate, with a metabolic rate of 7.92%. Besides, the prodrug showed a weak activity against E. granulosus protoscolices with a mortality of 45.9%.