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.

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.

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.

Evaluation of PEN2-ATP6AP1 axis as an antiparasitic target for metformin based on phylogeny analysis and molecular docking.

BACKGROUND: Metformin (Met), the first-line drug used in the treatment for type 2 diabetes mellitus, is effective against a variety of parasites. However, the molecular target of Met at clinical dose against various parasites remains unclear. Recently, low-dose Met (clinical dose) has been reported to directly bind PEN2 (presenilin enhancer protein 2) and initiate the lysosomal glucose-sensing pathway for AMPK activation via ATP6AP1 (V-type proton ATPase subunit S1), rather than perturbing AMP/ATP levels. METHODS: To explore the possibility of PEN2-ATP6AP1 axis as a drug target of Met for the treatment of parasitic diseases, we identified and characterized orthologs of PEN2 and ATP6AP1 genes in parasites, by constructing phylogenetic trees, analyzing protein sequences and predicting interactions between Met and parasite PEN2. RESULTS: The results showed that PEN2 and ATP6AP1 genes are only found together in a few of parasite species in the cestoda and nematoda groups. Indicated by molecular simulation, Met might function by interacting with PEN2 on V37/W38/E5 (Trichinella spiralis) with similar binding energy, and on F35/S39 (Caenorhabditis elegans) with higher binding energy, comparing to human PEN2. Hence, these results indicated that only the T. spiralis PEN2-ATP6AP1 axis has the potential to be the direct target of low-concentration Met. Together with contribution of host cells including immune cells in vivo, T. spiralis PEN2-ATP6AP1 axis might play roles in reducing parasite load at low-concentration Met. However, the mechanisms of low-concentration Met on other parasitic infections might be mainly achieved by regulating host cells, rather than directly targeting PEN2-ATP6AP1 axis. CONCLUSIONS: These findings revealed the potential mechanisms by which Met treats various parasitic diseases, and shed new light on the development of antiparasitic drugs.

Phylogeny-Related Variations in Venomics: A Test in a Subset of Habu Snakes (Protobothrops).

We conducted a comparative analysis to unveil the divergence among venoms from a subset of Old World habu snakes (Protobothrops) in terms of venomic profiles and toxicological and enzymatic activities. A total of 14 protein families were identified in the venoms from these habu snakes, and 11 of them were shared among these venoms. The venoms of five adult habu snakes were overwhelmingly dominated by SVMP (32.56 ± 13.94%), PLA2 (22.93 ± 9.26%), and SVSP (16.27 ± 4.79%), with a total abundance of over 65%, while the subadult P. mangshanensis had an extremely low abundance of PLA2 (1.23%) but a high abundance of CTL (51.47%), followed by SVMP (22.06%) and SVSP (10.90%). Apparent interspecific variations in lethality and enzymatic activities were also explored in habu snake venoms, but no variations in myotoxicity were found. Except for SVSP, the resemblance of the relatives within Protobothrops in other venom traits was estimated to deviate from Brownian motion evolution based on phylogenetic signals. A comparative analysis further validated that the degree of covariation between phylogeny and venom variation is evolutionarily labile and varies among clades of closely related snakes. Our findings indicate a high level of interspecific variation in the venom proteomes of habu snakes, both in the presence or absence and the relative abundance of venom protein families, and that these venoms might have evolved under a combination of adaptive and neutral mechanisms.

Extracellular vesicles secreted by Echinococcus multilocularis: important players in angiogenesis promotion.

The involvement of Echinococcus multilocularis, and other parasitic helminths, in regulating host physiology is well recognized, but molecular mechanisms remain unclear. Extracellular vesicles (EVs) released by helminths play important roles in regulating parasite-host interactions by transferring materials to the host. Analysis of protein cargo of EVs from E. multilocularis protoscoleces in the present study revealed a unique composition exclusively associated with vesicle biogenesis. Common proteins in various Echinococcus species were identified, including the classical EVs markers tetraspanins, TSG101 and Alix. Further, unique tegumental antigens were identified which could be exploited as Echinococcus EV markers. Parasite- and host-derived proteins within these EVs are predicted to support important roles in parasite-parasite and parasite-host communication. In addition, the enriched host-derived protein payloads identified in parasite EVs in the present study suggested that they can be involved in focal adhesion and potentially promote angiogenesis. Further, increased angiogenesis was observed in livers of mice infected with E. multilocularis and the expression of several angiogenesis-regulated molecules, including VEGF, MMP9, MCP-1, SDF-1 and serpin E1 were increased. Significantly, EVs released by the E. multilocularis protoscolex promoted proliferation and tube formation by human umbilical vein endothelial cells (HUVECs) in vitro. Taken together, we present the first evidence that tapeworm-secreted EVs may promote angiogenesis in Echinococcus-infections, identifying central mechanisms of Echinococcus-host interactions.

Silencing TUBB3 Expression Destroys the Tegument and Flame Cells of Echinococcus multilocularis Protoscoleces.

Alveolar echinococcosis (AE), caused by infection with the larvae of Echinococcus multilocularis, is a neglected tropical disease and zoonosis that causes remarkable morbidity in humans and has economic importance in the livestock industry worldwide. The growth of this parasite resembles the invasion and proliferation of malignant tumours. Microtubules, especially the ß-tubulin subunit in the exposed end, are the targets of many antitumour drugs. However, the role of TUBB3, which is the most studied isotype in solid tumours and is also a marker of biological aggressiveness associated with the modulation of tumour metastatic abilities in the growth and development of platyhelminths, is unknown. In this study, protoscoleces (PSCs) are cultivated in monophasic medium in vitro. Using electroporated short interfering RNA (siRNA), EmTUBB3 knockdown was performed with two EmTUBB3-specific siRNAs (siRNA-1 and siRNA-2). qRT-PCR was performed to detect the expression of TUBB3. PSCs viability and the evagination rate and number of body contractions were quantified under a light microscope. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to observe the ultra-morphological changes of the parasites. After siRNA interference, the EmTUBB3 expression in E. multilocularis PSCs was significantly reduced. Reduced viability, a decreased evagination rate and a decreased number of body contractions were also documented. In particular, shrinkage and roughness of the tegument were observed. Ultrastructural changes included marked damage to flame cells, cracked cilia structures enclosed in the cell body and ruptured microtubule structures. EmTUBB3 possibly plays a crucial role in tegument and flame cell integrity in E. multilocularis PSCs. Novel drugs targeting this specific beta-tubulin isotype in E. multilocularis are potential methods for disease control and deserve further attention.

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.

Evolutionary History of RNA Modifications at N6-Adenosine Originating from the R-M System in Eukaryotes and Prokaryotes.

Methylation at the N6-position of adenosine (N6mA) on mRNA (m6A) is one of the most widespread, highly selective and dynamically regulated RNA modifications and plays an important role in transcription and translation. In the present study, a comprehensive analysis of phylogenetic relationships, conserved domain sequence characteristics and protein structure comparisons were employed to explore the distribution of RNA N6mA modification (m6A, m6,6A, m6Am, m6, 6Am and m6t6A)-associated proteins (writers, readers and erasers) in three kingdoms of life and reveal the evolutionary history of these modifications. These findings further confirmed that the restriction-modification (R-M) system is the origin of DNA and RNA N6mA modifications. Among them, the existing mRNA m6A modification system derived from the last eukaryotic common ancestor (LECA) is the evolutionary product of elements from the last universal common ancestor (LUCA) or driven by horizontal gene transfer (HGT) from bacterial elements. The subsequent massive gene gains and losses contribute to the development of unique and diverse functions in distinct species. Particularly, RNA methyltransferases (MTases) as the writer responsible for adding N6mA marks on mRNA and ncRNAs may have evolved from class α and ß prokaryotic "orphan" MTases originating from the R-M system. The reader, YTH proteins that specifically recognize the m6A deposit, may be acquired by LECA from an individual prokaryotic YTH-domain protein that evolved from N-terminals of an R-M system endonuclease. The eraser, which emerged from the ALKB family (ALKBH5 and FTO) in eukaryotes, may be driven by independent HTG from bacterial ALKB proteins. The evolutionary history of RNA N6mA modifications was inferred in the present study, which will deepen our understanding of these modifications in different species.

Optimization of an Evaluation Method for Anti-Babesia microti Drug Efficacy.

Babesiosis is an emerging zoonotic disease that is typically caused by Babesia microti infection. Clinical treatment of B. microti infection is challenging; hence, it is crucial to find new effective drugs. The current laboratory screening methods for anti-B. microti drugs are not optimized. We conducted drug-suppressive and drug-therapeutic tests to investigate whether use of an immunosuppressant and the target gene-based qPCR are helpful to reduce the number of animals affected and to improve parasite detection in an immunocompetent mouse model. These results were verified by subpassage test. In the drug-suppressive test, no B. microti were observed after immunosuppressant administration or in subpassage mice in the 100 mg/kg robenidine hydrochloride (ROBH) group. The opposite results were observed in the control, 50 mg/kg ROBH, atovaquone (ATO) + azithromycin (AZM), and proguanil hydrochloride (PGH) groups. Significant differences were observed in the EIR and target gene relative values (both P < 0.001) between the control group and any ROBH groups. In the drug-therapeutic test, recrudescence occurred in the 50 mg/kg ROBH, ATO+AZM, and control groups. This was not observed in the 100 mg/kg ROBH group after immunosuppressant administration. Similar findings were observed in the subpassage test. This suggests that a 4-day anti-B. microti drug-suppressive test can be used in preliminary drug screening. Potentially effective drugs can be verified by immunosuppressant test in subsequent drug-therapeutic tests. Thus, a laboratory evaluation method of anti-B. microti drug efficacy was optimized, which is highly accurate and requires a short drug screening time.

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.

The RNA modification in Echinococcus granulosus cysts revealed by mass spectrometry.

RNA modifications, as one of epigenetic mechanisms, are important and conserved mechanisms for maintaining the homeostasis of organisms. Little is known about RNA modifications in Echinococcus granulosus, an obligate parasite that inhabits mammals and gives rise to a huge public health and economic impact. Here, we focused on the RNA modification characteristics of E. granulosus for the first time by using mass spectrometry (UPLC-MS/MS) to qualitatively and quantitatively analyze 47 types of RNA modifications in E. granulosus total RNA. Furthermore, the E. granulosus homologs of writer enzymes preforming RNA modifications were identified, and their gene expression pattern at different developmental stages were analyzed by bioinformatics analysis. Finally, 23 types of RNA modifications were found in E. granulosus cysts total RNA, of which m1A, Ψ and m5C are the most abundant. The homologs of writer enzymes involved in these modifications were identified in the E. granulosus genome, with the dynamic gene expression during the different parasitic developmental stages. This work confirms that E. granulosus retains the conserved RNA modification mechanism during evolution, suggesting the important role of RNA modification in regulating its development and parasitic process. Moreover, the differences of amino acid sequences of RNA modification writer enzymes between parasite and host make it possible to use these enzymes as the candidate drug targets in the follow-up in-depth researches.

Glycogen Phosphorylase: A Drug Target of Amino Alcohols in Echinococcus granulosus, Predicted by a Computer-Aided Method.

Echinococcosis is an important parasitic disease that threats human health and animal husbandry worldwide. However, the low cure rate of clinical drugs for this disease is a challenge. Hence, novel compounds and specific drug targets are urgently needed. In this study, we identified drug targets of amino alcohols with effects on Echinococcus species. The drug targets were predicted with the idTarget web server. Corresponding three-dimensional structures of the drug targets were built after sequence BLAST analysis and homology modeling. After further screening by molecular docking, the activities of the candidate targets were validated in vitro. We ultimately identified glycogen phosphorylase as a potential drug target for amino alcohols. There are two genes coding glycogen phosphorylase in Echinococcus granulosus (EgGp1 and EgGp2). EgGp1 was abundant in E. granulosus PSCs, while EgGp2 was abundant in the cysts. These proteins were located at suckers and somas of E. granulosus PSCs and near the rostellum of cysts developed from PSCs. The effective compounds docked into a pocket consisting of E124, K543 and K654 and affected (either inhibited or enhanced) the activity of E. granulosus glycogen phosphorylase. In this study, we designed a method to predict drug targets for echinococcosis treatment based on inverse docking. The candidate targets found by this method can contribute not only to understanding of the modes of action of amino alcohols but also to modeling-aided drug design based on targets.

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.

Contributions and achievements on schistosomiasis control and elimination in China by NIPD-CTDR.

Being a zoonotic parasitic disease, schistosomiasis was widely spread in 12 provinces of Southern China in the 1950s, severly harming human health and hindering economic development. The National Institute of Parasitic Diseases at the Chinese Center for Diseases Control and Prevention, and Chinese Center for Tropical Diseases Research (NIPD-CTDR), as the only professional institution focussing on parasitic diseases at the national level, has played an important role in schistosomiasis control in the country. In this article, we look back at the changes of schistosomiasis endemicity and the contribution of NIPD-CTDR to the national schistosomiasis control programme. We review NIPD-CTDR's activities, including field investigations, design of control strategies and measures, development of diagnostics and drugs, surveillance-response of endemic situation, and monitoring & evaluation of the programme. The NIPD-CTDR has mastered the transmission status of schistosomiasis, mapped the snail distribution, and explored strategies and measures suitable for different types of endemic areas in China. With a good understanding of the life cycle of Schistosoma japonicum and transmission patterns of the disease, advanced research carried out in the NIPD-CTDR based on genomics and modern technology has made it possible to explore highly efficient and soft therapeutic drugs and molluscicides, making it possible to develop new diagnostic tools and produce vaccine candidates. In the field, epidemiological studies, updated strategies and targeted intervention measures developed by scientists from the NIPD-CTDR have contributed significantly to the national schistosomiasis control programme. This all adds up to a strong foundation for eliminating schistosomiasis in China in the near future, and recommendations have been put forward how to reach this goal.

Contribution to the echinococcosis control programme in China by NIPD-CTDR.

As a zoonotic parasitosis caused by the parasitism of Echinococcus larvae, echinococcosis imposes serious disease and economic burdens on human beings and society, and is thus a global public health issue. Its complex life history, wide distribution, the combined influence of various epidemic factors, coupled with the unique natural environment, customs, and religious beliefs in endemic areas, pose a huge challenge to the national echinococcosis control programme in China. Accurate early detection and confirmation of diagnosis of echinococcosis, the use of effective drugs, real-time surveillance of the infection status of populations and various hosts, controlling the source of infection, and blocking the route of transmission are of enormous significance for control. In this paper, the work by NIPD-CTDR on the prevention and control of echinococcosis in China is reviewed, with a view to providing reference for the further promotion of the national echinococcosis control programme.

Pharmacophore-Based Virtual Screening Toward the Discovery of Novel Anti-echinococcal Compounds.

Echinococcosis is a serious helminthic zoonosis with a great impact on human health and livestock husbandry. However, the clinically used drugs (benzimidazoles) have a low cure rate, so alternative drugs are urgently needed. Currently, drug screenings for echinococcosis are mainly phenotype-based, and the efficiency of identifying active compounds is very low. With a pharmacophore model generated from the structures of active amino alcohols, we performed a virtual screening to discover novel compounds with anti-echinococcal activity. Sixty-two compounds from the virtual screening were tested on Echinococcus multilocularis protoscoleces, and 10 of these compounds were found to be active. After further evaluation of their cytotoxicity, S6 was selected along with two active amino alcohols for in vivo pharmacodynamic and pharmacokinetic studies. At the two tested doses (50 and 25 mg/kg), S6 inhibited the growth of E. multilocularis in mice (14.43 and 9.53%), but no significant difference between the treatment groups and control group was observed. Treatment with BTB4 and HT3 was shown to be ineffective. During the 28 days of treatment, the death of mice in the mebendazole, HT3, and BTB4 groups indicated their toxicity. The plasma concentration of S6 administered by both methods was very low, with the Cmax being only 1 ng/ml after oral administration and below the detection limit after intramuscular administration. In addition, the plasma concentrations of BTB4 and HT3 in vitro did not reach high enough levels to kill the parasites. The toxicities of these two amino alcohols indicated that they are not suitable for further development as anti-echinococcal drugs. However, further attempts should be made to increase the bioavailability of S6 and modify its structure. In this study, we demonstrate that pharmacophore-based virtual screenings with high drug identification efficiency could be used to find novel drugs for treating echinococcosis.

NiSe2/Ni(OH)2 Heterojunction Composite through Epitaxial-like Strategy as High-Rate Battery-Type Electrode Material.

Constructing heterojunction is a promising way to improve the charge transfer efficiency and can thus promote the electrochemical properties. Herein, a facile and effective epitaxial-like growth strategy is applied to NiSe2 nano-octahedra to fabricate the NiSe2-(100)/Ni(OH)2-(110) heterojunction. The heterojunction composite and Ni(OH)2 (performing high electrochemical activity) is ideal high-rate battery-type supercapacitor electrode. The NiSe2/Ni(OH)2 electrode exhibits a high specific capacity of 909 C g-1 at 1 A g-1 and 597 C g-1 at 20 A g-1. The assembled asymmetric supercapacitor composed of the NiSe2/Ni(OH)2 cathode and p-phenylenediamine-functional reduced graphene oxide anode achieves an ultrahigh specific capacity of 303 C g-1 at 1 A g-1 and a superior energy density of 76.1 Wh kg-1 at 906 W kg-1, as well as an outstanding cycling stability of 82% retention for 8000 cycles at 10 A g-1. To the best of our knowledge, this is the first example of NiSe2/Ni(OH)2 heterojunction exhibiting such remarkable supercapacitor performance. This work not only provides a promising candidate for next-generation energy storage device but also offers a possible universal strategy to fabricate metal selenides/metal hydroxides heterojunctions.

"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 .