Human alveolar echinococcosis is a hard-to-treat and largely untreated parasitic disease with high associated health care costs. The current antiparasitic treatment for alveolar echinococcosis relies exclusively on albendazole, which does not act parasiticidally and can induce severe adverse effects. Alternative, and most importantly, improved treatment options are urgently required. A drug repurposing strategy identified the approved antimalarial pyronaridine as a promising candidate against Echinococcus multilocularis infections. Following a 30-day oral regimen (80 mg kg−1 day−1), pyronaridine achieved an excellent therapeutic outcome in a clinically relevant hepatic alveolar echinococcosis murine model, showing a significant reduction in both metacestode size (72.0%) and counts (85.2%) compared to unmedicated infected mice, which revealed significantly more potent anti-echinococcal potency than albendazole treatment at an equal dose (metacestode size: 42.3%; counts: 4.1%). The strong parasiticidal activity of pyronaridine was further confirmed by the destructive damage to metacestode tissues observed morphologically. In addition, a screening campaign combined with computational similarity searching against an approved drug library led to the identification of pirenzepine, a gastric acid-inhibiting drug, exhibiting potent parasiticidal activity against protoscoleces and in vitro cultured small cysts, which warranted further in vivo investigation as a promising anti-echinococcal lead compound. Pyronaridine has a known drug profile and a long track record of safety, and its repurposing could translate rapidly to clinical use for human patients with alveolar echinococcosis as an alternative or salvage treatment.

Fast neutron absorption spectroscopy is widely used in the study of nuclear structure and element analysis. However, due to the traditional neutron source pulse duration being of the order of nanoseconds, it is difficult to obtain a high-resolution absorption spectrum. Thus, we present a method of ultrahigh energy-resolution absorption spectroscopy via a high repetition rate, picosecond duration pulsed neutron source driven by a terawatt laser. The technology of single neutron count is used, which results in easily distinguishing the width of approximately 20 keV at 2 MeV and an asymmetric shape of the neutron absorption peak. The absorption spectroscopy based on a laser neutron source has one order of magnitude higher energy-resolution power than the state-of-the-art traditional neutron sources, which could be of benefit for precisely measuring nuclear structure data.

Gripper is one of the most important parts of robot because of contacting with workpieces directly and has attracted lots of research interests. However, the existing grippers are either simple in function or complex in structure. In this paper, we will propose a one-DOF gripper based on a compliant mechanism with four identical twofold-symmetric Bricard linkages. A mobile network with four identical twofold-symmetric Bricard linkages with particular design parameters is constructed at first. Kinematics, such as mobility, singularity, and folding performance, is then analyzed to show the potential of realizing the function of grasping. The result is demonstrated with a physical prototype. To simplify the fabricating process, a compliant mechanism of the network is designed and fabricated with a single polypropylene board, and the grasping function is realized by a cable-driven scheme. Some grasping experiments are carried out on different types of objects which shows that the proposed and fabricated four-figure gripper is simple in structure and has a great grasping function. The work provides a new idea for the design of grippers with low cost, simple structure, and rich functions.

The subduction model of the Neo-Tethys during the Early Cretaceous has always been a controversial topic, and the scarcity of Early Cretaceous magmatic rocks in the southern part of the Gangdese batholith is the main cause of this debate. To address this issue, this article presents new zircon U–Pb chronology, zircon Hf isotope, whole-rock geochemistry and Sr–Nd isotope data for the Early Cretaceous quartz diorite dykes with adakite affinity in Liuqiong, Gongga. Zircon U–Pb dating of three samples yielded ages of c. 141–137 Ma, indicating that the Liuqiong quartz diorite was emplaced in the Early Cretaceous. The whole-rock geochemical analysis shows that the Liuqiong quartz diorite is enriched in large-ion lithophile elements (LILEs) and light rare-earth elements (LREEs) and is depleted in high-field-strength elements (HFSEs), which are related to slab subduction. Additionally, the Liuqiong quartz diorite has high SiO2, Al2O3 and Sr contents, high Sr/Y ratios and low heavy rare-earth element (HREE) and Y contents, which are compatible with typical adakite signatures. The initial 87Sr/86Sr values of the Liuqiong adakite range from 0.705617 to 0.705853, and the whole-rock ϵNd(t) values vary between +5.78 and +6.24. The zircon ϵHf(t) values vary from +11.5 to +16.4. Our results show that the Liuqiong adakite magma was derived from partial melting of the Neo-Tethyan oceanic plate (mid-ocean ridge basalt (MORB) + sediment + fluid), with some degree of subsequent peridotite interaction within the overlying mantle wedge. Combining regional data, we favour the interpretation that the Neo-Tethyan oceanic crust was subducted at a low angle beneath the Gangdese during the Early Cretaceous.

The quantum defect (QD) is an important issue that demands prompt attention in high-power fiber lasers. A large QD may aggravate the thermal load in the laser, which would impact the frequency, amplitude noise and mode stability, and threaten the security of the high-power laser system. Here, we propose and demonstrate a cladding-pumped Raman fiber laser (RFL) with QD of less than 1%. Using the Raman gain of the boson peak in a phosphorus-doped fiber to enable the cladding pump, the QD is reduced to as low as 0.78% with a 23.7 W output power. To our knowledge, this is the lowest QD ever reported in a cladding-pumped RFL. Furthermore, the output power can be scaled to 47.7 W with a QD of 1.29%. This work not only offers a preliminary platform for the realization of high-power low-QD fiber lasers, but also proves the great potential of low-QD fiber lasers in power scaling.

We present an experimental study on controlling the number of vortices and the torque in a Taylor–Couette flow of water for Reynolds numbers from 660 to 1320. Different flow states are achieved in the annulus of width $d$ between the inner rotating and outer stationary cylinders through manipulating the initial height of the water annulus. We show that the torque exerted on the inner cylinder of the Taylor–Couette system can be reduced by up to 20 % by controlling the flow at a state where fewer than the nominal number of vortices develop between the cylinders. This flow state is achieved by starting the system with an initial water annulus height $h_0$ (which nominally corresponds to $h_0/d$ vortices), then gradually adding water into the annulus while the inner cylinder keeps rotating. During this filling process the flow topology is so persistent that the number of vortices does not increase; instead, the vortices are greatly stretched in the axial (vertical) direction. We show that this state with stretched vortices is sustainable until the vortices are stretched to around 2.05 times their nominal size. Our experiments reveal that by manipulating the initial height of the liquid annulus we are able to generate different flow states and demonstrate how the different flow states manifest themselves in global momentum transport.

Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.

Underground Nuclear Astrophysics in China (JUNA) will take the advantage of the ultra-low background in Jinping underground lab. High current accelerator with an ECR source and detectors were commissioned. JUNA plans to study directly a number of nuclear reactions important to hydrostatic stellar evolution at their relevant stellar energies. At the first period, JUNA aims at the direct measurements of 25Mg(p,γ)26 Al, 19F(p,α) 16 O, 13C(α, n) 16O and 12C(α,γ) 16O near the Gamow window. The current progress of JUNA will be given.

This study aimed to investigate the impacts of dietary threonine on intestinal immunity and inflammation in juvenile grass carp. Six iso-nitrogenous semi-purified diets containing graded levels of threonine (3·99–21·66 g threonine/kg) were formulated and fed to fishes for 8 weeks, and then challenged with Aeromonas hydrophila for 14 d. Results showed that, compared with optimum threonine supplementation, threonine deficiency (1) decreased the ability of fish against enteritis, intestinal lysozyme activities (except in the distal intestine), acid phosphatase activities, complement 3 (C3) and C4 contents and IgM contents (except in the proximal intestine (PI)), and it down-regulated the transcript abundances of liver-expressed antimicrobial peptide (LEAP)-2A, LEAP-2B, hepcidin, IgZ, IgM and β-defensin1 (except in the PI) (P<0·05); (2) could up-regulate intestinal pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-8 and IL-17D mRNA levels partly related to NF-κB signalling; (3) could down-regulate intestinal anti-inflammatory cytokine transforming growth factor (TGF)-β1, TGF-β2, IL-4/13A (not IL-4/13B) and IL-10 mRNA levels partly by target of rapamycin signalling. Finally, on the basis of the specific growth rate, against the enteritis morbidity and IgM contents, the optimum threonine requirements were estimated to be 14·53 g threonine/kg diet (4·48 g threonine/100 g protein), 15.05 g threonine/kg diet (4·64 g threonine/100 g protein) and 15·17 g threonine/kg diet (4·68 g threonine/100 g protein), respectively.

The present study evaluated the effects of dietary microbial phytase on the growth and gut health of hybrid tilapia (Oreochromis niloticus ♀×Oreochromis aureus ♂), focusing on the effect on intestinal histology, adhesive microbiota and expression of immune-related cytokine genes. Tilapia were fed either control diet or diet supplemented with microbial phytase (1000 U/kg). Each diet was randomly assigned to four groups of fish reared in cages (3×3×2 m). After 12 weeks of feeding, weight gain and feed conversion ratio of tilapia were not significantly improved by dietary microbial phytase supplementation. However, significantly higher level of P content in the scales, tighter and more regular intestinal mucosa folds were observed in the microbial phytase group and the microvilli density was significantly increased. The adhesive gut bacterial communities were strikingly altered by microbial phytase supplementation (0·41<similarity coefficient<0·54). Stimulated intestinal inflammation and stress status were observed in the fish fed diet supplemented with microbial phytase, as indicated by the up-regulated intestinal expressions of the cytokine genes (tnf-α and tgf-β) and hsp70. In addition, the gut microvilli height was significantly decreased in the phytase group. These results indicate that dietary microbial phytase may exert mixed effects on hybrid tilapia, and can guide our future selection of phytases as aquafeed additives – that is, eliminating those that can stimulate intestinal inflammation.

The unified lattice Boltzmann model is extended to the quadtree grids for simulation of fluid flow through porous media. The unified lattice Boltzmann model is capable of simulating flow in porous media at various scales or in systems where multiple length scales coexist. The quadtree grid is able to provide a high-resolution approximation to complex geometries, with great flexibility to control local grid density. The combination of the unified lattice Boltzmann model and the quadtree grids results in an efficient numerical model for calculating permeability of multi-scale porous media. The model is used for permeability calculation for three systems, including a fractured system used in a previous study, a Voronoi tessellation system, and a computationally-generated pore structure of fractured shale. The results are compared with those obtained using the conventional lattice Boltzmann model or the unified lattice Boltzmann model on rectangular or uniform square grid. It is shown that the proposed model is an accurate and efficient tool for flow simulation in multi-scale porous media. In addition, for the fractured shale, the contribution of flow in matrix and fractures to the overall permeability of the fractured shale is studied systematically.

This study investigated the effects of glycinin on the growth, intestinal oxidative status, tight junction components, cytokines and apoptosis signalling factors of fish. The results showed that an 80 g/kg diet of glycinin exposure for 42 d caused poor growth performance and depressed intestinal growth and function of juvenile Jian carp (Cyprinus carpio var. Jian). Meanwhile, dietary glycinin exposure induced increases in lipid peroxidation and protein oxidation; it caused reductions in superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities; and it increased MnSOD, CuZnSOD, GPx1b and GPx4a mRNA levels, suggesting an adaptive mechanism against stress in the intestines of fish. However, dietary glycinin exposure decreased both the activity and mRNA levels of nine isoforms of glutathione-S-transferase (GST) (α, μ, π, ρ, θ, κ, mGST1, mGST2 and mGST3), indicating toxicity to this enzyme activity and corresponding isoform gene expressions. In addition, glycinin exposure caused partial disruption of intestinal cell–cell tight junction components, disturbances of cytokines and induced apoptosis signalling in the distal intestines>mid intestines>proximal intestines of fish. Glycinin exposure also disturbed the mRNA levels of intestinal-related signalling factors Nrf2, Keap1a, Keap1b, eleven isoforms of protein kinase C and target of rapamycin/4E-BP. Interestingly, glutamine was observed to partially block those negative influences. In conclusion, this study indicates that dietary glycinin exposure causes intestinal oxidative damage and disruption of intestinal physical barriers and functions and reduces fish growth, but glutamine can reverse those negative effects in fish. This study provides some information on the mechanism of glycinin-induced negative effects.

Large container ships can only be berthed in hub ports with deep water, which requires a feeder ship service to transit and transport containers from the hub ports. This paper presents a feeder routing optimisation method for container ships through an intelligent Electronic Chart Display and Information System (ECDIS). ECDIS has been adopted to design routes and calculate the estimated time of arrival in two ports, and a mixed integer programming model is established for container vessel regional transportation where the shortest ship sailing time is designated as the objective function. In this paper, through using heuristic tour-route coding, the solution of the model based on genetic algorithms is presented to select ship capacities and routes simultaneously. Taking the Pearl River in China as an example, for different types of vessel capacity, vessel costs and fuel costs, 100 TEU and 150 TEU ship capacities with six optimal routes are selected to minimise sailing time and operating costs.

In 2008 January the 24th Chinese expedition team successfully deployed the Chinese Small Telescope ARray (CSTAR) to Dome A, the highest point on the Antarctic plateau. CSTAR consists of four 14.5cm optical telescopes, each with a different filter (g, r, i and open) and has a 4.5°×4.5° field of view (FOV). Based on the CSTAR data, initial statistics of astronomical observational site quality and light curves of variable objects were obtained. To reach higher photometric quality, we are continuing to work to overcome the effects of uneven cirrus cloud cirrus, optical “ghosts” and intra-pixel sensitivity. The snow surface stability is also tested for further astronomical observational instrument and for glaciology studies.

This paper provides a brief outline of the current, detailed inter-disciplinary work on the Xiaoyangquiao section, trying to expose all the aspects for reference tied to the Global Single Stratigraphic Point (GSSP) Concept for defining the Cambrian–Ordovician Boundary. The 45 m critical interval of this section outcrops very well along the steep bank of a stream and is free from folding, faulting, intrusions, and has not been affected by weathering. Colour alternation of conodonts and acritarchs, and crystallinity indices of illite all indicate a maximum thermal grade of 100 °C. The lithofacies, being of great lateral persistence for a hundred kilometres, consists mainly of a rhythmical sequence of lime mudstone and shales deposited in a moderately deep outer shelf environment of quiet water, well below the normal storm wave base. Chemical investigation of the rocks demonstrates strong positive correlation between A12O3 content and those of K2O, MgO, Fe2O3, TiO2, Be, Cr, Co, Ni, Zn and Ba, indicating these components are tied to the clay fractions. A stable depositional environment is demonstrated by the uniform chemistries through the boundary interval. Close to the boundary itself P2O5 contents are low, indicating continuous sedimentation at fairly substantial rates.

The major biological events, the biostratigraphic framework, and the stratigraphic range of conodont, graptolite, trilobite, and acritarch taxa are illustrated briefly with diagrams. Following the majority views of the Calgary Plenary Session, the boundary level is to be chosen at a point marked by the First Appearance Datum (FAD) of the selected conodont taxon or taxa in the vicinity of the level close to, but below, the first influx of nematophorous graptolites. The following four points marked by the incoming of conodont taxon or taxa are recommended for consideration of the ‘Golden Spike'‘: (1) FAD of Cordylodus intermedius at 5.28 m below the first influx of nematophorous graptolites; (2) FAD of Hirsutodontus simpler–Cordylodus drucei–Albiconus postcostatus at 5.23 m; (3) FAD of Semiacontiodus lavadamensis–Utahconus utahensis–Monocostodus sevierensis at 3.85 m; (4) FAD of Cordylodus lindstromi at 2.23 m. For the following reasons the FAD of H. simplex–C. drucei–A. postcostatus is favoured: (1) the taxa are all distinct and widely dispersed; (2) intensive evolutionary change took place in conodonts, graptolites, trilobites and acritarchs prior to or after this point; all the fossil groups occur together, providing correlation with many regions throughout the world; (3) the point is in a position between the previously widely accepted boundary levels based on graptolites and trilobites; (4) the proposed point lies within a thin, laterally persistent, rhythmical sequence. The FAD of Cordylodus lindstromi is also a favourable point, sharing many advantages mentioned above. But this point is less satisfactory in being defined by the FAD of a single taxon C. lindstromi which also has an extremely small population size.

An isochron age of 500.7 ± 7.4 Ma is determined from clay fractions of mudstones 8.5 m below the proposed point by means of the Rubidium–Strontium method.

The ɛND signature determined from conodonts, trilobites hyolithids and acrotretid brachiopods has a mean value of −6.7, comparable with that of the coeval oceanic water mass occupying southeastern North America and Europe, and indicating that northeastern China bordered the same ocean. The mean Tdm model age determined was 1.26 Ga at the time of sedimentation, compatible with the mean Tdm model age of approximately 1.1 Ga for the Pacific Ocean today. The relatively low value of the Tdm model age indicates a substantial input from young orogenic volcanic island arcs and terranes.

A rapid real-time polymerase chain reaction (RT-PCR) for detecting West Nile virus (WNV) was established. Primers were designed according to the sequence of the capsid protein gene of WNV by Primer Premier 5.0. In this way, an inexpensive assay using the intercalating dye SYBR Green I was developed and validated. The amplifying curve showed that this method could successfully amplify 102 copies/μl of the WNV gene, while reference to Japanese encephalitis virus (JEV) and blank control were all negative. Tenfold successive dilutions of positive WNV DNA were used to measure the sensitivity of RT-PCR. The assay system showed high reproducibility with coefficient of variation (CV) <2%. Thus the newly established RT-PCR assay was shown to be a rapid, sensitive and specific test for detecting WNV.

Many isothiocyanates (ITC), which are available to human subjects mainly through consumption of cruciferous vegetables, demonstrate strong cancer-preventive activity in animal models. Human studies also show an inverse association between consumption of ITC and risk of cancer in several organs. Whereas earlier studies primarily focused on the ability of ITC to inhibit carcinogen-activating enzymes and induce carcinogen-detoxifying enzymes, more recent investigations have shown that ITC inhibit the proliferation of tumour cells both in vitro and in vivo by inducing apoptosis and arresting cell cycle progression. ITC cause acute cellular stress, which may be the initiating event for these effects. These findings shed new light on the mechanism of action of ITC and indicate that ITC may be useful both as cancer-preventive and therapeutic agents. ITC activate caspase 9-mediated apoptosis, apparently resulting from mitochondrial damage, and also activate caspase 8, but the mechanism remains to be defined. Cell cycle arrest caused by ITC occurs mainly in the G2/M phase, and both the G2 and M phases are targetted; critical G2-phase regulators, including cyclin B1, cell division cycle (Cdc) 2 and Cdc25C, are down regulated or inhibited, and tubulin polymerization and spindle assembly are disrupted. Moreover, ITC are metabolized in vivo through the mercapturic acid pathway, giving rise to thiol conjugates (dithiocarbamates). Studies show that these dithiocarbamates are similar to their parent ITC in exerting anti-proliferative activity. Taken together, dietary ITC are highly-promising anti-cancer agents, capable of targetting multiple cellular components that are important for tumour cell survival and proliferation.

The RNA-dependent RNA polymerase (RdRp) gene of Bombyx mori cypovirus 1 (BmCPV-1) (China strain) was cloned in three fragments using step-by-step reverse transcriptase-polymerase chain reaction (RT-PCR). The whole RdRp gene of 3691 bp was sequenced (GenBank accession number: AY496445). Vector pET-28b(+) was used to construct the expression vector pET28b–RdRp which was expressed in Escherichia coli BL21 (DE3) induced with isopropyl β-d-thiogalactoside (IPTG). The molecular weight of the expression product was about 138 Da. The primary antibody employed was rabbit antibody against BmCPV–RdRp recombinant protein and the secondary antibody was 15 nm immunogold-labelled goat anti-rabbit IgG. Immunogold was mostly bound to the virions which were dispersed in a virus generation matrix and polyhedron in the columnar cells of the midgut of the silkworms, and the average marking ratio was about 35%. This result demonstrated that BmCPV–RdRp complexes are indeed located at the BmCPV capsid.