Evodiamine Induces Transient Receptor Potential Vanilloid-1-Mediated Protective Autophagy in U87-MG Astrocytes

Cerebral ischemia is a leading cause of mortality and morbidity worldwide, which results in cognitive and motor dysfunction, neurodegenerative diseases, and death. Evodiamine (Evo) is extracted from Evodia rutaecarpa Bentham, a plant widely used in Chinese herbal medicine, which possesses variable biological abilities, such as anticancer, anti-inflammation, antiobesity, anti-Alzheimer’s disease, antimetastatic, antianoxic, and antinociceptive functions. But the effect of Evo on ischemic stroke is unclear. Increasing data suggest that activation of autophagy, an adaptive response to environmental stresses, could protect neurons from ischemia-induced cell death. In this study, we found that Evo induced autophagy in U87-MG astrocytes. A scavenger of extracellular calcium and an antagonist of transient receptor potential vanilloid-1 (TRPV-1) decreased the percentage of autophagy accompanied by an increase in apoptosis, suggesting that Evo may induce calcium-mediated protective autophagy resulting from an influx of extracellular calcium. The same phenomena were also confirmed by a small interfering RNA technique to knock down the expression of TRPV1. Finally, Evo-induced c-Jun N-terminal kinases (JNK) activation was reduced by a TRPV1 antagonist, indicating that Evo-induced autophagy may occur through a calcium/c-Jun N-terminal kinase (JNK) pathway. Collectively, Evo induced an influx of extracellular calcium, which led to JNK-mediated protective autophagy, and this provides a new option for ischemic stroke treatment

QGP flow fluctuations and the characteristics of higher moments

The dynamical development of expanding Quark-gluon Plasma (QGP) flow is studied in a 3+1D fluid dynamical model with a globally symmetric, initial condition. We minimize fluctuations arising from complex dynamical processes at finite impact parameters and from fluctuating random initial conditions to have a conservative fluid dynamical background estimate for the statistical distributions of the thermodynamical parameters. We also avoid a phase transition in the equation of state, and we let the matter supercool during the expansion. Then central Pb+Pb collisions at $\sqrt{s_{NN}} = 2.76$ TeV are studied in an almost perfect fluid dynamical model, with azimuthally symmetric initial state generated in a dynamical flux-tube model. The general development of thermodynamical extensives are also shown for lower energies. We observe considerable deviations from a thermal equilibrium source as a consequence of the fluid dynamical expansion arising from a least fluctuating initial state

Lattice Boltzmann simulation of alumina-water nanofluid in a square cavity

A lattice Boltzmann model is developed by coupling the density (D2Q9) and the temperature distribution functions with 9-speed to simulate the convection heat transfer utilizing Al2O3-water nanofluids in a square cavity. This model is validated by comparing numerical simulation and experimental results over a wide range of Rayleigh numbers. Numerical results show a satisfactory agreement between them. The effects of Rayleigh number and nanoparticle volume fraction on natural convection heat transfer of nanofluid are investigated in this study. Numerical results indicate that the flow and heat transfer characteristics of Al2O3-water nanofluid in the square cavity are more sensitive to viscosity than to thermal conductivity

Anodization of nanoporous alumina on impurity-induced hemisphere curved surface of aluminum at room temperature

Nanoporous alumina which was produced by a conventional direct current anodization [DCA] process at low temperatures has received much attention in various applications such as nanomaterial synthesis, sensors, and photonics. In this article, we employed a newly developed hybrid pulse anodization [HPA] method to fabricate the nanoporous alumina on a flat and curved surface of an aluminum [Al] foil at room temperature [RT]. We fabricate the nanopores to grow on a hemisphere curved surface and characterize their behavior along the normal vectors of the hemisphere curve. In a conventional DCA approach, the structures of branched nanopores were grown on a photolithography-and-etched low-curvature curved surface with large interpore distances. However, a high-curvature hemisphere curved surface can be obtained by the HPA technique. Such a curved surface by HPA is intrinsically induced by the high-resistivity impurities in the aluminum foil and leads to branching and bending of nanopore growth via the electric field mechanism rather than the interpore distance in conventional approaches. It is noted that by the HPA technique, the Joule heat during the RT process has been significantly suppressed globally on the material, and nanopores have been grown along the normal vectors of a hemisphere curve. The curvature is much larger than that in other literatures due to different fabrication methods. In theory, the number of nanopores on the hemisphere surface is two times of the conventional flat plane, which is potentially useful for photocatalyst or other applications

The Rat IgGFcγBP and Muc2 C-Terminal Domains and TFF3 in Two Intestinal Mucus Layers Bind Together by Covalent Interaction

The secreted proteins from goblet cells compose the intestinal mucus. The aims of this study were to determine how they exist in two intestinal mucus layers.The intestinal mucosa was fixed with Carnoy solution and immunostained. Mucus from the loose layer, the firm layer was gently suctioned or scraped, respectively, lysed in SDS sample buffer with or without DTT, then subjected to the western blotting of rTFF3, rIgGFcγBP or rMuc2. The non-reduced or reduced soluble mucus samples in RIPA buffer were co-immunoprecipitated to investigate their possible interactions. Polyclonal antibodies for rTFF3, the rIgGFcγBP C-terminal domain and the rMuc2 C-terminal domain confirmed their localization in the mucus layer and in the mucus collected from the rat intestinal loose layer or firm layer in both western blot and immunoprecipitation experiments. A complex of rTFF3, which was approximately 250 kDa, and a monomer of 6 kDa were present in both layers of the intestinal mucus; rIgGFcγBP was present in the complex (250-280 kDa) under non-reducing conditions, but shifted to 164 kDa under reducing conditions in both of the layers. rMuc2 was found mainly in a complex of 214-270 kDa under non-reducing conditions, but it shifted to 140 kDa under reducing conditions. The co-immunoprecipitation experiments showed that binding occurs among rTFF3, rIgGFcγBP and rMuc2 in the RIPA buffer soluble intestinal mucus. Blocking the covalent interaction by 100 mM DTT in the RIPA buffer soluble intestinal mucus disassociated their binding.Rat goblet cell-secreted TFF3, IgGFcγBP and Muc2, existing in the two intestinal mucus layers, are bound together by covalent interactions in the soluble fraction of intestinal mucus and form heteropolymers to be one of the biochemical mechanisms of composing the net-like structure of mucus

A strategy for emergency treatment of Schistosoma japonicum-infested water

<p>Abstract</p> <p>Background</p> <p>Schistosomiasis japonica, caused by contact with <it>Schistosoma japonicum </it>cercaria-infested water when washing, bathing or production, remains a major public-health concern in China. The purpose of the present study was to investigate the effect of a suspension concentrate of niclosamide (SCN) on killing cercaria of <it>S. japonicum </it>that float on the water surface, and its toxicity to fish, so as to establish an emergency-treatment intervention for rapidly killing cercaria and eliminating water infectivity.</p> <p>Results</p> <p>At 30 min after spraying 100 mg/L SCN, with niclosamide dosages of 0.01, 0.02, 0.03, 0.04 g/m², the water infectivity reduced significantly and no infectivity was found at 60 min after spraying SCN. The surface of static water was sprayed with 100 mg/L SCN, the peak concentration was found at 0 min, and the solution diffused to site with a water depth of 10 cm after 10 min. 30 min later, SCN diffused to the whole water body, and distributed evenly. After spraying 100 mg/L SCN onto the surface of the water with a volume of(3.14 × 20²×50)cm³, with niclosamide dosages of 0.02 g/m², 96 h later, no death of zebra fish was observed.</p> <p>Conclusions</p> <p>By spraying 100 mg/L SCN, with a niclosamide dosage of 0.02 g/m²onto the surface of <it>S. japonicum</it>-infested water, infectivity of the water can be eliminated after 30-60 min, and there is no evident toxicity to fish. This cercaria-killing method, as an emergency-treatment intervention for infested water, can be applied in those forecasting and early warning systems for schistosomiasis.</p

Compensatory density feedback of Oncomelania hupensis populations in two different environmental settings in China

BACKGROUND: The most recent strategy for schistosomiasis control in the People's Republic of China aims to reduce the likelihood of environmental contamination of schistosome eggs. Despite considerable progress, it is believed that achievements would be further consolidated with additional intermediate host snail control measures. We provide an empirical framework for discerning the relative contribution of intrinsic effects (density feedback) from other extrinsic drivers of snail population dynamics. METHODS: We set up experiments in two study locations to collect reproduction data of Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum. We applied a set of four population dynamic models that have been widely used to study phenomenological time-series data to examine the properties of demographic density feedback patterns from abundance data. We also contrasted the obtained results with the component feedback of density on survival rate to determine whether adult survival was the principal driver of the demographic feedback observed. RESULTS: Demographic density feedback models (Ricker- and Gompertz-logistic) accounted for <99% of Akaike's information criterion model weight, with the Gompertz ranking highest in all O. hupensis population groups. We found some evidence for stronger compensatory feedback in the O. hupensis population from Sichuan compared to a Jiangsu population. Survival rates revealed strong component feedback, but the log-linear relationships (i.e. Gompertz) had less support in the demographic feedback analysis. CONCLUSIONS: Our findings indicate that integrated schistosomiasis control measures must continue to reduce parasite abundance further because intermediate host snail populations tend to grow exponentially at low densities, especially O. hupensis populations in mountainous regions. We conclude that density feedback in adult survival is the principal component contribution to the demographic phenomenon observed in the population fitness (r)-abundance relationship

Adjunctive raloxifene treatment improves attention and memory in men and women with schizophrenia

There is increasing clinical and molecular evidence for the role of hormones and specifically estrogen and its receptor in schizophrenia. A selective estrogen receptor modulator, raloxifene, stimulates estrogen-like activity in brain and can improve cognition in older adults. The present study tested the extent to which adjunctive raloxifene treatment improved cognition and reduced symptoms in young to middle-age men and women with schizophrenia. Ninety-eight patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited into a dual-site, thirteen-week, randomized, double-blind, placebocontrolled, crossover trial of adjunctive raloxifene treatment in addition to their usual antipsychotic medications. Symptom severity and cognition in the domains of working memory, attention/processing speed, language and verbal memory were assessed at baseline, 6 and 13 weeks. Analyses of the initial 6-week phase of the study using a parallel groups design (with 39 patients receiving placebo and 40 receiving raloxifene) revealed that participants receiving adjunctive raloxifene treatment showed significant improvement relative to placebo in memory and attention/processing speed. There was no reduction in symptom severity with treatment compared with placebo. There were significant carryover effects, suggesting some cognitive benefits are sustained even after raloxifene withdrawal. Analysis of the 13-week crossover data revealed significant improvement with raloxifene only in attention/processing speed. This is the first study to show that daily, oral adjunctive raloxifene treatment at 120 mg per day has beneficial effects on attention/processing speed and memory for both men and women with schizophrenia. Thus, raloxifene may be useful as an adjunctive treatment for cognitive deficits associated with schizophrenia.TW Weickert, D Weinberg, R Lenroot, SV Catts, R Wells, A Vercammen, M O, Donnell, C Galletly, D Liu, R Balzan, B Short, D Pellen, J Curtis, VJ Carr, J Kulkarni, PR Schofield and CS Weicker