High-Resolution Profiles of Dissolved Reactive Phosphorus in the Porewaters of Lake Sediments Assessed by DGT Technique

The technique of DGT (diffusive gradients in thin films) was applied to obtain high-resolution vertical profiles of dissolved reactive phosphorus (DRP) in sediment porewater of Lake Chaohu, a shallow eutrophication lake. Three kinds of DGT probes (with three thicknesses of diffusive gel: 0.38 mm, 0.78 mm and 1.18 mm) measured vertical concentration and induced flux from solid to solution phase which had intricate variations with depth. The results indicated that higher concentrations and induced fluxes of DRP were achieved by using DGT probe with thicker diffusion layer (CDGT1.18 > CDGT0.78 > CDGT0.38) and relatively stable DRP concentration profiles using DGT probes with 0.78 mm diffusive gel were obtained in each sediment core. The DRP concentrations displayed a clear gradient from Core C1 to Core C3 in sediment porewaters due to different sources and exchange degrees of reactive phosphorus. Compared to the concentrations obtained by the centrifugation technique, the concentrations of DRP resulting from the DGT technique were higher because some dissolved reactive phosphorus compounds have always been neglected using conventional centrifugation method.

Structural insight into the dual-antagonistic mechanism of AB928 on adenosine A_(2)receptors

The adenosine subfamily G protein-coupled receptors A_(2A)R and A_(2B)R have been identified as promising cancer immunotherapy candidates.One of the A_(2A)R/A_(2B)R dual antagonists,AB928,has progressed to a phaseⅡclinical trial to treat rectal cancer.However,the precise mechanism underlying its dual-antagonistic properties remains elusive.Herein,we report crystal structures of the A_(2A)R complexed with AB928 and a selective A_(2A)R antagonist 2-118.The structures revealed a common binding mode on A_(2A)R,wherein the ligands established extensive interactions with residues from the orthosteric and secondary pockets.In contrast,the cAMP assay and A_(2A)R and A_(2B)R molecular dynamics simulations indicated that the ligands adopted distinct binding modes on A_(2B)R.Detailed analysis of their chemical structures suggested that AB928 readily adapted to the A_(2B)R pocket,while 2-118 did not due to intrinsic differences.This disparity potentially accounted for the difference in inhibitory efficacy between A_(2B)R and A_(2A)R.This study serves as a valuable structural template for the future development of selective or dual inhibitors targeting A_(2A)R/A_(2B)R for cancer therapy.

Bis(9)-(−)-Meptazinol,a novel dual-binding AChE inhibitor,rescues cognitive deficits and pathological changes in APP/PS1 transgenic mice

Background:Alzheimer’s disease(AD)is a progressive and irreversible neurodegenerative brain disorder,which is the most common form of dementia.Intensive efforts have been made to find effective and safe treatment against AD.Acetylcholinesterase inhibitors(AChEIs)have been widely used for the treatment of mild to moderate AD.In this study,we investigated the effect of Bis(9)-(−)-Meptazinol(B9M),a novel potential dual-binding acetylcholinesterase(AChE)inhibitor,on learning and memory abilities,as well as the underlying mechanism in the APP/PS1 mouse model of AD.Methods:B9M(0.1μg/kg,0.3μg/kg,and 1μg/kg)was administered by subcutaneous injection into eight-month-old APP/PS1 transgenic mice for four weeks.Morris water maze,nest-building and novel object recognition were used to examine learning and memory ability.Aβ levels and Aβplaque were evaluated by ELISA and immunochemistry.Results:Our results showed that chronic treatment with B9M significantly improved the cognitive function of APP/PS1 transgenic mice in the Morris water maze test,nest-building test and novel object recognition test.Moreover,B9M improved cognitive deficits in APP/PS1 mice by a mechanism that may be associated with its inhibition of the AChE activity,Aβ plaque burden,levels of Aβ and the consequent activation of astrocytes and microglia in the brain of APP/PS1 transgenic mice.Most of important,the most effective dose of B9M in the present study is 1μg/kg,which is one thousand of the dosage of Donepezil acted as the control treatment.Furthermore,B9M reduced Aβ plaque burden better than Donepezil.Conclusion:These results indicate that B9M appears to have potential as an effective AChE inhibitor for the treatment of AD with symptom-relieving and disease-modifying properties.

Effects of Different Oxidants on HCl-based Pickling Process of 430 Stainless Steel

To shorten the time required for the pickling process and to enhance the quality of ferritic stainless steel plates,the effects of oxidants including hydrogen peroxide（H2O2）,potassium permanganate（KMnO4）,and potassium chlorate（KClO3）on the pickling behavior in HCl-based electrolyte as well as the surface quality of hot-rolled and blasted 430 stainless steel（430-SS）were studied.Experiments were conducted using mass-loss tests,microstructure analyses,potentiodynamic polarization curves,and electrochemical impedance spectroscopy measurements.The results showed that the addition of oxidants substantially accelerated the pickling process of 430-SS by enhancing the cathodic reaction rate and reducing the charge transfer resistance.In electrolytes comprising 5-8mass% HCl at a temperature of 40-60 ℃ and at the same concentration within the range from 0to 2mass%,H2O2 was demonstrated to be superior to KMnO4 and KClO3in accelerating the pickling process.The surface quality of 430-SS pickled in the presence of H2O2 was better than those of specimens pickled in the presence of KMnO4 and KClO3 when the removal of the oxide layer,intergranular corrosion,and surface roughness were collectively considered.When 1mass% H2O2 was added,the mass loss rate of 430-SS was increased by 629%and no residual oxide layer or intergranular corrosion was observed on the surface of the steel;in addition,the roughness was only 1.7μm.H2O2 was determined to be a better oxidant than KMnO4 and KClO3 when the pickling process,surface quality,solution recycling,and environment protection were considered as a whole.