The solute carrier transporters and the brain:Physiological and pharmacological implications

Solute carriers(SLCs)are the largest family of transmembrane transporters that determine the exchange of various substances,including nutrients,ions,metabolites,and drugs across biological membranes.To date,the presence of about 287 SLC genes have been identified in the brain,among which mutations or the resultant dysfunctions of 71 SLC genes have been reported to be correlated with human brain disorders.Although increasing interest in SLCs have focused on drug development,SLCs are currently still under-explored as drug targets,especially in the brain.We summarize the main substrates and functions of SLCs that are expressed in the brain,with an emphasis on selected SLCs that are important physiologically,pathologically,and pharmacologically in the blood-brain barrier,astrocytes,and neurons.Evidence suggests that a fraction of SLCs are regulated along with the occurrences of brain disorders,among which epilepsy,neurodegenerative diseases,and autism are representative.Given the review of SLCs involved in the onset and procession of brain disorders,we hope these SLCs will be screened as promising drug targets to improve drug delivery to the brain.

Non-destructive Measurement of Magnetic Properties of Claw Pole

The magnetic properties of the claw pole have a direct effect on the output power of a generator Many methods can be used to measure these magnetic properties,each with its own advantages,but an important shortcoming is that all are destructive.In this study,a new non-destructive method to measure the magnetic properties of claw pole was proposed and a corresponding testing set-up was designed.A finite-element model was constructed to simulate the measurement process.Results proved that the measured magnetization-like curves had good agreement with the trend of the input magnetic curves and the effect of the positioning error in the measuring process could be neglected.To further validate the new method,seven types of claw poles of different materials subjected to different heat-treatment processes were forged and tested by both the new method and the conventional ring-sample method.Compared with the latter,the new method showed better consistency,relatively higher accuracy,and much stronger stability of measurement results;however,its sensitivity needs to be improved.The effects of material compositions and heat-treatment parameters on the magnetic properties of the claw pole were briefly analyzed.

Effect of die coating on surface crack depth of hot extruded 7075 aluminum alloy

The aluminum alloys belonging to the 7000 series are high-strength alloys used in a wide variety of products for weight reduction.They are primarily used in the field of transportation and aerospace.Among these,the A7075 alloy has the highest strength and is expected to be applicable in a wide range of fields,such as aircraft components and sports equipment.However,it has high deformation resistance and is prone to surface defects,which is called tearing.Tearing typically occurs at high temperatures and high ram speeds,and adversely affects productivity.The localized melting of Zn and additive compounds,due to the heat generated during the process,is considered to cause tearing.In this study,the effect of friction,heat,and tearing at the tool-metal interface was mitigated by improving the die surface quality.The reduced friction eliminated recrystallization by preventing the temperature from increasing to recrystallization temperature.In addition,an AlCrN coating was adopted instead of nitriding to improve the die surface quality.The tearing size and heat generated when using the AlCrN coating were found to be limited.Moreover,the grain size observed in the tearing region on the extruded surface was small.The simulations using the shear friction coefficient m observed from friction tests indicate that the use of the AlCrN coating improved the material flow.Thus,the AlCrN coating is considered effective for reducing friction at the interface and preventing the recrystallization of the extruded surface.From the aforementioned results,it can be inferred that a die coating can reduce the tearing sensitivity and increase the productivity of the A7075 alloy.

Evaluation of dry-in-place lubricants for cold forging by using an optimal steady combined forward and backward extrusion testing method

This study evaluated dry-in-place lubricants used for cold forging.A group of isothermal compression tests with a strain rate(ε)e&range of 0.001–1 s^(−1) and temperature(T)range of 30–400℃ were completed.The flow stress(σ)curves of annealed steel S45C were obtained,and a corresponding Hensel–Spittel model was developed to support finite element(FE)simulation.The sensitivity of the steady combined forward and backward extrusion(SCFBE)test proposed in another study was improved by approximately 20%after it was optimized using the results of the FE simulations.Key parameters were identified,and the calibration curves after optimization were obtained.On the basis of the optimized test,a friction testing setup with a heating system was developed,in which the die temperature could be adjusted from room temperature(RT)to 230℃.Three dry-in-place lubricants and conventional phosphating lubricant were tested,and the friction factors(m),forming loads,and ejection loads were measured.The surface features of the specimens after testing were also investigated.According to the testing results,of the three tested dry-in-place lubricants,the mica type was the best.In addition,the optimized friction testing design was verified as effective.

Galling phenomena in metal forming

Galling phenomena in metal forming not only affect the quality of the engineered surfaces but also the success or failure of the manufacturing operation itself.This paper reviews the different galling conditions in sheet and bulk metal forming processes along with their evolution and the effects of temperature on galling.A group of anti-galling methods employed to prevent galling defects are also presented in detail.The techniques for quantitatively measuring galling are introduced,and the related prediction models,including friction,wear,and galling growth models,are presented to better understand the underlying phenomena.Galling phenomena in other processes similar to those occurring in metal forming are also examined to suggest different ways of further studying galling in metal forming.Finally,future research directions for the study of galling in metal forming are suggested.

Highly dispersed silver nanoparticles for performance-enhanced lithium oxygen batteries

Aprotic lithium-oxygen batteries possess ultrahigh energy density but suffer from the sluggish decomposition of discharge product,quick depletion of Li anode and cleavage of electrolyte,in close association with oxygen reduction reaction at the cathode.Herein,highly dispersed silver nanoparticles are used to enhance the lithium-oxygen battery with 1.0 M lithium perchlorate in dimethyl sulfoxide.It is observed that film-like amorphous lithium peroxide is formed through surface pathway instead of bulk crystals,due to the incorporation of silver nanoparticles dispersed in the electrolyte,which subsequently accelerates the decomposition of the discharge product by offering more active sites and improved conductivity.The released silver nanoparticles after battery charging can be re-used in the following cycles.Experiments and theoretical calculation further indicate that the suspended silver nanoparticles can adsorb the soluble oxygen reduction intermediates,which are responsible for the alleviation of oxidative cleavage of electrolyte and corrosion of lithium anode.The lifespan of lithium oxygen batteries is therefore significantly extended from 55 to 390 cycles,and the rate performance and full-discharge capacity are also largely enhanced.The battery failure is attributed to the coalescence and growth of silver nanoparticles in the electrolyte,and further improvement on colloid stability is underway.

An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19

The global spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019(COVID-19).In this study,we developed an integrative drug repositioning framework,which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph,literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2.Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1(PARP1)inhibitor,CVL218,currently in Phase I clinical trial,may be repurposed to treat COVID-19.Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect.In addition,we showed that CVL218 can interact with the nucleocapsid(N)protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection.