The role of SLC12A family of cation-chloride cotransporters and drug discovery methodologies

The solute carrier family 12(SLC12)of cation-chloride cotransporters(CCCs)comprises potassium chloride cotransporters(KCCs,e.g.KCC1,KCC2,KCC3,and KCC4)-mediated Cl^(-)extrusion,and sodium potassium chloride cotransporters(N[K]CCs,NKCC1,NKCC2,and NCC)-mediated Cl^(-)loading.The CCCs play vital roles in cell volume regulation and ion homeostasis.Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues.In recent years,there have been considerable advances in our understanding of CCCs'control mechanisms in cell volume regulations,with many techniques developed in studying the functions and activities of CCCs.Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs.These techniques include the ammonium pulse technique,radioactive or nonradioactive rubidium ion uptakeassay,and thallium ion-uptake assay.CCCs'activity can also be indirectly observed by measuring gaminobutyric acid(GABA)activity with patch-clamp electrophysiology and intracellular chloride concentration with sensitive microelectrodes,radiotracer^(36)Cl^(-),and fluorescent dyes.Other techniques include directly looking at kinase regulatory sites phosphorylation,flame photometry,22Nat uptake assay,structural biology,molecular modeling,and high-throughput drug screening.This review summarizes the role of CCCs in genetic disorders and cell volume regulation,current methods applied in studying CCCs biology,and compounds developed that directly or indirectly target the CCCs for disease treatments.

中国战略性新兴产业结构变动与就业效应分析

随着中国战略性新兴产业的发展,新兴产业结构变动对劳动力就业、就业弹性将产生直接影响。本文分析了中国战略性新兴产业结构变动情况与产业就业现状,产业结构变动对就业的拉动效应,新兴产业平均就业弹性等。研究表明,新兴产业结构变动速度不够平稳,产业变动对就业的带动效应不够。因此合理调整战略性新兴产业结构,加强新兴产业结构变动对就业的良性带动作用,对实现产业结构有序平稳变动以及促进劳动就业率的上升意义重大。

Water chemistry controlled aggregation and photo-transformation of silver nanoparticles in environmental waters

The inevitable release of engineered silver nanoparticles(Ag NPs) into aquatic environments has drawn great concerns about its environmental toxicity and safety. Although aggregation and transformation play crucial roles in the transport and toxicity of Ag NPs, how the water chemistry of environmental waters influences the aggregation and transformation of engineered Ag NPs is still not well understood. In this study, the aggregation of polyvinylpyrrolidone(PVP) coated Ag NPs was investigated in eight typical environmental water samples(with different ionic strengths, hardness, and dissolved organic matter(DOM) concentrations) by using UV–visible spectroscopy and dynamic light scattering. Raman spectroscopy was applied to probe the interaction of DOM with the surface of Ag NPs. Further, the photo-transformation and morphology changes of Ag NPs in environmental waters were studied by UV–visible spectroscopy, inductively coupled plasma mass spectrometry, and transmission electron microscopy. The results suggested that both electrolytes(especially Ca2+and Mg2+) and DOM in the surface waters are key parameters for Ag NP aggregation, and sunlight could accelerate the morphology change, aggregation, and further sedimentation of Ag NPs. This water chemistry controlled aggregation and photo-transformation should have significant environmental impacts on the transport and toxicity of Ag NPs in the aquatic environments.

Simultaneous size characterization and mass quantification of the in vivo core-biocorona structure and dissolved species of silver nanoparticles

Size characterization of silver nanoparticles with biomolecule corona(AgNP@BCs) and mass quantification of various silver species in organisms are essential for understanding the in vivo transformation of Ag NPs. Herein, we report a versatile method that allows simultaneous determination of the size of AgNP@BCs and mass concentration of various silver species in rat liver. Both particulate and ionic silver were extracted in their original forms from the organs by alkaline digestion, and analyzed by size exclusion chromatography combined with inductively coupled plasma mass spectrometry(SEC-ICP-MS). While the silver mass concentrations were quantified by ICP-MS with a detection limit of 0.1 μg/g, the effective diameter of AgNP@BCs was determined based on the retention time in SEC separation with size discrimination of 0.6-3.3 nm. More importantly, we found that the BC thickness of AgNP@BCs is core size independent, and a linear correlation was found between the effective diameter and core diameter of AgNP@BCs in extracted tissues, which was used to calibrate the core diameter with standard deviations in the range of 0.2-1.1 nm. The utility of this strategy was demonstrated through application to rat livers in vivo. Our method is powerful for investigating the transformation mechanism of Ag NPs in vivo.

Efficacy and safety of light therapy for Parkinson disease

To the Editor:Parkinson disease(PD)is the second most common neurodegenerative disorder associated with significant disability and negative impact on quality of life(QoL),affecting 2%to 3%of the population≥65 years of age.^([1])Although the disorder is defined by motor features including asymmetric tremor,bradykinesia,and rigidity,various non-motor features are typically seen,including cognitive impairment,depression,sensory symptoms,autonomic dysfunction,and sleep disturbances.Due to the complexity,PD is challenging to treat.There are currently no effective treatments to prevent or halt the progression of PD.

Sodium carbonate-assisted synthesis of hierarchically porous single-crystalline nanosized zeolites

Hierarchically porous single-crystalline nanosized zeolites as heterogeneous catalysts show great potential in fine chemistry because they offer more rich hierarchically porous channels for the mass transfer and molecular diffusion. However, the synthesis of hierarchically porous nanosized zeolites generally requires the assistance of templates acting as the mesoporogens, which limits its popularity. Herein,we report a one-pot and template-free synthesis of hierarchically porous single-crystalline nanosized zeolite beta only by introducing sodium carbonate in precursor solution. The resulted sample features the extraordinary properties, including the uniform nanocrystal(200–300 nm), high pore volume(0.65 cm^3g^(-1)) and the hierarchical pore-size distribution(e.g. 2–8 and 90–150 nm). After slicing processing, it is interestingly found that a large number of interconnected mesopores penetrate throughout whole material, which enables the hierarchically porous nanosized zeolite beta remarkably superior catalytic activity than the conventional zeolite beta in condensation of benzaldehyde with ethanol at room temperature. More importantly, this one-pot sodium carbonate-assisted synthetic strategy is highly versatile, which has also been successfully developed to synthesize hierarchically porous nanosized singlecrystalline zeolites ZSM-5 and TS.

Release of ZrO2 nanoparticles from ZrO2/Polymer nanocomposite in wastewater treatment processes

The widespread use of nano-enabled water treatment composites(NWTCs)can result in the release of nanoparticles(NPs)into environmental waters.Studying the release of NPs from NWTCs is of great significance for evaluating the material stability,and environment and biological safety.This work evaluated the amount and species of Zr released from a NWTC,a ZrO2/polymer composite(HZO@D201),during the treatment of electroplating wastewater.About 5 g of the HZO@D201 particles,consisting of porous spheres(0.8 mm in diameter)loaded with ZrO2 NPs,were packed into a glass column(130 mm in length and20 mm in diameter)and treated with wastewater at a flow rate of 25 mL/hr.The release of Zr occurred mainly in the initial stages of water treatment,decreased with the increase of treatment volume,and approached an equilibrium value of approximately 3.79μg/L at the treatment volume of about 800 bed volumes.The total amount of Zr released in the effluent was in the range of 2.62-140μg/L,which was mainly present in the form of ZrO2 NPs.The amounts of Zr released under acidic and alkaline conditions were markedly higher than that under neutral conditions,while the presence of humic acid significantly inhibited the release of Zr.Our study implied that the NWTCs could be a source of engineered NPs in environmental waters,and should be considered in evaluating the safety of ZrO2/polymer composites in water treatment.

Functional hemispherectomy for patients with adult-onset Rasmussen’s encephalitis

Background:Surgical treatment for patients with adult-onset Rasmussen’s encephalitis(A-RE)is rarely reported.We investigated the clinical and surgical features of two patients with A-RE who underwent functional hemispherectomy.Case presentation:The data of clinical manifestations,neuroimaging,surgical treatment and surgical outcomes of two patients with A-RE was reviewed.The two patients initially presented with recurrent partial seizures or secondly generalized tonic clonic seizures.Gradually,the patients showed unilateral limb paralysis as well as chronic focal epileptic status.Both patients underwent functional hemispherectomy and achieved seizure freedom in the followup.The contralateral neurological deficits improved gradually after rehabilitation and were acceptable for the selfcare of daily living.The living quality improved prominently after surgery.Conclusions:Despite the risk of hemiplegia,functional hemispherectomy may be a choice for patients with A-RE for favorable seizure control and improved quality of life in selected patients.

Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson’s disease

Background:Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease(PD)risk factors;however,no comprehensive analyses of these genes in patients with PD have been undertaken.Therefore,we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods:Whole-exome sequencing(WES)was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls.Additionally,whole-genome sequencing(WGS)was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results:We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts,respectively.Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD.However,the significance did not pass the Bonferroni correction.Meanwhile,72 and 1730 common variants were found in the WES and WGS cohorts,respectively.Unfortunately,single-variant logistic association analyses did not identify significant associations between common variants and PD.Conclusions:Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients.However,we highlight the complexity of PD and the need for extensive research elucidating its etiology.