STAT3 ameliorates truncated tau-induced cognitive deficits

Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.

Regulation of interlayer channels of graphene oxide nanosheets in ultra-thin Pebax mixed-matrix membranes for CO_(2) capture

For the application of carbon capture by membrane process,it is crucial to develop a highly permeable CO_(2)-selective membrane.In this work,we reported an ultra-thin polyether-block-amide(Pebax)mixedmatrix membranes(MMMs)incorporated by graphene oxide(GO),in which the interlayer channels were regulated to optimize the CO_(2)/N_(2) separation performance.Various membrane preparation conditions were systematically investigated on the influence of the membrane structure and separation performance,including the lateral size of GO nanosheets,GO loading,thermal reduction temperature,and time.The results demonstrated that the precisely regulated interlayer channel of GO nanosheets can rapidly provide CO_(2)-selective transport channels due to the synergetic effects of size sieving and preferential adsorption.The GO/Pebax ultra-thin MMMs exhibited CO_(2)/N_(2) selectivity of 72 and CO_(2) permeance of 400 GPU(1 GPU=106 cm^(3)(STP)·cm^(2)·s^(-1)·cmHg^(-1)),providing a promising candidate for CO_(2) capture.

Two-dimensional MXene hollow fiber membrane for divalent ions exclusion from water

Two-dimensional material membranes with fast transport channels and versatile chemical functionality are promising for molecular separation.Herein,for the first time,we reported design and engineering of two-dimensional Ti_(3)C_(2)Tx MXene(called transition metal carbides and nitrides)membranes supported on asymmetric polymeric hollow fiber substrate for water desalination.The membrane morphology,physicochemical properties and ions exclusion performance were systematically investigated.The results demonstrated that surface hydrophilicity and electrostatic repulsion and size sieving effect of interlayer channels synergistically endowed the MXene hollow fiber membrane with fast water permeation and efficient rejection of divalent ions during nanofiltration process.

Natural gas purification by asymmetric membranes: An overview

Natural gas, as a very important source of energy and chemical feedstock, can be used in place of coal to lower net carbon dioxide emissions.Membrane separation technology is an attractive alternative for natural gas purification where the impurities represented by acid gases(CO_(2) and H_(2)S) as well as inert gases(N_(2)) must be removed to meet the transportation and usage specifications. From the economic benefits viewpoint,asymmetric membranes are required for industrial manufacture and applications. This paper aims to review the latest development of various kinds of asymmetric membranes for natural gas purification, mainly focusing on CO_(2) removal from CH_(4), including H_(2)S and N_(2) separation from CH_(4) as well. According to material types, polymeric, inorganic, mixed-matrix and carbon molecular sieve membranes are introduced. The associated fabrication approaches and transport properties are discussed for each kinds of asymmetric membranes. Towards the practical implementation, an emphasis is placed on hollow fiber asymmetric structure for these polymeric, mixed-matrix and carbon molecular sieve membranes.

Polydimethylsiloxane (PDMS) Composite Membrane Fabricated on the Inner Surface of a Ceramic Hollow Fiber: From Single-Channel to Multi-Channel

The fabrication of a separation layer on the inner surface of a hollow fiber (HF) substrate to form an HF composite membrane offers exciting opportunities for industrial applications, although challenges remain. This work reports on the fabrication of a polydimethylsiloxane (PDMS) composite membrane on the inner surface of a single-channel or multi-channel ceramic HF via a proposed coating/crossflow approach. The nanostructures and transport properties of the PDMS HF composite membranes were optimized by controlling the polymer concentration and coating time. The morphology, surface chemistry, interfacial adhesion, and separation performance of the membranes were characterized by fieldemission scanning electron microscope (FE-SEM), attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, the nano-indentation/scratch technique, and pervaporation (PV) recovery of bio-butanol, respectively. The formation mechanism for the deposition of the PDMS layer onto the inner surface of the ceramic HF was studied in detail. The optimized inner surface of the PDMS/ceramic HF composite membranes with a thin and defect-free separation layer exhibited a high flux of ~1800 gm-2h-1 and an excellent separation factor of 35–38 for 1 wt% n-butanol/water mixtures at 60
C. The facile coating/cross-flow methodology proposed here shows great potential for fabricating inner-surface polymer-coated HFs that have broad applications including membranes, adsorbents, composite materials, and more.

Graphene-based membranes for pervaporation processes

Two-dimensional graphene and its derivatives exhibiting distinct physiochemical properties are intriguing building blocks for researchers from a large variety of scientific fields.Assembling graphene-based materials into membrane layers brings great potentials for high-efficiency membrane processes.Particularly,pervaporation by graphene-based membranes has been intensively studied with respect to the membrane design and preparation.This review aims to provide an overview on the graphene-based membranes for pervaporation processes ranged from fabrication to application.Physical or chemical decoration of graphene-based materials is elaborated regarding their effects on the microstructure and performance.The mass transport of pervaporation through graphene-based membranes is introduced,and relevant mechanisms are described.Furthermore,performances of state-of-the-art graphene-based membranes for different pervaporation applications are summarized.Finally,the perspectives of current challenges and future directions are presented.

Graphene oxide membranes supported on the ceramic hollow fibre for efficient H2 recovery

The special channels and intrinsic defects within GO laminates make it a very potential candidate for gas separation in recent years. Herein, the gas separation performance of GO membranes prepared on the surface of ceramicα-Al_2O_3 hollow fibre was investigated systematically. The microstructures of ceramic hollow fibre supported GO membranes were optimized by adjusting operation conditions. And, the GO membrane fabricated at 30 min exhibited great promising H_2 recovery ability from H_2/CO_2 mixture. At room temperature, the H_2 permeance was over 1.00 × 10^(-7)mol·m^(-2)·s^(-1)·Pa^(-1)for both single gas and binary mixture. The corresponding ideal selectivity and mixture separation factor reached around 15 and 10, respectively. In addition, humility, operation temperature, H_2 concentration in the feed and the reproducibility were also studied in this work.

Thermoregulatory molecular sieving in crystals

Sub-nanometer channels for the selective recognition of the components in chemical mixtures from others play a crucial role in the adsorption and membrane separation[1].It remains a grand challenge to separate small molecular pairs with minor size/shape difference owing to the undesirable pore structure.

Mechanism of ethanol/water reverse separation through a functional graphene membrane:a molecular simulation investigation

Reverse-selective membranes have attracted considerable interest for bioethanol production.However,to date,the reverse-separation performance of ethanol/water is poor and the separation mechanism is unclear.Graphene-based membranes with tunable apertures and functional groups have shown substantial potential for use in molecular separation.Using molecular dynamics simulations,for the first time,we reveal twoway selectivity in ethanol/water separation through functional graphene membranes.Pristine graphene(PG)exhibits reverse-selective behavior with higher ethanol fluxes than water,resulting from the preferential adsorption for ethanol.Color flow mappings show that this ethanol-permselective process is initiated by the presence of ethanol-enriched and water-barren pores;this has not been reported in previous studies.In contrast,water molecules are preferred for hydroxylated graphene membranes because of the synergistic effects of molecular sieving and functional-group attraction.A simulation of the operando condition shows that the PG membrane with an aperture size of 3.8Åachieves good separation performance,with an ethanol/water separation factor of 34 and a flux value of 69.3 kg∙m‒2∙h‒1∙bar‒1.This study provides new insights into the reverse-selective mechanism of porous graphene membranes and a new avenue for efficient biofuel production.

A novel transgenic mouse line with hippocampus-dominant and inducible expression of truncated human tau

Background Intraneuronal accumulation of hyperphosphorylated tau is a defining hallmark of Alzheimer’s disease(AD).However,mouse models imitating AD-exclusive neuronal tau pathologies are lacking.Methods We generated a new tet-on transgenic mouse model expressing truncated human tau N1-368(termed hTau368),a tau fragment increased in the brains of AD patients and aged mouse brains.Doxycycline(dox)was administered in drinking water to induce hTau368 expression.Immunostaining and Western blotting were performed to measure the tau level.RNA sequencing was performed to evaluate gene expression,and several behavioral tests were conducted to evaluate mouse cognitive functions,emotion and locomotion.Results Dox treatment for 1-2 months at a young age induced overt and reversible human tau accumulation in the brains of hTau368 transgenic mice,predominantly in the hippocampus.Meanwhile,the transgenic mice exhibited AD-like high level of tau phosphorylation,glial activation,loss of mature neurons,impaired hippocampal neurogenesis,synaptic degeneration and cognitive deficits.Conclusions This study developed a well-characterized and easy-to-use tool for the investigations and drug development for AD and other tauopathies.

高配位数金属有机框架膜的通道构筑与应用研究

高渗透性、高选择性和高稳定性的膜材料是提高膜分离过程的核心.高配位数金属有机框架膜具有规整的纳米通道、孔道可调节、稳定性优异等特点,近十年来研究表明,其是一类极具潜力的分子尺度分离膜材料.本文系统综述了高配位数金属有机框架膜的传质通道精密构筑及其在分子尺度分离应用方面的研究进展,并深入探讨了该研究领域所面临的机遇和挑战,同时也对其未来发展方向进行了展望.

Graphene oxide membrane for molecular separation:challenges and opportunities

氧化石墨烯作为一种典型二维材料具有单原子层厚度和大量含氧官能团,可作为高性能分离膜的理想构筑单元,已成为近年来的研究热点.通过对氧化石墨烯纳米片的有序组装,可构筑亚纳米尺寸的分子传质通道,对水分子、有机小分子、气体分子具有快速选择性透过效应,在水处理、溶剂纯化和气体分离等膜过程展现出优异的分离性能.本文重点分析了近期氧化石墨烯膜的突破性进展,并指出氧化石墨烯膜用于分子分离过程所面临的机遇与挑战.

Humanin attenuates Alzheimer-like cognitive deficits and pathological changes induced by amyloid β-peptide in rats

Amyloid β-peptide（Aβ） has been implicated as a key molecule in the neurodegenerative cascades of Alzheimer ’s disease（AD）. Humanin（HN） is a secretory peptide that inhibits the neurotoxicity of Aβ. However, the mechanism（s） by which HN exerts its neuroprotection against Aβ-induced ADlike pathological changes and memory deficits are yet to be completely defined. In the present study,we provided evidence that treatment of rats with HN increases the number of dendritic branches and the density of dendritic spines, and upregulates pre- and post-synaptic protein levels; these effects lead to enhanced long-term potentiation and amelioration of the memory deficits induced by Aβ1-42. HN also attenuated Aβ1-42-induced tau hyperphosphorylation,apparently by inhibiting the phosphorylation of Tyr307 on the inhibitory protein phosphatase-2A（PP2A）catalytic subunit and thereby activating PP2 A. HN also inhibited apoptosis and reduced the oxidativestress induced by Aβ1-42. These findings provide novel mechanisms of action for the ability of HN to protect against Aβ1-42-induced AD-like pathological changes and memory deficits.

Cation-diffusion controlled formation of thin graphene oxide composite membranes for efficient ethanol dehydration

Structural manipulation of graphene oxide (GO) building blocks has been widely researched. Concerning GO membranes for separation applications, the validity and maintenance of their microscopic structures in the chemical environment are pivotal for effective separation at the molecular scale. Cationic interactions with both aromatic rings and oxygenated functional groups of GO make metal ions intriguing for physically and chemically structural reinforcement. By filtrating GO suspension through the substrate loaded with cations, stacking o f GO nanosheets and diffusion of cations steadily evolve simultaneously in an aqueous environment without flocculation. Thus, thin and homogeneous GO membrane is obtained. Divalent and monovalent cations were studied regarding their interactions with GO, and the performance of correspondingly functionalized membranes was evaluated. The divalent cation-stabilized membranes have favorable stability in the separation of water/ethanol. This facile fabrication and functionalization method may also be applicable for structure construction of other two-dimensional materials.

Discovery of the first potent proteolysis targeting chimera(PROTAC) degrader of indoleamine 2,3-dioxygenase 1

Cancer immunotherapy is revolutionizing oncology and has emerged as a promising strategy for the treatment of multiple cancers.Indoleamine 2,3-dioxygenase 1(IDO1),an immune checkpoint,plays an important role in tumor immune escape through the regulation of multiple immune cells and has been regarded as an attractive target for cancer immunotherapy.Proteolysis Targeting Chimeras(PROTAC)technology has emerged as a new model for drug research and development for its advantageous mechanism.Herein,we reported the application of PROTAC technology in targeted degradation of IDO 1,leading to the discovery of the first IDO1 PROTAC degrader 2 c,which induced significant and persistent degradation of IDO1 with maximum degradation(Dmax)of 93%in HeLa cells.Western-blot based mechanistic studies indicated that IDO 1 was degraded by 2 c through the ubiquitin proteasome system(UPS).Label-free real-time cell analysis(RTCA)indicated that 2 c moderately improved tumorkilling activity of chimeric antigen receptor-modified T(CAR-T)cells.Collectively,these data provide a new insight for the application of PROTAC technology in tumor immune-related proteins and a promising tool to study the function of IDO1.

Novel membrane separation technologies and membrane processes

Membrane-based separation technologies have received increasing attention attributing to lots of advantages such as the low energy consumption,easy operation,and environmental friendliness.In recent years,the emergence of novel two-dimensional(2D)materials,such as graphene,provides a new opportunity for membrane development.Thus,Frontiers of Chemical Science and Engineering(FCSE),one of the transactions of Chinese Academy of Engineering,organized this Special Issue aiming to illustrate some of the exciting progresses and achievements in the relevant research fields.

Two-Dimensional-Material Membranes:Manipulating the Transport Pathway for Molecular Separation

CONSPECTUS:The discovery of graphene triggers a new era of two-dimensional(2D)materials,which exhibit great potential in condensed matter physics,chemistry,and materials science.Meanwhile,the booming of 2D materials brings new opportunities for the next generation of high-performance(high permeability,selectivity,and stability)separation membranes.Two-dimensional materials with atomic thinness can serve as new building blocks for fabricating ultrathin membranes possessing the ultimate permeation rate.The plane structure with micrometer lateral dimensions provides an excellent platform for the orderly alignment of the nanosheets.Moreover,the apertures of two-dimensional-material membranes(2DMMs),including the in-plane nanopores and interlayer channels,can contribute to the fast and selective transport of small molecules/ions related to molecular separation.Therefore,the emerging 2D materials with various nanostructures,including graphene oxide(GO),zeolite nanosheets,metal−organic framework(MOF)nanosheets,and transition-metal carbides/carbonitrides(MXene),can be assembled into highperformance membranes.Various assembly methods such as filtration,spin coating,and hot dropping have been employed to fabricate 2DMMs,while the processes for separating small molecules/ions tend to demand higher precision,especially in water desalination and gas separation.The nanostructures of 2DMMs and the physicochemical properties of transport pathway need to be finely tuned to meet the requirement.In addition,the stability of 2DMMs,which is critical to the large-scale implementation,must be taken into consideration as well.In this Account,we discuss our recent progress in manipulating molecular transport pathways in 2DMMs by optimizing the assembly behavior of 2D nanosheets,tuning the microstructure of interlayer channels,and controlling the physicochemical properties of the membrane surface.Assembly methods,including vacuum suction assembly,polymer-induced assembly,and external force-driven assembly,have been proposed to construct ordered laminates for molecular transport.The size and chemical structure of interlayer channels were further tailored by strategies such as nanoparticle intercalation,cationic control,and chemical modification.Interestingly,the manipulation of surface properties of 2DMMs was proven to contribute to fast molecular transport through interlayer channels.Moreover,the issues concerning 2DMMs toward practical applications are discussed with an emphasis on the substrate effect,molecular bridge strategy,and preliminary progress in large-scale fabrication.Finally,we conclude this Account with an overview of the remaining challenges and the new opportunities that will be opened up for 2DMMs in molecular separation.

Theoretical study on Janus graphene oxide membrane for water transport

Graphene oxide(GO)membranes have received considerable attention owing to their outstanding water-permeation properties;however,the effect of the membrane’s microstructures(such as the distribution of oxidized and pristine regions)on the transport mechanism remains unclear.In this study,we performed molecular simulations to explore the permeation of a water-ethanol mixture using a new type of Janus GO membranes with different orientations of oxidized and pristine surfaces.The results indicate that the oxidized upper surface endows the GO membrane with considerable water-capture capability and the in-built oxidized interlayer promotes the effective vertical diffusion of water molecules.Consequently,using the optimized Janus GO membrane,infinite water selectivity and outstanding water flux(-40.9 kg·m^(-2) h^(-1))were achieved.This study contributes to explaining the role of oxidized regions in water permeation via GO membranes and suggests that Janus GO membranes could be used as potential candidates for water-ethanol separation.