Therapeutic functions of astrocytes to treat α-synuclein pathology in Parkinson's disease.

Intraneuronal inclusions of misfolded α-synuclein (α-syn) and prion-like spread of the pathologic α-syn contribute to progressive neuronal death in Parkinson's disease (PD). Despite the pathologic significance, no efficient therapeutic intervention targeting α-synucleinopathy has been developed. In this study, we provide evidence that astrocytes, especially those cultured from the ventral midbrain (VM), show therapeutic potential to alleviate α-syn pathology in multiple in vitro and in vivo α-synucleinopathic models. Regulation of neuronal α-syn proteostasis underlies the therapeutic function of astrocytes. Specifically, VM-derived astrocytes inhibited neuronal α-syn aggregation and transmission in a paracrine manner by correcting not only intraneuronal oxidative and mitochondrial stresses but also extracellular inflammatory environments, in which α-syn proteins are prone to pathologic misfolding. The astrocyte-derived paracrine factors also promoted disassembly of extracellular α-syn aggregates. In addition to the aggregated form of α-syn, VM astrocytes reduced total α-syn protein loads both by actively scavenging extracellular α-syn fibrils and by a paracrine stimulation of neuronal autophagic clearance of α-syn. Transplantation of VM astrocytes into the midbrain of PD model mice alleviated α-syn pathology and protected the midbrain dopamine neurons from neurodegeneration. We further showed that cografting of VM astrocytes could be exploited in stem cell-based therapy for PD, in which host-to-graft transmission of α-syn pathology remains a critical concern for long-term cell therapeutic effects.

LIN28A loss of function is associated with Parkinson's disease pathogenesis.

Parkinson's disease (PD) is neurodegenerative movement disorder characterized by degeneration of midbrain-type dopamine (mDA) neurons in the substantia nigra (SN). The RNA-binding protein Lin28 plays a role in neuronal stem cell development and neuronal differentiation. In this study, we reveal that Lin28 conditional knockout (cKO) mice show degeneration of mDA neurons in the SN, as well as PD-related behavioral deficits. We identify a loss-of-function variant of LIN28A (R192G substitution) in two early-onset PD patients. Using an isogenic human embryonic stem cell (hESC)/human induced pluripotent stem cell (hiPSC)-based disease model, we find that the Lin28 R192G variant leads to developmental defects and PD-related phenotypes in mDA neuronal cells that can be rescued by expression of wild-type Lin28A. Cell transplantation experiments in PD model rats show that correction of the LIN28A variant in the donor patient (pt)-hiPSCs leads to improved behavioral phenotypes. Our data link LIN28A to PD pathogenesis and suggest future personalized medicine targeting this variant in patients.

Graphene Nanoribbon Hybridization of Zeolitic Imidazolate Framework Membranes for Intrinsic Molecular Separation.

Zeolitic imidazolate frameworks (ZIFs) are promising for gas separation membrane, but their molecular cut-off differs from that expected from its intrinsic aperture structure because of their flexibility. Herein, we introduced graphene nanoribbons (GNRs) to rigidify the ZIF framework. Because the sp2 edge of the GNRs induces strong anchoring effects, the modified layer can be rigidified. Particularly, when the GNRs were embedded and distributed in the ZIF-8 layer, an intrinsic aperture size of 3.4 Šwas observed, resulting in high H2 /CO2 separation (H2 permeance: 5.2×10-6  mol/m2 Pa s, ideal selectivity: 142). The performance surpasses the upper bound of polycrystalline MOF membrane performance. In addition, the membrane can be applied to blue H2 production, as demonstrated with a simulated steam reformed gas containing H2 /CO2 /CH4 . The separation performance was retained in the presence of water. The fundamentals of the molecular transport through the rigid ZIF-8 framework were revealed using molecular dynamics simulations.

Neutrophil-to-lymphocyte ratio is a reliable marker of treatment response in rheumatoid arthritis patients during tocilizumab therapy.

OBJECTIVE: To investigate the reliable markers reflecting treatment response better than the traditional inflammatory indices in patients with rheumatoid arthritis (RA) receiving tocilizumab therapy. METHODS: A total of 58 RA patients treated with tocilizumab for more than six months from January 2013 to December 2014 were initially included. Flares were defined as events that required steroid dose escalation, intra-articular steroid injections, or switching tocilizumab to other biologic agents. The clinical and laboratory data were retrospectively collected from electronic medical records. RESULTS: Of the 52 patients except for six patients who were excluded, 16 experienced flares, and 36 were stable during tocilizumab therapy. The C-reactive protein (CRP) level did not significantly differ between a stable state before flares and at flares. Compared with those at the preflare time point, erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR) were significantly higher at flares; however, ESR levels (n = 9) were within the normal limit or decreased (n = 4) at flares. Interestingly, NLR increased at flares in all but one patient in the flare group. CONCLUSION: NLR is a more reliable marker than ESR or CRP for evaluating the disease activity in patients with RA during tocilizumab therapy.

A New Family of Perovskite Catalysts for Oxygen-Evolution Reaction in Alkaline Media: BaNiO3 and BaNi(0.83)O(2.5).

Establishment of a sustainable energy society has been strong driving force to develop cost-effective and highly active catalysts for energy conversion and storage devices such as metal-air batteries and electrochemical water splitting systems. This is because the oxygen evolution reaction (OER), a vital reaction for the operation, is substantially sluggish even with precious metals-based catalysts. Here, we show for the first time that a hexagonal perovskite, BaNiO3, can be a highly functional catalyst for OER in alkaline media. We demonstrate that the BaNiO3 performs OER activity at least an order of magnitude higher than an IrO2 catalyst. Using integrated density functional theory calculations and experimental validations, we unveil that the underlying mechanism originates from structural transformation from BaNiO3 to BaNi(0.83)O(2.5) (Ba6Ni5O15) over the OER cycling process.

N-Carbon-Doped Binary Nanophase of Metal Oxide/Metal-Organic Framework for Extremely Sensitive and Selective Gas Response.

Metal-organic frameworks (MOFs), which are highly ordered structures exhibiting sub-nanometer porosity, possess significant potential for diverse gas applications. However, their inherent insulative properties limit their utility in electrochemical gas sensing. This investigation successfully modifies the electrical conductivity of zeolitic imidazolte framework-8 (ZIF-8) employing a straightforward surface oxidation methodology. A ZIF-8 polycrystalline layer is applied on a wafer-scale oxide substrate and subjects to thermal annealing at 300 °C under ambient air conditions, resulting in nanoscale oxide layers while preserving the fundamental properties of the ZIF-8. Subsequent exposure to NO2 instigates the evolution of an electrically interconnected structure with the formation of electron-rich dopants derived from the decomposition of nitrogen-rich organic linkers. The N-carbon-hybridized ZnO/ZIF-8 device demonstrates remarkable sensitivity (≈130 ppm-1 ) and extreme selectivity in NO2 gas detection with a lower detection limit of 0.63 ppb under 150 °C operating temperature, surpassing the performance of existing sensing materials. The exceptional performances result from the Debye length scale dimensionality of ZnO and the high affinity of ZIF-8 to NO2 . The methodology for manipulating MOF conductivity through surface oxidation holds the potential to accelerate the development of MOF-hybridized conductive channels for a variety of electrical applications.

Metal-Organic Framework Membrane Hybridized with Graphitic Materials for Gas Separation.

Metal-organic frameworks (MOFs) are an exceptional class of crystalline materials that have been extensively used to fabricate membranes for various applications such as gas separation, ion transport, and desalination due to their well-defined pore structure, chemical features, and simple synthesis process. The incorporation of graphitic carbon materials in MOFs has garnered significant attention as it can provide abundant nucleation sites and modulate gas transport by influencing the orientation or rigidity of MOF crystals without changing their porous structure. This review insights of previous studies utilizing graphene, graphene oxide, carbon nanotubes, and graphene nanoribbons for MOF-based gas separation membranes, particularly focusing on polycrystalline MOF membrane hybridization with graphitic materials. We also briefly discuss the use of carbon/MOF hybrid materials for preparing mixed matrix membranes.

Effective single web-structured electrode for high membrane electrode assembly performance in polymer electrolyte membrane fuel cell.

To achieve a sustainable society, CO2 emissions must be reduced and efficiency of energy systems must be enhanced. The polymer electrolyte membrane fuel cell (PEMFC) has zero CO2 emissions and high effectiveness for various applications. A well-designed membrane electrolyte assembly (MEA) composed of electrode layers of effective materials and structure can alter the performance and durability of PEMFC. We demonstrate an efficient electrode deposition method through a well-designed carbon single web with a porous 3D web structure that can be commercially adopted. To achieve excellent electrochemical properties, active Pt nanoparticles are controlled by a nanoglue effect on a highly graphitized carbon surface. The developed MEA exhibits a notable maximum power density of 1082 mW/cm2 at 80°C, H2/air, 50% RH, and 1.8 atm; low cathode loading of 0.1 mgPt/cm2; and catalytic performance decays of only 23.18 and 13.42% under commercial-based durability protocols, respectively, thereby achieving all desirables for commercial applications.

Microwave-assisted design of nanoporous graphene membrane for ultrafast and switchable organic solvent nanofiltration.

Layered two-dimensional materials can potentially be utilized for organic solvent nanofiltration (OSN) membrane fabrication owing to their precise molecular sieving by the interlayer structure and excellent stability in harsh conditions. Nevertheless, the extensive tortuosity of nanochannels and bulky solvent molecules impede rapid permeability. Herein, nanoporous graphene (NG) with a high density of sp2 carbon domain was synthesized via sequential thermal pore activation of graphene oxide (GO) and microwave-assisted reduction. Due to the smooth sp2 carbon domain surfaces and dense nanopores, the microwave-treated nanoporous graphene membrane exhibited ultrafast organic solvent permeance (e.g., IPA: 2278 LMH/bar) with excellent stability under practical cross-flow conditions. Furthermore, the membrane molecular weight cut-off (MWCO) is switchable from 500 Da size of molecule to sub-nanometer-size molecules depending on the solvent type, and this switching occurs spontaneously with solvent change. These properties indicate feasibility of multiple (both binary and ternary) organic mixture separation using a single membrane. The nanochannel structure effect on solvent transport is also investigated using computation calculations.

High-aspect ratio zeolitic imidazolate framework (ZIF) nanoplates for hydrocarbon separation membranes.

Metal-organic frameworks with high aspect ratios have the potential to yield high-performance gas separation membranes. We demonstrate the scalable synthesis of high­aspect ratio zeolitic imidazolate framework (ZIF)­8 nanoplates via a direct template conversion method in which high aspect ratio­layered Zn hydroxide sheets [Zn5(NO3)2(OH)8] were used as the sacrificial precursor. Successful phase conversion occurs as a result of the collaboration of low template stability and delayed delivery of 2-methylimidazole in weakly interacting solvents, particularly using acetone. When the ZIF-8 nanoplates with an average aspect ratio of 20 were shear aligned in the 6FDA-DAM polymer matrix by bar coating, the separation performance for propylene/propane far surpassed that of the previously reported mixed matrix and polymeric membranes, showing a propylene permeability of 164 Barrer and selectivity of 33.4 at 40 weight % loadings.

Graphene Nanoribbon/Carbon Nanotube Hybrid Hydrogel: Rheology and Membrane for Ultrafast Molecular Diafiltration.

Hybrids based on carbon nanotubes (CNTs) and graphene nanoribbons (GNRs) are expected to have synergistic effects for various applications. Herein, we demonstrate a simple one-pot synthesis of a CNT/GNR hybrid material by adjusting the oxidation and unzipping conditions of multi-walled CNTs (MWNTs). The MWNT/graphene oxide nanoribbon (GONR) hybrid was dispersed in various solvents, particularly showing the hybrid hydrogel phase in water at a concentration of 40 mg mL-1. The MWNT/GONR hydrogel exhibited shear-thinning behavior, which can be beneficial for coating a large-area MWNT/GONR layer onto a polymeric porous support by using a scalable slot-die coater. The MWNT/GONR membrane exhibited an outstanding nanofiltration performance, with a molecular weight cutoff of 300 Da and a dye/salt diafiltration performance with a separation factor of 1000 and a water flux of 367.8 LMH, far surpassing the upper bound of diafiltration performance of the existing membranes.

Tuning the hierarchical pore structure of graphene oxide through dual thermal activation for high-performance supercapacitor.

Herein, we introduce a simple method to prepare hierarchical graphene with a tunable pore structure by activating graphene oxide (GO) with a two-step thermal annealing process. First, GO was treated at 600 °C by rapid thermal annealing in air, followed by subsequent thermal annealing in N2. The prepared graphene powder comprised abundant slit nanopores and micropores, showing a large specific surface area of 653.2 m2/g with a microporous surface area of 367.2 m2/g under optimized conditions. The pore structure was easily tunable by controlling the oxidation degree of GO and by the second annealing process. When the graphene powder was used as the supercapacitor electrode, a specific capacitance of 372.1 F/g was achieved at 0.5 A/g in 1 M H2SO4 electrolyte, which is a significantly enhanced value compared to that obtained using activated carbon and commercial reduced GO. The performance of the supercapacitor was highly stable, showing 103.8% retention of specific capacitance after 10,000 cycles at 10 A/g. The influence of pore structure on the supercapacitor performance was systematically investigated by varying the ratio of micro- and external surface areas of graphene.

Fabrication Techniques for Graphene Oxide-Based Molecular Separation Membranes: Towards Industrial Application.

Graphene oxide (GO) has been a prized material for fabricating separation membranes due to its immense potential and unique chemistry. Despite the academic focus on GO, the adoption of GO membranes in industry remains elusive. One of the challenges at hand for commercializing GO membranes lies with large-scale production techniques. Fortunately, emerging studies have acknowledged this issue, where many have aimed to deliver insights into scalable approaches showing potential to be employed in the commercial domain. The current review highlights eight physical methods for GO membrane fabrication. Based on batch-unit or continuous fabrication, we have further classified the techniques into five small-scale (vacuum filtration, pressure-assisted filtration, spin coating, dip coating, drop-casting) and three large-scale (spray coating, bar/doctor blade coating, slot die coating) approaches. The continuous nature of the large-scale approach implies that the GO membranes prepared by this method are less restricted by the equipment's dimensions but rather the availability of the material, whereas membranes yielded by small-scale methods are predominately limited by the size of the fabrication device. The current review aims to serve as an initial reference to provide a technical overview of preparing GO membranes. We further aim to shift the focus of the audience towards scalable processes and their prospect, which will facilitate the commercialization of GO membranes.

Diamine vapor treatment of viscoelastic graphene oxide liquid crystal for gas barrier coating.

A layered graphene oxide/ethylenediamine (GO/EDA) composite film was developed by exposing aqueous GO liquid crystal (GOLC) coating to EDA vapor and its effects on the gas barrier performance of GO film were systematically investigated. When a GO/EDA coating with a thickness of approximately 1 µm was applied to a neat polyethylene terephthalate (PET) film, the resultant film was highly impermeable to gas molecules, particularly reducing the gas permeance up to 99.6% for He and 98.5% for H2 in comparison to the neat PET film. The gas barrier properties can be attributed to the long diffusion length through stacked GO nanosheets. The EDA can crosslink oxygen-containing groups of GO, enhancing the mechanical properties of the GO/EDA coating with hardness and elastic modulus values up to 1.14 and 28.7 GPa, respectively. By the synergistic effect of the viscoelastic properties of GOLC and the volatility of EDA, this coating method can be applied to complex geometries and EDA intercalation can be spontaneously achieved through the scaffold of the GOLC.

Ultrafast H2-selective nanoporous multilayer graphene membrane prepared by confined thermal annealing.

H2 selective dense pores are generated in a graphene oxide (GO) layer by thermal-decomposition of oxygen-functional groups under high pressure. The nanoporous GO membrane shows H2/CO2 selectivity of 12.1 and H2 permeability of 10360 Barrer.

Large-Area Ti3C2Tx-MXene Coating: Toward Industrial-Scale Fabrication and Molecular Separation.

Large-scale fabrication of MXene films is in high demand for various applications, but it remains difficult to meet industrial requirements. In this study, we develop a slot-die coating method for the preparation of large-area MXene membranes. The technique allows the fabrication of continuous and scalable coatings with a rapid coating speed of 6 mm s-1. The thickness can be readily controlled from the nanometer scale to the micrometer scale, and the alignment of the nanosheet is enhanced by the shear force of the slot-die head. Molecular separation experiments employing a film with a thickness of approximately 100 nm are performed. A nanofiltration performance with water permeance of 190 LMH/bar and molecular weight cutoff of 269 Da is achieved, surpassing previously reported results obtained using MXene-based nanofiltration membranes. The stability of the membrane is highlighted by its nanofiltration performance of 30 days under harsh oxidizing conditions, which is the longest operation ever achieved for a 2D material-based membrane. The extraordinary stability of the film suggests its high potential for industrial and practical applications. The antioxidizing phenomena can be attributed to self-protection of the MXene surface by adsorbed organic molecules, which are particularly stabilized with positively charged molecules via chemisorption.

SGK1 inhibition in glia ameliorates pathologies and symptoms in Parkinson disease animal models.

Astrocytes and microglia are brain-resident glia that can establish harmful inflammatory environments in disease contexts and thereby contribute to the progression of neuronal loss in neurodegenerative disorders. Correcting the diseased properties of glia is therefore an appealing strategy for treating brain diseases. Previous studies have shown that serum/ glucocorticoid related kinase 1 (SGK1) is upregulated in the brains of patients with various neurodegenerative disorders, suggesting its involvement in the pathogenesis of those diseases. In this study, we show that inhibiting glial SGK1 corrects the pro-inflammatory properties of glia by suppressing the intracellular NFκB-, NLRP3-inflammasome-, and CGAS-STING-mediated inflammatory pathways. Furthermore, SGK1 inhibition potentiated glial activity to scavenge glutamate toxicity and prevented glial cell senescence and mitochondrial damage, which have recently been reported as critical pathologic features of and therapeutic targets in Parkinson disease (PD) and Alzheimer disease (AD). Along with those anti-inflammatory/neurotrophic functions, silencing and pharmacological inhibition of SGK1 protected midbrain dopamine neurons from degeneration and cured pathologic synuclein alpha (SNCA) aggregation and PD-associated behavioral deficits in multiple in vitro and in vivo PD models. Collectively, these findings suggest that SGK1 inhibition could be a useful strategy for treating PD and other neurodegenerative disorders that share the common pathology of glia-mediated neuroinflammation.

Evaluation of morphokinetic characteristics of zona pellucida free mouse pre-implantation embryos using time-lapse monitoring system.

The mammalian zygote cleaves and develops to blastocyst within the zona pellucida (ZP) in vivo. The presence or absence of ZP may affect the characteristics of the embryo, including blastomere alignment, cell-cell junction, and compaction. This study aimed to compare the morphokinetic characteristics of ZP intact and ZP free mouse pre-implantation embryos with time-lapse monitoring system. Mouse 2-cell embryos were collected 1.5 days post coitum (dpc), and their ZPs were removed by treatment with acid Tyrode's solution. All embryos were cultured in vitro up to the outgrowth stage at 7.5 dpc. In this study, ZP did not influence the cumulative times from 2-cell to further stages and blastulation. Interestingly, ZP free embryos at 4-cell stage have three patterns of blastomere alignment according to the number of contact points between blastomeres. However, blastomere alignment did not lead to any differences in morphokinetic comparisons. Regardless of the presence or absence of ZP, embryos compacted after the 8-cell stage took shorter time to become blastocysts than embryos compacted pre-8-cell stage. Nevertheless, cell-cell junction proteins required for successful compaction were similarly expressed between ZP intact and ZP free embryos. ZP intact embryos compacted post-8-cell stage had higher rate of reaching blastocysts than compacted ZP intact embryos before 8-cell stage while the outgrowth/blastocyst rate was similar. In this study, the presence or absence of ZP did not influence embryonic development and expression of cell surface glycoproteins, whereas compaction timing may be one of the criteria for evaluating embryo quality. ZP free embryos may become an alternative for overcoming cases with ZP problems in a human ART program.

Graphene Oxide Nanoribbon Hydrogel: Viscoelastic Behavior and Use as a Molecular Separation Membrane.

The preparation of carbon materials based hydrogels and their viscoelastic properties are essential for their broad application and scale-up. However, existing studies are mainly focused on graphene derivatives and carbon nanotubes, and the behavior of graphene nanoribbon (GNR), a narrow strip of graphene, remains elusive. Herein, we demonstrate the concentration-driven gelation of oxidized GNR (graphene oxide nanoribbon, GONR) in aqueous solvents. Exfoliated individual GONRs sequentially assemble into strings (∼1 mg/mL), nanoplates (∼20 mg/mL), and a macroporous scaffold (50 mg/mL) with increasing concentration. The GONR hydrogels exhibit viscoelastic shear-thinning behavior and can be shear-coated to form large-area GONR films on substrates. The entangled and stacked structure of the GONR film contributed to outstanding nanofiltration performance under high pressure, cross-flow, and long-term filtration, while the precise molecular separation with 100% rejection rate was maintained for sub-nanometer molecules.

Transparent Bendable Secondary Zinc-Air Batteries by Controlled Void Ionic Separators.

First ever transparent bendable secondary zinc-air batteries were fabricated. Transparent stainless-steel mesh was utilized as the current collector for the electrodes due to its reliable mechanical stability and electrical conductivity. After which separate methods were used to apply the active redox species. For the preparation of the anode, zinc was loaded by an electroplating process to the mesh. For the cathode, catalyst ink solution was spray coated with an airbrush for desired dimensions. An alkaline gel electrolyte layer was used for the electrolyte. Microscale domain control of the materials becomes a crucial factor for fabricating transparent batteries. As for the presented cell, anionic exchange polymer layer has been uniquely incorporated on to the cathode mesh as the separator which becomes a key procedure in the fabrication process for obtaining the desired optical properties of the battery. The ionic resin is applied in a fashion where controlled voids exist between the openings of the grid which facilitates light passage while guaranteeing electrical insulation between the electrodes. Further analysis correlates the electrode dimensions to the transparency of the system. Recorded average light transmittance is 48.8% in the visible light region and exhibited a maximum power density of 9.77 mW/cm2. The produced battery shows both transparent and flexible properties while maintaining a stable discharge/charge operation.