Healable and conductive sulfur iodide for solid-state Li-S batteries.

Solid-state Li-S batteries (SSLSBs) are made of low-cost and abundant materials free of supply chain concerns. Owing to their high theoretical energy densities, they are highly desirable for electric vehicles1-3. However, the development of SSLSBs has been historically plagued by the insulating nature of sulfur4,5 and the poor interfacial contacts induced by its large volume change during cycling6,7, impeding charge transfer among different solid components. Here we report an S9.3I molecular crystal with I2 inserted in the crystalline sulfur structure, which shows a semiconductor-level electrical conductivity (approximately 5.9 × 10-7 S cm-1) at 25 °C; an 11-order-of-magnitude increase over sulfur itself. Iodine introduces new states into the band gap of sulfur and promotes the formation of reactive polysulfides during electrochemical cycling. Further, the material features a low melting point of around 65 °C, which enables repairing of damaged interfaces due to cycling by periodical remelting of the cathode material. As a result, an Li-S9.3I battery demonstrates 400 stable cycles with a specific capacity retention of 87%. The design of this conductive, low-melting-point sulfur iodide material represents a substantial advancement in the chemistry of sulfur materials, and opens the door to the practical realization of SSLSBs.

Electrolyte design for Li-ion batteries under extreme operating conditions.

The ideal electrolyte for the widely used LiNi0.8Mn0.1Co0.1O2 (NMC811)||graphite lithium-ion batteries is expected to have the capability of supporting higher voltages (≥4.5 volts), fast charging (≤15 minutes), charging/discharging over a wide temperature range (±60 degrees Celsius) without lithium plating, and non-flammability1-4. No existing electrolyte simultaneously meets all these requirements and electrolyte design is hindered by the absence of an effective guiding principle that addresses the relationships between battery performance, solvation structure and solid-electrolyte-interphase chemistry5. Here we report and validate an electrolyte design strategy based on a group of soft solvents that strikes a balance between weak Li+-solvent interactions, sufficient salt dissociation and desired electrochemistry to fulfil all the aforementioned requirements. Remarkably, the 4.5-volt NMC811||graphite coin cells with areal capacities of more than 2.5 milliampere hours per square centimetre retain 75 per cent (54 per cent) of their room-temperature capacity when these cells are charged and discharged at -50 degrees Celsius (-60 degrees Celsius) at a C rate of 0.1C, and the NMC811||graphite pouch cells with lean electrolyte (2.5 grams per ampere hour) achieve stable cycling with an average Coulombic efficiency of more than 99.9 per cent at -30 degrees Celsius. The comprehensive analysis further reveals an impedance matching between the NMC811 cathode and the graphite anode owing to the formation of similar lithium-fluoride-rich interphases, thus effectively avoiding lithium plating at low temperatures. This electrolyte design principle can be extended to other alkali-metal-ion batteries operating under extreme conditions.

Evolution and Interplay of Lithium Metal Interphase Components Revealed by Experimental and Theoretical Studies.

Lithium metal batteries (LMB) have high energy densities and are crucial for clean energy solutions. The characterization of the lithium metal interphase is fundamentally and practically important but technically challenging. Taking advantage of synchrotron X-ray, which has the unique capability of analyzing crystalline/amorphous phases quantitatively with statistical significance, we study the composition and dynamics of the LMB interphase for a newly developed important LMB electrolyte that is based on fluorinated ether. Pair distribution function analysis revealed the sequential roles of the anion and solvent in interphase formation during cycling. The relative ratio between Li2O and LiF first increases and then decreases during cycling, suggesting suppressed Li2O formation in both initial and long extended cycles. Theoretical studies revealed that in initial cycles, this is due to the energy barriers in many-electron transfer. In long extended cycles, the anion decomposition product Li2O encourages solvent decomposition by facilitating solvent adsorption on Li2O which is followed by concurrent depletion of both. This work highlights the important role of Li2O in transitioning from an anion-derived interphase to a solvent-derived one.

Chelatococcus albus sp. nov., a bacterium isolated from hot spring microbial mat.

A Gram-stain-negative, non-endospore-forming, motile, short rod-shaped strain, designated SYSU G07232T, was isolated from a hot spring microbial mat, sampled from Rehai National Park, Tengchong, Yunnan Province, south-western China. Strain SYSU G07232T grew at 25-50 °C (optimum, 37 °C), at pH 5.5-9.0 (optimum, pH 6.0) and tolerated NaCl concentrations up to 1.0 % (w/v). Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain SYSU G07232T showed closest genetic affinity with Chelatococcus daeguensis K106T. The genomic features and taxonomic status of this strain were determined through whole-genome sequencing and a polyphasic approach. The predominant quinone of this strain was Q-10. Major cellular fatty acids comprised C19 : 0 cyclo ω8c and summed feature 8. The whole-genome length of strain SYSU G07232T was 4.02 Mbp, and the DNA G+C content was 69.26 mol%. The average nucleotide identity (ANIm ≤84.85 % and ANIb ≤76.08  %) and digital DNA-DNA hybridization (≤ 21.9 %) values between strain SYSU G07232T and the reference species were lower than the threshold values recommended for distinguishing novel prokaryotic species. Thus, based on the provided phenotypic, phylogenetic, and genetic data, it is proposed that strain SYSU G07232T (=KCTC 8141T=GDMCC 1.4178T) be designated as representing a novel species within the genus Chelatococcus, named Chelatococcus albus sp. nov.

Wavelength-Dependent Dynamics of the O(1D2) Channel in the 1Δu State Photodissociation of CO2.

The wavelength-dependent dynamics of the O(1D2) channel, formed by photoexcitation of CO2 to the 1Δu state at 143.53-153.03 nm, is investigated by using the time-sliced velocity-mapped ion imaging method. The measured ionic peaks of the O(1D2) images are analyzed to determine the total kinetic energy release (TKER) spectra and image anisotropy parameters. The structures observed in the TKER spectra can be directly assigned to the ro-vibrational state distributions of the counter CO photofragments. Compared to those observed at 157 and 155 nm, the highly rotationally excited CO photofragments still obviously appear in v = 0 and 1, but the fraction of rotational excitations is significantly reduced. Conversely, the CO photofragments exhibit substantially higher vibrational excitations, implying that the nearly linear 21A' state also contributes to dissociation in addition to the bend configuration. The image anisotropy parameters display an extremely slow decreasing trend with an increase of the CO ro-vibrational state besides those for the highest ro-vibrationally excited CO photofragments. Nevertheless, the nonaxial recoil effect, suggested in previous photodissociation studies of CO2 and other triatomic molecular systems, is still appropriate to explain the observations of internal energy dependences of image anisotropy parameters.

Realizing High Capacity and Zero Strain in Layered Oxide Cathodes via Lithium Dual-Site Substitution for Sodium-Ion Batteries.

Sodium-ion batteries have garnered unprecedented attention as an electrochemical energy storage technology, but it remains challenging to design high-energy-density cathode materials with low structural strain during the dynamic (de)sodiation processes. Herein, we report a P2-layered lithium dual-site-substituted Na0.7Li0.03[Mg0.15Li0.07Mn0.75]O2 (NMLMO) cathode material, in which Li ions occupy both transition-metal (TM) and alkali-metal (AM) sites. The combination of theoretical calculations and experimental characterizations reveals that LiTM creates Na-O-Li electronic configurations to boost the capacity derived from the oxygen anionic redox, while LiAM serves as LiO6 prismatic pillars to stabilize the layered structure through suppressing the detrimental phase transitions. As a result, NMLMO delivers a high specific capacity of 266 mAh g-1 and simultaneously exhibits the nearly zero-strain characteristic within a wide voltage range of 1.5-4.6 V. Our findings highlight the effective way of dual-site substitution to break the capacity-stability trade-off in cathode materials for advanced rechargeable batteries.

Inhibition of interaction between ROCK1 and Rubicon restores autophagy in endothelial cells and attenuates brain injury after prolonged ischemia.

Acute ischemic stroke (AIS) induces cerebral endothelial cell death resulting in the breakdown of the blood-brain barrier (BBB). Endothelial cell autophagy acts as a protective mechanism against cell death. Autophagy is activated in the very early stages of ischemic stroke and declines after prolonged ischemia. Previous studies have shown that Rubicon can inhibit autophagy. The current study aimed to investigate whether continuous long-term ischemia can inhibit autophagy in endothelial cells after ischemic stroke by regulating the function of Rubicon and its underlying mechanism. Wild-type male C57BL/6J mice were subjected to transient middle cerebral artery occlusion (tMCAO). ROCK1, ROCK2, and NOX2 inhibitors were injected into male mice 1 h before the onset of tMCAO. Disease severity and BBB permeability were evaluated. bEnd.3 cells were cultured in vitro and subjected to oxygen-glucose deprivation (OGD). bEnd.3 cells were pretreated with or without ROCK1, ROCK2, or NOX2 inhibitors overnight and then subjected to OGD. Cell viability and permeability were also evaluated. The expression of Rubicon, ROCK1, and autophagy-related proteins were analyzed. Increased BBB permeability was correlated with Rubicon expression in tMCAO mice and Rubicon was upregulated in endothelial cells subjected to OGD. Autophagy was inhibited in endothelial cells after long-term OGD treatment and knockdown of Rubicon expression restored autophagy and viability in endothelial cells subjected to 6-h OGD. ROCK1 inhibition decreased the interaction between Beclin1 and Rubicon and restored cell viability and autophagy suppressed by 6-h OGD treatment in endothelial cells. Additionally, ROCK1 inhibition suppressed Rubicon, attenuated BBB disruption, and brain injury induced by prolonged ischemia in 6-h tMCAO mice. Prolonged ischemia induced the death of brain endothelial cells and the breakdown of the BBB, thus aggravating brain injury by increasing the interaction of ROCK1 and Rubicon with Beclin1 while inhibiting canonical autophagy. Inhibition of ROCK1 signaling in endothelial cells could be a promising therapeutic strategy to prolong the therapeutic time window in AIS.

Decreased kynurenine in cerebrospinal fluid and potential role in neuromyelitis optica spectrum disorder.

Tryptophan (Trp) metabolism has been implicated in neuroinflammatory and neurodegenerative disorders, but its relationship with neuromyelitis optica spectrum disorder (NMOSD) is unclear. In this pilot study, cerebrospinal fluid (CSF) was prospectively collected from 26 NMOSD patients in relapse and 16 controls with noninflammatory diseases and 6 neurometabolites in the tryptophan metabolic pathway, including 5-hydroxytryptamine (5-HT), kynurenine (KYN), melatonin (MLT), 5-hydroxyindoleacetic acid (5HIAA), 3-hydroxy-o-aminobenzoic acid (3-HAA), and kynurenic acid (KYA), were measured by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The association of Trp metabolites with NMOSD and its clinical parameters was evaluated. The role of KYN, which is a Trp metabolite involved in the binding of NMOSD-IgG antibody to aquaporin 4 (AQP4), was also evaluated in vitro. CSF KYN was significantly decreased in patients with relapsing NMOSD compared to controls, and CSF KYN was associated with CSF white blood cells in NMOSD. In vitro experiments showed that NMOSD-IgG specifically recognized KYN, which reversed the NMOSD-IgG-induced downregulation of AQP4 expression. Our results show that abnormal Trp metabolism occurs in NMOSD and that KYN might be a potential target for the treatment of AQP4-IgG-positive NMOSD patients.

Toward Complete Transformation of Sodium Polysulfides by Regulating the Second-Shell Coordinating Environment of Atomically Dispersed Fe.

Room temperature sodium-sulfur (RT Na-S) batteries are highly competitive as potential energy storage devices. Nevertheless, their actually achieved reversible capacities are far below the theoretical value due to incomplete transformation of polysulfides. Herein, atomically dispersed Fe-N/S active center by regulating the second-shell coordinating environment of Fe single atom is proposed. The Fe-N4 S2 coordination structure with enhanced local electronic concentration around the Fermi level is revealed via synchrotron radiation X-ray absorption spectroscopy (XAS) and theoretical calculations, which can not only significantly promote the transformation kinetics of polysulfides, but induce uniform Na deposition for dendrite-free Na anode. As a result, the obtained S cathode delivers a high initial reversible capacity of 1590 mAh g-1 , nearly the theoretical value. This work opens up a new avenue to facilitate the complete transformation of polysulfides for RT Na-S batteries.

Thermus brevis sp. nov., a moderately thermophilic bacterium isolated from a hot spring microbial mat.

Three closely related, facultative anaerobic, Gram-stain-negative, twitching motile, short rod-shaped, non-endospore-forming, moderately thermophilic bacteria, designated strains SYSU G05001T, SYSU G05003 and SYSU G05004, were isolated from a hot spring microbial mat, collected from Rehai National Park, Tengchong, Yunnan Province, south-western China. The results of phylogenetic analysis based on the 16S rRNA gene sequences indicated that these three strains were closely related to Thermus scotoductus SE-1T (97.97, 98.18, 97.90 % sequence similarity). Whole genome sequencing and polyphasic taxonomic approach were used to determine the genomic profile and taxonomic status of the novel strain SYSU G05001T. Cell growth occurred at 37-80 °C (optimum, 55 °C), pH 6.0-8.0 (optimum, pH 7.0) and with 0-3.0 % (w/v) NaCl (optimum, 1%). Thiosulfate enhanced cell growth. MK-8 was the predominant menaquinone. The major cellular fatty acids included iso-C15 : 0, iso-C17 : 0 and anteiso-C15 : 0. The major polar lipids were consisted of aminophospholipid, glycolipid and phospholipids. The whole genome of strain SYSU G05001T consisted of 2.55 Mbp and the DNA G+C content was 64.94 mol%. The average nucleotide identity (≤94.95 %) and digital DNA-DNA hybridization (≤62.3 %) values between strain SYSU G05001T and other members of the genus Thermus were all lower than the threshold values recommended for distinguishing novel prokaryotic species. On the basis of the presented polyphasic evidence and genotypic data, it is proposed that strain SYSU G05001T (=KCTC 82627T=MCCC 1K06118T) represents a novel species of the genus Thermus, for which the name Thermus brevis sp. nov. is proposed.

Caldovatus aquaticus sp. nov., a moderately thermophilic bacterium isolated from hot spring microbial mat.

Two closely related, aerobic, Gram-stain-negative, motile, oval-shaped, non-endospore-forming, moderately thermophilic bacteria, designated strains SYSU G05006T and SYSU G05005, were isolated from a bioreactor enrichment and the original sample was collected from Rehai National Park, Tengchong, Yunnan Province, PR China. The results of phylogenetic analysis based on the 16S rRNA gene sequences indicated that these two strains were closely related to Caldovatus sediminis YIM 72346T (96.75 and 96.89 % sequence similarity, respectively). The whole genome size of strain SYSU G05006T was 3.87 Mbp with a DNA G+C content of 75.33 mol%. The average nucleotide identity (ANI based on the MUMmer algorithm≤90.31 % and ANI based on blast≤89.36 %) and digital DNA-DNA hybridization (≤35.10 %) values between strain SYSU G05006T and other members of the family Acetobacteraceae were all lower than the threshold values recommended for distinguishing novel prokaryotic species. Optimal growth of the strain was observed at 55 °C and pH 6.0. Ubiquinone-10 was the predominant respiratory lipoquinone. The major cellular fatty acids included iso-C14 : 0, C16 : 1 ω5c, summed feature 5 and summed feature 7. The major polar lipids consisted of diphosphatidylglycerol, one unidentified aminolipid, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, two unidentified phospholipids and two unidentified lipids. Based on results of phylogenetic analyses, comparative genomics and phenotypic characteristics, we describe a new species of the genus Caldovatus represented by strain SYSU G05006T (=KCTC 82831T=MCCC 1K06125T), for which we propose the name Caldovatus aquaticus sp. nov.

Flame-Retardant PEDOT:PSS/LDHs/Leather Flexible Strain Sensor for Human Motion Detection.

Flexible piezoresistive sensors have demonstrated great potential in human-motion-detection applications. However, it still remains a challenge to fabricate strain sensors with high sensitivity, broad sensing range, and good linear response to strain. In this report, a simple and scalable fabrication strategy is developed to construct high performance strain sensors by using leather as the substrates to filtrate poly(3,4-ethylenedioxythiophene): poly(4-styrenesulfonate) (PEDOT:PSS) modified layered double hydroxides (LDHs) suspensions. The naturally aligned collagen fibers in leather enable size selection for the 2D conductive materials and as such dual-conductive pathways are effectively formed on the surface and in the matrix of leather. Due to the unique design of conductive networks, the prepared sensor possesses high gauge factor (maximum value of 2326.84), tunable strain range (0-70%), fast tensile response time (160 ms), and good stability in 1000 stretching-relaxing/compression-relaxing cycles, making it suitable for various human motion detections including coughing and large-scale motions of joint bending. In addition, the incorporated LDHs is a non-toxic flame retardant, which is helpful to reduce electronic fire risk and can bring added value to the sensor.

The alteration of gut microbiome community play an important role in mercury biotransformation in largemouth bass.

Mercury (Hg) biotransformation is an important process that can affect the speciation and bioaccumulation of Hg in fish. The intestinal microbiota has been suggested to take part in this process. However, Hg biotransformation in fish is still unclear and the responses of gut microbiota to different Hg exposure scenarios have not been well addressed. The present study investigated the bioaccumulation and biotransformation of Hg in a freshwater fish (Micropterus salmoides) and characterized the gut microbiome community under dietary inorganic Hg (IHg) or methylmercury (MeHg) exposure, aiming to evaluate the effects of gut microbiome's activities on the internal-handling and fate of Hg in fish. Significant Hg methylation was observed in fish under IHg exposure, whereas there was no demethylation occurred in MeHg-treated fish. Both IHg and MeHg could significantly alter the community composition of gut microbiome. The administrated IHg in the food could enhance the growth of methylators, resulting in additional MeHg production in fish gut. However, abundance of demethylators was greatly decreased under either IHg or MeHg exposure, leading the demethylation process to be negligible. The results strongly suggested that the behaviors of gut bacterial community played an important role in the presence or absence of biotransformation processes. This study elucidated the importance of gut microbiome in Hg biotransformation process, and helped to develop a novel perspective to understand the Hg bioaccumulation of fish in realistic environment.

Vacancy-Enabled O3 Phase Stabilization for Manganese-Rich Layered Sodium Cathodes.

Manganese-rich layered oxide materials hold great potential as low-cost and high-capacity cathodes for Na-ion batteries. However, they usually form a P2 phase and suffer from fast capacity fade. In this work, an O3 phase sodium cathode has been developed out of a Li and Mn-rich layered material by leveraging the creation of transition metal (TM) and oxygen vacancies and the electrochemical exchange of Na and Li. The Mn-rich layered cathode material remains primarily O3 phase during sodiation/desodiation and can have a full sodiation capacity of ca. 220 mAh g-1 . It delivers ca. 160 mAh g-1 specific capacity between 2-3.8 V with >86 % retention over 250 cycles. The TM and oxygen vacancies pre-formed in the sodiated material enables a reversible migration of TMs from the TM layer to the tetrahedral sites in the Na layer upon de-sodiation and sodiation. The migration creates metastable states, leading to increased kinetic barrier that prohibits a complete O3-P3 phase transition.

Neutralization of interleukin-9 ameliorates experimental stroke by repairing the blood-brain barrier via down-regulation of astrocyte-derived vascular endothelial growth factor-A.

Astrocytes mediate the destruction of the blood-brain barrier (BBB) during ischemic stroke (IS). IL-9 is a pleiotropic cytokine that we previously found to be highly expressed in peripheral blood mononuclear cells from patients with IS, and the presence of IL-9 receptors on astrocytes has been reported in the literature. Here, we detected the effect of IL-9 on astrocytes using an anti-IL-9-neutralizing antibody to treat rats with experimental stroke. Supernatants from astrocytes treated with or without oxygen-glucose deprivation and/or IL-9 were incubated with bEnd.3 cell monolayers after blocking the IL-9 receptor on the endothelium. Immunofluorescence staining and Western blot analyses were conducted to observe the change in tight junction proteins (TJPs) in bEnd.3 cells as well as the level of VEGF-A and possible signal pathways in astrocytes. We also applied middle cerebral artery occlusion (MCAO) models to determine the effect of anti-IL-9-neutralizing antibodies on IS. As a result, astrocyte-conditioned medium treated with IL-9 aggravated the disruption of the BBB accomplished by the degradation of TJPs in endothelial cells. In addition, IL-9 increased the level of VEGF-A in astrocytes, and blocking the effect of VEGF-A reversed the breakdown of the BBB. In the MCAO model, anti-IL-9-neutralizing antibody reduced the infarct volume and BBB destruction. Mechanistically, the anti-IL-9-neutralizing antibody repaired the damaged TJPs (zonula occludens 1, occludin, and claudin-5) and induced a decrease in VEGF-A expression in ischemic lateral brain tissue. In contrast, a local injection of recombinant murine IL-9 to the brain resulted in a marked up-regulation of VEGF-A in the striatum. In conclusion, anti-IL-9-neutralizing antibody can reduce the severity of IS partially by alleviating the destruction of the BBB via down-regulation of astrocyte-derived VEGF-A. This finding suggests that targeting IL-9 or VEGF-A could provide a new direction for the treatment of IS.-Tan, S., Shan, Y., Lin, Y., Liao, S., Zhang, B., Zeng, Q., Wang, Y., Deng, Z., Chen, C., Hu, X., Peng, L., Qiu, W., Lu, Z. Neutralization of IL-9 ameliorates experimental stroke by repairing the blood-brain barrier via down-regulation of astrocyte-derived vascular endothelial growth factor-A.

The glucagon-like peptide-1 receptor agonist reduces inflammation and blood-brain barrier breakdown in an astrocyte-dependent manner in experimental stroke.

BACKGROUND: Preserving the integrity of the blood-brain barrier (BBB) is beneficial to avoid further brain damage after acute ischemic stroke (AIS). Astrocytes, an important component of the BBB, promote BBB breakdown in subjects with AIS by secreting inflammatory factors. The glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex-4) protects the BBB and reduces brain inflammation from cerebral ischemia, and GLP-1R is expressed on astrocytes. However, the effect of Ex-4 on astrocytes in subjects with AIS remains unclear. METHODS: In the present study, we investigated the effect of Ex-4 on astrocytes cultured under oxygen-glucose deprivation (OGD) plus reoxygenation conditions and determined whether the effect influences bEnd.3 cells. We used various methods, including permeability assays, western blotting, immunofluorescence staining, and gelatin zymography, in vitro and in vivo. RESULTS: Ex-4 reduced OGD-induced astrocyte-derived vascular endothelial growth factor (VEGF-A), matrix metalloproteinase-9 (MMP-9), chemokine monocyte chemoattractant protein-1 (MCP-1), and chemokine C-X-C motif ligand 1 (CXCL-1). The reduction in astrocyte-derived VEGF-A and MMP-9 was related to the increased expression of tight junction proteins (TJPs) in bEnd.3 cells. Ex-4 improved neurologic deficit scores, reduced the infarct area, and ameliorated BBB breakdown as well as decreased astrocyte-derived VEGF-A, MMP-9, CXCL-1, and MCP-1 levels in ischemic brain tissues from rats subjected to middle cerebral artery occlusion. Ex-4 reduced the activation of the JAK2/STAT3 signaling pathway in astrocytes following OGD. CONCLUSION: Based on these findings, ischemia-induced inflammation and BBB breakdown can be improved by Ex-4 through an astrocyte-dependent manner.

Nanoscale Perovskites as Catalysts and Supports for Direct Methanol Fuel Cells.

With the ultimate goal of simultaneously finding cost-effective, more earth-abundant, and high-performance alternatives to commercial Pt/Pd-based catalysts for electrocatalysis, this review article highlights advances in the use of perovskite metal oxides as both catalysts and catalyst supports towards the oxygen reduction reaction (ORR) and the methanol oxidation reaction (MOR) within a direct methanol fuel cell (DMFC) configuration. Specifically, perovskite metal oxides are promising as versatile functional replacements for conventional platinum-group metals, in part because of their excellent ionic conductivity, overall resistance to corrosion, good proton-transport properties, and potential for interesting acidic surface chemistry, all of which contribute to their high activity and reasonable stability, especially within an alkaline electrolytic environment.

Relapsing optic neuritis and meningoencephalitis in a child: case report of delayed diagnosis of MOG-IgG syndrome.

BACKGROUND: Recurrent optic neuritis (ON) was previously thought to be associated with multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Meningoencephalitis has recently been suggested to be a clinical finding typical of myelin oligodendrocyte glycoprotein (MOG) encephalomyelitis. We report a Chinese patient with recurrent ON at disease initiation, who had a delayed diagnosis of MOG-IgG syndrome, until recurrent meningoencephalitis appeared and serum MOG-IgG was detected. CASE PRESENTATION: From the age of 7 years, an AQP4-IgG negative female patient had 10 disease recurrences, including 4 episodes of recurrent ON, 4 episodes of fever and meningoencephalitis, and 2 episodes of ON as well as meningoencephalitis. She was initially diagnosed as recurrent ON and treated with glucocorticoids followed by gradual tapering when ON reoccurred. Later, she was diagnosed as central nervous system infection when fever and meningoencephalitis appeared, and antiviral drugs and glucocorticoids were used. However, when she returned to our department for follow-up on July 2017, the results of serum demyelinating autoimmune antibody revealed positive MOG-IgG (titer 1:320 by an in-house, cell-based assay using live cells transfected with full-length human MOG). A diagnosis of MOG-IgG syndrome was established. CONCLUSIONS: Testing for MOG-IgG in atypical MS and NMOSD patients, and patients with meningoencephalitis with a history of relapsing demyelinating symptoms is warranted.

Exacerbation of oxygen-glucose deprivation-induced blood-brain barrier disruption: potential pathogenic role of interleukin-9 in ischemic stroke.

Interleukin (IL)-9 exerts a variety of functions in autoimmune diseases. However, its role in ischemic brain injury remains unknown. The present study explored the biological effects of IL-9 in ischemic stroke (IS). We recruited 42 patients newly diagnosed with IS and 22 age- and sex-matched healthy controls. The expression levels of IL-9 and percentages of IL-9-producing T cells, including CD3+CD4+IL-9+ and CD3+CD8+IL-9+ cells, were determined in peripheral blood mononuclear cells (PBMCs) obtained from patients and control individuals. We also investigated the effects of IL-9 on the blood-brain barrier (BBB) following oxygen-glucose deprivation (OGD) and the potential downstream signaling pathways. We found that patients with IS had higher IL-9 expression levels and increased percentages of IL-9-producing T cells in their PBMCs. The percentages of CD3+CD4+IL-9+ and CD3+CD8+IL-9+ T cells were positively correlated with the severity of illness. In in vitro experiments using bEnd.3 cells, exogenously administered IL-9 exacerbated the loss of tight junction proteins (TJPs) in cells subjected to OGD plus reoxygenation (RO). This effect was mediated via activation of IL-9 receptors, which increased the level of endothelial nitric oxide synthase (eNOS), as well as through up-regulated phosphorylation of signal transducer and activator of transcription 1 and 3 and down-regulated phosphorylated protein kinase B/phosphorylated phosphatidylinositol 3-kinase signaling. These results indicate that IL-9 has a destructive effect on the BBB following OGD, at least in part by inducing eNOS production, and raise the possibility of targetting IL-9 for therapeutic intervention in IS.

Anti-inflammatory effect of cholera toxin B subunit in experimental stroke.

BACKGROUND: Cholera toxin B subunit (CTB) has multifaceted immunoregulatory functions. Immunity plays an important role in the mechanism of stroke. However, little is known about whether CTB is beneficial for stroke. METHODS: CTB was administered intraperitoneally after ischemia to rats subjected to transient focal ischemia. Infarct volumes, body weight loss, and neurologic deficits were measured. Cytokines, microglia/macrophage activation, and transcriptional factors in the ischemic brain were tested. The mRNA expressions of IL-1ß and TNF-α were tested in the microglia/macrophage isolated from the ischemic hemisphere. γδT cells, IL-17-producing γδT cells, Th17 cells, and regulatory T (Treg) cells in the ischemic brain were tested. γδT cells and Treg cells in the peripheral blood were also evaluated. RESULTS: CTB reduced infarct volumes, neurologic deficits, and body weight loss after ischemia. At 24 h after ischemia, CTB downregulated the levels of IL-1ß, TNF-α, NF-kB p65, phosphorylated-ERK1/2, and microglia/macrophage activation and suppressed NF-kB binding activity, but did not affect the level of ERK1/2. The mRNA expressions of IL-1ß and TNF-α in the microglia/macrophage isolated from the ischemic hemisphere were suppressed after CTB therapy. In the ischemic hemisphere, CTB treatment reduced the levels of γδT cells, IL-17-producing γδT cells, and IL-17 at both 24 and 72 h after ischemia, while Th17 cells were not affected. After CTB treatment, the levels of Treg cells, TGF-ß, and IL-10 remained unchanged at 24 h and upregulated at 72 h after ischemia. Inactivation of Treg cells using anti-CD25 attenuated the increase of TGF-ß and IL-10 induced by CTB at 72 h after ischemia. In the peripheral blood, CTB increased Treg cells and suppressed γδT cells at 24 h after ischemia. And then at 72 h after ischemia, it increased Treg cells but did not impact γδT cells. CTB had no effect on cytokines, transcription factors, infiltrating γδT cells, and Treg cells in the brain of shams. In the peripheral blood of shams, CTB increased Treg cells at both 24 and 72 h, while it did not affect γδT cells. CONCLUSIONS: CTB decreased neurologic impairment and tissue injury after cerebral ischemia via its immunomodulatory functions, including inhibiting microglia/macrophage activation, suppressing γδT cells, and inducing production of Treg cells, thus regulating the secretion of related cytokines. Suppression of NF-kB and ERK1/2 pathways is involved in the neuroprotective mechanism of CTB.