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Introduction: One rare type of autoimmune disease is called neuromyelitis optica spectrum disorder (NMOSD) and the peripheral immune characteristics of NMOSD remain unclear. Methods: Here, single-cell RNA sequencing (scRNA-seq) is used to characterize peripheral blood mononuclear cells from individuals with NMOSD. Results: The differentiation and activation of lymphocytes, expansion of myeloid cells, and an excessive inflammatory response in innate immunity are observed. Flow cytometry analyses confirm a significant increase in the percentage of plasma cells among B cells in NMOSD. NMOSD patients exhibit an elevated percentage of CD8+ T cells within the T cell population. Oligoclonal expansions of B cell receptors are observed after therapy. Additionally, individuals with NMOSD exhibit elevated expression of CXCL8, IL7, IL18, TNFSF13, IFNG, and NLRP3. Discussion: Peripheral immune response high-dimensional single-cell profiling identifies immune cell subsets specific to a certain disease and identifies possible new targets for NMOSD.
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Enfermedades Autoinmunes , Neuromielitis Óptica , Humanos , Leucocitos Mononucleares , Neuromielitis Óptica/genética , Procesos de Crecimiento Celular , Análisis de Secuencia de ARNRESUMEN
Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a type of autoimmune encephalitis (AE) characterized by antibodies against NMDA receptor. As the most common AE, anti-NMDAR encephalitis affects 54% ~ 80% of patients with AE. It is associated with a high percentage of severe illness. It typically manifests as behavioral and psychiatric disturbance, epilepsy, cognitive decline, decreased level of consciousness, involuntary movements, autonomic dysfunction, central hypoventilation, etc. We report two refractory anti-NMDAR encephalitis. One of them describes a case of anti-NMDA encephalitis coexisting with MOG antibodies. The two patients were administered first-line therapy with glucocorticoids and intravenous immunoglobulin but did not improve clinically. Therefore, the patient was switched to the fully human anti-CD20 monoclonal antibody, ofatumumab. Their consciousness, behavioral and psychiatric disturbance, and capacity to conduct daily tasks improved markedly after sequential therapy with ofatumumab, as demonstrated by the modified Rankin scale (mRS) score. For the first time, we report a successful approach to the treatment of refractory anti-NMDAR encephalitis using the fully human anti-CD20 monoclonal antibody ofatumumab, which serves as an important reference for the treatment of AE.
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Introduction: Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a rare autoimmune disease, and the peripheral immune characteristics associated with anti-NMDARE antibodies remain unclear. Methods: Herein, we characterized peripheral blood mononuclear cells from patients with anti-NMDARE and healthy individuals by single-cell RNA sequencing (scRNA-seq). Results: The transcriptional profiles of 129,217 cells were assessed, and 21 major cell clusters were identified. B-cell activation and differentiation, plasma cell expansion, and excessive inflammatory responses in innate immunity were all identified. Patients with anti-NMDARE showed higher expression levels of CXCL8, IL1B, IL6, TNF, TNFSF13, TNFSF13B, and NLRP3. We observed that anti-NMDARE patients in the acute phase expressed high levels of DC_CCR7 in human myeloid cells. Moreover, we observed that anti-NMDARE effects include oligoclonal expansions in response to immunizing agents. Strong humoral immunity and positive regulation of lymphocyte activation were observed in acute stage anti-NMDARE patients. Discussion: This high-dimensional single-cell profiling of the peripheral immune microenvironment suggests that potential mechanisms are involved in the pathogenesis and recovery of anti-NMDAREs.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Humanos , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Leucocitos Mononucleares , Transcriptoma , Procesos de Crecimiento Celular , Inmunidad Humoral , Microambiente TumoralRESUMEN
BACKGROUND: Cryptococcal meningitis (CM) has a high morbidity and mortality due to the low detection of Cryptococcus in cerebrospinal fluid (CSF) during the early stage of the disease with traditional methods. CASE PRESENTATION: In addition to the traditional methods of India ink staining and cryptococcal antigen (CrAg), we used nanopore sequencing and next-generation sequencing (NGS) to detect pathogenic DNA in CSF samples of three patients with CM. The CSF samples of all three patients were positive by India ink staining and CrAg. NGS also detected Cryptococcus in all three CSF samples. Nanopore sequencing detected Cryptococcus in two CSF samples. CONCLUSION: Nanopore sequencing may be useful in assisting with the clinical diagnosis of CM. Further research is needed to determine the sensitivity and specificity of nanopore sequencing of CSF.
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Cryptococcus/genética , Meningitis Criptocócica/líquido cefalorraquídeo , Secuenciación de Nanoporos/métodos , Adulto , Antígenos Fúngicos/inmunología , Biomarcadores/líquido cefalorraquídeo , Cryptococcus/inmunología , Femenino , Humanos , Masculino , Meningitis Criptocócica/diagnóstico , Persona de Mediana EdadRESUMEN
Effectively controlling and modulating the electronic structure and magnetism is critical for the application of spintronics devices which based on two dimensional (2D) materials. Herein, by using density functional theory (DFT), we investigate synergistic effect of Mn (or Fe) doping and biaxial strain on electronic structure and magnetism of arsenene system. Unstrained Mn-doped arsenene exhibits a half-metallic state, but unstrained Fe-doped structure is narrow and direct band-gap semiconductor. The emerging spin splitting is caused by orbital hybridization of 4pâ-3d. Therefore, by the Mn and Fe doing, the systems produce a net magnetic moment of 4.00 and 1.00 [Formula: see text], respectively. Particularly, the room temperature ferromagnetism (RTFM) can be achieved in two doping structures. Under the condition of coexistence of impurity atom and biaxial strain, for the Mn doping, the systems are still half-metal materials and magnetism remain stable. While the Fe-doped system translates into a magnetic metal state due to the closure of band gap under the tensile strain of 4%. And the magnetic moments have a sudden transition, increase to 3.92, 5.00 and 5.00 [Formula: see text] under strains of 4%, 6% and 8%, respectively. In addition, the electronic structure and magnetism of Fe doping can also be affected by doping concentration. This work broadens the way about application of arsenene-based spintronic devices.
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Utilizing density functional theory, we investigate the structural stabilities, electronic structures, and optical properties of monolayer violet phosphorene, i.e., Hittorfene, under an external vertical electric field and upon in-layer biaxial strain control. We find that compared with monolayer black phosphorene, monolayer violet phosphorene has a significantly larger direct band gap of 2.50 eV, and it is sensitive to an external vertical electric field, under which it undergoes an intriguing direct-indirect and insulator-metal transition. By applying an in-layer biaxial strain, the semiconductor characteristic of monolayer violet phosphorene is found to be robust and stable over a wide range of strains (-10 to 10%), with a minimum bulk gap still being up to 0.90 eV at a tensile strain of 10%. This demonstrates that the band edges of monolayer violet phosphorene not only can straddle water redox potentials in the equilibrium state but can also be available within the strain range of -7 to 7% for facilitating photocatalytic water splitting. In particular, the suitable band edges and intensive absorption of visible light suggest that a strain ratio of -7% would be the more favorable condition for water splitting under visible light.
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[This corrects the article DOI: 10.1186/1754-6834-7-53.].
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BACKGROUND: Bioethanol production from biomass is becoming a hot topic internationally. Traditional static solid state fermentation (TS-SSF) for bioethanol production is similar to the traditional method of intermittent operation. The main problems of its large-scale intensive production are the low efficiency of mass and heat transfer and the high ethanol inhibition effect. In order to achieve continuous production and high conversion efficiency, gas stripping solid state fermentation (GS-SSF) for bioethanol production from sweet sorghum stalk (SSS) was systematically investigated in the present study. RESULTS: TS-SSF and GS-SSF were conducted and evaluated based on different SSS particle thicknesses under identical conditions. The ethanol yield reached 22.7 g/100 g dry SSS during GS-SSF, which was obviously higher than that during TS-SSF. The optimal initial gas stripping time, gas stripping temperature, fermentation time, and particle thickness of GS-SSF were 10 h, 35°C, 28 h, and 0.15 cm, respectively, and the corresponding ethanol stripping efficiency was 77.5%. The ethanol yield apparently increased by 30% with the particle thickness decreasing from 0.4 cm to 0.05 cm during GS-SSF. Meanwhile, the ethanol yield increased by 6% to 10% during GS-SSF compared with that during TS-SSF under the same particle thickness. The results revealed that gas stripping removed the ethanol inhibition effect and improved the mass and heat transfer efficiency, and hence strongly enhanced the solid state fermentation (SSF) performance of SSS. GS-SSF also eliminated the need for separate reactors and further simplified the bioethanol production process from SSS. As a result, a continuous conversion process of SSS and online separation of bioethanol were achieved by GS-SSF. CONCLUSIONS: SSF coupled with gas stripping meet the requirements of high yield and efficient industrial bioethanol production. It should be a novel bioconversion process for bioethanol production from SSS biomass.