Inhibition of complement C3 signaling ameliorates locomotor and visual dysfunction in autoimmune inflammatory diseases.

Neuromyelitis optica (NMO) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by transverse myelitis and optic neuritis. The pathogenic serum IgG antibody against the aquaporin-4 (AQP4) on astrocytes triggers the activation of the complement cascade, causing astrocyte injury, followed by oligodendrocyte injury, demyelination, and neuronal loss. Complement C3 is positioned as a central player that relays upstream initiation signals to activate downstream effectors, potentially stimulating and amplifying host immune and inflammatory responses. However, whether targeting the inhibition of C3 signaling could ameliorate tissue injury, locomotor defects, and visual impairments in NMO remains to be investigated. In this study, using the targeted C3 inhibitor CR2-Crry led to a significant decrease in complement deposition and demyelination in both slice cultures and focal intracerebral injection models. Moreover, the treatment downregulated the expression of inflammatory cytokines and improved motor dysfunction in a systemic NMO mouse model. Similarly, employing serotype 2/9 adeno-associated virus (AAV2/9) to induce permanent expression of CR2-Crry resulted in a reduction in visual dysfunction by attenuating NMO-like lesions. Our findings reveal the therapeutic value of inhibiting the complement C3 signaling pathway in NMO.

Seven new pentasaccharides from the roots of Rehmannia glutinosa.

Seven new pentasaccharides (1-7), rehmaglupentasaccharides A-G, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known verbascose (8) and stachyose (9) were also obtained in the current investigation, and the structure of stachyose was unequivocally defined using X-ray diffraction data. Compounds 1-9 were tested for their cytotoxicity against five human tumor cell lines, influence on dopamine receptor activation, and proliferation effects against Lactobacillus reuteri.

[Rapid determination of 16 polycyclic aromatic hydrocarbons in atmospheric fine particles by molecularly imprinted column-high performance liquid chromatography].

OBJECTIVE: A high performance liquid chromatographic method based on the purification of polycyclic aromatic hydrocarbon molecularly imprinted columns was developed, this method was used for the rapid quantitative determination of 16 polycyclic aromatic hydrocarbons(PAHs) in fine particulate matter(PM_(2.5)). METHODS: The polycyclic aromatic hydrocarbons of the sample were extracted with acetonitrile ultrasonically, purified by molecular imprinting column(MIP-PAHs), and tested after being concentrated by nitrogen blowing. RESULTS: The 16 PAHs showed a good linear relationship in the range of 1-40 ng/mL, and the correlation coefficient r>0.9996; the recoveries were 77.13%-107.67% at the three standard addition levels of 5.0, 10.0 and 20.0 ng/mL, the relative standard deviation was 0.15%-4.63%(n=7); the detection limit of the method was 0.004-0.078 ng/m~3, and the quantification limit was 0.016-0.336 ng/m~3. CONCLUSION: The detection of 16 PAHs in PM_(2.5) using this method is more accurate, more sensitive and less time consuming than the result of the simple ultrasonic extraction method and the Soxhlet extraction method in Determination of PAHs in ambient air and exhaust gases in gas phase and particulate matter by high performance liquid chromatography(HJ 647-2013).

Blockade of Kv1.3 potassium channel inhibits CD8+ T cell-mediated neuroinflammation via PD-1/Blimp-1 signaling.

Kv1.3 potassium channel is considered as a target for the treatment of autoimmune diseases such as multiple sclerosis (MS), since Kv1.3 blockade suppresses memory T cell activation including cytotoxic CD8+ T cells. However, the underlying signaling pathway related to autoimmune CD8+ T cell inhibition by Kv1.3 channel in neuroinflammatory diseases remains unclear. We found that ImK, a selective Kv1.3 blocker, reduced auto-reactive CD8+ T cell infiltration in the spinal cords of experimental autoimmune encephalomyelitis (EAE) rats, an animal model of MS. ImK suppressed transcriptional factor Blimp-1 expression and reduced the cytotoxicity of CD8+ T cells on neuronal cells. Furthermore, ImK upregulated co-inhibitory molecule PD-1 to inhibit B lymphocyte-induced maturation protein (Blimp-1) in an IL-2 independent way. In addition, PD-1 inhibitor impaired the suppression of ImK on CD8+ T cells and accelerated EAE progression. Our study demonstrated a novel regulatory mechanism of Kv1.3 blockade on modulating CD8+ T cell differentiation through PD-1/Blimp-1 signaling. This work expands the understanding of Kv1.3 channel for modulating neuroinflammation.

Determination of optimum optoelectronic properties in vertically stacked MoS2/h-BN/WSe2 van der Waals heterostructures.

Current achievements show that inserting an insulator at the interface in van der Waals (vdW) heterostructures can improve the photoelectric conversion efficiency. However, the underlying mechanism of the intercalated insulator effect on photocarrier collection and recombination, etc., remains unclear at the atomic level. Herein, we investigate the influence of intercalated hexagonal boron nitride (h-BN) on the optoelectronic properties of MoS2/WSe2 vdW heterostructures based on the interface bond relaxation and detailed balance principles. It was found that the band offsets (barrier height) at the heterointerface decrease with increasing h-BN size and decreasing transition metal dichalcogenide (TMD) thickness. Moreover, the power conversion efficiency (PCE) in monolayer MoS2/11-layers h-BN/monolayer WSe2 can reach 3.23% and enhances with increasing thickness of TMDs. Also, the optimal thickness of h-BN in MoS2/h-BN/WSe2 decreases from 3.64 to 2.86 nm as the thickness of TMDs increases. Our results show that the PCE and open-circuit voltage of the MoS2/h-BN/WSe2 vdW heterostructure are obviously improved compared with the bilayer heterostructure without h-BN, and this further proves the feasibility of the intercalated insulator as a booster for highly efficient photovoltaic and optoelectronic nanodevices.

The impact of carbon trading on the "quantity" and "quality" of green technology innovation: A dynamic QCA analysis based on carbon trading pilot areas.

To study the multi-factor linkage effect of carbon trading on green technology innovation, this paper employs the dynamic QCA analysis method and uses panel data from China's carbon trading pilot areas. The aim is to explore the causal path considering the time effect. Additionally, the Kruskal-Wallis rank sum test is applied to investigate the provincial coverage difference of the configuration and reveal the variation in configuration preferences between regions from a spatial dimension. The results indicate that a single factor alone does not constitute the necessary conditions for the "quantity" and "quality" of high-green technology innovation. However, the necessity of carbon trading price exhibits a declining trend over the years, demonstrating the presence of a time effect. Regarding the sufficiency analysis of conditional configuration, it mainly includes a "price-market scale" dual effect model and a single market scale effect model, with three configuration paths for each model. Among them, the "price-market scale" dual effect model can drive the increase in the quantity of green technology innovation through carbon trading price, market scale, government intervention degree, and other factors. The single market scale effect model can promote the high-quality development of green technology innovation, but the impact of carbon trading price on the quality of green technology innovation is relatively insignificant. In terms of the time dimension, the three configurations still maintain good applicability to green technology innovation under normal conditions. However, when considering the spatial dimension, the coverage distribution of the three configurations exhibits evident regional differences. This study introduces the dynamic panel QCA method into the research field for the first time. It addresses the limitations of the traditional QCA method, which is constrained by cross-section data and lacks the ability to explore the linkage effect between factors over time. Additionally, the study analyzes the effects of carbon trading price and market size on the "quantity" and "quality" of green technology innovation, considering both time and space dimensions, from a configuration perspective.

Tunable electronic and photoelectric properties of Janus group-III chalcogenide monolayers and based heterostructures.

Janus group-III chalcogenide monolayers and based heterostructures with breaking vertical structural symmetry offer additional prospects in the upcoming high-performance photoelectric devices. We studied the geometrical, electronic, and photoelectric properties of Janus group-III chalcogenide monolayers and heterostructures. The most energy favorable stacking design of ten vertical heterostructures are considered. The results showed that the Janus Se-In-Ga-S and S-In-Ga-Se monolayers exhibit semiconducting characteristics with the band gaps of 1.295 eV and 1.752 eV, respectively. Furthermore, the different stacking configurations and surface termination at interface can realize the transition of band alignment between type I and type II due to the interlayer coupling. Moreover, we systematically investigated the photoelectric properties of Janus group-III chalcogenide heterostructures and predicated an optimized power conversion efficiency of 16.2%. These findings can aid in comprehending the customized characteristics of Janus group-III chalcogenide heterostructures, offering theoretical guidance for creating innovative photoelectric devices.

Unique attributes of official endorsers in destination marketing.

Along with the digital transformation of the administrative environment and the end of the COVID-19 pandemic, official endorsers have nurtured a new channel for tourism destination marketing, which is of great significance to local economic recovery. However, less attention has been paid to the different effects of endorsement between ordinary endorsers and official endorsers, mainly due to their contrasting social statuses. To bridge the research gap, the source credibility model and social identity theory are integrated to construct the distinctive attributes of officials, as well as structural equation model is utilized to explore the underlying mechanism of official endorsement. Findings indicate that trustworthiness, the sense of authority, expertise, and attractiveness have direct positive effects on official identification, while also indirectly influencing tourists' attitudes toward the destination through official identification. These findings provide theoretical and managerial implications for the local government managers involved in tourism destination marketing.

Teriflunomide Promotes Blood-Brain Barrier Integrity by Upregulating Claudin-1 via the Wnt/ß-catenin Signaling Pathway in Multiple Sclerosis.

The blood-brain barrier (BBB) and tight junction (TJ) proteins maintain the homeostasis of the central nervous system (CNS). The dysfunction of BBB allows peripheral T cells infiltration into CNS and contributes to the pathophysiology of multiple sclerosis (MS). Teriflunomide is an approved drug for the treatment of MS by suppressing lymphocytes proliferation. However, whether teriflunomide has a protective effect on BBB in MS is not understood. We found that teriflunomide restored the injured BBB in the EAE model. Furthermore, teriflunomide treatment over 6 months improved BBB permeability and reduced peripheral leakage of CNS proteins in MS patients. Teriflunomide increased human brain microvascular endothelial cell (HBMEC) viability and promoted BBB integrity in an in vitro cell model. The TJ protein claudin-1 was upregulated by teriflunomide and responsible for the protective effect on BBB. Furthermore, RNA sequencing revealed that the Wnt signaling pathway was affected by teriflunomide. The activation of Wnt signaling pathway increased claudin-1 expression and reduced BBB damage in cell model and EAE rats. Our study demonstrated that teriflunomide upregulated the expression of the tight junction protein claudin-1 in endothelial cells and promoted the integrity of BBB through Wnt signaling pathway.

Serum GLP-1 and IGF-1 levels are candidate diagnostic biomarkers for type 2 diabetes mellitus complicated by coronary heart disease.

BACKGROUND: Objective: The aim of this study was to analyze the role of blood Glucagon like peptide-1 (GLP-1), insulin-like growth element-1 (IGF-1), and type 2 diabetes mellitus (T2DM) in coronary heart disease (CHD). METHOD: In this study, the clinical data of T2DM patients (n=203) admitted to Baoding Second Hospital from June 2020 to June 2021 were retrospectively analyzed. The patients included 65 T2DM patients without CHD who were assigned to the T2DM group and 138 T2DM patients with a CHD and T2DM comorbidity assigned to the CHD group. The baseline demographic characteristics and laboratory indexes of the two groups were explored, and the relationship between expression profiles of GLP-1 and IGF-1 levels and T2DM complicated by CHD was evaluated. The patients in the CHD group were sub-classified by the SYNTAX score system according to the results of coronary angiography. The three groups included a low-risk group with 52 cases, medium-risk group with 45 cases, and high-risk group with 41 cases. The relationship between GLP-1 and IGF-1 levels and the risk level of T2DM complicated by CHD was evaluated. RESULTS: Significant differences in age, smoking history, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), fasting blood glucose, GLP-1, and IGF-1 were observed between the two groups. Multivariate analysis revealed that smoking history, LDL-C, GLP-1, and IGF-1 were risk factors for CHD. Spearman correlation analysis showed a positive correlation between GLP-1 level and the occurrence of T2DM complicated by CHD, whereas IGF1 level was negatively correlated with the occurrence of T2DM complicated by CHD. GLP-1 and IGF-1 levels showed significant differences between risk groups. The GLP-1 level in the high-risk group was higher than that in the low- and medium-risk groups whereas IGF-1 level was lower in the high-risk group relative to the other two groups. CONCLUSION: Blood GLP-1 and IGF1 levels were associated with occurrence of T2DM complicated by CHD. Elevated level of blood GLP-1 was positively correlated with high risk of T2DM complicated by CHD whereas a lower blood IGF1 level was positively correlated with risk of T2DM complicated by CHD.

Carbon emissions predicting and decoupling analysis based on the PSO-ELM combined prediction model: evidence from Chongqing Municipality, China.

The "14th Five-Year Plan" period is a crucial phase for China to achieve the goal of carbon peaking and carbon neutrality (referred to as the "double carbon"). Thus, it is very important to analyze the main factors affecting carbon emissions and accurately predict the change of carbon emissions to achieve the goal of double carbon. For the slow data updates and the low accuracy of traditional prediction models about the carbon emissions, the key factors of carbon emissions change selected by gray correlation method and the consumption of coal, oil, and natural gas were input into four single prediction models: gray prediction model GM(1,1), ridge regression, BP neural network, and WOA-BP neural network to obtain the fitted and predicted values of carbon emissions, which serve as input to the particle swarm optimization-extreme learning machine (PSO-ELM) model together. Based on the PSO-ELM combined prediction method above and the scenario prediction indicators constructed according to relevant policy documents of Chongqing Municipality, the carbon emission values of Chongqing Municipality during the 14th Five-Year Plan period are predicted in this paper. The empirical results show that carbon emissions of Chongqing Municipality still maintain an upward trend, but the growth rate slow down compared with 1998 to 2018. In general, the carbon emission and GDP of Chongqing Municipality showed a weak decoupling state during 1998 to 2025. By calculation, the PSO-ELM combined prediction model is superior to the above four single prediction models in carbon emission prediction and has good property by the robust testing. The research results can enrich the combined prediction method about the carbon emissions and provide policy suggestions for Chongqing's low-carbon development during the 14th Five-Year Plan period.

Efficacy and safety of glucagon-like peptide-1 receptor agonist combined with sodium-glucose co-transporter-2 inhibitor in the treatment of type 2 diabetes mellitus patients with obesity: a retrospective analysis study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and obesity are metabolic diseases characterized by high economic and health burdens. A combination of sodium glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (DAPA) and glucagon-like peptide-1 receptor agonist (GLP1-RA) exenatide (ExQW) has not been explored as a treatment strategy for T2DM patients with obesity. Therefore, this retrospective analysis compared the efficacy and safety of dapagliflozin (DAPA) combined with GLP1-RAs Exenatide (ExQW) and dapagliflozin alone in the treatment of 125 T2DM patients with obesity. METHODS: This study is a retrospective study. From May 2018 to December 2019, 62 T2DM patients with obesity were treated with DAPA + ExQW, labeled DAPA + ExQW group. From December 2019 to December 2020, 63 patients with T2DM and obesity were treated with DAPA + placebo, labeled the DAPA + placebo group. DAPA + ExQW group received DAPA at a dose of 10 mg/day plus ExQW at 2 mg/week and DAPA + placebo group was administered with DAPA at a dose of 10 mg/day plus a placebo. The primary outcome for the present study was change in HbA1c (%) at different treatment points relative to the baseline. The secondary outcomes included changes in fasting plasma glucose (FPG, mmol/L), systolic blood pressure (SBP, mm/Hg) and body weight (BW, kg). Study outcomes were evaluated at 0, 4, 8, 12, 24, and 52 weeks after initial treatment. All P values were two-sided, with a P value less than 0.05 indicating statistical significance. RESULTS: A total of 125 patients completed the present study (62 in the DAPA + ExQW group and 63 in the DAPA group). Patients in the DAPA group showed a significant decrease in the level of HbA1c during the first 4 weeks, but the HbA1c level in this group remained stable for the remaining 48 weeks. Similar results were observed for other variables such as FPG, SBP, and BW. Patients who received a combination of DAPA and ExQW exhibited a continuous decline in the evaluated variables. The decrease in all the variables was greater in the DAPA + ExQW group than that in the DAPA group. CONCLUSIONS: A combination of DAPA and ExQW exerts a synergistic effect in the treatment of T2DM patients with obesity. However, the potential synergistic mechanism of this combination should be studied further.

The impact of enterprise resilience and HRM practices on performance: Findings from fsQCA.

Background: Both enterprise resilience and HRM practices can have a positive impact on enterprise performance. The impact of enterprise resilience or human resource management (HRM) practices on enterprise performance independently has been studied widely. But few studies have combined the above two aspects to discuss their impact on enterprise performance. Objective: In order to provide positive conclusions for improving enterprise performance, the theoretical model is established to expound the relationship between enterprise resilience, HRM practices including their internal influencing factors and enterprise performance. According to this model, a series of hypotheses about the influence of the combination from these internal factors on enterprise performance are presented. Method: Based on the statistical data of the questionnaire survey with managers and general employees at different levels in enterprises as respondents, the correctness of these hypotheses is proved by the fuzzy set qualitative comparative analysis (fsQCA) method. Results and discussion: The impact of the combination of enterprise resilience for high enterprise performance is shown in Table 3. The positive impact on the configuration of HRM practices for enterprise performance is shown in Table 4. The influences of the various combinations of internal factors about enterprise resilience and HRM practices on enterprise performance are shown in Table 5. From Table 4, it is discovered that performance appraisal and training have a significant positive effect on high enterprise performance. From Table 5, it is found that information sharing capabilities play a critical role, and enterprise resilience capabilities have a relatively positive impact on enterprise performance. Therefore, managers need to seek the development of enterprise resilience and HRM practices simultaneously and choose the most suitable combination configuration according to the actual situation of the enterprise itself. Moreover, a meeting system should be set up to ensure the transmission of internal information efficiently and accurately.

Pressure and strain engineering of the structural and electronic transitions in ReS2.

The distinctive crystal structure and anisotropic electrical characteristics of rhenium disulfide (ReS2) have garnered growing interest. Pressure and strain engineering has been used to modulate structural and electronic transition. Here, we present a comprehensive study on the high-pressure phase transition and strain tunable electronic properties of ReS2. There occurs a structural transition from distorted-1T to distorted-1T' at 7.5 GPa. In addition, ReS2has opposite piezoresistive effects along the two principle axes in the plane. This study shows that pressure and strain may be used to tune the characteristics of ReS2for future optoelectronic applications.

Targeting L-Selectin Lymphocytes to Deliver Immunosuppressive Drug in Lymph Nodes for Durable Multiple Sclerosis Treatment.

Inflammation induced by autoreactive CD4+ T lymphocytes is a major factor in the pathogenesis of multiple sclerosis (MS). Immunosuppressive drugs, such as FTY720, are subsequently developed to prevent the migration of CD4+ T lymphocytes to the central nervous system (CNS). However, these immunosuppressive drugs have limited accumulation in lymph nodes (LNs), resulting in poor efficacy. Here, this work develops a nanoplatform for delivering immunosuppressive drugs to LNs for durable MS treatment. Human CD47 peptide and L-selectin targeting aptamer are modified on the nanoparticles encapsulated with FTY720 (clnFTY) for self-passivation and the targeting of L-selectin on lymphocytes, a homing receptor for T-cells entering LNs. Using this natural process, clnFTY nanoparticles efficiently deliver FTY720 to LNs and delay disease progression in experimental autoimmune encephalomyelitis (EAE) mice following a single dose treatment over a 42-day observational period. Considering the daily dosing requirement of FTY720, this strategy greatly improves its therapeutic efficiency. The ability of clnFTY nanoparticles to target lymphocytes, reduce sphingosine-1-phosphate receptor 1 (S1PR1) expression, and suppress inflammatory cytokines release are demonstrated in clinical blood samples from MS patients. Taken together, this study demonstrates that targeted LNs delivery may greatly extend the treatment cycle of immunosuppressive drugs for durable MS treatment.

Gut Microbiome and Bile Acid Metabolism Induced the Activation of CXCR5+ CD4+ T Follicular Helper Cells to Participate in Neuromyelitis Optica Spectrum Disorder Recurrence.

From the perspective of the role of T follicular helper (Tfh) cells in the destruction of tolerance in disease progression, more attention has been paid to their role in autoimmunity. To address the role of Tfh cells in neuromyelitis optica spectrum disorder (NMOSD) recurrence, serum C-X-C motif ligand 13 (CXCL13) levels reflect the effects of the Tfh cells on B-cell-mediated humoral immunity. We evaluated the immunobiology of the CXCR5+CD4+ Tfh cells in 46 patients with NMOSD, including 37 patients with NMOSD with an annual recurrence rate (ARR) of<1 and 9 patients with NMOSD with an ARR of ≥1. Herein, we reported several key observations. First, there was a lower frequency of circulating Tfh cells in patients with an ARR of<1 than in those with an ARR of ≥1 (P< 0.05). Second, the serum CXCL13 levels were downregulated in individuals with an ARR<1 (P< 0.05), processing the ability to promote Tfh maturation and chemotaxis. Third, the level of the primary bile acid, glycoursodeoxycholic acid (GUDCA), was higher in patients with NMOSD with an ARR of<1 than in those with NMOSD with an ARR of ≥1, which was positively correlated with CXCL13. Lastly, the frequency of the Tfh precursor cells decreased in the spleen of keyhole limpet haemocyanin-stimulated animals following GUDCA intervention. These findings significantly broaden our understanding of Tfh cells and CXCL13 in NMOSD. Our data also reveal the potential mechanism of intestinal microbiota and metabolites involved in NMOSD recurrence.

Neutrophil Nanovesicle Protects against Experimental Autoimmune Encephalomyelitis through Enhancing Myelin Clearance by Microglia.

Timely clearance of myelin debris is the premise of neuroinflammation termination and tissue regeneration in multiple sclerosis (MS). Microglia are the main scavengers of myelin debris in MS lesions, but its phagocytic capability is limited in MS patients. Here, we develop neutrophil-derived nanovesicles (NNVs) to enhance the efficiency of myelin debris clearance in microglia for MS therapy. RNA sequencing (RNAseq) results demonstrate that NNVs treatment ameliorates lesional neuroinflammation of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Consequently, EAE mice exhibit favorable neurological functions and white matter integrity after NNVs treatment. Specifically, NNVs treatment upregulates the expression of nuclear factor E2-related factor 2 (NRF2) in microglia, as revealed by Assay for Transposase Accessible Chromatin using sequencing (ATACseq). We also demonstrate that NRF2 can activate the transcription of RUBCN (RUN domain and cysteine-rich domain containing Beclin 1-interacting protein), which in turn enhances LC3-associated phagocytosis (LAP) in microglia. As a result, myelin debris engulfed by microglia can be efficiently catabolized in NNVs-treated EAE mice without obvious side effects. Together, this study proves that NNVs can modulate neuroinflammation by clearing myelin debris and is a promising MS treatment strategy.

A novel nonsense SOD1 mutation (p.Asn140Ter) in a sporadic amyotrophic lateral sclerosis case with rapid progression.

Sporadic amyotrophic lateral sclerosis (ALS; SALS) accounts for more than 90% of all cases of the fatal neurodegenerative disease ALS. Cu/Zn superoxide dismutase (SOD1) gene mutations are the confirmed causes of adult-onset ALS. Here, we report a novel nonsense mutation, c.417_418insT (p.Asn140Ter), in exon 5 of the SOD1 gene in a Chinese adult female patient with SALS who showed rapid disease progression. This novel mutation will help deepen our understanding of the genetic pathogenesis of ALS.

Optical coherence tomography angiography helps distinguish multiple sclerosis from AQP4-IgG-seropositive neuromyelitis optica spectrum disorder.

INTRODUCTION: The aim was to characterize the optical coherence tomography (OCT) angiography measures in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) and to evaluate their disease discrimination capacity. METHODS: Patients with MS (n = 83) and AQP4-IgG-seropositive NMOSD (n = 91) with or without a history of optic neuritis, together with healthy controls (n = 34), were imaged. The main outcome measures were peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell-inner plexiform layer (GC-IPL) thickness, macular vessel density (VD), and perfusion density (PD) in the superficial capillary plexus. Diagnostic accuracy was assessed using the area under the receiver operating characteristics curve. RESULTS: Compared with patients with MS, those with NMOSD had a significantly smaller average thickness of the pRNFL and GC-IPL (80.0 [59.0; 95.8] µm versus 92.0 [80.2; 101] µm, p < .001; 68.0 [56.0; 81.0] µm, versus 74.5 [64.2; 81.0] µm, p < .001) and significantly smaller whole VD and PD areas (15.6 [12.6; 17.0] mm-1 versus 16.7 [14.8; 17.7] mm-1 , p < .001; 0.38 [0.31; 0.42] mm-1 versus 0.40 [0.37; 0.43] mm-1 , p < .01). The combination of structural parameters (average thickness of the pRNFL and GC-IPL) with microvascular parameters (temporal-inner quadrant of VD, temporal-inner, nasal-inferior, and nasal-outer quadrant of PD) was revealed to have a good diagnostic capability for discriminating between NMOSD and MS. CONCLUSIONS: OCT angiography reveals different structural and microvascular retinal changes in MS and AQP4-IgG-seropositive NMOSD. These combined structural and microvascular parameters might be promising biomarkers for disease diagnosis.

Different Exosomal microRNA Profile in Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorders.

Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) are inflammatory demyelinating diseases of the central nervous system. Exosomal microRNAs (miRNAs) are emerging biomarkers for demyelinating diseases. In this study, 52 aquaporin-4 antibody serum-positive NMOSD patients, 18 relapsing-remitting multiple sclerosis (RRMS) patients and 17 healthy controls (HCs) were included for the next-generation sequencing (NGS). To validate the NGS results, the valuable miRNAs were selected for validation by real-time quantitative polymerase chain reaction in another cohort of patients, comprising 31 NMOSD patients and 14 HCs. In addition, these miRNAs were also validated in a longitudinal study. NGS data revealed the exosomal miRNAs profile in NMOSD patients was different from HCs. Among those potential exosomal miRNAs which can distinguish NMOSD status, hsa-miR-122-3p and hsa-miR-200a-5p were the most abundant miRNAs. In addition, hsa-miR-122-3p and hsa-miR-200a-5p were significantly upregulated in the serum exosome of relapsing NMOSD compared with that in remitting NMOSD. Hsa-miR-122-3p and hsa-miR-200a-5p had positive correlations with disease severity in NMOSD patients. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the MAPK, Wnt and Ras signaling pathways were enriched. Further biological function analysis demonstrated that these two miRNAs might be involved in the immunoregulation of NMOSD pathogenesis. Our results indicated that miRNAs delivered by exosomes could be applied as potential biomarkers for NMOSD.