Association of plasma sPD-1 and sPD-L1 with disease status and future relapse in AQP4-IgG (+) NMOSD.

OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune-mediated disorder with aquaporin 4-immunoglobulin G (AQP4-IgG) in most settings. Soluble programmed death-1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) play key roles in immunomodulation. We aim to assess the association of sPD-1 and sPD-L1 with cytokines and their clinical significance in AQP4-IgG (+) NMOSD. METHOD: We measured plasma sPD-1, sPD-L1, and 10 cytokines levels of 66 AQP4-IgG (+) NMOSD patients, including 40 patients in attack (attack-NMOSD) and 26 patients in remission (remission-NMOSD) phases, and 28 healthy controls through ultrasensitive Simoa and SP-X platform, respectively. We also performed >2 years (median) of follow-up after testing and analyzed the relationship between the detection index and current and future clinical parameters. RESULT: Plasma sPD-1 level discriminated attack-NMOSD from remission-NMOSD (AUC = 0.692, p = 0.009). sPD-1 and sPD-L1 levels positively correlated with IL-6 (rsPD-1 = 0.313; rsPD-L1 = 0.508), IFN-γ (rsPD-1 = 0.331; rsPD-L1 = 0.456), and TNF-α (rsPD-1 = 0.451; rsPD-L1 = 0.531) expression, as well as clinical indicators, including the EDSS score (rsPD-1 = 0.331; rsPD-L1 = 0.402), number of attacks (rsPD-1 = 0.431) and segments of spinal cord involvement (rsPD-1 = 0.462; rsPD-L1 = 0.508). The risk of relapse within 2 years after sampling was associated with higher sPD-1/sPD-L1 ratio in attack-NMOSD (p = 0.022; Exp(B) = 1.589). INTERPRETATION: Plasma sPD-1 and sPD-L1 levels reflected current disease severity and activity, and predicted future relapses in AQP4-IgG (+) NMOSD, suggesting that they hold the potential to guide timely and targeted treatment.

Miller-Fisher syndrome and Guillain-Barre syndrome overlap syndrome following inactivated COVID-19 vaccine: Case report and scope review.

Miller-Fisher syndrome (MFS) is a rare variant of Guillain-Barré syndrome (GBS) manifesting as the triad of ataxia, areflexia, and ophthalmoplegia. With the extensive 2019 coronavirus disease (COVID-19) immunization program, cases of GBS or MFS following vaccination are increasingly being reported. A 64-y-old Chinese man presented with new-onset paresthesia of the extremities, bilateral abduction limitation, right facial palsy, areflexia of bilateral lower limbs, and left-dominant limb ataxia 12 d after the second dose of inactivated vaccine against COVID-19. Cerebrospinal fluid analysis indicated albumin-cytological dissociation and was positive for anti-GQ1b IgG and anti-GT1b IgG. Nerve conduction studies of limbs showed evidence of axonal neuropathy with reduced sensory amplitudes. Based on the clinical presentations, temporal progression of symptoms, and laboratory findings, the diagnosis of MFS-GBS overlap syndrome was made. The patient was treated with intravenous immunoglobulin and acupuncture and made a complete recovery 54 d after the onset of his initial neurological signs. To the best of our knowledge, we report the first case of MFS-GBS overlap syndrome following the inactivated COVID-19 vaccination. However, a coincidental relationship with this inactivated vaccine cannot be excluded. Although the benefits of COVID-19 vaccination largely outweigh its risk and the prognosis of MFS is generally favorable, a close surveillance of neurological complications post-COVID-19 vaccination is always necessary, considering its potentially disabling and lethal effects on vaccinated populations.

Serum Aquaporin 4-Immunoglobulin G Titer and Neuromyelitis Optica Spectrum Disorder Activity and Severity: A Systematic Review and Meta-Analysis.

Background: Aquaporin 4-immunoglobulin G (AQP4-IgG) plays a major role in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). Seropositive status for this antibody has become one of the required indicators for NMOSD diagnosis. Objective: Our goal was to systematically review and perform a meta-analysis of the current works of literature evaluating the clinical relevance of serum AQP4-IgG titer in patients with NMOSD. We sought to determine whether AQP4-IgG could indicate disease activity or severity, in addition to its diagnostic value in NMOSD. Methods: Electronic databases were searched for published literature, yielding 4,402 hits. Of the 124 full articles screened, 17 were included in the qualitative analysis and 14 in the meta-analysis. Results: There were no significant differences in serum AQP4-IgG titers between the relapse and remission phases in patients with NMOSD [standard mean difference (SMD): 0.32, 95% CI (-0.10, 0.74), p = 0.14]. Subgroup meta-analysis of AQP4-IgG detected by cell-based assays (CBA), an AQP4-IgG testing method recommended by the 2015 international consensus diagnostic criteria for NMOSD, confirmed the aforementioned result [SMD: 0.27, 95% CI (-0.01, 0.55), p = 0.06]. Moreover, the serum AQP4-IgG titer was positively correlated with the number of involved spinal cord segments [correlation coefficient (COR): 0.70, 95% CI (0.28-0.89), p = 0.003] and the Expanded Disability Status Scale (EDSS) score [COR: 0.54, 95% CI (0.06-0.82), p = 0.03] in the attack phase in patients with NMOSD. Conclusions: The present study systematically assessed the association between serum AQP4-IgG titer and NMOSD activity and severity. The results demonstrated that the serum AQP4-IgG titer was not associated with disease activity but indicated the disease severity in the attack phase in patients with NMOSD. A further meta-analysis with a larger number of studies that employed standardized AQP4-IgG assays and detected attack-remission paired samples from the same patients with detailed medication information will be required to confirm our findings and shed more light on optimizing clinical AQP4-IgG monitoring. Systematic Review Registration: [www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=208209], PROSPERO, identifier [CRD42020208209].

Urban rainfall characteristics and permeable pavement structure optimization for sponge road in North China.

Permeable asphalt pavement types are generally selected according to local traffic volume and rainfall intensity. This study focuses on the design of the pavement drainage asphalt pavement combination scheme by analyzing the rainfall characteristics of five representative cities in North China. Furthermore, nine kinds of drainage pavement scheme applicable to Beijing are proposed. To this end, the permeable function design analysis, as well as the bearing capacity design analysis of permeable asphalt pavement, was carried out with the help of storm runoff simulation software SWMM5.1 and pavement structure analysis software BISAR3.0, respectively. The results indicate that the minimum total design thickness of permeable surface layer and permeable basic layer meeting the requirements of road drainage in this region is 170 mm, and the nine drainage pavement schemes meet the specification requirements.

Serum Sphingosine 1-Phosphate (S1P): A Novel Diagnostic Biomarker in Early Acute Ischemic Stroke.

Background: Sphingosine 1-phosphate (S1P) is a lipid metabolite that mediates various physiological processes, including vascular endothelial cell function, inflammation, coagulation/thrombosis, and angiogenesis. As a result, S1P may contribute to the pathogenesis of stroke. Objective: This study aimed to evaluate the diagnostic value of serum S1P in acute stroke. Method: A total of 72 patients with ischemic stroke, 36 patients with hemorrhagic stroke, and 65 controls were enrolled. Serum S1P was detected by enzyme-linked immunosorbent assay (ELISA). Results: Receiver operating characteristic curve analysis demonstrated that serum S1P could discriminate ischemic stroke from hemorrhagic stroke in both total population and subgroup analyses of samples obtained within 24 h of symptom onset (subgroup < 24h) (area under curve, AUCTotal = 0.64, P = 0.017; AUCSubgroup < 24h = 0.91, P < 0.001) and controls (AUCTotal = 0.62, P = 0.013; AUCSubgroup <24h = 0.83, P < 0.001). Furthermore, S1P showed higher efficacy than high-density lipoprotein cholesterol (HDL-C) in discriminating ischemic stroke from controls in the total population (P S1P = 0.013, P HDL-C = 0.366) and in the subgroup analysis (i.e., <24 h; P S1P < 0.001, P HDL-C = 0.081). Additionally, lower serum S1P was associated with cervical artery plaques (P = 0.021) in controls and with dyslipidemia (P = 0.036) and milder neurological impairment evaluated by the National Institute of Health Stroke Scale (NIHSS, P = 0.047) in the ischemic stroke group. Conclusions: The present study preliminarily investigated the diagnostic value of serum S1P in acute stroke. Decreased serum S1P may become a potential biomarker for early acute ischemic stroke and can indicate disease severity.

Sap flow of Amorpha fruticosa: implications of water use strategy in a semiarid system with secondary salinization.

A. fruticosa (Amorpha fruticosa L.) is widely used for revegetation in semiarid lands that undergo secondary salinization. Understanding A. fruticosa plants response to soil water and salt stress is essential for water irrigation management and proper revegetation practices. In this study, we measured sap flow, stomatal conductance, meteorological and soil characteristics in an A. fruticosa community that recently experienced secondary salinization in northwestern China. Results of our study showed that daytime and nocturnal sap flows averaged 804.37 g·cm-2·day-1 and 46.06 g·cm-2·day-1, respectively, during the growing season. Within individual days, the highest sap flow appeared around noon local time and followed a similar pattern of photosynthetically active radiation (PAR). Despite the significant effect of meteorological factors on the characteristics of sap flow, our study highlighted that the sap flow of A. fruticosa is strongly regulated by the availability of soil relative extractable water (REW). The daytime sap flow, which is predominant compared to nocturnal sap flow, was strongly affected by PAR, air temperature and vapor-pressure deficit. With water stress in the top 40 cm of the soil (REW0-40 cm < 0.4), daytime sap flow displayed a strong relationship with soil water content (SWC) (positive) and soil electrical conductivity (EC) (negative) in the relatively shallow soil profile (up to 40 cm). For the nocturnal sap flow, our results suggest that in the absence of soil water stress (REW0-40 cm > 0.4), the nocturnal sap flow is mainly used to replenish the stem water content and sustain nocturnal transpiration. Under soil water stress, nocturnal sap flow is mainly used to replenish stem water content. The results of our study indicate that it is necessary to shorten the irrigation cycle during the primary growing period (May-July) of A. fruticosa. Moreover, in the absence of soil water stress (REW0-40 cm > 0.4), A. fruticosa can survive well in an saline environment with soil EC < 5 mS·cm-1.

Ligand-free iron-catalyzed benzylic C (sp3)-H amination of methylarenes with N-fluorobenzenesulfonimide.

Direct conversion of cheap methylarenes to benzylic amines, which are essential structural units of important drugs, is of great significance. However, the known methodologies suffer from the requirement of noble metal catalysts, heavy metal residues or strong oxidants. Herein, the first biocompatible iron-catalyzed benzylic C (sp3)-H amination of methylarenes with N-fluorobenzenesulfonimide is described. The reactions of methylarenes bearing electron-donating groups and electron-withdrawing groups ran smoothly under ligand and additional oxidant free conditions. Both toluene derivatives and 8-methylquinoline can be aminated by the same iron catalyst.

Ecological stoichiometric characteristics and element reserves of three stands in a closed forest on the Chinese loess plateau.

Populus davidiana, Leuchtenbergia principis, and Pinus tabulaeformis are important greening tree species with a cosmopolitan distribution. However, the stoichiometric characteristics and element reserves of stands of these three species are not particularly clear. In this study, we conducted a plot-level investigation of forest stands of these species in the loess area; these have been closed forest stands more than 28 years. Trees were sampled from an area of 50 m × 20 m (in 6, 8, and 9 plots, respectively), which was sufficient for shrub (2 m × 2 m), herbal species, and litter (1 m × 1 m) investigations. The C, N, and P concentrations and the C:N:P stoichiometry in five different soil layers (0-10 cm, 10-20 cm, 20-30 cm, 30-50 cm, and 50-100 cm) and in the leaves, stems, branches, and roots of the plants were examined. The soil element concentrations and density were affected by soil depth. The element content had a significantly negative correlation with soil depth, and element density differed significantly among the soil layers. A particular element in a particular organ differed significantly between the forest stands, and the same element in different organs of the same stand was also significantly different. The C, N, and P element reserves in the soil were considerably higher than in the plants. Our results indicate that there are different stoichiometric characteristics and element reserves of the three stands in a closed forest on the Chinese loess plateau, which may provide a reference when we develop and optimize the structure of forest stands.