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The 3-DOF spherical gear is proposed and its tooth surface is composed of involute ring tooth surface and semi-spherical bevel tooth surface， the error-free transmission can be realized. Based on the involute forming principle and the coordinate transformation theory， the curved surface equations of annular tooth and arc tooth are derived. According to the meshing principle and motion analysis， the conjugate tooth surface of the arc tooth surface is obtained. The simulation tooth surface and 3D model of 3-DOF spherical gear are obtained by computer， the correctness of tooth surface equation is verified. The basis for the kinematics and dynamics analysis of the 3-dof spherical gear mechanism is provided.

The principle of tooth surface generating of skew bevel gear is analyzed about spherical involute， based on the theory that the line which in the plane that is tangent with the base cone of the skew bevel gear roll on the cone surface absolutely， a new milling method of gear surface is put forward. In this method， the alignment line obtained by the vertical intersection of the edge end circle and the base plane of the disk milling cutter is the tooth surface generation line， the relative motion between tool and workpiece is realized by using the relative motion relation generated by tooth surface. By analyzing the tooth surface generation motion， the machining motion process model of the tool and the workpiece is established. The tooth surface cutting is realized by the way of three-axis linkage of machine tool. The device for cutting test of skew bevel gear is designed and the correctness and feasibility of the method are verified by cutting test.

ObjectivesNumerous observational studies have reported associations between circulating cytokines and atopic dermatitis (AD); however, the causal relationships between them remain unclear. To explore the causal correlations and direction of causal effects between AD and levels of 91 circulating cytokines.MethodsTwo-sample Mendelian randomization (MR) analyses were conducted to examine the causal relationships between 91 circulating cytokines and AD using summary statistics from genome-wide association studies (GWAS). Reverse MR analyses were performed to investigate reverse causation. Pleiotropy and heterogeneity tests were conducted to assess the robustness of the findings. Additional transcriptome database and clinical peripheral blood mononuclear cells (PBMCs) samples were utilized to validate the results of MR analyses.ResultsLevels of interleukin (IL)-13, IL-18 Receptor 1, Tumor necrosis factor ligand superfamily member 14 (TNFSF14), TNF-related activation-induced cytokine (TRANCE), C-X-C motif chemokine (CXCL)11, IL-33, TNF-beta and CD5 were suggestively associated with the risk of AD (odds ratio, OR: 1.202, 95% CI: 1.018–1.422, p = 0.030; OR: 1.029, 95% CI: 1.029–1.157, p = 0.004; OR: 1.159, 95% CI: 1.018–1.320, p = 0.026; OR: 1.111, 95% CI: 1.016–1.214, p = 0.020; OR: 0.878, 95% CI: 0.783–0.984, p = 0.025; OR: 0.809, 95% CI: 0.661–0.991, p = 0.041; OR: 0.945, 95% CI: 0.896–0.997, p = 0.038; OR: 0.764, 95% CI: 0.652–0.895, p = 8.26e-04). In addition, levels of cytokines including Axin-1, CXCL5, CXCL10, Oncostatin-M (OSM), Sulfotransferase 1A1 (SULT1A1) and TNFSF14 were suggested to be consequences of AD (Beta: -0.080, p = 0.016; Beta: -0.062, p = 0.036; Beta: -0.066, p = 0.049; Beta: -0.073, p = 0.013; Beta: -0.089, p = 0.008; Beta: -0.079, p = 0.031). IL-13, IL-18R1, TNFSF14, and TRANCE were upregulated in both lesional skin biopsies and PBMCs from AD patients.ConclusionThe study indicates that several cytokines, including IL-13, IL-18R1, TNFSF14, TRANCE, CXCL11, IL-33, TNF-beta, and CD5, are upstream of AD development, whereas a few circulating cytokines are potentially downstream in the development of AD.

Fucoxanthin is the most abundant marine carotenoid derived from edible brown seaweeds and has been used as a functional ingredient for the treatment of obesity. However, poor brain bioavailability of fucoxanthin has limited its application in combating neurological diseases. In this study, we demonstrated that 40 % fucoxanthin was released from polylactic-co-glycolic acid-polyethylene glycol (PLGA-PEG) nanoparticles at one day after incubation. Fucoxanthin nanoparticles (20–40 mg/kg, i.v.) significantly prevented neurological and behavioral deficits in middle cerebral artery occlusion/reperfusion (MCAO)-treated rats via the reduction of M1 microglial activation, decrease of pro-inflammatory factor production, inactivation of the nuclear factor-κB (NF-κB) pathway, and elevation of the nuclear factor-E2-related factor 2 (Nrf2) pathway in ischemic penumbra. Moreover, fucoxanthin nanoparticles (5–15 μg/mL) inhibited hypoxia-stimulated neurotoxicity in a mouse hippocampal neuron cell line (HT22 cells). These results suggest that fucoxanthin nanoparticles enhanced brain bioavailability and produced neuroprotection against ischemic stroke in vivo with much lower effective concentrations than fucoxanthin itself, providing further support for the development of fucoxanthin as a functional ingredient for the prevention of ischemic stroke with proper nanoparticle formulations.