Severe acne is a chronic inflammatory skin disorder characterized by widespread inflammatory lesions including nodules, cysts and potential scarring. Here we perform the first genome-wide association study of severe acne in a Chinese Han population comprising 1,056 cases and 1,056 controls using the Illumina HumanOmniZhongHua-8 BeadChip. In an independent cohort of 1,860 cases and 3,660 controls of Chinese Han, we replicate 101 SNPs of which 3 showed consistent association. We identify two new susceptibility loci at 11p11.2 (DDB2, rs747650, P combined ¼ 4.41 Â 10 À 9 and rs1060573, P combined ¼ 1.28 Â 10 À 8 ) and 1q24.2 (SELL, rs7531806, P combined ¼ 1.20 Â 10 À 8 ) that are involved in androgen metabolism, inflammation processes and scar formation in severe acne. These results point to new genetic susceptibility factors and suggest several new biological pathways related to severe acne.

Myeloid-derived suppressor cells (MDSCs) have been reported to participate in immune suppression and autoimmune disorders. However, its role in autoimmune arthritis remains to be determined. We explored whether adoptive transfer of MDSCs in vivo would block joint inflammation and histological damage using collagen-induced arthritis (CIA) and antigen-induced arthritis (AIA) models. CD11b(+) Gr-1(+) MDSCs were isolated from the single cells from the spleens of CIA mice on day 41 or AIA mice on day 35. MDSCs (2 × 10(6)) were then transferred to AIA and CIA mice via tail vein before arthritis establishment at indicated time points. Phosphate buffered saline (PBS) was injected as control. Arthritis was evaluated by severity score and histology. The levels of TNF-α, IL-6, IL-17 and IL-10 in the serum and joints were detected by enzyme-linked immunosorbent assay (ELISA). The number of Th17 cells and macrophages in draining lymph nodes and joint tissues was assessed by flow cytometric analysis. Adoptive transfer of MDSCs significantly reduced the clinical score of arthritis, alleviated joint inflammation and histological damage both in AIA and CIA models compared with PBS-treated control groups. The levels of TNF-α, IL-6, IL-17, and IL-10 in the serum and joints were down-regulated by transfer of MDSCs. In addition, adoptive transfer of MDSCs significantly reduced the number of Th17 cells and macrophages in draining lymph nodes and joint tissues. Altogether, we demonstrate that adoptive transfer of MDSCs prevented autoimmune arthritis in mouse models of RA through inhibiting Th17 cells and macrophages. These new findings provide insights into the inhibitory functions of MDSCs and MDSCs may be used as a cell-based biotherapy in RA.

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Systemic lupus erythematosus (SLE) is an autoimmune disease accompanying excessive inflammatory responses. Phosphoinositide 3-kinase p110δ (PI3Kδ) is reported to associate with autoimmune conditions. We here aimed to determine whether selective inhibition of PI3Kδ is effective in a lupus model of BXSB mice, using the selective PI3Kδ inhibitor IC87114, which was intraperitoneally administrated to BXSB mice aged from 14 to 22 weeks. We showed that IC87114 improved renal function by decreasing the levels of proteinuria and serum creatinine, ameliorating the pathologic changes of kidneys and IgG and C3 deposition. Serum anti-autoantibody to nuclear antigen, anti-dsDNA, IL-1β, and IL-17 were markedly reduced by IC87114 therapy. Hepatic damage was also inhibited by administration of IC87114. Expression of phosphorylated AKT (p-AKT) and monocyte chemoattractant protein-1 was inhibited and mouse survival improved. In sum, PI3Kδ activation may be a critical factor for escalating autoimmune renal and hepatic damage, and its inhibition may alleviate the autoimmune damage. Our study reveals that the selective blockade of PI3Kδ is effective for mouse SLE.

The basic vibration generated during the tunneling process of hard rock tunnel results in the change of the support stiffness of the hydraulic pipe, which causes the problem of reduction of pipe transmission efficiency. A transverse motion equation of the hydraulic pipe was established by correlating with Hamilton’s principle under basic vibration. In consideration of the fluid-structure interaction (FSI), the support was simplified as an equivalent and a spring. The bidirectional fluid-solid coupling analysis method was used to investigate dynamic characteristics of the pipeline under different support stiffness conditions. The finite element method (FEM) and the experimental analysis are applied to verify the proposed methodology. The numerical results show that the maximum displacement of the pipe decreases with the increase of the support stiffness; the maximum stress of the pipe decreases first and then increases with the increase of the support stiffness; the amplitude of the fluid pressure fluctuation at the outlet of the pipe increases with the increase of the support stiffness. But the fluid pressure fluctuation with the higher stiffness is first stable, which can indicate that the support stiffness can increase the damping of the pipe system. This study can get a significant access to the structural design of the pipeline under basic vibration.