Seven new risk coding variants have been identified through an exome-wide association study (EWAS), which studied the contributions of protein-coding variants to leprosy susceptibility. But some potential susceptibility loci were not studied in the previous EWAS study because of the project consideration. Seventeen unstudied potential susceptibility loci of the previous EWAS were validated in 3169 cases and 9814 controls in this study. Four disease-associated exonic loci were identified: rs671 in ALDH2 (P = 2.0 × 10 , odds ratio [OR] = 1.35), rs13259978 in SLC7A2 (P = 1.74 × 10 , OR = 1.28), rs925368 in GIT2 (P = 9.18 × 10 , OR = 1.44), and rs75680863 in TCN2 (P = 8.37 × 10 , OR = 0.74). Potentially implicating ZFP36L1 as a new susceptibility gene, 1 intergenic single nucleotide polymorphism (SNP), rs1465788 (P = 7.81 × 10 , OR = 0.88), was also suggested to be associated with leprosy. A luciferase reporter assay showed that the rs1465788 risk allele notably decreased the transcription activity of the flanking sequence. These findings suggest the possible involvement of lipid metabolism, NF-κB homeostasis and macrophage antimicrobial pathways in leprosy pathogenesis.
The development of heterojunctions with a strong bonding interface between metals and non-metals has attracted much attention owing to their great potential for use in lightweight structures. Laser joining technology, which emerged as a fast and reliable method, has proven its feasibility and unique advantages in joining metal to polymer matrix composites. Herein, an optimized laser joining configuration has been employed to realize high-quality joining of titanium alloy and carbon fiber-reinforced composite. Cross-sectional microstructures of laser-produced joints reveal that micro-bubbles near the interface have been effectively suppressed and eliminated due to the continual clamping pressure applied to the joined area during the joining process. Tensile tests suggest that the joint strength increases with structure density on a titanium alloy surface, and the greatest fracture strength of joints reaches more than 60 MPa even after experiencing a high–low temperature alternating aging test. For higher structure density (>95%), the joints fail by the fracture of parent plastics near the joined area due to the tensile-loading-induced peel stress at the edges of the overlap region. Otherwise, the joints fail by interfacial shear fracture with breakage when the structure density is lower than 91.5%. The obtained high-performance heterojunctions show great potential in the aerospace and automotive fields.
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