BACKGROUND The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS We observed a significant association (P<1.00×10 −10) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P = 5.10×10 −5) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae.

Global development has been heavily reliant on the overexploitation of natural resources since the Industrial Revolution. With the extensive use of fossil fuels, deforestation, and other forms of land-use change, anthropogenic activities have contributed to the ever-increasing concentrations of greenhouse gases (GHGs) in the atmosphere, causing global climate change. In response to the worsening global climate change, achieving carbon neutrality by 2050 is the most pressing task on the planet. To this end, it is of utmost importance and a significant challenge to reform the current production systems to reduce GHG emissions and promote the capture of CO 2 from the atmosphere. Herein, we review innovative technologies that offer solutions achieving carbon (C) neutrality and sustainable development, including those for renewable energy production, food system transformation, waste valorization, C sink conservation, and C-negative manufacturing. The wealth of knowledge disseminated in this review could inspire the global community and drive the further development of innovative technologies to mitigate climate change and sustainably support human activities.

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