Distinct genomic traits of acral and mucosal melanomas revealed by targeted mutational profiling

The incidence of melanoma is rising globally including China. Comparing to Caucasians, the incidence of non‐cutaneous melanomas is significantly higher in Chinese. Herein, we performed genomic profiling of 89 Chinese surgically resected primary melanomas, including acral (n = 54), cutaneous (n = 22), and mucosal (n = 13), by hybrid capture‐based next‐generation sequencing. We show that mucosal melanomas tended to harbor more pathogenic mutations than other types of melanoma, though the biological significance of this finding remains uncertain. Chromosomal arm‐level alterations including 6q, 9p, and 10p/q loss were highly recurrent in all subtypes, but mucosal melanoma was significantly associated with increased genomic instability. Importantly, 7p gain significantly correlated with unfavorable clinical outcomes in non‐cutaneous melanomas, representing an intriguing prognostic biomarker of those subtypes. Furthermore, focal amplification of 4q12 (KIT, KDR, and PDGFRα) and RAD51 deletion were more abundant in mucosal melanoma, while NOTCH2 amplification was enriched in acral melanoma. Additionally, cutaneous melanomas had higher mutation load than acral melanomas, while mucosal melanomas did not differ from other subtypes in mutation burden. Together, our data revealed important features of acral and mucosal melanomas in Chinese including distinctive driver mutation pattern and increased genomic instability. These findings highlight the possibilities of combination therapies in the clinical management of melanoma.     

The Chimonanthus salicifolius genome provides insight into magnoliid evolution and flavonoid biosynthesis

Chimonanthus salicifolius, a member of the Calycanthaceae of magnoliids, is one of the most famous medicinal plants in Eastern China. Here, we report a chromosome‐level genome assembly of C. salicifolius, comprising 820.1 Mb of genomic sequence with a contig N50 of 2.3 Mb and containing 36 651 annotated protein‐coding genes. Phylogenetic analyses revealed that magnoliids were sister to the eudicots. Two rounds of ancient whole‐genome duplication were inferred in the C. salicifolious genome. One is shared by Calycanthaceae after its divergence with Lauraceae, and the other is in the ancestry of Magnoliales and Laurales. Notably, long genes with > 20 kb in length were much more prevalent in the magnoliid genomes compared with other angiosperms, which could be caused by the length expansion of introns inserted by transposon elements. Homologous genes within the flavonoid pathway for C. salicifolius were identified, and correlation of the gene expression and the contents of flavonoid metabolites revealed potential critical genes involved in flavonoids biosynthesis. This study not only provides an additional whole‐genome sequence from the magnoliids, but also opens the door to functional genomic research and molecular breeding of C. salicifolius.     

Studies on the effects of bone marrow stem cells on mitochondrial function and the alleviation of ARDS

Molecular and Cellular Biochemistry - Mesenchymal stem cells (MSCs) can alleviate acute respiratory distress syndrome (ARDS), but the mechanisms involved are unclear, especially about their...     

Genetics and Resistance Mechanism of the Cucumber (Cucumis sativus L.) Against Powdery Mildew

Journal of Plant Growth Regulation - Powdery mildew (PM) is one of the most severe foliar diseases in cucumbers (Cucumis sativus L.), but the inheritance of PM resistance remains unclear. The...     

The Salicylic Acid Signaling Pathway Plays an Important Role in the Resistant Process of Brassica rapa L. ssp. pekinensis to Plasmodiophora brassicae Woronin

Journal of Plant Growth Regulation - Clubroot disease, caused by Plasmodiophora brassicae Woronin infection, leads to significant yield and economic losses in cruciferous vegetables. However, the...     

Phosphorylation of Novel Interactors of Wild Soybean GsSnRK1 Protein Kinase

Plant Molecular Biology Reporter - Plant SnRK1 kinases have been reported to participate in regulating many aspects of plant biology including resistance to biotic and abiotic stresses. Wild...     

NLRP3 regulates alveolar bone loss in ligature‐induced periodontitis by promoting osteoclastic differentiation

ObjectivesNLRP3 inflammasome is a critical part of the innate immune system and plays an important role in a variety of inflammatory diseases. However, the effects of NLRP3 inflammasome on periodontitis have not been fully studied.Materials and methodsWe used ligature‐induced periodontitis models of NLRP3 knockout mice (NLRP3^KO) and their wildtype (WT) littermates to compare their alveolar bone phenotypes. We further used Lysm‐Cre/Rosa^nTnG mouse to trace the changes of Lysm‐Cre⁺ osteoclast precursors in ligature‐induced periodontitis with or without MCC950 treatment. At last, we explored MCC950 as a potential drug for the treatment of periodontitis in vivo and in vitro.ResultsHere, we showed that the number of osteoclast precursors, osteoclast differentiation and alveolar bone loss were reduced in NLRP3^KO mice compared with WT littermates, by using ligature‐induced periodontitis model. Next, MCC950, a specific inhibitor of the NLRP3 inflammasome, was used to inhibit osteoclast precursors differentiation into osteoclast. Further, we used Lysm‐Cre/Rosa^nTnG mice to demonstrate that MCC950 decreases the number of Lysm‐Cre⁺ osteoclast precursors in ligature‐induced periodontitis. At last, treatment with MCC950 significantly suppressed alveolar bone loss with reduced IL‐1β activation and osteoclast differentiation in ligature‐induced periodontitis.ConclusionOur findings reveal that NLRP3 regulates alveolar bone loss in ligature‐induced periodontitis by promoting osteoclastic differentiation.