Christensenella strain resources, genomic/metabolomic profiling, and association with host at species level.

The gut commensal bacteria Christensenellaceae species are negatively associated with many metabolic diseases, and have been seen as promising next-generation probiotics. However, the cultured Christensenellaceae strain resources were limited, and their beneficial mechanisms for improving metabolic diseases have yet to be explored. In this study, we developed a method that enabled the enrichment and cultivation of Christensenellaceae strains from fecal samples. Using this method, a collection of Christensenellaceae Gut Microbial Biobank (ChrisGMB) was established, composed of 87 strains and genomes that represent 14 species of 8 genera. Seven species were first described and the cultured Christensenellaceae resources have been significantly expanded at species and strain levels. Christensenella strains exerted different abilities in utilization of various complex polysaccharides and other carbon sources, exhibited host-adaptation capabilities such as acid tolerance and bile tolerance, produced a wide range of volatile probiotic metabolites and secondary bile acids. Cohort analyses demonstrated that Christensenellaceae and Christensenella were prevalent in various cohorts and the abundances were significantly reduced in T2D and OB cohorts. At species level, Christensenellaceae showed different changes among healthy and disease cohorts. C. faecalis, F. tenuis, L. tenuis, and Guo. tenuis significantly reduced in all the metabolic disease cohorts. The relative abundances of C. minuta, C. hongkongensis and C. massiliensis showed no significant change in NAFLD and ACVD. and C. tenuis and C. acetigenes showed no significant change in ACVD, and Q. tenuis and Geh. tenuis showed no significant change in NAFLD, when compared with the HC cohort. So far as we know, this is the largest collection of cultured resource and first exploration of Christensenellaceae prevalences and abundances at species level.

Long non-coding RNA MSL3P1 regulates CUL3 mRNA cytoplasmic transport and stability and promotes lung adenocarcinoma metastasis.

Lung adenocarcinoma (LUAD) is the most prevalent histological type of lung cancer. Previous studies have reported that specific long non-coding RNAs (lncRNAs) are involved in cancer development and progression. The phenotype and mechanism of ENST00000440028, named MSL3P1, a lncRNA which we referring to a cancer-testis gene with potential roles in tumorigenesis and progression, have not been reported. We found that MSL3P1 is overexpressed in LUAD tumor tissues, which is significantly associated with clinical characteristics, metastasis, and poor clinical prognosis. MSL3P1 promotes the metastasis of LUAD in vitro and in vivo. The enhancer reprogramming in LUAD tumor tissue is the major driver of the aberrantly expression of MSL3P1. Mechanistically, due to the competitive binding to CUL3 mRNA with ZFC3H1 protein (a protein involved in targeting polyadenylated RNA to exosomes and promoting the degradation of target mRNA), MSL3P1 can prevent the ZFC3H1-mediated RNA degradation of CUL3 mRNA and transport it to the cytoplasm. This activates the downstream epithelial-to-mesenchymal transition signaling pathway, and promote tumor invasion and metastasis. Implications: This study indicates that lncRNA MSL3P1 regulates CUL3 mRNA stability and promotes the metastasis and holds potential as a prognostic biomarker and therapeutic target in LUAD.

Anaerolentibacter hominis gen. nov. sp. nov., Diplocloster hominis sp. nov. and Pilosibacter fragilis gen. nov. sp. nov., isolated from human faeces.

Three Gram-positive, obligately anaerobic bacterial strains, namely CSJ-1T, CSJ-3T, and CSJ-4T, were isolated from faeces of healthy persons. They were characterized through a combination of whole-genome sequencing, phenotypic traits, and metabolomic analysis. The genome sizes of CSJ-1T, CSJ-4T, and CSJ-3T were 3.3, 3.8, and 6.1 Mbp, with DNA G+C contents of 47.2, 48.3, and 48.8 mol%, respectively. Strain CSJ-3T was identified as representing a novel species, Diplocloster hominis (type strain CSJ-3T=CGMCC 1.18033T=JCM 36512T) of the genus Diplocloster. The 16S rRNA gene sequence similarity and whole genome average nucleotide identity (gANI) of CSJ-4T to its closest related species, Diplocloster modestus ASD 4241T, were 98.3 and 91.4 %, respectively. Comparative analysis of 16S rRNA gene sequences showed 91.6 % similarity between CSJ-1T and its closest phylogenetic neighbour, Catenibacillus scindens DSM 106146T, and 93.3 % similarity between CSJ-4T and its closest relative strain, Clostridium fessum SNUG30386T. Based on the polyphasic taxonomic results, we proposed two novel genera and three novel species. Strain CSJ-1T was identified as representing a novel species of novel genus, Anaerolentibacter hominis gen. nov. sp. nov. (type strain CSJ-1T=CGMCC 1.18046T=JCM 36511T) of the family Lachnospiraceae, and strain CSJ-4T was identified as representing a novel species of novel genus Pilosibacter fragilis gen. nov. sp. nov. (type strain CSJ-4T=CGMCC 1.18026T= JCM 36513T) of the family Clostridiaceae.

Identification of Signal Pathways and Hub Genes of Pulmonary Arterial Hypertension by Bioinformatic Analysis.

Pulmonary arterial hypertension (PAH) is a progressive and complex pulmonary vascular disease with poor prognosis. The aim of this study was to provide a new understanding of the pathogenesis of disease and potential treatment targets for patients with PAH based on multiple-microarray analysis.Two microarray datasets (GSE53408 and GSE113439) downloaded from the Gene Expression Omnibus (GEO) database were analysed. All the raw data were processed by R, and differentially expressed genes (DEGs) were screened out by the "limma" package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed and visualized by R and Cytoscape software. Protein-protein interactions (PPI) of DEGs were analysed based on the NetworkAnalyst online tool. A total of 442 upregulated DEGs and 84 downregulated DEGs were identified. GO enrichment analysis showed that these DEGs were mainly enriched in mitotic nuclear division, organelle fission, chromosome segregation, nuclear division, and sister chromatid segregation. Significant KEGG pathway enrichment included ribosome biogenesis in eukaryotes, RNA transport, proteoglycans in cancer, dilated cardiomyopathy, rheumatoid arthritis, vascular smooth muscle contraction, focal adhesion, regulation of the actin cytoskeleton, and hypertrophic cardiomyopathy. The PPI network identified 10 hub genes including HSP90AA1, CDC5L, MDM2, LRRK2, CFTR, IQGAP1, CAND1, TOP2A, DDX21, and HIF1A. We elucidated potential biomarkers and therapeutic targets for PAH by bioinformatic analysis, which provides a theoretical basis for future study.