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xue, x.

Publications and source records attributed to xue, x..

3 recordsLinked to original sources

Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived sSCF

PurposeThe abundance and biological contribution of Natural killer (NK) cells in cancer are controversial. Here, we aim to uncover clinical relevance and cellular roles of NK cells in colon cancer liver metastasis (CCLM) MethodsWe integrated single-cell RNA sequencing, spatial transcriptomics, and bulk RNA-sequencing datasets to investigate NK cells biological properties and functions in the microenvironment of primary and liver metastatic tumors. Results were validated through an in vitro co-culture experiment based on bioinformatics analysis. ResultsWe used single-cell RNA sequencing and spatial transcriptomics to map the immune cellular landscape of colon cancer and well-matched liver metastatic cancer. We discovered that GZMK+ resting NK cells increased significantly in tumor tissues and were enriched in the tumor regions of both diseases. After combining bulk RNA and clinical data, we observed that these NK cell subsets contributed to a worse prognosis. Meanwhile, KIR2DL4+ activated NK cells exhibited the opposite position and relevance. Pseudotime cell trajectory analysis revealed the evolution of activated to resting NK cells. In vitro experiments further confirmed that tumor-cell-co-cultured NK cells exhibited a decidual-like status, as evidenced by remarkable increasing CD9 expression. Functional experiments finally revealed that NK cells exhibited tumor-activating characteristics by promoting the dissociation of SCF (stem cell factor) on the tumor cells membrane depending on cell-to-cell interaction, as the supernatant of the co-culture system enhanced tumor progression. ConclusionTogether, our findings revealed a population of protumorigenic NK cells that may be exploited for novel therapeutic strategies to improve therapeutic outcomes for patients with CCLM.

immunology↗

Molecular Epidemiology and Microbiological Characteristics of Cryptococcus gattii VGII isolates from China

Cryptococcus gattii (C. gattii) is a fungal pathogen that once caused an outbreak of cryptococcosis on Vancouver Island, and had spread worldwide, while few data were available in China. In this study, seven clinical isolates of C. gattii VGII were collected from 19 hospitals, Multi-locus Sequence Typing (MLST) analysis and whole-genome sequencing (WGS) was performed, and combined with published data for phylogenetic analysis. In addition, in vitro antifungal susceptibility testing, phenotypic analysis, and in vivo virulence studies were performed, subsequently, histopathological analysis of lung tissue was performed. C.gattii VGII infected patients were mainly immunocompetent male, and most of them had symptoms of central nervous system (CNS) involvement. MLST results showed that isolates from china exhibited high genetic diversity, and sequence type (ST) 7 was the major ST among the isolates. Some clinical isolates showed a close phylogenetic relationship with strains from Australia and South America. All clinical isolates did not show resistance to antifungal drugs. In addition, there was no correlation between virulence factors (temperature, melanin production, and capsule size) and virulence while in vivo experiments showed significant differences in virulence among strains. Lung fungal burden and damage to lung tissue correlated with virulence, and degree of damage to lung tissue in mice may highlight differences in virulence. Our work seeks to provide useful data for molecular epidemiology, antifungal susceptibility, and virulence differences of C. gattii VGII in China. Author SummaryCryptococcus gattii is one of the life-threatening fungal pathogens that can infect immunocompetent individuals. C.gattii can be invaded through the respiratory tract and can be spread to the brain, causing meningoencephalitis and even death. In 1999, an outbreak of C. gattii VGII occurred on Vancouver Island in Canada and spread in the Pacific Northwest region, which attracted more attention. Compared with other nations, the data of C gattii VGII in China was limited. To better understand the molecular epidemiology and microbiological characteristics of C.gattii VGII isolates from China, Bioinformatics analysis and in vivo and in vitro experiments were performed for clinical strains. Multi-locus Sequence Typing and whole-genome sequencing reveal the genetic diversity of the isolates and genetic relationships with isolates from other countries. We also investigated the antifungal drug susceptibility and virulence differences of the isolates. The authors expect that our work can provide useful data for the prevention and control of C. gattii VGII in China and to draw attention to C. gattii.

microbiology↗

Response of soil microbial communities to alpine meadow degradation severity levels in the Qinghai-Tibet Plateau

Soil microbial community structure is an effective indicator to reflect changes in soil quality. Little is known about the effect of alpine meadow degradation on the soil bacterial and fungal community. In this study, we used the Illumina MiSeq sequencing method to analyze the microbial community structure of alpine meadow soil in five different degradation levels (i.e., non-degraded (ND), slightly degraded (LD), moderately degraded (MD), severely degraded (SD), and very severely degraded (VD)) in the Qinghai-Tibet Plateau. Proteobacteria, Actinobacteria, and Acidobacteria were the mainly bacterial phyla in meadow soil across all five degradation levels investigated. Basidiomycota was the mainly fungal phylum in ND; however, we found a shift from Basidiomycota to Ascomycota with an increase (severity) in degradation level. The overall proportion of Cortinariaceae exhibited high fungal variability, and reads were highest in ND (62.80%). Heatmaps of bacterial genera and fungal families showed a two-cluster sample division on a genus/family level: (1) an ND and LD group and (2) an SD, VD, and MD group. Redundancy analysis (RDA) showed that 79.7%and 71.3% of the variance in bacterial and fungal composition, respectively, could be explained by soil nutrient conditions (soil organic carbon, total nitrogen, and moisture) and plant properties (below-ground biomass). Our results indicate that meadow degradation affects both plant and soil properties and consequently drives changes in soil microbial community structure.

microbiology↗