No abstract

No abstract

No abstract

No abstract

Sorafenib is the first-line therapeutic option for advanced hepatocellular carcinoma (HCC). Many patients exhibit a primary resistance (PR) response after initial treatment. In previous studies, compared to acquired resistance, the mechanism of PR is unclear. The present study aimed to evaluate the response of patient samples to sorafenib by patient-derived xenograft (PDX) models, and the differences at the transcriptome level between the sorafenib PR group and the sorafenib sensitive group were analyzed by single-cell sequencing technology. A specific cell cluster may be differentiated by the liver bud hepatic cells, and the JUN transcription factors in this cell cluster were highly activated. The albumin is secreted by other cell clusters, and the cluster stimulates the FcRn complex receptor to activate the HIF pathway and cell proliferation, resulting in a poor response to sorafenib. These findings are validated by both cell communication analysis and experiments. Thus, the current studies provided a novel approach for the treatment of sorafenib-resistant HCC.

IntroductionAltitude, as a comprehensive ecological factor, regulates the growth and development of plants and microbial distribution. Dendrobium nobile (D. nobile) planted in habitats at different elevations in Chishui city, also shows metabolic differences and endophytes diversity. What is the triangular relationship between altitude, endophytes, and metabolites?MethodsIn this study, the diversity and species of endophytic fungi were tested by ITS sequencing and metabolic differences in plants were tested by UPLC–ESI–MS/MS. Elevation regulated the colonization of plant endophytic fungal species and fatty acid metabolites in D. nobile.ResultsThe results indicate that and high altitude was better for the accumulation of fatty acid metabolites. Therefore, the high-altitude characteristic endophytic floras were screened, and the correlation with fatty acid metabolites of plants was built. The colonization of T. rubrigenum, P. Incertae sedis unclassified, Phoma. cf. nebulosa JZG 2008 and Basidiomycota unclassified showed a significantly positive correlation with fatty acid metabolites, especially 18-carbon-chain fatty acids, such as (6Z,9Z,12Z)-octadeca-6,9,12-trienoic acid, 3,7,11,15-tetramethyl-12-oxohexadeca-2,4-dienoic acid and Octadec-9-en-12-ynoic acid. What is more fascinating is these fatty acids are the essential substrates of plant hormones.DiscussionConsequently, it was speculated that the D. nobile- colonizing endophytic fungi stimulated or upregulated the synthesis of fatty acid metabolites and even some plant hormones, thus affecting the metabolism and development of D. nobile.

Alcoholic liver disease (ALD) is currently considered a global healthcare problem with limited pharmacological treatment options. There are abundant cell types in the liver, such as hepatocytes, endothelial cells, Kupffer cells and so on, but little is known about which kind of liver cells play the most important role in the process of ALD. To obtain a cellular resolution of alcoholic liver injury pathogenesis, 51,619 liver single-cell transcriptomes (scRNA-seq) with different alcohol consumption durations were investigated, 12 liver cell types were identified, and the cellular and molecular mechanisms of the alcoholic liver injury were revealed. We found that more aberrantly differential expressed genes (DEGs) were present in hepatocytes, endothelial cells, and Kupffer cells than in other cell types in alcoholic treatment mice. Alcohol promoted the pathological processes of liver injury; the specific mechanisms involved: lipid metabolism, oxidative stress, hypoxia, complementation and anticoagulation, and hepatocyte energy metabolism on hepatocytes; NO production, immune regulation, epithelial and cell migration on endothelial cells; antigen presentation and energy metabolism on Kupffer cells, based on the GO analysis. In addition, our results showed that some transcription factors (TFs) are activated in alcohol-treated mice. In conclusion, our study improves the understanding of liver cell heterogeneity in alcohol-fed mice at the single-cell level. It has potential value for understanding key molecular mechanisms and improving current prevention and treatment strategies for short-term alcoholic liver injury.

No abstract