Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Peripheral Mononuclear Cells in Patients With Ankylosing Spondylitis.

Objective: Genetic studies on ankylosing spondylitis (AS) have identified more than 100 pathogenic genes. Building a bridge between these genes and biologically targeted therapies is the current research hotspot. Methods: We integrated single-cell assaying transposase-accessible chromatin sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) to explore the key genes and related mechanisms associated with AS pathogenesis. Results: We identified 18 cell types in peripheral mononuclear cells from patients with AS and normal controls and summarized the cell-type-specific abnormal genes by scRNA-seq. Interestingly, we found that the pathogenic gene NFKB involved in AS progression originated from CD8+ T cells. Moreover, we observed an abnormal tumor TNF pathway mediated by abnormal expression of TNF, NFKB, FOS, JUN, and JUNB, and scATAC-seq results confirmed the abnormal accessible binding sites of transcriptional factors FOS, JUN, and JUNB. The final magnetic bead sorting and quantitative real-time PCR(RT-qPCR) confirmed that NFKB, FOS, JUN, and JUNB in CD8+ T cells differed in the AS group. Conclusions: Our results revealed a possible mechanism by which NFKB abnormally regulates FOS, JUN, and JUNB and drives AS progression, providing a novel perspective from a single cell point of view in AS.

Quantitative proteomics analysis of lysine 2-hydroxyisobutyrylation in IgA nephropathy.

BACKGROUND: Protein posttranslational modification is an indispensable regulatory element that can fine-tune protein functions and regulate diverse cellular processes. Lysine 2-hydroxyisobutyrylation (Khib) is a protein posttranslational modification that was recently identified and is thought to play a role in a wide variety of active cellular functions. METHODS: In this report, for the first time, we comparatively studied the 2-hydroxyisobutyrylation proteome in peripheral blood mononuclear cells from a biopsy-proven immunoglobulin A nephropathy (IgAN) group and a normal control group based on liquid chromatography-tandem mass spectrometry. RESULTS: Altogether, 7405 proteins were identified and added to a Khib library. Of these proteins, we identified 111 with upregulated expression and 83 with downregulated expression. Furthermore, we identified 428 Khib modification sites on 290 Khib-modified proteins, including 171 sites with increased modification on 122 Khib-modified proteins and 257 specific sites with reduced modification on 168 Khib-modified proteins. CONCLUSIONS: Importantly, the abundance of lipocalin 2 was increased in the differentially expressed proteins, and a KEGG-based functional enrichment analysis showed that Khib proteins clustered in the IL-17 signaling pathway and phagosome category, which may have important associations with IgAN. Our data enlighten our understanding of Khib in IgAN and indicate that Khib may have important regulatory roles in IgAN.

Controversial treatments: An updated understanding of the coronavirus disease 2019.

An outbreak of severe acute respiratory syndrome-related coronavirus 2 infection has posed significant threats to international health and the economy. In the absence of specific treatment for this virus, there is an urgent need to learn from the experience and lessons in China. To reduce the case-fatality rate among coronavirus disease 2019 patients, we should not ignore the complications, such as RNAaemia, acute respiratory distress syndrome, and multiple organ dysfunction. To help understand the advantages and limitations of differential treatments, we provide a timely review and discuss the complications and corresponding major treatments, especially controversial ones such as antiviral therapy (remdesivir, ribavirin, and chloroquine), glucocorticoid therapy, extracorporeal support including an artificial liver system, and extracorporeal membrane oxygenation based on available evidence. As a result, we suggest that antiviral therapy and organ function support are vital to reduce mortality for mild patients and critical patients, respectively.