Abnormally high expression of D1-like dopamine receptors on lupus CD4+ T cells promotes Tfh cell differentiation.

OBJECTIVE: SLE is a chronic autoimmune disease that places a great burden on human society. T follicular helper (Tfh) cells play a critical role in the pathological process of SLE. Therefore, elucidating the mechanism of Tfh cell differentiation will contribute to SLE treatment. Dopamine receptors (DRDs) are members of the family of G protein-coupled receptors and are primarily divided into D1-like and D2-like receptors. Previous studies have found that DRDs can regulate differentiation of immune cells. However, there is currently a lack of research on DRDs and Tfh cells. We here explore the relationship between DRDs and Tfh cells, and analyse the relationship between DRD expression on Tfh cells and the course of SLE. METHODS: We first detected plasma catecholamine concentrations in patients with SLE and healthy controls by mass spectrometry, followed by reverse transcription-quantitative PCR (RT-qPCR) to detect DRD messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMCs) and CD4+ T cells, and flow cytometry to detect DRD expression in Tfh cells. Finally, in vitro experiments and RNA sequencing (RNA-seq) were used to explore the possible pathway by which DRDs regulate Tfh cell differentiation. RESULTS: The plasma dopamine concentration in patients with SLE was significantly increased, and abnormal mRNA expression of DRDs was observed in both PBMCs and CD4+ T cells. The results of flow cytometry showed that D1-like receptors were highly expressed in Tfh cells of patients with SLE and associated with disease activity. In vitro induction experiments showed that differentiation of naïve T cells into Tfh cells was accompanied by an increase in D1-like receptor expression. RNA-seq and RT-qPCR results indicate that D1-like receptors might promote Tfh cell differentiation through the Phosphatidylinositol3-kinase (PI3K)/protein kinase B (AKT)/Forkhead box protein O1 (FOXO1)/Kruppel-like factor 2 (Klf2) pathway. CONCLUSION: Tfh cells in patients with SLE highly express D1-like receptors, which correlate with disease activity. D1-like receptors may promote Tfh cell differentiation through the PI3K/AKT/FOXO1/Klf2 pathway.

Changes in fungal community during different phases in conventional and bioreactor composting systems according to metatranscriptomics analysis.

We determined the changes that occurred in fungal community structures and their functions in conventional and bioreactor composting systems. The Illumina MiSeq platform was employed to sequence cDNA by reverse transcription to conduct metatranscriptomics analysis of RNA, and the FUNGuild tool was applied. The α-diversity of fungi in the bioreactor composter increased throughout composting, especially in the initial three phases, but decreased in the conventional composting system. The three dominant phyla in the bioreactor system were Ascomycota (30.27%-68.50%), Mortierellomycota (3.81%-39.51%), and Basidiomycota (9.17%-30.86%). Ascomycota (76.96%-97.18%) was the main phylum in the conventional composting system. Mortierella, Guehomyces, Plectosphaerella, Chaetomium, Millerozyma, and Coprinopsis were the main genera in the bioreactor composter. In the same phase, significant differences in the fungal functions were found between the two composting methods. Available phosphorus was the main factor that affected the community structures and functions of fungi in the bioreactor composter.

Serum biomarkers for liver fibrosis.

Liver fibrosis is a common pathway in most chronic liver diseases, characterized by excessive extracellular matrix accumulation. Without treatment, fibrosis will ultimately result in cirrhosis, portal hypertension, and even liver failure. It is considered that liver fibrosis is reversible while cirrhosis is not, making it significant to diagnose and evaluate liver fibrogenesis timely. As the gold standard, liver biopsy is imperfect due to its invasiveness and sampling error. Therefore, attempts at uncovering noninvasive tests have become a hot topic in liver fibrosis. Nowadays, as an important category of noninvasive tests, serum biomarkers, which are safer, convenient, repeatable, and more acceptable, are widely discussed and commonly used in clinical practice. Serum biomarkers of liver fibrosis can be divided into class I (direct) and classⅡ (indirect) markers. However, the diagnostic efficiency still varies among studies. This article summarizes the most established and newly discovered serum biomarkers for hepatic fibrogenesis.

Increased Levels of CHI3L1 and HA Are Associated With Higher Occurrence of Liver Damage in Patients With Obstructive Sleep Apnea.

Background: Obstructive sleep apnea-hypopnea syndrome (OSA) may cause liver fibrosis, and liver fibrosis serum biomarkers plays an important role on the diagnosis of liver fibrosis. In addition, this study aimed to observe the changes of 4 serum markers and Chitinase 3-like protein 1 (CHII3L1) levels in OSA patients with different disease severity and explore their interactions. And then, we examined whether intermittent hypoxia (IH) exposure can activate hepatic stellate cell. Methods: 74 OSA patients in Second Xiangya hospital from January 2021 to October 2021 was selected and categorized into mild, moderate, and severe groups according to AHI. In addition, 20 subjects were selected as the control group. Serum levels of liver fibrosis markers were determined by electrochemiluminescence immunoassay. Hepatic stellate cells were exposed to intermittent IH or normoxia (RA). Results were analyzed using the SPSS software. Results: There was a significant increase in serum hyaluronic acid (HA), collagen type IV (CIV) and CHI3L1 levels in OSA patients compared with control group. Specifically, serum liver fibrosis markers HA, CIV and CHI3L1 levels were positively correlated with apnea-hypopnea index (AHI), but negatively correlated with the lowest saturation oxygen (LSaO2) respectively. The LX-2 cells (human hepatic stellate cell line) exposed to IH showed significant increases in fibrotic protein expression. Conclusion: OSA might either directly or indirectly trigger or exacerbate liver fibrosis, possibly via IH-related pathways.

Palladium(II)-Catalyzed Dehydrogenative Strategy for Direct and Regioselective Oligomerization of BODIPY Dyes.

A family of directly ß,γ-linked BODIPY oligomers up to pentamers were regioselectively prepared via Pd(II)-catalyzed oxidative C-H cross-coupling. The structural integrity of ß,γ-linked dimers was unambiguously confirmed by X-ray crystallography. These structurally unprecedented oligomers showed red-shifted absorptions and near-infrared emissions along with efficient intersystem crossing, giving ΦΔ in the range of 12-43%, for potential use as heavy-atom-free photosensitizers.