Circulating TIGIT±PD1+TPH, TIGIT ± PD1+TFH cells are elevated and their predicting role in systemic lupus erythematosus.

It is well established that increased peripheral helper T cells (TPH) and follicular helper T cells (TFH) was found in systemic lupus erythematosus (SLE) patients. However, the expression patterns and immunomodulatory roles of TIGIT and PD1 on TPH/TFH in SLE are poorly understood. The expression patterns of TIGIT and PD1 on TPH and TFH cells were examined using flow cytometry and their expression patterns in SLE patients were then further evaluated for their correlation with auto-antibodies, disease activity and severity, B cell differentiation. Logistic regression was used to analyze the risk factors. And the receiver operating characteristic curves and logistic regression model were created to evaluate the predicting role in SLE. TIGIT±PD1+TPH, TIGIT±PD1+TFH cells in the peripheral blood of SLE patients were upregulated, whereas TIGIT+PD1-TFH was downregulated. TIGIT ± PD1+TPH, TIGIT ± PD1+TFH cells positively correlated with auto-antibodies production, disease activity and severity, whereas TIGIT+PD1-TFH cells negatively correlated. TIGIT ± PD1+TPH, TIGIT-PD1+TFH were positively correlated with the frequency of plasmablasts. Furthermore, higher TIGIT+PD1+TPH and TIGIT+PD1+TFH were shown to be risk factors for SLE, whereas TIGIT+PD1-TFH was found to be a protective factor, according to logistic regression analysis. A further logistic regression model showed that combination of TPH/TFH and routine blood indicators may has potential predicting value for SLE, with AUC of 0.957. The increased TIGIT ± PD1+TPH, increased TIGIT ± PD1+TFH, decreased TIGIT+PD1-TFH correlates with disease severity and activity, may boost our comprehending of the role of TIGIT and PD1 on TPH/TFH in SLE, and a logistic regression model based on combination of TPH/TFH and routine blood indicators shows prominent value for predicting SLE.

Expression and Clinical Significance of the m6A RNA-Binding Proteins YTHDF2 in Peripheral Blood Mononuclear Cells From New-Onset Ankylosing Spondylitis.

This study has focused on determining the association of m6A methyltransferase [methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), and Wilms tumor 1-associating protein (WTAP)], demethylase [fat mass and obesity-associated protein (FTO) and alkylation repair homolog protein 5 (ALKBH5)], RNA-binding proteins [YT521-B homology domains 2 (YTHDF2)], and ankylosing spondylitis (AS). A total of 154 specimens, containing 79 patients with new-onset AS and 75 healthy controls (HCs), participated in the study. The mRNA expressions of these m6A methyltransferase, demethylase, and RNA-binding protein in peripheral blood mononuclear cells (PBMCs) were detected by quantitative real-time PCR (qRT-PCR). The data showed that the mRNA expressions of YTHDF2 and ALKBH5 in PBMC from patients with new-onset AS were significantly decreased, and there was a positive correlation between RNA-binding proteins (YTHDF2) and demethylase (ALKBH5) in patients with new-onset AS. Logistic regression analysis demonstrated that the expression of YTHDF2 mRNA in PBMC is a risk factor of AS. Receiver operating characteristic (ROC) analysis of the area under the curve (AUC) for mRNA YTHDF2 in new-onset AS and HC was 0.692, with a cutoff value of <0.8724, a sensitivity of 67%, and a specificity of 63%. Moreover, we constructed a novel predictive model based on a combination of mRNA YTHDF2 and systemic immune-inflammation index (SII) for AS diagnosis (AUC = 0.865, sensitivity = 79.45%, specificity = 84.00%), and the predictive model correlated with the activity and severity of AS. This study indicates that the mRNA expression of YTHDF2 in PBMC may be involved in AS pathogenesis and a predictive model based on a combination of mRNA YTHDF2 and SII acts as a marker for diagnosis and progression of diseases.

Lytic polysaccharide monooxygenases promote oxidative cleavage of lignin and lignin-carbohydrate complexes during fungal degradation of lignocellulose.

Overcoming lignocellulosic biomass recalcitrance, especially the cleavage of cross-linkages in lignin-carbohydrate complexes (LCCs) and lignin, is essential for both the carbon cycle and industrial biorefinery. Lytic polysaccharide monooxygenases (LPMOs) are copper-containing enzymes that play a key role in fungal polysaccharide oxidative degradation. Nevertheless, comprehensive analysis showed that LPMOs from a white-rot fungus, Pleurotus ostreatus, correlated well with the Fenton reaction and were involved in the degradation of recalcitrant nonpolysaccharide fractions in this research. Thus, LPMOs participated in the extracellular Fenton reaction by enhancing iron reduction in quinone redox cycling. A Fenton reaction system consisting of LPMOs, hydroquinone, and ferric iron can efficiently produce hydroxy radicals and then cleave LCCs or lignin linkages. This finding indicates that LPMOs are underestimated auxiliary enzymes in eliminating biomass recalcitrance.

Multiple Site-Specific One-Pot Synthesis of Two Proteins by the Bio-Orthogonal Flexizyme System.

Lysine acetylation is a reversible post-translational modification (PTM) vastly employed in many biological events, including regulating gene expression and dynamic transitions in chromatin remodeling. We have developed the first one-pot bio-orthogonal flexizyme system in which both acetyl-lysine (AcK) and non-hydrolysable thioacetyl-lysine (ThioAcK) were site-specifically incorporated into human histone H3 and H4 at different lysine positions in vitro, either individually or in pairs. In addition, the high accuracy of this system moving toward one-pot synthesis of desired histone variants is also reported.

Carbaryl biodegradation by Xylaria sp. BNL1 and its metabolic pathway.

Although ascomycetes occupy a vaster niche in soil than the well-studied basidiomycetes, they have received limited attention in studies related to bioremediation. In this study, the degradation of carbaryl by Xylaria sp. was studied in different culture conditions and its possible metabolic pathway was elucidated. In liquid culture, 99% of the added carbaryl was eliminated when cytochrome P450 (CYP450) was active, which was similar to the degradation rate of Pleurotus ostreatus, a fungus with strong bioremediation ability. Mn2+ is beneficial to the degradation of carbaryl. Compared to the 72.17% degradation rate in sterile soil, 59.0% carbaryl was eliminated in non-sterile soil, which suggested that Xylaria sp. BNL1 can resist microorganismal infection. Furthermore, the intracellular fractions containing laccase, CYP450, and carbaryl esterase efficiently degraded carbaryl. The presence of carbaryl metabolites suggested that Xylaria sp. BNL1 initiated its attack on carbaryl via carbaryl esterase to release α-naphthol, which was further degraded to 1,4-naphthoquinone and benzoic acid by CYP450 and laccase. Thus, our study highlights the potential of using Xylaria sp. for bioremediation.

Differential Proteomic Profiles of Pleurotus ostreatus in Response to Lignocellulosic Components Provide Insights into Divergent Adaptive Mechanisms.

Pleurotus ostreatus is a white rot fungus that grows on lignocellulosic biomass by metabolizing the main constituents. Extracellular enzymes play a key role in this process. During the hydrolysis of lignocellulose, potentially toxic molecules are released from lignin, and the molecules are derived from hemicellulose or cellulose that trigger various responses in fungus, thereby influencing mycelial growth. In order to characterize the mechanism underlying the response of P. ostreatus to lignin, we conducted a comparative proteomic analysis of P. ostreatus grown on different lignocellulose substrates. In this work, the mycelium proteome of P. ostreatus grown in liquid minimal medium with lignin, xylan, and carboxymethyl cellulose (CMC) was analyzed using the complementary two-dimensional gel electrophoresis (2-DE) approach; 115 proteins were identified, most of which were classified into five types according to their function. Proteins with an antioxidant function that play a role in the stress response were upregulated in response to lignin. Most proteins involving in carbohydrate and energy metabolism were less abundant in lignin. Xylan and CMC may enhanced the process of carbohydrate metabolism by regulating the level of expression of various carbohydrate metabolism-related proteins. The change of protein expression level was related to the adaptability of P. ostreatus to lignocellulose. These findings provide novel insights into the mechanisms underlying the response of white-rot fungus to lignocellulose.