Acetylation licenses Th1 cell polarization to constrain Listeria monocytogenes infection.

T helper 1 (Th1) immunity is typically viewed as a critical adaptation by vertebrates against intracellular pathogens. Identifying novel targets to enhance Th1 cell differentiation and function is increasingly important for anti-infection immunity. Here, through small-molecule screening focusing on epigenetic modifiers during the in vitro Th1 cell differentiation process, we identified that the selective histone deacetylase 6 (HDAC6) inhibitors ricolinostat and nexturastat A (Nex A) promoted Th1 cell differentiation. HDAC6-depleted mice exhibit elevation of Th1 cell differentiation, and decreased severity of Listeria monocytogenes infection. Mechanistically, HDAC6 directly deacetylated CBP-catalyzed acetylation of signal transducer and activator of transcription 4 (STAT4)-lysine (K) 667 via its enzymatic activity. Acetylation of STAT4-K667 is required for JAK2-mediated phosphorylation and activation of STAT4. Stat4K667R mutant mice lost the ability to normally differentiate into Th1 cells and developed severe Listeria infection. Our study identifies acetylation of STAT4-K667 as an essential signaling event for Th1 cell differentiation and defense against intracellular pathogen infections, and highlights the therapeutic potential of HDAC6 inhibitors for controlling intracellular pathogen infections.

Identification of Immune-Related Gene Signature and Prediction of CeRNA Network in Active Ulcerative Colitis.

Background: Ulcerative colitis (UC) is an inflammatory disease of the intestinal mucosa, and its incidence is steadily increasing worldwide. Intestinal immune dysfunction has been identified as a central event in UC pathogenesis. However, the underlying mechanisms that regulate dysfunctional immune cells and inflammatory phenotype remain to be fully elucidated. Methods: Transcriptome profiling of intestinal mucosa biopsies were downloaded from the GEO database. Robust Rank Aggregation (RRA) analysis was performed to identify statistically changed genes and differentially expressed genes (DEGs). Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore potential biological mechanisms. CIBERSORT was used to evaluate the proportion of 22 immune cells in biopsies. Weighted co-expression network analysis (WGCNA) was used to determine key module-related clinical traits. Protein-Protein Interaction (PPI) network and Cytoscape were performed to explore protein interaction network and screen hub genes. We used a validation cohort and colitis mouse model to validate hub genes. Several online websites were used to predict competing endogenous RNA (ceRNA) network. Results: RRA integrated analysis revealed 1838 statistically changed genes from four training cohorts (adj. p-value < 0.05). GSEA showed that statistically changed genes were enriched in the innate immune system. CIBERSORT analysis uncovered an increase in activated dendritic cells (DCs) and M1 macrophages. The red module of WGCNA was considered the most critical module related to active UC. Based on the results of the PPI network and Cytoscape analyses, we identified six critical genes and transcription factor NF-κB. RT-PCR revealed that andrographolide (AGP) significantly inhibited the expression of hub genes. Finally, we identified XIST and three miRNAs (miR-9-5p, miR-129-5p, and miR-340-5p) as therapeutic targets. Conclusions: Our integrated analysis identified four hub genes (CXCL1, IL1B, MMP1, and MMP10) regulated by NF-κB. We further revealed that AGP decreased the expression of hub genes by inhibiting NF-κB activation. Lastly, we predicted the involvement of ceRNA network in the regulation of NF-κB expression. Collectively, our results provide valuable information in understanding the molecular mechanisms of active UC. Furthermore, we predict the use of AGP and small RNA combination for the treatment of UC.

[Evaluation of sustainable intensification in agriculture: Research progress and prospects]. / å†œä¸šå¯æŒç»­é›†çº¦åŒ–è¯„ä»·çš„ç ”ç©¶è¿›å±•ä¸Žå±•æœ›.

Sustainable intensification in agriculture (SI) is a realistic pathway to ensure global food security and deal with famine, poverty, and climate change. We constructed a SI research framework using methods such as literature, induction, and deduction. We reviewed the progress of SI research from four aspects, including the conceptual origin, index system, research scale, and evaluation methods. We discussed the future development path to provide reference for deepening related research of SI and its relation from the multi-disciplinary angle. There are many kinds of research on SI across the world, which give rich connotations to SI based on multiple dimensions of productivity, economy, environment, and society. The evaluation of SI involves productivity, economy, environment, human and society. It has formed a comprehensive evaluation system such as material input, resource productivity, environmental and economic efficiency, and other multiple indicators. Moreover, the evaluation methods of SI mainly include the factor comprehensive evaluation method and index model evaluation method. Studies on SI are not abundant in China, which needs to be enriched. We should break through the constraints of traditional theoretical and methodological frameworks, focus on the transformative scientific issues brought by international development, and explore the research paradigm of SI from the cross-disciplinary perspective.

Luminescence properties of Gd2MoO6:Eu3+ nanophosphors for WLEDs.

A series of Gd2-xMoO6:xEu3+ (x = 0.18-0.38) nanophosphors were synthesized by the solvothermal method. The properties of these nanophosphors were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), fluorescence spectroscopy and diffuse reflectance spectroscopy. Gd2-xMoO6:xEu3+ nanophosphors have a strong excitation band in the NUV region and emit red light with high color purity by efficient energy transfer from the MoO66- group to Eu3+ ions. Red LEDs and WLEDs were fabricated using a 370 nm chip and Gd2-xMoO6:0.26Eu3+ nanophosphors, which showed good electroluminescence performance. At a driving current of 20 mA, WLEDs displayed CIE coordinates of (0.3297, 0.3869), a correlated color temperature (CCT) of 5604 K and a high color rendering index (Ra) of 91.6. This work demonstrates that Gd2-xMoO6:xEu3+ phosphors are promising red phosphors excited by a NUV chip for WLEDs.