Visible-Light-Induced Desaturative ß-Alkoxyoxalylation of N-Aryl Cyclic Amines with Difluoromethyl Bromides and H2O Via a Triple Cleavage Process.

A visible-light-driven desaturative ß-alkoxyoxalyation of N-aryl cyclic amines with difluoromethyl bromides and H2O has been reported. This tandem reaction is triggered by homolysis of the C-Br bond to produce the difuoroalkyl radical, which undergoes the subsequent defluorinated ß-alkoxyoxalylation cascades to afford a wide range of ß-ketoester/ketoamides substituted enamines. The prominent feature of this reaction contains photocatalyst-free, transition-metal free, and mild conditions. The 18O labeling experiment disclosed that H2O is the oxygen source of the carbonyl unit.

Age-dependent changes in the anatomical and histological characteristics of the aggregated lymphoid nodules in the stomach of Dromedary camels (Camelus Dromedarius).

Gastrointestinal associated lymphoid tissue (GALT) is an important component of the mucosal immune system. It is the largest mass of lymphoid tissues in the body and makes up more than 70% immune cells of entire body. GALT is considered to be the origin of systemic mucosal immunity and consists of solitary lymphoid nodules, aggregated lymphoid nodules (Peyer's patches, PPs), scattered lymphoid tissues, and follicular associated epithelia. PPs play important roles as antigen inductive sites of the mucosal immune system, which are mainly distributed in the intestine of animals and humans (especially ileum and appendix). However, a special area of well-developed aggregated lymphoid nodules in the abomasum of Dromedary camel was found in our laboratory. Its existence was rarely described in the stomach before. In the present study, we investigated this special structure with the dromedary camels of different ages (young, 0.5-2 years; pubertal, 3-5 years; middle-aged, 6-16 years; old, 17-20 years), by the anatomical, histological and immunohistochemical approaches. The results showed that the special structure was mainly distributed in the cardiac glandular area of the abomasum, forming a triangular area. The mucosal folds in this area were significantly thicker than those in the surrounding region. These mucosal folds had two different forms, namely reticular mucosal folds (RMF) and longitudinal mucosal folds (LMF). There were abundant lymphoid nodules in the submucosa of RMF and LMF, which were arranged in one or multiple rows. The statistical analysis of the height and thickness of RMF and LMF showed that the structure was most developed in pubertal dromedary camels. The histological characteristics of the structure were the same as PPs in the intestine of the Dromedary camel, while anatomical appearance showed some difference. The immunohistochemical examination revealed that both immunoglobulin A (IgA) and G (IgG) antibodies-producing cells (APCs) were extensively distributed in the gastric lamina propria (LP) in all age group. Our finding suggest that camel stomach not only performs digestive functions, but also involves parts of body immunity.

Integrated omics analysis reveals the immunologic characteristics of cystic Peyer's patches in the cecum of Bactrian camels.

Bactrian camels have specific mucosa-associated lymphoid tissue (MALT) throughout the large intestine, with species-unique cystic Peyer's patches (PPS) as the main type of tissue. However, detailed information about the molecular characteristics of PPS remains unclear. This study applied a transcriptomic analysis, untargeted metabolomics, and 16S rDNA sequencing to compare the significant differences between PPS and the adjacent normal intestine tissues (NPPS) during the healthy stage of three young Bactrian camels. The results showed that samples from PPS could be easily differentiated from the NPPS samples based on gene expression profile, metabolites, and microbial composition, separately indicated using dimension reduction methods. A total of 7,568 up-regulated and 1,266 down-regulated differentially expressed genes (DEGs) were detected, and an enrichment analysis found 994 DEGs that participated in immune-related functions, and a co-occurance network analysis identified nine hub genes (BTK, P2RX7, Pax5, DSG1, PTPN2, DOCK11, TBX21, IL10, and HLA-DOB) during multiple immunologic processes. Further, PPS and NPPS both had a similar pattern of most compounds among all profiles of metabolites, and only 113 differentially expressed metabolites (DEMs) were identified, with 101 of these being down-regulated. Deoxycholic acid (DCA; VIP = 37.96, log2FC = -2.97, P = 0), cholic acid (CA; VIP = 13.10, log2FC = -2.10, P = 0.01), and lithocholic acid (LCA; VIP = 12.94, log2FC = -1.63, P = 0.01) were the highest contributors to the significant dissimilarities between groups. PPS had significantly lower species richness (Chao1), while Firmicutes (35.92% ± 19.39%), Bacteroidetes (31.73% ± 6.24%), and Proteobacteria (13.96% ± 16.21%) were the main phyla across all samples. The LEfSe analysis showed that Lysinibacillus, Rikenellaceae_RC9_gut_group, Candidatus_Stoquefichus, Mailhella, Alistipes, and Ruminococcaceae_UCG_005 were biomarkers of the NPPS group, while Escherichia_Shigella, Synergistes, Pyramidobacter, Odoribacter, Methanobrevibacter, Cloacibacillus, Fusobacterium, and Parabacteroides were significantly higher in the PPS group. In the Procrustes analysis, the transcriptome changes between groups showed no significant correlations with metabolites or microbial communities, whereas the alteration of metabolites significantly correlated with the alteration of the microbial community. In the co-occurrence network, seven DEMs (M403T65-neg, M329T119-neg, M309T38-neg, M277T42-2-neg, M473T27-neg, M747T38-1-pos, and M482t187-pos) and 14 genera (e.g., Akkermansia, Candidatus-Stoquefichus, Caproiciproducens, and Erysipelatoclostridium) clustered much more tightly, suggesting dense interactions. The results of this study provide new insights into the understanding of the immune microenvironment of the cystic PPS in the cecum of Bactrian camels.

The JMJD3 histone demethylase inhibitor GSK-J1 ameliorates lipopolysaccharide-induced inflammation in a mastitis model.

Jumonji domain-containing 3 (JMJD3/KDM6B) is a histone demethylase that plays an important role in regulating development, differentiation, immunity, and tumorigenesis. However, the mechanisms responsible for the epigenetic regulation of inflammation during mastitis remain incompletely understood. Here, we aimed to investigate the role of JMJD3 in the lipopolysaccharide (LPS)-induced mastitis model. GSK-J1, a small molecule inhibitor of JMJD3, was applied to treat LPS-induced mastitis in mice and in mouse mammary epithelial cells in vivo and in vitro. Breast tissues were then collected for histopathology and protein/gene expression examination, and mouse mammary epithelial cells were used to investigate the mechanism of regulation of the inflammatory response. We found that the JMJD3 gene and protein expression were upregulated in injured mammary glands during mastitis. Unexpectedly, we also found JMJD3 inhibition by GSK-J1 significantly alleviated the severity of inflammation in LPS-induced mastitis. These results are in agreement with the finding that GSK-J1 treatment led to the recruitment of histone 3 lysine 27 trimethylation (H3K27me3), an inhibitory chromatin mark, in vitro. Furthermore, mechanistic investigation suggested that GSK-J1 treatment directly interfered with the transcription of inflammatory-related genes by H3K27me3 modification of their promoters. Meanwhile, we also demonstrated that JMJD3 depletion or inhibition by GSK-J1 decreased the expression of toll-like receptor 4 and negated downstream NF-κB proinflammatory signaling and subsequently reduced LPS-stimulated upregulation of Tnfa, Il1b, and Il6. Together, we propose that targeting JMJD3 has therapeutic potential for the treatment of inflammatory diseases.

An electrochemiluminescent sensor based on functionalized conjugated polymer dots for the ultrasensitive detection of Cu2.

An ultrasensitive electrochemiluminescence (ECL) detection for Cu2+ was explored using the carboxyl functionalized poly(9,9-dioctylfluorenyl-2,7-diyl) (PS-COOH-co-PFO) dots as the signal label without adding any coreactant.