Photoinduced Desaturation of Amides by Palladium Catalysis

A photoinduced palladium-catalyzed desaturation method that is suitable for converting the linear amides to their α,β-unsaturated counterparts is reported. The reaction does not require strong base/acid or sulfur/selenium and oxidant reagents and can be carried out at room temperature through a simple one-step operation. The protocol exhibits great scalability and functional group tolerance. The reaction mechanism has been investigated through deuterium labeling experiments, radical clock, radical capture, and kinetic studies. Mechanistic studies suggested a radical pathway involving aryl/alkyl Pd-radical intermediates

Crocin Improves the Endothelial Function Regulated by Kca3.1 Through ERK and Akt Signaling Pathways

Background/Aims: Based on the protective effect of crocin against cardiovascular diseases, we hypothesize that crocin could improve endothelial function through activating the eNOS(endothelial nitric oxide synthase) /NO pathway and/or the intermediate-conductance Ca2+-activated K+ channels (KCa3.1). Methods: In this study, rat aortic rings were used to assess the regulatory effect of crocin on vascular tone and nitric oxide, prostacyclin, and KCa3.1, all endothelial vasodilators, were analyzed for effects by crocin. The expression profiles of p-eNOS, total-eNOS, p-ERK, total-ERK, p-Akt, total-Akt, KCa3.1, CD31, thrombomodulin, ICAM-1 and VCAM-1 were tested by western blotting. KCa3.1 was also analyzed by qPCR and immunofluorescence staining. Fluorescence and confocal microscopy were used to determine NO generation and intracellular Ca2+. Both EdU and MTT assays were used to evaluate cell viability. Cellular migration was assessed using transwell assay. Results: Crocin relaxed pre-contracted artery rings through either NO or KCa3.1, but not PGI, in an endothelium-dependent manner. Furthermore, crocin increased p-eNOS, total-eNOS expression and NO production as well as intracellular Ca2+ in both HUVECs and HUAECs (Human Umbilical Artery Endothelial cells). Crocin also stimulated the expression of CD31, thrombomodulin and vascular cell adhesion molecule 1 (VCAM-1), as well as increased cellular proliferation and migration in vitro. Interestingly, we determined for the first time that by blocking or silencing KCa3.1 there was inhibition of crocin induced upregulation of p-eNOS and total-eNOS. Correspondingly, the KCa3.1 inhibitor TRAM-34 also reduced the expression of CD31, thrombomodulin and VCAM-1, as well as diminished intracellular Ca2+, cellular proliferation and migration. Finally, crocin stimulated the expression of p-ERK, total-ERK, p-Akt and total-Akt, however suppression of MEK and Akt inhibited this expression profile in endothelial cells. Conclusion: In the present study, these data strongly support the hypothesis that crocin could improve endothelial function through stimulation of the eNOS/NO pathway and other endothelial markers. This functional improvement is regulated by KCa3.1 via the MEK/ERK and PI3K/Akt signaling pathway

Responses of soil microbial communities to concentration gradients of antibiotic residues in typical greenhouse vegetable soils

To explore the responses of soil microbial communities to concentration gradients of antibiotic residues in soil, 32 soil samples were collected from a typical greenhouse vegetable production base in Northern China in 2019. The total concentrations of 26 antibiotic residues in these soil samples was 83.24–4237.93 μg·kg−1, of which metabolites of tetracyclines were 23.34–1798.80 μg·kg−1. The total concentrations in 32 samples were clustered into three levels (L: 300 μg·kg−1) to elucidate the impacts of antibiotic residues on the diversity, structure, composition, function and antibiotic resistome of soil microbial community. Results showed that higher concentration of antibiotic residues in soil was prone to decrease the diversity and shift the structure and composition of soil microbial community. Antibiotic resistome occurred in soils with antibiotic residues exceeding 300 μg·kg−1. Interactions among soil bacteria followed the order of H > L > M, consistent with the relative abundances of mobile genetic elements. Bacteroidetes and Firmicutes were the top attributors impacting the profile of antibiotics in soil. According to weighted comprehensive pollution index of risk quotient, in 28.1 % of soil samples the residual antibiotics presented high ecological risk, whereas in the rest of soil samples the ecological risk is medium. The results will enrich the database and provide references for antibiotic contamination control in soils of the region and alike

PECAM-1 drives β-catenin-mediated EndMT via internalization in colon cancer with diabetes mellitus

Abstract Background Diabetes mellitus (DM) is considered to be a risk factor in carcinogenesis and progression, although the biological mechanisms are not well understood. Here we demonstrate that platelet-endothelial cell adhesion molecule 1 (PECAM-1) internalization drives β-catenin-mediated endothelial-mesenchymal transition (EndMT) to link DM to cancer. Methods The tumor microenvironment (TME) was investigated for differences between colon cancer with and without DM by mRNA-microarray analysis. The effect of DM on colon cancer was determined in clinical patients and animal models. Furthermore, EndMT, PECAM-1 and Akt/GSK-3β/β-catenin signaling were analyzed under high glucose (HG) and human colon cancer cell (HCCC) supernatant (SN) or coculture conditions by western and immunofluorescence tests. Results DM promoted the progression and EndMT occurrence of colon cancer (CC). Regarding the mechanism, DM induced PECAM-1 defection from the cytomembrane, internalization and subsequent accumulation around the cell nucleus in endothelial cells, which promoted β-catenin entry into the nucleus, leading to EndMT occurrence in CC with DM. Additionally, Akt/GSK-3β signaling was enhanced to inhibit the degradation of β-catenin, which regulates the process of EndMT. Conclusions PECAM-1 defects and/or internalization are key events for β-catenin-mediated EndMT, which is significantly boosted by enhanced Akt/GSK-3β signaling in the DM-associated TME. This contributes to the mechanism by which DM promotes the carcinogenesis and progression of CC. Graphical Abstract Video Abstrac

Additional file 1 of VDR promotes pancreatic cancer progression in vivo by activating CCL20-mediated M2 polarization of tumor associated macrophage

Supplementary Material