PTMA binds to HMGB1 to regulate mitochondrial oxidative phosphorylation and thus affect the malignant progression of esophageal squamous cell carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor of the digestive tract with complex pathogenesis. There is a pressing need to search for ESCC targeted therapy sites and explore its pathogenesis. Prothymosin alpha (PTMA) is abnormally expressed in numerous tumors and has a significant regulatory effect on tumor malignant progression. However, the regulatory role and mechanism of PTMA in ESCC have not yet been reported. Methods: We first detected the PTMA expression in ESCC patients, subcutaneous tumor xenograft models of ESCC, and ESCC cells. Subsequently, PTMA expression in ESCC cells was inhibited by cell transfection, and cell proliferation and apoptosis were detected by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, and Western blot. A dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay was used to detect reactive oxygen species (ROS) level in cells, and MitoSOX fluorescent probe, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl carbocyanine iodide (JC-1) staining, mitochondrial complex kit, and Western blot were used to detect the expression of mitochondrial oxidative phosphorylation. Next, the combination between PTMA and high mobility group box 1 (HMGB1) was detected using Co-immunoprecipitation (co-IP) and immunofluorescence (IF) techniques. Finally, the expression of PTMA was inhibited and the expression of HMGB1 was overexpressed in cells via cell transfection, and the regulatory effect of PTMA and HMGB1 binding on mitochondrial oxidative phosphorylation in ESCC was determined through related experiments. Results: The expression of PTMA in ESCC was abnormally elevated. The inhibition of PTMA expression in ESCC cells significantly decreased the activity of ESCC cells and increased their apoptosis. Moreover, interference with PTMA can induce ROS aggregation in ESCC cells by inhibiting mitochondrial oxidative phosphorylation, which may be achieved by binding to HMGB1. Conclusions: PTMA binds to HMGB1 to regulate mitochondrial oxidative phosphorylation, thereby affecting the malignant progression of ESCC.

TMSOTf mediated stereoselective synthesis of α-C-glycosides from unactivated aryl acetylenes.

A metal free and highly stereoselective procedure for the synthesis of 2,3-unsaturated-C-glycosides has been developed between glycals and unactivated aryl acetylenes in the presence of TMSOTf through a triflated C-vinyl glycosides intermediate. The flexibility of the procedure was tested by a wide variety of glycals and unactivated aryl acetylenes (20 examples). The corresponding alkynyl C-glycosides were obtained in good yields with completely α-selectivity in a short time (<25 min). And a plausible mechanism for the synthesis of alkynyl C-glycosides was depicted.

An efficient method for the synthesis of pyranoid glycals.

A simple and efficient procedure was designed for the preparation of pyranoid glycals. In a novel fashion, a series of protected glycopyranosyl bromides underwent reductive elimination in the presence of zinc dust and ammonium chloride in CH3CN at 30-60 °C. The corresponding glycals were obtained with excellent isolated yields (72-96%) in a short time (20-50 min). Furthermore, the transformation was compatible with different protection patterns and conveniently scalable (86% for 45 g acetobromoglucose) which made it very applicable in organic synthesis.