In nature, the attachment of sugars to small molecules is often used to mediate targeting, mechanism of action and/or pharmacology. As an alternative to pathway engineering or total synthesis, we report a useful method, in vitro glycorandomization (IVG), to diversify the glycosylation patterns of complex natural products. We have used flexible glycosyltransferases on nucleotide diphosphosugar (NDP-sugar) libraries to generate glycorandomized natural products and then applied chemoselective ligation to produce monoglycosylated vancomycins that rival vancomycin.

In vitro glycorandomization is a rapid chemoenzymatic strategy to diversify complex natural product scaffolds. The glycorandomization sugar activation pathway is dependent upon the efficient construction of diverse sugar-1-phosphate libraries. In the context of the previously evolved GalK Y371H "gatekeeper" mutation, the active site M173L mutation described herein presents a kinase with remarkably broadened substrate range to include 28 diverse natural and unnatural sugars. Among these new substrates, 6-azido-6-deoxy-galactose and 6-azido-6-deoxy-glucose present unique chemical probes to assess the utility of an E. coli Y371H/M173L-GalK-overproducing strain to generate unnatural sugar-1-phosphates in vivo. Remarkably, the in vivo conversion of both unnatural sugars rival that demonstrated in vitro. This notable in vivo success stands as the first step toward constructing short sugar-activation pathways in vivo and, ultimately, in vivo natural-product glycorandomization.

Previous studies revealed that polydatin, a natural small compound, possessed protective effect against ischemia/reperfusion injury and inflammation. However, the action and molecular mechanism of its potent anti-cancer activity remain poorly understood. In the present study, polydatin significantly killed several human tumor cell lines in a dose- and time-dependent manner. The compound also dose-dependently caused mitochondrial apoptosis in human nasopharyngeal carcinoma CNE cells. In addition, polydatin triggered endoplasmic reticulum (ER) stress and down-regulated the phosphorylation of Akt in CNE cells, while knock-down of CCAAT/enhancer-binding protein homologous protein (CHOP) dramatically abrogated the inactivation of Akt and reversed the pro-apoptotic effect of polydatin. Furthermore, polydatin provoked the generation of reactive oxygen species in CNE cells, while the antioxidant N-acetyl cysteine almost completely blocked the activation of ER stress and apoptosis, suggesting polydatin-induced reactive oxygen species is an early event that triggers ER stress mitochondrial apoptotic pathways in CNE cells. Taken together, these findings strongly suggest that polydatin might be a promising anti-tumor drug and our data provide the molecular theoretical basis for clinical application of polydatin.

Objectives: To provide anatomical data to help identify and locate the anterior ethmoidal artery (AEA) precisely during endoscopic procedures. Method: We dissected 15 adult cadaver heads, which provided 30 specimens, to study morphological characteristics, courses, and several types of variations. Results: We found the average diameter of the AEA to be 0.80 AE 0.24 mm. In 85.7% of the cases, the artery was seen between the second and third lamella. Other locations were over the roof of the frontal recess cells (10.7%) and the roof of the posterior ethmoid sinus (3.6%). The AEA ran parallel to the ethmoid roof and formed a slight curve. When viewed from the superior side, the angle formed by the long axis of the artery and the lamina papyracea was 60.5 degrees AE 16.4 degrees. In 83.3% of the cases, the anterior ethmoidal canal (AEC) was identified as a separate canal, and in 16.7% the canal was embedded in the ethmoid roof. In 10 of the 30 cases (33.3%), the AEC presented some degree of dehiscence. Conclusion: As a result of these dissections, we found that the AEA's course in the ethmoid roof varies. The morphological characteristics-that the AEA runs parallel to the ethmoid roof, forming a slight posterolateral to anteromedial curve as it passes from the orbit to the cribriform plate-are the most reliable factors used to identify the artery during surgery.

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