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Valanimycin is an azoxy‐containing natural product isolated from the fermentation broth of Streptomyces viridifaciens MG456‐hF10. While the biosynthesis of valanimycin has been partially characterized, how the azoxy group is constructed remains obscure. Herein, the membrane protein VlmO and the putative hydrazine synthetase ForJ from the formycin biosynthetic pathway are demonstrated to catalyze N−N bond formation converting O‐(l‐seryl)‐isobutyl hydroxylamine into N‐(isobutylamino)‐l‐serine. Subsequent installation of the azoxy group is shown to be catalyzed by the non‐heme diiron enzyme VlmB in a reaction in which the N−N single bond in the VlmO/ForJ product is oxidized by four electrons to yield the azoxy group. The catalytic cycle of VlmB appears to begin with a resting μ‐oxo diferric complex in VlmB, as supported by Mössbauer spectroscopy. This study also identifies N‐(isobutylamino)‐d‐serine as an alternative substrate for VlmB leading to two azoxy regioisomers. The reactions catalyzed by the kinase VlmJ and the lyase VlmK during the final steps of valanimycin biosynthesis are established as well. The biosynthesis of valanimycin was thus fully reconstituted in vitro using the enzymes VlmO/ForJ, VlmB, VlmJ and VlmK. Importantly, the VlmB‐catalyzed reaction represents the first example of enzyme‐catalyzed azoxy formation and is expected to proceed by an atypical mechanism. [ABSTRACT FROM AUTHOR]

Dendrimers are a family of nano‐sized three‐dimensional polymers with unique dendritic branching structures and compact spherical geometries. In recent years, dendrimers have made a series of breakthroughs in the biomedical field. In this review, we introduce the synthesis principles, modification methods, and new materials designed based on dendrimers; discuss the importance of cytotoxicity of dendrimers for applications; and elaborate on their applications in the field of molecular assembly and cancer diagnosis and treatment. We speculate that in the near future, more new materials based on dendrimers will be applied in the biomedical field. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The aim of this study was to explore the mechanism underlying the protective effects of 2,3,5,4‐tetrahydroxystilbene‐2‐o‐β‐D‐glucoside (TSG) against osteoporosis. Method: MC3T3‐E1 mouse osteoblast precursor cells were used to analyze the protective effects of TSG on osteoblast apoptosis and differential inhibition induced by oxidative stress to determine the gene expression of forkhead transcription factor FKHRL1 (FoxO3a), T cell factors (TCFs), and downstream genes. A mouse model was used to assess the protective effects of TSG on ovariectomy‐induced osteoporosis as well as on Cell Counting Kit‐8 (CCK) gene expression, including that of FoxO3a. The mechanism underlying the protective effects of TSG against osteoporosis was further explored using high‐throughput sequencing data. Results: A CCK‐8 assay in MC3T3‐E1 cells and hematoxylin and eosin staining in mouse tissue indicated that cell viability and bone tissue development were inhibited by oxidative stress and ovariectomy and that TSG neutralized or attenuated this effect. The expression levels of FoxO3a, TCF, and downstream genes and the indices of oxidative stress were the same in MC3T3‐E1 cells and the bone tissues of the mouse model. Bioinformatics analysis indicated that the cardiac muscle contraction and chemokine signaling pathway were disturbed in MC3T3‐E1 cells treated with hydrogen peroxide. Gene ontology‐biological process analysis revealed the influence of TSG treatment. Conclusion: Osteoporosis and cardiac diseases appear to share a common mechanism. In addition to Wnt/FoxO3a signaling, the immune system and the chemokine signaling pathway may contribute to the protective mechanism of TSG. [ABSTRACT FROM AUTHOR]