P450-mediated dehydrotyrosine formation during WS9326 biosynthesis proceeds via dehydrogenation of a specific acylated dipeptide substrate

WS9326A is a peptide antibiotic containing a highly unusual N-methyl-E-2-3-dehydrotyrosine (NMet-Dht) residue that is incorporated during peptide assembly on a non-ribosomal peptide synthetase (NRPS). The cytochrome P450 encoded by sas16 (P450Sas) has been shown to be essential for the formation of the alkene moiety in NMet-Dht, but the timing and mechanism of the P450Sas-mediated α,β-dehydrogenation of Dht remained unclear. Here, we show that the substrate of P450Sas is the NRPS-associated peptidyl carrier protein (PCP)-bound dipeptide intermediate (Z)-2-pent-1'-enyl-cinnamoyl-Thr-N-Me-Tyr. We demonstrate that P450Sas-mediated incorporation of the double bond follows N-methylation of the Tyr by the N-methyl transferase domain found within the NRPS, and further that P450Sas appears to be specific for substrates containing the (Z)-2-pent-1'-enyl-cinnamoyl group. A crystal structure of P450Sas reveals differences between P450Sas and other P450s involved in the modification of NRPS-associated substrates, including the substitution of the canonical active site alcohol residue with a phenylalanine (F250), which in turn is critical to P450Sas activity and WS9326A biosynthesis. Together, our results suggest that P450Sas catalyses the direct dehydrogenation of the NRPS-bound dipeptide substrate, thus expanding the repertoire of P450 enzymes that can be used to produce biologically active peptides.

Lung and gut microbiota and their interaction with the carcinogenesis and development of lung cancer: a review / 生物工程学报

Lung microbiota and gut microbiota are closely related to lung cancer. Studies have shown that the dysbiosis, i.e., the significantly altered composition and structure of gut and lung microbiota, usually occurs in patients with lung cancer. With the introduction of "Gut-Lung Axis", an increasing attention has been paid to the close relationship between the lung and gut microbiota in human body. A deeper insight into this relationship would facilitate understanding the mechanisms behind the carcinogenesis and development of lung cancer. This article summarizes the composition of lung and gut microbiota in patients with lung cancer and the possible interaction mechanisms, highlighting the importance of the immune system in the Gut-Lung Axis. The effects of lung and gut microbiota on the clinical treatment of lung cancer were summarized, based on which the authors propose that the lung and gut microbiota can be used as novel targets for early diagnosis and treatment of lung cancer.

CT features of adrenal schwannoma / 实用放射学杂志

Objective To analyze computed tomography imaging features of primary adrenal schwannoma.Methods The clinical and radiological data of six cases of adrenal schwannoma confirmed by histopathology were analyzed in this study.Results All six cases of adrenal schwannoma were well-circumscribed,round-like or oval-like,solid and cystic tumors,in which two cases were with calcification,and three cases with septations.On the enhanced CT images,all six tumors displayed progressive enhancement.Conclusion Adrenal schwannoma usually presents a well-defined heterogeneous mass with cystic degeneration,sepations,calcification and characteristic progressive contrast enhancement.

Imaging characteristics and clinical prognosis of nasopharygeal adenocarcinoma / 实用放射学杂志

Objective To analyze the different spreading patterns and the prognostic factors of nasopharyngeal adenocarcinoma (NPAC).Methods The clinical and radiological data of 39 pathologically confirmed consecutive cases of NPAC were retrospectively reviewed.Results In the 1 1 patients with CT/MRI-detected cranial nerve (CN)involvement,there were ACC (n=7),CAC (n=2)and MEC (n=2)(P <0.05).Lymph node metastasis occurred in 40% of CAC,7.7% of ACC and 1 6.7% of MEC (P =0.035). Significant differences were observed in 5 year OS and DFS rates between patients with and without CT/MRI-detected CN involve-ment (P <0.001;P =0.001).In 1 9 patients with early stage disease (stageⅠ-Ⅱ),significant difference was observed in 5 year OS rate between the surgical treatment group and non-surgical treatment group (P =0.038),and the difference was not significant in DFS (P =0.056).Conclusion CT and MRI are valuable tools not only for discovering the different spreading patterns of NPAC, but also for its prognosis.

The Value of Neutrophil to Lymphocyte Ratio in Predicting In-stent Restenosis in Patients with Coronary Heart Disease / 昆明医科大学学报

Objective To investigate the value of neutrophil to lymphocyte ratio (NLR) in predicting in-stent restenosis (ISR) in patients with coronary heart disease. Methods We collected the data of 618 patients with coronary heart disease hospitalized in the Department of Cardiology in the First Affiliated Hospital of Kunming Medical University from January 2011 to June 2012. All selected patients underwent coronary angiography and stent implantation, and were divided into two groups according to the average size of NLR. The relationship between the neutrophil to lymphocyte ratio and coronary heart disease in-stent restenosis was investigated. Results There were statistically significant differences in the presence of diabetes, high density lipoprotein, low density lipoprotein, the percentage of neutrophils and lymphocytes in patients between two groups (P<0.05) . We found 13 patients (4.2%) and 32 patients (10.4%) with in-stent restenosis in the first group and the second group, respectively, and there was a statistically significant difference between two groups (P<0.01) . Conclusion Neutrophil to lymphocyte ratio is correlated with ISR,and has clinical value in predicting ISR.