Characterization of a Reductively-Activated Elimination Pathway Relevant to the Biological Chemistry of the Kinamycins and Lomaiviticins

The lomaiviticins (1 and 2) and kinamycins (3–5) are bacterial metabolites with potent antimicrobial and antiproliferative activities. Herein we establish that 1–5 are capable of generating electrophilic acylfulvene intermediates (6) under mildly reducing conditions. These acylfulvenes 6 are formed by a multistep process comprising two-electron reduction and loss of dinitrogen to form an ortho-quinone methide, followed by elimination. Based on these studies, the structure of the product formed from 1 in DNA-cleavage assays is proposed (26). We also show that the bis(hydroxynaphthoquinone) substructures of the lomaiviticins activate the metabolites toward reduction. Finally, based on COMPARE and time-dependent cell response profiling analyses, we show that kinamycin C (4) and the monomeric lomaiviticin aglycon (24) operate by a mechanism of action that is distinct from simple diazofluorenes, such as 23

Detection of HBV Genotypes of Tumor Tissues and Serum by A Fluorescence Polarization Assay in North-Western China's Hepatocellular Carcinoma Patients

<p>Abstract</p> <p>Background</p> <p>The understanding of the distribution of hepatitis B virus genotypes and the occult hepatitis B virus infection in hepatocellular carcinoma may shed light into the prevention and treatment of hepatocellular carcinoma. The purpose of the study is to investigate hepatitis B virus genotypes distribution, the high-risk genotypes and the occult infection in north-western China's hepatocellular carcinoma patients.</p> <p>Methods</p> <p>Hepatitis B virus genotypes A-D of hepatocellular carcinoma tumor tissues and serum samples in 268 north-western China hepatocellular carcinoma patients were detected by fluorescence polarization assay. The hepatitis B virus genotypes in serum and matched primary tumor tissue samples were compared. Hepatitis B surface antigen and α-fetoprotein in serum were detected. Occult hepatitis B virus infections were analyzed. The relationship between hepatitis B virus genotypes and clinicopathologic characteristics were analyzed statistically using SPSS v.10.0.</p> <p>Results</p> <p>Intrahepatic hepatitis B virus DNA was detected in 83.6% of 268 patients, whereas serum hepatitis B virus DNA was detected in 78.7%. The hepatitis B virus genotypes in serum were consistent with the results in matched tumor tissue. Intrahepatic hepatitis B virus genotype B and C were detected respectively in 11.6% and 54.5% of the patients. Mixed intrahepatic hepatitis B virus genotypes were detected in 13.4% of 268 patients. There was not mixed hepatitis B virus infection in Edmondonson grade I. The patients with mixed HBV genotypes exhibited statistically significant different Edmondson grade than the patients with single type HBV infection (p < 0.05). Hepatitis B surface antigens were positive in 77.2% of 268 patients. Hepatitis B virus genotype C was detected in 64.7% of occult infected patients. There was no significant differences of patients' ages and α-fetoprotein level in different groups of intrahepatic hepatitis B virus genotypes (p > 0.05).</p> <p>Conclusions</p> <p>Hepatitis B virus genotype C was associated closely with the development of hepatocellular carcinoma and the occult hepatitis B virus infection in patients in north-western China. There was a relatively high prevalence of mixed hepatitis B virus infection in Edmondonson grade III-IV.</p

A Metabolomics Profiling Study in Hand-Foot-and-Mouth Disease and Modulated Pathways of Clinical Intervention Using Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry

Hand-foot-and-mouth disease (HFMD), with poorly understood pathogenesis, has become a major public health threat across Asia Pacific. In order to characterize the metabolic changes of HFMD and to unravel the regulatory role of clinical intervention, we have performed a metabolomics approach in a clinical trial. In this study, metabolites profiling was performed by liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) platform from the HFMD clinical patient samples. The outcome of this study suggested that 31 endogenous metabolites were mainly involved and showed marked perturbation in HFMD patients. In addition, combination therapy intervention showed normalized tendency in HFMD patients in differential pathway. Taken together, these results indicate that metabolomics approach can be used as a complementary tool for the detection and the study of the etiology of HFMD

Study on atomization mechanisms and spray fragmentation characteristics of water and emulsion butachlor

Agricultural chemicals are commonly used to control pests and weeds, but cause pesticide waste problems. Oil-based emulsions are often used as pesticide formulations to improve pesticide utilization. In this study, the spray visualization experiment of the water and oil-based emulsion butachlor is carried out using an ST flat fan nozzle at 0.1–0.5 MPa pressure. The dimensionless method is used to analyze the difference in liquid sheet fragmentation morphology and disintegration process and the influence of different fragmentation methods on droplet size. It is found that the hydrophobic components in pesticide have a significant effect on the morphology and process of atomization fragmentation. When spray liquid is water, the liquid sheet breaks up into liquid ligaments due to the Rayleigh instability, then the ligaments break up into droplets. The side view of a liquid sheet is a large-amplitude wave disturbance. When the spray liquid is the emulsion butachlor, holes are generated on the liquid sheet, then the holes break up into droplets. The fragmentation method of emulsion spray is the perforation mechanism. Compared with water spray, the presence of the pesticide butachlor increases the droplet size and spray angle and improves the uniformity of droplet size distribution but reduces the breakup length. The spray angle shows a power law dependence of the Weber number with a power of 0.17 for all conditions tested here. At 0.3 MPa, DV50 increases 25%, and span decreases from 1.187 to 1.172. This study could provide reference for the addition of agricultural additives, the improvement of spray operation efficiency, and the establishment of spray fragmentation mechanism

Major Miocene geological events in southern Tibet and eastern Asia induced by the subduction of the Ninetyeast Ridge

Cenozoic adakitic rocks in the Gangdese changed from barren continental melts to ore-forming slab melts at ~ 23 Ma. The distribution and chemical characteristics of the ore-forming adakites point to an association with the Ninetyeast Ridge. The subduction of the thick, rigid Ninetyeast Ridge changed the geometry and rheology of the eastern Tibetan Plateau lithosphere and asthenosphere, restrained the eastward escape of asthenospheric mantle as well as continental fragments, and promoted the uplift and building of the Tibetan Plateau, which consequently changed the tectonic and climatic regimes in eastern Asia.This study was supported by NSFC 91328204 to W.D.S. and Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB18020102) to W.D.S. and X.L.S