18 research outputs found
Supplementary document for Ultra-wideband Two-dimensional Airy Beam Generation with Amplitude-tailorable Metasurface - 6215144.pdf
working mode; coupling effect; different amplitude profiles; wideband performance;efficienc
Supplementary document for Ultra-wideband Two-dimensional Airy Beam Generation with Amplitude-tailorable Metasurface - 6221021.pdf
working mode; coupling effect; different amplitude profiles; wideband performance;efficienc
Supplementary document for Ultra-wideband Two-dimensional Airy Beam Generation with Amplitude-tailorable Metasurface - 6208183.pdf
working mode; coupling effect; different amplitude profiles; wideband performance
The retention time, predicted elemental compositions, observed mass and calculated mass, characteristic fragment ions, and description of metabolites of WS070117 in rat urine.
<p>The retention time, predicted elemental compositions, observed mass and calculated mass, characteristic fragment ions, and description of metabolites of WS070117 in rat urine.</p
The stack of <sup>13</sup>C NMR spectra of WS010117 and its four metabolites (in DMSO-d<sub>6</sub>).
<p>The stack of <sup>13</sup>C NMR spectra of WS010117 and its four metabolites (in DMSO-d<sub>6</sub>).</p
Structure Elucidation of the Metabolites of 2', 3', 5'-Tri-<i>O</i>-Acetyl-<i>N</i><sub>6</sub>-(3-Hydroxyphenyl) Adenosine in Rat Urine by HPLC-DAD, ESI-MS and Off-Line Microprobe NMR
<div><p>2', 3', 5'-tri-<i>O</i>-acetyl-<i>N<sub>6</sub></i>-(3-hydroxyphenyl) adenosine (also known as WS070117) is a new adenosine analog that displays anti-hyperlipidemic activity both <i>in vitro</i> and <i>in vivo</i> experiments as shown in many preliminary studies. Due to its new structure, little is known about the metabolism of WS070117. Hence, the <i>in vivo</i> metabolites of WS070117 in rat urine following oral administration were investigated. Identification of the metabolites was conducted using the combination of high-performance liquid chromatography (HPLC) coupled with diode array detector (DAD), ion trap electrospray ionization-mass spectrometry (ESI-MS), and off-line microprobe nuclear magnetic resonance (NMR) measurements. Seven metabolites were obtained as pure compounds at the sub-milligram to milligram levels. Results of structure elucidation unambiguously revealed that the phase I metabolite, <i>N<sub>6</sub></i>-(3-hydroxyphenyl) adenosine (M8), was a hydrolysate of WS070117 by hydrolysis on the three ester groups. <i>N<sub>6</sub></i>-(3-hydr-oxyphenyl) adenine (M7), also one of the phase I metabolites, was the derivative of M8 by the loss of ribofuranose. In addition to two phase I metabolites, there were five phase II metabolites of WS070117 found in rat urine. 8-hydroxy-<i>N<sub>6</sub></i>-(3-hydroxy-phenyl) adenosine (M6) was the product of M7 by hydrolysis at position 8. The other four were elucidated to be <i>N<sub>6</sub></i>-(3-<i>O-β</i>-D-glucuronyphenyl) adenine (M2), <i>N<sub>8</sub></i>-hydroxy-<i>N<sub>6</sub></i>-(3-<i>O</i>-sulfophenyl) adenine (M3), <i>N<sub>6</sub></i>-(3-<i>O-β</i>-D-glucuronyphenyl) adenosine (M4), and <i>N<sub>6</sub></i>-(3-<i>O</i>- sulfophenyl) adenosine (M5). Phase II metabolic pathways were proven to consist of hydroxylation, glucuronidation and sulfation. This study provides new and valuable information on the metabolism of WS070117, and also demonstrates the HPLC/MS/off-line microprobe NMR approach as a robust means for rapid identification of metabolites.</p></div
Beneficial Metabolic Effects of 2′,3′,5′-Triacetyl‑N<sub>6</sub>‑(3-hydroxylaniline) adenosine in Multiple Biological Matrices and Intestinal Flora of Hyperlipidemic Hamsters
Hyperlipidemia is one of the main
causes of obesity, type 2 diabetes
mellitus (T2DM), and atherosclerosis. The adenosine derivative, 2′,3′,5′-triacetyl-N<sub>6</sub>-(3-hydroxylaniline) adenosine (IMM-H007) is an effective
lipid-lowering compound that has important implications for the development
of lipid-lowering drugs. Metabolomic analysis based on <sup>1</sup>H NMR was used to monitor dynamic changes in diverse biological media
including serum, liver, urine, and feces in response to high-fat diet
(HFD) and IMM-H007 treatments. Ultraperformance liquid chromatography–tandem
mass spectrometry (UPLC–MS/MS) and gas chromatography (GC)
analyses were performed to quantify the bile acids and fatty acids
in the liver and feces. Fecal microbiome profiling was performed using
Illumina sequencing of the 16S rRNA (<i>16S rRNA</i>) gene.
IMM-H007 improved the metabolism of carbohydrate, ketone bodies, fatty
acids, amino acids, and bile acids in hyperlipidemic hamsters. The
correlation between metabolite changes was explored in different biological
media. Significant changes in gut microbiota were observed in the
HFD and IMM-H007 treatment groups. In the HFD group at the phylum
level, we found high levels of the Firmicutes genus and low levels
of Bacteroidetes. In contrast, the administration of IMM-H007 reversed
the levels of Firmicutes and Bacteroidetes. This reversal suggested
that IMM-H007 may have the ability to regulate the composition of
the gut flora. We also analyzed the correlation between the gut flora
and the metabolites. Our results indicate that IMM-H007 treatment
improves the hyperlipidemic metabolism and the structure of the gut
microbiota in hyperlipidemic hamsters
Structures of WS070117 metabolites in rat urine and the proposed metabolic pathways.
<p>Structures of WS070117 metabolites in rat urine and the proposed metabolic pathways.</p
<sup>1</sup>H NMR derived HSQC (A) and HMBC (B) spectra of <i>N</i><sub>8</sub>-hydroxy-<i>N</i><sub>6</sub>-(3-<i>O</i>-sulfophenyl) adenine (structure see formula insert).
<p><b>A</b> secondary metabolite in rat urine following WS070117 oral administration. The NMR spectra were obtained in deuterated DMSO on a 500 MHz NMR spectrometer, equipped with a 1.7 PA TXI microprobe. (A) HSQC (acquisition time: 2 h): red cross-peaks are stemming from CH, CH<sub>2</sub> and CH<sub>3</sub> protons. (B) HMBC (acquisition time: 6 h): the correlation information derived from the marked cross-peaks is summarized in the formula insert.</p
HPLC chromatogram of WS010117 metabolites in urine of control (A) and administrated (B) rats at 299 nm.
<p>Peak 1: 3.60 min (M1); 2: 14.15 min (M2); 3: 21.58 min (M3); 4: 23.25 min (M4); 5: 29.48 min (M5); 6: 47.68 min (M6); 7: 48.73 min (M7); 8: 49.44 min (M8).</p