High performance liquid chromatography with ultraviolet detection for the determination of SYUIQ-5, a novel telomerase inhibitor for cancer therapy: application to an enzyme kinetic study in rat liver microsomes

A sensitive assay for the determination of SYUIQ-5, a novel telomerase inhibitor and anti-tumor drug, in rat liver microsomes was developed by using high-performance liquid chromatography with ultraviolet detection. SYUIQ-5 was incubated in vitro with liver microsomes from rats pre-treated with control vehicle, beta-naphthofIavone, phenobarbital, 20% ethanol or dexamethasone. The analytes were extracted with diethyl ether and separated a C(18) 5-microm analytical column. Elution was conducted with 30 mM dipotassium hydrogen phosphate (pH 8.0)-methanol-triethylamine (30:70:0.05, v/v/v) at a flow-rate of 1.0 ml/min and the detection of UV absorbance was conducted at 278 nm. Intra-day and inter-day precision and accuracy of the method were within 10%. The mean analytical recoveries of SYUIQ-5 ranged from 78.8 to 95.3%. The linearity of the calibration curve was in the range of 1.0-80.0 microM. The lower limit of quantification (LOQ) was 1.0 microM. Kinetic analysis showed that beta-naphthofIavone and dexamethasone significantly induced SYUIQ-5 metabolism, suggesting that cytochrome P450 1A and 3A are the major contributor to SYUIQ-5 metabolism in rat liver microsomes.     

A Water-absorbent Mat Incorporating β-cyclodextrin/eugenol Inclusion Complex for Preservation of Cold Fresh Mutton

To extend the shelf life of cold fresh mutton, the water-absorbent antibacterial mat was developed. This mat was composed of polylactic acid-β-cyclodextrin/eugenol (PLA-β-CD/EUG) fiber membrane, super absorbent polymer (SAP) and filter paper, in which the fiber membrane was developed by the electrospinning technique. The β-CD/EUG inclusion complexes were shown to form successfully by scanning electron microscope (SEM), fourier transform infrared spectroscopy (FTIR), water contact angle (WCA) analysis. The release experiment indicated that the PLA-β-CD/EUG fiber membranes had a slow-release effect, especially in the fatty food simulant. The water-absorbent antibacterial mats can restrain the growth of six spoilage bacteria. The mats were evaluated for the preservation of cold fresh mutton. The results revealed that it displayed prolongation of shelf life upon 8 days during the mutton at 4 °C storage period. The water-absorbent antibacterial mat can slowly release natural antibacterial agents and absorb water to achieve preservation, suggesting a potential application in meat products.

     

Simulated nitrogen deposition induces shifts in growth and resource-use strategies during range expansion of an invasive plant

Biological Invasions - An appropriate resource-use strategy contributes to the invasion success of exotic plants. During range expansion, population density and nitrogen availability are two...     

Weighted double deep Q-network based reinforcement learning for bi-objective multi-workflow scheduling in the cloud

Cluster Computing - As a promising distributed paradigm, cloud computing provides a cost-effective deploying environment for hosting scientific applications due to its provisioning elastic,...     

The Effects of Heart Rate Variability (HRV) Biofeedback on HRV Reactivity and Recovery During and After Anger Recall Task for Patients with Coronary Artery Disease

Patients with coronary artery disease (CAD) often experience anger events before cardiovascular events. Anger is a psychological risk factor and causes underlying psychophysiological mechanisms to lose balance of the autonomic nervous system (ANS). The heart rate variability (HRV) was the common index for ANS regulation. It has been confirmed that heart rate variability biofeedback (HRV-BF) restored ANS balance in patients with CAD during the resting state. However, the effects of HRV-BF during and after the anger event remain unknown. This study aimed to examine the effects of HRV-BF on ANS reactivity and recovery during the anger recall task in patients with CAD. This study was a randomized control trial with a wait-list control group design, with forty patients in the HRV-BF group (for six sessions) and 44 patients in the control group. All patients received five stages of an anger recall task, including baseline, neutral recall task, neutral recovery, anger recall task, and anger recovery. HRV reactivity in the HRV-BF group at the post-test was lower than that in the control group. HRV recovery at the post-test in the HRV-BF group was higher than that in the control group. The HRV-BF reduced ANS reactivity during anger events and increased ANS recovery after anger events for CAD patients. The possible mechanisms of HRV-BF may increase total HRV, ANS regulation, and baroreflex activation at anger events for patients with CAD, and may be a suitable program for cardiac rehabilitation.

     

Purple sweet potato color attenuated NLRP3 inflammasome by inducing autophagy to delay endothelial senescence

Autophagy is a vital negative factor regulating cellular senescence. Purple sweet potato color (PSPC), one type of flavonoid, has been demonstrated to suppress endothelial senescence and restore endothelial function in diabetic mice by inhibiting the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome. However, the roles of autophagy in the inflammatory response during endothelial senescence are unknown. Here, we found that PSPC augmented autophagy to restrict high-glucose-induced premature endothelial senescence. In addition, PSPC administration impaired endothelium aging in diabetic mice by increasing autophagy. Inhibition of autophagy accelerated endothelial senescence, while enhancement of autophagy delayed senescence. Moreover, deactivation of the NLRP3 inflammasome triggered by PSPC was autophagy-dependent. Autophagy receptor microtubule-associated protein 1 light chain 3 and p62 interacted with the inflammasome component NLRP3, suggesting that autophagosomes target the NLRP3 inflammasome and deliver it to the lysosome for degradation. Altogether, PSPC amplified cellular autophagy, subsequently attenuated NLRP3 inflammasome activity and finally delayed endothelial senescence to ameliorate cardiovascular complication. These results suggest a potential therapeutic target in senescence-related cardiovascular diseases.     

Conch size evolution of Silurian–Devonian tentaculitoids

Conch size changes of tentaculitoids are reported from the Silurian and Devonian strata. The combination of measurements of diameters and apical angles allows the reconstruction of tentaculitoid volumes. The conch wall thickness and number of septa can be investigated through observations of thin sections. Within the examined groups, the average conch volume (including the adult part and the whole conch) of tentaculitids increased from the Llandovery to the Pragian and then decreased until the Frasnian. A similar trend was observed in the Devonian dacryoconarids, which peaked for average conch volume in the Emsian. Sea‐level change was probably the main factor controlling the conch volume of tentaculitids and dacryoconarids. The continuous decrease in the average number of septa and the average volume of tentaculitid and dacryoconarid juvenile part from the Pragian (or the Emsian) to the Frasnian indicates a reduction of juvenile duration and earlier reproductive behaviour. The ratio of adult part to juvenile part volumes increased from the Emsian to the Frasnian in tentaculitids, suggesting that the angle between the conch and the water–sediment interface decreased. The conch volume and thickness of the juvenile part and the adult part in all tentaculitoid groups demonstrated similar trends. The average volume of the initial chamber and the adult part of dacryoconarids changed synchronously, with the peak value in the Emsian. Homoctenids, with the smallest conch and the thinnest wall, probably lived in deeper water than dacryoconarids.     

Streptomycin-induced ribosome engineering complemented with fermentation optimization for enhanced production of 10-membered enediynes tiancimycin-A and tiancimycin-D

Tiancimycins (TNMs) are a group of 10-membered anthraquinone-fused enediynes, newly discovered from Streptomyces sp. CB03234. Among them, TNM-A and TNM-D have exhibited excellent antitumor performances and could be exploited as very promising warheads for the development of anticancer antibody-drug conjugates (ADCs). However, their low titers, especially TNM-D, have severely limited following progress. Therefore, the streptomycin-induced ribosome engineering was adopted in this work for strain improvement of CB03234, and a TNMs high producer S. sp. CB03234-S with the K43N mutation at 30S ribosomal protein S12 was successfully screened out. Subsequent media optimization revealed the essential effects of iodide and copper ion on the production of TNMs, while the substitution of nitrogen source could evidently promote the accumulation of TNM-D, and the ratio of produced TNM-A and TNM-D was responsive to the change of carbon and nitrogen ratio in the medium. Further amelioration of the pH control in scaled up 25 L fermentation increased the average titers of TNM-A and TNM-D up to 13.7 ± 0.3 and 19.2 ± 0.4 mg/L, respectively. The achieved over 45-fold titer improvement of TNM-A, and 109-fold total titer improvement of TNM-A and TNM-D enabled the efficient purification of over 200 mg of each target molecule from 25 L fermentation. Our efforts have demonstrated a practical strategy for titer improvement of anthraquinone-fused enediynes and set up a solid base for the pilot scale production and preclinical studies of TNMs to expedite the future development of anticancer ADC drugs.     

High-resolution imaging of rhizosphere oxygen (O2) dynamics in Potamogeton crispus: effects of light,temperature and O2 content in overlying water

Plant and Soil - Radial oxygen loss (ROL) for macrophytes is intimately involved in their survival and growth, thus detailed characterizations of ROL and its implication for geochemical processes...