α-Glucosidase Inhibitors from Two Mangrove-Derived Actinomycetes.

α-Glucosidase (AGS) inhibitors have been regarded as an ideal target for the management of type 2 diabetes mellitus (T2DM) since they can maintain an acceptable blood glucose level by delaying the digestion of carbohydrates and diminishing the absorption of monosaccharides. In the process of our endeavor in mining AGS inhibitors from natural sources, the culture broth of two mangrove-derived actinomycetes Streptomyces sp. WHUA03267 and Streptomyces sp. WHUA03072 exhibited an apparent inhibitory activity against AGS. A subsequent chemical investigation into the two extracts furnished 28 secondary metabolites that were identified by spectroscopic methods as two previously undescribed linear polyketides 1-2, four benzenoid ansamycins 3-6, fourteen cyclodipeptides 7-18, one prenylated indole derivative 19, two fusicoccane-type diterpenoids 20-21, two hydroxamate siderophore 22-23, and five others 24-28. Among all of the isolates, 11 and 24 were obtained from actinomycetes for the first time, while 20-21 had never been reported to occur in a marine-derived microorganism previously. In the in vitro AGS inhibitory assay, compounds 3, 8, 9, 11, 14, 16, and 17 exhibited potent to moderate activity with IC50 values ranging from 35.76 ± 0.40 to 164.5 ± 15.5 µM, as compared with acarbose (IC50 = 422.3 ± 8.4 µM). The AGS inhibitory activity of 3, 9, 14, 16, and 17 was reported for the first time. In particular, autolytimycin (3) represented the first ansamycin derivative reported to possess the AGS inhibitory activity. Kinetics analysis and molecular docking were performed to determine the inhibition types and binding modes of these inhibitors, respectively. In the MTT assay, 3, 8, 9, 11, 14, 16, and 17 exhibited no apparent cytotoxicity to the human normal hepatocyte (LO2) cells, suggesting satisfactory safety of these AGS inhibitors.

Improvement of sand-washing performance and internal flow field analysis of a novel downhole sand removal device.

With the progression of many shale gas wells in the Sichuan-Chongqing region of China into the middle and late stages of exploitation, the problem of sand production in these wells is a primary factor influencing production. Failure to implement measures to remove sand from the gas wells will lead to a sharp decline in production after a certain period of exploitation. Moreover, As the amount of sand produced in the well increases, the production layer will be potentially buried by sand. To boost the production of shale gas wells in the Sichuan-Chongqing region and improve production efficiency, a novel downhole jet sand-washing device has been developed. Upon analyzing the device's overall structure, it is revealed that the device adopts a structural design integrating a jet pump with an efficient sand- washing nozzle, providing dual capabilities for jet sand- washing and sand conveying via negative pressure. To enhance the sand- washing and unblocking performance of the device, various sand- washing fluids and the structures of different sand- washing nozzles are compared for selection, aiming to elevate the device's sand- washing and unblocking performance from a macro perspective. Subsequently, drawing on simulation and internal flow field analysis of the device's sand- washing and unblocking process through CFD and the control variable method, it is ultimately found that the length diameter ratio of the cylindrical segment of the nozzle outlet, the outlet diameter, and the contraction angle of the nozzle greatly influence the device's sand- washing and unblocking performance. And the optimum ranges for the length-diameter ratio of the cylindrical segment of the nozzle outlet, the outlet diameter, the contraction angle of the nozzle, and the inlet diameter are 2 to 4, 6 mm to 10 mm, 12° to 16°, and 18 mm and 22 mm, respectively. The findings of the research not only provide new insights into existing sand removal processes but also offer a novel structure for current downhole sand removal devices and a specific range for the optimal size of the nozzle.

Prediction of Hydrogel Degradation Time Based on Central Composite Design.

In this study, a self-degrading hydrogel was formed by free-radical-initiated copolymerization, which can be used for oil and gas well strip pressure operations. Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1H NMR), scanning electron microscopy (SEM), and thermogravimetry-mass spectrometry (TGA-MS) were used to study the reaction mechanism as well as the microstructure of the gels. Then, the effects of the four factors and their interactions on gel degradation time were determined by central composite design (CCD). Then, the effects of copolymer concentration, cross-linker, initiator, and reaction temperature and their interactions on gel degradation time were determined by central composite design (CCD), and the corresponding second-order polynomial models were generated. Finally, the gelation conditions were optimized by a response surface methodology and verified by degradation experiments. Both FTIR and 1H NMR indicated that the gel was formed by a copolymerization reaction between the monomer and the cross-linker. SEM showed that the gel structure collapsed, which was caused by the poor mechanical properties of the gel, but it was also able to withstand some wellbore pressure and degraded more easily. TGA-MS showed that the gel possessed good degradation properties. In addition, analysis of variance (ANOVA) showed that the second-order polynomial model was highly significant. The results also showed that the expected values of the gelation conditions optimized by the response surface methodology did not differ significantly from the actual values. The degradation model can be used to predict the degradation time of the gel and optimization of gelation conditions. This study can help petroleum engineers in applying self-degrading gels to seal the wellbore pressure.

α-Glucosidase and Bacterial ß-Glucuronidase Inhibitors from the Stems of Schisandra sphaerandra Staph.

α-Glucosidase (AGS) is a therapeutic target for Type 2 diabetes mellitus (T2DM) that tends to complicate with other diseases. Some medications for the treatment of T2DM complications have the risk of inducing severe adverse reactions such as diarrhea via the metabolism of intestinal bacterial ß-glucuronidase (BGUS). The development of new AGS and/or BGUS inhibitors may improve the therapeutic effects of T2DM and its complications. The present work focused on the isolation and characterization of AGS and/or BGUS inhibitors from the medicinal plant Schisandra sphaerandra. A total of eight compounds were isolated and identified. Sphaerandralide A (1) was obtained as a previously undescribed triterpenoid, which may have chemotaxonomy significance in the authentication of the genus Schisandra and Kadsura. 2'-acetyl-4',4-dimethoxybiphenyl-2-carbaldehyde (8) was obtained from a plant source for the first time, while compounds 2-7 were isolated from S. sphaerandra for the first time. In the in vitro assay, compounds 1-5 showed potent to moderate activity against AGS. Interestingly, compound 3 also exhibited significant BGUS inhibitory activity, demonstrating the potential of being developed as a bifunctional inhibitor that may find application in the therapy of T2DM and/or the diarrhea induced by medications for the treatment of T2DM complications.

[Determination of notoginsenoside R1, ginsenoside Rg1 and Rb1 in Radix Notoginseng and its preparation by HPLC-ELSD].

OBJECTIVE: To establish the quantitative method of notoginsenoside R1, ginsenoside Rg1 and Rb1 in Radix Notoginseng and its preparation Xuesaitong injection by HPLC-ELSD. METHOD: The column was packed with 5 microm Diamonsil C18 stationary phase. The mobile phase consisted of acetonitrile-water, eluted in gradient mode. The temperature of drift tube was 105 degrees C and the nebulizer nitrogen flow rate was 2.9 L x min(-1). RESULT: The linear ranges of the three components were 0.456-2.25 microg, 1.47-7.38 microg and 1.20-6.03 microg respectively. The average recoveries of the three components in Radix Notoginseng were 97.1% (RSD 1.9%), 96.8% (RSD 2.0%), 97.0% (RSD 2.2%) respectively; in Xuesaitong Injection were 98.7% (RSD 1.9%), 98.5% (RSD 1.8%), 98.1% (RSD 1.4%) respectively. CONCLUSION: It was proved that the method was reliable, simple, and precise, that could be used for quality control.