AIM: To characterize the intestinal transport and mechanism of metformin in rats and to investigate whether or not metformin is a substrate for P-glycoprotein (P-gp). METHODS: The effective intestinal permeability...AIM: To characterize the intestinal transport and mechanism of metformin in rats and to investigate whether or not metformin is a substrate for P-glycoprotein (P-gp). METHODS: The effective intestinal permeability of metformin was investigated using single-pass intestinal perfusion (SPIP) technique in male Waster rats. SPIP was performed in three isolated intestinal segments (duodenum, jejunum and ileum) at the same concentration of metformin (50 μg/mL) to test if the intestinal transport of metformin exhibited site- dependent changes, and in a same isolated intestinal segment (duodenal segment) at three different concentrations of metformin (10, 50, 200 μg/mL) to test if the intestinal transport of metformin exhibited concentration-dependent changes. Besides, P-gp inhibitor verapamil (400 μg/mL) was co-perfused with metformin (50 μg/mL) in the duodenum segment to find out if the intestinal absorption of metformin was affected by P-gp exiting along the gastrointestinal track. Stability studies were conducted to ensure that the loss of metformin could be attributed to intestinal absorption. RESULTS: The effective permeability values (Peff) of metformin in the jejunum and ileum at 50μg/mL were significantly lower than those in the duodenum at the same concentration. Besides, Peff values in the duodenum at high concentration (200 μg/mL) were found to be significantly lower than those at low and medium concentrations (10 and 50 μg/mL). Moreover the coperfusion with verapamil did not increase the Peff value of metformin at 50 μg/mL in the duodenum.CONCLUSION: Metformin could be absorbed from the whole intestine, with the main absorption site at duodenum. This concentration-dependent permeability behavior in the duodenum indicates that metformin is transported by both passive and active carrier-mediated saturable mechanism. The Peff value can not be increased by co-perfusion with verapamil, indicating that absorption of metformin is not efficiently transported by P-gp in the gut wall. Furthermore metformin is neither a substrate nor an inducer of P-gp. Based on the Peff values obtained in the present study and using established relationships, the human fraction dose absorbed for metformin is estimated to be 74%-90% along human intestine.展开更多
Single-pass is commonly used in topic detection and tracking( TDT) due to its simplicity,high efficiency and low cost. When dealing with large-scale data,time cost will increase sharply and clustering performance will...Single-pass is commonly used in topic detection and tracking( TDT) due to its simplicity,high efficiency and low cost. When dealing with large-scale data,time cost will increase sharply and clustering performance will be affected greatly. Aiming at this problem,hierarchical clustering algorithm based on single-pass is proposed,which is inspired by hierarchical and concurrent ideas to divide clustering process into three stages. News reports are classified into different categories firstly.Then there are twice single-pass clustering processes in the same category,and one agglomerative clustering among different categories. In addition,for semantic similarity in news reports,topic model is improved based on named entities. Experimental results show that the proposed method can effectively accelerate the process as well as improve the performance.展开更多
The most important grinding processes were realized in a single pass of the grinding wheel,such as continuous path controlled grinding (CPCG/Peelgrinding/HSP),CPCG with reduced contact of the grinding wheel (Quickpoin...The most important grinding processes were realized in a single pass of the grinding wheel,such as continuous path controlled grinding (CPCG/Peelgrinding/HSP),CPCG with reduced contact of the grinding wheel (Quickpoint),single-pass longitudinal internal grinding,creep feed grinding (CFG),longitudinal cylindrical grinding with grinding wheels made of conventional abrasive materials and longitudinal internal cylindrical grinding using grinding wheels with zone-diversified structure.展开更多
Aim Paeoniflorin-6'O-benzene sulfonate (CP-25) was synthesized to improve oral absorption. This study was performed to investigate absorptive behavior and mechanism of CP-25 in intestine. Methods The effects of dru...Aim Paeoniflorin-6'O-benzene sulfonate (CP-25) was synthesized to improve oral absorption. This study was performed to investigate absorptive behavior and mechanism of CP-25 in intestine. Methods The effects of drug concentration, intestinal segments, gender as well as ATP binding cassette (ABC) transporter inhibitors on absorption of CP-25 were studied in a situ single-pass intestinal perfusion rat model. Meanwhile, Paeoniflorin (Pae) was tested and served as control group. The concentration of tested drugs was measured by HPLC. Results The results showed intestinal absorption of CP-25 was neither segmental dependent changes nor gender difference. Transepithelial transportation would not change with increasing concentrations of CP-25, which suggest a passive transport was the main pattern of CP-25. Additionally, absorption of CP-25 was much better than that of Pae in small intestine. When compared with Pae, CP-25 gave a 1.82-fold permeability rate. Finally, the results indicated Pae was substrate of P-glycoprotein (P-gp) , but was not the substrate of breast cancer resistance protein and muhi- drug resistance associated protein 2. Among the used ABC inhibitors, the absorption rate of Pae could only be in- creased by? P-gp inhibitor Verapamil and GF120918, while CP-25 had no remarkable alteration. Conclusion CP-25 has better absorptive features than that of Pae, which may be attributed to its lipophicity enhancement and be unaffected by P-gp efflux.展开更多
Sickle-cell intrahepatic cholestasis (SCIC) is an uncommon complication of sickle-cell disease (SCD), which can be life-threating if left untreated. We present the case of a 28-year-old man with SCD, who presented wit...Sickle-cell intrahepatic cholestasis (SCIC) is an uncommon complication of sickle-cell disease (SCD), which can be life-threating if left untreated. We present the case of a 28-year-old man with SCD, who presented with jaundice and abdominal pain, one month after hydroxyurea discontinuation. Laboratory investigation revealed solely increased serum bilirubin, mainly conjugated, and imaging studies revealed choledocholithiasis. The patient unterwent an endoscopic sphincterectomy, but his jaundice deteriorated. Sickle-cell intrahepatic cholestasis was suspected and he received aggressive exchange transfusion therapy in combination with hydroxyurea. The jaundice had no signs of improvement;in fact total bilirubin raised up to 1053.7 μmol/L (61.62 mg/dl). Subsequently, the patient was treated with single-pass albumin dialysis (SPAD), in order to remove the excess bilirubin and protect mainly the brain and liver cells from its toxic effects. His laboratory values started to improve after one-and-a-half months of treatment. For the next two months, exchange transfusions were continued and bilirubin gradually returned to baseline values. The successful response appeared after the combined use of exchange transfusion and SPAD, which is being reported for the first time.展开更多
Electronics For Imaging, Inc.(Nasdaq: EFII) showcased the advanced, leading-edge technologies that make EFI? Reggiani a textile innovator at ITMA 2019, June 20th - 26th in Barcelona, including the gamechanging EFI Reg...Electronics For Imaging, Inc.(Nasdaq: EFII) showcased the advanced, leading-edge technologies that make EFI? Reggiani a textile innovator at ITMA 2019, June 20th - 26th in Barcelona, including the gamechanging EFI Reggiani BOLT single-pass inkjet printer – the first digital textile solution capable of high-quality output at record production speeds of up to 90 linear meters (295 linear feet) per minute.展开更多
Understandings of the effect of hot deformation parameters close to the practical production line on grain refinement are crucial for enhancing both the strength and toughness of future rail steels.In this work,the au...Understandings of the effect of hot deformation parameters close to the practical production line on grain refinement are crucial for enhancing both the strength and toughness of future rail steels.In this work,the austenite dynamic recrystallization(DRX)behaviors of a eutectoid pearlite rail steel were studied using a thermo-mechanical simulator with hot deformation parameters frequently employed in rail production lines.The single-pass hot deformation results reveal that the prior austenite grain sizes(PAGSs)for samples with different deformation reductions decrease initially with an increase in deformation temperature.However,once the deformation temperature is beyond a certain threshold,the PAGSs start to increase.It can be attributed to the rise in DRX volume fraction and the increase of DRX grain with deformation temperature,respectively.Three-pass hot deformation results show that the accumulated strain generated in the first and second deformation passes can increase the extent of DRX.In the case of complete DRX,PAGS is predominantly determined by the deformation temperature of the final pass.It suggests a strategic approach during industrial production where part of the deformation reduction in low temperature range can be shifted to the medium temperature range to release rolling mill loads.展开更多
This study investigates the single-pass absorption(SPA) of ion cyclotron range of frequency(ICRF) heating in hydrogen plasma of the EXL-50U spherical tokamak,which is an upgraded EXL-50 device with a central solenoid ...This study investigates the single-pass absorption(SPA) of ion cyclotron range of frequency(ICRF) heating in hydrogen plasma of the EXL-50U spherical tokamak,which is an upgraded EXL-50 device with a central solenoid and a stronger magnetic field.The reliability of the kinetic dispersion equation is confirmed by the one-dimensional full-wave code,and the applicability of Porkolab's simplified theoretical SPA model is discussed based on the kinetic dispersion equation.Simulations are conducted to investigate the heating effects of the fundamental and second harmonic frequencies.The results indicate that with the design parameters of the EXL-50U device,the SPA for second harmonic heating is 63%,while the SPA for fundamental heating is 13%.Additionally,the optimal injection frequencies are 23 MHz at 0.9 T and 31 MHz at 1.2 T.The wave vector of the antenna parallel to the magnetic field,with a value of k_‖=7.5 m^(-1),falls within the optimal heating region.Simulations reveal that the ICRF heating system can play an important role in the ion heating of the EXL-50U.展开更多
基金Supported by the National "863" Program of China, No.2003AA2Z347Dthe National "973" Program of China, No.2004CB518902
文摘AIM: To characterize the intestinal transport and mechanism of metformin in rats and to investigate whether or not metformin is a substrate for P-glycoprotein (P-gp). METHODS: The effective intestinal permeability of metformin was investigated using single-pass intestinal perfusion (SPIP) technique in male Waster rats. SPIP was performed in three isolated intestinal segments (duodenum, jejunum and ileum) at the same concentration of metformin (50 μg/mL) to test if the intestinal transport of metformin exhibited site- dependent changes, and in a same isolated intestinal segment (duodenal segment) at three different concentrations of metformin (10, 50, 200 μg/mL) to test if the intestinal transport of metformin exhibited concentration-dependent changes. Besides, P-gp inhibitor verapamil (400 μg/mL) was co-perfused with metformin (50 μg/mL) in the duodenum segment to find out if the intestinal absorption of metformin was affected by P-gp exiting along the gastrointestinal track. Stability studies were conducted to ensure that the loss of metformin could be attributed to intestinal absorption. RESULTS: The effective permeability values (Peff) of metformin in the jejunum and ileum at 50μg/mL were significantly lower than those in the duodenum at the same concentration. Besides, Peff values in the duodenum at high concentration (200 μg/mL) were found to be significantly lower than those at low and medium concentrations (10 and 50 μg/mL). Moreover the coperfusion with verapamil did not increase the Peff value of metformin at 50 μg/mL in the duodenum.CONCLUSION: Metformin could be absorbed from the whole intestine, with the main absorption site at duodenum. This concentration-dependent permeability behavior in the duodenum indicates that metformin is transported by both passive and active carrier-mediated saturable mechanism. The Peff value can not be increased by co-perfusion with verapamil, indicating that absorption of metformin is not efficiently transported by P-gp in the gut wall. Furthermore metformin is neither a substrate nor an inducer of P-gp. Based on the Peff values obtained in the present study and using established relationships, the human fraction dose absorbed for metformin is estimated to be 74%-90% along human intestine.
基金Supported by the National Natural Science Foundation of China(No.61502312)the Fundamental Research Funds for the Central Universities(No.2017BQ024)+1 种基金the Natural Science Foundation of Guangdong Province(No.2017A030310428)the Science and Technology Programm of Guangzhou(No.201806020075,20180210025)
文摘Single-pass is commonly used in topic detection and tracking( TDT) due to its simplicity,high efficiency and low cost. When dealing with large-scale data,time cost will increase sharply and clustering performance will be affected greatly. Aiming at this problem,hierarchical clustering algorithm based on single-pass is proposed,which is inspired by hierarchical and concurrent ideas to divide clustering process into three stages. News reports are classified into different categories firstly.Then there are twice single-pass clustering processes in the same category,and one agglomerative clustering among different categories. In addition,for semantic similarity in news reports,topic model is improved based on named entities. Experimental results show that the proposed method can effectively accelerate the process as well as improve the performance.
文摘The most important grinding processes were realized in a single pass of the grinding wheel,such as continuous path controlled grinding (CPCG/Peelgrinding/HSP),CPCG with reduced contact of the grinding wheel (Quickpoint),single-pass longitudinal internal grinding,creep feed grinding (CFG),longitudinal cylindrical grinding with grinding wheels made of conventional abrasive materials and longitudinal internal cylindrical grinding using grinding wheels with zone-diversified structure.
文摘Aim Paeoniflorin-6'O-benzene sulfonate (CP-25) was synthesized to improve oral absorption. This study was performed to investigate absorptive behavior and mechanism of CP-25 in intestine. Methods The effects of drug concentration, intestinal segments, gender as well as ATP binding cassette (ABC) transporter inhibitors on absorption of CP-25 were studied in a situ single-pass intestinal perfusion rat model. Meanwhile, Paeoniflorin (Pae) was tested and served as control group. The concentration of tested drugs was measured by HPLC. Results The results showed intestinal absorption of CP-25 was neither segmental dependent changes nor gender difference. Transepithelial transportation would not change with increasing concentrations of CP-25, which suggest a passive transport was the main pattern of CP-25. Additionally, absorption of CP-25 was much better than that of Pae in small intestine. When compared with Pae, CP-25 gave a 1.82-fold permeability rate. Finally, the results indicated Pae was substrate of P-glycoprotein (P-gp) , but was not the substrate of breast cancer resistance protein and muhi- drug resistance associated protein 2. Among the used ABC inhibitors, the absorption rate of Pae could only be in- creased by? P-gp inhibitor Verapamil and GF120918, while CP-25 had no remarkable alteration. Conclusion CP-25 has better absorptive features than that of Pae, which may be attributed to its lipophicity enhancement and be unaffected by P-gp efflux.
文摘Sickle-cell intrahepatic cholestasis (SCIC) is an uncommon complication of sickle-cell disease (SCD), which can be life-threating if left untreated. We present the case of a 28-year-old man with SCD, who presented with jaundice and abdominal pain, one month after hydroxyurea discontinuation. Laboratory investigation revealed solely increased serum bilirubin, mainly conjugated, and imaging studies revealed choledocholithiasis. The patient unterwent an endoscopic sphincterectomy, but his jaundice deteriorated. Sickle-cell intrahepatic cholestasis was suspected and he received aggressive exchange transfusion therapy in combination with hydroxyurea. The jaundice had no signs of improvement;in fact total bilirubin raised up to 1053.7 μmol/L (61.62 mg/dl). Subsequently, the patient was treated with single-pass albumin dialysis (SPAD), in order to remove the excess bilirubin and protect mainly the brain and liver cells from its toxic effects. His laboratory values started to improve after one-and-a-half months of treatment. For the next two months, exchange transfusions were continued and bilirubin gradually returned to baseline values. The successful response appeared after the combined use of exchange transfusion and SPAD, which is being reported for the first time.
文摘Electronics For Imaging, Inc.(Nasdaq: EFII) showcased the advanced, leading-edge technologies that make EFI? Reggiani a textile innovator at ITMA 2019, June 20th - 26th in Barcelona, including the gamechanging EFI Reggiani BOLT single-pass inkjet printer – the first digital textile solution capable of high-quality output at record production speeds of up to 90 linear meters (295 linear feet) per minute.
基金financially supported by the National Natural Science Foundation of China(Nos.52293395 and 52293393)the Xiongan Science and Technology Innovation Talent Project of MOST,China(No.2022XACX0500)。
文摘Understandings of the effect of hot deformation parameters close to the practical production line on grain refinement are crucial for enhancing both the strength and toughness of future rail steels.In this work,the austenite dynamic recrystallization(DRX)behaviors of a eutectoid pearlite rail steel were studied using a thermo-mechanical simulator with hot deformation parameters frequently employed in rail production lines.The single-pass hot deformation results reveal that the prior austenite grain sizes(PAGSs)for samples with different deformation reductions decrease initially with an increase in deformation temperature.However,once the deformation temperature is beyond a certain threshold,the PAGSs start to increase.It can be attributed to the rise in DRX volume fraction and the increase of DRX grain with deformation temperature,respectively.Three-pass hot deformation results show that the accumulated strain generated in the first and second deformation passes can increase the extent of DRX.In the case of complete DRX,PAGS is predominantly determined by the deformation temperature of the final pass.It suggests a strategic approach during industrial production where part of the deformation reduction in low temperature range can be shifted to the medium temperature range to release rolling mill loads.
基金supported by the National Magnetic Confinement Fusion Energy Program of China (No.2018 YFE0311300)the High-End Talents Program of Hebei Province, Innovative Approaches Towards Development of Carbon-Free Clean Fusion Energy (No.2021HBQZYCSB 006)the Compact Fusion Project of the ENN Group。
文摘This study investigates the single-pass absorption(SPA) of ion cyclotron range of frequency(ICRF) heating in hydrogen plasma of the EXL-50U spherical tokamak,which is an upgraded EXL-50 device with a central solenoid and a stronger magnetic field.The reliability of the kinetic dispersion equation is confirmed by the one-dimensional full-wave code,and the applicability of Porkolab's simplified theoretical SPA model is discussed based on the kinetic dispersion equation.Simulations are conducted to investigate the heating effects of the fundamental and second harmonic frequencies.The results indicate that with the design parameters of the EXL-50U device,the SPA for second harmonic heating is 63%,while the SPA for fundamental heating is 13%.Additionally,the optimal injection frequencies are 23 MHz at 0.9 T and 31 MHz at 1.2 T.The wave vector of the antenna parallel to the magnetic field,with a value of k_‖=7.5 m^(-1),falls within the optimal heating region.Simulations reveal that the ICRF heating system can play an important role in the ion heating of the EXL-50U.