The lubrication characteristics of magnetized journal bearings affected by magnetic fluids considering the elasticity of its liner

In order to investigate the lubrication characteristics of journal bearings with the elasticity of liner affected by magnetic fluids, a theoretic computation model was developed based on magnetic fluids supporting force parameter ((Formula presented.)) and couple-stress factor ((Formula presented.)). The results indicate that maximum dimensionless pressure peak ((Formula presented.)) of oil-film increases with increase in magnetic fluids supporting force parameter ((Formula presented.)), couple-stress factor ((Formula presented.)) and with decrease in elastic deformation coefficient (Ce) of the liner. The loading capacity ((Formula presented.)) increases with increase in (Formula presented.), (Formula presented.) and with decrease in Ce particularly in the high eccentricity ratio (ε); The attitude angle ((Formula presented.)) of S with different (Formula presented.) and (Formula presented.) decreases in a small range of ε at first, and then increases, it increases with the decrease of (Formula presented.) and (Formula presented.), and with the increase of (Formula presented.), theses phenomena are more obvious for (Formula presented.) at low ε and for (Formula presented.) and (Formula presented.) at moderate and high ε; the modified coefficient of friction ((Formula presented.)) decreases with increase in (Formula presented.), (Formula presented.) and with decrease in Ce; the side leakage (Q) decreases with increase in (Formula presented.), with decrease in (Formula presented.) and with increase in Ce particularly in the low (ε). Moreover, the increase of elastic deformation coefficient (Ce) weaken the impacts of (Formula presented.), (Formula presented.) on the increase of (Formula presented.), (Formula presented.), (Formula presented.), and the decrease of (Formula presented.), Q. </p

The lubrication characteristics of magnetized journal bearings affected by magnetic fluids considering the elasticity of its liner

In order to investigate the lubrication characteristics of journal bearings with the elasticity of liner affected by magnetic fluids, a theoretic computation model was developed based on magnetic fluids supporting force parameter ((Formula presented.)) and couple-stress factor ((Formula presented.)). The results indicate that maximum dimensionless pressure peak ((Formula presented.)) of oil-film increases with increase in magnetic fluids supporting force parameter ((Formula presented.)), couple-stress factor ((Formula presented.)) and with decrease in elastic deformation coefficient (Ce) of the liner. The loading capacity ((Formula presented.)) increases with increase in (Formula presented.), (Formula presented.) and with decrease in Ce particularly in the high eccentricity ratio (ε); The attitude angle ((Formula presented.)) of S with different (Formula presented.) and (Formula presented.) decreases in a small range of ε at first, and then increases, it increases with the decrease of (Formula presented.) and (Formula presented.), and with the increase of (Formula presented.), theses phenomena are more obvious for (Formula presented.) at low ε and for (Formula presented.) and (Formula presented.) at moderate and high ε; the modified coefficient of friction ((Formula presented.)) decreases with increase in (Formula presented.), (Formula presented.) and with decrease in Ce; the side leakage (Q) decreases with increase in (Formula presented.), with decrease in (Formula presented.) and with increase in Ce particularly in the low (ε). Moreover, the increase of elastic deformation coefficient (Ce) weaken the impacts of (Formula presented.), (Formula presented.) on the increase of (Formula presented.), (Formula presented.), (Formula presented.), and the decrease of (Formula presented.), Q. </p

Metabolism and disposition of corylifol A from <i>Psoralea corylifolia</i>: metabolite mapping, isozyme contribution, species differences and identification of efflux transporters for corylifol A-<i>O</i>-glucuronide in HeLa1A1 cells

Corylifol A (CA), a phenolic compound from Psoralea corylifolia, possessed several biological properties but poor bioavailability. Here we aimed to investigate the roles of cytochromes P450s (CYPs), UDP-glucuronosyltransferases (UGTs) and efflux transporters in metabolism and disposition of CA.Metabolism of CA was evaluated in HLM, expressed CYPs and UGTs. Chemical inhibitors and shRNA-mediated gene silencing of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP) were performed to assess the roles of transporters in CA disposition.Three oxidated metabolites (M1–M3) and two glucuronides (M4–M5) were detected. The intrinsic clearances (CLint) values of M1 and M4 in HLM were 48.10 and 184.03 μL/min/mg, respectively. Additionally, CYP1A1, 2C8 and 2C19 were identified as main contributors with CLint values of 13.01–49.36 μL/min/mg, while UGT1A1, 1A7, 1A8 and 1A9 were with CLint values ranging from 85.01 to 284.07 μL/min/mg. Furthermore, activity correlation analysis proved CYP2C8, UGT1A1 and 1A9 were the main active hepatic isozymes. Besides, rats and monkeys were appropriate model animals. Moreover, dipyridamole and MK571 both could significantly inhibit M4 efflux. Gene silencing results also indicated MRP4 and BCRP were major contributors in HeLa1A1 cells.Taken together, CYPs, UGTs, MRP4 and BCRP were important determinants of CA pharmacokinetics. Corylifol A (CA), a phenolic compound from Psoralea corylifolia, possessed several biological properties but poor bioavailability. Here we aimed to investigate the roles of cytochromes P450s (CYPs), UDP-glucuronosyltransferases (UGTs) and efflux transporters in metabolism and disposition of CA. Metabolism of CA was evaluated in HLM, expressed CYPs and UGTs. Chemical inhibitors and shRNA-mediated gene silencing of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP) were performed to assess the roles of transporters in CA disposition. Three oxidated metabolites (M1–M3) and two glucuronides (M4–M5) were detected. The intrinsic clearances (CLint) values of M1 and M4 in HLM were 48.10 and 184.03 μL/min/mg, respectively. Additionally, CYP1A1, 2C8 and 2C19 were identified as main contributors with CLint values of 13.01–49.36 μL/min/mg, while UGT1A1, 1A7, 1A8 and 1A9 were with CLint values ranging from 85.01 to 284.07 μL/min/mg. Furthermore, activity correlation analysis proved CYP2C8, UGT1A1 and 1A9 were the main active hepatic isozymes. Besides, rats and monkeys were appropriate model animals. Moreover, dipyridamole and MK571 both could significantly inhibit M4 efflux. Gene silencing results also indicated MRP4 and BCRP were major contributors in HeLa1A1 cells. Taken together, CYPs, UGTs, MRP4 and BCRP were important determinants of CA pharmacokinetics.</p

DataSheet1_Identification of naturally occurring inhibitors in Xian-Ling-Gu-Bao capsule against the glucuronidation of estrogens.docx

Xian-Ling-Gu-Bao (XLGB) capsule, a well-known traditional Chinese medicine prescription, is widely used for the treatment of osteoporosis. It could significantly increase the levels of estrogen in ovariectomized rats and mice. However, this working mechanism has not been well elucidated. Considering that UDP-glucuronosyltransferase (UGT) enzymes are the important enzymes that inactivate and regulate estrogen activity in vivo, this study aimed to identify the bioactive compounds from XLGB against the glucuronidation of estrogens. First, thirty compounds were considered as candidate bioactive compounds based on our previous studies including pharmacological evaluation, chemical profiles, and metabolic profiles. Second, the characteristics of estrogen glucuronidation by uridine diphosphate glucuronic acid (UDPGA)-supplemented human liver microsomes (HLM), human intestine microsomes (HIM), and expressed UGT enzymes were determined, and the incubation systems of their key UGT enzymes were optimized. Then, inhibitory effects and mechanisms of XLGB and its main compounds toward the key UGT isozymes were further investigated. As a result, estrogen underwent efficient glucuronidation by HLM and HIM. UGT1A10, 1A1, and 2B7 were mainly responsible for the glucuronidation of estrone, β-estradiol, and estriol, respectively. For E1 and E2, UGT1A10 and 1A1 tended to mediate estrogen-3-O-glucuronidation, while UGT2B7 preferred catalyzing estrogen-16-O-glucuronidation. Furthermore, the incubation system for active UGT isoforms was optimized including Tris-HCl buffer, detergents, MgCl2 concentration, β-glucuronidase inhibitors, UDPGA concentration, protein concentration, and incubation time. Based on optimal incubation conditions, eleven, nine, and nine compounds were identified as the potent inhibitors for UGT1A10, 1A1, and 2B7, respectively (IC50 i < 3.35 μM). Among them, six compounds (bavachin, isobavachin, isobavachalcone, neobavaisoflavone, corylifol A, and icariside II) simultaneously demonstrated potent inhibitory effects against these three active enzymes. Prenylated flavanols from Epimedium brevicornu Maxim., prenylated flavonoids from Psoralea corylifolia L., and salvianolic acids from Salvia miltiorrhiza Bge. were characterized as the most important and effective compounds. The identification of potent natural inhibitors of XLGB against the glucuronidation of estrogen laid an important foundation for the pharmacodynamic material basis.</p