BACKGROUND It is well known that nonalcoholic fatty liver disease(NAFLD)is associated with insulin resistance(IR).LB100,a serine/threonine protein phosphatase 2A(PP2A)inhibitor,is closely related to IR.However,there i...BACKGROUND It is well known that nonalcoholic fatty liver disease(NAFLD)is associated with insulin resistance(IR).LB100,a serine/threonine protein phosphatase 2A(PP2A)inhibitor,is closely related to IR.However,there is little data regarding its direct influence on NAFLD.AIM To elucidate the effect and underlying mechanism of LB100 in NAFLD.METHODS After 10 wk of high fat diet(HFD)feeding,male C57BL/6 mice were injected intraperitoneally with vehicle or LB100 for an additional 6 wk(three times a week).The L02 cell line was treated with LB100 and free fatty acids(FFAs)for 24 h.Hematoxylin and eosin and oil red O staining were performed for histological examination.Western blot analysis was used to detect the protein expression of Sirtuin 1(Sirt1),total and phosphorylated AMP-activated protein kinaseα(AMPKα),and the proteins involved in lipogenesis and fatty acid oxidation.The mRNA levels were determined by qPCR.Pharmacological inhibition of AMPK was performed to further examine the exact mechanism of LB100 in NAFLD.RESULTS LB100 significantly ameliorated HFD-induced obesity,hepatic lipid accumulation and hepatic injury in mice.In addition,LB100 significantly downregulated the protein levels of acetyl-CoA carboxylase,sterol regulatory element-binding protein 1 and its lipogenesis target genes,including stearoyl-CoA desaturase-1 and fatty acid synthase,and upregulated the levels of proteins involved in fatty acidβ-oxidation,such as peroxisome proliferator-activated receptorα(PPARα),peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α),carnitine palmitoyltransferase 1α,acyl-CoA oxidase 1 and uncoupling protein 2,as well as the upstream mediators Sirt1 and AMPKαin the livers of HFD-fed mice.In vitro,LB100 alleviated FFA-induced lipid accumulation in L02 cells through the AMPK/Sirt1 signaling pathway.Further studies showed that the curative effect of LB100 on lipid accumulation was abolished by inhibiting AMPKαin L02 cells.CONCLUSION PP2A inhibition by LB100 significantly ameliorates hepatic steatosis by regulating hepatic lipogenesis and fatty acid oxidation via the AMPK/Sirt1 pathway.LB100 may be a potential therapeutic agent for NAFLD.展开更多
The microstructure evolution law and the structure of precipitates produced during the tempering of steel AerMet100 based on TEM observation and the calibration of diffraction spot were revealed.The electronic structu...The microstructure evolution law and the structure of precipitates produced during the tempering of steel AerMet100 based on TEM observation and the calibration of diffraction spot were revealed.The electronic structure and the stability of the MoxCr2-xC phase were calculated using the plane-wave pseudo-potential method on basis of density functional theory.TEM observations show that the precipitation phases Fe3C and Fe2-xCx(x=0.05～0.14) between martensite lath are produced at 425 and 480 ℃,respectively.The increase of tempering temperature or time can lead to the redissolution of both phases Fe3C and Fe2-xCx,and also lead to the precipitation of the phase Cr2C in martensite lath.The calculation results of formation energies and the density of state(DOS) demonstrate that in point of MoxCr2-xC structures formed during tempering,the early precipitation phase is Cr2C and finally later evolves into Mo2C phase with diffusing of incorporation of Mo atom into the Cr2C crystal cell,lattice,which can results in a energy decreases of the structure MoxCr2-xC phase with the increase of x.展开更多
A new highly sensitive solid substrate room temperature phosphorimetry for the determination of trace titanium is proposed based on the sensitization of Triton X-100 to the SS-RTP intensity of 4,5-dibromophenylfluoron...A new highly sensitive solid substrate room temperature phosphorimetry for the determination of trace titanium is proposed based on the sensitization of Triton X-100 to the SS-RTP intensity of 4,5-dibromophenylfluorone-titanium complex adsorbed on the filter paper substrate modified by gelatin. When Triton X-100 was added into the luminescence system, the RTP intensity was raised 3 times stronger than that of the system without Triton X-100. The linear dynamic range of the new method is 0 64~3 2 fg/spot(0 4 μL) with a detection limit of 12 8 ag/spot, and the regression equation of the working curve is Δ I p =482 0+119 5 m Ti(Ⅳ) (fg/spot), the correlation coefficient r =0 9992, n =6. The phosphorescence lifetime( τ =0 85 ms) was also determined. The recoveries(and RSD) for the determinations of titanium in human hair and tea samples were 101 0%(3 0%) and 99 97%(4 2%), respectively.展开更多
文摘BACKGROUND It is well known that nonalcoholic fatty liver disease(NAFLD)is associated with insulin resistance(IR).LB100,a serine/threonine protein phosphatase 2A(PP2A)inhibitor,is closely related to IR.However,there is little data regarding its direct influence on NAFLD.AIM To elucidate the effect and underlying mechanism of LB100 in NAFLD.METHODS After 10 wk of high fat diet(HFD)feeding,male C57BL/6 mice were injected intraperitoneally with vehicle or LB100 for an additional 6 wk(three times a week).The L02 cell line was treated with LB100 and free fatty acids(FFAs)for 24 h.Hematoxylin and eosin and oil red O staining were performed for histological examination.Western blot analysis was used to detect the protein expression of Sirtuin 1(Sirt1),total and phosphorylated AMP-activated protein kinaseα(AMPKα),and the proteins involved in lipogenesis and fatty acid oxidation.The mRNA levels were determined by qPCR.Pharmacological inhibition of AMPK was performed to further examine the exact mechanism of LB100 in NAFLD.RESULTS LB100 significantly ameliorated HFD-induced obesity,hepatic lipid accumulation and hepatic injury in mice.In addition,LB100 significantly downregulated the protein levels of acetyl-CoA carboxylase,sterol regulatory element-binding protein 1 and its lipogenesis target genes,including stearoyl-CoA desaturase-1 and fatty acid synthase,and upregulated the levels of proteins involved in fatty acidβ-oxidation,such as peroxisome proliferator-activated receptorα(PPARα),peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α),carnitine palmitoyltransferase 1α,acyl-CoA oxidase 1 and uncoupling protein 2,as well as the upstream mediators Sirt1 and AMPKαin the livers of HFD-fed mice.In vitro,LB100 alleviated FFA-induced lipid accumulation in L02 cells through the AMPK/Sirt1 signaling pathway.Further studies showed that the curative effect of LB100 on lipid accumulation was abolished by inhibiting AMPKαin L02 cells.CONCLUSION PP2A inhibition by LB100 significantly ameliorates hepatic steatosis by regulating hepatic lipogenesis and fatty acid oxidation via the AMPK/Sirt1 pathway.LB100 may be a potential therapeutic agent for NAFLD.
文摘The microstructure evolution law and the structure of precipitates produced during the tempering of steel AerMet100 based on TEM observation and the calibration of diffraction spot were revealed.The electronic structure and the stability of the MoxCr2-xC phase were calculated using the plane-wave pseudo-potential method on basis of density functional theory.TEM observations show that the precipitation phases Fe3C and Fe2-xCx(x=0.05～0.14) between martensite lath are produced at 425 and 480 ℃,respectively.The increase of tempering temperature or time can lead to the redissolution of both phases Fe3C and Fe2-xCx,and also lead to the precipitation of the phase Cr2C in martensite lath.The calculation results of formation energies and the density of state(DOS) demonstrate that in point of MoxCr2-xC structures formed during tempering,the early precipitation phase is Cr2C and finally later evolves into Mo2C phase with diffusing of incorporation of Mo atom into the Cr2C crystal cell,lattice,which can results in a energy decreases of the structure MoxCr2-xC phase with the increase of x.
基金Supported by the National Natural Science Foundation of China( No.2 0 175 0 11) and the Natural Science Foundation ofFujian Province( No.C0 110 0 2 8)
文摘A new highly sensitive solid substrate room temperature phosphorimetry for the determination of trace titanium is proposed based on the sensitization of Triton X-100 to the SS-RTP intensity of 4,5-dibromophenylfluorone-titanium complex adsorbed on the filter paper substrate modified by gelatin. When Triton X-100 was added into the luminescence system, the RTP intensity was raised 3 times stronger than that of the system without Triton X-100. The linear dynamic range of the new method is 0 64~3 2 fg/spot(0 4 μL) with a detection limit of 12 8 ag/spot, and the regression equation of the working curve is Δ I p =482 0+119 5 m Ti(Ⅳ) (fg/spot), the correlation coefficient r =0 9992, n =6. The phosphorescence lifetime( τ =0 85 ms) was also determined. The recoveries(and RSD) for the determinations of titanium in human hair and tea samples were 101 0%(3 0%) and 99 97%(4 2%), respectively.
