Diamonds were formed in the mantle lithosphere,mostly at depths of 150~200km in the centres of Precambrian cratons,the buoyant ancient cores of continents.From there they were normally transported into the upper crust...Diamonds were formed in the mantle lithosphere,mostly at depths of 150~200km in the centres of Precambrian cratons,the buoyant ancient cores of continents.From there they were normally transported into the upper crust in kimberlite pipes whose diamonds are largely colourless and light yellow related to trace element N(Ia type),although brown,green,and more rarely blue-coloured diamonds are related to lattice defect and trace amounts of H,more rarely B and Ni.Pink diamonds are extremely rare in the approximately 90 diamondiferous pipes mined globally.Although small quantities have been discovered elsewhere,about 90%have been mined from the ca.1.3Ga Argyle diamond pipe in Western Australia,with the Arkhangelskaya diamond pipe in Russia the only other significant source.The pink colour at both Argyle and Arkhangelskaya is unrelated to trace elements and instead results from absorption of light from nanoscale(550nm)defects related to shear stress and plastic deformation.Macroscopically,defects are shown by glide planes,lamellae,and grain lines imposed on the originally colourless diamonds derived from their mantle source.The key question is why these defects were uniquely acquired in diamonds in the Argyle and Arkhangelskaya pipes.Unlike most diamondiferous pipes,Argyle is a rare diamondiferous volatile-rich lamproite pipe that was emplaced into the multiply deformed and rifted NNE-trending Halls Creek Orogen on the margin of the Kimberley Craton.Similarly,Arkhangelskaya in the Devonian Lomonosov kimberlite cluster is a volatile-rich low-Ti type kimberlite,a close relative to lamproite,that was emplaced into the multiply deformed Lapland-Kola Orogen on the rifted margin of the Kola Craton.These craton margins are underlain by subduction-induced volatile-enriched metasomatized mantle lithosphere in contrast to the more primeval mantle under craton centres.It is thus likely that shear stresses were exacerbated at Argyle and Arkangelskaya by rapid vertical emplacement of the anomalous volatile-enriched magmas at supercritical pressures and temperatures,that induced catastrophic phase separation of these volatiles and'mini seismic events'during rapid pressure drops during ascent from 200km depth to the surface.Such a mechanism is consistent with the presence of strongly resorbed and plastically deformed small brown industrial diamonds in the Argyle pipe.From a China perspective,it is potentially important that at 1.3Ga the alkaline Argyle pipe in northern Australia is placed adjacent to the North China Craton(NCC),with numerous world-class mineral deposits including the giant ca.1.4~1.2Ga alkaline Bayan Obo REE system on its margin.However,it is the southeastern margin of the Yangtze Craton and the Jiangnan Orogen with their lamproite pipes derived from metasomatized mantle lithosphere that present the most prospective regions for pink diamond occurrences.展开更多
Objective:To investigate the protective effects of gypenoside XVII(GP-17)against cisplatin-induced acute kidney injury and to elucidate whether its mechanism involves the activation of PINK1/Parkin-mediated mitophagy....Objective:To investigate the protective effects of gypenoside XVII(GP-17)against cisplatin-induced acute kidney injury and to elucidate whether its mechanism involves the activation of PINK1/Parkin-mediated mitophagy.Methods:Sprague-Dawley rats were randomly divided into four groups:control,cisplatin,cisplatin+GP-17,and GP-17 alone.Cisplatin was administered intraperitoneally at 20 mg/kg to induce acute kidney injury,while GP-17 was given orally at 40 mg/kg/day for 7 d.The levels of serum creatinine and blood urea nitrogen,superoxide dismutase activity,and malondialdehyde content were measured.Histopathological analysis and transmission electron microscopy were also performed to evaluate the effects of GP-17 on renal injury.Moreover,the expression of mitophagy-related proteins,including PINK1,Parkin,LC3,and p62,and the mRNA expression of inflammatory markers were determined by Western blot and quantitative RT-PCR assays.Furthermore,human renal tubular epithelial HK-2 cells were treated with cisplatin and GP-17,with or without PINK1 siRNA transfection.Cell viability,apoptosis,reactive oxygen species levels,mitochondrial membrane potential,and the protein expression associated with the PINK1/Parkin pathway were measured.Results:In rats with cisplatin-induced acute kidney injury,GP-17 significantly ameliorated cisplatin-induced elevations in serum creatinine and blood urea nitrogen,attenuated tubular damage and mitochondrial ultrastructural injury,and reduced oxidative stress by increasing superoxide dismutase activity and decreasing malondialdehyde content.GP-17 further upregulated the protein levels of PINK1,Parkin,and LC3-Ⅱ/Ⅰratio while promoting p62 degradation,indicating enhanced mitophagic flux.In HK-2 cells,GP-17(20μM)co-treatment markedly attenuated cisplatin-induced cytotoxicity,apoptosis,reactive oxygen species overproduction,and mitochondrial depolarization.However,all these protective effects of GP-17 were completely abolished upon PINK1 knockdown.Conclusions:GP-17 protects against cisplatin-induced nephrotoxicity by activating PINK1/Parkin-mediated mitophagy,which facilitates the clearance of damaged mitochondria,alleviates oxidative stress,and inhibits renal cell apoptosis.These findings identify GP-17 as a promising candidate for mitigating chemotherapy-induced acute kidney injury.展开更多
文摘Diamonds were formed in the mantle lithosphere,mostly at depths of 150~200km in the centres of Precambrian cratons,the buoyant ancient cores of continents.From there they were normally transported into the upper crust in kimberlite pipes whose diamonds are largely colourless and light yellow related to trace element N(Ia type),although brown,green,and more rarely blue-coloured diamonds are related to lattice defect and trace amounts of H,more rarely B and Ni.Pink diamonds are extremely rare in the approximately 90 diamondiferous pipes mined globally.Although small quantities have been discovered elsewhere,about 90%have been mined from the ca.1.3Ga Argyle diamond pipe in Western Australia,with the Arkhangelskaya diamond pipe in Russia the only other significant source.The pink colour at both Argyle and Arkhangelskaya is unrelated to trace elements and instead results from absorption of light from nanoscale(550nm)defects related to shear stress and plastic deformation.Macroscopically,defects are shown by glide planes,lamellae,and grain lines imposed on the originally colourless diamonds derived from their mantle source.The key question is why these defects were uniquely acquired in diamonds in the Argyle and Arkhangelskaya pipes.Unlike most diamondiferous pipes,Argyle is a rare diamondiferous volatile-rich lamproite pipe that was emplaced into the multiply deformed and rifted NNE-trending Halls Creek Orogen on the margin of the Kimberley Craton.Similarly,Arkhangelskaya in the Devonian Lomonosov kimberlite cluster is a volatile-rich low-Ti type kimberlite,a close relative to lamproite,that was emplaced into the multiply deformed Lapland-Kola Orogen on the rifted margin of the Kola Craton.These craton margins are underlain by subduction-induced volatile-enriched metasomatized mantle lithosphere in contrast to the more primeval mantle under craton centres.It is thus likely that shear stresses were exacerbated at Argyle and Arkangelskaya by rapid vertical emplacement of the anomalous volatile-enriched magmas at supercritical pressures and temperatures,that induced catastrophic phase separation of these volatiles and'mini seismic events'during rapid pressure drops during ascent from 200km depth to the surface.Such a mechanism is consistent with the presence of strongly resorbed and plastically deformed small brown industrial diamonds in the Argyle pipe.From a China perspective,it is potentially important that at 1.3Ga the alkaline Argyle pipe in northern Australia is placed adjacent to the North China Craton(NCC),with numerous world-class mineral deposits including the giant ca.1.4~1.2Ga alkaline Bayan Obo REE system on its margin.However,it is the southeastern margin of the Yangtze Craton and the Jiangnan Orogen with their lamproite pipes derived from metasomatized mantle lithosphere that present the most prospective regions for pink diamond occurrences.
基金supported by grants from the Health Commission of Zigong High-Level Talent Development Project(WJW-GCCRC007).
文摘Objective:To investigate the protective effects of gypenoside XVII(GP-17)against cisplatin-induced acute kidney injury and to elucidate whether its mechanism involves the activation of PINK1/Parkin-mediated mitophagy.Methods:Sprague-Dawley rats were randomly divided into four groups:control,cisplatin,cisplatin+GP-17,and GP-17 alone.Cisplatin was administered intraperitoneally at 20 mg/kg to induce acute kidney injury,while GP-17 was given orally at 40 mg/kg/day for 7 d.The levels of serum creatinine and blood urea nitrogen,superoxide dismutase activity,and malondialdehyde content were measured.Histopathological analysis and transmission electron microscopy were also performed to evaluate the effects of GP-17 on renal injury.Moreover,the expression of mitophagy-related proteins,including PINK1,Parkin,LC3,and p62,and the mRNA expression of inflammatory markers were determined by Western blot and quantitative RT-PCR assays.Furthermore,human renal tubular epithelial HK-2 cells were treated with cisplatin and GP-17,with or without PINK1 siRNA transfection.Cell viability,apoptosis,reactive oxygen species levels,mitochondrial membrane potential,and the protein expression associated with the PINK1/Parkin pathway were measured.Results:In rats with cisplatin-induced acute kidney injury,GP-17 significantly ameliorated cisplatin-induced elevations in serum creatinine and blood urea nitrogen,attenuated tubular damage and mitochondrial ultrastructural injury,and reduced oxidative stress by increasing superoxide dismutase activity and decreasing malondialdehyde content.GP-17 further upregulated the protein levels of PINK1,Parkin,and LC3-Ⅱ/Ⅰratio while promoting p62 degradation,indicating enhanced mitophagic flux.In HK-2 cells,GP-17(20μM)co-treatment markedly attenuated cisplatin-induced cytotoxicity,apoptosis,reactive oxygen species overproduction,and mitochondrial depolarization.However,all these protective effects of GP-17 were completely abolished upon PINK1 knockdown.Conclusions:GP-17 protects against cisplatin-induced nephrotoxicity by activating PINK1/Parkin-mediated mitophagy,which facilitates the clearance of damaged mitochondria,alleviates oxidative stress,and inhibits renal cell apoptosis.These findings identify GP-17 as a promising candidate for mitigating chemotherapy-induced acute kidney injury.
