BACKGROUND Gastric cancer(GC)is associated with high mortality rates.Bile acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains unclear.During GC development in both humans and animals...BACKGROUND Gastric cancer(GC)is associated with high mortality rates.Bile acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains unclear.During GC development in both humans and animals,BAs serve as signaling molecules that induce metabolic reprogramming.This confers additional cancer phenotypes,including ferroptosis sensitivity.Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression.However,it is not fully defined if BAs can influence GC progression by modulating ferroptosis.AIM To reveal the mechanism of BAs regulation in ferroptosis of GC cells.METHODS In this study,we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis.We used gain and loss of function assays to examine the impacts of farnesoid X receptor(FXR)and BTB and CNC homology 1(BACH1)overexpression and knockdown to obtain further insights into the molecular mechanism involved.RESULTS Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells.This effect correlated with increased glutathione(GSH)concentrations,a reduced GSH to oxidized GSH ratio,and higher GSH peroxidase 4(GPX4)expression levels.Subsequently,we confirmed that BAs exerted these effects by activating FXR,which markedly increased the expression of GSH synthetase and GPX4.Notably,BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR.Finally,our results suggested that FXR could significantly promote GC cell proliferation,which may be closely related to its anti-ferroptosis effect.CONCLUSION This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSHGPX4 axis in GC cells.This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.展开更多
It is challenging to make an ultrafast diagnosis of the temporal evolution of small and short-lived plasma in two dimensions. To overcome this difficulty, we have developed a well-timed diagnostic utilizing an x-ray s...It is challenging to make an ultrafast diagnosis of the temporal evolution of small and short-lived plasma in two dimensions. To overcome this difficulty, we have developed a well-timed diagnostic utilizing an x-ray streak camera equipped with a row of multi-pinhole arrays. By processing multiple sets of one-dimensional streaked image data acquired from various pinholes, we are capable of reconstructing high-resolution two-dimensional images with a temporal resolution of 38 ps and a spatial resolution of 18 μm. The temporal fiducial pulses accessed from external sources can advance the precise timing and accurately determine the arrival time of the laser. Moreover, it can correct the nonlinear sweeping speed of the streak camera. The effectiveness of this diagnostic has been successfully verified at the Shenguang-II laser facility,providing an indispensable tool for observing complex physical phenomena, such as the implosion process of laser-fusion experiments.展开更多
The variation of 90 Laminaria gametophyte clones representing the introduced Laminaria japonica （Group 1） and Laminaria Iongissima （Group 2）, the varieties of L. japonica （Group 3） and the varieties derived from...The variation of 90 Laminaria gametophyte clones representing the introduced Laminaria japonica （Group 1） and Laminaria Iongissima （Group 2）, the varieties of L. japonica （Group 3） and the varieties derived from interspecific hybrids （Group 4） was determined with 18 microsatellite markers. The allelic diversity and Nei＇s gene diversity of Group 1 were significantly higher than those of Group 2 （2.9 vs. 1.8 and 0.414 vs. 0.161, respectively）, demonstrating that the variation of the introduced L. japonica is richer than that of L. Iongissima. Both allelic diversity and Nei＇s gene diversity of Group 3 were lower than those of Group 1, indicating that only a portion of variation of L. japonica was incorporated into the varieties of L. japonica. Significant genetic differentiation was detected between four groups and between female （Population 1 ） and male （Population 2） gametophyte clones in each group. The variation among groups accounted for 39.95%, while that among populations accounted for 21.65% of the total. The genetic distance between Group 1 and Group 4 was obviously longer than that between Group 2 and Group 4 （0.686 vs. 0.291）, indicating that maternal gametophyte clone contributed more variation to the hybrids than the paternal gametophyte clone did.展开更多
基金Supported by the Major Basic Research Project of Natural Science Foundation of Shandong Province,No.ZR2020ZD15.
文摘BACKGROUND Gastric cancer(GC)is associated with high mortality rates.Bile acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains unclear.During GC development in both humans and animals,BAs serve as signaling molecules that induce metabolic reprogramming.This confers additional cancer phenotypes,including ferroptosis sensitivity.Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression.However,it is not fully defined if BAs can influence GC progression by modulating ferroptosis.AIM To reveal the mechanism of BAs regulation in ferroptosis of GC cells.METHODS In this study,we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis.We used gain and loss of function assays to examine the impacts of farnesoid X receptor(FXR)and BTB and CNC homology 1(BACH1)overexpression and knockdown to obtain further insights into the molecular mechanism involved.RESULTS Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells.This effect correlated with increased glutathione(GSH)concentrations,a reduced GSH to oxidized GSH ratio,and higher GSH peroxidase 4(GPX4)expression levels.Subsequently,we confirmed that BAs exerted these effects by activating FXR,which markedly increased the expression of GSH synthetase and GPX4.Notably,BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR.Finally,our results suggested that FXR could significantly promote GC cell proliferation,which may be closely related to its anti-ferroptosis effect.CONCLUSION This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSHGPX4 axis in GC cells.This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant Nos. XDA25030700 and XDA25030500)the National Key R&D Program of China (Grant Nos. 2022YFA1603200 and 2022YFA1603203)the National Natural Science Foundation of China (Grant Nos. 12175018, 12135001, 12075030, and 11903006)。
文摘It is challenging to make an ultrafast diagnosis of the temporal evolution of small and short-lived plasma in two dimensions. To overcome this difficulty, we have developed a well-timed diagnostic utilizing an x-ray streak camera equipped with a row of multi-pinhole arrays. By processing multiple sets of one-dimensional streaked image data acquired from various pinholes, we are capable of reconstructing high-resolution two-dimensional images with a temporal resolution of 38 ps and a spatial resolution of 18 μm. The temporal fiducial pulses accessed from external sources can advance the precise timing and accurately determine the arrival time of the laser. Moreover, it can correct the nonlinear sweeping speed of the streak camera. The effectiveness of this diagnostic has been successfully verified at the Shenguang-II laser facility,providing an indispensable tool for observing complex physical phenomena, such as the implosion process of laser-fusion experiments.
基金The Key Laboratory of Mariculture of Chinese Ministry ofEducation, Ocean University of China (200405)Provincial Departmentof Science and Technology of Shandong (2005GG3205190).
文摘The variation of 90 Laminaria gametophyte clones representing the introduced Laminaria japonica （Group 1） and Laminaria Iongissima （Group 2）, the varieties of L. japonica （Group 3） and the varieties derived from interspecific hybrids （Group 4） was determined with 18 microsatellite markers. The allelic diversity and Nei＇s gene diversity of Group 1 were significantly higher than those of Group 2 （2.9 vs. 1.8 and 0.414 vs. 0.161, respectively）, demonstrating that the variation of the introduced L. japonica is richer than that of L. Iongissima. Both allelic diversity and Nei＇s gene diversity of Group 3 were lower than those of Group 1, indicating that only a portion of variation of L. japonica was incorporated into the varieties of L. japonica. Significant genetic differentiation was detected between four groups and between female （Population 1 ） and male （Population 2） gametophyte clones in each group. The variation among groups accounted for 39.95%, while that among populations accounted for 21.65% of the total. The genetic distance between Group 1 and Group 4 was obviously longer than that between Group 2 and Group 4 （0.686 vs. 0.291）, indicating that maternal gametophyte clone contributed more variation to the hybrids than the paternal gametophyte clone did.
