To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be elucidated.Here,Piezo1 channel was identified as a key iron transporter in response to mechanica...To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be elucidated.Here,Piezo1 channel was identified as a key iron transporter in response to mechanical stress.Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron gatekeeper.Furthermore,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical stress.Moreover,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.展开更多
Objective Gastrointestinal stromal tumors(GISTs)can rapidly proliferate through angiogenesis.Previous studies indicated the potential influence of microRNA on the progression of tumor immature angiogenesis.This study ...Objective Gastrointestinal stromal tumors(GISTs)can rapidly proliferate through angiogenesis.Previous studies indicated the potential influence of microRNA on the progression of tumor immature angiogenesis.This study aimed to explore the specific mechanism by which microRNA-409-5p(miR-409-5p)contributes to GIST.Methods To identify genes potentially involved in the development and progression of GIST,the differences of miR-409-5p between tumors and adjacent tissues were first analyzed.Following this analysis,target genes were predicted.To further investigate the function of miRNA in GIST cells,two GIST cell lines(GIST-T1 and GIST882)were transfected with lentiviruses that stably expressed miR-409-5p and scrambled miRNA(negative control).Later,the cells were subjected to Western blotting and ELSA to determine any differences in angiogenesis-related genes.Results In GISTs,there was a decrease in the expression levels of miR-409-5p compared to the adjacent tissues.It was observed that the upregulation of miR-409-5p in GIST cell lines effectively inhibited the proteins hypoxia-inducible transcription factor 1β(HIF1β)and vascular endothelial growth factor A(VEGF-A).Further investigations revealed that miR-409-5p acted as an inhibitor of angiogenesis by binding to the 3′-UTR of Lysine-specific demethylase 4D(KDM4D)mRNA.Moreover,the combination of miR-409-5p with imatinib enhanced its inhibitory effect on angiogenesis.Conclusion This study demonstrated that the miRNA-409-5p/KDM4D/HIF1β/VEGF-A signaling pathway could serve as a novel target for the development of therapeutic strategies for the treatment of imatinib-resistance in GIST patients.展开更多
The semiconductor laser array with single-mode emission is presented in this paper.The 6-μm-wide ridge waveguides(RWGs)are fabricated to select the lateral mode.Thus the fundamental mode of laser array can be obtaine...The semiconductor laser array with single-mode emission is presented in this paper.The 6-μm-wide ridge waveguides(RWGs)are fabricated to select the lateral mode.Thus the fundamental mode of laser array can be obtained by the RWGs.And the maximum output power of single-mode emission can reach 36 W at an injection current of 43 A,after that,a kink will appear.The slow axis(SA)far-field divergence angle of the unit is 13.65.The beam quality factor M;of the units determined by the second-order moment(SOM)method,is 1.2.This single-mode emission laser array can be used for laser processing.展开更多
Water management in proton exchange membrane fuel cells(PEMFC)is a topic of great importance for the optimization of these systems.Effective proton conductivity calls for moderate moisture content in the membrane,whil...Water management in proton exchange membrane fuel cells(PEMFC)is a topic of great importance for the optimization of these systems.Effective proton conductivity calls for moderate moisture content in the membrane,while uneven water distribution can lead to instability of the whole flow field,thereby decreasing the performance of the fuel cell.In the present study,a simplified two-tier hybrid structure is used to investigate the impact of the dynamic behavior of liquid water on the current density of the PEMFC.Simulation results show that water droplets attached to wall sides tend to increase current density.Visualization experiments confirm the existence of liquid droplets and the enhancement of current density,while indicating that the best performance and stability of fuel cell are attained for a cathode air flow rate of 300 ml/min.展开更多
基金supported in part by the National Nature Science Foundation(81874022 and 82172483 to Xinyu Liu,82102522 to Lianlei Wang,82072478 to Yunpeng Zhao,82072435 to Qiang Yang,82073437 to Weiwei Li,81930070 to Shiqing Feng,82272548 to Lei Cheng)Key R&D Project of Shandong Province(2022CXGC010503 to Xinyu Liu)+1 种基金Shandong Natural Science Foundation(ZR202102210113 to Lianlei Wang,ZR2020YQ54 to Yunpeng Zhao)Shandong Province Taishan Scholar Project(tsqn202211317 to Lianlei Wang).The authors thank the Translational Medicine Core Facility of Shandong University for the consultation and instrument availability that supported this work.
文摘To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be elucidated.Here,Piezo1 channel was identified as a key iron transporter in response to mechanical stress.Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron gatekeeper.Furthermore,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical stress.Moreover,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.
基金supported by the National Natural Science Foundation of China(No.81372323 and No.81802426).
文摘Objective Gastrointestinal stromal tumors(GISTs)can rapidly proliferate through angiogenesis.Previous studies indicated the potential influence of microRNA on the progression of tumor immature angiogenesis.This study aimed to explore the specific mechanism by which microRNA-409-5p(miR-409-5p)contributes to GIST.Methods To identify genes potentially involved in the development and progression of GIST,the differences of miR-409-5p between tumors and adjacent tissues were first analyzed.Following this analysis,target genes were predicted.To further investigate the function of miRNA in GIST cells,two GIST cell lines(GIST-T1 and GIST882)were transfected with lentiviruses that stably expressed miR-409-5p and scrambled miRNA(negative control).Later,the cells were subjected to Western blotting and ELSA to determine any differences in angiogenesis-related genes.Results In GISTs,there was a decrease in the expression levels of miR-409-5p compared to the adjacent tissues.It was observed that the upregulation of miR-409-5p in GIST cell lines effectively inhibited the proteins hypoxia-inducible transcription factor 1β(HIF1β)and vascular endothelial growth factor A(VEGF-A).Further investigations revealed that miR-409-5p acted as an inhibitor of angiogenesis by binding to the 3′-UTR of Lysine-specific demethylase 4D(KDM4D)mRNA.Moreover,the combination of miR-409-5p with imatinib enhanced its inhibitory effect on angiogenesis.Conclusion This study demonstrated that the miRNA-409-5p/KDM4D/HIF1β/VEGF-A signaling pathway could serve as a novel target for the development of therapeutic strategies for the treatment of imatinib-resistance in GIST patients.
基金Project supported by the National Science and Technology Major Project of China(Grant Nos.2018YFB0504600and 2017YFB0405102)the Frontier Science Key Program of the President of the Chinese Academy of Sciences(Grant No.QYZDY-SSW-JSC006)+7 种基金the Pilot Project of the Chinese Academy of Sciences(Grant No.XDB43030302)the National Natural Science Foundation of China(Grant Nos.62090051,62090052,62090054,11874353,61935009,61934003,61904179,61727822,61805236,62004194,and 61991433)the Science and Technology Development Project of Jilin Province,China(Grant Nos.20200401062GX,202001069GX,20200501006GX,20200501007GX,20200501008GX,and 20190302042GX)the Key Research and Development Project of Guangdong Province,China(Grant No.2020B090922003)the Equipment Pre-researchChina(Grant No.2006ZYGG0304)the Special Scientific Research Project of the Academician Innovation Platform in Hainan Province,China(Grant No.YSPTZX202034)the Dawn Talent Training Program of CIOMP,China。
文摘The semiconductor laser array with single-mode emission is presented in this paper.The 6-μm-wide ridge waveguides(RWGs)are fabricated to select the lateral mode.Thus the fundamental mode of laser array can be obtained by the RWGs.And the maximum output power of single-mode emission can reach 36 W at an injection current of 43 A,after that,a kink will appear.The slow axis(SA)far-field divergence angle of the unit is 13.65.The beam quality factor M;of the units determined by the second-order moment(SOM)method,is 1.2.This single-mode emission laser array can be used for laser processing.
基金by the National Natural Science Foundation of China(51175472)the Natural Science Foundation of Zhejiang Province(LQ20E060008)the Foundation of Department of Education of Zhejiang Province(Y201737452).
文摘Water management in proton exchange membrane fuel cells(PEMFC)is a topic of great importance for the optimization of these systems.Effective proton conductivity calls for moderate moisture content in the membrane,while uneven water distribution can lead to instability of the whole flow field,thereby decreasing the performance of the fuel cell.In the present study,a simplified two-tier hybrid structure is used to investigate the impact of the dynamic behavior of liquid water on the current density of the PEMFC.Simulation results show that water droplets attached to wall sides tend to increase current density.Visualization experiments confirm the existence of liquid droplets and the enhancement of current density,while indicating that the best performance and stability of fuel cell are attained for a cathode air flow rate of 300 ml/min.
