Sorafenib is the first-line chemotherapeutic therapy for advanced hepatocellular carcinoma(HCC).However,sorafenib resistance significantly limits its therapeutic efficacy,and the mechanisms underlying resistance have ...Sorafenib is the first-line chemotherapeutic therapy for advanced hepatocellular carcinoma(HCC).However,sorafenib resistance significantly limits its therapeutic efficacy,and the mechanisms underlying resistance have not been fully clarified.Here we report that a circular RNA,circRNA-SORE(a circular RNA upregulated in sorafenib-resistant HCC cells),plays a significant role in sorafenib resistance in HCC.We found that circRNA-SORE is upregulated in sorafenib-resistant HCC cells and depletion of circRNA-SORE substantially increases the cell-killing ability of sorafenib.Further studies revealed that circRNA-SORE binds the master oncogenic protein YBX1 in the cytoplasm,which prevents YBX1 nuclear interaction with the E3 ubiquitin ligase PRP19 and thus blocks PRP19-mediated YBX1 degradation.Moreover,our in vitro and in vivo results suggest that circRNA-SORE is transported by exosomes to spread sorafenib resistance among HCC cells.Using different HCC mouse models,we demonstrated that silencing circRNA-SORE by injection of siRNA could substantially overcome sorafenib resistance.Our study provides a proof-of-concept demonstration for a potential strategy to overcome sorafenib resistance in HCC patients by targeting circRNA-SORE or YBX1.展开更多
Electrochemical CO_(2) reduction reaction (CO_(2) RR) offers a practical solution to current global greenhouse effect by converting excessive CO_(2) into value-added chemicals or fuels. Noble metal-based nanomaterials...Electrochemical CO_(2) reduction reaction (CO_(2) RR) offers a practical solution to current global greenhouse effect by converting excessive CO_(2) into value-added chemicals or fuels. Noble metal-based nanomaterials have been considered as efficient catalysts for the CO_(2) RR owing to their high catalytic activity, long-term stability and superior selectivity to targeted products. On the other hand, they are usually loaded on different support materials in order to minimize their usage and maximize the utilization because of high price and limited reserve. The strong metal-support interaction (MSI) between the metal and substrate plays an important role in affecting the CO_(2) RR performance. In this review, we mainly focus on different types of support materials (e.g., oxides, carbons, ligands, alloys and metal carbides) interacting with noble metal as electrocatalysts for CO_(2) RR. Moreover, the positive effects about MSI for boosting the CO_(2) RR performance via regulating the adsorption strength, electronic structure, coordination environment and binding energy are presented. Lastly, emerging challenges and future opportunities on noble metal electrocatalysts with strong MSI are discussed.展开更多
Southern corn rust(SCR),caused by the fungal pathogen Puccinia polysora,is a major threat to maize pro-duction worldwide.Efficient breeding and deployment of resistant hybrids are key to achieving durable control of S...Southern corn rust(SCR),caused by the fungal pathogen Puccinia polysora,is a major threat to maize pro-duction worldwide.Efficient breeding and deployment of resistant hybrids are key to achieving durable control of SCR.Here,we report the molecular cloning and characterization of RppC,which encodes an NLR-type immune receptor and is responsible for a major SCR resistance quantitative trait locus.Further-more,we identified the corresponding avirulence effector,AvrRppC,which is secreted by P.polysora and triggers RppC-mediated resistance.Allelic variation of AvrRppC directly determines the effectiveness of RppC-mediated resistance,indicating that monitoring of AvrRppC variants in the field can guide the rational deployment of RppC-containing hybrids in maize production.Currently,RppC is the most frequently deployed SCR resistance gene in China,and a better understanding of its mode of action is crit-ical for extending its durability.展开更多
At GMT time 13：19, August 8, 2017, an M1.0 earthquake struck the Jiuzhaigou region in Sichuan Province, China, causing severe damages and casualties. To investigate the source properties, seismogenic structures, and ...At GMT time 13：19, August 8, 2017, an M1.0 earthquake struck the Jiuzhaigou region in Sichuan Province, China, causing severe damages and casualties. To investigate the source properties, seismogenic structures, and seismic hazards, we systematically analyzed the tectonic environment, crustal velocity structure in the source region, source parameters and rupture process, Coulomb failure stress changes, and 3-D features of the rupture plane of the Jiuzhaigou earthquake. Our results indicate the following： （1） The Jiuzhaigou earthquake occurred on an unmarked fault belonging to the transition zone of the east Kunlun fault system and is located northwest of the Huya fault. （2） Both the mainshock and aftershock rupture zones are located in a region where crustal seismic velocity changes dramatically. Southeast to the source region, shear wave velocity at the middle to lower crust is significantly low, but it rapidly increases northeastward and lies close to the background velocity across the rupture fault. （3） The aftershock zone is narrow and distributes along the northwest-southeast trend, and most aftershocks occur within a depth range of 5-20 km. （4） The focal mechanism of the Jiuzhaigou earthquake indicates a left-lateral strike-slip fault, with strike, dip, and rake angles of 152~, 74~ and 8~, respectively. The hypocenter depth measures 20 km, whereas the centroid depth is about 6 kin. The co-seismic rupture mainly concentrates at depths of 3-13 km, with a moment magnitude （Mw） of 6.5. （5） The co-seismic rupture also strengthens the Coulomb failure stress at the two ends of the rupture fault and the east segment of the Tazang fault. Aftershocks relocation results together with geological surveys indicate that the causative fault is a near vertical fault with notable spatial variations： dip angle varies within 660-89~ from northwest to southeast and the average dip angle measures -84~. The results of this work are of fundamental importance for further studies on the source character展开更多
基金supported by the National Natural Science Foundation of China under Grant No.81772546(to X.C.),No.81827804(to X.C.)and No.81902367(to J.X.)Zhejiang Provincial Natural Science Foundation of China under Grant No.LQ19H160026(to J.X.)and LGF18H160011(to Y.L.)+6 种基金China Postdoctoral Science Foundation under Grant No.2020M671755(to J.X.)Key Research and Development Project of Zhejiang Province under Grant No.2018C03083(to X.C.)Zhejiang Clinical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases under Grant No.2018E50003(to X.C.)Special fund for basic scientific research operating expenses of Zhejiang University under Grant No.2019XZZX005-4-05(to Y.L.)Hepatobiliary and Pancreatic Cancer Research of Hubei Chen Xiaoping Science and Technology Development Foundation under Grant No.CXPJJH11900001-2019308(to J.X.)CXPJJH11900001-2019209(to X.L.)CXPJJH11900009-03(to X.L.).
文摘Sorafenib is the first-line chemotherapeutic therapy for advanced hepatocellular carcinoma(HCC).However,sorafenib resistance significantly limits its therapeutic efficacy,and the mechanisms underlying resistance have not been fully clarified.Here we report that a circular RNA,circRNA-SORE(a circular RNA upregulated in sorafenib-resistant HCC cells),plays a significant role in sorafenib resistance in HCC.We found that circRNA-SORE is upregulated in sorafenib-resistant HCC cells and depletion of circRNA-SORE substantially increases the cell-killing ability of sorafenib.Further studies revealed that circRNA-SORE binds the master oncogenic protein YBX1 in the cytoplasm,which prevents YBX1 nuclear interaction with the E3 ubiquitin ligase PRP19 and thus blocks PRP19-mediated YBX1 degradation.Moreover,our in vitro and in vivo results suggest that circRNA-SORE is transported by exosomes to spread sorafenib resistance among HCC cells.Using different HCC mouse models,we demonstrated that silencing circRNA-SORE by injection of siRNA could substantially overcome sorafenib resistance.Our study provides a proof-of-concept demonstration for a potential strategy to overcome sorafenib resistance in HCC patients by targeting circRNA-SORE or YBX1.
基金This work was financially supported by National Key Research and Development Program(No.2018YFB1502503)and Sichuan Science and Technology Program(No.2020YJ0299).
文摘Electrochemical CO_(2) reduction reaction (CO_(2) RR) offers a practical solution to current global greenhouse effect by converting excessive CO_(2) into value-added chemicals or fuels. Noble metal-based nanomaterials have been considered as efficient catalysts for the CO_(2) RR owing to their high catalytic activity, long-term stability and superior selectivity to targeted products. On the other hand, they are usually loaded on different support materials in order to minimize their usage and maximize the utilization because of high price and limited reserve. The strong metal-support interaction (MSI) between the metal and substrate plays an important role in affecting the CO_(2) RR performance. In this review, we mainly focus on different types of support materials (e.g., oxides, carbons, ligands, alloys and metal carbides) interacting with noble metal as electrocatalysts for CO_(2) RR. Moreover, the positive effects about MSI for boosting the CO_(2) RR performance via regulating the adsorption strength, electronic structure, coordination environment and binding energy are presented. Lastly, emerging challenges and future opportunities on noble metal electrocatalysts with strong MSI are discussed.
基金supported by grants from the National Key Research and Development Program of China(2021YFF1000302)the National Natural Science Foundation of China(31901550)+2 种基金the Ministry of Science and Technology of China(2016YFD0101803)the National Natural Science Foundation of China(31501326)Innovative Talents in Colleges and Universities of Henan Province(19HASTIT010)was a funding pro-vided by Henan Province government of China.
文摘Southern corn rust(SCR),caused by the fungal pathogen Puccinia polysora,is a major threat to maize pro-duction worldwide.Efficient breeding and deployment of resistant hybrids are key to achieving durable control of SCR.Here,we report the molecular cloning and characterization of RppC,which encodes an NLR-type immune receptor and is responsible for a major SCR resistance quantitative trait locus.Further-more,we identified the corresponding avirulence effector,AvrRppC,which is secreted by P.polysora and triggers RppC-mediated resistance.Allelic variation of AvrRppC directly determines the effectiveness of RppC-mediated resistance,indicating that monitoring of AvrRppC variants in the field can guide the rational deployment of RppC-containing hybrids in maize production.Currently,RppC is the most frequently deployed SCR resistance gene in China,and a better understanding of its mode of action is crit-ical for extending its durability.
基金funded by the Seismological Bureau Spark Program Project(Grant No.XH15007)the National Natural Science Foundation of China(Grant Nos.41604058,41574057,41621091)the Sichuan-Yunnan National Seismological Monitoring and Prediction Experimental Station Project(Grant No.2016CESE0204)
文摘At GMT time 13：19, August 8, 2017, an M1.0 earthquake struck the Jiuzhaigou region in Sichuan Province, China, causing severe damages and casualties. To investigate the source properties, seismogenic structures, and seismic hazards, we systematically analyzed the tectonic environment, crustal velocity structure in the source region, source parameters and rupture process, Coulomb failure stress changes, and 3-D features of the rupture plane of the Jiuzhaigou earthquake. Our results indicate the following： （1） The Jiuzhaigou earthquake occurred on an unmarked fault belonging to the transition zone of the east Kunlun fault system and is located northwest of the Huya fault. （2） Both the mainshock and aftershock rupture zones are located in a region where crustal seismic velocity changes dramatically. Southeast to the source region, shear wave velocity at the middle to lower crust is significantly low, but it rapidly increases northeastward and lies close to the background velocity across the rupture fault. （3） The aftershock zone is narrow and distributes along the northwest-southeast trend, and most aftershocks occur within a depth range of 5-20 km. （4） The focal mechanism of the Jiuzhaigou earthquake indicates a left-lateral strike-slip fault, with strike, dip, and rake angles of 152~, 74~ and 8~, respectively. The hypocenter depth measures 20 km, whereas the centroid depth is about 6 kin. The co-seismic rupture mainly concentrates at depths of 3-13 km, with a moment magnitude （Mw） of 6.5. （5） The co-seismic rupture also strengthens the Coulomb failure stress at the two ends of the rupture fault and the east segment of the Tazang fault. Aftershocks relocation results together with geological surveys indicate that the causative fault is a near vertical fault with notable spatial variations： dip angle varies within 660-89~ from northwest to southeast and the average dip angle measures -84~. The results of this work are of fundamental importance for further studies on the source character
