Developing transition metal-nitrogen-carbon materials(M-N-C)as electrocatalysts for the oxygen evolution reaction(OER)is significant for low-cost energy conversion systems.Further d-orbital adjustment of M center in M...Developing transition metal-nitrogen-carbon materials(M-N-C)as electrocatalysts for the oxygen evolution reaction(OER)is significant for low-cost energy conversion systems.Further d-orbital adjustment of M center in M-N-C is beneficial to the improvement of OER performance.Herein,we synthesize a single-Mn-atom catalyst based on carbon skeleton(Mn_(1)-N_(2)S_(2)C_(x))with isolated Mn-N_(2)S_(2)sites,which exhibits high alkaline OER activity(η10=280 mV),low Tafel slope(44 mV·dec^(−1)),and excellent stability.Theoretical calculations reveal the pivotal function of isolated Mn-N_(2)S_(2)sites in promoting OER,including the adsorption kinetics of intermediates and activation mechanism of active sites.The doping of S causes the increase in both charge density and work function of active Mn center,and ortho-Mn_(1)-N_(2)S_(2)C_(x)expresses the fastest OER kinetics due to the asymmetric plane.展开更多
Base editing using CRISPR technologies is an invaluable tool for crop breeding. One of the major base editors, the adenine base editor(ABE), has been successfully used in both model plants and many crops.However, owin...Base editing using CRISPR technologies is an invaluable tool for crop breeding. One of the major base editors, the adenine base editor(ABE), has been successfully used in both model plants and many crops.However, owing to limited editing efficiency, the ABE has been difficult to apply in polyploid crops such as allohexaploid bread wheat that often require simultaneous mutation of multiple alleles for fast breeding. We have designed a wheat high-efficiency ABE(Whie ABE), using the newly developed high-activity adenosine deaminase Tad A8 e. In vivo and in vitro analysis demonstrated the improved applicability of Tad A8 e over the commonly used Tad A7.10. Dinitroaniline is a widely used herbicide with high effectiveness and low toxicity to animals. However, wheat cultivars with tolerance to dinitroaniline are rare, limiting the application of dinitroaniline in wheat planting. Using A-to-G editing with Whie ABE, we found that a Met-to-Thr mutation in wheat tubulin alleles located on chromosomes 1 A, 1 B, 1 D, 4 A, and 4 D increased the resistance of wheat to dinitroaniline, revealing a dosage effect of edited tubulins in resistance. The Whie ABE promises to be a valuable editing tool for accelerating crop improvement and developing herbicide-resistant wheat germplasm.展开更多
γδ T cells have the unique ability to detect a wide range of tumors with low mutation burdens,making them attractive candidates for CAR-T-cell therapy.Unlike aβT cells and other immune cells,γδ T cells are superi...γδ T cells have the unique ability to detect a wide range of tumors with low mutation burdens,making them attractive candidates for CAR-T-cell therapy.Unlike aβT cells and other immune cells,γδ T cells are superior in MHC non-restriction,selective cell recruitment,and rapid activation.However,clinical trials have shown limited clinical benefits,and the adoptive transplantation of γδ T cells has often fallen short of expectations.We hypothesized that the limited effectiveness of γδ T cells in eradicating tumor cells may be attributed to the inhibitory tumor microenvironment induced by the suppressive PD-1/PD-L1 axis.Herein,we constructed novel armored γδ T cells capable of secreting humanized anti-PD-1 antibodies,referred to as"Lv-PD1-ys T cells.Lv-PD1-γδ T cells showed improved proliferation and enhanced cytotoxicity against tumor cells,resulting in augmented therapeutic effects and survival benefits in ovarian tumor-bearing mice.These engineered cells demonstrated a prolonged in vivo survival of more than 29 days,without any potential for tumorigenicity in immunodeficient NOD/SCID/null mice.We also found that Lv-PD1-γδ T cells exhibited excellent tolerance and safety in humanized NOD/SCID/null mice.With attenuated or eliminated immunosuppression and maximized cytotoxicity efficacy by the local secretion of anti-PD1 antibodies in tumors,Lv-PD1-γδ T cells can serve as a promising"off-the-shelf"cell therapy against cancers.展开更多
Background:Acute respiratory distress syndrome(ARDS)is a common cause of respiratory failure in many critically ill patients.Although inflammasome activation plays an important role in the induction of acute lung inju...Background:Acute respiratory distress syndrome(ARDS)is a common cause of respiratory failure in many critically ill patients.Although inflammasome activation plays an important role in the induction of acute lung injury(ALI)and ARDS,the regulatory mechanism of this process is still unclear.When cells are stimulated by inflammation,the integrity and physiological function of mitochondria play a crucial part in pyroptosis.However,the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known.Here,we identified the 18-kDa translocator protein(TSPO),a mitochondrial outer membrane protein,as an important mediator regulating nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome activation in macrophages during ALI.Methods:TSPO gene knockout(KO)and lipopolysaccharide(LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS.Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway.Activation of NLRP3 inflammasome was preformed through LPS+adenosine triphosphate(ATP)co-stimulation,followed by detection of mitochondrial membrane potential,reactive oxygen species(ROS)production,and cell death to evaluate the potential biological function of TSPO.Comparisons between two groups were performed with a two-sided unpaired t-test.Results:TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI.TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway,promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue,including interleukin(IL)-1β,IL-18,and macrophage inflammatory protein(MIP)-2.Mitochondria in TSPO-KO macrophages tended to depolarize in response to cellular stress.The increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO-KO cells.Conclusion:TSPO may be the key regulator of cellular pyroptosis,and it plays a vital protective role in ARDS occurrence and development.展开更多
As a four-electron transfer reaction,oxygen evolution reaction(OER)is limited by large overpotential and slow kinetics.Here,we in-situ synthesized two-dimensional(2D)Ni-Fe metal-organic framework nanosheets on nickel ...As a four-electron transfer reaction,oxygen evolution reaction(OER)is limited by large overpotential and slow kinetics.Here,we in-situ synthesized two-dimensional(2D)Ni-Fe metal-organic framework nanosheets on nickel foam(NixFe-TPA/NF,TPA=terephthalic acid)for oxygen evolution in alkaline and alkaline seawater electrolytes.In 1 M KOH,Ni3Fe-TPA/NF shows a low overpotential(η10)of 189 mV at 10 mA·cm^(-2) and an ultra-low overpotential of only 260 mV at 500 mA·cm^(-2).In alkaline seawater,Ni3Fe-TPA/NF still provides impressive OER performance,with anη10 of 265 mV.In-situ Raman characterization results show that the phase transition occurs during the OER,and Ni3FeOOH with more oxygen vacancies is in-situ formed,reducing the OER energy barrier.Density functional theory(DFT)reveals that the synergy between Ni and Fe reduces the energy barrier and accelerates the rate-determining step.In addition,the ultra-thin 2D sheet structure and the close combination of Ni3FeOOH and highly conductive NF support ensure the high catalytic OER activity.Therefore,the surface reconstruction and structural modification strategy can be used to design and prepare high-performance OER electrocatalysts for energy-related applications.展开更多
The design of diatomic catalysts with uniformly dispersed metal atoms is expected to improve catalytic performance,which is conducive to the intensive comprehending of the synergistic mechanism between dual-metal site...The design of diatomic catalysts with uniformly dispersed metal atoms is expected to improve catalytic performance,which is conducive to the intensive comprehending of the synergistic mechanism between dual-metal sites for the oxygen evolution reaction(OER)at the atomic level.Herein,we design a strategy to immobilize bimetallic Fe-Co atoms onto nitrogen-doped graphene to obtain a diatomic catalyst(DA-FC-NG)with FeN_(3)-CoN_(3) configuration.The DA-FC-NG shows excellent OER activity with a low overpotential(η_(10)=268 mV),which is superior to commercial iridium dioxide catalysts.Theoretical calculations uncover that the excellent activity of DA-FC-NG is due to the interaction between Fe and Co diatoms,which causes charge rearrangement and induces the adsorption of intermediates on the Fe-O-Co bridge structure,thus improving the catalytic OER performance.This work is of great significance for the design of highly active diatomic catalysts to replace noble metal catalysts for energy-related applications.展开更多
To realize large-scale hydrogen production by electrolysis of water,it is essential to develop non-precious metal catalysts for oxygen evolution reaction(OER)and hydrogen evolution reaction(HER).Here,we fabricate Sn-,...To realize large-scale hydrogen production by electrolysis of water,it is essential to develop non-precious metal catalysts for oxygen evolution reaction(OER)and hydrogen evolution reaction(HER).Here,we fabricate Sn-,Fe-,and Co-based sulfide/oxyhydroxide heterostructural catalyst on nickel foam(FeSnCo_(0.2)S_(x)O_(y)/NF)by solvothermal method.The FeSnCo_(0.2)S_(x)O_(y)/NF requires low overpotentials of 48 and 186 mV at 10 mA·cm^(-2),respectively,for HER and OER.When it is assembled into an electrolytic cell as a bifunctional electrocatalyst,it only needs 1.54 V to reach 10 mA·cm^(-2),far better than IrO_(2)||Pt/C electrolyzer.The formation of sulfide/hydroxide heterostructural interfaces improves the electron transfer and reduces the reaction energy barrier,thus promoting the electrocatalytic processes.展开更多
Oxygen evolution reaction(OER)is the core electrode reaction in energy-related technologies,such as electrolytic water,electrocatalytic carbon dioxide reduction,rechargeable metal-air batteries,and renewable fuel cell...Oxygen evolution reaction(OER)is the core electrode reaction in energy-related technologies,such as electrolytic water,electrocatalytic carbon dioxide reduction,rechargeable metal-air batteries,and renewable fuel cells.Development of well-stocked,cost-effective,and high-performance OER electrocatalysts is the key to the improvement of energy efficiency and the large-scale commercial implementation of these technologies.Multicomponent transition metal oxides and(oxy)hydroxides are the most promising OER catalysts due to their low cost,adjustable structure,high electrocatalytic activity,and outstanding durability.In this review,a brief overview about the mechanisms of OER is first offered,accompanied with the theory and calculation criteria.Then,the latest advances in the rational design of the related OER electrocatalysts and the modulation of the electronic structure of active sites are comprehensively summarized.Specifically,various strategies(including element doping,defect engineering,and fabrication of binderless catalysts)used to improve the OER performance are detailedly discussed,emphasizing the structure–function relationships.Finally,the challenges and perspectives on this promising field are proposed.展开更多
Background:Although Mex3 RNA-binding family member A(Mex3a)has demonstrated an important role in multiple cancers,its role and regulatory mechanism in CRC is unclear.In this study,we aimed to investigate the role and ...Background:Although Mex3 RNA-binding family member A(Mex3a)has demonstrated an important role in multiple cancers,its role and regulatory mechanism in CRC is unclear.In this study,we aimed to investigate the role and clinical significance of Mex3a in CRC and to explore its underlying mechanism.Methods:Western blotting and quantitative real-time polymerase chain reaction(qRT-PCR)were performed to detect the expression levels of genes.5-Ethynyl-2’-deoxyuridine(EDU)and transwell assays were utilized to examine CRC cell proliferation and metastatic ability.The R software was used to do hierarchical clustering analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Overexpression and rescue experiments which included U0126,a specific mitogen activated protein kinase kinase/extracellular regulated protein kinase(MEK/ERK)inhibitor,and PX-478,a hypoxia-inducible factor 1 subunit alpha(HIF-1α)inhibitor,were used to study the molecularmechanisms of Mex3a in CRC cells.Co-immunoprecipitation(Co-IP)assay was performed to detect the interaction between two proteins.Bioinformatics analysis including available public database and Starbase software(starbase.sysu.edu.cn)were used to evaluate the expression and prognostic significance of genes.TargetScan(www.targetscan.org)and the miRDB(mirdb.org)website were used to predict the combination site between microRNA and target mRNA.BALB/c nude micewere used to study the function of Mex3a and hsa-miR-6887-3p in vivo.Results:Clinicopathological and immunohistochemical(IHC)studies of 101 CRC tissues and 79 normal tissues demonstrated that Mex3a was a significant prognostic factor for overall survival(OS)in CRC patients.Mex3a knockdown substantially inhibited the migration,invasion,and proliferation of CRC cells.Transcriptome analysis and mechanism verification showed that Mex3a regulated the RAP1 GTPase activating protein(RAP1GAP)/MEK/ERK/HIF-1αpathway.Furthermore,RAP1GAP was identified to interact with Mex3a in Co-IP experiments.Bioinformatics and dual-luciferase reporter experiments revealed that hsa-miR-6887-3p could bind to the 3’-untranslated regions(3’-UTR)of the Mex3amRNA.hsa-miR-6887-3p downregulated Mex3a expression and inhibited the tumorigenesis of CRC both in vitro and in vivo.Conclusions:Our study demonstrated that the hsa-miR-6887-3p/Mex3a/RAP1GAP signaling axis was a key regulator of CRC and Mex3a has the potential to be a new diagnostic marker and treatment target for CRC.展开更多
基金supported by the National Natural Science Foundation of China(No.22075099)the Natural Science Foundation of Jilin Province(No.20220101051JC)the Education Department of Jilin Province(No.JJKH20220967KJ)。
文摘Developing transition metal-nitrogen-carbon materials(M-N-C)as electrocatalysts for the oxygen evolution reaction(OER)is significant for low-cost energy conversion systems.Further d-orbital adjustment of M center in M-N-C is beneficial to the improvement of OER performance.Herein,we synthesize a single-Mn-atom catalyst based on carbon skeleton(Mn_(1)-N_(2)S_(2)C_(x))with isolated Mn-N_(2)S_(2)sites,which exhibits high alkaline OER activity(η10=280 mV),low Tafel slope(44 mV·dec^(−1)),and excellent stability.Theoretical calculations reveal the pivotal function of isolated Mn-N_(2)S_(2)sites in promoting OER,including the adsorption kinetics of intermediates and activation mechanism of active sites.The doping of S causes the increase in both charge density and work function of active Mn center,and ortho-Mn_(1)-N_(2)S_(2)C_(x)expresses the fastest OER kinetics due to the asymmetric plane.
基金funded by the Agricultural Variety Improvement Project of Shandong Province(2019LZGC015)the National Natural Science Foundation of China(31901432)。
文摘Base editing using CRISPR technologies is an invaluable tool for crop breeding. One of the major base editors, the adenine base editor(ABE), has been successfully used in both model plants and many crops.However, owing to limited editing efficiency, the ABE has been difficult to apply in polyploid crops such as allohexaploid bread wheat that often require simultaneous mutation of multiple alleles for fast breeding. We have designed a wheat high-efficiency ABE(Whie ABE), using the newly developed high-activity adenosine deaminase Tad A8 e. In vivo and in vitro analysis demonstrated the improved applicability of Tad A8 e over the commonly used Tad A7.10. Dinitroaniline is a widely used herbicide with high effectiveness and low toxicity to animals. However, wheat cultivars with tolerance to dinitroaniline are rare, limiting the application of dinitroaniline in wheat planting. Using A-to-G editing with Whie ABE, we found that a Met-to-Thr mutation in wheat tubulin alleles located on chromosomes 1 A, 1 B, 1 D, 4 A, and 4 D increased the resistance of wheat to dinitroaniline, revealing a dosage effect of edited tubulins in resistance. The Whie ABE promises to be a valuable editing tool for accelerating crop improvement and developing herbicide-resistant wheat germplasm.
基金the National Natural Science Foundation of China(U20A20374,32270915,82071791,31970843,and 81972866)the CAMS Initiative for Innovative Medicine(2021-/2M-1-005,2021-12M-1-035,and 2021-/2M-1-053)+3 种基金Haihe Laboratory of Cell Ecosystem Innovation Fund(HH22KYZX0028)the National Key Research and Development Program of China(2022YFC3602004)State Key Laboratory Special Fund 2060204,Changzhou Science and Technology Support Plan(CE20215008)the CAMS Central Public Welfare Scientific Research Institute Basal Research Expenses(3332020035,2018PT32004,and 2018PT31052).
文摘γδ T cells have the unique ability to detect a wide range of tumors with low mutation burdens,making them attractive candidates for CAR-T-cell therapy.Unlike aβT cells and other immune cells,γδ T cells are superior in MHC non-restriction,selective cell recruitment,and rapid activation.However,clinical trials have shown limited clinical benefits,and the adoptive transplantation of γδ T cells has often fallen short of expectations.We hypothesized that the limited effectiveness of γδ T cells in eradicating tumor cells may be attributed to the inhibitory tumor microenvironment induced by the suppressive PD-1/PD-L1 axis.Herein,we constructed novel armored γδ T cells capable of secreting humanized anti-PD-1 antibodies,referred to as"Lv-PD1-ys T cells.Lv-PD1-γδ T cells showed improved proliferation and enhanced cytotoxicity against tumor cells,resulting in augmented therapeutic effects and survival benefits in ovarian tumor-bearing mice.These engineered cells demonstrated a prolonged in vivo survival of more than 29 days,without any potential for tumorigenicity in immunodeficient NOD/SCID/null mice.We also found that Lv-PD1-γδ T cells exhibited excellent tolerance and safety in humanized NOD/SCID/null mice.With attenuated or eliminated immunosuppression and maximized cytotoxicity efficacy by the local secretion of anti-PD1 antibodies in tumors,Lv-PD1-γδ T cells can serve as a promising"off-the-shelf"cell therapy against cancers.
基金National Natural Science Foundation of China(Nos.82071791,32270915,U20A20374,31970843,and 81972886)National Key Research and Development Program of China(No.2022YFC3602004)+4 种基金CAMS Initiative for Innovative Medicine(Nos.2021-I2M-1-005,2021-I2M-1-035,2021-I2M-1-053,and 2022-I2M-CoV19-007)Haihe Laboratory of Cell Ecosystem Innovation Fund(No.22HHXBSS00028)CAMS Central Public Welfare Scientific Research Institute Basal Research Expenses(No.3332020035)Changzhou Science and Technology Support Plan(No.CE20215008)Beijing Municipal Commission of Science and Technology Fund for Innovative Drugs(No.Z221100007922040)
文摘Background:Acute respiratory distress syndrome(ARDS)is a common cause of respiratory failure in many critically ill patients.Although inflammasome activation plays an important role in the induction of acute lung injury(ALI)and ARDS,the regulatory mechanism of this process is still unclear.When cells are stimulated by inflammation,the integrity and physiological function of mitochondria play a crucial part in pyroptosis.However,the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known.Here,we identified the 18-kDa translocator protein(TSPO),a mitochondrial outer membrane protein,as an important mediator regulating nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome activation in macrophages during ALI.Methods:TSPO gene knockout(KO)and lipopolysaccharide(LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS.Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway.Activation of NLRP3 inflammasome was preformed through LPS+adenosine triphosphate(ATP)co-stimulation,followed by detection of mitochondrial membrane potential,reactive oxygen species(ROS)production,and cell death to evaluate the potential biological function of TSPO.Comparisons between two groups were performed with a two-sided unpaired t-test.Results:TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI.TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway,promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue,including interleukin(IL)-1β,IL-18,and macrophage inflammatory protein(MIP)-2.Mitochondria in TSPO-KO macrophages tended to depolarize in response to cellular stress.The increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO-KO cells.Conclusion:TSPO may be the key regulator of cellular pyroptosis,and it plays a vital protective role in ARDS occurrence and development.
基金supported by the National Natural Science Foundation of China(No.22075099)the Natural Science Foundation of Jilin Province(Nos.20220101051JC and 20200201395JC)the Education Department of Jilin Province(Nos.JJKH20220967KJ and JJKH20220968CY).
文摘As a four-electron transfer reaction,oxygen evolution reaction(OER)is limited by large overpotential and slow kinetics.Here,we in-situ synthesized two-dimensional(2D)Ni-Fe metal-organic framework nanosheets on nickel foam(NixFe-TPA/NF,TPA=terephthalic acid)for oxygen evolution in alkaline and alkaline seawater electrolytes.In 1 M KOH,Ni3Fe-TPA/NF shows a low overpotential(η10)of 189 mV at 10 mA·cm^(-2) and an ultra-low overpotential of only 260 mV at 500 mA·cm^(-2).In alkaline seawater,Ni3Fe-TPA/NF still provides impressive OER performance,with anη10 of 265 mV.In-situ Raman characterization results show that the phase transition occurs during the OER,and Ni3FeOOH with more oxygen vacancies is in-situ formed,reducing the OER energy barrier.Density functional theory(DFT)reveals that the synergy between Ni and Fe reduces the energy barrier and accelerates the rate-determining step.In addition,the ultra-thin 2D sheet structure and the close combination of Ni3FeOOH and highly conductive NF support ensure the high catalytic OER activity.Therefore,the surface reconstruction and structural modification strategy can be used to design and prepare high-performance OER electrocatalysts for energy-related applications.
基金supported by the National Natural Science Foundation of China(No.22075099)the Natural Science Foundation of Jilin Province(No.20220101051JC)+1 种基金the Education Department of Jilin Province(No.JJKH20220968CY)the Graduate Innovation Fund of Jilin University(No.2023CX036).
文摘The design of diatomic catalysts with uniformly dispersed metal atoms is expected to improve catalytic performance,which is conducive to the intensive comprehending of the synergistic mechanism between dual-metal sites for the oxygen evolution reaction(OER)at the atomic level.Herein,we design a strategy to immobilize bimetallic Fe-Co atoms onto nitrogen-doped graphene to obtain a diatomic catalyst(DA-FC-NG)with FeN_(3)-CoN_(3) configuration.The DA-FC-NG shows excellent OER activity with a low overpotential(η_(10)=268 mV),which is superior to commercial iridium dioxide catalysts.Theoretical calculations uncover that the excellent activity of DA-FC-NG is due to the interaction between Fe and Co diatoms,which causes charge rearrangement and induces the adsorption of intermediates on the Fe-O-Co bridge structure,thus improving the catalytic OER performance.This work is of great significance for the design of highly active diatomic catalysts to replace noble metal catalysts for energy-related applications.
基金the National Natural Science Foundation of China(No.22075099)the Natural Science Foundation of Jilin Province(No.20220101051JC).
文摘To realize large-scale hydrogen production by electrolysis of water,it is essential to develop non-precious metal catalysts for oxygen evolution reaction(OER)and hydrogen evolution reaction(HER).Here,we fabricate Sn-,Fe-,and Co-based sulfide/oxyhydroxide heterostructural catalyst on nickel foam(FeSnCo_(0.2)S_(x)O_(y)/NF)by solvothermal method.The FeSnCo_(0.2)S_(x)O_(y)/NF requires low overpotentials of 48 and 186 mV at 10 mA·cm^(-2),respectively,for HER and OER.When it is assembled into an electrolytic cell as a bifunctional electrocatalyst,it only needs 1.54 V to reach 10 mA·cm^(-2),far better than IrO_(2)||Pt/C electrolyzer.The formation of sulfide/hydroxide heterostructural interfaces improves the electron transfer and reduces the reaction energy barrier,thus promoting the electrocatalytic processes.
基金supported by the National Natural Science Foundation of China(No.22075099)the Natural Science Foundation of Jilin Province(No.20220101051JC)the Education Department of Jilin Province(No.JJKH20220967KJ).
文摘Oxygen evolution reaction(OER)is the core electrode reaction in energy-related technologies,such as electrolytic water,electrocatalytic carbon dioxide reduction,rechargeable metal-air batteries,and renewable fuel cells.Development of well-stocked,cost-effective,and high-performance OER electrocatalysts is the key to the improvement of energy efficiency and the large-scale commercial implementation of these technologies.Multicomponent transition metal oxides and(oxy)hydroxides are the most promising OER catalysts due to their low cost,adjustable structure,high electrocatalytic activity,and outstanding durability.In this review,a brief overview about the mechanisms of OER is first offered,accompanied with the theory and calculation criteria.Then,the latest advances in the rational design of the related OER electrocatalysts and the modulation of the electronic structure of active sites are comprehensively summarized.Specifically,various strategies(including element doping,defect engineering,and fabrication of binderless catalysts)used to improve the OER performance are detailedly discussed,emphasizing the structure–function relationships.Finally,the challenges and perspectives on this promising field are proposed.
基金supported by the National Scientific Foundation of China(NSFC32071127 and 31871160)。
文摘Background:Although Mex3 RNA-binding family member A(Mex3a)has demonstrated an important role in multiple cancers,its role and regulatory mechanism in CRC is unclear.In this study,we aimed to investigate the role and clinical significance of Mex3a in CRC and to explore its underlying mechanism.Methods:Western blotting and quantitative real-time polymerase chain reaction(qRT-PCR)were performed to detect the expression levels of genes.5-Ethynyl-2’-deoxyuridine(EDU)and transwell assays were utilized to examine CRC cell proliferation and metastatic ability.The R software was used to do hierarchical clustering analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Overexpression and rescue experiments which included U0126,a specific mitogen activated protein kinase kinase/extracellular regulated protein kinase(MEK/ERK)inhibitor,and PX-478,a hypoxia-inducible factor 1 subunit alpha(HIF-1α)inhibitor,were used to study the molecularmechanisms of Mex3a in CRC cells.Co-immunoprecipitation(Co-IP)assay was performed to detect the interaction between two proteins.Bioinformatics analysis including available public database and Starbase software(starbase.sysu.edu.cn)were used to evaluate the expression and prognostic significance of genes.TargetScan(www.targetscan.org)and the miRDB(mirdb.org)website were used to predict the combination site between microRNA and target mRNA.BALB/c nude micewere used to study the function of Mex3a and hsa-miR-6887-3p in vivo.Results:Clinicopathological and immunohistochemical(IHC)studies of 101 CRC tissues and 79 normal tissues demonstrated that Mex3a was a significant prognostic factor for overall survival(OS)in CRC patients.Mex3a knockdown substantially inhibited the migration,invasion,and proliferation of CRC cells.Transcriptome analysis and mechanism verification showed that Mex3a regulated the RAP1 GTPase activating protein(RAP1GAP)/MEK/ERK/HIF-1αpathway.Furthermore,RAP1GAP was identified to interact with Mex3a in Co-IP experiments.Bioinformatics and dual-luciferase reporter experiments revealed that hsa-miR-6887-3p could bind to the 3’-untranslated regions(3’-UTR)of the Mex3amRNA.hsa-miR-6887-3p downregulated Mex3a expression and inhibited the tumorigenesis of CRC both in vitro and in vivo.Conclusions:Our study demonstrated that the hsa-miR-6887-3p/Mex3a/RAP1GAP signaling axis was a key regulator of CRC and Mex3a has the potential to be a new diagnostic marker and treatment target for CRC.
