Water splitting powered by clean electricity is a sustainable and promising approach to produce green hydrogen.Currently,noble metal(e.g.Iridium,Ruthenium,Platinum)-based catalysts are most widely used for water split...Water splitting powered by clean electricity is a sustainable and promising approach to produce green hydrogen.Currently,noble metal(e.g.Iridium,Ruthenium,Platinum)-based catalysts are most widely used for water splitting electrolysis.However,noble metal-based catalysts often suffer from multiple disadvantages,including high cost,low selectivity and poor durability.The emergence of metal-organic framework nanosheets(MOFNSs)attracts significant attention due to their unique advantages.Here,a concise,yet comprehensive and critical,review of recent advances in the field of MOFNSs is provided.This review explains the fundamental oxygen evolution reaction(OER)and hydrogen evolution reaction(HER)catalytic mechanisms as well as key characterization techniques for the structure-activity relationship study are discussed.Moreover,it discusses efficient design strategies and the brief research advances of MOFNSs in HER,OER,and bifunctional electrocatalysis,along with some challenges and opportunities.展开更多
Radiation belt electron dropouts indicate electron flux decay to the background level during geomagnetic storms,which is commonly attributed to the effects of wave-induced pitch angle scattering and magnetopause shado...Radiation belt electron dropouts indicate electron flux decay to the background level during geomagnetic storms,which is commonly attributed to the effects of wave-induced pitch angle scattering and magnetopause shadowing.To investigate the loss mechanisms of radiation belt electron dropouts triggered by a solar wind dynamic pressure pulse event on 12 September 2014,we comprehensively analyzed the particle and wave measurements from Van Allen Probes.The dropout event was divided into three periods:before the storm,the initial phase of the storm,and the main phase of the storm.The electron pitch angle distributions(PADs)and electron flux dropouts during the initial and main phases of this storm were investigated,and the evolution of the radial profile of electron phase space density(PSD)and the(μ,K)dependence of electron PSD dropouts(whereμ,K,and L^*are the three adiabatic invariants)were analyzed.The energy-independent decay of electrons at L>4.5 was accompanied by butterfly PADs,suggesting that the magnetopause shadowing process may be the major loss mechanism during the initial phase of the storm at L>4.5.The features of electron dropouts and 90°-peaked PADs were observed only for>1 MeV electrons at L<4,indicating that the wave-induced scattering effect may dominate the electron loss processes at the lower L-shell during the main phase of the storm.Evaluations of the(μ,K)dependence of electron PSD drops and calculations of the minimum electron resonant energies of H+-band electromagnetic ion cyclotron(EMIC)waves support the scenario that the observed PSD drop peaks around L^*=3.9 may be caused mainly by the scattering of EMIC waves,whereas the drop peaks around L^*=4.6 may result from a combination of EMIC wave scattering and outward radial diffusion.展开更多
Using wave measurements from the EMFISIS instrument onboard Van Allen Probes,we investigate statistically the spatial distributions of the intensity of plasmaspheric hiss waves.To reproduce these empirical results,we ...Using wave measurements from the EMFISIS instrument onboard Van Allen Probes,we investigate statistically the spatial distributions of the intensity of plasmaspheric hiss waves.To reproduce these empirical results,we establish a fitting model that is a thirdorder polynomial function of L-shell,magnetic local time(MLT),magnetic latitude(MLAT),and AE*.Quantitative comparisons indicate that the model’s fitting functions can reflect favorably the major empirical features of the global distribution of hiss wave intensity,including substorm dependence and the MLT asymmetry.Our results therefore provide a useful analytic model that can be readily employed in future simulations of global radiation belt electron dynamics under the impact of plasmaspheric hiss waves in geospace.展开更多
In order to investigate the differences between agronomic traits of dwarf mutant and original material 260 and whether the cause of dwarf is related to GA synthesis or signaling pathway,this experiment used dwarf muta...In order to investigate the differences between agronomic traits of dwarf mutant and original material 260 and whether the cause of dwarf is related to GA synthesis or signaling pathway,this experiment used dwarf mutant 778 and its original material 260 as experimental materials.Morphological observation and determination were performed for agronomic traits on plant height,ear length,internode length,internode number,seed length,seed width and number of seeds in different growth periods and different concentrations.The plants were treated by GA spraying,and the changes of plant height,root length,stem width,leaf length and leaf width were measured.The results are as follows:①The plant height of the dwarf mutant material was significantly different from that of the original high material,which was mainly caused by the difference between above-ground basal part and the length of the first and second elongation joints.②Comparing and analyzing the differences of traits between dwarf mutant material 778 and original high material 260,it was found that the plant height,ear length,internode number,grain number per ear and internode length of dwarf mutant 778 were significantly lower than that of high stalk 260(P<0.01),and the seed length of dwarf mutant 778 was significantly higher than that of high stalk 260(P<0.05).③Different concentrations of gibberellin(0,50,100,200 mg/L)had no significant effect on plant height and root length of dwarf mutant 778(P>0.05).Different concentrations of gibberellin had significant effects on plant height,root length and sensitivity coefficient of high stalk 260(P<0.05).And compared with the control group,all high materials 260 treated with different concentrations of gibberellin performed differently in plant morphology and growth potential.④Under the conditions of 100 and 200 mg/L GA,the difference of plant height between the dwarf mutant and the high stalk control decreased with time,and there was no difference at the end.There were no differences in sensitivity coefficient GRI between different concentrations of gibberellin treatment groups,indicating that the external gibberellin could restore the scorpion dwarf mutant to the original high stalk,and the gene that causes the mutation might be related with the gibberellin synthesis pathway.展开更多
Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuc...Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16α-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR-FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.展开更多
Systematic and in-depth explorations of the effects of side-chain modulation on the molecular assembly,optoelectronic properties,and photocatalytic properties of supramolecular systems,as well as the kinetics of charg...Systematic and in-depth explorations of the effects of side-chain modulation on the molecular assembly,optoelectronic properties,and photocatalytic properties of supramolecular systems,as well as the kinetics of charge separation and migration in these systems,are rare.In this study,a novel supramolecular photocatalyst with an alkoxy side chain(S-EPDI)was successfully developed through subtle design of the short and linear alkoxyl side chains,affording a phenol degradation efficiency approximately four times that of the counterpart with an alkyl side chain(S-APDI).Notably,combined density functional theory(DFT)calculations,absorption spectroscopy,and other characterizations revealed that the perylene diimide(PDI)molecular units,throughπ-πstacking,formed a unique rotationally offset stacked supramolecular structure,exhibiting a significant dipole moment.This gave rise to the formation of a larger inherent electric field within S-EPDI compared to S-APDI.Moreover,the study quantitatively demonstrated that a stronger inherent electric field and lower rate of surface charge recombination facilitate efficient separation of the photogenerated carriers.Therefore,the side-chain molecular engineering method employed in this study offers an effective approach for modulating the kinetics of charge migration.展开更多
The compaction characteristics of biomimetic press roller with ridge structures, inspired from the geometrical features of the ventral surface of dung beetle （Copris ochus Motschulsky）, were investigated in this wor...The compaction characteristics of biomimetic press roller with ridge structures, inspired from the geometrical features of the ventral surface of dung beetle （Copris ochus Motschulsky）, were investigated in this work. Field tests were carried out at three weights （300 N, 500 N and 700 N） and two forward velocities （0.64 m·s^-1 and 1.04 m·s^-1） for biomimetic press roller and conventional press roller. To determine compaction performance, rolling resistance, soil bulk density, soil moisture content, emergence rate and percent change of plant spacing were measured. Roller weight was proved to be the major contributory factor on soil compaction. Biomimetic press roller decreased rolling resistance by 2.98% -17.69% at the velocity of 0.64 m·s^-1, and by 6.59% -18.57% at the velocity of 1.04 m·s^-1 compared with the conventional press roller. Both biomimetic roller and conventional roller can achieve proper bulk density for corn seeds under the experimental conditions. However, compared with the conventional roller, biomimetic roller helped soil conserve more moisture. The highest emergence rate was found when the biomimetic roller worked with a weight of 700 N and velocity of 0.64 m·s^-1. Percent change of plant spacing was lower using the biomimetic press roller compared with that using the conventional roller, because that adjacent ridge structures of the biomi- metic roller can well constrain the flow of soil during compacting process.展开更多
Polyethylene glycols(PEGs)in general use are polydisperse molecules with molecular weight(MW)distributed around an average value applied in their designation e.g.,PEG 4000.Previous research has shown that PEGs can act...Polyethylene glycols(PEGs)in general use are polydisperse molecules with molecular weight(MW)distributed around an average value applied in their designation e.g.,PEG 4000.Previous research has shown that PEGs can act as P-glycoprotein(P-gp)inhibitors with the potential to affect the absorption and efflux of concomitantly administered drugs.However,questions related to the mechanism of cellular uptake of PEGs and the exact role played by P-gp has not been addressed.In this study,we examined the mechanism of uptake of PEGs by MDCK-mock cells,in particular,the effect of MW and interaction with P-gp by MDCK-hMDRl and A549 cells.The results show that:(a)the uptake of PEGs by MDCK-hMDR1 cells is enhanced by P-gp inhibitors;(b)PEGs stimulate P-gp ATPase activity but to a much lesser extent than verapamil;and(c)uptake of PEGs of low MW(<2000 Da)occurs by passive diffusion whereas uptake of PEGs of hish MW(>5000 Da)occurs by a combination of passive diffusion and caveolae-mediated endocytosis.These findings suggest that PEGs can engage in P-gp-based drug interactions which we believe should be taken into account when using PEGs as excipients and in PEGylated drugs and drug delivery systems.展开更多
Prime editing(PE)is a versatile genome editing tool without the need for double-stranded DNA breaks or donor DNA templates,but is limited by low editing efficiency.We previously fused the M-MLV reverse transcriptase t...Prime editing(PE)is a versatile genome editing tool without the need for double-stranded DNA breaks or donor DNA templates,but is limited by low editing efficiency.We previously fused the M-MLV reverse transcriptase to the Cas9 nickase,generating the PE2(v1)system,but the editing efficiency of this system is still low.Here we develop different versions of PE2 by adding the 50-to-30 exonuclease at different positions of the nCas9-M-MLV RT fusion protein.PE2(v2),in which the T5 exonuclease fused to the N-terminus of the nCas9-MMLV fusion protein enhances prime editing efficiency of base substitutions,deletions,and insertions at several genomic sites by 1.7-to 2.9-fold in plant cells compared to PE2(v1).The improved editing efficiency of PE2(v2)is further confirmed by generating increased heritable prime edits in stable transgenic plants compared to the previously established PE-P1,PE-P2,and PPE systems.Using PE2(v2),we generate herbicide-resistant rice by simultaneously introducing mutations causing amino acid substitutions at two target sites.The PE efficiency is further improved by combining PE2(v2)and dualpegRNAs.Taken together,the increased genome editing efficiency of PE2(v2)developed in this study may enhance the applications of PE in plants.展开更多
A novel bunched cerium oxide(CeO_(2))was prepared and its binary composite material with multi-walled carbon nanotubes presented an excellent microwave absorbing properties.The morphology,structure,and absorbing prope...A novel bunched cerium oxide(CeO_(2))was prepared and its binary composite material with multi-walled carbon nanotubes presented an excellent microwave absorbing properties.The morphology,structure,and absorbing properties of the composite material were investigated.It was found that the minimum reflection loss(RL)of the composite material at 15.79 GHz was−45.7 dB when the thickness was 5.5 mm.It was worth noting that when the composite material was in the thickness range of 5.0-7.5 mm and the frequency was 11.36-17.77 GHz,the electromagnetic wave RL was<−30 dB,which illustrated that the composite material had a good absorbing effect over a wide thickness range.The results of the study contributed to the design and preparation of efficient microwave absorbing materials(MAM)with rare earth oxide composites and their applications,which demonstrated the importance of new composites with special structures in the field of MAM.展开更多
Dear Editor,In recent years,CRISPR/Cas9-mediated genome editing has been successfully applied in various plants for functional analysis or crop improvement(Chen et al.,2019).We previously reported DNA-free genome-edit...Dear Editor,In recent years,CRISPR/Cas9-mediated genome editing has been successfully applied in various plants for functional analysis or crop improvement(Chen et al.,2019).We previously reported DNA-free genome-editing methods to generate transgene-free mutants(Liang et al.,2017;Zhang et al.,2016).展开更多
文摘Water splitting powered by clean electricity is a sustainable and promising approach to produce green hydrogen.Currently,noble metal(e.g.Iridium,Ruthenium,Platinum)-based catalysts are most widely used for water splitting electrolysis.However,noble metal-based catalysts often suffer from multiple disadvantages,including high cost,low selectivity and poor durability.The emergence of metal-organic framework nanosheets(MOFNSs)attracts significant attention due to their unique advantages.Here,a concise,yet comprehensive and critical,review of recent advances in the field of MOFNSs is provided.This review explains the fundamental oxygen evolution reaction(OER)and hydrogen evolution reaction(HER)catalytic mechanisms as well as key characterization techniques for the structure-activity relationship study are discussed.Moreover,it discusses efficient design strategies and the brief research advances of MOFNSs in HER,OER,and bifunctional electrocatalysis,along with some challenges and opportunities.
基金This work was supported by the B-type Strategic Priority Program of the Chinese Academy of Sciences(grant no.XDB41000000)the National Natural Science Foundation of China(grant nos.42025404,41704162,41974186,41674163,41904144,41904143)+1 种基金the pre-research projects on Civil Aerospace Technologies(grant nos.D020303,D020308,D020104)the China National Space Administration,and the China Postdoctoral Science Foundation Project(grant no.2019M662700).We also acknowledge the Van Allen Probes mission,particularly the ECT and EMFISIS team,for providing particle and wave data.The electron flux data were obtained from http://www.rbsp-ect.lanl.gov/data_pub/.The wave data from the EMFISIS instrument were obtained from http://emfisis.physics.uiowa.edu/data/index.The solar wind parameters and geomagnetic indices were obtained from the online OMNIWeb(http://omniweb.gsfc.nasa.gov/).
文摘Radiation belt electron dropouts indicate electron flux decay to the background level during geomagnetic storms,which is commonly attributed to the effects of wave-induced pitch angle scattering and magnetopause shadowing.To investigate the loss mechanisms of radiation belt electron dropouts triggered by a solar wind dynamic pressure pulse event on 12 September 2014,we comprehensively analyzed the particle and wave measurements from Van Allen Probes.The dropout event was divided into three periods:before the storm,the initial phase of the storm,and the main phase of the storm.The electron pitch angle distributions(PADs)and electron flux dropouts during the initial and main phases of this storm were investigated,and the evolution of the radial profile of electron phase space density(PSD)and the(μ,K)dependence of electron PSD dropouts(whereμ,K,and L^*are the three adiabatic invariants)were analyzed.The energy-independent decay of electrons at L>4.5 was accompanied by butterfly PADs,suggesting that the magnetopause shadowing process may be the major loss mechanism during the initial phase of the storm at L>4.5.The features of electron dropouts and 90°-peaked PADs were observed only for>1 MeV electrons at L<4,indicating that the wave-induced scattering effect may dominate the electron loss processes at the lower L-shell during the main phase of the storm.Evaluations of the(μ,K)dependence of electron PSD drops and calculations of the minimum electron resonant energies of H+-band electromagnetic ion cyclotron(EMIC)waves support the scenario that the observed PSD drop peaks around L^*=3.9 may be caused mainly by the scattering of EMIC waves,whereas the drop peaks around L^*=4.6 may result from a combination of EMIC wave scattering and outward radial diffusion.
基金supported by the B-type Strategic Priority Program of the Chinese Academy of Sciences (Grant No. XDB41000000)the NSFC grants 41674163, 41974186, 41704162, 41904144, and 41904143+1 种基金the pre-research projects on Civil Aerospace Technologies No. D020308, D020104 and D020303funded by China National Space Administration。
文摘Using wave measurements from the EMFISIS instrument onboard Van Allen Probes,we investigate statistically the spatial distributions of the intensity of plasmaspheric hiss waves.To reproduce these empirical results,we establish a fitting model that is a thirdorder polynomial function of L-shell,magnetic local time(MLT),magnetic latitude(MLAT),and AE*.Quantitative comparisons indicate that the model’s fitting functions can reflect favorably the major empirical features of the global distribution of hiss wave intensity,including substorm dependence and the MLT asymmetry.Our results therefore provide a useful analytic model that can be readily employed in future simulations of global radiation belt electron dynamics under the impact of plasmaspheric hiss waves in geospace.
基金Supported by Project of Hebei Province Department of Science and Technology(17396310D).
文摘In order to investigate the differences between agronomic traits of dwarf mutant and original material 260 and whether the cause of dwarf is related to GA synthesis or signaling pathway,this experiment used dwarf mutant 778 and its original material 260 as experimental materials.Morphological observation and determination were performed for agronomic traits on plant height,ear length,internode length,internode number,seed length,seed width and number of seeds in different growth periods and different concentrations.The plants were treated by GA spraying,and the changes of plant height,root length,stem width,leaf length and leaf width were measured.The results are as follows:①The plant height of the dwarf mutant material was significantly different from that of the original high material,which was mainly caused by the difference between above-ground basal part and the length of the first and second elongation joints.②Comparing and analyzing the differences of traits between dwarf mutant material 778 and original high material 260,it was found that the plant height,ear length,internode number,grain number per ear and internode length of dwarf mutant 778 were significantly lower than that of high stalk 260(P<0.01),and the seed length of dwarf mutant 778 was significantly higher than that of high stalk 260(P<0.05).③Different concentrations of gibberellin(0,50,100,200 mg/L)had no significant effect on plant height and root length of dwarf mutant 778(P>0.05).Different concentrations of gibberellin had significant effects on plant height,root length and sensitivity coefficient of high stalk 260(P<0.05).And compared with the control group,all high materials 260 treated with different concentrations of gibberellin performed differently in plant morphology and growth potential.④Under the conditions of 100 and 200 mg/L GA,the difference of plant height between the dwarf mutant and the high stalk control decreased with time,and there was no difference at the end.There were no differences in sensitivity coefficient GRI between different concentrations of gibberellin treatment groups,indicating that the external gibberellin could restore the scorpion dwarf mutant to the original high stalk,and the gene that causes the mutation might be related with the gibberellin synthesis pathway.
基金National Natural Science Foundation of China(Grant Nos.82020108031,82404752,81730103,81573507 and 81973398)National Key Research and Development Program(Grant Nos.2017YFC0909300 and 2016YFC0905000,China)+7 种基金Guangdong Provincial Key Laboratory of Construction Foundation(Grant Nos.2017B030314030 and 2020B1212060034,China)Science and Technology Program of Guangzhou(Grant No.201607020031,China)National Engineering and Technology Research Center for New drug Druggability Evaluation Seed Program of Guangdong Province(Grant No.2017B090903004,China)111 project(Grant No.B16047,China)Guangdong Basic and Applied Basic Research Foundation(Grant Nos.2022A1515012549 and 2023A1515012667,China)Marine Medicine Innovation Platform for the Integration of Production and Education Project of Guangdong Provincial Education Department(No.2021CJPT014,China)Shenzhen Stability Support Project for Colleges and Universities(No.20220814205518001,China)Shenzhen Sustainable Development Project(No.KCXFZ20230731094501002,China).
文摘Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16α-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR-FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.
基金supported by the Chinese National Science Foundation(21806181)Fundamental Research Funds for the Central Universities(2023ZKPYHH05,2024ZKPYHH01).
文摘Systematic and in-depth explorations of the effects of side-chain modulation on the molecular assembly,optoelectronic properties,and photocatalytic properties of supramolecular systems,as well as the kinetics of charge separation and migration in these systems,are rare.In this study,a novel supramolecular photocatalyst with an alkoxy side chain(S-EPDI)was successfully developed through subtle design of the short and linear alkoxyl side chains,affording a phenol degradation efficiency approximately four times that of the counterpart with an alkyl side chain(S-APDI).Notably,combined density functional theory(DFT)calculations,absorption spectroscopy,and other characterizations revealed that the perylene diimide(PDI)molecular units,throughπ-πstacking,formed a unique rotationally offset stacked supramolecular structure,exhibiting a significant dipole moment.This gave rise to the formation of a larger inherent electric field within S-EPDI compared to S-APDI.Moreover,the study quantitatively demonstrated that a stronger inherent electric field and lower rate of surface charge recombination facilitate efficient separation of the photogenerated carriers.Therefore,the side-chain molecular engineering method employed in this study offers an effective approach for modulating the kinetics of charge migration.
基金This work was supported by the National Natural Science Foundation of China （Grant No. 51475204）, the Development Program of Science and Technology of Jilin Province of China （Grant No. 20100711）, the Pro- ject of Graduate Innovation Fund of Jilin University （Grant No. 20121093 and Grant No. 20121096） and the Natioanal “985 Project” in Jilin University.
文摘The compaction characteristics of biomimetic press roller with ridge structures, inspired from the geometrical features of the ventral surface of dung beetle （Copris ochus Motschulsky）, were investigated in this work. Field tests were carried out at three weights （300 N, 500 N and 700 N） and two forward velocities （0.64 m·s^-1 and 1.04 m·s^-1） for biomimetic press roller and conventional press roller. To determine compaction performance, rolling resistance, soil bulk density, soil moisture content, emergence rate and percent change of plant spacing were measured. Roller weight was proved to be the major contributory factor on soil compaction. Biomimetic press roller decreased rolling resistance by 2.98% -17.69% at the velocity of 0.64 m·s^-1, and by 6.59% -18.57% at the velocity of 1.04 m·s^-1 compared with the conventional press roller. Both biomimetic roller and conventional roller can achieve proper bulk density for corn seeds under the experimental conditions. However, compared with the conventional roller, biomimetic roller helped soil conserve more moisture. The highest emergence rate was found when the biomimetic roller worked with a weight of 700 N and velocity of 0.64 m·s^-1. Percent change of plant spacing was lower using the biomimetic press roller compared with that using the conventional roller, because that adjacent ridge structures of the biomi- metic roller can well constrain the flow of soil during compacting process.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.81430087,81673396,81872831 and 81603182)the National Science and Technology Major Projects for‘significant new drugs creation’of the 13th five-year plan(2017ZX09101001 and 2018ZX09721002007,China)
文摘Polyethylene glycols(PEGs)in general use are polydisperse molecules with molecular weight(MW)distributed around an average value applied in their designation e.g.,PEG 4000.Previous research has shown that PEGs can act as P-glycoprotein(P-gp)inhibitors with the potential to affect the absorption and efflux of concomitantly administered drugs.However,questions related to the mechanism of cellular uptake of PEGs and the exact role played by P-gp has not been addressed.In this study,we examined the mechanism of uptake of PEGs by MDCK-mock cells,in particular,the effect of MW and interaction with P-gp by MDCK-hMDRl and A549 cells.The results show that:(a)the uptake of PEGs by MDCK-hMDR1 cells is enhanced by P-gp inhibitors;(b)PEGs stimulate P-gp ATPase activity but to a much lesser extent than verapamil;and(c)uptake of PEGs of low MW(<2000 Da)occurs by passive diffusion whereas uptake of PEGs of hish MW(>5000 Da)occurs by a combination of passive diffusion and caveolae-mediated endocytosis.These findings suggest that PEGs can engage in P-gp-based drug interactions which we believe should be taken into account when using PEGs as excipients and in PEGylated drugs and drug delivery systems.
基金supported by grants from the National Key Research and Development Program of China(2022YFF1002802)the National Natural Science Foundation of China(32170410)the Science and Technology Innovation Young Talent Team of Shanxi Province(202204051001019).
文摘Prime editing(PE)is a versatile genome editing tool without the need for double-stranded DNA breaks or donor DNA templates,but is limited by low editing efficiency.We previously fused the M-MLV reverse transcriptase to the Cas9 nickase,generating the PE2(v1)system,but the editing efficiency of this system is still low.Here we develop different versions of PE2 by adding the 50-to-30 exonuclease at different positions of the nCas9-M-MLV RT fusion protein.PE2(v2),in which the T5 exonuclease fused to the N-terminus of the nCas9-MMLV fusion protein enhances prime editing efficiency of base substitutions,deletions,and insertions at several genomic sites by 1.7-to 2.9-fold in plant cells compared to PE2(v1).The improved editing efficiency of PE2(v2)is further confirmed by generating increased heritable prime edits in stable transgenic plants compared to the previously established PE-P1,PE-P2,and PPE systems.Using PE2(v2),we generate herbicide-resistant rice by simultaneously introducing mutations causing amino acid substitutions at two target sites.The PE efficiency is further improved by combining PE2(v2)and dualpegRNAs.Taken together,the increased genome editing efficiency of PE2(v2)developed in this study may enhance the applications of PE in plants.
文摘A novel bunched cerium oxide(CeO_(2))was prepared and its binary composite material with multi-walled carbon nanotubes presented an excellent microwave absorbing properties.The morphology,structure,and absorbing properties of the composite material were investigated.It was found that the minimum reflection loss(RL)of the composite material at 15.79 GHz was−45.7 dB when the thickness was 5.5 mm.It was worth noting that when the composite material was in the thickness range of 5.0-7.5 mm and the frequency was 11.36-17.77 GHz,the electromagnetic wave RL was<−30 dB,which illustrated that the composite material had a good absorbing effect over a wide thickness range.The results of the study contributed to the design and preparation of efficient microwave absorbing materials(MAM)with rare earth oxide composites and their applications,which demonstrated the importance of new composites with special structures in the field of MAM.
基金supported by grants from the National Transgenic Science and Technology Program(2019ZX08010-003-001-010)the National Natural Science Foundation of China(31900306)Key Research and Development Program of Shanxi Province(201903D221095)。
文摘Dear Editor,In recent years,CRISPR/Cas9-mediated genome editing has been successfully applied in various plants for functional analysis or crop improvement(Chen et al.,2019).We previously reported DNA-free genome-editing methods to generate transgene-free mutants(Liang et al.,2017;Zhang et al.,2016).
