In this study,we identified that a conserved circular RNA(circRNA)DICAR,which was downregulated in diabetic mouse hearts.DICAR had an inhibitory effect on diabetic cardiomyopathy(DCM),as the spontaneous cardiac dysfun...In this study,we identified that a conserved circular RNA(circRNA)DICAR,which was downregulated in diabetic mouse hearts.DICAR had an inhibitory effect on diabetic cardiomyopathy(DCM),as the spontaneous cardiac dysfunction,cardiac cell hypertrophy,and cardiac fibrosis occurred in DICAR deficiency(DICAR+/−)mice,whereas the DCM was alleviated in DICARoverexpressed DICARTg mice.At the cellular level,we found that overexpression of DICAR inhibited,but knockdown of DICAR enhanced the diabetic cardiomyocyte pyroptosis.At the molecular level,we identified that DICAR-VCP-Med12 degradation could be the underlying molecular mechanism in DICAR-mediated effects.The synthesized DICAR junction part(DICAR-JP)exhibited a similar effect to the entire DICAR.In addition,the expression of DICAR in circulating blood cells and plasma from diabetic patients was lower than that from health controls,which was consistent with the decreased DICAR expression in diabetic hearts.DICAR and the synthesized DICAR-JP may be drug candidates for DCM.展开更多
Cytokinins(CKs),primarily trans-zeatin(tZ)and isopentenyladenine(iP)types,play critical roles in plant growth,development,and various stress responses.Long-distance transport of tZ-type CKs meidated by Arabidopsis ATP...Cytokinins(CKs),primarily trans-zeatin(tZ)and isopentenyladenine(iP)types,play critical roles in plant growth,development,and various stress responses.Long-distance transport of tZ-type CKs meidated by Arabidopsis ATP-binding cassette transporter subfamily G14(AtABCG14)has been well studied;however,less is known about the biochemical properties of AtABCG14 and its transporter activity toward iP-type CKs.Here we reveal the biochemical properties of AtABCG14 and provide evidence that it is also required for long-distance transport of iP-type CKs.AtABCG14 formed homodimers in human(Homo sapiens)HEK293T,tobacco(Nicotiana tabacum),and Arabidopsis cells.Transporter activity assays of AtABCG14 in Arabidopsis,tobacco,and yeast(Saccharomyces cerevisiae)showed that AtABCG14 may directly transport multiple CKs,including iP-and tZ-type species.AtABCG14 expression was induced by iP in a tZ-type CKdeficient double mutant(cypDM)of CYP735A1 and CYP735A2.The atabcg14 cypDM triple mutant exhibited stronger CK-deficiency phenotypes than cypDM.Hormone profiling,reciprocal grafting,and 2H6-iP isotope tracer experiments showed that root-to-shoot and shoot-to-root long-distance transport of iP-type CKs were suppressed in atabcg14 cypDM and atabcg14.These results suggest that AtABCG14 participates in three steps of the circular long-distance transport of iP-type CKs:xylem loading in the root for shootward transport,phloem unloading in the shoot for shoot distribution,and phloemunloading in the root for root distribution.We found that AtABCG14 displays transporter activity toward multiple CK species and revealed its versatile roles in circular long-distance transport of iP-type CKs.These findings provide newinsights into the transport mechanisms of CKs and other plant hormones.展开更多
A key to tackling the coronavirus disease 2019(COVID-19)pandemic is to understand how severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)manages to outsmart host antiviral defense mechanisms.Stress granules(S...A key to tackling the coronavirus disease 2019(COVID-19)pandemic is to understand how severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)manages to outsmart host antiviral defense mechanisms.Stress granules(SGs),which are assembled during viral infection and function to sequester host and viral m RNAs and proteins,are part of the antiviral responses.Here,we show that the SARS-Co V-2 nucleocapsid(N)protein,an RNA binding protein essential for viral production,interacted with RasGTPase-activating protein SH3-domain-binding protein(G3 BP)and disrupted SG assembly,both of which require intrinsically disordered region1(IDR1)in N protein.The N protein partitioned into SGs through liquid-liquid phase separation with G3 BP,and blocked the interaction of G3 BP1 with other SG-related proteins.Moreover,the N protein domains important for phase separation with G3 BP and SG disassembly were required for SARS-Co V-2 viral production.We propose that N protein-mediated SG disassembly is crucial for SARS-Co V-2 production.展开更多
The hypoxic nature of solid tumors has severely negative effects on oxygen-based photodynamic therapy.In this study,we used porous Pt nanoparticles as a catalase(CAT)nanozyme,the second near-infrared(NIR-Ⅱ)region pho...The hypoxic nature of solid tumors has severely negative effects on oxygen-based photodynamic therapy.In this study,we used porous Pt nanoparticles as a catalase(CAT)nanozyme,the second near-infrared(NIR-Ⅱ)region photothermal transition agents(PTAs),and carriers of photosensitizer chlorin e6(Ce6)to synthesize a composite nanosystem Pt-Ce6.In this system,Pt-Ce6 can continuously and stably decompose H2O2 into oxygen,thereby alleviating tumor hypoxia and improving the effect of photodynamic therapy(PDT).With 650 nm illumination,the reactive oxygen species(ROS)produced by Ce6 will decrease the mitochondrial membrane potential(MMP,ΔΨm)to release cytochrome c(Cyt-c)from the mitochondria into the cytoplasm,eventually leading to mitochondrial-mediated cellular apoptosis during the PDT process.In addition,Pt-Ce6 has good photothermal stability and high photothermal conversion efficiency(52.62%)in the NIR-II region.In U14 tumor-bearing mice,Pt-Ce6 completely suppressed tumor growth and recurrence under laser irradiation.Thus the nanocomposite shows excellent PDT/photothermal therapy(PTT)synergistic performance in vitro and in vivo.展开更多
As a consequence of contamination of soil with heavy metals,cadmium accumulation in grain is of great concern worldwide,but especially in southern China.It is important to evaluate the Cd accumulation potential of gra...As a consequence of contamination of soil with heavy metals,cadmium accumulation in grain is of great concern worldwide,but especially in southern China.It is important to evaluate the Cd accumulation potential of grain before or when examining and approving new cultivars.An evaluation method and criteria for verifying Cd accumulation potential in rice are proposed,and the Cd accumulation potential of 56 mid-season indica hybrids collected from the provincial cultivar trials in 2016 were investigated.Genotype,environment and their interactions strongly affected the variation in grain Cd accumulation.Two hybrids were identified as slightly Cd accumulating.Hybrids with slight Cd accumulation potential would be suitable for safe grain production on polluted land(total Cd under 2.0 mg$kg–1)in Hunan Province(China)and should be considered for new cultivar evaluation and approval.This evaluation method and criterion could be applied for certifying Cd accumulation potential of rice cultivars.展开更多
基金National Natural Science Foundation of China(#81770377,#82030007)Hubei Province Funds for Distinguished Young Scholars(#2020CFA076)+2 种基金High-level Hospital Construction Project(#DFJH201807)Scientific Research Plan Project of Hubei Provincial Department of Education(#D20211105)Health Commission of Hubei Province Scientific Research Project(#WJ2021M215).
文摘In this study,we identified that a conserved circular RNA(circRNA)DICAR,which was downregulated in diabetic mouse hearts.DICAR had an inhibitory effect on diabetic cardiomyopathy(DCM),as the spontaneous cardiac dysfunction,cardiac cell hypertrophy,and cardiac fibrosis occurred in DICAR deficiency(DICAR+/−)mice,whereas the DCM was alleviated in DICARoverexpressed DICARTg mice.At the cellular level,we found that overexpression of DICAR inhibited,but knockdown of DICAR enhanced the diabetic cardiomyocyte pyroptosis.At the molecular level,we identified that DICAR-VCP-Med12 degradation could be the underlying molecular mechanism in DICAR-mediated effects.The synthesized DICAR junction part(DICAR-JP)exhibited a similar effect to the entire DICAR.In addition,the expression of DICAR in circulating blood cells and plasma from diabetic patients was lower than that from health controls,which was consistent with the decreased DICAR expression in diabetic hearts.DICAR and the synthesized DICAR-JP may be drug candidates for DCM.
基金the National Natural Science Foundation of China(31470370 to K.Z.and 32100270 to J.Z.)the Natural Science Foundation of Zhejiang Province(LY22C020003 to J.Z.)C.-J.L.was supported by the DOE Office of Basic Energy Sciences,specifically through the Physical Biosciences Program of the Chemical Sciences,Geosciences and Biosciences Division,under contract DESC0012704.
文摘Cytokinins(CKs),primarily trans-zeatin(tZ)and isopentenyladenine(iP)types,play critical roles in plant growth,development,and various stress responses.Long-distance transport of tZ-type CKs meidated by Arabidopsis ATP-binding cassette transporter subfamily G14(AtABCG14)has been well studied;however,less is known about the biochemical properties of AtABCG14 and its transporter activity toward iP-type CKs.Here we reveal the biochemical properties of AtABCG14 and provide evidence that it is also required for long-distance transport of iP-type CKs.AtABCG14 formed homodimers in human(Homo sapiens)HEK293T,tobacco(Nicotiana tabacum),and Arabidopsis cells.Transporter activity assays of AtABCG14 in Arabidopsis,tobacco,and yeast(Saccharomyces cerevisiae)showed that AtABCG14 may directly transport multiple CKs,including iP-and tZ-type species.AtABCG14 expression was induced by iP in a tZ-type CKdeficient double mutant(cypDM)of CYP735A1 and CYP735A2.The atabcg14 cypDM triple mutant exhibited stronger CK-deficiency phenotypes than cypDM.Hormone profiling,reciprocal grafting,and 2H6-iP isotope tracer experiments showed that root-to-shoot and shoot-to-root long-distance transport of iP-type CKs were suppressed in atabcg14 cypDM and atabcg14.These results suggest that AtABCG14 participates in three steps of the circular long-distance transport of iP-type CKs:xylem loading in the root for shootward transport,phloem unloading in the shoot for shoot distribution,and phloemunloading in the root for root distribution.We found that AtABCG14 displays transporter activity toward multiple CK species and revealed its versatile roles in circular long-distance transport of iP-type CKs.These findings provide newinsights into the transport mechanisms of CKs and other plant hormones.
基金supported by the National Natural Science Foundation of China(81830004,31970755,and 31970173)the Local Grant(608285568031)。
文摘A key to tackling the coronavirus disease 2019(COVID-19)pandemic is to understand how severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)manages to outsmart host antiviral defense mechanisms.Stress granules(SGs),which are assembled during viral infection and function to sequester host and viral m RNAs and proteins,are part of the antiviral responses.Here,we show that the SARS-Co V-2 nucleocapsid(N)protein,an RNA binding protein essential for viral production,interacted with RasGTPase-activating protein SH3-domain-binding protein(G3 BP)and disrupted SG assembly,both of which require intrinsically disordered region1(IDR1)in N protein.The N protein partitioned into SGs through liquid-liquid phase separation with G3 BP,and blocked the interaction of G3 BP1 with other SG-related proteins.Moreover,the N protein domains important for phase separation with G3 BP and SG disassembly were required for SARS-Co V-2 viral production.We propose that N protein-mediated SG disassembly is crucial for SARS-Co V-2 production.
基金the National Natural Science Foundation of China(51872263 and 31970755)Zhejiang Provincial Natural Science Foundation(LZ19E020001 and LQ18B010002)。
文摘The hypoxic nature of solid tumors has severely negative effects on oxygen-based photodynamic therapy.In this study,we used porous Pt nanoparticles as a catalase(CAT)nanozyme,the second near-infrared(NIR-Ⅱ)region photothermal transition agents(PTAs),and carriers of photosensitizer chlorin e6(Ce6)to synthesize a composite nanosystem Pt-Ce6.In this system,Pt-Ce6 can continuously and stably decompose H2O2 into oxygen,thereby alleviating tumor hypoxia and improving the effect of photodynamic therapy(PDT).With 650 nm illumination,the reactive oxygen species(ROS)produced by Ce6 will decrease the mitochondrial membrane potential(MMP,ΔΨm)to release cytochrome c(Cyt-c)from the mitochondria into the cytoplasm,eventually leading to mitochondrial-mediated cellular apoptosis during the PDT process.In addition,Pt-Ce6 has good photothermal stability and high photothermal conversion efficiency(52.62%)in the NIR-II region.In U14 tumor-bearing mice,Pt-Ce6 completely suppressed tumor growth and recurrence under laser irradiation.Thus the nanocomposite shows excellent PDT/photothermal therapy(PTT)synergistic performance in vitro and in vivo.
基金This research was supported by grants from the National Key Technology Research and Development Program of China(2016YFD0101801)the Rice Cadmium Accumulation Characteristics Identification Project of the Seed Management Service Station of Hunan,Special Project of National Independent Innovation Demonstration Zone(2018XK2005)Science and Technology Innovation Program(2018NK1020).
文摘As a consequence of contamination of soil with heavy metals,cadmium accumulation in grain is of great concern worldwide,but especially in southern China.It is important to evaluate the Cd accumulation potential of grain before or when examining and approving new cultivars.An evaluation method and criteria for verifying Cd accumulation potential in rice are proposed,and the Cd accumulation potential of 56 mid-season indica hybrids collected from the provincial cultivar trials in 2016 were investigated.Genotype,environment and their interactions strongly affected the variation in grain Cd accumulation.Two hybrids were identified as slightly Cd accumulating.Hybrids with slight Cd accumulation potential would be suitable for safe grain production on polluted land(total Cd under 2.0 mg$kg–1)in Hunan Province(China)and should be considered for new cultivar evaluation and approval.This evaluation method and criterion could be applied for certifying Cd accumulation potential of rice cultivars.