The demand for Erigeron breviscapus,a medicinal Compositae plant with cardiovascular therapeutic properties,has been increasing by 15%annually,exceeding production capacity and necessitating improvements in yield and ...The demand for Erigeron breviscapus,a medicinal Compositae plant with cardiovascular therapeutic properties,has been increasing by 15%annually,exceeding production capacity and necessitating improvements in yield and bioactive compound content.Genetic transformation remains essential for functional genomics,yet current Agrobacterium and biolistic methods are inefficient and expensive.In this study,we cloned the full-length sequences of the BABY BOOM,WUSCHEL and GROWTH-REGULATING FACTOR(GRF)genes of E.breviscapus and then transformed them into E.breviscapus explants.The transformation efficiency for the GRF gene reached 45%,and all the transgenic E.breviscapus plants were fertile without obvious developmental defects.Furthermore,we inserted EbGRF4 and Cas9-EbPDS-sgRNA into the same vector for Agrobacterium-mediated transformation to effectively knock out the PDS gene,resulting in albino seedlings,with a gene editing efficiency of 33.3%.These findings provide a solid foundation for functional genomic research and the genetic improvement of E.breviscapus,as well as an important reference for establishing high-efficiency genetic transformation systems for other medicinal plants.展开更多
Cilia are indispensable for organ development and function,and their dysfunction causes a range of syndromic diseases known as ciliopathies,including obesity,cystic kidney disease,situs inversus,and male infertility(R...Cilia are indispensable for organ development and function,and their dysfunction causes a range of syndromic diseases known as ciliopathies,including obesity,cystic kidney disease,situs inversus,and male infertility(Reiter and Leroux,2017;Wallmeier et al.,2020).To date,over 180 ciliopathy-associated genes have been identified(Reiter and Leroux,2017),yet the underlying mechanisms remain poorly understood.展开更多
Agrochemicals,especially plant growth regulators(PGRs),are extensively used to modulate endogenous phytohormone signals in small quantities,significantly infiuencing plant growth and development.Plant hormones typical...Agrochemicals,especially plant growth regulators(PGRs),are extensively used to modulate endogenous phytohormone signals in small quantities,significantly infiuencing plant growth and development.Plant hormones typically exhibit diverse chemical structures,with common examples including indole rings,terpenoid frameworks,adenine motifs,cyclic lactones,cyclopentanones,and steroidal compounds,which are extensively employed in pesticides.This article explores the interactions and biological activities of small molecules on proteins,enzymes,and other reactive sites involved in the biosynthesis,metabolism,transport,and signal transduction pathways of various plant hormones.Additionally,it analyzes the structure-activity relationships(SARs)of pesticides incorporating these structural motifs to elucidate the relationship between active fragments,pharmacophores,and targets,highlighting the characteristics of potent small molecules and their derivatives.This comprehensive review aims to provide novel perspectives for the development and design of pesticides,offering valuable insights for researchers in the field.展开更多
AIM:To explore the immune cell infiltration and molecular mechanisms of retinal ischemia-reperfusion injury(RIRI)to identify potential therapeutic targets.METHODS:In the bulk RNA-seq analysis,This study performed diff...AIM:To explore the immune cell infiltration and molecular mechanisms of retinal ischemia-reperfusion injury(RIRI)to identify potential therapeutic targets.METHODS:In the bulk RNA-seq analysis,This study performed differential gene expression analysis,weighted gene co-expression network analysis,and protein-protein interaction network analysis to identify hub genes.QuanTIseq was used to determine the composition of infiltrating immune cells.Following the identification of hub genes,single-cell RNA-seq analysis was employed to pinpoint the specific immune cell types expressing these hub genes.Cell-cell communication analysis to explore signaling pathways and interactions between immune cells was further performed.Finally,the expression of these key immune regulators in vivo using quantitative real-time polymerase chain reaction(qRT-PCR)was validated.RESULTS:Bulk RNA-seq analysis identified Stat2,Irf7,Irgm1,Igtp,Parp9,Irgm2,Nlrc5,and Tap1 as hub genes,with strong correlations to immune cell infiltration.Single-cell RNA-seq analysis further revealed six immune cell clusters,showing Irf7 predominantly in microglia and Tap1 in dendritic cells(DCs).And cell-cell communication analysis showed that microglia and DCs play central roles in coordinating immune activity.qRT-PCR validated the upregulation of these genes.CONCLUSION:In the acute phase of RIRI,Irf7 and Tap1 may be the potential therapeutic targets to reduce inflammation and promote neurological function recovery.展开更多
This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression...This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression pattern in OSCC,and the expression levels of PERs in OSCC patients are correlated with a favorable prognosis.PERs impact the occurrence and development of OSCC through multiple pathways.In the regulation of cell proliferation,they can function not only through cell cycle regultion but also via metabolic pathways.For example,PER1 can interact with receptors for activated C kinase 1(RACK1)and phosphatidylinositol 3-kinase(PI3K)through its PAS domain to inhibit glycolysis and thereby reduce cell proliferation.Regarding the regulation of cell death,PERs mediate various types of cell death in OSCC cells,such as p53-dependent apoptosis,protein kinase B(AKT)/mammalian target of rapamycin(mTOR)dependent autophagy,or hypoxia-inducible factor l-alpha(HIF-1a)mediated ferroptosis.In regulating epithelia-mesenchymal transition(EMT),PERs can lead to the downregulation of EMT related genes,such as zinc finger E-box binding homeobox 1/2(ZEBI/2),twist family BHLH transcription factor 1/2(TWIST1/2),and Vimentin,thereby influencing the migration and invasion capabilities of OSCC cells.In tumor angiogenesis,PERs exert regulatory effects on related factors,such as methionyl aminopeptidase 2(MetAP2)and vascular endothelial growth factor(VEGF).In the tumor immune microenvironment,PERs can inhibit the inhibitor of kappa B kinase(IKK)/nuclear factor kappa B(NF-kB)pathway and programmed cell death ligand 1(PD-L1)expression,thereby enhancing the cytotoxic effect of CD8+T cells on OSCC cells.In-depth studies focusing on elucidating the precise regulatory mechanisms of PERs can facilitate the development of therapeutic strategies targeting PERs,including restoration of PERs expression/activity,targeting PERs-regulated pathways,combination therapies,and chronotherapy.These furnish a theoretical foundation for formulating individualized treatment plans to achieve precise treatment for patients with OSCC.展开更多
This paper reviewed the toxicity,maximum residue limits(MRLs)and current residue status of commonly used plant growth regulators in vegetables,including 2,4-dichlorophenoxyacetic acid(2,4-D),naphthaleneacetic acid(NAA...This paper reviewed the toxicity,maximum residue limits(MRLs)and current residue status of commonly used plant growth regulators in vegetables,including 2,4-dichlorophenoxyacetic acid(2,4-D),naphthaleneacetic acid(NAA),ethephon,gibberellin,and paclobutrazol.Methods for reducing residues of plant growth regulators in vegetables were discussed,and recommendations and strategies for their application were proposed.展开更多
Background Zonal application maps are designed to represent field variability using key variables that can be translated into tailored management practices.For cotton,zonal maps for crop growth regulator(CGR)applicati...Background Zonal application maps are designed to represent field variability using key variables that can be translated into tailored management practices.For cotton,zonal maps for crop growth regulator(CGR)applications under variable-rate(VR)strategies are commonly based exclusively on vegetation indices(VIs)variability.However,VIs often saturate in dense crop vegetation areas,limiting their effectiveness in distinguishing variability in crop growth.This study aimed to compare unsupervised framework(UF)and supervised framework(SUF)approaches for generat-ing zonal application maps for CGR under VR conditions.During 2022-2023 agricultural seasons,an UF was employed to generate zonal maps based on locally collected field data on plant height of cotton,satellite imagery,soil texture,and phenology data.Subsequently,a SUF(based on historical data between 2020-2021 to 2022-2023 agricultural seasons)was developed to predict plant height using remote sensing and phenology data,aiming to replicate same zonal maps but without relying on direct field measurements of plant height.Both approaches were tested in three fields and on two different dates per field.Results The predictive model for plant height of SUF performed well,as indicated by the model metrics.However,when comparing zonal application maps for specific field-date combinations,the predicted plant height exhibited lower variability compared with field measurements.This led to variable compatibility between SUF maps,which utilized the model predictions,and the UF maps,which were based on the real field data.Fields characterized by much pronounced soil texture variability yielded the highest compatibility between the zonal application maps produced by both SUF and UF approaches.This was predominantly due to the greater consistency in estimating plant development patterns within these heterogeneous field environments.While VR application approach can facilitate product savings during the application operation,other key factors must be considered.These include the availability of specialized machinery required for this type of applications,as well as the inherent operational costs associated with applying a single CGR product which differs from the typical uniform rate applications that often integrate multi-ple inputs.Conclusion Predictive modeling shows promise for assisting in the creation of zonal application maps for VR of CGR applications.However,the degree of agreement with the actual variability in crop growth found in the field should be evaluated on a field-by-field basis.The SUF approach,which is based on plant heigh prediction,demonstrated potential for supporting the development of zonal application maps for VR of CGR applications.However,the degree to which this approach aligns itself with the actual variability in crop growth observed in the field may vary,necessi-tating field-by-field evaluation.展开更多
CRISPR-based tran-scription regulators(CRISPR-TRs)have revolutionized the field of synthetic biol-ogy by enabling tar-geted activation or repression of any de-sired gene.However,the majority of exist-ing inducible CRI...CRISPR-based tran-scription regulators(CRISPR-TRs)have revolutionized the field of synthetic biol-ogy by enabling tar-geted activation or repression of any de-sired gene.However,the majority of exist-ing inducible CRISPR-TRs are limited by their dependence on specific sequences,which restricts their flex-ibility and controllability in genetic engineering applications.In this study,we proposed a novel strategy to construct sequence-independent inducible CRISPR-TRs,which is achieved by the design of stem loop 2 in the single guide RNA(sgRNA).Under this strategy,by utiliz-ing toehold-mediated strand displacement(TMSD)reactions between small endogenous molecules(miR-20a and TK1 mRNA)and bridge RNA(bRNA)to link bRNA with sgRNA,we achieved synergistic transcriptional activation of VP64 and p65-HSF1 in response to en-dogenous molecules.To enable response to exogenous molecules,we added response se-quences and bRNA sequences to the 5'end of sgRNA to block sgRNA activity,and achieved activation of sgRNA by shearing the response sequence,called sequential unlimited interlock-ing(SUI).Compared with conventional sequence-restricted interlocking(spacer-blocking hairpin(SBH)),the transcriptional activation ratio between response and non-response to the Cas6A protein using our approach was increased by 2.28-fold.Our work presents a modular and versatile framework for endogenous and exogenous molecule-responsive CRISPR-TRs in mammalian cells,without limitations imposed by sequence dependence.展开更多
[Objective] This study aimed to investigate the influence of different plant growth regulators on apricot pollen germination and pollen tube growth. [Method] Pollens of six kinds of Xinjiang apricots were cultured in ...[Objective] This study aimed to investigate the influence of different plant growth regulators on apricot pollen germination and pollen tube growth. [Method] Pollens of six kinds of Xinjiang apricots were cultured in solid media supplemented with five plant growth regulators (GA3 , NAA, 2, 4-D, 6-BA, IAA). Then the rate of pollen germination and the length of pollen tube were respectively measured. [Result] In a certain concentration range, GA3 most significantly promoted the pollen germination and the pollen tube growth of Shushanggan, Kalayulvke, Dayoujia, Yiliakeyulvke and Kabakehuanna; NNA had the strongest improvement function on Kumaiti’s pollen germination and pollen tube growth. [Conclusion] All the five plant growth regulators promoted the pollen germination and the pollen tube growth of apricots at low concentration but inhibited them at high concentration.展开更多
基金supported by the National Natural Science Foundation of China(82160727)the Major Science and Technique Programs in Yunnan Province(202304BT090021-ML05)Yunnan Agricultural University research start-up Fund(KY2022-02).
文摘The demand for Erigeron breviscapus,a medicinal Compositae plant with cardiovascular therapeutic properties,has been increasing by 15%annually,exceeding production capacity and necessitating improvements in yield and bioactive compound content.Genetic transformation remains essential for functional genomics,yet current Agrobacterium and biolistic methods are inefficient and expensive.In this study,we cloned the full-length sequences of the BABY BOOM,WUSCHEL and GROWTH-REGULATING FACTOR(GRF)genes of E.breviscapus and then transformed them into E.breviscapus explants.The transformation efficiency for the GRF gene reached 45%,and all the transgenic E.breviscapus plants were fertile without obvious developmental defects.Furthermore,we inserted EbGRF4 and Cas9-EbPDS-sgRNA into the same vector for Agrobacterium-mediated transformation to effectively knock out the PDS gene,resulting in albino seedlings,with a gene editing efficiency of 33.3%.These findings provide a solid foundation for functional genomic research and the genetic improvement of E.breviscapus,as well as an important reference for establishing high-efficiency genetic transformation systems for other medicinal plants.
基金supported by grants from the National Key Research and Development Program of China(2019YFA0802704)the National Natural Science Foundation of China(31771620)+2 种基金the Natural Science Foundation of Chongqing,China(CSTB2022NSCQMSX1424)Research Startup Fund of Southwest University(SWU117064)Open Research Fund of National Health Commission Key Laboratory of Birth Defects Prevention&Henan Key Laboratory of Population Defects Prevention(ZD202302)。
文摘Cilia are indispensable for organ development and function,and their dysfunction causes a range of syndromic diseases known as ciliopathies,including obesity,cystic kidney disease,situs inversus,and male infertility(Reiter and Leroux,2017;Wallmeier et al.,2020).To date,over 180 ciliopathy-associated genes have been identified(Reiter and Leroux,2017),yet the underlying mechanisms remain poorly understood.
基金The financial support from the National Key Research and Development Program of China(No.2023YFD1700600)。
文摘Agrochemicals,especially plant growth regulators(PGRs),are extensively used to modulate endogenous phytohormone signals in small quantities,significantly infiuencing plant growth and development.Plant hormones typically exhibit diverse chemical structures,with common examples including indole rings,terpenoid frameworks,adenine motifs,cyclic lactones,cyclopentanones,and steroidal compounds,which are extensively employed in pesticides.This article explores the interactions and biological activities of small molecules on proteins,enzymes,and other reactive sites involved in the biosynthesis,metabolism,transport,and signal transduction pathways of various plant hormones.Additionally,it analyzes the structure-activity relationships(SARs)of pesticides incorporating these structural motifs to elucidate the relationship between active fragments,pharmacophores,and targets,highlighting the characteristics of potent small molecules and their derivatives.This comprehensive review aims to provide novel perspectives for the development and design of pesticides,offering valuable insights for researchers in the field.
基金Supported by the National Natural Science Foundation of China(No.82071312).
文摘AIM:To explore the immune cell infiltration and molecular mechanisms of retinal ischemia-reperfusion injury(RIRI)to identify potential therapeutic targets.METHODS:In the bulk RNA-seq analysis,This study performed differential gene expression analysis,weighted gene co-expression network analysis,and protein-protein interaction network analysis to identify hub genes.QuanTIseq was used to determine the composition of infiltrating immune cells.Following the identification of hub genes,single-cell RNA-seq analysis was employed to pinpoint the specific immune cell types expressing these hub genes.Cell-cell communication analysis to explore signaling pathways and interactions between immune cells was further performed.Finally,the expression of these key immune regulators in vivo using quantitative real-time polymerase chain reaction(qRT-PCR)was validated.RESULTS:Bulk RNA-seq analysis identified Stat2,Irf7,Irgm1,Igtp,Parp9,Irgm2,Nlrc5,and Tap1 as hub genes,with strong correlations to immune cell infiltration.Single-cell RNA-seq analysis further revealed six immune cell clusters,showing Irf7 predominantly in microglia and Tap1 in dendritic cells(DCs).And cell-cell communication analysis showed that microglia and DCs play central roles in coordinating immune activity.qRT-PCR validated the upregulation of these genes.CONCLUSION:In the acute phase of RIRI,Irf7 and Tap1 may be the potential therapeutic targets to reduce inflammation and promote neurological function recovery.
基金supported by the following funding:National Natural Science Foundations of China(82002888,82272899 and 82370974)Sichuan Science and Technology Program(2022YFS0207 and 2023YFS0127)+1 种基金Scientific Research Foundation,WestChinaHospital of Stomatology SichuanUniversity(RCDWJS2021-8)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-004).
文摘This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression pattern in OSCC,and the expression levels of PERs in OSCC patients are correlated with a favorable prognosis.PERs impact the occurrence and development of OSCC through multiple pathways.In the regulation of cell proliferation,they can function not only through cell cycle regultion but also via metabolic pathways.For example,PER1 can interact with receptors for activated C kinase 1(RACK1)and phosphatidylinositol 3-kinase(PI3K)through its PAS domain to inhibit glycolysis and thereby reduce cell proliferation.Regarding the regulation of cell death,PERs mediate various types of cell death in OSCC cells,such as p53-dependent apoptosis,protein kinase B(AKT)/mammalian target of rapamycin(mTOR)dependent autophagy,or hypoxia-inducible factor l-alpha(HIF-1a)mediated ferroptosis.In regulating epithelia-mesenchymal transition(EMT),PERs can lead to the downregulation of EMT related genes,such as zinc finger E-box binding homeobox 1/2(ZEBI/2),twist family BHLH transcription factor 1/2(TWIST1/2),and Vimentin,thereby influencing the migration and invasion capabilities of OSCC cells.In tumor angiogenesis,PERs exert regulatory effects on related factors,such as methionyl aminopeptidase 2(MetAP2)and vascular endothelial growth factor(VEGF).In the tumor immune microenvironment,PERs can inhibit the inhibitor of kappa B kinase(IKK)/nuclear factor kappa B(NF-kB)pathway and programmed cell death ligand 1(PD-L1)expression,thereby enhancing the cytotoxic effect of CD8+T cells on OSCC cells.In-depth studies focusing on elucidating the precise regulatory mechanisms of PERs can facilitate the development of therapeutic strategies targeting PERs,including restoration of PERs expression/activity,targeting PERs-regulated pathways,combination therapies,and chronotherapy.These furnish a theoretical foundation for formulating individualized treatment plans to achieve precise treatment for patients with OSCC.
文摘This paper reviewed the toxicity,maximum residue limits(MRLs)and current residue status of commonly used plant growth regulators in vegetables,including 2,4-dichlorophenoxyacetic acid(2,4-D),naphthaleneacetic acid(NAA),ethephon,gibberellin,and paclobutrazol.Methods for reducing residues of plant growth regulators in vegetables were discussed,and recommendations and strategies for their application were proposed.
文摘Background Zonal application maps are designed to represent field variability using key variables that can be translated into tailored management practices.For cotton,zonal maps for crop growth regulator(CGR)applications under variable-rate(VR)strategies are commonly based exclusively on vegetation indices(VIs)variability.However,VIs often saturate in dense crop vegetation areas,limiting their effectiveness in distinguishing variability in crop growth.This study aimed to compare unsupervised framework(UF)and supervised framework(SUF)approaches for generat-ing zonal application maps for CGR under VR conditions.During 2022-2023 agricultural seasons,an UF was employed to generate zonal maps based on locally collected field data on plant height of cotton,satellite imagery,soil texture,and phenology data.Subsequently,a SUF(based on historical data between 2020-2021 to 2022-2023 agricultural seasons)was developed to predict plant height using remote sensing and phenology data,aiming to replicate same zonal maps but without relying on direct field measurements of plant height.Both approaches were tested in three fields and on two different dates per field.Results The predictive model for plant height of SUF performed well,as indicated by the model metrics.However,when comparing zonal application maps for specific field-date combinations,the predicted plant height exhibited lower variability compared with field measurements.This led to variable compatibility between SUF maps,which utilized the model predictions,and the UF maps,which were based on the real field data.Fields characterized by much pronounced soil texture variability yielded the highest compatibility between the zonal application maps produced by both SUF and UF approaches.This was predominantly due to the greater consistency in estimating plant development patterns within these heterogeneous field environments.While VR application approach can facilitate product savings during the application operation,other key factors must be considered.These include the availability of specialized machinery required for this type of applications,as well as the inherent operational costs associated with applying a single CGR product which differs from the typical uniform rate applications that often integrate multi-ple inputs.Conclusion Predictive modeling shows promise for assisting in the creation of zonal application maps for VR of CGR applications.However,the degree of agreement with the actual variability in crop growth found in the field should be evaluated on a field-by-field basis.The SUF approach,which is based on plant heigh prediction,demonstrated potential for supporting the development of zonal application maps for VR of CGR applications.However,the degree to which this approach aligns itself with the actual variability in crop growth observed in the field may vary,necessi-tating field-by-field evaluation.
基金supported by the National Natural Science Foundation of China(No.22073090,No.21991132,No.52021002)the National Key R&D Program of China(No.2020YFA0710700)the Funds of Youth Innovation Promotion Association,and the Fundamental Research Funds for the Central Universities(WK3450000009).
文摘CRISPR-based tran-scription regulators(CRISPR-TRs)have revolutionized the field of synthetic biol-ogy by enabling tar-geted activation or repression of any de-sired gene.However,the majority of exist-ing inducible CRISPR-TRs are limited by their dependence on specific sequences,which restricts their flex-ibility and controllability in genetic engineering applications.In this study,we proposed a novel strategy to construct sequence-independent inducible CRISPR-TRs,which is achieved by the design of stem loop 2 in the single guide RNA(sgRNA).Under this strategy,by utiliz-ing toehold-mediated strand displacement(TMSD)reactions between small endogenous molecules(miR-20a and TK1 mRNA)and bridge RNA(bRNA)to link bRNA with sgRNA,we achieved synergistic transcriptional activation of VP64 and p65-HSF1 in response to en-dogenous molecules.To enable response to exogenous molecules,we added response se-quences and bRNA sequences to the 5'end of sgRNA to block sgRNA activity,and achieved activation of sgRNA by shearing the response sequence,called sequential unlimited interlock-ing(SUI).Compared with conventional sequence-restricted interlocking(spacer-blocking hairpin(SBH)),the transcriptional activation ratio between response and non-response to the Cas6A protein using our approach was increased by 2.28-fold.Our work presents a modular and versatile framework for endogenous and exogenous molecule-responsive CRISPR-TRs in mammalian cells,without limitations imposed by sequence dependence.
基金Supported by Key Technology Integration and Demonstration of Xinjiang Characteristic Fruit Trees'High Efficiency and Safe Production,Science and Technical Plan Project of Xinjiang Uygur Autonomous Region(201130102)Key Technology Integration and Demonstration of Xinjiang Apricot Industrial Development,Science and Technical Plan Project of Xinjiang Uygur Autonomous Region(200931101)Financial Support from Xinjiang Uygur Autonomous Region Fruit Trees Key Subject~~
文摘[Objective] This study aimed to investigate the influence of different plant growth regulators on apricot pollen germination and pollen tube growth. [Method] Pollens of six kinds of Xinjiang apricots were cultured in solid media supplemented with five plant growth regulators (GA3 , NAA, 2, 4-D, 6-BA, IAA). Then the rate of pollen germination and the length of pollen tube were respectively measured. [Result] In a certain concentration range, GA3 most significantly promoted the pollen germination and the pollen tube growth of Shushanggan, Kalayulvke, Dayoujia, Yiliakeyulvke and Kabakehuanna; NNA had the strongest improvement function on Kumaiti’s pollen germination and pollen tube growth. [Conclusion] All the five plant growth regulators promoted the pollen germination and the pollen tube growth of apricots at low concentration but inhibited them at high concentration.