Organoids are three-dimensional stem cell-derived models that offer a more physiologically relevant representation of tumor biology compared to traditional two-dimensional cell cultures or animal models.Organoids pres...Organoids are three-dimensional stem cell-derived models that offer a more physiologically relevant representation of tumor biology compared to traditional two-dimensional cell cultures or animal models.Organoids preserve the complex tissue architecture and cellular diversity of human cancers,enabling more accurate predictions of tumor growth,metastasis,and drug responses.Integration with microfluidic platforms,such as organ-on-a-chip systems,further enhances the ability to model tumor-environment interactions in real-time.Organoids facilitate in-depth exploration of tumor heterogeneity,molecular mechanisms,and the development of personalized treatment strategies when coupled with multi-omics technologies.Organoids provide a platform for investigating tumor-immune cell interactions,which aid in the design and testing of immune-based therapies and vaccines.Taken together,these features position organoids as a transformative tool in advancing cancer research and precision medicine.展开更多
Recent studies on leaf development demonstrate that the mechanism on the adaxial-abaxial polarity pattern formation could be well conserved among the far-related species, in which PHANTASTICA （PAHN）-Iike genes play ...Recent studies on leaf development demonstrate that the mechanism on the adaxial-abaxial polarity pattern formation could be well conserved among the far-related species, in which PHANTASTICA （PAHN）-Iike genes play important roles. In this study, we explored the conservation and diversity on functions of PHAN-Iike genes during the compound leaf development in Lotusjaponicus, a papilionoid legume. Two PHAN-Iike genes in L. japonicus, LjPHANa and LjPHANb, were found to originate from a gene duplication event and displayed different expression patterns during compound leaf development. Two mutants, reduced leafletsl （rell） and reduced leaflets3 （rel3）, which exhibited decreased adaxial identity of leaflets and reduced leaflet initiation, were identified and investigated. The expression patterns of both LjPHANs in rel mutants were altered and correlated with abnormalities of compound leaves. Our data suggest that LjPHANa and LjPHANb play important but divergent roles in regulating adaxial-abaxial polarity of compound leaves in L. japonicus.展开更多
Tumor microenvironment(TME),as the“soil”of tumor growth and metastasis,exhibits significant differences from normal physiological conditions.However,how to manipulate the distinctions to achieve the accurate therapy...Tumor microenvironment(TME),as the“soil”of tumor growth and metastasis,exhibits significant differences from normal physiological conditions.However,how to manipulate the distinctions to achieve the accurate therapy of primary and metastatic tumors is still a challenge.Herein,an innovative nanoreactor(AH@MBTF)is developed to utilize the apparent differences(copper concentration and H_(2)O_(2)level)between tumor cells and normal cells to eliminate primary tumor based on H_(2)O_(2)-dependent photothermal-chemodynamic therapy and suppress metastatic tumor through copper complexation.This nanoreactor is constructed using functionalized MSN incorporating benzoyl thiourea(BTU),triphenylphosphine(TPP),and folic acid(FA),while being co-loaded with horseradish peroxidase(HRP)and its substrate ABTS.During therapy,the BTU moieties on AH@MBTF could capture excessive copper(highly correlated with tumor metastasis),presenting exceptional anti-metastasis activity.Simultaneously,the complexation between BTU and copper triggers the formation of cuprous ions,which further react with H_(2)O_(2)to generate cytotoxic hydroxyl radical(•OH),inhibiting tumor growth via che-modynamic therapy.Additionally,the stepwise targeting of FA and TPP guides AH@MBTF to accurately accu-mulate in tumor mitochondria,containing abnormally high levels of H_(2)O_(2).As a catalyst,HRP mediates the oxidation reaction between ABTS and H_(2)O_(2)to yield activated ABTS•^(+).Upon 808 nm laser irradiation,the activated ABTS•^(+)performs tumor-specific photothermal therapy,achieving the ablation of primary tumor by raising the tissue temperature.Collectively,this intelligent nanoreactor possesses profound potential in inhib-iting tumor progression and metastasis.展开更多
Chemotherapy is restricted by efficient drug outflow due to the multiple drug resistance(MDR)in heterogenous nature of tumor.Herein,we present a dual-responsive hyaluronic acid(HA)nanocomposite hydrogel that can not o...Chemotherapy is restricted by efficient drug outflow due to the multiple drug resistance(MDR)in heterogenous nature of tumor.Herein,we present a dual-responsive hyaluronic acid(HA)nanocomposite hydrogel that can not only response to the tumor microenvironment but also enhance chemotherapy.This HA hydrogel consists of a core-shell SiO_(2)(GOD@SiO_(2)-Arg)and mesoporous silica nanoparticles(MSNs)with doxorubicin(DOX)as the cargo(DOX@MSN).It could rapidly release the GOD@SiO_(2)-Arg nanoparticles at the low p H tumor-specific environment due to the cleavage of imine bond.GOD@SiO_(2)-Arg activated by over-expressed glutathione(GSH)in tumor cells releases GOD due to the cleavage of disulfide bonds,which could oxidize glucose to produce hydrogen peroxide(H2O2)for in situ NO generation via reaction between Arg and H2O2.The validity of this study might provide a method to modulate the tumor microenvironment for enhancing chemotherapy.展开更多
The rate of soybean canopy establishment largely determines photoperiodic sensitivity,subsequently influencing yield potential.However,assessing the rate of soybean canopy development in large-scale field breeding tri...The rate of soybean canopy establishment largely determines photoperiodic sensitivity,subsequently influencing yield potential.However,assessing the rate of soybean canopy development in large-scale field breeding trials is both laborious and time-consuming.High-throughput phenotyping methods based on unmanned aerial vehicle(UAV)systems can be used to monitor and quantitatively describe the development of soybean canopies for different genotypes.In this study,high-resolution and time-series raw data from field soybean populations were collected using UAVs.展开更多
The pod and seed counts are important yield-related traits in soybean.High-precision soybean breeders face the major challenge of accurately phenotyping the number of pods and seeds in a high-throughput manner.Recent ...The pod and seed counts are important yield-related traits in soybean.High-precision soybean breeders face the major challenge of accurately phenotyping the number of pods and seeds in a high-throughput manner.Recent advances in artificial intelligence,especially deep learning(DL)models,have provided new avenues for high-throughput phenotyping of crop traits with increased precision.However,the available DL models are less effective for phenotyping pods that are densely packed and overlap in insitu soybean plants;thus,accurate phenotyping of the number of pods and seeds in soybean plant is an important challenge.To address this challenge,the present study proposed a bottom-up model,DEKR-SPrior(disentangled keypoint regression with structural prior),for insitu soybean pod phenotyping,which considers soybean pods and seeds analogous to human people and joints,respectively.In particular,we designed a novel structural prior(SPrior)module that utilizes cosine similarity to improve feature discrimination,which is important for differentiating closely located seeds from highly similar seeds.To further enhance the accuracy of pod location,we cropped full-sized images into smaller and high-resolution subimages for analysis.The results on our image datasets revealed that DEKR-SPrior outperformed multiple bottom-up models,viz.,Lightweight-Open Pose,OpenPose,HigherH R Net,and DEKR,reducing the mean absolute error from 25.81(in the original DEKR)to 21.11(in the DEKR-SPrior)in pod phenotyping.This paper demonstrated the great potential of DEKR-SPrior for plant phenotyping,and we hope that DEKR-SPrior will help future plant phenotyping.展开更多
Inflammatory response plays a critical role in myocardial infarction(MI)repair.The neutrophil apoptosis and subsequent macrophage ingestion can result in inflammation resolution and initiate regeneration,while the the...Inflammatory response plays a critical role in myocardial infarction(MI)repair.The neutrophil apoptosis and subsequent macrophage ingestion can result in inflammation resolution and initiate regeneration,while the therapeutic strategy that simulates and enhances this natural process has not been established.Here,we constructed engineered neutrophil apoptotic bodies(eNABs)to simulate natural neutrophil apoptosis,which regulated inflammation response and enhanced MI repair.The eNABs were fabricated by combining natural neutrophil apoptotic body membrane which has excellent inflammation-tropism and immunoregulatory properties,and mesoporous silica nanoparticles loaded with hexyl 5-aminolevulinate hydrochloride(HAL).The eNABs actively targeted to macrophages and the encapsulated HAL simultaneously initiated the biosynthesis pathway of heme to produce anti-inflammatory bilirubin after intracellular release,thereby further enhancing the anti-inflammation effects.In in vivo studies,the eNABs efficiently modulated inflammation responses in the infarcted region to ameliorate cardiac function.This study demonstrates an effective biomimetic construction strategy to regulate macrophage functions for MI repair.展开更多
During organ development, many key regulators have been identified in plant genomes, which play a conserved role among plant species to control the organ identities and/or determine the organ size and shape. It is int...During organ development, many key regulators have been identified in plant genomes, which play a conserved role among plant species to control the organ identities and/or determine the organ size and shape. It is intriguing whether these key regulators can acquire diverse function and be integrated into different molecular pathways among different species, giving rise to the immense diversity of organ forms in nature. In this study, we have characterized and cloned LATHYROIDES （LATH）, a classical locus in pea, whose mutation displays pleiotropic alteration of lateral growth of organs and predominant effects on tendril and dorsal petal development. LATH encodes a WUSCHEL-related home- oboxl （WOX1） transcription factor, which has a conserved function in determining organ lateral growth among different plant species. Furthermore, we showed that LATH regulated the expression level of TENDRIL-LESS （TL）, a key factor in the control of tendril development in compound leaf, and LATH genetically interacted with LOBED STANDARD （LST）, a floral dorsal factor, to affect the dorsal petal identity. Thus, LATH plays multiple roles during organ development in pea： it maintains a conserved function controlling organ lateral outgrowth, and modulates organ identities in compound leaf and zygomorphic flower development, respectively. Our data indicated that a key regulator can play important roles in different aspects of organ development and dedicate to the complexity of the molecular mechanism in the control of organ development so as to create distinct organ forms in different species.展开更多
Transcription factors and phytohormones have been reported to play crucial roles to regulate leaf complexity among plant species. Using the compound-leafed species Lotus japonicus, a model legume plant with five visib...Transcription factors and phytohormones have been reported to play crucial roles to regulate leaf complexity among plant species. Using the compound-leafed species Lotus japonicus, a model legume plant with five visible leaflets, we characterized four independent mutants with reduced leaf complexity, proliferating floral meristem （pfm）, proliferating floral organ-2 （pfo-2）, fused leaflets1 （ful1） and umbrella leaflets （uml）, which were further identified as loss-of-function mutants of Arabidopsis orthologs LEAFY （LFY ）, UNUSUAL FLORAL ORGANS （UFO）, CUP-SHAPED COTYLEDON 2 （CUC2） and PIN-FORMED 1 （PIN1）, respectively. Comparing the leaf development of wild-type and mutants by a scanning electron microscopy approach, leaflet initiation and/or dissection were found to be affected in these mutants. Expression and phenotype analysis indicated that PFM/LjLFY and PFO/LjUFO determined the basipetal leaflet initiation manner in L. japonicus. Genetic analysis of ful1 and uml mutants and their double mutants revealed that the CUC2-like gene and auxin pathway also participated in leaflet dissection in L. japonicus, and their functions might influence cytokinin biogenesis directly or indirectly. Our results here suggest that multiple genes were interplayed and played conserved functions in controlling leaf complexity during compound leaf development in L. japonicus.展开更多
Previous studies have demonstrated that petal shape and size in legume flowers are determined by two separate mechanisms, dorsoventral （DV） and organ internal （IN） asymmetric mechanisms, respectively. However, lit...Previous studies have demonstrated that petal shape and size in legume flowers are determined by two separate mechanisms, dorsoventral （DV） and organ internal （IN） asymmetric mechanisms, respectively. However, little is known about the molecular mechanisms controlling petal development in legumes. To address this question, we investigated petal development along the floral DV axis in Lotus japonicus with respect to cell and developmental biology by comparing wild-type legumes to mutants. Based on morphological markers, the entire course of petal development, from initiation to maturity, was grouped to define 3 phases or 13 stages. In terms of epidermal micromorphology from adaxial surface, mature petals were divided into several distinct domains, and characteristic epidermal cells of each petal differentiated at stage 9, while epidermal cells of all domains were observed until stage 12. TCP and MIXTA-like genes were found to be differentially expressed in various domains of petals at stages 9 and 12. Our results suggest that DV and IN mechanisms interplay at different stages of petal development, and their interaction at the cellular and molecular level guides the elaboration of domains within petals to achieve their ideal shape, and further suggest that TCP genes determine petal identity along the DV axis by regulatincl MIXTA-like clene expression.展开更多
Background:Corneal stromal stem cells(CSSC)reduce corneal inflammation,prevent fibrotic scarring,and regenerate transparent stromal tissue in injured corneas.These effects rely on factors produced by CSSC to block the...Background:Corneal stromal stem cells(CSSC)reduce corneal inflammation,prevent fibrotic scarring,and regenerate transparent stromal tissue in injured corneas.These effects rely on factors produced by CSSC to block the fibrotic gene expression.This study investigated the mechanism of the scar-free regeneration effect.Methods:Primary human CSSC(hCSSC)from donor corneal rims were cultivated to passage 3 and co-cultured with mouse macrophage RAW264.7 cells induced to M1 pro-inflammatory phenotype by treatment with interferonγand lipopolysaccharides,or to M2 anti-inflammatory phenotype by interleukin-4,in a Transwell system.The timecourse expression of human transforming growth factorβ3(hTGFβ3)and hTGFβ1 were examined by immunofluorescence and qPCR.TGFβ3 knockdown for>70%in hCSSC[hCSSC-TGFβ3(si)]was achieved by small interfering RNA transfection.Naïve CSSC and hCSSC-TGFβ3(si)were transplanted in a fibrin gel to mouse corneas,respectively,after wounding by stromal ablation.Corneal clarity and the expression of mouse inflammatory and fibrosis genes were examined.Results:hTGFβ3 was upregulated by hCSSC when co-cultured with RAW cells under M1 condition.Transplantation of hCSSC to wounded mouse corneas showed significant upregulation of hTGFβ3 at days 1 and 3 post-injury,along with the reduced expression of mouse inflammatory genes(CD80,C-X-C motif chemokine ligand 5,lipocalin 2,plasminogen activator urokinase receptor,pro-platelet basic protein,and secreted phosphoprotein 1).By day 14,hCSSC treatment significantly reduced the expression of fibrotic and scar tissue genes(fibronectin,hyaluronan synthase 2,Secreted protein acidic and cysteine rich,tenascin C,collagen 3a1 andα-smooth muscle actin),and the injured corneas remained clear.However,hCSSC-TGFβ3(si)lost these anti-inflammatory and anti-scarring functions,and the wounded corneas showed intense scarring.Conclusion:This study has demonstrated that the corneal regenerative effect of hCSSC is mediated by TGFβ3,inducing a scar-free tissue response.展开更多
Fruit size is largely defined by the number and size of cells in the fruit.Endoreduplication–a specialized cell cycle–is highly associated with cell expansion during tomato fruit growth.However,how endoreduplication...Fruit size is largely defined by the number and size of cells in the fruit.Endoreduplication–a specialized cell cycle–is highly associated with cell expansion during tomato fruit growth.However,how endoreduplication coupled with cell size is regulated remains poorly understood.In this study,we identified a zinc finger gene SlPZF1(Solanum lycopersicum PERICARP-ASSOCIATED ZINC FINGER PROTEIN 1)that was highly expressed in the pericarp of developing fruits.Plants with altered SlPZF1 expression produced smaller fruits due to the reduction in cell size associated with weakened endoreduplication.Overexpressing SlPZF1 delayed cell division phase by enhancing early expression of several key cell cycle regulators including SlCYCD3;1 and two plant specific mitotic cyclin-dependent protein kinase(SlCDKB1 and SlCDKB2)in the pericarp tissue.Furthermore,we identified 14 putative SlPZF1 interacting proteins(PZFIs)via yeast two hybrid screening.Several PZFIs,including Pre-mRNA-splicing factor(SlSMP1/PZFI4),PAPA-1-like conserved region family protein(PZFI6),Fanconi anemia complex components(PZFI3 and PZFI10)and bHLH transcription factor LONESOME HIGHWAY(SILHW/PZFI14),are putatively involved in cell cycle regulation.Our results demonstrate that fruit growth in tomato requires balanced expression of the novel cell size regulator SlPZF1.展开更多
基金supported by the Chinese Academy of Medical Sciences(Grant No.2021RU002)Beijing Natural Science Foundation(Grant No.Z240013)+2 种基金National Natural Science Foundation of China(Grant Nos.82450111,82388102,82373416,and 92259303)Beijing Research Ward Excellence Program(Grant Nos.BRWEP2024W034080200 and BRWEP2024W034080204)Peking University People’s Hospital Research and Development Funds(Grant No.RZG2024-02).
文摘Organoids are three-dimensional stem cell-derived models that offer a more physiologically relevant representation of tumor biology compared to traditional two-dimensional cell cultures or animal models.Organoids preserve the complex tissue architecture and cellular diversity of human cancers,enabling more accurate predictions of tumor growth,metastasis,and drug responses.Integration with microfluidic platforms,such as organ-on-a-chip systems,further enhances the ability to model tumor-environment interactions in real-time.Organoids facilitate in-depth exploration of tumor heterogeneity,molecular mechanisms,and the development of personalized treatment strategies when coupled with multi-omics technologies.Organoids provide a platform for investigating tumor-immune cell interactions,which aid in the design and testing of immune-based therapies and vaccines.Taken together,these features position organoids as a transformative tool in advancing cancer research and precision medicine.
文摘Recent studies on leaf development demonstrate that the mechanism on the adaxial-abaxial polarity pattern formation could be well conserved among the far-related species, in which PHANTASTICA （PAHN）-Iike genes play important roles. In this study, we explored the conservation and diversity on functions of PHAN-Iike genes during the compound leaf development in Lotusjaponicus, a papilionoid legume. Two PHAN-Iike genes in L. japonicus, LjPHANa and LjPHANb, were found to originate from a gene duplication event and displayed different expression patterns during compound leaf development. Two mutants, reduced leafletsl （rell） and reduced leaflets3 （rel3）, which exhibited decreased adaxial identity of leaflets and reduced leaflet initiation, were identified and investigated. The expression patterns of both LjPHANs in rel mutants were altered and correlated with abnormalities of compound leaves. Our data suggest that LjPHANa and LjPHANb play important but divergent roles in regulating adaxial-abaxial polarity of compound leaves in L. japonicus.
基金supported by the National High Level Talents Special Support Plan(X.C.)the National Natural Science Foundation of China(82272141 to X.C.)+4 种基金the“Young Talent Support Plan”of Xi’an Jiaotong University(X.C.)the Shaanxi Innovative Research Team of Science and Technology(S2023-ZC-TD-0152)the Natural Science Foundation of Shaanxi Province(2022JZ-48 to X.C.)the National Key Research and Development Program of China(2023YFC2509104 to X.C.)the Postdoctoral Science Foundation of China(2023M732812 to T.L.).
文摘Tumor microenvironment(TME),as the“soil”of tumor growth and metastasis,exhibits significant differences from normal physiological conditions.However,how to manipulate the distinctions to achieve the accurate therapy of primary and metastatic tumors is still a challenge.Herein,an innovative nanoreactor(AH@MBTF)is developed to utilize the apparent differences(copper concentration and H_(2)O_(2)level)between tumor cells and normal cells to eliminate primary tumor based on H_(2)O_(2)-dependent photothermal-chemodynamic therapy and suppress metastatic tumor through copper complexation.This nanoreactor is constructed using functionalized MSN incorporating benzoyl thiourea(BTU),triphenylphosphine(TPP),and folic acid(FA),while being co-loaded with horseradish peroxidase(HRP)and its substrate ABTS.During therapy,the BTU moieties on AH@MBTF could capture excessive copper(highly correlated with tumor metastasis),presenting exceptional anti-metastasis activity.Simultaneously,the complexation between BTU and copper triggers the formation of cuprous ions,which further react with H_(2)O_(2)to generate cytotoxic hydroxyl radical(•OH),inhibiting tumor growth via che-modynamic therapy.Additionally,the stepwise targeting of FA and TPP guides AH@MBTF to accurately accu-mulate in tumor mitochondria,containing abnormally high levels of H_(2)O_(2).As a catalyst,HRP mediates the oxidation reaction between ABTS and H_(2)O_(2)to yield activated ABTS•^(+).Upon 808 nm laser irradiation,the activated ABTS•^(+)performs tumor-specific photothermal therapy,achieving the ablation of primary tumor by raising the tissue temperature.Collectively,this intelligent nanoreactor possesses profound potential in inhib-iting tumor progression and metastasis.
基金supported by Sichuan Science and Technology Program(No.2022NSFSC0363)the Introduction Program of Scientific Researcher of Sichuan University of Science&Engineering(No.2020RC40)Key Laboratories of Fine Chemicals and Surfactants in Sichuan Provincial Universities(No.2020JXY02)。
文摘Chemotherapy is restricted by efficient drug outflow due to the multiple drug resistance(MDR)in heterogenous nature of tumor.Herein,we present a dual-responsive hyaluronic acid(HA)nanocomposite hydrogel that can not only response to the tumor microenvironment but also enhance chemotherapy.This HA hydrogel consists of a core-shell SiO_(2)(GOD@SiO_(2)-Arg)and mesoporous silica nanoparticles(MSNs)with doxorubicin(DOX)as the cargo(DOX@MSN).It could rapidly release the GOD@SiO_(2)-Arg nanoparticles at the low p H tumor-specific environment due to the cleavage of imine bond.GOD@SiO_(2)-Arg activated by over-expressed glutathione(GSH)in tumor cells releases GOD due to the cleavage of disulfide bonds,which could oxidize glucose to produce hydrogen peroxide(H2O2)for in situ NO generation via reaction between Arg and H2O2.The validity of this study might provide a method to modulate the tumor microenvironment for enhancing chemotherapy.
基金supported by the National Natural Science Foundation of China(grant no.U21A20215)Zhejiang Lab(grant no.2021PE0AC04)+1 种基金Hainan Yazhou Bay Seed Laboratory(B21HJ0101)the Natural Science Foundation of Jilin Province(20220101277JC).
文摘The rate of soybean canopy establishment largely determines photoperiodic sensitivity,subsequently influencing yield potential.However,assessing the rate of soybean canopy development in large-scale field breeding trials is both laborious and time-consuming.High-throughput phenotyping methods based on unmanned aerial vehicle(UAV)systems can be used to monitor and quantitatively describe the development of soybean canopies for different genotypes.In this study,high-resolution and time-series raw data from field soybean populations were collected using UAVs.
基金supported in part by the National Key Research and Development Program of China(2023YFD-1202600)the National Natural Science Foundation of China(62103380)+3 种基金the Research and Development Project from the Department of Science and Technology of Zhejiang Province(2023C01042)Soybean Intelligent Computational Breeding and Application of the Zhejiang Lab(2021PE0AC04)Intelligent Technology and Platform Development for Rice Breeding of the Zhejiang Lab(2021PE0AC05)Fine-grained Semantic Modeling and Cross modal Encoding-Decoding for Multilingual Scene Text Extraction(2022M722911).
文摘The pod and seed counts are important yield-related traits in soybean.High-precision soybean breeders face the major challenge of accurately phenotyping the number of pods and seeds in a high-throughput manner.Recent advances in artificial intelligence,especially deep learning(DL)models,have provided new avenues for high-throughput phenotyping of crop traits with increased precision.However,the available DL models are less effective for phenotyping pods that are densely packed and overlap in insitu soybean plants;thus,accurate phenotyping of the number of pods and seeds in soybean plant is an important challenge.To address this challenge,the present study proposed a bottom-up model,DEKR-SPrior(disentangled keypoint regression with structural prior),for insitu soybean pod phenotyping,which considers soybean pods and seeds analogous to human people and joints,respectively.In particular,we designed a novel structural prior(SPrior)module that utilizes cosine similarity to improve feature discrimination,which is important for differentiating closely located seeds from highly similar seeds.To further enhance the accuracy of pod location,we cropped full-sized images into smaller and high-resolution subimages for analysis.The results on our image datasets revealed that DEKR-SPrior outperformed multiple bottom-up models,viz.,Lightweight-Open Pose,OpenPose,HigherH R Net,and DEKR,reducing the mean absolute error from 25.81(in the original DEKR)to 21.11(in the DEKR-SPrior)in pod phenotyping.This paper demonstrated the great potential of DEKR-SPrior for plant phenotyping,and we hope that DEKR-SPrior will help future plant phenotyping.
基金This work was supported by National Key Research and Development Program of China(2016YFC1101400)National Natural Science Foundation of China(31800817)+4 种基金Innovative Talent Project of Shaanxi province(2020KJXX-057)National Natural Science Foundation of China(31870970)National Natural Science Foundation of China(81991504)Key Research and Development Program of Shaanxi Province(2019SF-073)Young Talent Support Program of Stomatology of FMMU(41741835-MZ2020D5).
文摘Inflammatory response plays a critical role in myocardial infarction(MI)repair.The neutrophil apoptosis and subsequent macrophage ingestion can result in inflammation resolution and initiate regeneration,while the therapeutic strategy that simulates and enhances this natural process has not been established.Here,we constructed engineered neutrophil apoptotic bodies(eNABs)to simulate natural neutrophil apoptosis,which regulated inflammation response and enhanced MI repair.The eNABs were fabricated by combining natural neutrophil apoptotic body membrane which has excellent inflammation-tropism and immunoregulatory properties,and mesoporous silica nanoparticles loaded with hexyl 5-aminolevulinate hydrochloride(HAL).The eNABs actively targeted to macrophages and the encapsulated HAL simultaneously initiated the biosynthesis pathway of heme to produce anti-inflammatory bilirubin after intracellular release,thereby further enhancing the anti-inflammation effects.In in vivo studies,the eNABs efficiently modulated inflammation responses in the infarcted region to ameliorate cardiac function.This study demonstrates an effective biomimetic construction strategy to regulate macrophage functions for MI repair.
基金National Natural Science Foundation of China，Science and Technology Planning Project of Guangdong Province,China
文摘During organ development, many key regulators have been identified in plant genomes, which play a conserved role among plant species to control the organ identities and/or determine the organ size and shape. It is intriguing whether these key regulators can acquire diverse function and be integrated into different molecular pathways among different species, giving rise to the immense diversity of organ forms in nature. In this study, we have characterized and cloned LATHYROIDES （LATH）, a classical locus in pea, whose mutation displays pleiotropic alteration of lateral growth of organs and predominant effects on tendril and dorsal petal development. LATH encodes a WUSCHEL-related home- oboxl （WOX1） transcription factor, which has a conserved function in determining organ lateral growth among different plant species. Furthermore, we showed that LATH regulated the expression level of TENDRIL-LESS （TL）, a key factor in the control of tendril development in compound leaf, and LATH genetically interacted with LOBED STANDARD （LST）, a floral dorsal factor, to affect the dorsal petal identity. Thus, LATH plays multiple roles during organ development in pea： it maintains a conserved function controlling organ lateral outgrowth, and modulates organ identities in compound leaf and zygomorphic flower development, respectively. Our data indicated that a key regulator can play important roles in different aspects of organ development and dedicate to the complexity of the molecular mechanism in the control of organ development so as to create distinct organ forms in different species.
基金supported by the National Natural Science Foundation of China(30930009)the Ministry of Agriculture of China for Transgenic Research(2011ZX08009-003)the Foundation from the Institute of Plant Physiology and Ecology,SIBS
文摘Transcription factors and phytohormones have been reported to play crucial roles to regulate leaf complexity among plant species. Using the compound-leafed species Lotus japonicus, a model legume plant with five visible leaflets, we characterized four independent mutants with reduced leaf complexity, proliferating floral meristem （pfm）, proliferating floral organ-2 （pfo-2）, fused leaflets1 （ful1） and umbrella leaflets （uml）, which were further identified as loss-of-function mutants of Arabidopsis orthologs LEAFY （LFY ）, UNUSUAL FLORAL ORGANS （UFO）, CUP-SHAPED COTYLEDON 2 （CUC2） and PIN-FORMED 1 （PIN1）, respectively. Comparing the leaf development of wild-type and mutants by a scanning electron microscopy approach, leaflet initiation and/or dissection were found to be affected in these mutants. Expression and phenotype analysis indicated that PFM/LjLFY and PFO/LjUFO determined the basipetal leaflet initiation manner in L. japonicus. Genetic analysis of ful1 and uml mutants and their double mutants revealed that the CUC2-like gene and auxin pathway also participated in leaflet dissection in L. japonicus, and their functions might influence cytokinin biogenesis directly or indirectly. Our results here suggest that multiple genes were interplayed and played conserved functions in controlling leaf complexity during compound leaf development in L. japonicus.
基金supported by the Ministry of Agriculture of China for Transgenic Research(2011ZX08009003and2009ZX08009-112B)the National Natural Science Foundation of China(30930009and30528016)the Instituteof Plant Physiology and Ecology,SIBS
文摘Previous studies have demonstrated that petal shape and size in legume flowers are determined by two separate mechanisms, dorsoventral （DV） and organ internal （IN） asymmetric mechanisms, respectively. However, little is known about the molecular mechanisms controlling petal development in legumes. To address this question, we investigated petal development along the floral DV axis in Lotus japonicus with respect to cell and developmental biology by comparing wild-type legumes to mutants. Based on morphological markers, the entire course of petal development, from initiation to maturity, was grouped to define 3 phases or 13 stages. In terms of epidermal micromorphology from adaxial surface, mature petals were divided into several distinct domains, and characteristic epidermal cells of each petal differentiated at stage 9, while epidermal cells of all domains were observed until stage 12. TCP and MIXTA-like genes were found to be differentially expressed in various domains of petals at stages 9 and 12. Our results suggest that DV and IN mechanisms interplay at different stages of petal development, and their interaction at the cellular and molecular level guides the elaboration of domains within petals to achieve their ideal shape, and further suggest that TCP genes determine petal identity along the DV axis by regulatincl MIXTA-like clene expression.
基金This work was supported by the Department of Defence Grant W81WH-19-1-0778(JLF,YD),NIH Grants RO1 EY016415(JLF)and P30 EY008098(JLF),Stein Innovator Award from Research to Prevent Blindness(JLF),Eye and Ear Foundation of Pittsburgh,and Louis J Fox Centre for Vision Restoration.
文摘Background:Corneal stromal stem cells(CSSC)reduce corneal inflammation,prevent fibrotic scarring,and regenerate transparent stromal tissue in injured corneas.These effects rely on factors produced by CSSC to block the fibrotic gene expression.This study investigated the mechanism of the scar-free regeneration effect.Methods:Primary human CSSC(hCSSC)from donor corneal rims were cultivated to passage 3 and co-cultured with mouse macrophage RAW264.7 cells induced to M1 pro-inflammatory phenotype by treatment with interferonγand lipopolysaccharides,or to M2 anti-inflammatory phenotype by interleukin-4,in a Transwell system.The timecourse expression of human transforming growth factorβ3(hTGFβ3)and hTGFβ1 were examined by immunofluorescence and qPCR.TGFβ3 knockdown for>70%in hCSSC[hCSSC-TGFβ3(si)]was achieved by small interfering RNA transfection.Naïve CSSC and hCSSC-TGFβ3(si)were transplanted in a fibrin gel to mouse corneas,respectively,after wounding by stromal ablation.Corneal clarity and the expression of mouse inflammatory and fibrosis genes were examined.Results:hTGFβ3 was upregulated by hCSSC when co-cultured with RAW cells under M1 condition.Transplantation of hCSSC to wounded mouse corneas showed significant upregulation of hTGFβ3 at days 1 and 3 post-injury,along with the reduced expression of mouse inflammatory genes(CD80,C-X-C motif chemokine ligand 5,lipocalin 2,plasminogen activator urokinase receptor,pro-platelet basic protein,and secreted phosphoprotein 1).By day 14,hCSSC treatment significantly reduced the expression of fibrotic and scar tissue genes(fibronectin,hyaluronan synthase 2,Secreted protein acidic and cysteine rich,tenascin C,collagen 3a1 andα-smooth muscle actin),and the injured corneas remained clear.However,hCSSC-TGFβ3(si)lost these anti-inflammatory and anti-scarring functions,and the wounded corneas showed intense scarring.Conclusion:This study has demonstrated that the corneal regenerative effect of hCSSC is mediated by TGFβ3,inducing a scar-free tissue response.
基金The work was supported by National Key Research and Development Program of China(2016YFD0101900)the National Natural Science Foundation of China(31672164)Agriculture and Rural Affairs Commission of Shanghai municipality(Agriculture Applied Technology Development Program,HuNongKeGong Grant No.2015-6-1-7).
文摘Fruit size is largely defined by the number and size of cells in the fruit.Endoreduplication–a specialized cell cycle–is highly associated with cell expansion during tomato fruit growth.However,how endoreduplication coupled with cell size is regulated remains poorly understood.In this study,we identified a zinc finger gene SlPZF1(Solanum lycopersicum PERICARP-ASSOCIATED ZINC FINGER PROTEIN 1)that was highly expressed in the pericarp of developing fruits.Plants with altered SlPZF1 expression produced smaller fruits due to the reduction in cell size associated with weakened endoreduplication.Overexpressing SlPZF1 delayed cell division phase by enhancing early expression of several key cell cycle regulators including SlCYCD3;1 and two plant specific mitotic cyclin-dependent protein kinase(SlCDKB1 and SlCDKB2)in the pericarp tissue.Furthermore,we identified 14 putative SlPZF1 interacting proteins(PZFIs)via yeast two hybrid screening.Several PZFIs,including Pre-mRNA-splicing factor(SlSMP1/PZFI4),PAPA-1-like conserved region family protein(PZFI6),Fanconi anemia complex components(PZFI3 and PZFI10)and bHLH transcription factor LONESOME HIGHWAY(SILHW/PZFI14),are putatively involved in cell cycle regulation.Our results demonstrate that fruit growth in tomato requires balanced expression of the novel cell size regulator SlPZF1.
