The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can...The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.展开更多
Three-Dimensional(3D)swirling flow structures,generated by a counter-rotating dualstage swirler in a confined chamber with a confinement ratio of 1.53,were experimentally investigated at Re=2.3×10^(5)using Tomogr...Three-Dimensional(3D)swirling flow structures,generated by a counter-rotating dualstage swirler in a confined chamber with a confinement ratio of 1.53,were experimentally investigated at Re=2.3×10^(5)using Tomographic Particle Image Velocimetry(Tomo-PIV)and planar Particle Image Velocimetry(PIV).Based on the analysis of the 3D time-averaged swirling flow structures and 3D Proper Orthogonal Decomposition(POD)of the Tomo-PIV data,typical coherent flow structures,including the Corner Recirculation Zone(CRZ),Central Recirculation Zone(CTRZ),and Lip Recirculation Zone(LRZ),were extracted.The counter-rotating dual-stage swirler with a Venturi flare generates the independence process of vortex breakdown from the main stage and pilot stage,leading to the formation of an LRZ and a smaller CTRZ near the nozzle outlet.The confinement squeezes the CRZ to the corner and causes a reverse rotation flow to limit the shape of the CTRZ.A large-scale flow structure caused by the main stage features an explosive breakup,flapping,and Precessing Vortex Core(PVC).The explosive breakup mode dominates the swirling flow structures owing to the expansion and construction of the main jet,whereas the flapping mode is related to the wake perturbation.Confinement limits the expansion of PVC and causes it to contract after the impacting area.展开更多
Objective:To establish a progressive research strategy for“colonic components analysis-efficacy verification and mechanism exploration-gut microbiota”,screen pharmacodynamic substances,and investigate their mechanis...Objective:To establish a progressive research strategy for“colonic components analysis-efficacy verification and mechanism exploration-gut microbiota”,screen pharmacodynamic substances,and investigate their mechanism via gut microbiota.Methods:The pharmacodynamics of Gegen Qinlian decoction(GQD)were assessed using a mouse model of dextran sulfate sodium-induced ulcerative colitis(UC).Ultra-performance liquid chromatographyquadrupole-orbitrap mass spectrometer was used to identify the prototype and metabolic components of GQD in the colon during UC.To analyze the structure and function of characteristic genera of GQD and its active components,16S rRNA sequencing was performed.Results:We identified 67 prototypic and 14 metabolic components of GQD in the UC colon.The primary prototype components are flavonoids and alkaloids,including puerarin(PUE),baicalin(BAI),and berberine(BER).The metabolism was predominantly sulfonation.Efficacy verification showed that the main active components,puerarin,baicalin,and berberine,had good therapeutic effects on UC.The results of 16S rRNA gene sequencing showed that GQD improved UC by regulating the structure and function of the gut microbiota.The abundance of gut microbiota involved in the metabolism of the prototype componentswas influenced by the corresponding components.The function prediction results showed that PUE was the most comparable to GQD,with 24 consistent pathways.BAI and BER showed comparable gut microbiota regulation pathways.Characteristic pathways of BER include glucometabolic processes.Conclusion:This study focused on the key issues in the gut microbiota pathway and developed a progressive research strategy to understand the transformation mechanisms of colonic components.This research systematically analyzed the active components and metabolic transformation of GQD in the colon during the pathological state of UC,as well as changes in the structure and function of the gut microbiota,clarified the mechanism of GQD and its active components in improving UC via the gut microbiota pathway.展开更多
Maize(Zea mays L.),a globally significant cereal crop,is produced in vast quantities worldwide.However,its growth is severely constrained by low temperatures,particularly during seed germination,which significantly im...Maize(Zea mays L.),a globally significant cereal crop,is produced in vast quantities worldwide.However,its growth is severely constrained by low temperatures,particularly during seed germination,which significantly impairs seedling emergence.In this study,genetic diversity across six germination-associated phenotypic traits(RGR,RSL,RTL,RRSA,RRV,and RSVI)of 304 inbred lines was analyzed,to evaluate the capacity of these lines for low-temperature tolerance.Genome-wide association study(GWAS)was carried out by combining six germination-associated phenotypic traits and genotypic data from 30-fold resequencing.The gene ZmBARK1 was identified through integrated GWAS and RNA-seq analyses,and its association with low-temperature tolerance during maize germination was validated by quantitative real-time PCR(qRT-PCR).ZmBARK1,encoding BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1,was located on the bin 4.09 region of maize chromosome 4.Amino acid comparison and subcellular localization analyses revealed that ZmBARK1 is highly homologous to AtBAK1 and is localized to the plasma membrane of the cell,which may be involved in regulating brassinosteroid(BR)signaling.In addition,we revealed the role of ZmBARK1 in low-temperature tolerance during maize germination.Compared with wild-type(WT),the ethyl methanesulfonate(EMS)mutant zmbark1 was characterized by substantially enhanced low-temperature tolerance.Overall,these findings provide promising candidate genes,improve low-temperature tolerance in maize,and advance the understanding of regulatory mechanisms underlying maize's response to low-temperature stress.展开更多
Three sandstone specimens common in rock engineering were selected to study the differences in the mechanical properties of rocks with different lithologies.The development and expansion of the internal cracks in the ...Three sandstone specimens common in rock engineering were selected to study the differences in the mechanical properties of rocks with different lithologies.The development and expansion of the internal cracks in the specimens were observed by combining the simulation system with the acoustic emission system.Through the combination of dynamic and static stresses,the deformation and damage of rocks under deep rock excavation and blasting were simulated.As the results show,the acoustic emission events of specimens with different lithologies under combined static and dynamic cyclic loading can be roughly divided into three phases:weakening,stabilizing,and surging periods.In addition,the acoustic emission characteristics of specimens with different lithologies show general consistency in different compression phases.The degree of fragmentation of specimens increases with the applied stress level;therefore,the stress level is one of the important factors influencing the damage pattern of specimens.The acoustic emission system was used to simulate the deformation and damage of rocks subjected to deep rock body excavation and engineering blasting.Cyclic dynamic perturbations under sinusoidal waves with a frequency of 5 Hz,a loading rate of 0.1 mm/min,a cyclic amplitude of 5 MPa,and a loading rate of 0.1 mm/min were applied to the three rock samples during the experiments.Among them,the fine-grained sandstones are the most sensitive to the sinusoidal cyclic perturbation,followed by the muddy siltstone and the medium-grained sandstones.On this basis,the acoustic emission energy release characteristics were analyzed,and the waveform characteristics in the damage evolution of the specimen under dynamic perturbation were studied by extracting the key points and searching for the main frequency eigenvalues.展开更多
Planting density is a major limiting factor for maize yield,and breeding for density tolerance has become an urgent issue.The leaf structure of the maize ear leaf is the main factor that restricts planting density and...Planting density is a major limiting factor for maize yield,and breeding for density tolerance has become an urgent issue.The leaf structure of the maize ear leaf is the main factor that restricts planting density and yield components.In this study,a natural population of 201 maize inbred lines was used for genome-wide association analysis,which identified nine SNPs on chromosomes 2,5,8,9,and 10 that were significantly associated with ear leaf type structure.Further verification through qRT-PCR confirmed the association of five candidate genes with these SNPs,with the Zm00001d008651 gene showing significant differential expression in the compact and flat maize inbred lines.Enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)databasessuggested that this gene is involved in the glycolysis process.An analysis of the basic properties of this gene revealed that it encodes a stable,basic protein consisting of 593 amino acids with some hydrophobic properties.The promoter region contains stress and hormone(abscisic acid(ABA))related elements.The mutant of this gene increased the first ear leaf angle(eLA)and leaf angle of the first leaf below the first ear(bLA)by 4.96 and 0.97°,respectively,compared with normal inbred lines.Overall,this research sheds light on the regulatory mechanism of ear and leaf structures that influence density tolerance and provides solid foundational work for the development of new varieties.展开更多
基金Hongguang Wu,Both authors contributed equally to this work and share first authorshipLing Dong,Both authors contributed equally to this work and share first authorship。
文摘The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.
基金supported by the National Natural Science Foundation of China(Nos.12232002,12072017,12002199,and 11721202)。
文摘Three-Dimensional(3D)swirling flow structures,generated by a counter-rotating dualstage swirler in a confined chamber with a confinement ratio of 1.53,were experimentally investigated at Re=2.3×10^(5)using Tomographic Particle Image Velocimetry(Tomo-PIV)and planar Particle Image Velocimetry(PIV).Based on the analysis of the 3D time-averaged swirling flow structures and 3D Proper Orthogonal Decomposition(POD)of the Tomo-PIV data,typical coherent flow structures,including the Corner Recirculation Zone(CRZ),Central Recirculation Zone(CTRZ),and Lip Recirculation Zone(LRZ),were extracted.The counter-rotating dual-stage swirler with a Venturi flare generates the independence process of vortex breakdown from the main stage and pilot stage,leading to the formation of an LRZ and a smaller CTRZ near the nozzle outlet.The confinement squeezes the CRZ to the corner and causes a reverse rotation flow to limit the shape of the CTRZ.A large-scale flow structure caused by the main stage features an explosive breakup,flapping,and Precessing Vortex Core(PVC).The explosive breakup mode dominates the swirling flow structures owing to the expansion and construction of the main jet,whereas the flapping mode is related to the wake perturbation.Confinement limits the expansion of PVC and causes it to contract after the impacting area.
基金supported by Fundamental Research Funds for the Central Universities(2022-ZXFZJJ-028).
文摘Objective:To establish a progressive research strategy for“colonic components analysis-efficacy verification and mechanism exploration-gut microbiota”,screen pharmacodynamic substances,and investigate their mechanism via gut microbiota.Methods:The pharmacodynamics of Gegen Qinlian decoction(GQD)were assessed using a mouse model of dextran sulfate sodium-induced ulcerative colitis(UC).Ultra-performance liquid chromatographyquadrupole-orbitrap mass spectrometer was used to identify the prototype and metabolic components of GQD in the colon during UC.To analyze the structure and function of characteristic genera of GQD and its active components,16S rRNA sequencing was performed.Results:We identified 67 prototypic and 14 metabolic components of GQD in the UC colon.The primary prototype components are flavonoids and alkaloids,including puerarin(PUE),baicalin(BAI),and berberine(BER).The metabolism was predominantly sulfonation.Efficacy verification showed that the main active components,puerarin,baicalin,and berberine,had good therapeutic effects on UC.The results of 16S rRNA gene sequencing showed that GQD improved UC by regulating the structure and function of the gut microbiota.The abundance of gut microbiota involved in the metabolism of the prototype componentswas influenced by the corresponding components.The function prediction results showed that PUE was the most comparable to GQD,with 24 consistent pathways.BAI and BER showed comparable gut microbiota regulation pathways.Characteristic pathways of BER include glucometabolic processes.Conclusion:This study focused on the key issues in the gut microbiota pathway and developed a progressive research strategy to understand the transformation mechanisms of colonic components.This research systematically analyzed the active components and metabolic transformation of GQD in the colon during the pathological state of UC,as well as changes in the structure and function of the gut microbiota,clarified the mechanism of GQD and its active components in improving UC via the gut microbiota pathway.
基金supported by the Key Research and Development Project of Heilongjiang Province(2022ZX02B01)the Natural Science Foundation Project of Heilongjiang Province(YQ2022C009)the Natural Science Foundation of Shandong Province(K22LB56)。
文摘Maize(Zea mays L.),a globally significant cereal crop,is produced in vast quantities worldwide.However,its growth is severely constrained by low temperatures,particularly during seed germination,which significantly impairs seedling emergence.In this study,genetic diversity across six germination-associated phenotypic traits(RGR,RSL,RTL,RRSA,RRV,and RSVI)of 304 inbred lines was analyzed,to evaluate the capacity of these lines for low-temperature tolerance.Genome-wide association study(GWAS)was carried out by combining six germination-associated phenotypic traits and genotypic data from 30-fold resequencing.The gene ZmBARK1 was identified through integrated GWAS and RNA-seq analyses,and its association with low-temperature tolerance during maize germination was validated by quantitative real-time PCR(qRT-PCR).ZmBARK1,encoding BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1,was located on the bin 4.09 region of maize chromosome 4.Amino acid comparison and subcellular localization analyses revealed that ZmBARK1 is highly homologous to AtBAK1 and is localized to the plasma membrane of the cell,which may be involved in regulating brassinosteroid(BR)signaling.In addition,we revealed the role of ZmBARK1 in low-temperature tolerance during maize germination.Compared with wild-type(WT),the ethyl methanesulfonate(EMS)mutant zmbark1 was characterized by substantially enhanced low-temperature tolerance.Overall,these findings provide promising candidate genes,improve low-temperature tolerance in maize,and advance the understanding of regulatory mechanisms underlying maize's response to low-temperature stress.
基金Open Project of State Key Laboratory for Geomechanics and Deep Underground Engineering in CUMTB,Grant/Award Number:SKLGDUEK2023National Natural Science Foundation of China,Grant/Award Number:52204101Natural Science Foundation of Shandong Province,Grant/Award Number:ZR2022QE137。
文摘Three sandstone specimens common in rock engineering were selected to study the differences in the mechanical properties of rocks with different lithologies.The development and expansion of the internal cracks in the specimens were observed by combining the simulation system with the acoustic emission system.Through the combination of dynamic and static stresses,the deformation and damage of rocks under deep rock excavation and blasting were simulated.As the results show,the acoustic emission events of specimens with different lithologies under combined static and dynamic cyclic loading can be roughly divided into three phases:weakening,stabilizing,and surging periods.In addition,the acoustic emission characteristics of specimens with different lithologies show general consistency in different compression phases.The degree of fragmentation of specimens increases with the applied stress level;therefore,the stress level is one of the important factors influencing the damage pattern of specimens.The acoustic emission system was used to simulate the deformation and damage of rocks subjected to deep rock body excavation and engineering blasting.Cyclic dynamic perturbations under sinusoidal waves with a frequency of 5 Hz,a loading rate of 0.1 mm/min,a cyclic amplitude of 5 MPa,and a loading rate of 0.1 mm/min were applied to the three rock samples during the experiments.Among them,the fine-grained sandstones are the most sensitive to the sinusoidal cyclic perturbation,followed by the muddy siltstone and the medium-grained sandstones.On this basis,the acoustic emission energy release characteristics were analyzed,and the waveform characteristics in the damage evolution of the specimen under dynamic perturbation were studied by extracting the key points and searching for the main frequency eigenvalues.
基金supported by the Key Research and Development Project of Heilongjiang Province,China(2022ZX02B01)。
文摘Planting density is a major limiting factor for maize yield,and breeding for density tolerance has become an urgent issue.The leaf structure of the maize ear leaf is the main factor that restricts planting density and yield components.In this study,a natural population of 201 maize inbred lines was used for genome-wide association analysis,which identified nine SNPs on chromosomes 2,5,8,9,and 10 that were significantly associated with ear leaf type structure.Further verification through qRT-PCR confirmed the association of five candidate genes with these SNPs,with the Zm00001d008651 gene showing significant differential expression in the compact and flat maize inbred lines.Enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)databasessuggested that this gene is involved in the glycolysis process.An analysis of the basic properties of this gene revealed that it encodes a stable,basic protein consisting of 593 amino acids with some hydrophobic properties.The promoter region contains stress and hormone(abscisic acid(ABA))related elements.The mutant of this gene increased the first ear leaf angle(eLA)and leaf angle of the first leaf below the first ear(bLA)by 4.96 and 0.97°,respectively,compared with normal inbred lines.Overall,this research sheds light on the regulatory mechanism of ear and leaf structures that influence density tolerance and provides solid foundational work for the development of new varieties.
