Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that pla...Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that plays an important role in a broad range of cellular activities from calcium regulation to protein synthesis and trafficking.In neurons,the ER extends from the soma through the axon to presynaptic terminals,and throughout the dendritic arbor into as many as half of all postsynaptic dendritic spines at any given time(Falahati et al.,2022).展开更多
Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are ne...Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.展开更多
5-Aminolevulinic acid(ALA),is a novel plant growth regulator that can enhance plant tolerance against salt stress.However,the molecular mechanism of ALA is not well studied.In this study,ALA improved salt tolerance of...5-Aminolevulinic acid(ALA),is a novel plant growth regulator that can enhance plant tolerance against salt stress.However,the molecular mechanism of ALA is not well studied.In this study,ALA improved salt tolerance of apple(Malus×domestica'Gala')when the detached leaves or cultured calli were used as the materials.The expression of MdWRKY71,a WRKY transcription factor(TF)gene was found to be responsive to NaCl as well as ALA treatment.Functional analysis showed that overexpressing(OE)-MdWRKY71 significantly improved the salt tolerance of the transgenic apple,while RNA interfering(RNAi)-MdWRKY71 reduced the salt tolerance.However,exogenous ALA alleviated the salt damage in the RNAi-MdWRKY71 apple.When MdWRKY71 was transferred into tobacco,the salt tolerance of transgenic plants was enhanced,which was further improved by exogenous ALA.Subsequently,MdWRKY71 bound to the W-box of promoters of MdSOS2,MdNHX1,MdCLC-g,MdSOD1,MdCAT1 and MdAPX1,transcriptionally activating the gene expressions.Since the genes are responsible for Na+and Cl-transport and antioxidant enzyme activity respectively,it can be concluded that MdWRKY71,a new TF,is involved in ALA-improved salt tolerance by regulating ion homeostasis and redox homeostasis.These results provided new insights into the transcriptional regulatory mechanism of ALA in enhancing apple salt tolerance.展开更多
Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rode...Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.展开更多
The proper flowering time of rose(Rosa hybrida)is vital for the market value of this horticultural crop,but the mechanism regulating this trait is largely unclear.Here,we found that the transcription factor SQUAMOSA P...The proper flowering time of rose(Rosa hybrida)is vital for the market value of this horticultural crop,but the mechanism regulating this trait is largely unclear.Here,we found that the transcription factor SQUAMOSA PROMOTER BINDING PROTEIN-LIKE4(RhSPL4)positively regulates flowering time in rose.Transient silencing or overexpression transgenic rose plants of RhSPL4 exhibited delayed or early flowering,respectively.Analysis of transcriptome data from transgenic lines overexpressing RhSPL4 compared to the wild type indicated that differentially expressed genes were significantly enriched in the circadian rhythm pathway.Among the proteins encoded by these genes,RhSPL4 binds to the promoter of PSEUDO-RESPONSE REGULATOR 5-LIKE(RhPRR5L),as revealed in yeast one-hybrid,dual-Luciferase/Renilla luciferase reporter,chromatin immunoprecipitation-quantitative PCR and electrophoretic mobility shift assay.Furthermore,RhSPL4 specifically binds to the478 to441 bp region of the RhPRR5L promoter and activates its transcription.The silencing of RhPRR5L delayed flowering time in rose,resembling the phenotype of RhSPL4-silenced plants.Together,these results indicate that the RhSPL4-RhPRR5L module positively regulates flowering time in rose,laying the foundation for the genetic improvement of flowering time in this important horticultural crop.展开更多
The postharvest senescence phase of table grapes comprises a series of biological processes.MicroRNAs(miRNAs)regulate downstream genes at the post-transcriptional level;however,whether miRNAs are involved in postharve...The postharvest senescence phase of table grapes comprises a series of biological processes.MicroRNAs(miRNAs)regulate downstream genes at the post-transcriptional level;however,whether miRNAs are involved in postharvest grape senescence remains unclear.We used small RNA sequencing to identify postharvest-related miRNAs in‘Red Globe'(Vitis vinifera)grapes harvested after 0,30,and 60 d of storage at 4℃(RG0,RG30,RG60).In total,42 known and 219 novel miRNA candidates were obtained.During fruit senescence,the expression of PC-3p-3343_1921,mi R2950,miR395k,miR2111,miR159c,miR169q,PC-5p-1112_4500,and miR167b changed signifcantly(P<0.05).Degradation sequencing identifed 218 targets associated with cell wall organization,tricarboxylic acid(TCA)cycling,pathogen defense,carbon metabolism,hormone signaling,the anthocyanin metabolism pathway,and energy regulation,of which ARF6,GRF3,TCP2,CP1,MYBA2,and WRKY72 were closely related to fruit senescence.We also verified that VIT_00s2146g00010,VIT_02s0012g01750,and VIT_03s0038g00160 with unknown functions are cleaved by senescence-related PC-5p-1112_4500 via the dual luciferase assay,and the transient transformation of grape berries showed that they regulate berry senescence.These results deepen our understanding of the role of mi RNAs in regulating grape berry senescence and prolonging the shelf life of horticultural products.Based on these results,we propose a new theoretical strategy for delaying the postharvest senescence of horticultural products by regulating the expression of key miRNAs(e.g.,PC-5p-1112_4500),thereby extending their shelf life.展开更多
In this study,a dynamic model for an inverted pendulum system(IPS)attached to a car is created,and two different control methods are applied to control the system.The designed control algorithms aim to stabilize the p...In this study,a dynamic model for an inverted pendulum system(IPS)attached to a car is created,and two different control methods are applied to control the system.The designed control algorithms aim to stabilize the pendulum arms in the upright position and the car to reach the equilibrium position.Grey Wolf Optimization-based Linear Quadratic Regulator(GWO-LQR)and GWO-based Fuzzy LQR(FLQR)control algorithms are used in the control process.To improve the performance of the LQR and FLQR methods,the optimum values of the coefficients corresponding to the foot points of the membership functions are determined by the GWO algorithm.Both a graphic and a numerical analysis of the outcomes are provided.In the comparative analysis,it is observed that the GWO-based FLQR method reduces the settling time by 22.58% and the maximum peak value by 18.2% when evaluated in terms of the angular response of the pendulum arm.Furthermore,this approach outperformed comparable research in the literature with a settling time of 2.4 s.These findings demonstrate that the suggested GWO-based FLQR controlmethod outperforms existing literature in terms of the time required for the pendulum arm to reach equilibrium.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
Maize(Zea mays L.)is one of the world's most important staple crops,and is used for manufacturing food,feed,and industrial products.A key factor in maize yield is the grain weight,which directly influences product...Maize(Zea mays L.)is one of the world's most important staple crops,and is used for manufacturing food,feed,and industrial products.A key factor in maize yield is the grain weight,which directly influences productivity.In this study,we revealed the role of smk23 in maize kernel development.The ethyl methanesulfonate mutant smk23 is characterized by substantially reduced kernel weight.Through map-based cloning,smk23 was found to be located on Chr5 and encode a putative B-type response regulator,Zm RR5.A change from G to A occurs in the coding sequence of Zm RR5,resulting in the early termination of smk23.In Arabidopsis,B-type response regulators are involved in cytokinin signaling.Histological analysis and in situ hybridization of the mutant revealed abnormal endosperm development,particularly in the basal endosperm transfer layer(BETL),a specialized tissue critical for nutrient transport from the maternal tissues to the developing kernel.Zm RR5 positively regulates key genes involved in BETL development and function,including MRP1 and TCRR1.Furthermore,RNA sequencing revealed that several genes closely linked to BETL development,including BETL2,MEG1,and MN1,were significantly downregulated in smk23.These genes are essential for nutrient transport,tissue development and signal transduction.In addition,haploid analysis of Zm RR5 revealed natural variations(Hap 2)that may contribute to the increased kernel yield.Disruption of Zm RR5 function in smk23 leads to defects in BETL development,impairing its ability to transport nutrients,and ultimately resulting in a smaller kernel size.This study provides new insights into the molecular mechanisms through which Zm RR5 regulates maize kernel development and offers potential strategies for improving grain yield.展开更多
[Objectives]This study was conducted to quickly qualitatively and quantitatively analyze the residues of 10 plant growth regulators(PGRs)in bean sprouts.[Methods]Using bean sprouts as the test material,a high-performa...[Objectives]This study was conducted to quickly qualitatively and quantitatively analyze the residues of 10 plant growth regulators(PGRs)in bean sprouts.[Methods]Using bean sprouts as the test material,a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method was established to determine the residual levels of 10 PGRs in bean sprouts.[Results]Under optimized conditions,the retention time of the 10 PGRs ranged from 6.45 to 11.43 min.When the mass concentration ranged from 0.005 to 0.05μg/ml,all PGRs exhibited good linearity,with correlation coefficients(r)≥0.9991.The limits of detection(LODs,S/N=3)were in the range of 0.30-0.92μg/kg,and the limits of quantification(LOQs)were in the range of 0.50-2.10μg/kg.The average recovery values at three concentration levels ranged from 80%to 105.8%,with relative standard deviations(RSD s,n=6)of 2.8%-7.5%.[Conclusions]This method is simple and accurate,and provides technical reference for food safety monitoring.展开更多
Waveform regulator in charge is a method that can realize multi-source detonation wave superposition through a single point detonation.The method does not need to weaken the strength of shell,and relies on the high st...Waveform regulator in charge is a method that can realize multi-source detonation wave superposition through a single point detonation.The method does not need to weaken the strength of shell,and relies on the high stress generated by superposition to cut shell into regular fragments.Additionally,it can be combined with different initiation methods to alter the fragmentation outcomes.In this study,aiming at the fracture strain of metal cylindrical shell driven by explosive charge with waveform regulator,theoretical analysis was first adopted to obtain the prediction model of the fracture strain of cylindrical shell with waveform regulator and the model of the axial distribution of the stress concentration factor.On this basis,both theoretical analysis and numerical models were utilized to investigate the effect of waveform regulator on the initial velocity of fragments.Finally,experiments were conducted to validate the fracture strain prediction model for cylindrical shell with waveform regulator.The research results show that the collision angles of the detonation waves at different axial positions are different,which leads to the stress concentration factor on the shell presenting a trend of gradually decreasing,then sharply increasing,and then rapidly decreasing along the axial direction.Additionally,the changes in the slot spacing and the thickness of outer charge will also affect the stress concentration factor,and the influence of outer charge thickness is relatively large.The smaller the ratio of charge volume to waveform regulator volume,the larger the axial sparse wave intensity and the more the fragment initial velocity decrease.From the initiation end to the non-initiation end,the failure modes of the shell sequentially change from pure shear,to mixed tensile-shear,and finally to pure tensile failure.The experimental results are in good agreement with the calculated results of the fracture strain model,and the maximum relative error is less than 10%,which indicates that the fracture strain prediction model of the cylindrical shell with waveform regulator established in this paper by considering the increase of elastic energy per unit volume caused by stress concentration on the shell is reliable.展开更多
Plants have evolved complex immune networks to adapt to survival needs,and their immune mechanisms have unique regulatory patterns to cope with different environments.In rice,the maintenance of immune balance involves...Plants have evolved complex immune networks to adapt to survival needs,and their immune mechanisms have unique regulatory patterns to cope with different environments.In rice,the maintenance of immune balance involves the synergistic action of many factors.Yue Wu et al.'s latest research results on the immunomodulatory mechanism of rice(ROD1 and the interaction between various proteins in rice)are introduced in this paper.展开更多
Objective To analyze the current situation of drug regulation after introducing the new policy for China’s online pharmacy,and to provide reference for the regulation of online pharmacy based on the international exp...Objective To analyze the current situation of drug regulation after introducing the new policy for China’s online pharmacy,and to provide reference for the regulation of online pharmacy based on the international experience.Methods Through literature research and comparative analysis,the history of policies for online pharmacy in China was investigated,and the current situation and problems of regulation for online pharmacy were explored.Results and Conclusion It is found that the body,basis and behavior of online prescription drug supervision in China should be improved.Combining experience in regulating online prescription drug at home and abroad,we provide some suggestions for the implementation of China’s online prescription drug policy by establishing a government-led multiple regulatory mechanism,standardizing the access qualifications for enterprises with business in online prescription drugs,improving the prescription inquiry and review system,and paying attention to consumer needs.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:Salvia miltiorrhiza is widely used in traditional Chinese medicine for treating cardiovascular and cerebrovascular diseases,with tanshinones being its major active components.This study aims to systematicall...Objective:Salvia miltiorrhiza is widely used in traditional Chinese medicine for treating cardiovascular and cerebrovascular diseases,with tanshinones being its major active components.This study aims to systematically elucidate the core transcriptional circuitry controlling tanshinone production,thereby establishing a mechanistic framework to optimize phytochemical yield and advance sustainable cultivation strategies for this pharmaceutically vital species.Methods:Transcriptome profiling revealed that the transcription factor SmWRKY69 is specifically expressed in the root periderm of S.miltiorrhiza.DNA affinity purification sequencing(DAPseq)was used to identify its potential target genes,and cis-element analysis predicted W-box motifs in the promoters of SmCPS1 and SmKSL1.Yeast one-hybrid(Y1H)assays were employed to validate its regulatory interactions with candidate gene promoters.Results:SmWRKY69 was found to directly bind to the promoters of SmCPS1 and SmKSL1,key genes in the tanshinone biosynthetic pathway,through W-box elements,indicating its role as a transcriptional regulator.Conclusion:SmWRKY69 regulates tanshinone biosynthesis by directly targeting SmCPS1 and SmKSL1,providing a valuable genetic target for metabolic engineering to enhance the therapeutic quality of S.miltiorrhiza.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
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
基金supported by AHA Career Development Award 938683 (to PJD)NIH grant R01MH123700 (to MLD)
文摘Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that plays an important role in a broad range of cellular activities from calcium regulation to protein synthesis and trafficking.In neurons,the ER extends from the soma through the axon to presynaptic terminals,and throughout the dendritic arbor into as many as half of all postsynaptic dendritic spines at any given time(Falahati et al.,2022).
基金supported by the Natural Science Foundation of Fujian Province,No.2021J02035(to WX).
文摘Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.
基金funded by the Natural Science Foundation of China(Grant Nos.32230097 and 32172512)the Jiangsu Agricultural Science and Technology Innovation Fund[Grant No.CX(20)2023]+1 种基金the Jiangsu Special Fund for Frontier Foundation Research of Carbon Peaking and Carbon Neutralization(Grant No.BK20220005)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘5-Aminolevulinic acid(ALA),is a novel plant growth regulator that can enhance plant tolerance against salt stress.However,the molecular mechanism of ALA is not well studied.In this study,ALA improved salt tolerance of apple(Malus×domestica'Gala')when the detached leaves or cultured calli were used as the materials.The expression of MdWRKY71,a WRKY transcription factor(TF)gene was found to be responsive to NaCl as well as ALA treatment.Functional analysis showed that overexpressing(OE)-MdWRKY71 significantly improved the salt tolerance of the transgenic apple,while RNA interfering(RNAi)-MdWRKY71 reduced the salt tolerance.However,exogenous ALA alleviated the salt damage in the RNAi-MdWRKY71 apple.When MdWRKY71 was transferred into tobacco,the salt tolerance of transgenic plants was enhanced,which was further improved by exogenous ALA.Subsequently,MdWRKY71 bound to the W-box of promoters of MdSOS2,MdNHX1,MdCLC-g,MdSOD1,MdCAT1 and MdAPX1,transcriptionally activating the gene expressions.Since the genes are responsible for Na+and Cl-transport and antioxidant enzyme activity respectively,it can be concluded that MdWRKY71,a new TF,is involved in ALA-improved salt tolerance by regulating ion homeostasis and redox homeostasis.These results provided new insights into the transcriptional regulatory mechanism of ALA in enhancing apple salt tolerance.
基金supported by the National Institutes of Health,Nos.AA025919,AA025919-03S1,and AA025919-05S1(all to RAF).
文摘Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.
基金supported by Yunnan Province Agricultural Joint Key Project(Grant No.202401BD070001-016)the National Natural Science Foundation of China(Grant No.32202530)+3 种基金Talent Introduction and Training Project of Yunnan Academy of Agricultural Sciences(Grant No.2024RCYP-09)Fundamental Research Project(Grant No.202401CF070046)Xingdian Talent support program(XDYC-QNRC-2023-0457)Yunnan Technology Innovation Center of Flower Technique.
文摘The proper flowering time of rose(Rosa hybrida)is vital for the market value of this horticultural crop,but the mechanism regulating this trait is largely unclear.Here,we found that the transcription factor SQUAMOSA PROMOTER BINDING PROTEIN-LIKE4(RhSPL4)positively regulates flowering time in rose.Transient silencing or overexpression transgenic rose plants of RhSPL4 exhibited delayed or early flowering,respectively.Analysis of transcriptome data from transgenic lines overexpressing RhSPL4 compared to the wild type indicated that differentially expressed genes were significantly enriched in the circadian rhythm pathway.Among the proteins encoded by these genes,RhSPL4 binds to the promoter of PSEUDO-RESPONSE REGULATOR 5-LIKE(RhPRR5L),as revealed in yeast one-hybrid,dual-Luciferase/Renilla luciferase reporter,chromatin immunoprecipitation-quantitative PCR and electrophoretic mobility shift assay.Furthermore,RhSPL4 specifically binds to the478 to441 bp region of the RhPRR5L promoter and activates its transcription.The silencing of RhPRR5L delayed flowering time in rose,resembling the phenotype of RhSPL4-silenced plants.Together,these results indicate that the RhSPL4-RhPRR5L module positively regulates flowering time in rose,laying the foundation for the genetic improvement of flowering time in this important horticultural crop.
基金supported by the Natural Science Foundation of Ningxia,China(2024AAC02039)the Scientific and Technological Innovation Leadership Talent Program of Ningxia,China(2022GKLRLX07)+1 种基金the National Natural Science Foundation of China(32260727 and 32371924)China Agriculture Research System(CARS-29-zp-6)。
文摘The postharvest senescence phase of table grapes comprises a series of biological processes.MicroRNAs(miRNAs)regulate downstream genes at the post-transcriptional level;however,whether miRNAs are involved in postharvest grape senescence remains unclear.We used small RNA sequencing to identify postharvest-related miRNAs in‘Red Globe'(Vitis vinifera)grapes harvested after 0,30,and 60 d of storage at 4℃(RG0,RG30,RG60).In total,42 known and 219 novel miRNA candidates were obtained.During fruit senescence,the expression of PC-3p-3343_1921,mi R2950,miR395k,miR2111,miR159c,miR169q,PC-5p-1112_4500,and miR167b changed signifcantly(P<0.05).Degradation sequencing identifed 218 targets associated with cell wall organization,tricarboxylic acid(TCA)cycling,pathogen defense,carbon metabolism,hormone signaling,the anthocyanin metabolism pathway,and energy regulation,of which ARF6,GRF3,TCP2,CP1,MYBA2,and WRKY72 were closely related to fruit senescence.We also verified that VIT_00s2146g00010,VIT_02s0012g01750,and VIT_03s0038g00160 with unknown functions are cleaved by senescence-related PC-5p-1112_4500 via the dual luciferase assay,and the transient transformation of grape berries showed that they regulate berry senescence.These results deepen our understanding of the role of mi RNAs in regulating grape berry senescence and prolonging the shelf life of horticultural products.Based on these results,we propose a new theoretical strategy for delaying the postharvest senescence of horticultural products by regulating the expression of key miRNAs(e.g.,PC-5p-1112_4500),thereby extending their shelf life.
文摘In this study,a dynamic model for an inverted pendulum system(IPS)attached to a car is created,and two different control methods are applied to control the system.The designed control algorithms aim to stabilize the pendulum arms in the upright position and the car to reach the equilibrium position.Grey Wolf Optimization-based Linear Quadratic Regulator(GWO-LQR)and GWO-based Fuzzy LQR(FLQR)control algorithms are used in the control process.To improve the performance of the LQR and FLQR methods,the optimum values of the coefficients corresponding to the foot points of the membership functions are determined by the GWO algorithm.Both a graphic and a numerical analysis of the outcomes are provided.In the comparative analysis,it is observed that the GWO-based FLQR method reduces the settling time by 22.58% and the maximum peak value by 18.2% when evaluated in terms of the angular response of the pendulum arm.Furthermore,this approach outperformed comparable research in the literature with a settling time of 2.4 s.These findings demonstrate that the suggested GWO-based FLQR controlmethod outperforms existing literature in terms of the time required for the pendulum arm to reach equilibrium.
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.
基金supported by National Key Research and Development Program of China(2023YFD1200500,2022YFD1201700)the National Natural Science Foundation of China(32071921)+1 种基金Key Research and Development Program of Shandong Province,China(2021LZGC022)the Taishan Scholars Project。
文摘Maize(Zea mays L.)is one of the world's most important staple crops,and is used for manufacturing food,feed,and industrial products.A key factor in maize yield is the grain weight,which directly influences productivity.In this study,we revealed the role of smk23 in maize kernel development.The ethyl methanesulfonate mutant smk23 is characterized by substantially reduced kernel weight.Through map-based cloning,smk23 was found to be located on Chr5 and encode a putative B-type response regulator,Zm RR5.A change from G to A occurs in the coding sequence of Zm RR5,resulting in the early termination of smk23.In Arabidopsis,B-type response regulators are involved in cytokinin signaling.Histological analysis and in situ hybridization of the mutant revealed abnormal endosperm development,particularly in the basal endosperm transfer layer(BETL),a specialized tissue critical for nutrient transport from the maternal tissues to the developing kernel.Zm RR5 positively regulates key genes involved in BETL development and function,including MRP1 and TCRR1.Furthermore,RNA sequencing revealed that several genes closely linked to BETL development,including BETL2,MEG1,and MN1,were significantly downregulated in smk23.These genes are essential for nutrient transport,tissue development and signal transduction.In addition,haploid analysis of Zm RR5 revealed natural variations(Hap 2)that may contribute to the increased kernel yield.Disruption of Zm RR5 function in smk23 leads to defects in BETL development,impairing its ability to transport nutrients,and ultimately resulting in a smaller kernel size.This study provides new insights into the molecular mechanisms through which Zm RR5 regulates maize kernel development and offers potential strategies for improving grain yield.
基金Supported by Outstanding Talent Development Program of Hebei ProvinceTangshan Talent Funding Project(A202202005).
文摘[Objectives]This study was conducted to quickly qualitatively and quantitatively analyze the residues of 10 plant growth regulators(PGRs)in bean sprouts.[Methods]Using bean sprouts as the test material,a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method was established to determine the residual levels of 10 PGRs in bean sprouts.[Results]Under optimized conditions,the retention time of the 10 PGRs ranged from 6.45 to 11.43 min.When the mass concentration ranged from 0.005 to 0.05μg/ml,all PGRs exhibited good linearity,with correlation coefficients(r)≥0.9991.The limits of detection(LODs,S/N=3)were in the range of 0.30-0.92μg/kg,and the limits of quantification(LOQs)were in the range of 0.50-2.10μg/kg.The average recovery values at three concentration levels ranged from 80%to 105.8%,with relative standard deviations(RSD s,n=6)of 2.8%-7.5%.[Conclusions]This method is simple and accurate,and provides technical reference for food safety monitoring.
基金supported by the National Natural Science Foundation of China(Grant No.12302437)Natural Science Foundation of Jiangsu Province(Grant No.SBK2023045424)。
文摘Waveform regulator in charge is a method that can realize multi-source detonation wave superposition through a single point detonation.The method does not need to weaken the strength of shell,and relies on the high stress generated by superposition to cut shell into regular fragments.Additionally,it can be combined with different initiation methods to alter the fragmentation outcomes.In this study,aiming at the fracture strain of metal cylindrical shell driven by explosive charge with waveform regulator,theoretical analysis was first adopted to obtain the prediction model of the fracture strain of cylindrical shell with waveform regulator and the model of the axial distribution of the stress concentration factor.On this basis,both theoretical analysis and numerical models were utilized to investigate the effect of waveform regulator on the initial velocity of fragments.Finally,experiments were conducted to validate the fracture strain prediction model for cylindrical shell with waveform regulator.The research results show that the collision angles of the detonation waves at different axial positions are different,which leads to the stress concentration factor on the shell presenting a trend of gradually decreasing,then sharply increasing,and then rapidly decreasing along the axial direction.Additionally,the changes in the slot spacing and the thickness of outer charge will also affect the stress concentration factor,and the influence of outer charge thickness is relatively large.The smaller the ratio of charge volume to waveform regulator volume,the larger the axial sparse wave intensity and the more the fragment initial velocity decrease.From the initiation end to the non-initiation end,the failure modes of the shell sequentially change from pure shear,to mixed tensile-shear,and finally to pure tensile failure.The experimental results are in good agreement with the calculated results of the fracture strain model,and the maximum relative error is less than 10%,which indicates that the fracture strain prediction model of the cylindrical shell with waveform regulator established in this paper by considering the increase of elastic energy per unit volume caused by stress concentration on the shell is reliable.
基金support of the National Natural Science Foundation of China(32472594)the Independent Deployment Project of Institute of Zoology,Chinese Academy of Sciences(2023IOZ010).
文摘Plants have evolved complex immune networks to adapt to survival needs,and their immune mechanisms have unique regulatory patterns to cope with different environments.In rice,the maintenance of immune balance involves the synergistic action of many factors.Yue Wu et al.'s latest research results on the immunomodulatory mechanism of rice(ROD1 and the interaction between various proteins in rice)are introduced in this paper.
文摘Objective To analyze the current situation of drug regulation after introducing the new policy for China’s online pharmacy,and to provide reference for the regulation of online pharmacy based on the international experience.Methods Through literature research and comparative analysis,the history of policies for online pharmacy in China was investigated,and the current situation and problems of regulation for online pharmacy were explored.Results and Conclusion It is found that the body,basis and behavior of online prescription drug supervision in China should be improved.Combining experience in regulating online prescription drug at home and abroad,we provide some suggestions for the implementation of China’s online prescription drug policy by establishing a government-led multiple regulatory mechanism,standardizing the access qualifications for enterprises with business in online prescription drugs,improving the prescription inquiry and review system,and paying attention to consumer needs.
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.
文摘Objective:Salvia miltiorrhiza is widely used in traditional Chinese medicine for treating cardiovascular and cerebrovascular diseases,with tanshinones being its major active components.This study aims to systematically elucidate the core transcriptional circuitry controlling tanshinone production,thereby establishing a mechanistic framework to optimize phytochemical yield and advance sustainable cultivation strategies for this pharmaceutically vital species.Methods:Transcriptome profiling revealed that the transcription factor SmWRKY69 is specifically expressed in the root periderm of S.miltiorrhiza.DNA affinity purification sequencing(DAPseq)was used to identify its potential target genes,and cis-element analysis predicted W-box motifs in the promoters of SmCPS1 and SmKSL1.Yeast one-hybrid(Y1H)assays were employed to validate its regulatory interactions with candidate gene promoters.Results:SmWRKY69 was found to directly bind to the promoters of SmCPS1 and SmKSL1,key genes in the tanshinone biosynthetic pathway,through W-box elements,indicating its role as a transcriptional regulator.Conclusion:SmWRKY69 regulates tanshinone biosynthesis by directly targeting SmCPS1 and SmKSL1,providing a valuable genetic target for metabolic engineering to enhance the therapeutic quality of S.miltiorrhiza.
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.
