Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,wi...Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.展开更多
With the growth of global protein demand and the development of plant-based foods,pea protein,as a low-allergenic,nutritionally balanced and environmentally friendly plant protein,has shown great potential in replacin...With the growth of global protein demand and the development of plant-based foods,pea protein,as a low-allergenic,nutritionally balanced and environmentally friendly plant protein,has shown great potential in replacing animal protein.Pea protein is mainly composed of globulin and albumin,with a protein content of 20%to 30%,and has a balanced amino acid composition,as well as being rich in minerals and dietary fiber.It also possesses good foaming,gelling,emulsifying and antioxidant functional properties.However,pea protein also has inherent defects that limit its application in the food industry.This article systematically reviews the extraction techniques,functional properties,modification methods and application fields of pea protein,and focuses on evaluating the effects of different extraction and modification strategies on protein yield and functional properties.Research shows that ultrasonic-assisted alkaline extraction can reduce solvent usage by 55%,shorten extraction time by 50%,and increase extraction rate by 12.51%;under optimized conditions,ultrafiltration membrane technology can achieve a protein purity of 91%.In terms of modification,ultrasonic treatment increases foaming capacity by 37.4%,and phenolic cross-linking increases gel strength from 3.0 kPa to 48 kPa.This article provides data support and theoretical reference for the efficient extraction and functional optimization of pea protein,and has promoting significance for its wide application in plant-based foods.展开更多
The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR...The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR.However,their clinical translation is hindered by their inherently low immunogenicity,often requiring potent adjuvants and advanced delivery systems.Biomembrane nanostructures(e.g.,liposomes,exosomes,and cell membrane-derived nanostructures),characterized by superior biocompatibility,intrinsic targeting ability,and immune-modulating properties,could serve as versatile platforms that potentiate vaccine efficacy by increasing antigen stability,enabling codelivery of immunostimulants,and facilitating targeted delivery to lymphoid tissues/antigen-presenting cells.This intrinsic immunomodulation promotes robust humoral and cellular immune responses to combat bacteria.This review critically reviews(1)key biomembrane nanostructure classes for bacterial protein antigens,(2)design strategies leveraging biomembrane nanostructures to enhance humoral and cellular immune responses,(3)preclinical efficacy against diverse pathogens,and(4)translational challenges and prospects.Biomembrane nanostructure-driven approaches represent a paradigm shift in the development of next-generation bacterial protein vaccines against resistant infections.展开更多
Directional three-dimensional carbon-based foams are emerging as highly attractive candidates for promising electromagnetic wave absorbing materials(EWAMs)thanks to their unique architecture,but their construction usu...Directional three-dimensional carbon-based foams are emerging as highly attractive candidates for promising electromagnetic wave absorbing materials(EWAMs)thanks to their unique architecture,but their construction usually involves complex procedures and extremely depends on unidirectional freezing technique.Herein,we propose a groundbreaking approach that leverages the assemblies of salting-out protein induced by ammonium metatungstate(AM)as the precursor,and then acquire directional three-dimensional carbon-based foams through simple pyrolysis.The electrostatic interaction between AM and protein ensures well dispersion of WC_(1−x)nanoparticles on carbon frameworks.The content of WC_(1−x)nanoparticles can be rationally regulated by AM dosage,and it also affects the electromagnetic(EM)properties of final carbon-based foams.The optimized foam exhibits exceptional EM absorption performance,achieving a remarkable minimum reflection loss of−72.0 dB and an effective absorption bandwidth of 6.3 GHz when EM wave propagates parallel to the directional pores.Such performance benefits from the synergistic effects of macroporous architecture and compositional design.Although there is a directional dependence of EM absorption,radar stealth simulation demonstrates that these foams can still promise considerable reduction in radar cross section with the change of incident angle.Moreover,COMSOL simulation further identifies their good performance in preventing EM interference among different electronic components.展开更多
α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively dete...α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.展开更多
Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immun...Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.展开更多
Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
Improving protein quality and grain yield traits coordinately is an important goal for crop breeding.To date,many protein-quality or grain-yield regulation genes have been identified.However,the genetic strategies int...Improving protein quality and grain yield traits coordinately is an important goal for crop breeding.To date,many protein-quality or grain-yield regulation genes have been identified.However,the genetic strategies integrating these genes in good-protein-quality and high-yield crop breeding practice are far from established.Here,we characterized the functions of the MADS domain-containing protein Zm MADS8 and Zea mays G protein gamma subunit 1(Zm GG1)in regulating protein quality and grain yield of maize.Zm MADS8 positively regulates zein protein accumulation and negatively regulates nonzein protein and lysine levels in kernels by interacting with Zm MADS47 to promote the transcriptional activation of Opaque2.Additionally,Zm MADS8 regulates starch content of kernels by targeting genes involved in starch biosynthesis.Zm GG1,a putative interactor of Zm MADS8,negatively regulates kernel number with a trade-off effect on kernel starch accumulation.The mads8;zmgg1 double mutant improved protein quality by attenuating zein biosynthesis and increasing essential lysine level,and increased grain yield by increasing kernel number,compensating for decreased starch biosynthesis.Our findings revealed the biological function of Zm MADS8 and Zm GG1 in regulating protein quality and yield related traits and suggested a genetic strategy by direct editing of Zm MADS8 and Zm GG1 to improve grain yield and protein quality simultaneously.展开更多
【目的】MADS-box转录因子是植物最大的转录因子家族之一,在植物生长发育和胁迫响应中均发挥重要功能。前期通过转录组数据获得一个辣椒热响应基因,该基因编码MADS-box转录因子家族成员CaAGL61(Agamous-like MADS-box protein AGL61)。...【目的】MADS-box转录因子是植物最大的转录因子家族之一,在植物生长发育和胁迫响应中均发挥重要功能。前期通过转录组数据获得一个辣椒热响应基因,该基因编码MADS-box转录因子家族成员CaAGL61(Agamous-like MADS-box protein AGL61)。在此基础上,进一步研究CaAGL61在辣椒耐热性调控中的功能,为深入了解辣椒耐热分子机制提供理论参考,为辣椒耐热性的遗传改良提供基因位点。【方法】通过SMART在线工具预测CaAGL61保守结构域,使用MEGA7构建辣椒和其他植物物种AGL61蛋白的系统发育树,利用实时荧光定量PCR技术探究CaAGL61在辣椒中的表达模式,运用烟草亚细胞定位技术和酵母双杂交自激活系统检测CaAGL61的转录因子特性,利用病毒诱导的基因沉默技术和基因瞬时过表达技术探究CaAGL61表达对辣椒耐热性的影响。【结果】CaAGL61编码179个氨基酸,包含一个MADS结构域,在系统进化方面高度保守。CaAGL61在辣椒花器官中的表达量最高、其次是茎和果实,根中的表达量最低;进一步分析发现CaAGL61的表达量随着花器官的成熟而增加,尤其在授粉坐果期的花药中表达量最高;45℃高温处理显著上调了CaAGL61的表达水平。亚细胞定位显示,CaAGL61定位于细胞核中;酵母转录激活分析表明,CaAGL61具有转录激活活性。CaAGL61沉默植株的耐热性显著增强,热胁迫处理后,与对照相比,CaAGL61沉默植株生长点萎蔫程度减轻,叶片相对电导率降低,丙二醛含量、死细胞和活性氧积累减少,而叶绿素含量升高。相反,CaAGL61瞬时过表达降低了辣椒的耐热性,与对照相比,表现为植株受热胁迫损伤程度更严重,叶片相对电导率升高,丙二醛含量、死细胞和活性氧积累增多,叶绿素含量下降。【结论】鉴定了一个辣椒热响应MADS-box转录因子基因CaAGL61,该基因通过加剧氧化胁迫而负调控辣椒耐热性。展开更多
Ma et al recently reported in the World Journal of Diabetes that ferroptosis occurs in osteoblasts under high glucose conditions,reflecting diabetes pathology.This condition could be protected by the upregulation of t...Ma et al recently reported in the World Journal of Diabetes that ferroptosis occurs in osteoblasts under high glucose conditions,reflecting diabetes pathology.This condition could be protected by the upregulation of the gene encoding polycytosine RNA-binding protein 1(PCBP1).Additionally,Ma et al used a lentivirus infection system to express PCBP1.As the authors’method of administration can be improved in terms of stability and cost,we propose delivering PCBP1 to treat type 2 diabetic osteoporosis by encapsulating it in protein nanoparticles.First,PCBP1 is small and druggable.Second,intravenous injection can help deliver PCBP1 across the mucosa while avoiding acid and enzyme-catalyzed degradation.Furthermore,incorporating PCBP1 into nanoparticles prevents its interaction with water or oxygen and protects PCBP1’s structure and activity.Notably,the safety of the protein materials and the industrialization techniques for large-scale production of protein nanoparticles must be comprehensively investigated before clinical application.展开更多
The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed...The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.展开更多
Maize(Zea mays),which is a vital source of food,feed,and energy feedstock globally,has significant potential for higher yields.However,environmental stress conditions,including drought and salt stress,severely restric...Maize(Zea mays),which is a vital source of food,feed,and energy feedstock globally,has significant potential for higher yields.However,environmental stress conditions,including drought and salt stress,severely restrict maize plant growth and development,leading to great yield losses.Leucine-rich repeat receptor-like kinases(LRR-RLKs)function in biotic and abiotic stress responses in the model plant Arabidopsis(Arabidopsis thaliana),but their roles in abiotic stress responses in maize are not entirely understood.In this study,we determine that the LRR-RLK ZmMIK2,a homolog of the Arabidopsis LRR-RK MALE DISCOVERER 1(MDIS1)-INTERACTING RECEPTOR LIKE KINASE 2(MIK2),functions in resistance to both drought and salt stress in maize.Zmmik2 plants exhibit enhanced resistance to both stresses,whereas overexpressing ZmMIK2 confers the opposite phenotypes.Furthermore,we identify C2-DOMAIN-CONTAINING PROTEIN 1(ZmC2DP1),which interacts with the intracellular region of ZmMIK2.Notably,that region of ZmMIK2 mediates the phosphorylation of ZmC2DP1,likely by increasing its stability.Both ZmMIK2 and ZmC2DP1 are mainly expressed in roots.As with ZmMIK2,knockout of ZmC2DP1 enhances resistance to both drought and salt stress.We conclude that ZmMIK2-ZmC2DP1 acts as a negative regulatory module in maize drought-and salt-stress responses.展开更多
基金financially supported by the Hainan Province Science and Technology Special Fund(Grant no:ZDYF2024XDNY187).
文摘Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.
文摘With the growth of global protein demand and the development of plant-based foods,pea protein,as a low-allergenic,nutritionally balanced and environmentally friendly plant protein,has shown great potential in replacing animal protein.Pea protein is mainly composed of globulin and albumin,with a protein content of 20%to 30%,and has a balanced amino acid composition,as well as being rich in minerals and dietary fiber.It also possesses good foaming,gelling,emulsifying and antioxidant functional properties.However,pea protein also has inherent defects that limit its application in the food industry.This article systematically reviews the extraction techniques,functional properties,modification methods and application fields of pea protein,and focuses on evaluating the effects of different extraction and modification strategies on protein yield and functional properties.Research shows that ultrasonic-assisted alkaline extraction can reduce solvent usage by 55%,shorten extraction time by 50%,and increase extraction rate by 12.51%;under optimized conditions,ultrafiltration membrane technology can achieve a protein purity of 91%.In terms of modification,ultrasonic treatment increases foaming capacity by 37.4%,and phenolic cross-linking increases gel strength from 3.0 kPa to 48 kPa.This article provides data support and theoretical reference for the efficient extraction and functional optimization of pea protein,and has promoting significance for its wide application in plant-based foods.
基金the National Natural Science Foundation of China(82573571)the Shanghai 2025 Basic Research Plan Natural Science Foundation(25ZR1401393)the First Batch of Open Topics of the Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices(2025QN13)。
文摘The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR.However,their clinical translation is hindered by their inherently low immunogenicity,often requiring potent adjuvants and advanced delivery systems.Biomembrane nanostructures(e.g.,liposomes,exosomes,and cell membrane-derived nanostructures),characterized by superior biocompatibility,intrinsic targeting ability,and immune-modulating properties,could serve as versatile platforms that potentiate vaccine efficacy by increasing antigen stability,enabling codelivery of immunostimulants,and facilitating targeted delivery to lymphoid tissues/antigen-presenting cells.This intrinsic immunomodulation promotes robust humoral and cellular immune responses to combat bacteria.This review critically reviews(1)key biomembrane nanostructure classes for bacterial protein antigens,(2)design strategies leveraging biomembrane nanostructures to enhance humoral and cellular immune responses,(3)preclinical efficacy against diverse pathogens,and(4)translational challenges and prospects.Biomembrane nanostructure-driven approaches represent a paradigm shift in the development of next-generation bacterial protein vaccines against resistant infections.
基金financially supported by the National Natural Science Foundation of China(Nos.22475057 and No.52373262).
文摘Directional three-dimensional carbon-based foams are emerging as highly attractive candidates for promising electromagnetic wave absorbing materials(EWAMs)thanks to their unique architecture,but their construction usually involves complex procedures and extremely depends on unidirectional freezing technique.Herein,we propose a groundbreaking approach that leverages the assemblies of salting-out protein induced by ammonium metatungstate(AM)as the precursor,and then acquire directional three-dimensional carbon-based foams through simple pyrolysis.The electrostatic interaction between AM and protein ensures well dispersion of WC_(1−x)nanoparticles on carbon frameworks.The content of WC_(1−x)nanoparticles can be rationally regulated by AM dosage,and it also affects the electromagnetic(EM)properties of final carbon-based foams.The optimized foam exhibits exceptional EM absorption performance,achieving a remarkable minimum reflection loss of−72.0 dB and an effective absorption bandwidth of 6.3 GHz when EM wave propagates parallel to the directional pores.Such performance benefits from the synergistic effects of macroporous architecture and compositional design.Although there is a directional dependence of EM absorption,radar stealth simulation demonstrates that these foams can still promise considerable reduction in radar cross section with the change of incident angle.Moreover,COMSOL simulation further identifies their good performance in preventing EM interference among different electronic components.
基金supported by the Natural Science Foundation of Guangxi Zhuang Automomous Region,Nos.2019GXNSFDA245015(to MC),2022GXNSFBA035654(to HL)the National Natural Science Foundation of China,Nos.82360241(to MC),82304876(to HL)+1 种基金Scientific Research and Technology Development Project of Guilin City,Nos.20220139-3(to MC),20210218-5(to HL)Guangxi Medical and Health Key Discipline Construction Project(to QL)。
文摘α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.
基金supported by the National Natural Science Foundation of China(Nos.82573045,82460602,82560459)the Hainan Provincial Graduate Student Innovative Research Project(No.Qhys2024-440).
文摘Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
文摘Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
基金supported by the Biological Breeding-National Science and Technology Major Project(2023ZD0406804,2023ZD0402701)Major Project of Hubei Hongshan Laboratory(2022hszd019)First-Class Discipline Construction Funds of the College of Plant Science and Technology at Huazhong Agricultural University(2022ZK PY002)。
文摘Improving protein quality and grain yield traits coordinately is an important goal for crop breeding.To date,many protein-quality or grain-yield regulation genes have been identified.However,the genetic strategies integrating these genes in good-protein-quality and high-yield crop breeding practice are far from established.Here,we characterized the functions of the MADS domain-containing protein Zm MADS8 and Zea mays G protein gamma subunit 1(Zm GG1)in regulating protein quality and grain yield of maize.Zm MADS8 positively regulates zein protein accumulation and negatively regulates nonzein protein and lysine levels in kernels by interacting with Zm MADS47 to promote the transcriptional activation of Opaque2.Additionally,Zm MADS8 regulates starch content of kernels by targeting genes involved in starch biosynthesis.Zm GG1,a putative interactor of Zm MADS8,negatively regulates kernel number with a trade-off effect on kernel starch accumulation.The mads8;zmgg1 double mutant improved protein quality by attenuating zein biosynthesis and increasing essential lysine level,and increased grain yield by increasing kernel number,compensating for decreased starch biosynthesis.Our findings revealed the biological function of Zm MADS8 and Zm GG1 in regulating protein quality and yield related traits and suggested a genetic strategy by direct editing of Zm MADS8 and Zm GG1 to improve grain yield and protein quality simultaneously.
文摘【目的】MADS-box转录因子是植物最大的转录因子家族之一,在植物生长发育和胁迫响应中均发挥重要功能。前期通过转录组数据获得一个辣椒热响应基因,该基因编码MADS-box转录因子家族成员CaAGL61(Agamous-like MADS-box protein AGL61)。在此基础上,进一步研究CaAGL61在辣椒耐热性调控中的功能,为深入了解辣椒耐热分子机制提供理论参考,为辣椒耐热性的遗传改良提供基因位点。【方法】通过SMART在线工具预测CaAGL61保守结构域,使用MEGA7构建辣椒和其他植物物种AGL61蛋白的系统发育树,利用实时荧光定量PCR技术探究CaAGL61在辣椒中的表达模式,运用烟草亚细胞定位技术和酵母双杂交自激活系统检测CaAGL61的转录因子特性,利用病毒诱导的基因沉默技术和基因瞬时过表达技术探究CaAGL61表达对辣椒耐热性的影响。【结果】CaAGL61编码179个氨基酸,包含一个MADS结构域,在系统进化方面高度保守。CaAGL61在辣椒花器官中的表达量最高、其次是茎和果实,根中的表达量最低;进一步分析发现CaAGL61的表达量随着花器官的成熟而增加,尤其在授粉坐果期的花药中表达量最高;45℃高温处理显著上调了CaAGL61的表达水平。亚细胞定位显示,CaAGL61定位于细胞核中;酵母转录激活分析表明,CaAGL61具有转录激活活性。CaAGL61沉默植株的耐热性显著增强,热胁迫处理后,与对照相比,CaAGL61沉默植株生长点萎蔫程度减轻,叶片相对电导率降低,丙二醛含量、死细胞和活性氧积累减少,而叶绿素含量升高。相反,CaAGL61瞬时过表达降低了辣椒的耐热性,与对照相比,表现为植株受热胁迫损伤程度更严重,叶片相对电导率升高,丙二醛含量、死细胞和活性氧积累增多,叶绿素含量下降。【结论】鉴定了一个辣椒热响应MADS-box转录因子基因CaAGL61,该基因通过加剧氧化胁迫而负调控辣椒耐热性。
文摘Ma et al recently reported in the World Journal of Diabetes that ferroptosis occurs in osteoblasts under high glucose conditions,reflecting diabetes pathology.This condition could be protected by the upregulation of the gene encoding polycytosine RNA-binding protein 1(PCBP1).Additionally,Ma et al used a lentivirus infection system to express PCBP1.As the authors’method of administration can be improved in terms of stability and cost,we propose delivering PCBP1 to treat type 2 diabetic osteoporosis by encapsulating it in protein nanoparticles.First,PCBP1 is small and druggable.Second,intravenous injection can help deliver PCBP1 across the mucosa while avoiding acid and enzyme-catalyzed degradation.Furthermore,incorporating PCBP1 into nanoparticles prevents its interaction with water or oxygen and protects PCBP1’s structure and activity.Notably,the safety of the protein materials and the industrialization techniques for large-scale production of protein nanoparticles must be comprehensively investigated before clinical application.
基金supported by the National Natural Science Foundation of China,Nos.91849115 and U1904207(to YX),81974211 and 82171247(to CS)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No.2020-PT310-01(to YX).
文摘The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.
基金supported by the National Key Research and Development Program of China(2021YFD1200703 and 2022YFF1001602)the National Science Foundation of China(32272024 and 32171940)+2 种基金the Pinduoduo-China Agricultural University Research Fund(PC2023B01001)the Chinese Universities Scientific Fund(2022TC142)the 2115 Talent Development Program of China Agricultural University。
文摘Maize(Zea mays),which is a vital source of food,feed,and energy feedstock globally,has significant potential for higher yields.However,environmental stress conditions,including drought and salt stress,severely restrict maize plant growth and development,leading to great yield losses.Leucine-rich repeat receptor-like kinases(LRR-RLKs)function in biotic and abiotic stress responses in the model plant Arabidopsis(Arabidopsis thaliana),but their roles in abiotic stress responses in maize are not entirely understood.In this study,we determine that the LRR-RLK ZmMIK2,a homolog of the Arabidopsis LRR-RK MALE DISCOVERER 1(MDIS1)-INTERACTING RECEPTOR LIKE KINASE 2(MIK2),functions in resistance to both drought and salt stress in maize.Zmmik2 plants exhibit enhanced resistance to both stresses,whereas overexpressing ZmMIK2 confers the opposite phenotypes.Furthermore,we identify C2-DOMAIN-CONTAINING PROTEIN 1(ZmC2DP1),which interacts with the intracellular region of ZmMIK2.Notably,that region of ZmMIK2 mediates the phosphorylation of ZmC2DP1,likely by increasing its stability.Both ZmMIK2 and ZmC2DP1 are mainly expressed in roots.As with ZmMIK2,knockout of ZmC2DP1 enhances resistance to both drought and salt stress.We conclude that ZmMIK2-ZmC2DP1 acts as a negative regulatory module in maize drought-and salt-stress responses.
