Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal neurogenesis.In this study,we applied in vivo fluorescent tracing using NestinCreERT2::Ro...Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal neurogenesis.In this study,we applied in vivo fluorescent tracing using NestinCreERT2::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells(NSCs)and dendritic spine formation of newborn neurons in the subgranular zone of the dentate gyrus.We found abnormal orientation of tamoxifen-induced tdTomato+(tdTom^(+))NSCs in adult mice 2 months after treatment with EtOH(5.0 g/kg,i.p.)for 7 consecutive days.EtOH markedly inhibited tdTom^(+)NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to adulthood.EtOH(100 mM)also significantly inhibited the proliferation to 39.2%and differentiation of primary NSCs in vitro.Adult mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus,which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycinenhancer of zeste homolog 2 pathway.In vivo tracing revealed that EtOH induced abnormal orientation of tdTom+NSCs and spatial misposition defects of newborn neurons,thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.展开更多
Background Kabukisyndrome(KS)is arare developmental disorder characterised by multiple congenital anomalies and intellectual disability.UTX(ubiquitously transcribed tetratricopeptide repeat,X chromosome),which encodes...Background Kabukisyndrome(KS)is arare developmental disorder characterised by multiple congenital anomalies and intellectual disability.UTX(ubiquitously transcribed tetratricopeptide repeat,X chromosome),which encodes a histone demethylase,is one of the two major pathogenic risk genes for KS.Although intellectual disability is a key phenotype of KS,the role of UTX in cognitive function remains unclear.Currently,no targeted therapies are available for KS.Aims This study aimed to investigate how UTX regulates cognition,to explore the mechanisms underlying UTX dysfunction and to identify potential molecular targets for treatment.Methods WegeneratedUTXconditional knockoutmice and found that UTX deletion downregulated calmodulin transcription by disrupting H3K27me3(trimethylated histone H3 at lysine 27)demethylation.Results UTX-knockout mice showeddecreased phosphorylation of calcium/calmodulin-dependent protein kinase I,impaired long-term potentiation and deficit in remote contextual fear memory.These effects were reversed by an Food and Drug Administration-approved drug desipramine.Conclusions Our results reveal an epigenetic mechanism underlying the important role of UTX in synaptic plasticity and cognitive function,and suggest that desipramine could be a potential treatment for KS.展开更多
Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we...Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.展开更多
Graphene as a lubricating additive holds great potential for industrial lubrication. However, its poor dispersity and compatibility with base oils and grease hinder maximizing performance. Here, the infuence of graphe...Graphene as a lubricating additive holds great potential for industrial lubrication. However, its poor dispersity and compatibility with base oils and grease hinder maximizing performance. Here, the infuence of graphene dispersion on the thickening efect and lubrication function is considered. A well-dispersed lubricant additive was obtained via trihexyl tetradecyl phosphonium bis(2-ethylhexyl) phosphate modifed graphene ([P_(66614)][DEHP]-G). Then lithium complex grease was prepared by saponifcation with 12-OH stearic acid, sebacic acid, and lithium hydroxide, using polyalphaolefn (PAO20) as base oil and the modifed-graphene as lubricating additive, with the original graphene as a comparison. The physicochemical properties and lubrication performance of the as-prepared greases were evaluated in detail. The results show that the as-prepared greases have high dropping point and colloidal stability. Furthermore, modifed-graphene lithium complex grease ofered the best friction reduction and anti-wear abilities, manifesting the reduction of friction coefcient and wear volume up to 18.84% and 67.34%, respectively. With base oil overfow and afux, well-dispersed [P_(66614)][DEHP]-G was readily adsorbed to the worn surfaces, resulting in the formation of a continuous and dense graphene deposition flm. The synergy of deposited graphene-flm, spilled oil, and adhesive grease greatly improves the lubrication function of grease. This research paves the way for modulating high-performance lithium complex grease to reduce the friction and wear of movable machinery.展开更多
The dysregulation of exosomal microRNAs(miRNAs)plays a crucial role in the development and progression of cancer.This study investigated the role of a newly identified serum exosomal miRNA miR-4256 in gastric cancer(G...The dysregulation of exosomal microRNAs(miRNAs)plays a crucial role in the development and progression of cancer.This study investigated the role of a newly identified serum exosomal miRNA miR-4256 in gastric cancer(GC)and the underlying mechanisms.The differentially expressed miRNAs were firstly identified in serum exosomes of GC patients and healthy individuals using next-generation sequencing and bioinformatics.Next,the expression of serum exosomal miR-4256 was analyzed in GC cells and GC tissues,and the role of miR-4256 in GC was investigated by in vitro and in vivo experiments.Then,the effect of miR-4256 on its downstream target genes HDAC5/p16^(INK4a) was studied in GC cells,and the underlying mechanisms were evaluated using dual luciferase reporter assay and Chromatin Immunoprecipitation(ChIP).Additionally,the role of the miR-4256/HDAC5/p16^(INK4a) axis in GC was studied using in vitro and in vivo experiments.Finally,the upstream regulators SMAD2/p300 that regulate miR-4256 expression and their role in GC were explored using in vitro experiments.miR-4256 was the most significantly upregulated miRNA and was overexpressed in GC cell lines and GC tissues;in vitro and in vivo results showed that miR-4256 promoted GC growth and progression.Mechanistically,miR-4256 enhanced HDAC5 expression by targeting the promoter of the HDAC5 gene in GC cells,and then restrained the expression of p16^(INK4a) through the epigenetic modulation of HDAC5 at the p16INK4a promoter.Furthermore,miR-4256 overexpression was positively regulated by the SMAD2/p300 complex in GC cells.Our data indicate that miR-4256 functions as an oncogene in GC via the SMAD2/miR-4256/HDAC5/p16^(INK4a) axis,which participates in GC progression and provides novel therapeutic and prognostic biomarkers for GC.展开更多
Shape Memory Alloy(SMA)is a typical material with memory effect,and it is widely used in many engineering fields.Based on the elastic theory and Galerkin method,a vibration system of SMA beam with rigid constraints is...Shape Memory Alloy(SMA)is a typical material with memory effect,and it is widely used in many engineering fields.Based on the elastic theory and Galerkin method,a vibration system of SMA beam with rigid constraints is proposed.The non⁃smooth transformation was employed to deal with the discontinuous position,and the original system was turned into an approximate equivalent system associated with the Dirac function.Then,using the stochastic averaging method,the drift and diffusion coefficients of the corresponding Fokker Planck Kolmogorov equation were described.Lastly,the approximate probability response of the system was formulated analytically.Meanwhile,numerical simulation was carried out to verify the effectiveness of analytical results.Furthermore,stochastic bifurcation was discussed.Results show that the stationary probability response of the system was affected by the increase of noise amplitude and restitution force,and a certain restitution value and damping could induce P⁃bifurcation.展开更多
The purpose of this study was to develop poly(amidoamine)(PAMAM)-functionalized multi-walled carbon nanotubes(MWNTs)loaded with a poorly water-soluble drug,intended to improve the drug-loading capacity,dissolution an...The purpose of this study was to develop poly(amidoamine)(PAMAM)-functionalized multi-walled carbon nanotubes(MWNTs)loaded with a poorly water-soluble drug,intended to improve the drug-loading capacity,dissolution and design a sustained release system.MWNTs were modified with a carboxyl group by acid treatment and then complex with PAMAM.PAMAM-MWNTs were investigated as a scaffold for loading the model drug,Carvedilol(CAR),using three different methods(the fusion method,the incipient wetness impregnation method,and the solvent method).The effects of different pore size,specific surface area and physical state were systematically studied using FT-IR,TGA,SEM,DSC,nitrogen adsorption,XPS and XRD.All the samples made by PAMAM-MWNTs to load the drug had a marked effect on the drug-loading capacity as well as drug dissolution,especially theⅡ-30%.展开更多
Cancer has long been amajor threat to human health.Recent advancements inmolecular imaging have revolutionized cancer research by enabling early and precise disease localization,essential for effective management.In p...Cancer has long been amajor threat to human health.Recent advancements inmolecular imaging have revolutionized cancer research by enabling early and precise disease localization,essential for effective management.In particular,optical molecular imaging is an invaluable cancer detection tool in preoperative planning,intraoperative guidance,and postoperative monitoring owing to its noninvasive nature,rapid turnover,safety,and ease of use.The tumor microenvironment and cells within it express distinct biomarkers.Optical imaging technology leverages these markers to differentiate tumor tissues from surrounding tissues and capture real-time images with high resolution.Nevertheless,a robust understanding of these cancer-relatedmolecules and their dynamic changes is crucial for effectivelymanaging cancer.Recent advancements in opticalmolecular imaging technologies offer novel approaches for cancer investigation in research and practice.This review investigates themodern opticalmolecular imaging techniques employed in both preclinical and clinical research,including bioluminescence,fluorescence,chemiluminescence,photoacoustic imaging,and Raman spectroscopy.We explore the current paradigm of optical molecular imaging modalities,their current status in preclinical cancer research and clinical applications,and future perspectives in the fields of cancer research and treatment.展开更多
Hydrogen energy has been recognized as “Ultimate Power Source” in the 21st century, which could be the best solution to the looming energy crisis and climate degeneration in the near future. Due to its high safety, ...Hydrogen energy has been recognized as “Ultimate Power Source” in the 21st century, which could be the best solution to the looming energy crisis and climate degeneration in the near future. Due to its high safety, low price, abundant resources and decent hydrogen storage density, magnesium based solid-state hydrogen storage materials are becoming the leading candidate for onboard hydrogen storage. However,the high operation temperature and slow reaction rate of MgH_(2), as a result of the large formation enthalpy and high reaction activation energy,respectively, are the first and most difficult problems we need to face and overcome to realize its industrialization. Herein, a state-of-the-art review on tailoring the stable thermodynamics and sluggish kinetics of hydrogen storage in MgH_(2), particularly through nanoengnieering and catalysis is presented, aiming to provide references and solutions for its promotion and application. Promising methods to overcome the challenges faced by MgH_(2)/Mg, such as bidirectional catalysts and nanoconfinement with in-situ catalysis are compared and the required improvements are discussed to stimulate further discussions and ideas in the rational design of MgH_(2)/Mg systems with ability for hydrogen release/uptake at lower temperatures and cycle stability in the near future.展开更多
Aqueous zinc ion batteries(AZIBs) demonstrate tremendous competitiveness and application prospects because of their abundant resources,low cost, high safety, and environmental friendliness. Although the advanced elect...Aqueous zinc ion batteries(AZIBs) demonstrate tremendous competitiveness and application prospects because of their abundant resources,low cost, high safety, and environmental friendliness. Although the advanced electrochemical energy storage systems based on zinc ion batteries have been greatly developed, many severe problems associated with Zn anode impede its practical application, such as the dendrite formation,hydrogen evolution, corrosion and passivation phenomenon. To address these drawbacks, electrolytes, separators, zinc alloys, interfacial modification and structural design of Zn anode have been employed at present by scientists. Among them, the structural design for zinc anode is relatively mature, which is generally believed to enhance the electroactive surface area of zinc anode, reduce local current density, and promote the uniform distribution of zinc ions on the surface of anode. In order to explore new research directions, it is crucial to systematically summarize the structural design of anode materials. Herein, this review focuses on the challenges in Zn anode, modification strategies and the three-dimensional(3D) structure design of substrate materials for Zn anode including carbon substrate materials, metal substrate materials and other substrate materials. Finally, future directions and perspectives about the Zn anode are presented for developing high-performance AZIBs.展开更多
With global warming, high-temperature(HT) stress has become a major abiotic stress for crops, in particular summer maize in China. Photosynthesis is sensitive to HT. Salicylic acid(SA) and 6-benzyladenine(6-BA) can im...With global warming, high-temperature(HT) stress has become a major abiotic stress for crops, in particular summer maize in China. Photosynthesis is sensitive to HT. Salicylic acid(SA) and 6-benzyladenine(6-BA) can improve the adaptation of plants to various biotic and abiotic stresses. However, their contribution to maintaining photosynthetic activity and alleviating photoinhibition in maize leaves under HT stress is still unclear. The effects of exogenous SA or 6-BA on growth, photosynthesis capacity, photosystem Ⅱ(PSII) activity, subcellular ultrastructure, antioxidant system, and plant hormones in maize leaves under HT stress were investigated. Under HT conditions, application of SA or 6-BA up-regulated gibberellin and zeatin content in leaves, increasing leaf area index(LAI). It also expanded the stomata by reducing abscisic acid and jasmonic acid content in leaves, cooling them and increasing CO2supply to photosynthesis. A higher net photosynthetic rate, combined with increased activity of the antioxidant system, alleviated oxidative stress in maize plants sprayed with SA or 6-BA, allowing them to maintain their chloroplast ultrastructure and PSII activity, in particular electron transfer from QAto QB. The increased LAI and net photosynthetic rate per unit leaf area also resulted in the accumulation of more biomass.展开更多
Treatments for lesions in central nervous system(CNS)are always faced with challenges due to the anatomical and physiological particularity of the CNS despite the fact that several achievements have been made in early...Treatments for lesions in central nervous system(CNS)are always faced with challenges due to the anatomical and physiological particularity of the CNS despite the fact that several achievements have been made in early diagnosis and precision medicine to improve the survival and quality of life of patients with brain tumors in recent years.Understanding the complexity as well as role of the microenvironment of brain tumors may suggest a better revealing of the molecular mechanism of brain tumors and new therapeutic directions,which requires an accurate recapitulation of the complex microenvironment of human brain in vitro.Here,a 3D bioprinted in vitro brain matrix-mimetic microenvironment model with hyaluronic acid(HA)and normal glial cells(HEBs)is developed which simulates both mechanical and biological properties of human brain microenvironment in vivo through the investigation of the formulation of bioinks and optimization of printing process and parameters to study the effects of different concentration of gelatin(GA)within the bioink and different printing structures of the scaffold on the performance of the brain matrix-mimetic microenvironment models.The study provides experimental models for the exploration of the multiple factors in the brain microenvironment and scaffolds for GBM invasion study.展开更多
Cancer is characterized by a high fatality rate,complex molecular mechanism,and costly therapies.The microenvironment of a tumor consists of multiple biochemical cues and the interaction between tumor cells,stromal ce...Cancer is characterized by a high fatality rate,complex molecular mechanism,and costly therapies.The microenvironment of a tumor consists of multiple biochemical cues and the interaction between tumor cells,stromal cells,and extracellular matrix plays a key role in tumor initiation,development,angiogenesis,invasion and metastasis.To better understand the biological features of tumor and reveal the critical factors of therapeutic treatments against cancer,it is of great significance to build in vitro tumor models that could recapitulate the stages of tumor progression and mimic tumor behaviors in vivo for efficient and patient-specific drug screening and biological studies.Since conventional tissue engineering methods of constructing tumor models always fail to simulate the later stages of tumor development due to the lack of ability to build complex structures and angiogenesis potential,three-dimensional(3D)bioprinting techniques have gradually found its applications in tumor microenvironment modeling with accurate composition and well-organized spatial distribution of tumor-related cells and extracellular components in the past decades.The capabilities of building tumor models with a large range of scale,complex structures,multiple biomaterials and vascular network with high resolution and throughput make 3D bioprinting become a versatile platform in bio-manufacturing aswell as inmedical research.In this review,wewill focus on 3D bioprinting strategies,design of bioinks,current 3D bioprinted tumor models in vitro classified with their structures and propose future perspectives.展开更多
Organ-on-a-chip technology,a promising three-dimensional(3D)dynamic culture method,ensures accu-rate and efficient cell culture and has great potential for replacing animal models in preclinical testing.The circulator...Organ-on-a-chip technology,a promising three-dimensional(3D)dynamic culture method,ensures accu-rate and efficient cell culture and has great potential for replacing animal models in preclinical testing.The circulatory system,the most abundant organ in the human body,plays a crucial role in oxygen exchange and mass transfer,which is the determining factor for the survival of tissues and organs.Thus,it is essential to integrate the circulatory system into an organ-on-a-chip to recreate tissue and organ microenvironments and physiological functions.This review discusses the synergy between the vasculature and the emerging organ-on-a-chip technology,which offers even better possibilities of dupli-cating physiology and disease characteristics.In addition,we review the different steps of a vascularized organ-on-a-chip fabrication process,including structure fabrication and tissue construction using differ-ent biofabrication strategies.Finally,we outline the applicability of this technology in the fascinating and fast-developing field of organ and tumor culture.展开更多
Three-dimensional （3D） printing is a novel promising technology based on 3D imaging and layer-by-layer additive fabrication. It has a profound influence on all aspects of our lives and is playing an increasing impor...Three-dimensional （3D） printing is a novel promising technology based on 3D imaging and layer-by-layer additive fabrication. It has a profound influence on all aspects of our lives and is playing an increasing important role in many areas including engineering, manufacturing, art, education and medicine. ＂3D bioprinting＂ has been put forward with the technical progress in 3D printing and might be a possible way to solve the serious problem of human organ shortage in tissue engineering and regenerative medicine. Many research groups flung them into this area and have already made some gratifying achievements. However, it is a long way to fabricate a live organ. Many elements lead to the limitation of 3D bioprinting. This review introduces the background and development history of 3D bioprinting, compares different approaches of 3D bioprinting and illustrates the key factors of the printing process. Meanwhile, this review also points out existing challenges of 3D bioprinting and has a great prospect. Some points proposed in this review might be served as reference for the research of this field.展开更多
Anthocyanins are essential for the quality of perennial horticultural crops,such as grapes.In grapes,ELONGATED HYPOCOTYL 5(HY5)and MYBA1 are two critical transcription factors that regulate anthocyanin biosynthesis.Ou...Anthocyanins are essential for the quality of perennial horticultural crops,such as grapes.In grapes,ELONGATED HYPOCOTYL 5(HY5)and MYBA1 are two critical transcription factors that regulate anthocyanin biosynthesis.Our previous work has shown that Vitis vinifera B-box protein 44(VvBBX44)inhibits anthocyanin synthesis and represses VvHY5 expression in grape calli.However,the regulatory mechanism underlying this regulation was unclear.In this study,we found that loss of VvBBX44 function resulted in increased anthocyanin accumulation in grapevine callus.VvBBX44 directly represses VvMYBA1,which activates VvBBX44.VvMYBA1,but not VvBBX44,directly modulates the expression of grape UDP flavonoid 3-O-glucosyltransferase(VvUFGT).We demonstrated that VvBBX44 represses the transcriptional activation of VvUFGT and VvBBX44 induced by VvMYBA1.However,VvBBX44 and VvMYBA1 did not physically interact in yeast.The application of exogenous anthocyanin stimulated VvBBX44 expression in grapevine suspension cells and tobacco leaves.These findings suggest that VvBBX44 and VvMYBA1 form a transcriptional feedback loop to prevent overaccumulation of anthocyanin and reduce metabolic costs.Our work sheds light on the complex regulatory network that controls anthocyanin biosynthesis in grapevine.展开更多
[Objectives] This study aimed to optimize the conditions for pressurized synchronous extraction of volatile oils, total flavonoids and tannic acid from Artemisia argyi .[Methods] Single factor experiments and orthogon...[Objectives] This study aimed to optimize the conditions for pressurized synchronous extraction of volatile oils, total flavonoids and tannic acid from Artemisia argyi .[Methods] Single factor experiments and orthogonal experiments were conducted.[Results] Pressurization had a significant effect on the extraction rate of chemical constituents of A. argyi . The optimal conditions for pressurized synchronous extraction of volatile oils, total flavonoids and tannic acid from A. argyi were as follows: solvent concentration of 70%, solid to liquid ratio of 1∶ 30 (g/mL), extraction pressure of 0.9 MPa, extraction time of 40 min and extraction temperature of 90 ℃. Under the optimal extraction conditions, the yields of volatile oils, total flavonoids and tannic acid were 0.852%, 4.66% and 6.79%, respectively.[Conclusions] Compared with other extraction methods, the pressurized assistant solvent extraction method can achieve the synchronous extraction of volatile oils, total flavonoids and tannic acid from A. argyi . The process is stable, short in extraction time, high in solvent utilization rate and ideal in extraction effect of the three components from A. argyi .展开更多
[Objectives]To determine and analyze amino acid content in Maca from different habitats and varieties.[Methods]Maca from two habitats and three colors were selected and a kind of turnip commonly used was to fake Maca....[Objectives]To determine and analyze amino acid content in Maca from different habitats and varieties.[Methods]Maca from two habitats and three colors were selected and a kind of turnip commonly used was to fake Maca.After optimizing the hydrolysis conditions,100 mg Maca samples were hydrolyzed in the concentration of 6 mol/L hydrochloric acid at 110℃for 24 h.The content range of amino acids in each sample was detected by HPLC.[Results]The average total content of amino acids in Maca was 9.52 g/100 g.Yunnan yellow Maca contained 16 kinds of amino acids,including 7 kinds of human essential amino acids,accounting for 17.2%of the total amino acids while Yunnan purple Maca held 16 kinds of amino acids,counting 7 kinds of human essential amino acids,accounting for 16.5%of the total amino acids.The amino acid ratio coefficient method also showed that the two kinds of Maca had higher nutritional value than the others.15 kinds of amino acids were detected in Yunnan black Maca,including 6 kinds of essential amino acids,accounting for 9.60%of the total amino acids.Among amino acids in Yunnan Maca,the highest content was Arg.A total of 12 kinds of amino acids,together with 6 essential human amino acids,were determined in Peru black Maca,accounting for 11.6%of the total amino acids.In Peru black Maca the highest concentration of amino acid was Pro.It was noteworthy that the amino acid species were comprehensive in Maca,and high level of amino acids resulted in high nutritional value.Its specific amino acid composition ratio was obviously different from Turnip,the counterfeit goods to deceive customers.[Conclusions]The method of automatic amino acid analyzer is simple and accurate,and can be used for the identification and content determination of amino acids in Maca as amino acid is an essential nutrient in Maca.展开更多
基金supported by the National Natural Science Foundation of China,Nos.31601175(to YL),81803508(to KZ),82074056(to JY)the Natural Science Foundation of Liaoning Province of China,No.20180550335(to YL)the Scientific Research Project of Educational Commission of Liaoning Province of China,No.201610163L22(to YL)。
文摘Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal neurogenesis.In this study,we applied in vivo fluorescent tracing using NestinCreERT2::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells(NSCs)and dendritic spine formation of newborn neurons in the subgranular zone of the dentate gyrus.We found abnormal orientation of tamoxifen-induced tdTomato+(tdTom^(+))NSCs in adult mice 2 months after treatment with EtOH(5.0 g/kg,i.p.)for 7 consecutive days.EtOH markedly inhibited tdTom^(+)NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to adulthood.EtOH(100 mM)also significantly inhibited the proliferation to 39.2%and differentiation of primary NSCs in vitro.Adult mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus,which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycinenhancer of zeste homolog 2 pathway.In vivo tracing revealed that EtOH induced abnormal orientation of tdTom+NSCs and spatial misposition defects of newborn neurons,thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.
基金supported by STI2030-Major Projects(2022ZD0204900)the National Natural Science Foundation of China(NSFC)(91632103,31900732,31771157)+5 种基金the Program of Shanghai Subject Chief Scientist(17XD1401700)National Key Research and Development Program of China(2018YFE0126700)the Shanghai Education Commission Research and Innovation Program(2019-01-07-00-02-E00037)Natural Science Foundation of Chongqing cstc2021jcyjmsxmX1176,the‘111’Program of Higher Education Discipline Innovation,‘Eastern Scholar’(Shanghai Municipal Education Commission),Shanghai Municipal Commission of Science and Technology Program(21dz2210100)China Postdoctoral Science Foundation(202N1702133,2021M702137)The National Science Fund for Distinguished Young Scholars(31900732).
文摘Background Kabukisyndrome(KS)is arare developmental disorder characterised by multiple congenital anomalies and intellectual disability.UTX(ubiquitously transcribed tetratricopeptide repeat,X chromosome),which encodes a histone demethylase,is one of the two major pathogenic risk genes for KS.Although intellectual disability is a key phenotype of KS,the role of UTX in cognitive function remains unclear.Currently,no targeted therapies are available for KS.Aims This study aimed to investigate how UTX regulates cognition,to explore the mechanisms underlying UTX dysfunction and to identify potential molecular targets for treatment.Methods WegeneratedUTXconditional knockoutmice and found that UTX deletion downregulated calmodulin transcription by disrupting H3K27me3(trimethylated histone H3 at lysine 27)demethylation.Results UTX-knockout mice showeddecreased phosphorylation of calcium/calmodulin-dependent protein kinase I,impaired long-term potentiation and deficit in remote contextual fear memory.These effects were reversed by an Food and Drug Administration-approved drug desipramine.Conclusions Our results reveal an epigenetic mechanism underlying the important role of UTX in synaptic plasticity and cognitive function,and suggest that desipramine could be a potential treatment for KS.
基金The authors gratefully acknowledge financial support from National Natural Science Foundation of China(81872818)National Key R&D Program of China(2021YFE0115200).
文摘Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.
基金Supported by National Natural Science Foundation of China(Grant Nos.52075458 and U2141211).
文摘Graphene as a lubricating additive holds great potential for industrial lubrication. However, its poor dispersity and compatibility with base oils and grease hinder maximizing performance. Here, the infuence of graphene dispersion on the thickening efect and lubrication function is considered. A well-dispersed lubricant additive was obtained via trihexyl tetradecyl phosphonium bis(2-ethylhexyl) phosphate modifed graphene ([P_(66614)][DEHP]-G). Then lithium complex grease was prepared by saponifcation with 12-OH stearic acid, sebacic acid, and lithium hydroxide, using polyalphaolefn (PAO20) as base oil and the modifed-graphene as lubricating additive, with the original graphene as a comparison. The physicochemical properties and lubrication performance of the as-prepared greases were evaluated in detail. The results show that the as-prepared greases have high dropping point and colloidal stability. Furthermore, modifed-graphene lithium complex grease ofered the best friction reduction and anti-wear abilities, manifesting the reduction of friction coefcient and wear volume up to 18.84% and 67.34%, respectively. With base oil overfow and afux, well-dispersed [P_(66614)][DEHP]-G was readily adsorbed to the worn surfaces, resulting in the formation of a continuous and dense graphene deposition flm. The synergy of deposited graphene-flm, spilled oil, and adhesive grease greatly improves the lubrication function of grease. This research paves the way for modulating high-performance lithium complex grease to reduce the friction and wear of movable machinery.
基金The studies involving human participants were approved by The First Affiliated Hospital of Jinan University Ethics Committee(KY-2021-095)The participants provided their written informed consent to participate in this study+1 种基金Animalinvolved experimental protocols were compliance with guidelines and licensesapproved by the Laboratory Animal Center of Jinan University(20220225-65).
文摘The dysregulation of exosomal microRNAs(miRNAs)plays a crucial role in the development and progression of cancer.This study investigated the role of a newly identified serum exosomal miRNA miR-4256 in gastric cancer(GC)and the underlying mechanisms.The differentially expressed miRNAs were firstly identified in serum exosomes of GC patients and healthy individuals using next-generation sequencing and bioinformatics.Next,the expression of serum exosomal miR-4256 was analyzed in GC cells and GC tissues,and the role of miR-4256 in GC was investigated by in vitro and in vivo experiments.Then,the effect of miR-4256 on its downstream target genes HDAC5/p16^(INK4a) was studied in GC cells,and the underlying mechanisms were evaluated using dual luciferase reporter assay and Chromatin Immunoprecipitation(ChIP).Additionally,the role of the miR-4256/HDAC5/p16^(INK4a) axis in GC was studied using in vitro and in vivo experiments.Finally,the upstream regulators SMAD2/p300 that regulate miR-4256 expression and their role in GC were explored using in vitro experiments.miR-4256 was the most significantly upregulated miRNA and was overexpressed in GC cell lines and GC tissues;in vitro and in vivo results showed that miR-4256 promoted GC growth and progression.Mechanistically,miR-4256 enhanced HDAC5 expression by targeting the promoter of the HDAC5 gene in GC cells,and then restrained the expression of p16^(INK4a) through the epigenetic modulation of HDAC5 at the p16INK4a promoter.Furthermore,miR-4256 overexpression was positively regulated by the SMAD2/p300 complex in GC cells.Our data indicate that miR-4256 functions as an oncogene in GC via the SMAD2/miR-4256/HDAC5/p16^(INK4a) axis,which participates in GC progression and provides novel therapeutic and prognostic biomarkers for GC.
基金Sponsored by the National Natural Science Foundation of China(Grant No.11302158)the Natural Science Foundation of Shaanxi Province,China(Grant No.2018JM1044)
文摘Shape Memory Alloy(SMA)is a typical material with memory effect,and it is widely used in many engineering fields.Based on the elastic theory and Galerkin method,a vibration system of SMA beam with rigid constraints is proposed.The non⁃smooth transformation was employed to deal with the discontinuous position,and the original system was turned into an approximate equivalent system associated with the Dirac function.Then,using the stochastic averaging method,the drift and diffusion coefficients of the corresponding Fokker Planck Kolmogorov equation were described.Lastly,the approximate probability response of the system was formulated analytically.Meanwhile,numerical simulation was carried out to verify the effectiveness of analytical results.Furthermore,stochastic bifurcation was discussed.Results show that the stationary probability response of the system was affected by the increase of noise amplitude and restitution force,and a certain restitution value and damping could induce P⁃bifurcation.
基金the National Basic Research Program of China(973 Program)(No.2009CB930300)National Natural Science Foundation of China(No.81273449).
文摘The purpose of this study was to develop poly(amidoamine)(PAMAM)-functionalized multi-walled carbon nanotubes(MWNTs)loaded with a poorly water-soluble drug,intended to improve the drug-loading capacity,dissolution and design a sustained release system.MWNTs were modified with a carboxyl group by acid treatment and then complex with PAMAM.PAMAM-MWNTs were investigated as a scaffold for loading the model drug,Carvedilol(CAR),using three different methods(the fusion method,the incipient wetness impregnation method,and the solvent method).The effects of different pore size,specific surface area and physical state were systematically studied using FT-IR,TGA,SEM,DSC,nitrogen adsorption,XPS and XRD.All the samples made by PAMAM-MWNTs to load the drug had a marked effect on the drug-loading capacity as well as drug dissolution,especially theⅡ-30%.
基金supported by the National Key R&D Program(the 14th Five-Year Plan)(no.2023YFC2706001 and no.2023YFC2706003).
文摘Cancer has long been amajor threat to human health.Recent advancements inmolecular imaging have revolutionized cancer research by enabling early and precise disease localization,essential for effective management.In particular,optical molecular imaging is an invaluable cancer detection tool in preoperative planning,intraoperative guidance,and postoperative monitoring owing to its noninvasive nature,rapid turnover,safety,and ease of use.The tumor microenvironment and cells within it express distinct biomarkers.Optical imaging technology leverages these markers to differentiate tumor tissues from surrounding tissues and capture real-time images with high resolution.Nevertheless,a robust understanding of these cancer-relatedmolecules and their dynamic changes is crucial for effectivelymanaging cancer.Recent advancements in opticalmolecular imaging technologies offer novel approaches for cancer investigation in research and practice.This review investigates themodern opticalmolecular imaging techniques employed in both preclinical and clinical research,including bioluminescence,fluorescence,chemiluminescence,photoacoustic imaging,and Raman spectroscopy.We explore the current paradigm of optical molecular imaging modalities,their current status in preclinical cancer research and clinical applications,and future perspectives in the fields of cancer research and treatment.
基金funded by Chongqing Special Key Project of Technology Innovation and Application Development(Grant No.cstc2019jscx-dxwt BX0016)Guiding Project of Scientific Research Program in Ministry of Education of Hubei Province (No. B2021025)Fundamental Research Funds for the Central Universities (2022CDJXY-010 and 2022CDJQY-013)。
文摘Hydrogen energy has been recognized as “Ultimate Power Source” in the 21st century, which could be the best solution to the looming energy crisis and climate degeneration in the near future. Due to its high safety, low price, abundant resources and decent hydrogen storage density, magnesium based solid-state hydrogen storage materials are becoming the leading candidate for onboard hydrogen storage. However,the high operation temperature and slow reaction rate of MgH_(2), as a result of the large formation enthalpy and high reaction activation energy,respectively, are the first and most difficult problems we need to face and overcome to realize its industrialization. Herein, a state-of-the-art review on tailoring the stable thermodynamics and sluggish kinetics of hydrogen storage in MgH_(2), particularly through nanoengnieering and catalysis is presented, aiming to provide references and solutions for its promotion and application. Promising methods to overcome the challenges faced by MgH_(2)/Mg, such as bidirectional catalysts and nanoconfinement with in-situ catalysis are compared and the required improvements are discussed to stimulate further discussions and ideas in the rational design of MgH_(2)/Mg systems with ability for hydrogen release/uptake at lower temperatures and cycle stability in the near future.
基金financially supported by the National Natural Science Foundation of China (Grants Nos. 52064013, 52064014, 52072323 and 52122211)the “Double-First Class” Foundation of Materials and Intelligent Manufacturing Discipline of Xiamen University。
文摘Aqueous zinc ion batteries(AZIBs) demonstrate tremendous competitiveness and application prospects because of their abundant resources,low cost, high safety, and environmental friendliness. Although the advanced electrochemical energy storage systems based on zinc ion batteries have been greatly developed, many severe problems associated with Zn anode impede its practical application, such as the dendrite formation,hydrogen evolution, corrosion and passivation phenomenon. To address these drawbacks, electrolytes, separators, zinc alloys, interfacial modification and structural design of Zn anode have been employed at present by scientists. Among them, the structural design for zinc anode is relatively mature, which is generally believed to enhance the electroactive surface area of zinc anode, reduce local current density, and promote the uniform distribution of zinc ions on the surface of anode. In order to explore new research directions, it is crucial to systematically summarize the structural design of anode materials. Herein, this review focuses on the challenges in Zn anode, modification strategies and the three-dimensional(3D) structure design of substrate materials for Zn anode including carbon substrate materials, metal substrate materials and other substrate materials. Finally, future directions and perspectives about the Zn anode are presented for developing high-performance AZIBs.
基金support by the National Natural Science Foundation of China(32071959)the Natural Science Foundation of Shandong Province(ZR2020QC104)Taishan Industrial Leading Talents Project.
文摘With global warming, high-temperature(HT) stress has become a major abiotic stress for crops, in particular summer maize in China. Photosynthesis is sensitive to HT. Salicylic acid(SA) and 6-benzyladenine(6-BA) can improve the adaptation of plants to various biotic and abiotic stresses. However, their contribution to maintaining photosynthetic activity and alleviating photoinhibition in maize leaves under HT stress is still unclear. The effects of exogenous SA or 6-BA on growth, photosynthesis capacity, photosystem Ⅱ(PSII) activity, subcellular ultrastructure, antioxidant system, and plant hormones in maize leaves under HT stress were investigated. Under HT conditions, application of SA or 6-BA up-regulated gibberellin and zeatin content in leaves, increasing leaf area index(LAI). It also expanded the stomata by reducing abscisic acid and jasmonic acid content in leaves, cooling them and increasing CO2supply to photosynthesis. A higher net photosynthetic rate, combined with increased activity of the antioxidant system, alleviated oxidative stress in maize plants sprayed with SA or 6-BA, allowing them to maintain their chloroplast ultrastructure and PSII activity, in particular electron transfer from QAto QB. The increased LAI and net photosynthetic rate per unit leaf area also resulted in the accumulation of more biomass.
基金We would like to thank the support by the National Key Research and Development Program of China(2018YFA0703000)National Natural Science Foundation of China(Grant No.51875518)+1 种基金Key Research and Development Projects of Zhejiang Province(Grant No.2017C01054 and No.2018C03062)the Fundamental Research Funds for the Central Universities(Grant No.2019XZZX003-02,2019FZA4002).
文摘Treatments for lesions in central nervous system(CNS)are always faced with challenges due to the anatomical and physiological particularity of the CNS despite the fact that several achievements have been made in early diagnosis and precision medicine to improve the survival and quality of life of patients with brain tumors in recent years.Understanding the complexity as well as role of the microenvironment of brain tumors may suggest a better revealing of the molecular mechanism of brain tumors and new therapeutic directions,which requires an accurate recapitulation of the complex microenvironment of human brain in vitro.Here,a 3D bioprinted in vitro brain matrix-mimetic microenvironment model with hyaluronic acid(HA)and normal glial cells(HEBs)is developed which simulates both mechanical and biological properties of human brain microenvironment in vivo through the investigation of the formulation of bioinks and optimization of printing process and parameters to study the effects of different concentration of gelatin(GA)within the bioink and different printing structures of the scaffold on the performance of the brain matrix-mimetic microenvironment models.The study provides experimental models for the exploration of the multiple factors in the brain microenvironment and scaffolds for GBM invasion study.
基金We would like to thank the support by National KeyResearch andDevelopment Program of China(2018YFA0703000)Key Research and Development Projects of Zhejiang Province(Grant No.2017C01054)+1 种基金Natural Science Foundation of China(Grant Nos.51875518,51821093)the Fundamental Research Funds for the Central Universities(Grant Nos.2019XZZX003-02,2019FZA4002).
文摘Cancer is characterized by a high fatality rate,complex molecular mechanism,and costly therapies.The microenvironment of a tumor consists of multiple biochemical cues and the interaction between tumor cells,stromal cells,and extracellular matrix plays a key role in tumor initiation,development,angiogenesis,invasion and metastasis.To better understand the biological features of tumor and reveal the critical factors of therapeutic treatments against cancer,it is of great significance to build in vitro tumor models that could recapitulate the stages of tumor progression and mimic tumor behaviors in vivo for efficient and patient-specific drug screening and biological studies.Since conventional tissue engineering methods of constructing tumor models always fail to simulate the later stages of tumor development due to the lack of ability to build complex structures and angiogenesis potential,three-dimensional(3D)bioprinting techniques have gradually found its applications in tumor microenvironment modeling with accurate composition and well-organized spatial distribution of tumor-related cells and extracellular components in the past decades.The capabilities of building tumor models with a large range of scale,complex structures,multiple biomaterials and vascular network with high resolution and throughput make 3D bioprinting become a versatile platform in bio-manufacturing aswell as inmedical research.In this review,wewill focus on 3D bioprinting strategies,design of bioinks,current 3D bioprinted tumor models in vitro classified with their structures and propose future perspectives.
基金National Key Research and Development Program of China (2018YFA0703000)the National Natural Science Foundation of China (51875518)+1 种基金the Key Research and Development Projects of Zhejiang Province (2017C01054)the Fundamental Research Funds for the Central Universities(2020QNA4001 and 2019XZZX003-02) for their support
文摘Organ-on-a-chip technology,a promising three-dimensional(3D)dynamic culture method,ensures accu-rate and efficient cell culture and has great potential for replacing animal models in preclinical testing.The circulatory system,the most abundant organ in the human body,plays a crucial role in oxygen exchange and mass transfer,which is the determining factor for the survival of tissues and organs.Thus,it is essential to integrate the circulatory system into an organ-on-a-chip to recreate tissue and organ microenvironments and physiological functions.This review discusses the synergy between the vasculature and the emerging organ-on-a-chip technology,which offers even better possibilities of dupli-cating physiology and disease characteristics.In addition,we review the different steps of a vascularized organ-on-a-chip fabrication process,including structure fabrication and tissue construction using differ-ent biofabrication strategies.Finally,we outline the applicability of this technology in the fascinating and fast-developing field of organ and tumor culture.
基金Acknowledgements The authors would like to acknowledge the support from National Natural Science Foundation of China under Grant 81501607 and 51475419, Natural Science Foundation of Zhejiang Province of China under Grant LY15H160019, Key Research and Development Projects of Zhejiang Province under Grant 2017C 1054.
文摘Three-dimensional （3D） printing is a novel promising technology based on 3D imaging and layer-by-layer additive fabrication. It has a profound influence on all aspects of our lives and is playing an increasing important role in many areas including engineering, manufacturing, art, education and medicine. ＂3D bioprinting＂ has been put forward with the technical progress in 3D printing and might be a possible way to solve the serious problem of human organ shortage in tissue engineering and regenerative medicine. Many research groups flung them into this area and have already made some gratifying achievements. However, it is a long way to fabricate a live organ. Many elements lead to the limitation of 3D bioprinting. This review introduces the background and development history of 3D bioprinting, compares different approaches of 3D bioprinting and illustrates the key factors of the printing process. Meanwhile, this review also points out existing challenges of 3D bioprinting and has a great prospect. Some points proposed in this review might be served as reference for the research of this field.
基金We thank professor Yu-Jin Hao(College of Horticulture Science and Engineering,Shandong Agricultural University)for providing the plasmid for the EMSA experiment.All data generated and analyzed in this study are shown in the article or attached as supplementary data.All the materials used in the study are available upon reasonable request fromthe corresponding author.This work was supported by the National Natural Science Foundation of China(Grant no.U21A20227)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant no.XDA23080602).Research conducted as part of the LIA INNOGRAPE International Associated Laboratory.
文摘Anthocyanins are essential for the quality of perennial horticultural crops,such as grapes.In grapes,ELONGATED HYPOCOTYL 5(HY5)and MYBA1 are two critical transcription factors that regulate anthocyanin biosynthesis.Our previous work has shown that Vitis vinifera B-box protein 44(VvBBX44)inhibits anthocyanin synthesis and represses VvHY5 expression in grape calli.However,the regulatory mechanism underlying this regulation was unclear.In this study,we found that loss of VvBBX44 function resulted in increased anthocyanin accumulation in grapevine callus.VvBBX44 directly represses VvMYBA1,which activates VvBBX44.VvMYBA1,but not VvBBX44,directly modulates the expression of grape UDP flavonoid 3-O-glucosyltransferase(VvUFGT).We demonstrated that VvBBX44 represses the transcriptional activation of VvUFGT and VvBBX44 induced by VvMYBA1.However,VvBBX44 and VvMYBA1 did not physically interact in yeast.The application of exogenous anthocyanin stimulated VvBBX44 expression in grapevine suspension cells and tobacco leaves.These findings suggest that VvBBX44 and VvMYBA1 form a transcriptional feedback loop to prevent overaccumulation of anthocyanin and reduce metabolic costs.Our work sheds light on the complex regulatory network that controls anthocyanin biosynthesis in grapevine.
基金Supported by Guiding Science and Technology Plan Project of Yongzhou City(Yong Ke Fa[2015]10)
文摘[Objectives] This study aimed to optimize the conditions for pressurized synchronous extraction of volatile oils, total flavonoids and tannic acid from Artemisia argyi .[Methods] Single factor experiments and orthogonal experiments were conducted.[Results] Pressurization had a significant effect on the extraction rate of chemical constituents of A. argyi . The optimal conditions for pressurized synchronous extraction of volatile oils, total flavonoids and tannic acid from A. argyi were as follows: solvent concentration of 70%, solid to liquid ratio of 1∶ 30 (g/mL), extraction pressure of 0.9 MPa, extraction time of 40 min and extraction temperature of 90 ℃. Under the optimal extraction conditions, the yields of volatile oils, total flavonoids and tannic acid were 0.852%, 4.66% and 6.79%, respectively.[Conclusions] Compared with other extraction methods, the pressurized assistant solvent extraction method can achieve the synchronous extraction of volatile oils, total flavonoids and tannic acid from A. argyi . The process is stable, short in extraction time, high in solvent utilization rate and ideal in extraction effect of the three components from A. argyi .
基金Supported by Scientific Research Project of Hunan Provincial Department of Education (21C1516)the Scientific Research Project of Education Department of Yongzhou City,Hunan Province,China (2020-YZKJ-036)
文摘[Objectives]To determine and analyze amino acid content in Maca from different habitats and varieties.[Methods]Maca from two habitats and three colors were selected and a kind of turnip commonly used was to fake Maca.After optimizing the hydrolysis conditions,100 mg Maca samples were hydrolyzed in the concentration of 6 mol/L hydrochloric acid at 110℃for 24 h.The content range of amino acids in each sample was detected by HPLC.[Results]The average total content of amino acids in Maca was 9.52 g/100 g.Yunnan yellow Maca contained 16 kinds of amino acids,including 7 kinds of human essential amino acids,accounting for 17.2%of the total amino acids while Yunnan purple Maca held 16 kinds of amino acids,counting 7 kinds of human essential amino acids,accounting for 16.5%of the total amino acids.The amino acid ratio coefficient method also showed that the two kinds of Maca had higher nutritional value than the others.15 kinds of amino acids were detected in Yunnan black Maca,including 6 kinds of essential amino acids,accounting for 9.60%of the total amino acids.Among amino acids in Yunnan Maca,the highest content was Arg.A total of 12 kinds of amino acids,together with 6 essential human amino acids,were determined in Peru black Maca,accounting for 11.6%of the total amino acids.In Peru black Maca the highest concentration of amino acid was Pro.It was noteworthy that the amino acid species were comprehensive in Maca,and high level of amino acids resulted in high nutritional value.Its specific amino acid composition ratio was obviously different from Turnip,the counterfeit goods to deceive customers.[Conclusions]The method of automatic amino acid analyzer is simple and accurate,and can be used for the identification and content determination of amino acids in Maca as amino acid is an essential nutrient in Maca.
