Substance P is an endogenous neurokinin that is present in the central and peripheral nervous systems. The neuropeptide substance P and its high-affinity receptor neurokinin 1 receptor are known to play an important r...Substance P is an endogenous neurokinin that is present in the central and peripheral nervous systems. The neuropeptide substance P and its high-affinity receptor neurokinin 1 receptor are known to play an important role in the central nervous system in inflammation, blood pressure, motor behavior and anxiety. The effects of substance P in the hippocampus and the marginal di- vision of the striatum on memory remain poorly understood. Compared with the hippocampus as a control, immunofluorescence showed high expression of the substance P receptor, neuro- kinin 1, in the marginal division of the striatum of normal rats. Unilateral or bilateral injection of an antisense oligonucleotide against neurokinin 1 receptor mRNA in the rat hippocampus or marginal division of the striatum effectively reduced neurokinin 1 receptor expression. Indepen- dent of injection site, rats that received this antisense oligonucleotide showed obviously increased footshock times in a Y-maze test. These results indicate that the marginal division of the striatum plays a similar function in learning and memory to the hippocampus, which is a valuable addi- tion to our mechanistic understanding of the learning and memory functions of the marginal division of the striatum.展开更多
SQUAMOSA-promoter binding protein-like (SPL) proteins are plant-specific transcription factors and participate in different pathways, including the vegetative to reproductive transition, male sterility, biosynthesis o...SQUAMOSA-promoter binding protein-like (SPL) proteins are plant-specific transcription factors and participate in different pathways, including the vegetative to reproductive transition, male sterility, biosynthesis of gibberellic acid (GA), plant morphogenesis and response to environmental stress. In this study, we generated transgenic Arabidopsis that overexpressed Betula BplSPL8 and confirmed that BplSPL8 is a transcription factor with transcriptional activation activity and is located in the nucleus. Functional analysis of BplSPL8 showed that it is involved in regulating different development processes: (1) BplSPL8 can delay flowering by reducing sensitivity to GA under short days; (2) BplSPL8 controls the number and morphogenesis of leaves, including up-rolling leaves under long days and folded leaves mediated by GA under short days; (3) BplSPL8 can promote root elongation during late development of roots and inhibit lateral root formation; (4) BplSPL8 may be involved in regulating carotenoid biosynthesis and secretion metabolism. These results show that there is a complex regulatory network for the SPL family genes that is mediated by other components and may provide a new insights for the functional research of SPL genes.展开更多
Objective:To provide guidelines for the prevention of post-stroke dementia,we investigated whether stroke patients were aware of post-stroke dementia and their level of dementia-related knowledge.Methods:Five dementia...Objective:To provide guidelines for the prevention of post-stroke dementia,we investigated whether stroke patients were aware of post-stroke dementia and their level of dementia-related knowledge.Methods:Five dementia-related questions were designed.A field survey was conducted in a questionand-answer method using the designed questions.The surveys assessed 3000 stroke patients(2 weekse6 months after stroke attacks)from 14 hospitals/clinical centers in 7 provinces and cities across China.Results:Among 3000 stroke patients,80.5%had heard of dementia,39.1%knew that stroke can lead to dementia,55.7%believed dementia can be prevented,50.8%thought dementia can be cured,and only 8.8%had ever seen a doctor because of memory deterioration.Then,patients were classified into three groups,including a no cognitive impairment(NCI)group,a mild cognitive impairment(MCI)group,and a mild dementia(MD)group.Among the MCI and MD groups,only 8.7%(75/861)and 9.9%(64/649)of patients,respectively,had ever seen a doctor because of memory deterioration.According to our results,patients with a higher level of cognitive impairment had a lower awareness of dementia(P<.001).Conclusion:The awareness of dementia in stroke patients in China is low,and the consultation rate is even lower.Moreover,patients with a higher level of cognitive impairment have a lower awareness of dementia.To improve public awareness and improve prevention,more emphasis should be put on education regarding post-stroke dementia.Routine cognitive function screening should be conducted on stroke patients as an effective way to assess dementia.展开更多
Based on results of previous studies,through investigations,the status quo,main advantages and disadvantages of using small hand-power scutchers and large-scale automatic sisal production lines to process sisal fiber ...Based on results of previous studies,through investigations,the status quo,main advantages and disadvantages of using small hand-power scutchers and large-scale automatic sisal production lines to process sisal fiber were summarized and analyzed; the traditional uses and latest products of sisal fiber were studied,especially the comprehensive utilization of byproducts produced during sisal fiber processing as well as the broad prospects of new sisal products.展开更多
[Objectives]To explore the molecular mechanism of Zhizi Ganjiang Decoction(ZZGJD)regulating sleep disorders based on the network pharmacology.[Methods]The BATMAN-TCM server was used to predict the potential targets of...[Objectives]To explore the molecular mechanism of Zhizi Ganjiang Decoction(ZZGJD)regulating sleep disorders based on the network pharmacology.[Methods]The BATMAN-TCM server was used to predict the potential targets of ZZGJD and constructed a compound-disease-target network map,and the GeneCards database was used to search for insomnia-related targets;with the aid of Cytoscape 3.5.1 software,the compound-insomnia target interaction network and protein-protein interaction(PPI)network were constructed,and gene ontology(GO)enrichment,Reactome pathway enrichment,and biological pathway enrichment analysis based on KEGG(Kyoto Encyclopedia of Genes and Enomes)was performed.[Results]The constructed PPI network of ZZGJD involves 204 nodes and 645 interaction relationships.Key nodes involve G protein-coupled receptors,rhodopsin-like adrenaline receptor families,zinc finger proteins,nuclear hormone receptor superfamilies,ligand-binding domains of hormone receptors,voltage-gated calcium(Ca^(2+))channel IQ domains,and neuropituitary hormones.The related entries of GO enrichment analysis pathway mainly involve G protein-coupled receptor activity,neurotransmitter receptor activity,adrenergic receptor activity,ammonium ion binding,catecholamine binding,G protein-coupled serotonin receptor activity,serotonin receptor activity,and steroid hormone receptors(SHRs)activity.Reactome pathway mainly involves amine ligand binding receptors,rhodopsin-like receptors,G protein-coupled receptor ligand binding,adrenergic receptors,neuronal systems and signal transduction,etc.KEGG channel analysis mainly involves neural activity ligand-receptor interaction,calcium ion messenger pathway,cAMP signaling pathway,serotonergic synapse,dopaminergic synapse,cGMP-PKG signaling pathway,and cholinergic synapse pathway,etc.[Conclusions]The potential targets of ZZGJD in the treatment of insomnia mainly involve G protein-coupled receptors,and regulate various neural receptor pathways such as calcium ion channels,serotonin,dopamine,and adrenergic receptors.INS,IGF-1,CTNNB1,ESR1,HIF-1A,etc.may be the key targets of ZZGJD in regulating sleep disorders,reflecting the multi-target and overall function characteristics of Chinese herbal compounds.ZZGJD is of great significance in the treatment of sleep disorders caused by blood sugar abnormality in patients with diabetes and perimenopausal hormones in women.This article is expected to It provide new ideas for in-depth study of the molecular mechanism of ZZGJD.展开更多
A new type of grain-interior planar defect in a ceramic phase in TiC doped cemented tungsten carbides was discovered.It is unique in that the monolayers of metal atoms exist stably in ceramic grains.The planar defects...A new type of grain-interior planar defect in a ceramic phase in TiC doped cemented tungsten carbides was discovered.It is unique in that the monolayers of metal atoms exist stably in ceramic grains.The planar defects were induced by the ordered heteroatoms distributing on certain crystal planes of the matrix,which are distinct from the known planar defects such as phase-,grain-,and twin-boundaries,stacking faults,and complexions.Detailed characterization on the atomic scale was performed for the composition,structure,and crystallography of the planar defects,and their energy state and stability were evaluated by modeling.It was found that the Ti monolayer assists nucleation of the new WC crystal along the normal direction to its basal plane.Due to the disturbance of the heteroatom layer,the deposition of W and C atoms deviates from the regular sites occupied in the perfect crystal lattice,resulting in variations of the W–C arrangement in the grain structure.Experiments confirmed that tailoring the distribution density of the planar defects could give the best comprehensive mechanical performance with simultaneously outstanding strength and fracture toughness in the materials containing the grain-interior planar defects.This study provides a new strategy to greatly enhance the mechanical properties of materials by introducing and tailoring planar defects in the grain interiors.展开更多
Winter plants rely on vernalization,a crucial process for adapting to cold conditions and ensuring successful reproduction.However,understanding the role of histone modifications in guiding the vernalization process i...Winter plants rely on vernalization,a crucial process for adapting to cold conditions and ensuring successful reproduction.However,understanding the role of histone modifications in guiding the vernalization process in winter wheat remains limited.In this study,we investigated the transcriptome and chromatin dynamics in the shoot apex throughout the life cycle of winter wheat in the field.Two core histone modifications,H3K27me3 and H3K36me3,exhibited opposite patterns on the key vernalization gene VERNALIZATION1(VRN1),correlating with its induction during cold exposure.Moreover,the H3K36me3 level remained high at VRN1 after cold exposure,which may maintain its active state.Mutations in FERTILIZATION-INDEPENDENT ENDOSPERM(TaFIE)and SET DOMAIN GROUP 8/EARLY FLOWERING IN SHORT DAYS(TaSDG8/TaEFS),components of the writer complex for H3K27me3 and H3K36me3,respectively,affected flowering time.Intriguingly,VRN1 lost its high expression after the cold exposure memory in the absence of H3K36me3.During embryo development,VRN1 was silenced with the removal of active histone modifications in both winter and spring wheat,with selective restoration of H3K27me3 in winter wheat.The mutant of Tafie-cr-87,a component of H3K27me3“writer”complex,did not influence the silence of VRN1during embryo development,but rather attenuated the cold exposure requirement of winter wheat.Integrating gene expression with H3K27me3 and H3K36me3 patterns identified potential regulators of flowering.This study unveils distinct roles of H3K27me3 and H3K36me3 in controlling vernalization response,maintenance,and resetting in winter wheat.展开更多
The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still epidemic around the world.The manipulation of SARS-CoV-2 is restricted to biosafety level 3 laboratories(BSL-3).In this study,we developed a SARS...The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still epidemic around the world.The manipulation of SARS-CoV-2 is restricted to biosafety level 3 laboratories(BSL-3).In this study,we developed a SARS-CoV-2ΔN-GFP-HiBiT replicon delivery particles(RDPs)encoding a dual reporter gene,GFP-HiBiT,capable of producing both GFP signal and luciferase activities.Through optimal selection of the reporter gene,GFP-HiBiT demonstrated superior stability and convenience for antiviral evaluation.Additionally,we established a RDP infection mouse model by delivering the N gene into K18-hACE2 KI mouse through lentivirus.This mouse model supports RDP replication and can be utilized for in vivo antiviral evaluations.In summary,the RDP system serves as a valuable tool for efficient antiviral screening and studying the gene function of SARS-CoV-2.Importantly,this system can be manipulated in BSL-2 laboratories,decreasing the threshold of experimental requirements.展开更多
A unique feature of coronaviruses is their utilization of self-encoded nonstructural protein 16(nsp16),20-Omethyltransferase(20-O-MTase),to cap their RNAs through ribose 20-O-methylation modification.This process is c...A unique feature of coronaviruses is their utilization of self-encoded nonstructural protein 16(nsp16),20-Omethyltransferase(20-O-MTase),to cap their RNAs through ribose 20-O-methylation modification.This process is crucial for maintaining viral genome stability,facilitating efficient translation,and enabling immune escape.Despite considerable advances in the ultrastructure of SARS-CoV-2 nsp16/nsp10,insights into its molecular mechanism have so far been limited.In this study,we systematically characterized the 20-O-MTase activity of nsp16 in SARS-CoV-2,focusing on its dependence on nsp10 stimulation.We observed cross-reactivity between nsp16 and nsp10 in various coronaviruses due to a conserved interaction interface.However,a single residue substitution(K58T)in SARS-CoV-2 nsp10 restricted the functional activation of MERS-CoV nsp16.Furthermore,the cofactor nsp10 effectively enhanced the binding of nsp16 to the substrate RNA and the methyl donor Sadenosyl-L-methionine(SAM).Mechanistically,His-80,Lys-93,and Gly-94 of nsp10 interacted with Asp-102,Ser-105,and Asp-106 of nsp16,respectively,thereby effectively stabilizing the SAM binding pocket.Lys-43 of nsp10 interacted with Lys-38 and Gly-39 of nsp16 to dynamically regulate the RNA binding pocket and facilitate precise binding of RNA to the nsp16/nsp10 complex.By assessing the conformational epitopes of nsp16/nsp10 complex,we further determined the critical residues involved in 20-O-MTase activity.Additionally,we utilized an in vitro biochemical platform to screen potential inhibitors targeting 20-O-MTase activity.Overall,our results significantly enhance the understanding of viral 20-O methylation process and mechanism,providing valuable targets for antiviral drug development.展开更多
Molecular subtyping of gastric cancer(GC)aims to comprehend its genetic landscape.However,the efficacy of current subtyping methods is hampered by their mixed use of molecular features,a lack of strategy optimization,...Molecular subtyping of gastric cancer(GC)aims to comprehend its genetic landscape.However,the efficacy of current subtyping methods is hampered by their mixed use of molecular features,a lack of strategy optimization,and the limited availability of public GC datasets.There is a pressing need for a precise and easily adoptable subtyping approach for early DNA-based screening and treatment.Based on TCGA subtypes,we developed a novel DNA-based hierarchical classifier for gastric cancer molecular subtyping(HCG),which employs gene mutations,copy number aberrations,and methylation patterns as predictors.By incorporating the closely related esophageal adenocarcinomas dataset,we expanded the TCGA GC dataset for the training and testing of HCG(n=453).The optimization of HCG was achieved through three hierarchical strategies using Lasso-Logistic regression,evaluated by their overall the area under receiver operating characteristic curve(auROC),accuracy,F1 score,the area under precision-recall curve(auPRC)and their capability for clinical stratification using multivariate survival analysis.Subtype-specific DNA alteration biomarkers were discerned through difference tests based on HCG defined subtypes.Our HCG classifier demonstrated superior performance in terms of overall auROC(0.95),accuracy(0.88),F1 score(0.87)and auPRC(0.86),significantly improving the clinical stratification of patients(overall p-value=0.032).Difference tests identified 25 subtype-specific DNA alterations,including a high mutation rate in the SYNE1,ITGB4,and COL22A1 genes for the MSI subtype,and hypermethylation of ALS2CL,KIAA0406,and RPRD1B genes for the EBV subtype.HCG is an accurate and robust classifier for DNA-based GC molecular subtyping with highly predictive clinical stratification performance.The training and test datasets,along with the analysis programs of HCG,are accessible on the GitHub website(github.com/LabxSCUT).展开更多
Combining multiple crop protection Unmanned Aerial Vehicles(UAVs)as a team for a scheduled spraying mission over farmland now is a common way to significantly increase efficiency.However,given some issues such as diff...Combining multiple crop protection Unmanned Aerial Vehicles(UAVs)as a team for a scheduled spraying mission over farmland now is a common way to significantly increase efficiency.However,given some issues such as different configurations,irregular borders,and especially varying pesticide requirements,it is more important and more complex than other multi-Agent Systems(MASs)in common use.In this work,we focus on the mission arrangement of UAVs,which is the foundation of other high-level cooperations,systematically propose Efficiency-first Spraying Mission Arrangement Problem(ESMAP),and try to construct a united problem framework for the mission arrangement of crop protection UAVs.Besides,to characterise the differences in sub-areas,the varying pesticide requirement per unit is well considered based on Normalized Difference Vegetation Index(NDVI).Firstly,the mathematical model of multiple crop-protection UAVs is established and ESMAP is defined.Furthermore,an acquisition method of a farmland’s NDVI map is proposed,and the calculation method of pesticide volume based on NDVI is discussed.Secondly,an improved Genetic Algorithm(GA)is proposed to solve ESMAP,and a comparable combination algorithm is introduced.Numerical simulations for algorithm analysis are carried out within MATLAB,and it is determined that the proposed GA is more efficient and accurate than the latter.Finally,a mission arrangement tested with three UAVs was carried out to validate the effectiveness of the proposed GA in spraying operation.Test results illustrated that it performed well,which took only 90.6%of the operation time taken by the combination algorithm.展开更多
Studying the regulatory mechanisms that drive nitrogen-use efficiency(NUE)in crops is important for sustainable agriculture and environmental protection.In this study,we generated a high-quality genome assembly for th...Studying the regulatory mechanisms that drive nitrogen-use efficiency(NUE)in crops is important for sustainable agriculture and environmental protection.In this study,we generated a high-quality genome assembly for the high-NUE wheat cultivar Kenong 9204 and systematically analyzed genes related to nitrogen uptake and metabolism.By comparative analyses,we found that the high-affinity nitrate transporter gene family had expanded in Triticeae.Further studies showed that subsequent functional differentiation endowed the expanded family members with saline inducibility,providing a genetic basis for improving the adaptability of wheat to nitrogen deficiency in various habitats.To explore the genetic and molecular mechanisms of high NUE,we compared genomic and transcriptomic data from the high-NUE cultivar Kenong 9204(KN9204)and the low-NUE cultivar Jing 411 and quantified their nitrogen accumulation under high-and low-nitrogen conditions.Compared with Jing 411,KN9204 absorbed significantly more nitrogen at the reproductive stage after shooting and accumulated it in the shoots and seeds.Transcriptome data analysis revealed that nitrogen deficiency clearly suppressed the expression of genes related to cell division in the young spike of Jing 411,whereas this suppression of gene expression was much lower in KN9204.In addition,KN9204 maintained relatively high expression of NPF genes for a longer time than Jing 411 during seed maturity.Physiological and transcriptome data revealed that KN9204 was more tolerant of nitrogen deficiency than Jing 411,especially at the reproductive stage.The high NUE of KN9204 is an integrated effect controlled at different levels.Taken together,our data provide new insights into the molecular mechanisms of NUE and important gene resources for improving wheat cultivars with a higher NUE trait.展开更多
The grain-size dependence of wear resistance of WC-Co cemented carbides(with mean WC grain sizes of 2.2μm,1.6μm,0.8μm and 0.4μm,respectively)was investigated under different tribological conditions.The results sho...The grain-size dependence of wear resistance of WC-Co cemented carbides(with mean WC grain sizes of 2.2μm,1.6μm,0.8μm and 0.4μm,respectively)was investigated under different tribological conditions.The results showed that the grain size had opposite effects on wear resistance of the cemented carbides in dry sliding wear and microabrasion tests.In the former condition,with decrease of WC grain size hence the increase of hardness,plastic deformation,fracture,fragmentation and oxidation were all mitigated,leading to a drastic decrease in the wear rate.In the latter condition,pull-out of WC grains after Co removal dominated the wear,so that the hardness of cemented carbide was not a core factor.As a result,the wear resistance of the cemented carbide generally showed a decreasing trend with decrease of the grain size,except for a slight increase in the ultrafine-grained cemented carbide.Single-pass scratching of the cemented carbides under various loads indicated the same failure mechanism as that in the sliding wear tests.Furthermore,the reasons for severe surface oxidation of the coarse-grained cemented carbides were disclosed.展开更多
A deficit in spatial memory has been taken as an early predictor of Alzheimer’s disease(AD) or mild cognitive impairment(MCI). The uncinate fasciculus(UF) is a long-range white-matter tract that connects the anterior...A deficit in spatial memory has been taken as an early predictor of Alzheimer’s disease(AD) or mild cognitive impairment(MCI). The uncinate fasciculus(UF) is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex(OFC)in primates. Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD, but its exact role in spatial memory is not well understood. The pathway arising from the postrhinal cortex(POR) and projecting to the ventrolateral orbitofrontal cortex(vlOFC)performs most of the functions of the UF in rodents.Although the literature suggests an association between spatial memory and the regions connected by the POR–vlOFC pathway, the function of the pathway in spatialmemory is relatively unknown. To further illuminate the function of the UF in spatial memory, we dissected the POR–vlOFC pathway in mice. We determined that the POR–vlOFC pathway is a glutamatergic structure, and that glutamatergic neurons in the POR regulate spatial memory retrieval. We also demonstrated that the POR–vlOFC pathway specifically transmits spatial information to participate in memory retrieval. These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory, as in MCI and AD.展开更多
Based on a unique method to synthesize WC-Co composite powder by in-situ reactions of metal oxides and carbon, the effects of the carbon addition in the initial powders on the phase constitution, microstructure and me...Based on a unique method to synthesize WC-Co composite powder by in-situ reactions of metal oxides and carbon, the effects of the carbon addition in the initial powders on the phase constitution, microstructure and mechanical properties of the cemented carbides were investigated. It is found that with a suitable carbon addition the pure phase constitution can be obtained in the sintered bulk from the composite powder. The mechanical properties of the cemented carbides depend on the phase constitution and the WC grain structure. To obtain the excellent properties of the WC-Co bulk, it is important to obtain the pure phase constitution from the appropriate carbon addition in the initial powders and a suitable grain size.展开更多
Estrogen deficiency is one of the most frequent causes of osteoporosis in postmenopausal women.Under chronic inflammatory conditions caused by estrogen deficiency,activated T cells contribute to elevated levels of pro...Estrogen deficiency is one of the most frequent causes of osteoporosis in postmenopausal women.Under chronic inflammatory conditions caused by estrogen deficiency,activated T cells contribute to elevated levels of proinflammatory cytokines,impaired osteogenic differentiation capabilities of bone marrow mesenchymal stem cells(BMMSCs),and disturbed regulatory T cell(Treg)/Th17 cell balance.However,therapeutic strategies that re-establish immune homeostasis in this disorder have not been well developed.Here,we produced T cell-depleting nanoparticles(TDNs)that ameliorated the osteopenia phenotype and rescued the osteogenic deficiency of BMMSCs in ovariectomized(OVX)mice.TDNs consist of monocyte chemotactic protein-1(MCP-1)-encapsulated mesoporous silica nanoparticles as the core and Fas-ligand(FasL)as the corona.We showed that the delicate design of the TDNs enables rapid release of MCP-1 to recruit activated T cells and then induces their apoptosis through the conjugated FasL both in vitro and in vivo.Apoptotic signals recognized by macrophages help skew the Treg/Th17 cell balance and create an immune tolerant state,further attenuating the osteogenic deficiency of BMMSCs and the osteopenia phenotype.Mechanistically,we found that the therapeutic effects of TDNs were partially mediated by apoptotic T cell-derived extracellular vesicles(ApoEVs),which promoted macrophage transformation towards the M2 phenotype.These findings demonstrate that TDNs may represent a promising strategy for treating osteoporosis and other immune disorders.展开更多
As one of the most important crops in the world,rice(Oryza sativa)is a model plant for metabolome research.Although many studies have focused on the analysis of specific tissues,the changes in metab-olite abundance ac...As one of the most important crops in the world,rice(Oryza sativa)is a model plant for metabolome research.Although many studies have focused on the analysis of specific tissues,the changes in metab-olite abundance across the entire life cycle have not yet been determined.In this study,combining both tar-geted and nontargeted metabolite profiling methods,a total of 825 annotated metabolites were quantified in rice samples from different tissues covering the entire life cycle.The contents of metabolites in different tissues of rice were significantly different,with various metabolites accumulating in the plumule and radicle during seed germination.Combining these data with transcriptome data obtained from the same time period,we constructed the Rice Metabolic Regulation Network.The metabolites and co-expressed genes were further divided into 12 clusters according to their accumulation patterns,with members within each cluster displaying a uniform and clear pattern of abundance across development.Using this dataset,we established a comprehensive metabolic profile of the rice life cycle and used two independent strategies to identify novel transcription factors-namely the use of known regulatory genes as bait to screen for new networks underlying lignin metabolism and the unbiased identification of new glycerophospholipid metabolism regulators on the basis of tissue specificity.This study thus demonstrates how guilt-by-association analysis of metabolome and transcriptome data spanning the entire life cycle in cereal crops provides novel resources and tools to aid in understanding the mechanisms underlying important agro-nomic traits.展开更多
基金supported by the National Natural Science Foundation of China,No.30600797,30873238
文摘Substance P is an endogenous neurokinin that is present in the central and peripheral nervous systems. The neuropeptide substance P and its high-affinity receptor neurokinin 1 receptor are known to play an important role in the central nervous system in inflammation, blood pressure, motor behavior and anxiety. The effects of substance P in the hippocampus and the marginal di- vision of the striatum on memory remain poorly understood. Compared with the hippocampus as a control, immunofluorescence showed high expression of the substance P receptor, neuro- kinin 1, in the marginal division of the striatum of normal rats. Unilateral or bilateral injection of an antisense oligonucleotide against neurokinin 1 receptor mRNA in the rat hippocampus or marginal division of the striatum effectively reduced neurokinin 1 receptor expression. Indepen- dent of injection site, rats that received this antisense oligonucleotide showed obviously increased footshock times in a Y-maze test. These results indicate that the marginal division of the striatum plays a similar function in learning and memory to the hippocampus, which is a valuable addi- tion to our mechanistic understanding of the learning and memory functions of the marginal division of the striatum.
基金financially supported by the National Science and Technology Program of China(2013AA102704)the National Natural Science Foundation of China(J1210053)the Fundamental Research Funds for the Central Universities(2572015EA05)
文摘SQUAMOSA-promoter binding protein-like (SPL) proteins are plant-specific transcription factors and participate in different pathways, including the vegetative to reproductive transition, male sterility, biosynthesis of gibberellic acid (GA), plant morphogenesis and response to environmental stress. In this study, we generated transgenic Arabidopsis that overexpressed Betula BplSPL8 and confirmed that BplSPL8 is a transcription factor with transcriptional activation activity and is located in the nucleus. Functional analysis of BplSPL8 showed that it is involved in regulating different development processes: (1) BplSPL8 can delay flowering by reducing sensitivity to GA under short days; (2) BplSPL8 controls the number and morphogenesis of leaves, including up-rolling leaves under long days and folded leaves mediated by GA under short days; (3) BplSPL8 can promote root elongation during late development of roots and inhibit lateral root formation; (4) BplSPL8 may be involved in regulating carotenoid biosynthesis and secretion metabolism. These results show that there is a complex regulatory network for the SPL family genes that is mediated by other components and may provide a new insights for the functional research of SPL genes.
基金This work was supported by the TCM Special Research Projects Program 2010,China Ministry of Science and Technology(201007002)the TCM Special Research Projects Program 2014Ministry of Science and Technology(201407001-8).
文摘Objective:To provide guidelines for the prevention of post-stroke dementia,we investigated whether stroke patients were aware of post-stroke dementia and their level of dementia-related knowledge.Methods:Five dementia-related questions were designed.A field survey was conducted in a questionand-answer method using the designed questions.The surveys assessed 3000 stroke patients(2 weekse6 months after stroke attacks)from 14 hospitals/clinical centers in 7 provinces and cities across China.Results:Among 3000 stroke patients,80.5%had heard of dementia,39.1%knew that stroke can lead to dementia,55.7%believed dementia can be prevented,50.8%thought dementia can be cured,and only 8.8%had ever seen a doctor because of memory deterioration.Then,patients were classified into three groups,including a no cognitive impairment(NCI)group,a mild cognitive impairment(MCI)group,and a mild dementia(MD)group.Among the MCI and MD groups,only 8.7%(75/861)and 9.9%(64/649)of patients,respectively,had ever seen a doctor because of memory deterioration.According to our results,patients with a higher level of cognitive impairment had a lower awareness of dementia(P<.001).Conclusion:The awareness of dementia in stroke patients in China is low,and the consultation rate is even lower.Moreover,patients with a higher level of cognitive impairment have a lower awareness of dementia.To improve public awareness and improve prevention,more emphasis should be put on education regarding post-stroke dementia.Routine cognitive function screening should be conducted on stroke patients as an effective way to assess dementia.
文摘Based on results of previous studies,through investigations,the status quo,main advantages and disadvantages of using small hand-power scutchers and large-scale automatic sisal production lines to process sisal fiber were summarized and analyzed; the traditional uses and latest products of sisal fiber were studied,especially the comprehensive utilization of byproducts produced during sisal fiber processing as well as the broad prospects of new sisal products.
文摘[Objectives]To explore the molecular mechanism of Zhizi Ganjiang Decoction(ZZGJD)regulating sleep disorders based on the network pharmacology.[Methods]The BATMAN-TCM server was used to predict the potential targets of ZZGJD and constructed a compound-disease-target network map,and the GeneCards database was used to search for insomnia-related targets;with the aid of Cytoscape 3.5.1 software,the compound-insomnia target interaction network and protein-protein interaction(PPI)network were constructed,and gene ontology(GO)enrichment,Reactome pathway enrichment,and biological pathway enrichment analysis based on KEGG(Kyoto Encyclopedia of Genes and Enomes)was performed.[Results]The constructed PPI network of ZZGJD involves 204 nodes and 645 interaction relationships.Key nodes involve G protein-coupled receptors,rhodopsin-like adrenaline receptor families,zinc finger proteins,nuclear hormone receptor superfamilies,ligand-binding domains of hormone receptors,voltage-gated calcium(Ca^(2+))channel IQ domains,and neuropituitary hormones.The related entries of GO enrichment analysis pathway mainly involve G protein-coupled receptor activity,neurotransmitter receptor activity,adrenergic receptor activity,ammonium ion binding,catecholamine binding,G protein-coupled serotonin receptor activity,serotonin receptor activity,and steroid hormone receptors(SHRs)activity.Reactome pathway mainly involves amine ligand binding receptors,rhodopsin-like receptors,G protein-coupled receptor ligand binding,adrenergic receptors,neuronal systems and signal transduction,etc.KEGG channel analysis mainly involves neural activity ligand-receptor interaction,calcium ion messenger pathway,cAMP signaling pathway,serotonergic synapse,dopaminergic synapse,cGMP-PKG signaling pathway,and cholinergic synapse pathway,etc.[Conclusions]The potential targets of ZZGJD in the treatment of insomnia mainly involve G protein-coupled receptors,and regulate various neural receptor pathways such as calcium ion channels,serotonin,dopamine,and adrenergic receptors.INS,IGF-1,CTNNB1,ESR1,HIF-1A,etc.may be the key targets of ZZGJD in regulating sleep disorders,reflecting the multi-target and overall function characteristics of Chinese herbal compounds.ZZGJD is of great significance in the treatment of sleep disorders caused by blood sugar abnormality in patients with diabetes and perimenopausal hormones in women.This article is expected to It provide new ideas for in-depth study of the molecular mechanism of ZZGJD.
基金supported by the National Natural Science Foundation of China(92163107,52171061,52101003,52271085,and 52101032).
文摘A new type of grain-interior planar defect in a ceramic phase in TiC doped cemented tungsten carbides was discovered.It is unique in that the monolayers of metal atoms exist stably in ceramic grains.The planar defects were induced by the ordered heteroatoms distributing on certain crystal planes of the matrix,which are distinct from the known planar defects such as phase-,grain-,and twin-boundaries,stacking faults,and complexions.Detailed characterization on the atomic scale was performed for the composition,structure,and crystallography of the planar defects,and their energy state and stability were evaluated by modeling.It was found that the Ti monolayer assists nucleation of the new WC crystal along the normal direction to its basal plane.Due to the disturbance of the heteroatom layer,the deposition of W and C atoms deviates from the regular sites occupied in the perfect crystal lattice,resulting in variations of the W–C arrangement in the grain structure.Experiments confirmed that tailoring the distribution density of the planar defects could give the best comprehensive mechanical performance with simultaneously outstanding strength and fracture toughness in the materials containing the grain-interior planar defects.This study provides a new strategy to greatly enhance the mechanical properties of materials by introducing and tailoring planar defects in the grain interiors.
基金supported by National Natural Science Foundation(31970529)Beijing Natural Science Foundation Outstanding Youth Project(JQ23026)+1 种基金National Key Research and Development Program of China(2021YFD1201500)the Major Basic Research Program of Shandong Natural Science Foundation(ZR2019ZD15)。
文摘Winter plants rely on vernalization,a crucial process for adapting to cold conditions and ensuring successful reproduction.However,understanding the role of histone modifications in guiding the vernalization process in winter wheat remains limited.In this study,we investigated the transcriptome and chromatin dynamics in the shoot apex throughout the life cycle of winter wheat in the field.Two core histone modifications,H3K27me3 and H3K36me3,exhibited opposite patterns on the key vernalization gene VERNALIZATION1(VRN1),correlating with its induction during cold exposure.Moreover,the H3K36me3 level remained high at VRN1 after cold exposure,which may maintain its active state.Mutations in FERTILIZATION-INDEPENDENT ENDOSPERM(TaFIE)and SET DOMAIN GROUP 8/EARLY FLOWERING IN SHORT DAYS(TaSDG8/TaEFS),components of the writer complex for H3K27me3 and H3K36me3,respectively,affected flowering time.Intriguingly,VRN1 lost its high expression after the cold exposure memory in the absence of H3K36me3.During embryo development,VRN1 was silenced with the removal of active histone modifications in both winter and spring wheat,with selective restoration of H3K27me3 in winter wheat.The mutant of Tafie-cr-87,a component of H3K27me3“writer”complex,did not influence the silence of VRN1during embryo development,but rather attenuated the cold exposure requirement of winter wheat.Integrating gene expression with H3K27me3 and H3K36me3 patterns identified potential regulators of flowering.This study unveils distinct roles of H3K27me3 and H3K36me3 in controlling vernalization response,maintenance,and resetting in winter wheat.
基金supported by grants from the National Key R&D Program of China(2021YFA1300801 and 2018YFA0900801)National Natural Science Foundation of China(82172243 and 82372223)Fundamental Research Funds for the Central Universities(2042021kf0220 and 2042022dx0003).
文摘The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still epidemic around the world.The manipulation of SARS-CoV-2 is restricted to biosafety level 3 laboratories(BSL-3).In this study,we developed a SARS-CoV-2ΔN-GFP-HiBiT replicon delivery particles(RDPs)encoding a dual reporter gene,GFP-HiBiT,capable of producing both GFP signal and luciferase activities.Through optimal selection of the reporter gene,GFP-HiBiT demonstrated superior stability and convenience for antiviral evaluation.Additionally,we established a RDP infection mouse model by delivering the N gene into K18-hACE2 KI mouse through lentivirus.This mouse model supports RDP replication and can be utilized for in vivo antiviral evaluations.In summary,the RDP system serves as a valuable tool for efficient antiviral screening and studying the gene function of SARS-CoV-2.Importantly,this system can be manipulated in BSL-2 laboratories,decreasing the threshold of experimental requirements.
基金supported by grants from the National Natural Science Foundation of China(82372223 and 82172243)the National Key R&D Program of China(2021YFF0702004)the Fundamental Research Funds for the Central Universities of China(2042022dx0003).
文摘A unique feature of coronaviruses is their utilization of self-encoded nonstructural protein 16(nsp16),20-Omethyltransferase(20-O-MTase),to cap their RNAs through ribose 20-O-methylation modification.This process is crucial for maintaining viral genome stability,facilitating efficient translation,and enabling immune escape.Despite considerable advances in the ultrastructure of SARS-CoV-2 nsp16/nsp10,insights into its molecular mechanism have so far been limited.In this study,we systematically characterized the 20-O-MTase activity of nsp16 in SARS-CoV-2,focusing on its dependence on nsp10 stimulation.We observed cross-reactivity between nsp16 and nsp10 in various coronaviruses due to a conserved interaction interface.However,a single residue substitution(K58T)in SARS-CoV-2 nsp10 restricted the functional activation of MERS-CoV nsp16.Furthermore,the cofactor nsp10 effectively enhanced the binding of nsp16 to the substrate RNA and the methyl donor Sadenosyl-L-methionine(SAM).Mechanistically,His-80,Lys-93,and Gly-94 of nsp10 interacted with Asp-102,Ser-105,and Asp-106 of nsp16,respectively,thereby effectively stabilizing the SAM binding pocket.Lys-43 of nsp10 interacted with Lys-38 and Gly-39 of nsp16 to dynamically regulate the RNA binding pocket and facilitate precise binding of RNA to the nsp16/nsp10 complex.By assessing the conformational epitopes of nsp16/nsp10 complex,we further determined the critical residues involved in 20-O-MTase activity.Additionally,we utilized an in vitro biochemical platform to screen potential inhibitors targeting 20-O-MTase activity.Overall,our results significantly enhance the understanding of viral 20-O methylation process and mechanism,providing valuable targets for antiviral drug development.
基金Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2022A1515-011426National Natural Science Foundation of China,Grant/Award Numbers:61873027,32000466Shenzhen Science and Technology Program,Grant/Award Number:RCBS20200714114909234。
文摘Molecular subtyping of gastric cancer(GC)aims to comprehend its genetic landscape.However,the efficacy of current subtyping methods is hampered by their mixed use of molecular features,a lack of strategy optimization,and the limited availability of public GC datasets.There is a pressing need for a precise and easily adoptable subtyping approach for early DNA-based screening and treatment.Based on TCGA subtypes,we developed a novel DNA-based hierarchical classifier for gastric cancer molecular subtyping(HCG),which employs gene mutations,copy number aberrations,and methylation patterns as predictors.By incorporating the closely related esophageal adenocarcinomas dataset,we expanded the TCGA GC dataset for the training and testing of HCG(n=453).The optimization of HCG was achieved through three hierarchical strategies using Lasso-Logistic regression,evaluated by their overall the area under receiver operating characteristic curve(auROC),accuracy,F1 score,the area under precision-recall curve(auPRC)and their capability for clinical stratification using multivariate survival analysis.Subtype-specific DNA alteration biomarkers were discerned through difference tests based on HCG defined subtypes.Our HCG classifier demonstrated superior performance in terms of overall auROC(0.95),accuracy(0.88),F1 score(0.87)and auPRC(0.86),significantly improving the clinical stratification of patients(overall p-value=0.032).Difference tests identified 25 subtype-specific DNA alterations,including a high mutation rate in the SYNE1,ITGB4,and COL22A1 genes for the MSI subtype,and hypermethylation of ALS2CL,KIAA0406,and RPRD1B genes for the EBV subtype.HCG is an accurate and robust classifier for DNA-based GC molecular subtyping with highly predictive clinical stratification performance.The training and test datasets,along with the analysis programs of HCG,are accessible on the GitHub website(github.com/LabxSCUT).
基金the China Postdoctoral Science Foundation Grant(2019M661912)Major Scientific and Technological Innovation Projects in Shandong Province(2019JZZY020616)+1 种基金Opening Foundation of Key Laboratory of Modern Agricultural Equipment(Ministry of Agriculture and Rural Affairs),the Project of Scientific Research and Development of the University in Shandong Province(J18KA128)Cotton innovation team of Shandong modern agricultural industry technology system(SDAIT-03-09).
文摘Combining multiple crop protection Unmanned Aerial Vehicles(UAVs)as a team for a scheduled spraying mission over farmland now is a common way to significantly increase efficiency.However,given some issues such as different configurations,irregular borders,and especially varying pesticide requirements,it is more important and more complex than other multi-Agent Systems(MASs)in common use.In this work,we focus on the mission arrangement of UAVs,which is the foundation of other high-level cooperations,systematically propose Efficiency-first Spraying Mission Arrangement Problem(ESMAP),and try to construct a united problem framework for the mission arrangement of crop protection UAVs.Besides,to characterise the differences in sub-areas,the varying pesticide requirement per unit is well considered based on Normalized Difference Vegetation Index(NDVI).Firstly,the mathematical model of multiple crop-protection UAVs is established and ESMAP is defined.Furthermore,an acquisition method of a farmland’s NDVI map is proposed,and the calculation method of pesticide volume based on NDVI is discussed.Secondly,an improved Genetic Algorithm(GA)is proposed to solve ESMAP,and a comparable combination algorithm is introduced.Numerical simulations for algorithm analysis are carried out within MATLAB,and it is determined that the proposed GA is more efficient and accurate than the latter.Finally,a mission arrangement tested with three UAVs was carried out to validate the effectiveness of the proposed GA in spraying operation.Test results illustrated that it performed well,which took only 90.6%of the operation time taken by the combination algorithm.
基金supported by the National Natural Science Foundation of China(grant nos.31921005 and 31991211)the Strategic Priority Research Program of the Chinese Academy of Sciences(grant nos.XDA24010104,XDA24010204,and XDA24030102)+1 种基金the Special Information Program of the Chinese Academy of Sciences(grant no.XXH13506-408)the China Agricultural Research System(grant no.CARS-03).
文摘Studying the regulatory mechanisms that drive nitrogen-use efficiency(NUE)in crops is important for sustainable agriculture and environmental protection.In this study,we generated a high-quality genome assembly for the high-NUE wheat cultivar Kenong 9204 and systematically analyzed genes related to nitrogen uptake and metabolism.By comparative analyses,we found that the high-affinity nitrate transporter gene family had expanded in Triticeae.Further studies showed that subsequent functional differentiation endowed the expanded family members with saline inducibility,providing a genetic basis for improving the adaptability of wheat to nitrogen deficiency in various habitats.To explore the genetic and molecular mechanisms of high NUE,we compared genomic and transcriptomic data from the high-NUE cultivar Kenong 9204(KN9204)and the low-NUE cultivar Jing 411 and quantified their nitrogen accumulation under high-and low-nitrogen conditions.Compared with Jing 411,KN9204 absorbed significantly more nitrogen at the reproductive stage after shooting and accumulated it in the shoots and seeds.Transcriptome data analysis revealed that nitrogen deficiency clearly suppressed the expression of genes related to cell division in the young spike of Jing 411,whereas this suppression of gene expression was much lower in KN9204.In addition,KN9204 maintained relatively high expression of NPF genes for a longer time than Jing 411 during seed maturity.Physiological and transcriptome data revealed that KN9204 was more tolerant of nitrogen deficiency than Jing 411,especially at the reproductive stage.The high NUE of KN9204 is an integrated effect controlled at different levels.Taken together,our data provide new insights into the molecular mechanisms of NUE and important gene resources for improving wheat cultivars with a higher NUE trait.
基金supported financially by the National Natural Science Foundation of China (Nos.51601004,51631002,51425101 and 51621003)the China Scholarship Council (201806545002)the Program of Top Disciplines Construction in Beijing (No. PXM2019_014204_500031)
文摘The grain-size dependence of wear resistance of WC-Co cemented carbides(with mean WC grain sizes of 2.2μm,1.6μm,0.8μm and 0.4μm,respectively)was investigated under different tribological conditions.The results showed that the grain size had opposite effects on wear resistance of the cemented carbides in dry sliding wear and microabrasion tests.In the former condition,with decrease of WC grain size hence the increase of hardness,plastic deformation,fracture,fragmentation and oxidation were all mitigated,leading to a drastic decrease in the wear rate.In the latter condition,pull-out of WC grains after Co removal dominated the wear,so that the hardness of cemented carbide was not a core factor.As a result,the wear resistance of the cemented carbide generally showed a decreasing trend with decrease of the grain size,except for a slight increase in the ultrafine-grained cemented carbide.Single-pass scratching of the cemented carbides under various loads indicated the same failure mechanism as that in the sliding wear tests.Furthermore,the reasons for severe surface oxidation of the coarse-grained cemented carbides were disclosed.
基金supported by the National Major Science and Technology Program of China(2016YFC1306700)the National Natural Science Foundation of China(81420108012,81671046,81425010 and 31630031)+1 种基金the Jiangsu Provincial Medical Program for Distinguished Scholars(2016006)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX18_0167),China
文摘A deficit in spatial memory has been taken as an early predictor of Alzheimer’s disease(AD) or mild cognitive impairment(MCI). The uncinate fasciculus(UF) is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex(OFC)in primates. Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD, but its exact role in spatial memory is not well understood. The pathway arising from the postrhinal cortex(POR) and projecting to the ventrolateral orbitofrontal cortex(vlOFC)performs most of the functions of the UF in rodents.Although the literature suggests an association between spatial memory and the regions connected by the POR–vlOFC pathway, the function of the pathway in spatialmemory is relatively unknown. To further illuminate the function of the UF in spatial memory, we dissected the POR–vlOFC pathway in mice. We determined that the POR–vlOFC pathway is a glutamatergic structure, and that glutamatergic neurons in the POR regulate spatial memory retrieval. We also demonstrated that the POR–vlOFC pathway specifically transmits spatial information to participate in memory retrieval. These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory, as in MCI and AD.
基金supported by the Chinese National Programs for Fundamental Research and Development (Grant No.2011CB612207)the National Natural Science Foundation of China (Grant No. 51174009)+1 种基金the Program of National Science Infrastructure Platformthe State Key Laboratory of Powder Metallurgy of Central South University
文摘Based on a unique method to synthesize WC-Co composite powder by in-situ reactions of metal oxides and carbon, the effects of the carbon addition in the initial powders on the phase constitution, microstructure and mechanical properties of the cemented carbides were investigated. It is found that with a suitable carbon addition the pure phase constitution can be obtained in the sintered bulk from the composite powder. The mechanical properties of the cemented carbides depend on the phase constitution and the WC grain structure. To obtain the excellent properties of the WC-Co bulk, it is important to obtain the pure phase constitution from the appropriate carbon addition in the initial powders and a suitable grain size.
基金This work was supported by the National Natural Science Foundation of China(81930025,31800817,81670915,and 31870970)Innovative Talent Project of Shaanxi province(2020KJXX-057)Key Research and Development Program of Shaanxi Province(2019SF-073).
文摘Estrogen deficiency is one of the most frequent causes of osteoporosis in postmenopausal women.Under chronic inflammatory conditions caused by estrogen deficiency,activated T cells contribute to elevated levels of proinflammatory cytokines,impaired osteogenic differentiation capabilities of bone marrow mesenchymal stem cells(BMMSCs),and disturbed regulatory T cell(Treg)/Th17 cell balance.However,therapeutic strategies that re-establish immune homeostasis in this disorder have not been well developed.Here,we produced T cell-depleting nanoparticles(TDNs)that ameliorated the osteopenia phenotype and rescued the osteogenic deficiency of BMMSCs in ovariectomized(OVX)mice.TDNs consist of monocyte chemotactic protein-1(MCP-1)-encapsulated mesoporous silica nanoparticles as the core and Fas-ligand(FasL)as the corona.We showed that the delicate design of the TDNs enables rapid release of MCP-1 to recruit activated T cells and then induces their apoptosis through the conjugated FasL both in vitro and in vivo.Apoptotic signals recognized by macrophages help skew the Treg/Th17 cell balance and create an immune tolerant state,further attenuating the osteogenic deficiency of BMMSCs and the osteopenia phenotype.Mechanistically,we found that the therapeutic effects of TDNs were partially mediated by apoptotic T cell-derived extracellular vesicles(ApoEVs),which promoted macrophage transformation towards the M2 phenotype.These findings demonstrate that TDNs may represent a promising strategy for treating osteoporosis and other immune disorders.
基金supported by the Hainan Province Major Research Project(modern agricuture,ZDYF2020066)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China 01821005)+1 种基金the Hainan Major Science and Technolgy Project(No,ZDKJ202002).the Hainan Academician Innovaton Platform(HD-YSZX-202003)and the Hainan University Startup Fund(KYQD(ZR)1866).
文摘As one of the most important crops in the world,rice(Oryza sativa)is a model plant for metabolome research.Although many studies have focused on the analysis of specific tissues,the changes in metab-olite abundance across the entire life cycle have not yet been determined.In this study,combining both tar-geted and nontargeted metabolite profiling methods,a total of 825 annotated metabolites were quantified in rice samples from different tissues covering the entire life cycle.The contents of metabolites in different tissues of rice were significantly different,with various metabolites accumulating in the plumule and radicle during seed germination.Combining these data with transcriptome data obtained from the same time period,we constructed the Rice Metabolic Regulation Network.The metabolites and co-expressed genes were further divided into 12 clusters according to their accumulation patterns,with members within each cluster displaying a uniform and clear pattern of abundance across development.Using this dataset,we established a comprehensive metabolic profile of the rice life cycle and used two independent strategies to identify novel transcription factors-namely the use of known regulatory genes as bait to screen for new networks underlying lignin metabolism and the unbiased identification of new glycerophospholipid metabolism regulators on the basis of tissue specificity.This study thus demonstrates how guilt-by-association analysis of metabolome and transcriptome data spanning the entire life cycle in cereal crops provides novel resources and tools to aid in understanding the mechanisms underlying important agro-nomic traits.