How to deal with the relations between roles and actors is the core question of the performance,and there are two opposite performance theories to this question:"Expressionism"and "Experimentalism"...How to deal with the relations between roles and actors is the core question of the performance,and there are two opposite performance theories to this question:"Expressionism"and "Experimentalism".Can these two different performance styles coexist harmoniously? The film Happy Together directed by Karwai Wong has provided a very good answer.展开更多
Quantitative real-time PCR(qPCR)is widely used for gene expression analysis,but its accuracy critically depends on stable internal reference genes for normalization.In marine invertebrates,especially non-model taxa su...Quantitative real-time PCR(qPCR)is widely used for gene expression analysis,but its accuracy critically depends on stable internal reference genes for normalization.In marine invertebrates,especially non-model taxa such as cephalopods,systematic evaluation of reference genes is limited,leading to potential bias.The cuttlefish Sepiella japonica is ecologically and economically important in China,yet previous molecular studies have often relied on single unvalidated reference genes,which may compromise data reliability.This study aimed to systematically evaluate the stability of five commonly used reference genes(18S,ef-1α,ef-1γ,gapdh,andβ-actin)across multiple tissues and sexes of S.japonica,and to identify the most suitable reference genes and optimal number for qPCR normalization.Fifteen to sixteen tissue types were collected from ten healthy adults(five males and five females).Total RNA was extracted,reverse-transcribed,and analyzed by qPCR.Gene stability was assessed using four algorithms(geNorm,NormFinder,BestKeeper,andΔCt)integrated with RefFinder,and the optimal gene number was determined using geNorm pairwise variation(V_(n/n+1)<0.15).Four transcriptome-derived genes(creld2,cd109,acy1,and miox)were used for validation.The C_(t)values of the five genes ranged from 15.47 to 20.83.β-actin and gapdh showed pronounced variability in expression stability among tissues and sexes,indicating their limited suitability for normalization.18S exhibited the highest expression(mean C_(t):15.47-16.29)and lowest variability but displayed sex-biased expression,whereas ef-1αand ef-1γremained consistently stable across most tissues in both sexes,with ef-1αbeing the most robust and showing no sex-related bias.Although specific rankings varied among tissues and sexes,the comprehensive results indicated that ef-1αand ef-1γpossessed the highest overall stability,followed by 18S,whileβ-actin and gapdh were the least stable.The final comprehensive rankings were ef-1γ>ef-1α>18S>gapdh>β-actin(male)and ef-1α>ef-1γ>18S>gapdh>β-actin(female).geNorm analysis(V2/3<0.15)indicated that two genes,mainly ef-1αand ef-1γ,were generally sufficient for reliable normalization in most tissues.Validation confirmed that normalization using the stable ef-1αand ef-1γaccurately reflected the expression differences among tissues,whereasβ-actin and gapdh can bias or confound statistical analyses.ef-1αand ef-1γare identified as the most reliable reference gene combination for qPCR analysis in S.japonica,while 18S can serve as an auxiliary gene for within-sex comparisons.The use ofβ-actin or gapdh alone is not recommended.This study establishes a systematic framework for selecting reliable reference genes in S.japonica,thereby facilitating robust qPCR normalization and providing a foundation for future gene expression research in S.japonica and other cephalopods.展开更多
Background:The mechanisms underlying the beneficial effects of exercise on the human placenta are poorly understood.The objective of the current study was to ascertain the influence of a supervised concurrent exercise...Background:The mechanisms underlying the beneficial effects of exercise on the human placenta are poorly understood.The objective of the current study was to ascertain the influence of a supervised concurrent exercise intervention from gestational Week 17 until birth on key cytokines involved in placental development and function.Secondary aims were to explore:(a)the moderating effects of fetal sex and maternal weight status;and(b)whether gestational weight gain,lifestyle behaviors(diet,sleep patterns,and physical activity),and physical fitness(strength and cardiorespiratory fitness)mediated the effects of exercise on placental cytokines.Methods:Seventy-six pregnant women(33±4 years,mean±SD),divided into exercise(n=40)and control(n=36)groups,participated in this study.The exercise group followed a 60-min,3 days/week(aerobic+resistance)training program of moderate-to-vigorous intensity.Placental cytokines—including granulocyte-macrophage colony-stimulating factor(GM-CSF),granulocyte colony-stimulating factor(G-CSF),plateletderived growth factor AA(PDGF-AA),epidermal growth factor(EGF),monocyte chemoattractant protein-1(MCP-1),fractalkine,interleukin(IL)-8,IL-6,IL-1β,interleukin 1-receptor antagonist(IL-1ra),IL-10,tumor necrosis factor alpha(TNF-a),and interferon gamma(IFN-γ)were analyzed using Luminex multi-analyte profiling(x MAP)technology.Results:The exercise group presented higher placental levels of G-CSF and lower concentrations of EGF and IL-1ra than the control group(p<0.05).Significant effects of exercise on placental G-CSF and TNF-a(p<0.05)and a trend toward lower IL-6(p=0.08)were observed only in female placentas.Additionally,a reduction in weight gain partially mediated the effects of exercise on G-CSF(p<0.05).Conclusion:Maternal exercise during pregnancy is related to increased placental levels of G-CSF and lower EGF and IL-1ra levels.Some exercise-induced effects are observed exclusively in female placentas,including increased G-CSF and lower TNF-a and IL-6 concentrations.Notably,the increased levels of G-CSF observed with exercise might be due to a more adequate gestational weight gain.展开更多
The fertile soil of the countryside is also rich in artistic inspiration.“If farmers pick up a brush,they can become artists.If one devotes oneself wholeheartedly to something,a stroke of genius will follow,”said Mi...The fertile soil of the countryside is also rich in artistic inspiration.“If farmers pick up a brush,they can become artists.If one devotes oneself wholeheartedly to something,a stroke of genius will follow,”said Miao Huixin,a cultural envoy to Shengfeng Village in Youchegang Town,Xiuzhou District,Jiaxing City,Zhejiang Province.展开更多
The development of skeletal muscle are complicated processes involving genes responsible for proper muscle morphology,contractility,cell proliferation,differentiation,interactions,migration,and death.The three-dimensi...The development of skeletal muscle are complicated processes involving genes responsible for proper muscle morphology,contractility,cell proliferation,differentiation,interactions,migration,and death.The three-dimensional chromatin architecture of skeletal muscle development has not been studied intensively although dynamic transcriptional regulation during differentiation of muscle cells is one of the most deeply studied processes.The RNA-seq was used to analyze the transcriptome pattern during chicken muscle development across 12 stages.Hi-C was used to build chromatin architectures during four representative stages.Ch IP-seq was conducted to identify enhancers and promoters in these four stages,which are occupied by histone H3K27ac and H3K4me3 peaks.Results show that large-scale genome architecture changes are mostly unidirectional,and coupled by complex on/off dynamic patterns of gene expression.Specifically,we observed 258.30 Mb of the genome undergoing A/B compartment switching.Notable alterations(316.57 Mb)of interaction frequencies within TADs were observed.Substantial aging-associated genes exhibited ascending connectivity with the compartment transition from repressive to active status during muscle development.Some muscle-related gene promoters that interacted with active enhancers during development,and some myopathy/aging-associated genes that were activated in aging muscle were founded.These results provide key insights into skeletal muscle development in vivo,and offer a valuable resource that allows in-depth functional characterization of candidate genes.展开更多
Mangicol-type sesterterpenoids possess potent anti-inflammatory activity,characterized by a 5-5-6-5tetracyclic carbon skeleton formed by mangicdiene synthase Fg MS.Two proposed mechanisms for mangicdiene formation inv...Mangicol-type sesterterpenoids possess potent anti-inflammatory activity,characterized by a 5-5-6-5tetracyclic carbon skeleton formed by mangicdiene synthase Fg MS.Two proposed mechanisms for mangicdiene formation involve either C6-C10 cyclization(path a) or C2-C10 cyclization(path b) after the C10carbocation formation,but neither has been experimentally validated.Here,we have identified a second mangicdiene synthase Man D,which is derived from Fusarium sp.JNU-XJ070152-01 and shares high amino acid sequence identity with Fg MS.Through heterologous expression of man D in Aspergillus oryzae NSAR1,we observed production not only of mangicdiene(1) and variecoltetraene(2),previously identified by expression of Fg MS in Escherichia coli,but also two novel sesterterpene skeletons fusadiene(3)and fusatriene(4).The identification of fusadiene and fusatriene supports the occurrence of two key carbocation intermediates in path b,thus experimentally confirming that mangicdiene is built via path b for the first time,consistent with previous density functional theory(DFT) calculation results.展开更多
The pathogenesis-related protein PR10 plays a vital role in plant growth,development,and stress responses.This study systematically identified and analyzed PR10 genes in cultivated peanut(Arachis hypogaea L.),examinin...The pathogenesis-related protein PR10 plays a vital role in plant growth,development,and stress responses.This study systematically identified and analyzed PR10 genes in cultivated peanut(Arachis hypogaea L.),examining their phylogenetic relationships,conserved motifs,gene structures,and syntenic relationships.The analysis identified 54 Ah PR10 genes,which were classified into eight groups based on phylogenetic relationships,supported by gene structure and conserved motif characterization.Analysis of chromosomal distribution and synteny demonstrated that segmental duplications played a crucial role in the expansion of the Ah PR10 gene family.The identified Ah PR10 genes exhibited both constitutive and inducible expression patterns.Significantly,Ah PR10-7,Ah PR10-33,and Ah PR10-41 demonstrated potential importance in peanut resistance to Aspergillus flavus.In vitro fungistatic experiments demonstrated that recombinant Ah PR10-33 effectively inhibited A.flavus mycelial growth.These findings provide valuable insights for future investigations into Ah PR10 functions in protecting peanut from A.flavus infection.展开更多
[Objectives]The present study was conducted to investigate the change rule ofβ-fructofuranosidase gene expression and its enzyme activity in the midgut of 5 th instar silkworm(Bombyx mori),in order to provide a refer...[Objectives]The present study was conducted to investigate the change rule ofβ-fructofuranosidase gene expression and its enzyme activity in the midgut of 5 th instar silkworm(Bombyx mori),in order to provide a reference for illustrating the enzymatic mechanism of usingβ-fructofuranosidase to absorb sucrose nutrition from mulberry leaves.[Methods]Real-time fluorescent quantitative PCR was applied to analyze the expression of BmSuc1 and BmSuc2 in midgut of 5 th-instar silkworm larvae,meanwhile the activities ofβ-fructofuranosidase was determined.[Results]BmSuc1 was expressed in the midgut of 5 th-instar silkworm larvae at different developmental stages.Its expression was upregulated at the beginning of the 5 th instar and during the peak feeding period,whereas BmSuc2 expression remained very low throughout the entire 5 th instar.The activity ofβ-fructofuranosidase was relatively high during the peak feeding period of 5 th-instar larvae,showing a trend of increasing first and then decreasing.[Conclusions]The expression pattern of the BmSuc1 gene and the changes inβ-fructofuranosidase activity were generally consistent with the physiological process of sugar nutrient absorption and utilization from mulberry leaves in 5 th-instar silkworms.It suggests that BmSuc1,as a sucrose hydrolase gene,plays a major role in the digestion and absorption of sucrose nutrients from mulberry leaves in the midgut tissue.展开更多
Betalain,an economically valuable water-soluble natural plant pigment,is prized for its strong antioxidant activity,making it popular as a dietary supplement and a visual marker for plant transformation.However,market...Betalain,an economically valuable water-soluble natural plant pigment,is prized for its strong antioxidant activity,making it popular as a dietary supplement and a visual marker for plant transformation.However,market demand significantly outstrips current production capacity.This study reports the development of an efficient push-and-pull multigene strategy based on polycistronic expression and metabolic flux regulation to enhance betalain biosynthesis in transgenic maize(Zea mays L.)endosperm.We engineered a novel enhanced RUBY(eRUBY)system derived from the original polycistronic RUBY construct(CYP76AD1P2ADODA1P2ADOPA5GT unit,abbreviated CDG)by introducing arogenate dehydrogenase(ADHα)to increase the L-tyrosine substrate supply.All the genes were driven by the endosperm-specific promoter.Fusion of ADHαinto a single polycistronic eRUBY construct(CDGA)produced significantly higher betanin(6.88 mg g−1 dry weight)and isobetanin(1.81 mg g−1 dry weight)levels than in CDG+A,which stacked the ADHαcassette independently with CDG.The high betalain accumulation in CDGA lines(which also exhibited higher transgene copy number)resulted in a 2.85–7.58-fold improvement in endosperm antioxidant capacity compared to WT(versus 2.48–2.80-fold in CDG+A).Importantly,transgenic plants maintained a normal phenotype.Transcriptome and metabolome analyses further indicated that metabolism of phenylalanine,alanine,aspartate,and glutamate contributes to betalain production.Hybridization with sweet corn successfully created a high-sugar eRUBY maize variety.Collectively,these results demonstrate the successful development of a novel maize germplasm with significantly enhanced nutritional value through high betalain accumulation.展开更多
A Tibetan art form bridges the past and present and connects cultures around the world.THANGKA,a unique form of Tibetan sacred painting,is gaining prominence globally due to its vibrant colors,exquisite craftsmanship,...A Tibetan art form bridges the past and present and connects cultures around the world.THANGKA,a unique form of Tibetan sacred painting,is gaining prominence globally due to its vibrant colors,exquisite craftsmanship,and profound religious and cultural significance.With the acceleration of globalization,this symbol of Tibetan culture that combines artistic expression with spirituality has become a bridge for cultural exchange between the East and the West.Recently,China Today spoke to Yixi Puncog,art collector and council member of the China Association for Preservation and Development of Tibetan Culture,to learn more about Thangka art,its role in international exchange,and how it is enhancing China’s cultural soft power.展开更多
Botrytis cinerea is a major necrotrophic pathogen responsible for significant crop losses worldwide.Alternative strategies to control B.cinerea are urgently needed to reduce dependence on chemical fungicides,which are...Botrytis cinerea is a major necrotrophic pathogen responsible for significant crop losses worldwide.Alternative strategies to control B.cinerea are urgently needed to reduce dependence on chemical fungicides,which are increasingly ineffective due to resistance and pose environmental risks.In this study,we identified two immunogenic epitopes derived from the B.cinerea cell death-inducing protein BcCrh1 and used them to engineer disease-resistant plants through a novel,spatially compartmentalized dual-epitope immune activation strategy.The first epitope is derived from a 35-amino acid intracellular peptide that exhibits both immunogenicity and cell death-inducing activity,which was mutated to separate these two properties.The second peptide represents an immunogenic portion of the protein that activates extracellular plant immunity.Transcriptomic and metabolomic analyses revealed that these epitopes trigger complementary defense pathways,and their co-expression integrates these responses into a robust,multilayered immunity,providing significantly enhanced protection compared with individual expression.Although constitutive expression of two epitopes conferred resistance,it also led to growth penalties.In contrast,pathogen-inducible expression of two epitopes preserved normal plant development while maintaining strong resistance to both B.cinerea and Pseudomonas syringae in Arabidopsis and tomato.This inducible strategy offers a major advantage by minimizing fitness costs while maximizing protection,highlighting the potential of spatially and temporally targeted epitope-based immune activation for durable and sustainable crop protection.展开更多
AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induc...AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.展开更多
Due to the unique microstructure and diverse opsin genes of the trinocular compound eye,stomatopoda possess an extraordinary ability to perceive multiple properties of light.They not only can detect natural light(NL)a...Due to the unique microstructure and diverse opsin genes of the trinocular compound eye,stomatopoda possess an extraordinary ability to perceive multiple properties of light.They not only can detect natural light(NL)and linearly polarized light(LPL),but also are the only animals capable of recognizing circularly polarized light(CPL).Here,we integrated single-cell RNA sequencing,previously published Illumina data,and in-situ hybridization(ISH)to quantify and localize functional opsin genes in Oratosquilla oratoria,a common stomatopoda species in the China Sea.A total of high-quality 31777 cells were captured for the first time in the O.oratoria compound eye,which were classified into 25 cell subpopulations,and hypothesized that cluster 22 is a critical cell subpopulation responsible for light(whether NL,LPL,or CPL)response in O.oratoria.Furthermore,we propose that the long-wavelengthsensitive opsin gene(lws)gene family,retinol dehydrogenase(rdh),voltage-gated ion channel(vgic),arrestin(arr),and myosin(myo)collectively mediate the light response in O.oratoria.Considering that very few vision-related opsin genes show differential expression in right-handed CPL(RCPL)-vs.-dark(DL),which provides additional evidence that stomatopoda cannot recognize RCPL.Meanwhile,we believe that UV-stimulated scaffold protein A(uvssa)and red pigment concentrating hormone(rpch)play special contributions in the left-handed CPL(LCPL)environment response.ISH revealing that 16 lws,6 middle-wavelength-sensitive(mws),and 2 ultraviolet(uv)opsin genes were expressed in the photoreceptors of the O.oratoria compound eye.Although the inability to determine the functional types of cell subpopulations limits the resolution of opsin genes,these findings systematically elucidate the specific expression patterns of opsin genes in O.oratoria and represent a significant step toward refining the visual ecological theory of O.oratoria and other stomatopod species.展开更多
Coconut(Cocos nucifera L.),a major oil and fruit crop of the Arecaceae family,is extensively cultivated across the Asia—Pacific region.Despite its agricultural importance,genome assembly in coconut remains challengin...Coconut(Cocos nucifera L.),a major oil and fruit crop of the Arecaceae family,is extensively cultivated across the Asia—Pacific region.Despite its agricultural importance,genome assembly in coconut remains challenging due to its large genome size and high proportion of repetitive sequences.Allele-specific expression(ASE)plays a key role in regulating plant development and evolution,yet research on ASE in coconut is limited(Shao et al.,2019;Li et al.,2021;Zhang et al.,2021;Hu et al.,2022).Among phenotypic traits,fruit color is especially important as an indicator of maturity,guiding harvest timing and post-harvest processes(Kapoor et al.,2022).While prior studies have explored various coconut traits such as salt tolerance,fiber content,and plant height(Wang et al.,2021;Yang et al.,2021),investigations into ASE and fruit color remain scarce.展开更多
Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for sign...Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.展开更多
Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological s...Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.展开更多
Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regula...Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.展开更多
The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant ...The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant genes,are crucial formaintaining genome stability,yet their prognostic significance in eBCremains unclear.This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients.Significant correlations were observed between the messenger ribonucleic acid(mRNA)expression levels of the genes Ataxia-telangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM was associated with longer metastasis-free survival(MFS).Conversely,lower mRNA expression of BLM correlated with favorable outcomes,particularly in triple-negative tumors.Additionally,high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels.This study highlights the prognostic significance of ATM,BLM,and WRN in predicting survival outcomes in eBC patients.Background:The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer(eBC)remains unclear and warrants further investigation.This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer.Methods:Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid(mRNA)expression levels.Statistical analysis,including Kaplan-Meier curves,univariable,andmultivariable Cox regression analyses,was performed to assess metastasis-free survival(MFS)of mRNA expression of non-BRCA genes.Subgroup analyses were also conducted among four different molecular subtypes of eBC.Results:Our analysis revealed significant correlations between mRNA-expression levels of Ataxiatelangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM correlated with longer MFS in the entire cohort(p=0.022,Log Rank),and in luminal-B-like tumors(p=0.036).Lower mRNA expression of BLM was associated with favorable outcomes(p=0.011,Log Rank),particularly in triple-negative eBC(p=0.030,Log Rank).Finally,high levels of WRN mRNA expression correlated with significantly longerMFS compared to lowmRNA expression levels(p=0.009,Log Rank).Conclusions:This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes,such as ATM,BLM,and WRN,for survival outcomes in eBC.展开更多
This article is devoted to the study of the neural mechanisms of the binary substance of the brain in the process of creating,presenting and evaluating new approaches,methods and tools in the field of art.The interrel...This article is devoted to the study of the neural mechanisms of the binary substance of the brain in the process of creating,presenting and evaluating new approaches,methods and tools in the field of art.The interrelation and interdependence of genetically determined neural structures in the subcortical sphere and the neocortex in the creative process are shown.The scientific interpretation of the concepts of trance and bifurcation as mechanisms for the emergence of a new approach,method,and means for an innovator is given,and the peculiarities of perception and identification of innovations by art connoisseurs are characterized.展开更多
Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor...Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental monitoring.The ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous system.Insights gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent deficits.Understanding the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's disease.Olfa ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian body.This ectopic expression provides insights into the chemical structures that can activate olfactory receptors.In addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing microbiota.The analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation mechanisms.This review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative processes.Evidence suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous system injuries.展开更多
文摘How to deal with the relations between roles and actors is the core question of the performance,and there are two opposite performance theories to this question:"Expressionism"and "Experimentalism".Can these two different performance styles coexist harmoniously? The film Happy Together directed by Karwai Wong has provided a very good answer.
文摘Quantitative real-time PCR(qPCR)is widely used for gene expression analysis,but its accuracy critically depends on stable internal reference genes for normalization.In marine invertebrates,especially non-model taxa such as cephalopods,systematic evaluation of reference genes is limited,leading to potential bias.The cuttlefish Sepiella japonica is ecologically and economically important in China,yet previous molecular studies have often relied on single unvalidated reference genes,which may compromise data reliability.This study aimed to systematically evaluate the stability of five commonly used reference genes(18S,ef-1α,ef-1γ,gapdh,andβ-actin)across multiple tissues and sexes of S.japonica,and to identify the most suitable reference genes and optimal number for qPCR normalization.Fifteen to sixteen tissue types were collected from ten healthy adults(five males and five females).Total RNA was extracted,reverse-transcribed,and analyzed by qPCR.Gene stability was assessed using four algorithms(geNorm,NormFinder,BestKeeper,andΔCt)integrated with RefFinder,and the optimal gene number was determined using geNorm pairwise variation(V_(n/n+1)<0.15).Four transcriptome-derived genes(creld2,cd109,acy1,and miox)were used for validation.The C_(t)values of the five genes ranged from 15.47 to 20.83.β-actin and gapdh showed pronounced variability in expression stability among tissues and sexes,indicating their limited suitability for normalization.18S exhibited the highest expression(mean C_(t):15.47-16.29)and lowest variability but displayed sex-biased expression,whereas ef-1αand ef-1γremained consistently stable across most tissues in both sexes,with ef-1αbeing the most robust and showing no sex-related bias.Although specific rankings varied among tissues and sexes,the comprehensive results indicated that ef-1αand ef-1γpossessed the highest overall stability,followed by 18S,whileβ-actin and gapdh were the least stable.The final comprehensive rankings were ef-1γ>ef-1α>18S>gapdh>β-actin(male)and ef-1α>ef-1γ>18S>gapdh>β-actin(female).geNorm analysis(V2/3<0.15)indicated that two genes,mainly ef-1αand ef-1γ,were generally sufficient for reliable normalization in most tissues.Validation confirmed that normalization using the stable ef-1αand ef-1γaccurately reflected the expression differences among tissues,whereasβ-actin and gapdh can bias or confound statistical analyses.ef-1αand ef-1γare identified as the most reliable reference gene combination for qPCR analysis in S.japonica,while 18S can serve as an auxiliary gene for within-sex comparisons.The use ofβ-actin or gapdh alone is not recommended.This study establishes a systematic framework for selecting reliable reference genes in S.japonica,thereby facilitating robust qPCR normalization and providing a foundation for future gene expression research in S.japonica and other cephalopods.
基金funded by the Regional Ministry of Health of the Junta de Andalucıa(PI-0395-2016)the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement(No.101027215)+1 种基金supported by the PLACENTRAINING project,funded through the FEDER-UGR23 funding call(European Regional Development Fund University of Granada programGrant No.C-EXP-336UGR23)。
文摘Background:The mechanisms underlying the beneficial effects of exercise on the human placenta are poorly understood.The objective of the current study was to ascertain the influence of a supervised concurrent exercise intervention from gestational Week 17 until birth on key cytokines involved in placental development and function.Secondary aims were to explore:(a)the moderating effects of fetal sex and maternal weight status;and(b)whether gestational weight gain,lifestyle behaviors(diet,sleep patterns,and physical activity),and physical fitness(strength and cardiorespiratory fitness)mediated the effects of exercise on placental cytokines.Methods:Seventy-six pregnant women(33±4 years,mean±SD),divided into exercise(n=40)and control(n=36)groups,participated in this study.The exercise group followed a 60-min,3 days/week(aerobic+resistance)training program of moderate-to-vigorous intensity.Placental cytokines—including granulocyte-macrophage colony-stimulating factor(GM-CSF),granulocyte colony-stimulating factor(G-CSF),plateletderived growth factor AA(PDGF-AA),epidermal growth factor(EGF),monocyte chemoattractant protein-1(MCP-1),fractalkine,interleukin(IL)-8,IL-6,IL-1β,interleukin 1-receptor antagonist(IL-1ra),IL-10,tumor necrosis factor alpha(TNF-a),and interferon gamma(IFN-γ)were analyzed using Luminex multi-analyte profiling(x MAP)technology.Results:The exercise group presented higher placental levels of G-CSF and lower concentrations of EGF and IL-1ra than the control group(p<0.05).Significant effects of exercise on placental G-CSF and TNF-a(p<0.05)and a trend toward lower IL-6(p=0.08)were observed only in female placentas.Additionally,a reduction in weight gain partially mediated the effects of exercise on G-CSF(p<0.05).Conclusion:Maternal exercise during pregnancy is related to increased placental levels of G-CSF and lower EGF and IL-1ra levels.Some exercise-induced effects are observed exclusively in female placentas,including increased G-CSF and lower TNF-a and IL-6 concentrations.Notably,the increased levels of G-CSF observed with exercise might be due to a more adequate gestational weight gain.
文摘The fertile soil of the countryside is also rich in artistic inspiration.“If farmers pick up a brush,they can become artists.If one devotes oneself wholeheartedly to something,a stroke of genius will follow,”said Miao Huixin,a cultural envoy to Shengfeng Village in Youchegang Town,Xiuzhou District,Jiaxing City,Zhejiang Province.
基金supported by the National Key R&D Program of China(2023YFD1300040 and 2022YFF1000100)the Sichuan Science and Technology Program,China(2022NSFSC0132,2021YFYZ0009 and 2022JDJQ0054)the National Natural Science Foundation of China(32225046)。
文摘The development of skeletal muscle are complicated processes involving genes responsible for proper muscle morphology,contractility,cell proliferation,differentiation,interactions,migration,and death.The three-dimensional chromatin architecture of skeletal muscle development has not been studied intensively although dynamic transcriptional regulation during differentiation of muscle cells is one of the most deeply studied processes.The RNA-seq was used to analyze the transcriptome pattern during chicken muscle development across 12 stages.Hi-C was used to build chromatin architectures during four representative stages.Ch IP-seq was conducted to identify enhancers and promoters in these four stages,which are occupied by histone H3K27ac and H3K4me3 peaks.Results show that large-scale genome architecture changes are mostly unidirectional,and coupled by complex on/off dynamic patterns of gene expression.Specifically,we observed 258.30 Mb of the genome undergoing A/B compartment switching.Notable alterations(316.57 Mb)of interaction frequencies within TADs were observed.Substantial aging-associated genes exhibited ascending connectivity with the compartment transition from repressive to active status during muscle development.Some muscle-related gene promoters that interacted with active enhancers during development,and some myopathy/aging-associated genes that were activated in aging muscle were founded.These results provide key insights into skeletal muscle development in vivo,and offer a valuable resource that allows in-depth functional characterization of candidate genes.
基金financially supported by grants from the National Key Research and Development Program of China (No.2024YFE0102000)the National Natural Science Foundation of China (Nos.81925037,82321004,U22A20371,U24A20782,32170060,22177037,22207039,22307045)+6 种基金the Guangdong Major Project of Basic and Applied Basic Research (No.2023B0303000026)the Guangdong Natural Science Funds for Distinguished Young Scholars (No.2022B1515020028,China)the Guangdong International Science and Technology Cooperation Base (No.2021A0505020015,China)the Guangdong Basic and Applied Basic Research Foundation (Nos.2023B1515040016,2023A1515110388)the Innovative and Research Teams Project of Guangdong Higher Education Institution (No.2021KCXTD001,China)the Guangzhou Science and Technology Project (Nos.202206010020,2024A04J6241,2023A04J0080,China)the Fundamental Research Funds for the Central Universities (Nos.21623105,21624210)。
文摘Mangicol-type sesterterpenoids possess potent anti-inflammatory activity,characterized by a 5-5-6-5tetracyclic carbon skeleton formed by mangicdiene synthase Fg MS.Two proposed mechanisms for mangicdiene formation involve either C6-C10 cyclization(path a) or C2-C10 cyclization(path b) after the C10carbocation formation,but neither has been experimentally validated.Here,we have identified a second mangicdiene synthase Man D,which is derived from Fusarium sp.JNU-XJ070152-01 and shares high amino acid sequence identity with Fg MS.Through heterologous expression of man D in Aspergillus oryzae NSAR1,we observed production not only of mangicdiene(1) and variecoltetraene(2),previously identified by expression of Fg MS in Escherichia coli,but also two novel sesterterpene skeletons fusadiene(3)and fusatriene(4).The identification of fusadiene and fusatriene supports the occurrence of two key carbocation intermediates in path b,thus experimentally confirming that mangicdiene is built via path b for the first time,consistent with previous density functional theory(DFT) calculation results.
基金supported by the National Key R&D Program of China(2022YFD1200400)the National Natural Science Foundation of China(32301851)。
文摘The pathogenesis-related protein PR10 plays a vital role in plant growth,development,and stress responses.This study systematically identified and analyzed PR10 genes in cultivated peanut(Arachis hypogaea L.),examining their phylogenetic relationships,conserved motifs,gene structures,and syntenic relationships.The analysis identified 54 Ah PR10 genes,which were classified into eight groups based on phylogenetic relationships,supported by gene structure and conserved motif characterization.Analysis of chromosomal distribution and synteny demonstrated that segmental duplications played a crucial role in the expansion of the Ah PR10 gene family.The identified Ah PR10 genes exhibited both constitutive and inducible expression patterns.Significantly,Ah PR10-7,Ah PR10-33,and Ah PR10-41 demonstrated potential importance in peanut resistance to Aspergillus flavus.In vitro fungistatic experiments demonstrated that recombinant Ah PR10-33 effectively inhibited A.flavus mycelial growth.These findings provide valuable insights for future investigations into Ah PR10 functions in protecting peanut from A.flavus infection.
基金Supported by General Project of Yunnan Provincial Agricultural Basic Research Joint Special Project(202301BD070001-229)Yunnan Provincial Key R&D Program(202403AK140075)+1 种基金Modern Sericulture Industry Technology System of Yunan Province(KJTX-07)Honghe Comprehensive Test Station of National Sericulture Industry Technology System(CARS-18).
文摘[Objectives]The present study was conducted to investigate the change rule ofβ-fructofuranosidase gene expression and its enzyme activity in the midgut of 5 th instar silkworm(Bombyx mori),in order to provide a reference for illustrating the enzymatic mechanism of usingβ-fructofuranosidase to absorb sucrose nutrition from mulberry leaves.[Methods]Real-time fluorescent quantitative PCR was applied to analyze the expression of BmSuc1 and BmSuc2 in midgut of 5 th-instar silkworm larvae,meanwhile the activities ofβ-fructofuranosidase was determined.[Results]BmSuc1 was expressed in the midgut of 5 th-instar silkworm larvae at different developmental stages.Its expression was upregulated at the beginning of the 5 th instar and during the peak feeding period,whereas BmSuc2 expression remained very low throughout the entire 5 th instar.The activity ofβ-fructofuranosidase was relatively high during the peak feeding period of 5 th-instar larvae,showing a trend of increasing first and then decreasing.[Conclusions]The expression pattern of the BmSuc1 gene and the changes inβ-fructofuranosidase activity were generally consistent with the physiological process of sugar nutrient absorption and utilization from mulberry leaves in 5 th-instar silkworms.It suggests that BmSuc1,as a sucrose hydrolase gene,plays a major role in the digestion and absorption of sucrose nutrients from mulberry leaves in the midgut tissue.
基金supported by grants from the Biological Breeding-National Science and Technology Major Project(2024ZD04077)the Invigorate the Seed Industry of Guangdong Province(2024-NPY-00-044)+3 种基金the National Natural Science Foundation of China(32272120)the Guangxi Science and Technology Major Project(GKAA24206023)the National Key Research and Development Program of China(2024YFF1000800)the Guangdong Basic Research Center of Excellence for Precise Breeding of Future Crops Major Project(FCBRCE-202502,FCBRCE-202504).
文摘Betalain,an economically valuable water-soluble natural plant pigment,is prized for its strong antioxidant activity,making it popular as a dietary supplement and a visual marker for plant transformation.However,market demand significantly outstrips current production capacity.This study reports the development of an efficient push-and-pull multigene strategy based on polycistronic expression and metabolic flux regulation to enhance betalain biosynthesis in transgenic maize(Zea mays L.)endosperm.We engineered a novel enhanced RUBY(eRUBY)system derived from the original polycistronic RUBY construct(CYP76AD1P2ADODA1P2ADOPA5GT unit,abbreviated CDG)by introducing arogenate dehydrogenase(ADHα)to increase the L-tyrosine substrate supply.All the genes were driven by the endosperm-specific promoter.Fusion of ADHαinto a single polycistronic eRUBY construct(CDGA)produced significantly higher betanin(6.88 mg g−1 dry weight)and isobetanin(1.81 mg g−1 dry weight)levels than in CDG+A,which stacked the ADHαcassette independently with CDG.The high betalain accumulation in CDGA lines(which also exhibited higher transgene copy number)resulted in a 2.85–7.58-fold improvement in endosperm antioxidant capacity compared to WT(versus 2.48–2.80-fold in CDG+A).Importantly,transgenic plants maintained a normal phenotype.Transcriptome and metabolome analyses further indicated that metabolism of phenylalanine,alanine,aspartate,and glutamate contributes to betalain production.Hybridization with sweet corn successfully created a high-sugar eRUBY maize variety.Collectively,these results demonstrate the successful development of a novel maize germplasm with significantly enhanced nutritional value through high betalain accumulation.
文摘A Tibetan art form bridges the past and present and connects cultures around the world.THANGKA,a unique form of Tibetan sacred painting,is gaining prominence globally due to its vibrant colors,exquisite craftsmanship,and profound religious and cultural significance.With the acceleration of globalization,this symbol of Tibetan culture that combines artistic expression with spirituality has become a bridge for cultural exchange between the East and the West.Recently,China Today spoke to Yixi Puncog,art collector and council member of the China Association for Preservation and Development of Tibetan Culture,to learn more about Thangka art,its role in international exchange,and how it is enhancing China’s cultural soft power.
基金supported by the National Natural Science Foundation of China(grant no.32372514)the Research and Innovation Initiatives of WHPU(grant no.2024J02)+1 种基金Y.L.(202108280009)was funded by the China Scholarship Councilsupported by BARD(grant no.5261-20C)to A.S and T.M.
文摘Botrytis cinerea is a major necrotrophic pathogen responsible for significant crop losses worldwide.Alternative strategies to control B.cinerea are urgently needed to reduce dependence on chemical fungicides,which are increasingly ineffective due to resistance and pose environmental risks.In this study,we identified two immunogenic epitopes derived from the B.cinerea cell death-inducing protein BcCrh1 and used them to engineer disease-resistant plants through a novel,spatially compartmentalized dual-epitope immune activation strategy.The first epitope is derived from a 35-amino acid intracellular peptide that exhibits both immunogenicity and cell death-inducing activity,which was mutated to separate these two properties.The second peptide represents an immunogenic portion of the protein that activates extracellular plant immunity.Transcriptomic and metabolomic analyses revealed that these epitopes trigger complementary defense pathways,and their co-expression integrates these responses into a robust,multilayered immunity,providing significantly enhanced protection compared with individual expression.Although constitutive expression of two epitopes conferred resistance,it also led to growth penalties.In contrast,pathogen-inducible expression of two epitopes preserved normal plant development while maintaining strong resistance to both B.cinerea and Pseudomonas syringae in Arabidopsis and tomato.This inducible strategy offers a major advantage by minimizing fitness costs while maximizing protection,highlighting the potential of spatially and temporally targeted epitope-based immune activation for durable and sustainable crop protection.
基金Supported by the National Natural Science Fundation of China(No.82101107No.81471575).
文摘AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.
基金Supported by the Natural Science Foundation of Shandong Province(No.ZR2021QD110)the National Natural Science Foundation of China(No.42106128)。
文摘Due to the unique microstructure and diverse opsin genes of the trinocular compound eye,stomatopoda possess an extraordinary ability to perceive multiple properties of light.They not only can detect natural light(NL)and linearly polarized light(LPL),but also are the only animals capable of recognizing circularly polarized light(CPL).Here,we integrated single-cell RNA sequencing,previously published Illumina data,and in-situ hybridization(ISH)to quantify and localize functional opsin genes in Oratosquilla oratoria,a common stomatopoda species in the China Sea.A total of high-quality 31777 cells were captured for the first time in the O.oratoria compound eye,which were classified into 25 cell subpopulations,and hypothesized that cluster 22 is a critical cell subpopulation responsible for light(whether NL,LPL,or CPL)response in O.oratoria.Furthermore,we propose that the long-wavelengthsensitive opsin gene(lws)gene family,retinol dehydrogenase(rdh),voltage-gated ion channel(vgic),arrestin(arr),and myosin(myo)collectively mediate the light response in O.oratoria.Considering that very few vision-related opsin genes show differential expression in right-handed CPL(RCPL)-vs.-dark(DL),which provides additional evidence that stomatopoda cannot recognize RCPL.Meanwhile,we believe that UV-stimulated scaffold protein A(uvssa)and red pigment concentrating hormone(rpch)play special contributions in the left-handed CPL(LCPL)environment response.ISH revealing that 16 lws,6 middle-wavelength-sensitive(mws),and 2 ultraviolet(uv)opsin genes were expressed in the photoreceptors of the O.oratoria compound eye.Although the inability to determine the functional types of cell subpopulations limits the resolution of opsin genes,these findings systematically elucidate the specific expression patterns of opsin genes in O.oratoria and represent a significant step toward refining the visual ecological theory of O.oratoria and other stomatopod species.
基金supported by Central Public-interest Scientific Institution Basal Research Fund(CATAS-Nos.1630152023007,1630152023011,1630152023012,1630152023013)the National Natural Science Foundation of China(Grant No.32071805).
文摘Coconut(Cocos nucifera L.),a major oil and fruit crop of the Arecaceae family,is extensively cultivated across the Asia—Pacific region.Despite its agricultural importance,genome assembly in coconut remains challenging due to its large genome size and high proportion of repetitive sequences.Allele-specific expression(ASE)plays a key role in regulating plant development and evolution,yet research on ASE in coconut is limited(Shao et al.,2019;Li et al.,2021;Zhang et al.,2021;Hu et al.,2022).Among phenotypic traits,fruit color is especially important as an indicator of maturity,guiding harvest timing and post-harvest processes(Kapoor et al.,2022).While prior studies have explored various coconut traits such as salt tolerance,fiber content,and plant height(Wang et al.,2021;Yang et al.,2021),investigations into ASE and fruit color remain scarce.
基金supported by the National Natural Science Foundation of China(NSFC/RGC/JRF N_HKU735/21)Research Grant Council of Hong Kong,China(17102120,17108821,17103922,C1024-22GF,C7074-21G)+1 种基金Health and Medical Research Fund(HMRF 09200966)(to CSWL)FRQS Postdoctoral Fellowship(to AHKF).
文摘Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.
基金supported by Deutsche Forschungsgemeinschaft,German Research Foundation grant GA 654/13-2 to OG.
文摘Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.
基金supported by Shenzhen Science and Technology Program, No. JCYJ20230807110259002 (to JL)The Seventh Affiliated Hospital of Sun Yat-sen University, No. ZSQYRSFPD0050 (to JL)The Postdoctoral Fellowship Program of CPSF, No. GZC20242074 (to KT)
文摘Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.
文摘The prognostic and therapeutic roles of biological markers in early-stage breast cancer(eBC)warrant further investigation.Non-Breast Cancer(BRCA)genes,along with moderate-and low-penetrance breast cancer risk variant genes,are crucial formaintaining genome stability,yet their prognostic significance in eBCremains unclear.This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients.Significant correlations were observed between the messenger ribonucleic acid(mRNA)expression levels of the genes Ataxia-telangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM was associated with longer metastasis-free survival(MFS).Conversely,lower mRNA expression of BLM correlated with favorable outcomes,particularly in triple-negative tumors.Additionally,high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels.This study highlights the prognostic significance of ATM,BLM,and WRN in predicting survival outcomes in eBC patients.Background:The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer(eBC)remains unclear and warrants further investigation.This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer.Methods:Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid(mRNA)expression levels.Statistical analysis,including Kaplan-Meier curves,univariable,andmultivariable Cox regression analyses,was performed to assess metastasis-free survival(MFS)of mRNA expression of non-BRCA genes.Subgroup analyses were also conducted among four different molecular subtypes of eBC.Results:Our analysis revealed significant correlations between mRNA-expression levels of Ataxiatelangiectasia mutated(ATM),Bloom helicase gene(BLM),and WRN RecQ Like Helicase(WRN)and patient prognosis.High mRNA expression of ATM correlated with longer MFS in the entire cohort(p=0.022,Log Rank),and in luminal-B-like tumors(p=0.036).Lower mRNA expression of BLM was associated with favorable outcomes(p=0.011,Log Rank),particularly in triple-negative eBC(p=0.030,Log Rank).Finally,high levels of WRN mRNA expression correlated with significantly longerMFS compared to lowmRNA expression levels(p=0.009,Log Rank).Conclusions:This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes,such as ATM,BLM,and WRN,for survival outcomes in eBC.
文摘This article is devoted to the study of the neural mechanisms of the binary substance of the brain in the process of creating,presenting and evaluating new approaches,methods and tools in the field of art.The interrelation and interdependence of genetically determined neural structures in the subcortical sphere and the neocortex in the creative process are shown.The scientific interpretation of the concepts of trance and bifurcation as mechanisms for the emergence of a new approach,method,and means for an innovator is given,and the peculiarities of perception and identification of innovations by art connoisseurs are characterized.
文摘Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental monitoring.The ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous system.Insights gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent deficits.Understanding the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's disease.Olfa ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian body.This ectopic expression provides insights into the chemical structures that can activate olfactory receptors.In addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing microbiota.The analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation mechanisms.This review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative processes.Evidence suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous system injuries.
