Pyraclostrobin(PYR),a widely used fungicide,has negative effects on fish and algae,but its toxicity in protozoa remains unclear.In this study,the effects of PYR on the growth,oxidative stress,and gene expression relat...Pyraclostrobin(PYR),a widely used fungicide,has negative effects on fish and algae,but its toxicity in protozoa remains unclear.In this study,the effects of PYR on the growth,oxidative stress,and gene expression related to stress and ATP-binding cassette(ABC)transporters in Tetrahymena thermophila were investigated.The result showed that the 96-h IC_(50)of PYR against T.thermophila was 17.2 mg/L.Moreover,PYR inhibited the growth of T.thermophila in concentration-or time-dependent manner.A morphological study revealed that the shape and size of T.thermophila changed,and damage of cell membrane surface was observed by scanning electron microscopy after 96 h of PYR exposure.The activities of superoxide dismutase(SOD)and catalase(CAT)increased throughout the experiment.In contrast,the glutathione(GSH)content was increased at 24 h and 48 h of exposure and decreased at 96 h.Moreover,a significant increase in malondialdehyde(MDA)level was observed in T.thermophila after96 h of exposure.Furthermore,PYR upregulated the HSP703,HSP705,GPx2,and ABAC15 gene expression in the 0.1–5-mg/L groups and downregulated the HSP704,HSP90,TGR,and ABCC52 mRNA levels at 96 h of exposure.These results suggest that PYR may exert adverse effects on T.thermophila by inducing oxidative stress and changing the gene expression related to ABC transporters and stress,which may enrich the understanding of the toxicity mechanism of PYR in aquatic organisms and provide reference data for aquatic ecological risk assessments.展开更多
Deep learning(DL)plays a critical role in processing and converting data into knowledge and decisions.DL technologies have been applied in a variety of applications,including image,video,and genome sequence analysis.I...Deep learning(DL)plays a critical role in processing and converting data into knowledge and decisions.DL technologies have been applied in a variety of applications,including image,video,and genome sequence analysis.In deep learning the most widely utilized architecture is Convolutional Neural Networks(CNN)are taught discriminatory traits in a supervised environment.In comparison to other classic neural networks,CNN makes use of a limited number of artificial neurons,therefore it is ideal for the recognition and processing of wheat gene sequences.Wheat is an essential crop of cereals for people around the world.Wheat Genotypes identification has an impact on the possible development of many countries in the agricultural sector.In quantitative genetics prediction of genetic values is a central issue.Wheat is an allohexaploid(AABBDD)with three distinct genomes.The sizes of the wheat genome are quite large compared to many other kinds and the availability of a diversity of genetic knowledge and normal structure at breeding lines of wheat,Therefore,genome sequence approaches based on techniques of Artificial Intelligence(AI)are necessary.This paper focuses on using the Wheat genome sequence will assist wheat producers in making better use of their genetic resources and managing genetic variation in their breeding program,as well as propose a novel model based on deep learning for offering a fundamental overview of genomic prediction theory and current constraints.In this paper,the hyperparameters of the network are optimized in the CNN to decrease the requirement for manual search and enhance network performance using a new proposed model built on an optimization algorithm and Convolutional Neural Networks(CNN).展开更多
Hippeastrum, a highly diverse genus in the Amaryllidaceae family, is a valuable ornamental bulbous flowering plant. Somatic embryogenesis(SE) is an efficient method for mass production of Hippeastrum plantlets. Previo...Hippeastrum, a highly diverse genus in the Amaryllidaceae family, is a valuable ornamental bulbous flowering plant. Somatic embryogenesis(SE) is an efficient method for mass production of Hippeastrum plantlets. Previous studies have been devoted to the in vitro propagation of Hippeastrum, but the SE and its regulatory networks are rarely reported. In this study, we established a direct SE method of Hippeastrum Bangkok Rose' using leaf bases as explants. MS supplemented with 1.00 mg·L^(-1)NAA +1.00 mg·L^(-1)KT + 0.25 mg·L^(-1)TDZ was the optimal medium for SE. Histological observations showed that the bipolar somatic embryo originated from the epidermal cell layer and underwent initiation,globular, scutellar and coleoptile stages. During SE, endogenous hormones of IAA, CTK, ABA, and SA were highly accumulated. Transcriptomic analysis revealed the genes encoding auxin biosynthesis/metabolic enzymes and efflux carriers were induced, while the auxin receptor of TIR1 and ARF transcriptional repressor of Aux/IAA were down-regulated and up-regulated, respectively, leading to suppression of auxin signaling. In contrast, cytokine signaling was promoted at the early stage of SE, as biosynthesis, transport, and signaling components were up-regulated.Various stress-related genes were up-regulated at the early or late stages of SE. Chromatin remodeling could also be dynamically regulated via distinct expression enzymes that control histone methylation and acetylation during SE. Moreover, key SE regulators, including WOXs and SERKs were highly expressed along with SE. Overall, the present study provides insights into the SE regulatory mechanisms of the Hippeastrum.展开更多
Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,...Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.展开更多
As an irreplaceable dietary constituent,lipids play a vital important role in health,but their effects on aging process and longevity are still not well known yet.In this paper,the metabolic profiling and gene express...As an irreplaceable dietary constituent,lipids play a vital important role in health,but their effects on aging process and longevity are still not well known yet.In this paper,the metabolic profiling and gene expression levels of Caenorhabditis elegans were investigated to explore the effects of different edible oils on senescence and lifespan.The results showed that teaseed oil(TO)could prolong the life expectancy and slow down the aging process of C.elegans.Compared to the control group,the intake of lard oil(LO)and TO increased the expression levels of genes related to inhibition of protein aggregation(akt-1,daf-16,hsf-1,hsp-16.2)and lipid metabolism(daf-7,daf-1,mdt-15,lipl-4,fat-5,fat-6,fat-7),with a more significant alteration in TO group.Metabolomics revealed that palm oil can upregulated plenty of fatty acids(palmitic acid,stearic acid,tetracosanoic acid),together with some amino acids(tryptophan,L-aspartate,L-valine)and carbohydrate(D-glucose),while the trend was opposite in TO group.Besides,moderate-to-strong correlations were found between differential metabolites and changed genes.In general,this paper claimed that TO could prolong lifespan and slow down aging process via regulating the lipids,amino acids and carbohydrates metabolism.展开更多
Gene expression(GE)classification is a research trend as it has been used to diagnose and prognosis many diseases.Employing machine learning(ML)in the prediction of many diseases based on GE data has been a flourishin...Gene expression(GE)classification is a research trend as it has been used to diagnose and prognosis many diseases.Employing machine learning(ML)in the prediction of many diseases based on GE data has been a flourishing research area.However,some diseases,like Alzheimer’s disease(AD),have not received considerable attention,probably owing to data scarcity obstacles.In this work,we shed light on the prediction of AD from GE data accurately using ML.Our approach consists of four phases:preprocessing,gene selection(GS),classification,and performance validation.In the preprocessing phase,gene columns are preprocessed identically.In the GS phase,a hybrid filtering method and embedded method are used.In the classification phase,three ML models are implemented using the bare minimum of the chosen genes obtained from the previous phase.The final phase is to validate the performance of these classifiers using different metrics.The crux of this article is to select the most informative genes from the hybrid method,and the best ML technique to predict AD using this minimal set of genes.Five different datasets are used to achieve our goal.We predict AD with impressive values forMultiLayer Perceptron(MLP)classifier which has the best performance metrics in four datasets,and the Support Vector Machine(SVM)achieves the highest performance values in only one dataset.We assessed the classifiers using sevenmetrics;and received impressive results,allowing for a credible performance rating.The metrics values we obtain in our study lie in the range[.97,.99]for the accuracy(Acc),[.97,.99]for F1-score,[.94,.98]for kappa index,[.97,.99]for area under curve(AUC),[.95,1]for precision,[.98,.99]for sensitivity(recall),and[.98,1]for specificity.With these results,the proposed approach outperforms recent interesting results.With these results,the proposed approach outperforms recent interesting results.展开更多
Themulti-skill resource-constrained project scheduling problem(MS-RCPSP)is a significantmanagement science problem that extends from the resource-constrained project scheduling problem(RCPSP)and is integrated with a r...Themulti-skill resource-constrained project scheduling problem(MS-RCPSP)is a significantmanagement science problem that extends from the resource-constrained project scheduling problem(RCPSP)and is integrated with a real project and production environment.To solve MS-RCPSP,it is an efficient method to use dispatching rules combined with a parallel scheduling mechanism to generate a scheduling scheme.This paper proposes an improved gene expression programming(IGEP)approach to explore newly dispatching rules that can broadly solve MS-RCPSP.A new backward traversal decoding mechanism,and several neighborhood operators are applied in IGEP.The backward traversal decoding mechanism dramatically reduces the space complexity in the decoding process,and improves the algorithm’s performance.Several neighborhood operators improve the exploration of the potential search space.The experiment takes the intelligent multi-objective project scheduling environment(iMOPSE)benchmark dataset as the training set and testing set of IGEP.Ten newly dispatching rules are discovered and extracted by IGEP,and eight out of ten are superior to other typical dispatching rules.展开更多
Rock strength is a crucial factor to consider when designing and constructing underground projects.This study utilizes a gene expression programming(GEP)algorithm-based model to predict the true triaxial strength of r...Rock strength is a crucial factor to consider when designing and constructing underground projects.This study utilizes a gene expression programming(GEP)algorithm-based model to predict the true triaxial strength of rocks,taking into account the influence of rock genesis on their mechanical behavior during the model building process.A true triaxial strength criterion based on the GEP model for igneous,metamorphic and magmatic rocks was obtained by training the model using collected data.Compared to the modified Weibols-Cook criterion,the modified Mohr-Coulomb criterion,and the modified Lade criterion,the strength criterion based on the GEP model exhibits superior prediction accuracy performance.The strength criterion based on the GEP model has better performance in R2,RMSE and MAPE for the data set used in this study.Furthermore,the strength criterion based on the GEP model shows greater stability in predicting the true triaxial strength of rocks across different types.Compared to the existing strength criterion based on the genetic programming(GP)model,the proposed criterion based on GEP model achieves more accurate predictions of the variation of true triaxial strength(s1)with intermediate principal stress(s2).Finally,based on the Sobol sensitivity analysis technique,the effects of the parameters of the three obtained strength criteria on the true triaxial strength of the rock are analysed.In general,the proposed strength criterion exhibits superior performance in terms of both accuracy and stability of prediction results.展开更多
The presence of selenium(Se)is not widely established as crucial for crops,although it is commonly recognized as an important nutrient for animals as well as humans.Even so,it is inevitably accepted that Se usually co...The presence of selenium(Se)is not widely established as crucial for crops,although it is commonly recognized as an important nutrient for animals as well as humans.Even so,it is inevitably accepted that Se usually contributes positively to the life cycle of plants.Previousfindings suggested that small amounts of Se seem to have a productive role in growth and production.As a result,Se is assumed to function in multiple ways,primarily by influencing a variety of biochemical and physiological functions.Also,Se also acts as a plant antioxidant and pro-oxidant and confers tolerance against different abiotic stresses,including salinity,drought,extreme temperature,and toxic metals/metalloids stresses.It reflects a defensive barrier against stress by increasing chlorophyll content synthesis,photosynthesis,oxygen supply,osmoprotectant concentration,and secondary metabolite acquisition.One other crucial role of Se is its ability to strengthen antioxidant performance in plants,thereby decreasing the concentration of reactive-oxygen-species(ROS).Furthermore,Se generates and modifies genes and proteins that respond situationally to stress,and the presence of high Se concentrations in the growth-medium can cause phytotoxic conditions via excessive ROS production,and through pro-oxidative Se occurrence,suppression of chlorophyll contents in the biosynthetic pathway,and the inhibition of plant developmental and normal physiological functions.Like a phytofortifier,the correct amount of Se can indeed enhance the nutrient quality of both crop and fodder production.Furthermore,crops have naturally developed ways to combat Se-deficiency and Se-toxicity.The current review focuses on recent advances in understanding the dynamics of Se,the positive and negative roles of Se in crop management,and its efficiency in countering abiotic stress.展开更多
Myzus persicae(M.persicae)is now considered a threat to agricultural crops due to economic losses.Numerous synthetic insecticides applied every year against M.persicae,are reported to be unsafe for environment,humans,...Myzus persicae(M.persicae)is now considered a threat to agricultural crops due to economic losses.Numerous synthetic insecticides applied every year against M.persicae,are reported to be unsafe for environment,humans,and beneficial insects.Furthermore,several species of Myzus have been found to develop resistance due to over application of these insecticides.Therefore,it is required to find some novel insecticide that would be safe for the environment as well as for humans.In the current study,two major pure constituentsα-pinene andβ-caryophyllene were evaluated for their insecticidal potential against M.persicae using a fumigant toxicity assay.Furthermore,impact ofα-pinene andβ-caryophyllene on expression of five different genes,e.g.,HSP 60,FPPS I,OSD,TOL and ANT responsible for reproduction,dispersion,and growth of M.persicae has also been investigated.To perform fumigant toxicity assay,five different concentrations(3.5,4,4.5,5 and 6μL L−1)ofα-pinene andβ-caryophyllene were prepared.Lethal concentration(LC)was calculated,and gene expression studies were executed through qRT PCR at LC30 ofα-pinene andβ-caryophyllene.Both constituents demonstrated excellent fumigant toxicity effects against M.persicae at all five concentrations.However,α-pinene shows significantly better results(98%)as compared toβ-caryophyllene(80%)after 72 h at 6μL L−1 of dose.The highest upregulation in expression was demonstrated at LC30 dose ofα-pinene in five in three out of five genes understudy(TOL,ANT,and FPPS I).Conversely,two genes HSP 60 and OSD demonstrated downregulation at LC30 dose ofβ-caryophyllene.Conclusively,our results highlighted the promising insecticidal potential of both compoundsα-pinene andβ-caryophylleneby interfering with the reproduction and development related processes in M.persicae,allowing us to recommend the phytoconstituents under investigation as an ecofriendly alternative to synthetic insecticides.展开更多
BACKGROUND The incidence rate of cerebral infarction in young people is increasing day by day,the age of onset tends to be younger,and its internal pathogenesis and mechanism are very complicated,which leads to greate...BACKGROUND The incidence rate of cerebral infarction in young people is increasing day by day,the age of onset tends to be younger,and its internal pathogenesis and mechanism are very complicated,which leads to greater difficulties in treatment.Therefore,it is essential to analyze the key pathway that affects the onset of cerebral infarction in young people from the perspective of genetics.AIM To compare the differentially expressed genes in the brain tissue of young and aged rats with middle cerebral artery occlusion and to analyse their effect on the key signalling pathway involved in the development of cerebral ischaemia in young rats.METHODS The Gene Expression Omnibus 2R online analysis tool was used to analyse the differentially expressed genes in the GSE166162 dataset regarding the development of cerebral ischaemia in young and aged groups of rats.DAVID 6.8 software was further used to filter the differentially expressed genes.These genes were subjected to Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to determine the key gene pathway that affects the occurrence of cerebral ischaemia in young rats.RESULTS Thirty-five differentially expressed genes(such as Igf2,Col1a2,and Sfrp1)were obtained;73 GO enrichment analysis pathways are mainly involved in biological processes such as drug response,amino acid stimulation response,blood vessel development,various signalling pathways,and enzyme regulation.They are involved in molecular functions such as drug binding,protein binding,dopamine binding,metal ion binding,and dopamine neurotransmitter receptor activity.KEGG pathway enrichment analysis showed a significantly enriched pathway:The cyclic adenosine monophosphate(c-AMP)signalling pathway.CONCLUSION The c-AMP signalling pathway might be the key pathway in the intervention of cerebral infarction in young people.展开更多
To explore how manganese affects the antioxidant system and the expression levels of related genes of“Hong yang”seedlings,the leaves of its tissue cultured seedlings were taken as test materials,and single factor tr...To explore how manganese affects the antioxidant system and the expression levels of related genes of“Hong yang”seedlings,the leaves of its tissue cultured seedlings were taken as test materials,and single factor treatment was performed by changing the manganese chloride(MnCl_(2)·4H_(2)O)solution concentration when spraying the leaves.The expression levels of Mn-SOD,POD64 and POD27 genes in leaves were quantitatively analyzed by real-time quantitative PCR(qRT-PCR)at different determination times.Meanwhile,the contents of malondial-dehyde(MDA),hydrogen peroxide(H_(2)O_(2)),the activities of antioxidant enzymes,including catalase(CAT),peroxidase(POD),and superoxide dismutase(SOD).The results showed that the SOD,CAT,POD,ascorbate peroxidase(APX),and reduced glutathione(GSH)activities in leaves were the highest at 12 h post-treatment with 50μM MnCl_(2)·4H_(2)O.Furthermore,the contents of MDA and H_(2)O_(2) in leaves also peaked when the concentration of H_(2)O_(2) is 50μM,which is the minimum value.Additionally at 50μM Mn^(2+),the Mn-SOD and POD27 expression was up-regulated as compared to the control,which promoted the expression of their respective enzyme activities.However,POD64 expression increased with the increasing Mn^(2+) concentration.Therefore,50μM is the optimal concentration of Mn when exogenously applied on“Hong yang”,which improve the antioxidant enzyme activity and regulate the plant’s physiological and biochemical functions.展开更多
BACKGROUND Breast cancer is regarded as a highly malignant neoplasm in the female population,posing a significant risk to women’s overall well-being.The prevalence of breast cancer has been observed to rise in China,...BACKGROUND Breast cancer is regarded as a highly malignant neoplasm in the female population,posing a significant risk to women’s overall well-being.The prevalence of breast cancer has been observed to rise in China,accompanied by an earlier age of onset when compared to Western countries.Breast cancer continues to be a prominent contributor to cancer-related mortality and morbidity among women,primarily due to its limited responsiveness to conventional treatment modalities.The diagnostic process is challenging due to the presence of non-specific clinical manifestations and the suboptimal precision of conventional diagnostic tests.There is a prevailing uncertainty regarding the most effective screening method and target populations,as well as the specificities and execution of screening programs.AIM To identify diagnostic and prognostic biomarkers for breast cancer.METHODS Overlapping differentially expressed genes were screened based on Gene Expression Omnibus(GSE36765,GSE10810,and GSE20086)and The Cancer Genome Atlas datasets.A protein-protein interaction network was applied to excavate the hub genes among these differentially expressed genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses,as well as gene set enrichment analyses,were conducted to examine the functions of these genes and their potential mechanisms in the development of breast cancer.For clarification of the diagnostic and prognostic roles of these genes,Kaplan–Mei-er and Cox proportional hazards analyses were conducted.RESULTS This study demonstrated that calreticulin,heat shock protein family B member 1,insulin-like growth Factor 1,interleukin-1 receptor 1,Krüppel-like factor 4,suppressor of cytokine signaling 3,and triosephosphate isomerase 1 are potential diagnostic biomarkers of breast cancer as well as potential treatment targets with clinical implications.CONCLUSION The screening of biomarkers is of guiding significance for the diagnosis and prognosis of the diseases.展开更多
Hypertension and metabolic syndrome, both of which increase with age, are multifactorial disorders. Their etiology is complex, making it challenging to isolate involved genes. This study aimed to characterize the hepa...Hypertension and metabolic syndrome, both of which increase with age, are multifactorial disorders. Their etiology is complex, making it challenging to isolate involved genes. This study aimed to characterize the hepatic gene expression in spontaneously hypertensive rats (SHR) at different ages. Blood pressure in SHR was determined by tail-cuff method at one and three months of age. Hepatic RNA was isolated and gene expression was compared using microarrays. Comparison between SHR and normotensive rats revealed significant variation in gene expression: 98 genes were upregulated and 122 were downregulated in SHR;while 88 genes were upregulated and 139 genes were downregulated in age-matched normotensive rats. Furthermore, within the SHR group, 110 genes were found to be upregulated and 168 genes downregulated across different ages. Analyses via the Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathways revealed that several genes are potentially implicated in both, hypertension and metabolic syndrome. The results suggest that SHR display variations in gene expression due to aging, and when compared to normotensive rats. These variations could contribute to the development of hypertension and metabolic syndrome. Microarray studies involving older rats are necessary to further validate these findings.展开更多
Tumor immunotherapy has emerged as a promising method in cancer treatment,but patient responses vary,necessitating personalized strategies and prognostic biomarkers.This study aimed to identify prognostic factors and ...Tumor immunotherapy has emerged as a promising method in cancer treatment,but patient responses vary,necessitating personalized strategies and prognostic biomarkers.This study aimed to identify prognostic factors and construct a predictive model for patient survival outcomes and immunotherapy response.We curated six immunotherapy datasets representing diverse cancer types and treatment regimens.After data preprocessing,patients were stratified based on immunotherapy response.Differential gene expression analysis identified 22 genes consistently dysregulated across multiple datasets.Functional analysis provided critical insights,highlighting the enrichment of these dysregulated genes in immune response pathways and tumor microenvironment-related processes.To create a robust prognostic model,we meticulously employed a multistep approach.Initially,the identified 22 genes underwent rigorous univariate Cox regression analysis to evaluate their individual associations with patient survival outcomes.Genes showing statistical significance(p-values<0.05)at this stage advanced to the subsequent multivariate Cox regression analysis,which aimed to address potential confounding factors and collinearity among genes.From this analysis,we ultimately identified four key genes—ST6GALNAC2,SNORA65,MFAP2,and CDKN2B—that were significantly associated with patient survival outcomes.Incorporating these four key genes along with their corresponding coefficients,we constructed a predictive model.This model’s efficacy was validated through extensive Cox regression analyses,demonstrating its robustness in predicting patient survival outcomes.Furthermore,our model exhibited promising predictive capability for immunotherapy response,providing a potential tool for anticipating treatment efficacy.These findings provide insights into immunotherapy response mechanisms and suggest potential prognostic biomarkers for personalized treatment.Our study contributes to advancing cancer immunotherapy and personalized medicine.展开更多
Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence ...Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines.Thus,there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors.Herein,we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions.We show that positively charged human serum albumin nanoparticles((+)HSAnp),which are capable of forming a complex with Ad5,significantly increase the transgene expression of Ad5 in both coxsackievirus–adenovirus receptor-positive and-negative cells.Furthermore,in charge-and dose-dependent manners,Ad5/(+)HSAnp complexes achieve robust(up to227-fold higher)and long-term(up to 60 days)transgene expression in the lungs of mice following intranasal instillation.Importantly,in the presence of preexisting anti-Ad5 immunity,complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity.These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.展开更多
The appropriate reference gene is a prerequisite for accurate normalization of gene expression level,and research on suitable reference genes in clam Cyclina sinensis is scarce.To improve the situation,we selected fiv...The appropriate reference gene is a prerequisite for accurate normalization of gene expression level,and research on suitable reference genes in clam Cyclina sinensis is scarce.To improve the situation,we selected five commonly used housekeeping genes,including β-actin,Elongation factor 1-α(EF1-α),Glyceraldehyde-3-pho sphate dehydrogenase(GAPDH),40S ribosomal protein S18(RPS18),and Tubulin a(TUB-α),then evaluated their expression stability in different adult tissues and under different experimental treatments(salinity stress and Vibrio parahaemolyticus infection).Their expression stability was analyzed by three frequently used programs,geNorm,NormFinder,and BestKeeper.This analysis indicated that multiple genes should be used for normalization,and we concluded that the reference gene combination GAPDH-RPS18-β-actin,should be used for qRT-PCR analysis in different tissues of C.sinensis under normal physiological conditions.For the clams under salinity stress and Vibrio infection,EF1-α-GAPDHRPS18 was recommended as the gene combination for qRT-PCR normalization.TUB-αwas generally poorly ranked by all programs,and should not be used in future studies.This study should provide fundamental support for accurate quantitative gene expression analysis of this species.展开更多
BACKGROUND Antidepressants,particularly selective serotonin reuptake inhibitors,are currently considered the first-line treatment for panic disorder(PD).However,little is known about the relationship between the bioma...BACKGROUND Antidepressants,particularly selective serotonin reuptake inhibitors,are currently considered the first-line treatment for panic disorder(PD).However,little is known about the relationship between the biomarkers that may predict better treatment.AIM To compare genome-wide methylation and gene expression patterns between responsive and non-responsive patients with PD after 4 wk of escitalopram treatment.METHODS Thirty patients with PD were enrolled in this study(responders=13;nonresponders=17).All patients were assessed using the PD Severity Scale-Chinese version before and after treatment.The Illumina Infinium MethylationEPIC(850k)BeadChip for genome-wide methylation screening and mRNA sequencing was used in all patients with PD.RESULTS A total of 701 differentially methylated positions(DMPs)were found between responders and non-responders(|Δβ|≥0.06,q<0.05),and the hyper-and hypomethylated CpG sites were 511(72.9%)and 190(27.1%),respectively.Relative to non-responders,there were 59 differential transcripts,of which 20 were downregulated and 39 were upregulated(q<0.05).However,no differen tially expressed genes were identified by mRNA sequencing after correcting for multiple testing(|log2(FC)|>1,q>0.05).CONCLUSION This preliminary study showed that DMPs might be associated with the treatment response to escitalopram in PD;however,these DMPs need to be verified in large samples.展开更多
Objective:To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine(TCM)based on the regulation of gene expression.Methods:Genome-wide gene expression profiles ...Objective:To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine(TCM)based on the regulation of gene expression.Methods:Genome-wide gene expression profiles of Michigan Cancer Foundation-7(MCF-7)cells treated with or without 4 cholic acid derivatives were detected by gene chip technology.Similarities in upregulated and downregulated genes were analyzed using the Connectivity Map(CMap)database.The affinity between cholic acid derivatives and the potential target was confirmed by molecular docking.The cholic acid derivative-regulated pathway enrichment analysis was performed by the STRING database,and the potential pathway was confirmed by in vitro experiments on MD Anderson-Metastatic Breast-231(MDA-MB-231)cells.Results:Compared with the reference genome in the CMap database,the gene expression profiles of cholic acid derivatives were similar to those of antipsychotic,anticancer,anti-inflammatory,and antiinfective drugs.Among them,4 derivatives were associated with antianxiety drugs,and molecular docking results showed that these compounds may act by binding to the ligand-binding site of gammaaminobutyric acid(GABA)receptors.Moreover,the cytoskeletal pathway is one of the pathways enriched in the derivatives.Of them,ursodeoxycholic acid showed significant inhibitory activity on the cytoskeleton formation of MDA-MB-231 cells.Conclusion:The gene expression detection method,combined with CMap and pathway enrichment analysis,could be used to study the mechanism of the active ingredients of TCM.In addition,our research showed that cholic acid derivatives have a potential affinity for membrane receptors,where they can exert anxiolytic activity by modulating opioid receptor,GABA receptor,and dopamine receptor.Moreover,ursodeoxycholic and chenodeoxycholic acid inhibit cytoskeleton formation,probably by acting on membrane proteins to activate the corresponding cytoskeletal pathways.展开更多
BACKGROUND The distal-less homeobox(DLX)gene family plays an important role in the development of several tumors.However,the expression pattern,prognostic and diagnostic value,possible regulatory mechanisms,and the re...BACKGROUND The distal-less homeobox(DLX)gene family plays an important role in the development of several tumors.However,the expression pattern,prognostic and diagnostic value,possible regulatory mechanisms,and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported.AIM We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer.METHODS Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases.Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue.cBioPortal was used to analyze DLX gene family variants.R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map.The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family.The pROC package was used to analyze the diagnostic value of the DLX gene family.R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes.The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration.The ggplot2,the survminer package,and the clusterProfiler package were used for visualization.RESULTS DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients.The expression of DLX genes were associated with M stage,pathologic stage,primary therapy outcome,residual tumor,lymphatic invasion,T stage,N stage,age,perineural invasion,and history of colon polyps.DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis.DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways,including the Hippo signaling pathway,the Wnt signaling pathway,several signaling pathways regulating the pluripotency of stem cells,and Staphylococcus aureus infection.CONCLUSION The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.展开更多
基金the Key Scientific Research Projects of Henan Province to College Youth Backbone Teacher(No.2021118)the National Key Research and Development Program of China(No.2021YFE0112000)。
文摘Pyraclostrobin(PYR),a widely used fungicide,has negative effects on fish and algae,but its toxicity in protozoa remains unclear.In this study,the effects of PYR on the growth,oxidative stress,and gene expression related to stress and ATP-binding cassette(ABC)transporters in Tetrahymena thermophila were investigated.The result showed that the 96-h IC_(50)of PYR against T.thermophila was 17.2 mg/L.Moreover,PYR inhibited the growth of T.thermophila in concentration-or time-dependent manner.A morphological study revealed that the shape and size of T.thermophila changed,and damage of cell membrane surface was observed by scanning electron microscopy after 96 h of PYR exposure.The activities of superoxide dismutase(SOD)and catalase(CAT)increased throughout the experiment.In contrast,the glutathione(GSH)content was increased at 24 h and 48 h of exposure and decreased at 96 h.Moreover,a significant increase in malondialdehyde(MDA)level was observed in T.thermophila after96 h of exposure.Furthermore,PYR upregulated the HSP703,HSP705,GPx2,and ABAC15 gene expression in the 0.1–5-mg/L groups and downregulated the HSP704,HSP90,TGR,and ABCC52 mRNA levels at 96 h of exposure.These results suggest that PYR may exert adverse effects on T.thermophila by inducing oxidative stress and changing the gene expression related to ABC transporters and stress,which may enrich the understanding of the toxicity mechanism of PYR in aquatic organisms and provide reference data for aquatic ecological risk assessments.
基金This research was supported by Korea Institute for Advancement of Technology(KIAT)grant funded by the Korea Government(MOTIE)(P0012724,The Competency Development Program for Industry Specialist)the National Research Foundation of Korea(NRF)grant funded by theKorea government(MSIT)(No.RS-2023-00218176),and the Soonchunhyang University Research Fund.
文摘Deep learning(DL)plays a critical role in processing and converting data into knowledge and decisions.DL technologies have been applied in a variety of applications,including image,video,and genome sequence analysis.In deep learning the most widely utilized architecture is Convolutional Neural Networks(CNN)are taught discriminatory traits in a supervised environment.In comparison to other classic neural networks,CNN makes use of a limited number of artificial neurons,therefore it is ideal for the recognition and processing of wheat gene sequences.Wheat is an essential crop of cereals for people around the world.Wheat Genotypes identification has an impact on the possible development of many countries in the agricultural sector.In quantitative genetics prediction of genetic values is a central issue.Wheat is an allohexaploid(AABBDD)with three distinct genomes.The sizes of the wheat genome are quite large compared to many other kinds and the availability of a diversity of genetic knowledge and normal structure at breeding lines of wheat,Therefore,genome sequence approaches based on techniques of Artificial Intelligence(AI)are necessary.This paper focuses on using the Wheat genome sequence will assist wheat producers in making better use of their genetic resources and managing genetic variation in their breeding program,as well as propose a novel model based on deep learning for offering a fundamental overview of genomic prediction theory and current constraints.In this paper,the hyperparameters of the network are optimized in the CNN to decrease the requirement for manual search and enhance network performance using a new proposed model built on an optimization algorithm and Convolutional Neural Networks(CNN).
基金funded by Guangdong Basic and Applied Basic Research Foundation (Grant No.2023A1515010237)the 2021 Dongguan Provincial Rural Revitalization Program (Grant No.20211800400022)+2 种基金the Guangdong Key Technology Research and Development Program (Grant Nos.2020B020220005,2022B1111040003)the Guangdong Modern Agricultural Industry Technology System Program (Grant No.2023KJ121)the South China Botanical Garden,the Chinese Academy of Sciences (Grant No.QNXM-02)。
文摘Hippeastrum, a highly diverse genus in the Amaryllidaceae family, is a valuable ornamental bulbous flowering plant. Somatic embryogenesis(SE) is an efficient method for mass production of Hippeastrum plantlets. Previous studies have been devoted to the in vitro propagation of Hippeastrum, but the SE and its regulatory networks are rarely reported. In this study, we established a direct SE method of Hippeastrum Bangkok Rose' using leaf bases as explants. MS supplemented with 1.00 mg·L^(-1)NAA +1.00 mg·L^(-1)KT + 0.25 mg·L^(-1)TDZ was the optimal medium for SE. Histological observations showed that the bipolar somatic embryo originated from the epidermal cell layer and underwent initiation,globular, scutellar and coleoptile stages. During SE, endogenous hormones of IAA, CTK, ABA, and SA were highly accumulated. Transcriptomic analysis revealed the genes encoding auxin biosynthesis/metabolic enzymes and efflux carriers were induced, while the auxin receptor of TIR1 and ARF transcriptional repressor of Aux/IAA were down-regulated and up-regulated, respectively, leading to suppression of auxin signaling. In contrast, cytokine signaling was promoted at the early stage of SE, as biosynthesis, transport, and signaling components were up-regulated.Various stress-related genes were up-regulated at the early or late stages of SE. Chromatin remodeling could also be dynamically regulated via distinct expression enzymes that control histone methylation and acetylation during SE. Moreover, key SE regulators, including WOXs and SERKs were highly expressed along with SE. Overall, the present study provides insights into the SE regulatory mechanisms of the Hippeastrum.
文摘Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.
基金supported by National Key R&D Program of China(2019YFC1606205)Natural Science Foundation of China(32172136)Jiangsu distinguished professor project and Talent plan of Taihu Lake.
文摘As an irreplaceable dietary constituent,lipids play a vital important role in health,but their effects on aging process and longevity are still not well known yet.In this paper,the metabolic profiling and gene expression levels of Caenorhabditis elegans were investigated to explore the effects of different edible oils on senescence and lifespan.The results showed that teaseed oil(TO)could prolong the life expectancy and slow down the aging process of C.elegans.Compared to the control group,the intake of lard oil(LO)and TO increased the expression levels of genes related to inhibition of protein aggregation(akt-1,daf-16,hsf-1,hsp-16.2)and lipid metabolism(daf-7,daf-1,mdt-15,lipl-4,fat-5,fat-6,fat-7),with a more significant alteration in TO group.Metabolomics revealed that palm oil can upregulated plenty of fatty acids(palmitic acid,stearic acid,tetracosanoic acid),together with some amino acids(tryptophan,L-aspartate,L-valine)and carbohydrate(D-glucose),while the trend was opposite in TO group.Besides,moderate-to-strong correlations were found between differential metabolites and changed genes.In general,this paper claimed that TO could prolong lifespan and slow down aging process via regulating the lipids,amino acids and carbohydrates metabolism.
文摘Gene expression(GE)classification is a research trend as it has been used to diagnose and prognosis many diseases.Employing machine learning(ML)in the prediction of many diseases based on GE data has been a flourishing research area.However,some diseases,like Alzheimer’s disease(AD),have not received considerable attention,probably owing to data scarcity obstacles.In this work,we shed light on the prediction of AD from GE data accurately using ML.Our approach consists of four phases:preprocessing,gene selection(GS),classification,and performance validation.In the preprocessing phase,gene columns are preprocessed identically.In the GS phase,a hybrid filtering method and embedded method are used.In the classification phase,three ML models are implemented using the bare minimum of the chosen genes obtained from the previous phase.The final phase is to validate the performance of these classifiers using different metrics.The crux of this article is to select the most informative genes from the hybrid method,and the best ML technique to predict AD using this minimal set of genes.Five different datasets are used to achieve our goal.We predict AD with impressive values forMultiLayer Perceptron(MLP)classifier which has the best performance metrics in four datasets,and the Support Vector Machine(SVM)achieves the highest performance values in only one dataset.We assessed the classifiers using sevenmetrics;and received impressive results,allowing for a credible performance rating.The metrics values we obtain in our study lie in the range[.97,.99]for the accuracy(Acc),[.97,.99]for F1-score,[.94,.98]for kappa index,[.97,.99]for area under curve(AUC),[.95,1]for precision,[.98,.99]for sensitivity(recall),and[.98,1]for specificity.With these results,the proposed approach outperforms recent interesting results.With these results,the proposed approach outperforms recent interesting results.
基金funded by the National Natural Science Foundation of China(Nos.51875420,51875421,52275504).
文摘Themulti-skill resource-constrained project scheduling problem(MS-RCPSP)is a significantmanagement science problem that extends from the resource-constrained project scheduling problem(RCPSP)and is integrated with a real project and production environment.To solve MS-RCPSP,it is an efficient method to use dispatching rules combined with a parallel scheduling mechanism to generate a scheduling scheme.This paper proposes an improved gene expression programming(IGEP)approach to explore newly dispatching rules that can broadly solve MS-RCPSP.A new backward traversal decoding mechanism,and several neighborhood operators are applied in IGEP.The backward traversal decoding mechanism dramatically reduces the space complexity in the decoding process,and improves the algorithm’s performance.Several neighborhood operators improve the exploration of the potential search space.The experiment takes the intelligent multi-objective project scheduling environment(iMOPSE)benchmark dataset as the training set and testing set of IGEP.Ten newly dispatching rules are discovered and extracted by IGEP,and eight out of ten are superior to other typical dispatching rules.
基金supported by the National Natural Science Foundation of China(Grant No.42177164)the Distinguished Youth Science Foundation of Hunan Province of China(Grant No.2022JJ10073)the Innovation-Driven Project of Central South University(Grant No.2020CX040).
文摘Rock strength is a crucial factor to consider when designing and constructing underground projects.This study utilizes a gene expression programming(GEP)algorithm-based model to predict the true triaxial strength of rocks,taking into account the influence of rock genesis on their mechanical behavior during the model building process.A true triaxial strength criterion based on the GEP model for igneous,metamorphic and magmatic rocks was obtained by training the model using collected data.Compared to the modified Weibols-Cook criterion,the modified Mohr-Coulomb criterion,and the modified Lade criterion,the strength criterion based on the GEP model exhibits superior prediction accuracy performance.The strength criterion based on the GEP model has better performance in R2,RMSE and MAPE for the data set used in this study.Furthermore,the strength criterion based on the GEP model shows greater stability in predicting the true triaxial strength of rocks across different types.Compared to the existing strength criterion based on the genetic programming(GP)model,the proposed criterion based on GEP model achieves more accurate predictions of the variation of true triaxial strength(s1)with intermediate principal stress(s2).Finally,based on the Sobol sensitivity analysis technique,the effects of the parameters of the three obtained strength criteria on the true triaxial strength of the rock are analysed.In general,the proposed strength criterion exhibits superior performance in terms of both accuracy and stability of prediction results.
文摘The presence of selenium(Se)is not widely established as crucial for crops,although it is commonly recognized as an important nutrient for animals as well as humans.Even so,it is inevitably accepted that Se usually contributes positively to the life cycle of plants.Previousfindings suggested that small amounts of Se seem to have a productive role in growth and production.As a result,Se is assumed to function in multiple ways,primarily by influencing a variety of biochemical and physiological functions.Also,Se also acts as a plant antioxidant and pro-oxidant and confers tolerance against different abiotic stresses,including salinity,drought,extreme temperature,and toxic metals/metalloids stresses.It reflects a defensive barrier against stress by increasing chlorophyll content synthesis,photosynthesis,oxygen supply,osmoprotectant concentration,and secondary metabolite acquisition.One other crucial role of Se is its ability to strengthen antioxidant performance in plants,thereby decreasing the concentration of reactive-oxygen-species(ROS).Furthermore,Se generates and modifies genes and proteins that respond situationally to stress,and the presence of high Se concentrations in the growth-medium can cause phytotoxic conditions via excessive ROS production,and through pro-oxidative Se occurrence,suppression of chlorophyll contents in the biosynthetic pathway,and the inhibition of plant developmental and normal physiological functions.Like a phytofortifier,the correct amount of Se can indeed enhance the nutrient quality of both crop and fodder production.Furthermore,crops have naturally developed ways to combat Se-deficiency and Se-toxicity.The current review focuses on recent advances in understanding the dynamics of Se,the positive and negative roles of Se in crop management,and its efficiency in countering abiotic stress.
基金funded by the Researchers Supporting Project Number(RSP2023R123),King Saud University,Riyadh,Saudi Arabia.
文摘Myzus persicae(M.persicae)is now considered a threat to agricultural crops due to economic losses.Numerous synthetic insecticides applied every year against M.persicae,are reported to be unsafe for environment,humans,and beneficial insects.Furthermore,several species of Myzus have been found to develop resistance due to over application of these insecticides.Therefore,it is required to find some novel insecticide that would be safe for the environment as well as for humans.In the current study,two major pure constituentsα-pinene andβ-caryophyllene were evaluated for their insecticidal potential against M.persicae using a fumigant toxicity assay.Furthermore,impact ofα-pinene andβ-caryophyllene on expression of five different genes,e.g.,HSP 60,FPPS I,OSD,TOL and ANT responsible for reproduction,dispersion,and growth of M.persicae has also been investigated.To perform fumigant toxicity assay,five different concentrations(3.5,4,4.5,5 and 6μL L−1)ofα-pinene andβ-caryophyllene were prepared.Lethal concentration(LC)was calculated,and gene expression studies were executed through qRT PCR at LC30 ofα-pinene andβ-caryophyllene.Both constituents demonstrated excellent fumigant toxicity effects against M.persicae at all five concentrations.However,α-pinene shows significantly better results(98%)as compared toβ-caryophyllene(80%)after 72 h at 6μL L−1 of dose.The highest upregulation in expression was demonstrated at LC30 dose ofα-pinene in five in three out of five genes understudy(TOL,ANT,and FPPS I).Conversely,two genes HSP 60 and OSD demonstrated downregulation at LC30 dose ofβ-caryophyllene.Conclusively,our results highlighted the promising insecticidal potential of both compoundsα-pinene andβ-caryophylleneby interfering with the reproduction and development related processes in M.persicae,allowing us to recommend the phytoconstituents under investigation as an ecofriendly alternative to synthetic insecticides.
文摘BACKGROUND The incidence rate of cerebral infarction in young people is increasing day by day,the age of onset tends to be younger,and its internal pathogenesis and mechanism are very complicated,which leads to greater difficulties in treatment.Therefore,it is essential to analyze the key pathway that affects the onset of cerebral infarction in young people from the perspective of genetics.AIM To compare the differentially expressed genes in the brain tissue of young and aged rats with middle cerebral artery occlusion and to analyse their effect on the key signalling pathway involved in the development of cerebral ischaemia in young rats.METHODS The Gene Expression Omnibus 2R online analysis tool was used to analyse the differentially expressed genes in the GSE166162 dataset regarding the development of cerebral ischaemia in young and aged groups of rats.DAVID 6.8 software was further used to filter the differentially expressed genes.These genes were subjected to Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to determine the key gene pathway that affects the occurrence of cerebral ischaemia in young rats.RESULTS Thirty-five differentially expressed genes(such as Igf2,Col1a2,and Sfrp1)were obtained;73 GO enrichment analysis pathways are mainly involved in biological processes such as drug response,amino acid stimulation response,blood vessel development,various signalling pathways,and enzyme regulation.They are involved in molecular functions such as drug binding,protein binding,dopamine binding,metal ion binding,and dopamine neurotransmitter receptor activity.KEGG pathway enrichment analysis showed a significantly enriched pathway:The cyclic adenosine monophosphate(c-AMP)signalling pathway.CONCLUSION The c-AMP signalling pathway might be the key pathway in the intervention of cerebral infarction in young people.
基金supported by the following grants:Science and Technology Support Plan of Guizhou Province:Breeding Research and Demonstration of All-Red Bud Transformation of“GH-1”Clone of“Hong Yang”Kiwifruit(Guizhou Family Combination Support[2021]General 234)Innovation Capacity Construction Project of Scientific Research Institutions in Guizhou Province:Technology R&D and Service Capacity Construction of Fine Fruit(Kiwifruit,Passion Fruit)Industry in Guizhou Province[2019]4004the National Key Research and Development Program“Quality and Efficiency Improvement Technology Integration and Demonstration of Advantageous Characteristic Industries in Guizhou Karst Mountain Area(2021YFD1100300)”Post-Subsidy Fund.
文摘To explore how manganese affects the antioxidant system and the expression levels of related genes of“Hong yang”seedlings,the leaves of its tissue cultured seedlings were taken as test materials,and single factor treatment was performed by changing the manganese chloride(MnCl_(2)·4H_(2)O)solution concentration when spraying the leaves.The expression levels of Mn-SOD,POD64 and POD27 genes in leaves were quantitatively analyzed by real-time quantitative PCR(qRT-PCR)at different determination times.Meanwhile,the contents of malondial-dehyde(MDA),hydrogen peroxide(H_(2)O_(2)),the activities of antioxidant enzymes,including catalase(CAT),peroxidase(POD),and superoxide dismutase(SOD).The results showed that the SOD,CAT,POD,ascorbate peroxidase(APX),and reduced glutathione(GSH)activities in leaves were the highest at 12 h post-treatment with 50μM MnCl_(2)·4H_(2)O.Furthermore,the contents of MDA and H_(2)O_(2) in leaves also peaked when the concentration of H_(2)O_(2) is 50μM,which is the minimum value.Additionally at 50μM Mn^(2+),the Mn-SOD and POD27 expression was up-regulated as compared to the control,which promoted the expression of their respective enzyme activities.However,POD64 expression increased with the increasing Mn^(2+) concentration.Therefore,50μM is the optimal concentration of Mn when exogenously applied on“Hong yang”,which improve the antioxidant enzyme activity and regulate the plant’s physiological and biochemical functions.
基金Supported by the Natural Science Foundation of Inner Mongolia,No.2021GG0298.
文摘BACKGROUND Breast cancer is regarded as a highly malignant neoplasm in the female population,posing a significant risk to women’s overall well-being.The prevalence of breast cancer has been observed to rise in China,accompanied by an earlier age of onset when compared to Western countries.Breast cancer continues to be a prominent contributor to cancer-related mortality and morbidity among women,primarily due to its limited responsiveness to conventional treatment modalities.The diagnostic process is challenging due to the presence of non-specific clinical manifestations and the suboptimal precision of conventional diagnostic tests.There is a prevailing uncertainty regarding the most effective screening method and target populations,as well as the specificities and execution of screening programs.AIM To identify diagnostic and prognostic biomarkers for breast cancer.METHODS Overlapping differentially expressed genes were screened based on Gene Expression Omnibus(GSE36765,GSE10810,and GSE20086)and The Cancer Genome Atlas datasets.A protein-protein interaction network was applied to excavate the hub genes among these differentially expressed genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses,as well as gene set enrichment analyses,were conducted to examine the functions of these genes and their potential mechanisms in the development of breast cancer.For clarification of the diagnostic and prognostic roles of these genes,Kaplan–Mei-er and Cox proportional hazards analyses were conducted.RESULTS This study demonstrated that calreticulin,heat shock protein family B member 1,insulin-like growth Factor 1,interleukin-1 receptor 1,Krüppel-like factor 4,suppressor of cytokine signaling 3,and triosephosphate isomerase 1 are potential diagnostic biomarkers of breast cancer as well as potential treatment targets with clinical implications.CONCLUSION The screening of biomarkers is of guiding significance for the diagnosis and prognosis of the diseases.
文摘Hypertension and metabolic syndrome, both of which increase with age, are multifactorial disorders. Their etiology is complex, making it challenging to isolate involved genes. This study aimed to characterize the hepatic gene expression in spontaneously hypertensive rats (SHR) at different ages. Blood pressure in SHR was determined by tail-cuff method at one and three months of age. Hepatic RNA was isolated and gene expression was compared using microarrays. Comparison between SHR and normotensive rats revealed significant variation in gene expression: 98 genes were upregulated and 122 were downregulated in SHR;while 88 genes were upregulated and 139 genes were downregulated in age-matched normotensive rats. Furthermore, within the SHR group, 110 genes were found to be upregulated and 168 genes downregulated across different ages. Analyses via the Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathways revealed that several genes are potentially implicated in both, hypertension and metabolic syndrome. The results suggest that SHR display variations in gene expression due to aging, and when compared to normotensive rats. These variations could contribute to the development of hypertension and metabolic syndrome. Microarray studies involving older rats are necessary to further validate these findings.
文摘Tumor immunotherapy has emerged as a promising method in cancer treatment,but patient responses vary,necessitating personalized strategies and prognostic biomarkers.This study aimed to identify prognostic factors and construct a predictive model for patient survival outcomes and immunotherapy response.We curated six immunotherapy datasets representing diverse cancer types and treatment regimens.After data preprocessing,patients were stratified based on immunotherapy response.Differential gene expression analysis identified 22 genes consistently dysregulated across multiple datasets.Functional analysis provided critical insights,highlighting the enrichment of these dysregulated genes in immune response pathways and tumor microenvironment-related processes.To create a robust prognostic model,we meticulously employed a multistep approach.Initially,the identified 22 genes underwent rigorous univariate Cox regression analysis to evaluate their individual associations with patient survival outcomes.Genes showing statistical significance(p-values<0.05)at this stage advanced to the subsequent multivariate Cox regression analysis,which aimed to address potential confounding factors and collinearity among genes.From this analysis,we ultimately identified four key genes—ST6GALNAC2,SNORA65,MFAP2,and CDKN2B—that were significantly associated with patient survival outcomes.Incorporating these four key genes along with their corresponding coefficients,we constructed a predictive model.This model’s efficacy was validated through extensive Cox regression analyses,demonstrating its robustness in predicting patient survival outcomes.Furthermore,our model exhibited promising predictive capability for immunotherapy response,providing a potential tool for anticipating treatment efficacy.These findings provide insights into immunotherapy response mechanisms and suggest potential prognostic biomarkers for personalized treatment.Our study contributes to advancing cancer immunotherapy and personalized medicine.
基金supported in part by the grant from National Natural Science Foundation of China(82171818,81703048,82041019,and 82101919)the grant from Defense Industrial Technology Development Program of China(JCKY2020802B001)Beijing Municipal Science and Technology Commission(Z201100005420024)。
文摘Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines.Thus,there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors.Herein,we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions.We show that positively charged human serum albumin nanoparticles((+)HSAnp),which are capable of forming a complex with Ad5,significantly increase the transgene expression of Ad5 in both coxsackievirus–adenovirus receptor-positive and-negative cells.Furthermore,in charge-and dose-dependent manners,Ad5/(+)HSAnp complexes achieve robust(up to227-fold higher)and long-term(up to 60 days)transgene expression in the lungs of mice following intranasal instillation.Importantly,in the presence of preexisting anti-Ad5 immunity,complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity.These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.
基金Supported by the funding for school-level research projects of Yancheng Institute of Technology(No.xjr2019047)the National Natural Science Foundation of China(No.31902362)。
文摘The appropriate reference gene is a prerequisite for accurate normalization of gene expression level,and research on suitable reference genes in clam Cyclina sinensis is scarce.To improve the situation,we selected five commonly used housekeeping genes,including β-actin,Elongation factor 1-α(EF1-α),Glyceraldehyde-3-pho sphate dehydrogenase(GAPDH),40S ribosomal protein S18(RPS18),and Tubulin a(TUB-α),then evaluated their expression stability in different adult tissues and under different experimental treatments(salinity stress and Vibrio parahaemolyticus infection).Their expression stability was analyzed by three frequently used programs,geNorm,NormFinder,and BestKeeper.This analysis indicated that multiple genes should be used for normalization,and we concluded that the reference gene combination GAPDH-RPS18-β-actin,should be used for qRT-PCR analysis in different tissues of C.sinensis under normal physiological conditions.For the clams under salinity stress and Vibrio infection,EF1-α-GAPDHRPS18 was recommended as the gene combination for qRT-PCR normalization.TUB-αwas generally poorly ranked by all programs,and should not be used in future studies.This study should provide fundamental support for accurate quantitative gene expression analysis of this species.
基金Supported by The Sichuan Provincial People’s Hospital Translational Medicine Fund,No.2021LY02.
文摘BACKGROUND Antidepressants,particularly selective serotonin reuptake inhibitors,are currently considered the first-line treatment for panic disorder(PD).However,little is known about the relationship between the biomarkers that may predict better treatment.AIM To compare genome-wide methylation and gene expression patterns between responsive and non-responsive patients with PD after 4 wk of escitalopram treatment.METHODS Thirty patients with PD were enrolled in this study(responders=13;nonresponders=17).All patients were assessed using the PD Severity Scale-Chinese version before and after treatment.The Illumina Infinium MethylationEPIC(850k)BeadChip for genome-wide methylation screening and mRNA sequencing was used in all patients with PD.RESULTS A total of 701 differentially methylated positions(DMPs)were found between responders and non-responders(|Δβ|≥0.06,q<0.05),and the hyper-and hypomethylated CpG sites were 511(72.9%)and 190(27.1%),respectively.Relative to non-responders,there were 59 differential transcripts,of which 20 were downregulated and 39 were upregulated(q<0.05).However,no differen tially expressed genes were identified by mRNA sequencing after correcting for multiple testing(|log2(FC)|>1,q>0.05).CONCLUSION This preliminary study showed that DMPs might be associated with the treatment response to escitalopram in PD;however,these DMPs need to be verified in large samples.
基金supported by the National Natural Science Foundation of China(22067016).
文摘Objective:To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine(TCM)based on the regulation of gene expression.Methods:Genome-wide gene expression profiles of Michigan Cancer Foundation-7(MCF-7)cells treated with or without 4 cholic acid derivatives were detected by gene chip technology.Similarities in upregulated and downregulated genes were analyzed using the Connectivity Map(CMap)database.The affinity between cholic acid derivatives and the potential target was confirmed by molecular docking.The cholic acid derivative-regulated pathway enrichment analysis was performed by the STRING database,and the potential pathway was confirmed by in vitro experiments on MD Anderson-Metastatic Breast-231(MDA-MB-231)cells.Results:Compared with the reference genome in the CMap database,the gene expression profiles of cholic acid derivatives were similar to those of antipsychotic,anticancer,anti-inflammatory,and antiinfective drugs.Among them,4 derivatives were associated with antianxiety drugs,and molecular docking results showed that these compounds may act by binding to the ligand-binding site of gammaaminobutyric acid(GABA)receptors.Moreover,the cytoskeletal pathway is one of the pathways enriched in the derivatives.Of them,ursodeoxycholic acid showed significant inhibitory activity on the cytoskeleton formation of MDA-MB-231 cells.Conclusion:The gene expression detection method,combined with CMap and pathway enrichment analysis,could be used to study the mechanism of the active ingredients of TCM.In addition,our research showed that cholic acid derivatives have a potential affinity for membrane receptors,where they can exert anxiolytic activity by modulating opioid receptor,GABA receptor,and dopamine receptor.Moreover,ursodeoxycholic and chenodeoxycholic acid inhibit cytoskeleton formation,probably by acting on membrane proteins to activate the corresponding cytoskeletal pathways.
文摘BACKGROUND The distal-less homeobox(DLX)gene family plays an important role in the development of several tumors.However,the expression pattern,prognostic and diagnostic value,possible regulatory mechanisms,and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported.AIM We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer.METHODS Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases.Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue.cBioPortal was used to analyze DLX gene family variants.R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map.The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family.The pROC package was used to analyze the diagnostic value of the DLX gene family.R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes.The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration.The ggplot2,the survminer package,and the clusterProfiler package were used for visualization.RESULTS DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients.The expression of DLX genes were associated with M stage,pathologic stage,primary therapy outcome,residual tumor,lymphatic invasion,T stage,N stage,age,perineural invasion,and history of colon polyps.DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis.DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways,including the Hippo signaling pathway,the Wnt signaling pathway,several signaling pathways regulating the pluripotency of stem cells,and Staphylococcus aureus infection.CONCLUSION The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.
