Transcriptome analysis of adherens junction pathway-related genes after peripheral nerve injury

The neural regeneration process is driven by a wide range of molecules and pathways. Adherens junctions are critical cellular junctions for the integrity of peripheral nerves. However, few studies have systematically characterized the transcript changes in the adherens junction pathway following injury. In this study, a rat model of sciatic nerve crush injury was established by forceps. Deep sequencing data were analyzed using comprehensive transcriptome analysis at 0, 1, 4, 7, and 14 days after injury. Results showed that most individual molecules in the adherens junctions were either upregulated or downregulated after nerve injury. The m RNA expression of ARPC1 B, ARPC3, TUBA8, TUBA1 C, CTNNA2, ACTN3, MET, HGF, NME1 and ARF6, which are involved in the adherens junction pathway and in remodeling of adherens junctions, was analyzed using quantitative real-time polymerase chain reaction. Most of these genes were upregulated in the sciatic nerve stump following peripheral nerve injury, except for CTNNA2, which was downregulated. Our findings reveal the dynamic changes of key molecules in adherens junctions and in remodeling of adherens junctions. These key genes provide a reference for the selection of clinical therapeutic targets for peripheral nerve injury.

Pathway analysis for genome-wide genetic variation data:Analytic principles,latest developments,and new opportunities

Pathway analysis,also known as gene-set enrichment analysis,is a multilocus analytic strategy that integrates a priori,biological knowledge into the statistical analysis of high-throughput genetics data.Originally developed for the studies of gene expression data,it has become a powerful analytic procedure for indepth mining of genome-wide genetic variation data.Astonishing discoveries were made in the past years,uncovering genes and biological mechanisms underlying common and complex disorders.However,as massive amounts of diverse functional genomics data accrue,there is a pressing need for newer generations of pathway analysis methods that can utilize multiple layers of high-throughput genomics data.In this review,we provide an intellectual foundation of this powerful analytic strategy,as well as an update of the state-of-the-art in recent method developments.The goal of this review is threefold:(1)introduce the motivation and basic steps of pathway analysis for genome-wide genetic variation data;(2)review the merits and the shortcomings of classic and newly emerging integrative pathway analysis tools;and(3)discuss remaining challenges and future directions for further method developments.

A pan-cancer integrative pathway analysis of multi-omics data

Background:Multi-view-omics datasets offer rich opportunities for integrative analysis across genomic,transcriptomic,and epigenetic data platforms.Statistical methods are needed to rigorously implement current research on functional biology,matching the complex dynamics of systems genomic datasets.Methods:We apply imputation for missing data and a structural,graph-theoretic pathway model to a dataset of 22 cancers across 173 signaling pathways.Our pathway model integrates multiple data platforms,and we test for differential activation between cancerous tumor and healthy tissue populations.Results:Our pathway analysis reveals significant disturbance in signaling pathways that are known to relate to oncogenesis.We identify several pathways that suggest new research directions,including the Trk signaling and focal adhesion kinase activation pathways in sarcoma.Conclusions:Our integrative analysis confirms contemporary research findings,which supports the validity of our findings.We implement an interactive data visualization for exploration of the pathway analyses,which is available online for public access.

Expression Profile Analysis of Genes Involved in Brassinosteroid Biosynthesis Pathway in Cotton Fiber Development

Cotton(Gossypium hirsutum L.) is the leading fiber crop and one of the mainstays of the economy in the world.Cotton fibers,as the main product of cotton plants,are unicellular,linear

Transcriptomic analysis reveals essential microRNAs after peripheral nerve injury

Studies have shown that microRNAs(miRNAs) mediate posttranscriptional regulation of target genes and participate in various physiological and pathological processes, including peripheral nerve injury. However, it is hard to select key miRNAs with essential biological functions among a large number of differentially expressed miRNAs. Previously, we collected injured sciatic nerve stumps at multiple time points after nerve crush injury, examined gene changes at different stages(acute, sub-acute, and post-acute), and obtained mRNA expression profiles. Here, we jointly analyzed mRNAs and miRNAs, and investigated upstream miRNAs of differentially expressed mRNAs using Ingenuity Pathway Analysis bioinformatic software. A total of 31, 42, 30, and 23 upstream miRNAs were identified at 1, 4, 7, and 14 days after rat sciatic nerve injury, respectively. Temporal expression patterns and biological involvement of commonly involved upstream miRNAs(miR-21, let-7, miR-223, miR-10 b, miR-132, miR-15 b, miR-127, miR-29 a, miR-29 b, and miR-9) were then determined at multiple time points. Expression levels of miR-21, miR-132, miR-29 a, and miR-29 b were robustly increased after sciatic nerve injury. Biological processes involving these miRNAs include multicellular organismal response to stress, positive regulation of the epidermal growth factor receptor signaling pathway, negative regulation of epithelial cell differentiation, and regulation of myocardial tissue growth. Moreover, we constructed mechanistic networks of let-7, miR-21, and miR-223, the most significantly involved upstream miRNAs. Our findings reveal that multiple upstream miRNAs(i.e., let-7, miR-21, and miR-223) were associated with gene expression changes in rat sciatic nerve stumps after nerve injury, and these miRNAs play an important role in peripheral nerve regeneration. This study was approved by the Experimental Animal Ethics Committee of Jiangsu Province of China(approval No. 20190303-18) on March 3, 2019.

Identification of commonly regulated protein targets and molecular pathways in PC-3 and DU145 androgen-independent human prostate cancer cells treated with the curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one

Objective: To identify mutually regulated proteins in PC-3 and DU145 androgen-independent prostate cancer cell lines treated with 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17), and to study the molecular pathways that contributed to the anticancer activity of MS17.Methods: PC-3 and DU145 cells were treated with 3 × EC_(50)(15 μM) concentration of MS17 for 24 h and were subjected to protein expression profiling using two-dimensional gel electrophoresis and protein identification by mass spectrometry.Selected differentially expressed proteins with significant P-value of P<0.05 and fold change over 1.5-folds were filtered through and ontologically classified.Mutually regulated proteins were ranked by fold change and identified as common protein targets of MS17.Results: Profiling data revealed that, the mutually down-regulated proteins included ACTB and ACTG associated with structural molecule activity, ACTN1 with cell cycle, ACTN4 with cell migration, HNRPK with apoptosis, PLST with morphogenesis and TERA with proteolysis.However, the expressions of CH60 and HS71 A respectively associated with response to unfolded protein demonstrated opposing regulation in PC-3 and DU145 cells.Pathway analysis of the differentially expressed proteins in PC-3 cells demonstrated the modulation of top pathways associated with cell-cell adhesion and cytoskeletal organization while in DU145 cells the pathways were associated with proteosomal degradation, regulation of electrolytes and water, regulation control of germ cells and organization of filament assembly/disassembly.Conclusions: The findings of the present study provide an understanding on the anti-tumorigenic activity of MS17 at the proteome level and warrant further research for its potential application for the management and treatment of androgen-independent prostate cancer.

Patient Health Seeking Behavior and Choice of Place of Care among Tuberculosis Clients in Selected States in Nigeria

Background: Tuberculosis (TB) remains a major global public health problem. Early detection and initiation of treatment shortens infectious period and is key to TB control. A considerable proportion of TB patients presenting with advanced symptoms suggests delay in seeking care. As TB control programs rely on passive case finding, TB care-seeking behavior is critical as un-diagnosed cases act as reservoirs for transmission. This study assessed patient health seeking behavior and choice of place of care among TB patients in Nigeria. Methods: This was a pro-gramme implementation, facility-based cross-sectional study in 14 states, 92 facilities across three levels of care. Interviewer-administered semi-structured questionnaires were used. Information on personal characteristics and health seeking behavior was collected from June 2020 to December 2021. The analysis was based on the various healthcare providers where the respondents first sought care. Data analysis was done using IBM SPSS and summarized using frequency and percentages. Chi square test was used for associations of characteristics of patients and choice of place of care at p Results: In all 14 states, distribution of overall first place of seeking care for TB symptoms was: 7208 (75.8%) health facilities (range 57% to 88%), while 2294 (24.2%) visited other places including community pharmacist, patent medicine vendor, traditional/home, un-specified/none. For Health facilities, the majority were at public facilities 6563 (69.1%) and private 641 (6.7%). Moreover, 6 states had >20% of respondents who first sought care at PMVs, while 3 states (Delta, Imo, and Rivers) had 10% of respondents who first sought care at Community Pharmacist. Conclusions: Nearly a quarter of people with TB first sought care outside health facilities, suggesting the need to align availability of services with their needs.

Design and thermodynamic analysis of a pathway enabling anaerobic production of poly-3-hydroxybutyrate in Escherichia coli

Utilizing anaerobic metabolisms for the production of biotechnologically relevant products presents potential advantages,such as increased yields and reduced energy dissipation.However,lower energy dissipation may indicate that certain reactions are operating closer to their thermodynamic equilibrium.While stoichiometric analyses and genetic modifications are frequently employed in metabolic engineering,the use of thermodynamic tools to evaluate the feasibility of planned interventions is less documented.In this study,we propose a novel metabolic engineering strategy to achieve an efficient anaerobic production of poly-(R)-3-hydroxybutyrate(PHB)in the model organism Escherichia coli.Our approach involves re-routing of two-thirds of the glycolytic flux through non-oxidative glycolysis and coupling PHB synthesis with NADH re-oxidation.We complemented our stoichiometric analysis with various thermodynamic approaches to assess the feasibility and the bottlenecks in the proposed engineered pathway.According to our calculations,the main thermodynamic bottleneck are the reactions catalyzed by the acetoacetyl-CoAβ-ketothiolase(EC 2.3.1.9)and the acetoacetyl-CoA reductase(EC 1.1.1.36).Furthermore,we calculated thermodynamically consistent sets of kinetic parameters to determine the enzyme amounts required for sustaining the conversion fluxes.In the case of the engineered conversion route,the protein pool necessary to sustain the desired fluxes could account for 20%of the whole cell dry weight.

Study on the mechanism of cholic acid derivatives in traditional Chinese medicine based on the regulation of gene expression

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.

Biological characteristics of dynamic expression of nerve regeneration related growth factors in dorsal root ganglia after peripheral nerve injury

The regenerative capacity of peripheral nerves is limited after nerve injury.A number of growth factors modulate many cellular behaviors,such as proliferation and migration,and may contribute to nerve repair and regeneration.Our previous study observed the dynamic changes of genes in L4–6 dorsal root ganglion after rat sciatic nerve crush using transcriptome sequencing.Our current study focused on upstream growth factors and found that a total of 19 upstream growth factors were dysregulated in dorsal root ganglions at 3,9 hours,1,4,or 7 days after nerve crush,compared with the 0 hour control.Thirty-six rat models of sciatic nerve crush injury were prepared as described previously.Then,they were divided into six groups to measure the expression changes of representative genes at 0,3,9 hours,1,4 or 7 days post crush.Our current study measured the expression levels of representative upstream growth factors,including nerve growth factor,brain-derived neurotrophic factor,fibroblast growth factor 2 and amphiregulin genes,and explored critical signaling pathways and biological process through bioinformatic analysis.Our data revealed that many of these dysregulated upstream growth factors,including nerve growth factor,brain-derived neurotrophic factor,fibroblast growth factor 2 and amphiregulin,participated in tissue remodeling and axon growth-related biological processes Therefore,the experiment described the expression pattern of upstream growth factors in the dorsal root ganglia after peripheral nerve injury.Bioinformatic analysis revealed growth factors that may promote repair and regeneration of damaged peripheral nerves.All animal surgery procedures were performed in accordance with Institutional Animal Care Guidelines of Nantong University and ethically approved by the Administration Committee of Experimental Animals,China(approval No.20170302-017)on March 2,2017.

Quantitative proteomic determination of diethylstilbestrol action on prostate cancer

Diethylstilbestrol （DES） has a direct cellular mechanism inhibition on prostate cancer. Its action is independent from the oestrogen receptors and is preserved after a first-line hormonal therapy. We aimed to identify proteins involved in the direct cellular inhibition effects of DES on prostate cancer. We used a clonogenic assay to establish the median lethal concentration of DES on 22RV1 cells. 22RV1 cells were exposed to standard and DES-enriched medium. After extraction, protein expression levels were obtained by two-dimensional differential in-gel electrophoresis （2D-DIGE） and isotope labelling tags for relative and absolute quantification （iTRAQ）. Proteins of interest were analysed by quantitative RT-PCR and western blotting. The differentially regulated proteins （P〈0.01） were interrogated against a global molecular network based on the ingenuity knowledge base. The 2D-DIGE analyses revealed DES-induced expression changes for 14 proteins （〉 1.3 fold; P〈0.05）. The iTRAQ analyses allowed the identification of 895 proteins. Among these proteins, 65 had a modified expression due to DES exposure （i.e., 23 overexpressed and 42 underexpressed）. Most of these proteins were implicated in apoptosis and redox processes and had a predicted mitochondrial expression. Additionally, ingenuity pathway analysis placed the OAT and HSBP1 genes at the centre of a highly significant network. RT-PCR confirmed the overexpression of OAT （P=0.006） and HSPB1 （P=0.046）.

Prediction of Triptolide Targets in Colorectal Cancer Using Network Pharmacology and Molecular Docking

[Objectives]To investigate the potential mechanisms of action of triptolide,an active component in the traditional Chinese medicine Tripterygium wilfordii Hook F,in colorectal cancer(CRC).[Methods]Public databases were first searched for genes and proteins known to be associated with CRC,as well as those predicted to be targets of triptolide,and then Ingenuity Pathway Analysis(IPA)was applied to identify enriched gene pathways and networks.Networks and pathways that overlapped between CRC-associated proteins and triptolide target proteins were then used to predict candidate protein targets of triptolide in CRC.[Results]The following proteins were found to be expressed in both CRC-associated networks and triptolide target networks:JUN,FOS,CASP3,BCL2,IFNG,and VEGFA.Docking studies suggested that triptolide can fit in the binding pocket of the four top candidate triptolide target proteins(CASP3,BCL2,VEGFA and IFNG).The overlapping pathways were activation of neuroinflammation signaling,glucocorticoid receptor signaling,T helper(Th)cell differentiation,Th1/Th2 activation,and colorectal cancer metastasis signaling.[Conclusions]These results show that network pharmacology can be used to generate hypotheses about how triptolide exerts therapeutic effects in CRC.Network pharmacology may be a useful method for characterizing multi-target drugs in complex diseases.

Prediction of Apigenin Targets in Lung Cancer Using Network Pharmacology and Molecular Docking

[Objectives]To elucidate the mechanism of action of apigenin against lung cancer.[Methods]First,drug-target pathways and networks were constructed to predict potential protein targets of apigenin and their main interactions with the drug.Then,the ingenuity pathway analysis(IPA)was carried out to identify enriched gene pathways and networks,and the candidate protein targets of apigenin were predicted using networks and pathways that overlapped between proteins associated with lung cancer and proteins targeted by apigenin.[Results]Docking studies with apigenin indicated that BCL-2,CASP9,CDK2,CYCLIND1,PI3K,NF-κB,Rb1,p53,and AKT are the top candidate targets of apigenin,suggesting that the drug acts against lung cancer by regulating proteins involved in molecular mechanisms of cancer,as well as small cell lung cancer,pancreatic adenocarcinoma,glucocorticoid receptor,and p53 signaling.It was also found that apigenin affects networks mainly involved in the cell cycle,cell-to-cell signaling and interactions,hematological system development and function,cell death and survival,and organismal injury and abnormalities.[Conclusions]This study shows that network pharmacology is useful in generating hypotheses about how apigenin exerts therapeutic effects in lung cancer,as well as in discovering new multitarget drugs against other complex diseases.

Differential Expression of Genes in HepG2 Cells Caused by UC001kfo RNAi as Shown by RNA-seq

The differential expression of genes in HepG2 cells caused by UC001 kfo RNAi was investigated using RNA-seq. HepG2 cells were infected by Lenti-sh UC001 kfo lentivirus particles. The expression of UC001 kfo m RNA in the HepG2-sh UC001 kfo cell line was detected by real-time PCR. RNA-seq technology was used to identify the difference in the expression of genes regulated by lnc RNA UC001 kfo in the HepG2 cell line. Gene ontology and signaling pathway analysis were performed to reveal the biological functions of the genes encoding of significantly different m RNAs. The results showed that m RNAs were differentially expressed between the HepG2-sh UC001 kfo cell line and the HepG2 cell line. The UC001 kfo m RNA was significantly down-regulated in the stable cell line HepG2-sh UC001kfo（P〈0.001）. Additionally, we found 19 signaling pathways or functional classifications encompassing 30 genes that played a role in cancer characteristics, cell adhesion, invasion and migration. The results also showed that the expression of many genes associated with cancer cell invasion and metastasis was decreased with the down-regulation of the lnc RNA UC001 kfo. Lnc RNA UC001 kfo may play a role in regulating cancer cell invasion and metastasis. It was suggested that m RNAs were differentially expressed in the HepG2 cell line after the down-regulation of lnc RNA-UC001 kfo. Some took part in the extracellular matrix, cell adhesion, motility, growth, and localization. The genes encoding of differentially expressed m RNAs may participate in cell invasion and metastasis.

Mechanism of Wumei Pill in the Treatment of Non-Erosive reflux disease from the Perspective of Network Pharmacology and Molecular docking

Objective:Based on network pharmacology and molecular docking to explore the mechanism of Wumei Pill in the treatment of non-erosive reflux disease(NERD).Method:We collected the active ingredients and targets of Wumei Pill by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and collected NERD related targets through Genecards,PharmGKB,Drugbank,DisGeNET,OMIM,CTD and TTD databases.Intersection targets of Wumei Pill targets and NERD related targets were the potential targets of Wumei Pill in the treatment of NERD.We imported the intersection targets into the STRING database to obtain the PPI network,and obtained the hub targets.The network diagram of"Drugs-Potential active ingredients-Potential targets"was constructed by Cytoscape 3.7.2 software.We used R software to perform Gene Ontology function enrichment analysis(GO)and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis(KEGG)on hub targets,and then performed molecular docking verification.Results:There were 129 active ingredients and 213 drug targets of Wumei Pill of which 114 were the intersection targets.1587 GO enrichment items were identified(P<0.05),including 1,491 biological processes,11 cell components,and 85 molecular functions.143 KEGG pathways(P<0.05),mainly related to Kaposi sarcoma-associated herpesvirus infection,IL-17 signaling pathway,the TNF signaling pathway,MAPK signaling pathway.Results of molecular docking showed that the potential active ingredients in Wumei Pill had relatively stable binding activity to the key targets.Conclusion:Wumei pill for the treatment of non-erosive reflux disease are main active ingredients quercetin,kaempferol,beta sitosterol,Isocorypalmine,Stigmasterol,rutaecarpine,etc,the main targets is JUN,TP53,AKT1,may inhibit excessive inflammation,antioxidant therapy effect into full play.This provided a certain theoretical basis for clinical application.

Integrative omics analysis identifies macrophage migration inhibitory factor signaling pathways underlying human hepatic fibrogenesis and fibrosis

The genetic basis underlying liver fibrosis remains largely unknown.We conducted a study to identify genetic alleles and underlying pathways associated with hepatic fibrogenesis and fibrosis at the genome-wide level in 121 human livers.By accepting a liberal significance level of P<1e-4,we identified 73 and 71 candidate loci respectively affecting the variability in alpha-smooth muscle actin(a-SMA)levels(fibrogenesis)and total collagen content(fibrosis).The top genetic loci associated with the two markers were BAZA1 and NOL10 for a-SMA expression and FAM46A for total collagen content(P<1e-6).We further investigated the relationship between the candidate loci and the nearby gene transcription levels(cis-expression quantitative trait loci)in the same liver samples.We found that 44 candidate loci for a-SMA expression and 44 for total collagen content were also associated with the transcription of the nearby genes(P<0.05).Pathway analyses of these genes indicated that macrophage migration inhibitory factor(MIF)related pathway is significantly associated with fibrogenesis and fibrosis,though different genes were enriched for each marker.The association between the single nucleotide polymorphisms,MIF and a-SMA showed that decreased MIF expression is correlated with increased a-SMA expression,suggesting that variations in MIF locus might affect the susceptibility of fibrogenesis through controlling MIF gene expression.In summary,our study identified candidate alleles and pathways underlying both fibrogenesis and fibrosis in human livers.Our bioinformatics analyses suggested MIF pathway as a strong candidate involved in liver fibrosis,thus further investigation for the role of the MIF pathway in liver fibrosis is warranted.The study was reviewed and approved by the Institutional Review Board(IRB)of Wayne State University(approval No.201842)on May 17,2018.

Effect of Curcumin on Aged Drosophila Melanogaster:A Pathway Prediction Analysis

Objective： To re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin. Methods： Microarray data generated from other study aiming to investigate effect of curcumin on extending lifespan of Drosophila melanogaster were further used for pathway prediction analysis. The differentially expressed genes were identified by using GeneSpdng GX with a criterion of 3.0-fold change. Two Cytoscape plugins including BisoGenet and molecular complex detection （MCODE） were used to establish the protein-protein interaction （PPI） network based upon differential genes in order to detect highly connected regions. The function annotation clustering tool of Database for Annotation, Visualization and Integrated Discovery （DAVID） was used for pathway analysis. Results： A total of 87 genes expressed differentially in D. melanogaster treated with curcumin were identified, among which 50 were up-regulated significantly and 37 were remarkably down-regulated in D. melanogaster treated with curcumin. Based upon these differential genes, PPI network was constructed with 1,082 nodes and 2,412 edges. Five highly connected regions in PPI networks were detected by MCODE algorithm, suggesting anti-aging effect of curcumin may be underlined through five different pathways including Notch signaling pathway, basal transcription factors, cell cycle regulation, ribosome, Wnt signaling pathway, and p53 pathway. Conclusion： Genes and their associated pathways in D. rnelanogaster treated with anti-aging agent curcumin were identified using PPI network and MCODE algorithm, suggesting that curnumin may be developed as an alternative therapeutic medicine for treating aging-associated diseases.

Differential gene expression by fiber-optic beadarray and pathway in adrenocorticotrophin-secreting pituitary adenomas

Background Adrenocorticotrophin （ACTH）-secreting pituitary adenomas account for approximately 7%-14% of all pituitary adenomas, but its pathogenesis is still enigmatic. This study aimed to explore mechanisms underlying the pathogenesis of ACTH-secreting pituitary adenomas.Methods We used fiber-optic beadarray to examine gene expression in three ACTH-secreting adenomas compared with three normal pituitaries. Four differentially expressed genes from the three ACTH-secreting adenomas and three normal pituitaries were chosen randomly for validation by reverse transcriptase-real time quantitative polymerase chain reaction （RT-qPCR）. We then analyzed the differentially expressed gene profile with Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway.Results Fiber-optic beadarray analysis showed that the expression of 28 genes and 8 expressed sequence tags （ESTs）were significantly increased and the expression of 412 genes and 31 ESTs were significantly decreased. Bioinformatic and pathway analysis showed that the genes HIGD1B, EPS8, HPGD, DAPK2, and IGFBP3 and the transforming growth factor （TGF）-β signaling pathway and extracellular matrix （ECM）-receptor interaction pathway may play important roles in tumorigenesis and progression of ACTH-secreting pituitary adenomas.Conclusions Our data suggest that numerous aberrantly expressed genes and several pathways are involved in the pathogenesis of ACTH-secreting pituitary adenomas. Fiber-optic beadarray combined with pathway analysis of differential gene expression appears to be a valid method of investigating tumour pathogenesis.

Metabolomics analysis of poly(L-lactic acid)nanofibers’performance on PC12 cell differentiation

The aim of this article is to reveal the influence of aligned/random poly(L-lactic acid)(PLLA)nanofibers on PC12 cell differentiation from the perspective of metabolic level.First,three materials-PLLA aligned nanofibers(PLLA AF),PLLA random nanofibers(PLLA RF)and PLLA films(control)-were prepared by electrospinning and spin coating.Their surface morphologies were characterized.Subsequently,the cell viability,cell morphology and neurite length of PC12 cells on the surface of the three materials were evaluated,indicating more neurites in the PLLA RF groups but the longer average neurite length in the PLLA AF groups.Next,the metabolite profiles of PC12 cells cultured on the surface of the three nanofibers after 12 h,24 h and 36 h showed that,compared with the control,51,48 and 31 types of differential metabolites were detected at the three time points among the AF groups,respectively;and 56,45 and 41 types among the RF groups,respectively.Furthermore,the bioinformatics analysis of differential metabolites identified two pathways and three metabolites critical to PC12 cell differentiation influenced by the nanofibers.In addition,the verification experiment on critical metabolites and metabolic pathways were performed.The integrative analysis combining cytology,metabolomics and bioinformatics approaches revealed that though both PLLA AF and RF were capable of stimulating the synthesis of neurotransmitters,the PLLA AF were more beneficial for PC12 cell differentiation,whereas the PLLA RF were less effective.

Current state and influencing factors in airbag management among emergency department nurses:A multicenter study

BACKGROUND The emergency department(ED)plays a critical role in establishing artificial airways and implementing mechanical ventilation.Managing airbags in the ED presents a prime opportunity to mitigate the risk of ventilator-associated pneumonia.Nonetheless,existing research has largely overlooked the understanding,beliefs,and practical dimensions of airway airbag management among ED nurses,with a predominant focus on intensive care unit nurses.AIM To investigate the current status of ED nurses'knowledge,beliefs,and practical behaviors in airway airbag management and their influencing factors.METHODS A survey was conducted from July 10th to August 10th,2023,using convenience sampling on 520 ED nurses from 15 tertiary hospitals and 5 sary hospitals in Shanghai.Pathway analysis was utilized to analyze the influencing factors.RESULTS The scores for ED nurses'airway airbag management knowledge were 60.26±23.00,belief was 88.65±13.36,and behavior was 75.10±19.84.The main influencing factors of airbag management knowledge included participation in specialized nurse or mechanical ventilation training,department,and work experience in the department.Influencing factors of airbag management belief comprised knowledge,department,and participation in specialized nurse or mechanical ventilation training.Primary influencing factors of airbag management behavior included knowledge,belief,department,participation in specialized nurse or mechanical ventilation training,and professional title.The belief in airbag management among ED nurses acted as a partial mediator between knowledge and behavior,with a total effect value of 0.513,and an indirect effect of 0.085,constituting 16.6%of the total effect.CONCLUSION ED nurses exhibit a positive attitude toward airbag management with relatively standardized practices,yet there remains room for improvement in their knowledge levels.Nursing managers should implement interventions tailored to the characteristics of ED nurses'airbag management knowledge,beliefs,and practices to enhance their airbag management proficiency.