Key Regulatory Hub Research Articles

Integrated Metabolomics and Transcriptomic Analysis of Cellular Stress Responses: Elucidating Metabolic Pathways and Regulatory Networks

Cellular stress responses are vital for maintaining homeostasis and enabling adaptation to environmental and physiological challenges. This study employed an integrated metabolomic and transcriptomic approach to investigate the regulatory networks and metabolic pathways underlying these responses. Conducted between July 2023 and December 2024 in Karachi, Pakistan, the research utilized cutting-edge technologies, including real-time PCR, high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and next-generation sequencing (NGS). Biological samples representing various stress conditions, such as oxidative stress, nutrient deprivation, and environmental stressors, were collected and analyzed under strict ethical protocols. RNA sequencing (RNA-Seq) revealed 1,250 differentially expressed genes (DEGs), with notable upregulation of GPX1 and SOD2, indicating enhanced detoxification pathways under oxidative stress. Concurrently, metabolomic profiling identified significant alterations in metabolites, such as elevated glutathione, lactate, and proline, highlighting adaptive shifts in glycolysis, reactive oxygen species (ROS) detoxification, and osmoprotection. Integrative analysis using Weighted Gene Co-expression Network Analysis (WGCNA) pinpointed key regulatory hubs, including HIF1A and succinate, as central nodes in stress-specific networks. This comprehensive multi-omics approach provided actionable insights into the molecular and metabolic mechanisms of cellular stress. The findings hold significant translational potential in agriculture and medicine, particularly for enhancing crop resilience and developing targeted therapies for stress-related disorders. Despite the limitations of in vitro models, this study underscores the value of multi-layered omics analyses in elucidating stress adaptation and lays the groundwork for future integrative research

Combined Physiological and Transcriptomic Analysis Reveals Key Regulatory Networks and Potential Hub Genes Controlling Chilling Tolerance During Soybean Germination.

Chilling is an important limiting factor for seed germination of soybean (Glycine max [L.] Merr.). To reveal the regulatory mechanism of chilling tolerance during the soybean germination stage, based on previous studies, the chilling tolerance line R48 and chilling sensitive line R89 in chromosome segment substitution lines were selected for physiological index determination and transcriptome sequencing. It was found that reactive oxygen species (ROS) scavenging system related enzymes, ROS, and osmotic regulators were significantly different between the two lines. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment were performed on the differentially expressed genes obtained by transcriptome sequencing. It was found that terms or pathways related to flavonoids, unsaturated fatty acids, and abscisic acid were highly enriched. In addition, weighted gene coexpression network analysis (WGCNA) method was used to analyze the physiological index data and transcriptome sequencing data. Four main coexpression modules significantly related to physiological indicators were obtained, and the hub genes in each module were screened according to eigengene-based connectivity value. Haplotype analysis of important candidate genes using soybean germplasm resources showed that there were significant differences in germination indexes between different major haplotypes of Glyma.17G163200. Based on the results of enrichment analysis and WGCNA, the regulation model of low temperature tolerance during soybean germination was preliminarily drawn. This study will provide theoretical guidance for analyzing the molecular regulation mechanism of cold tolerance in soybean germination stage.

An integrated multi-omics analysis identifies novel regulators of circadian rhythm and sleep disruptions under unique light environment in Antarctica.

Light is the dominant zeitgeber for biological clocks, and its regulatory mechanism for sleep-wake activity has been extensively studied. However, the molecular pathways through which the unique Antarctic light environment, with polar days in summer and polar nights in winter, affects human sleep and circadian rhythm remain largely unidentified, although previous studies have observed delayed circadian rhythm and sleep disruptions among expeditioners during polar nights. In this study, we conducted comprehensive dynamic research on the expeditioners residing in Antarctica for over one year. By integrating the phenotypic changes with multi-omics data, we tried to identify the novel candidate regulators and their correlation networks involved in circadian and sleep disorders under abnormal light exposure. We found that during the austral winter, expeditioners exhibited delayed bedtime and getting up time, reduced sleep efficiency, and increased sleep fragmentation. Meanwhile, serum dopamine metabolite levels significantly increased, while serotonin metabolites and antioxidants decreased. These changes were accompanied by altered expression of genes and proteins associated with neural functions, cellular activities, transcriptional regulation, and so on. Through the correlation and causal mediation analysis, we identified several potential pathways modulating human sleep-wake activity, involving genes and proteins related to neural function, glucose metabolism, extracellular matrix homeostasis, and some uncharacterized lncRNAs. Based on the identified causal mediators, LASSO regression analysis further revealed a novel candidate gene, Shisa Family Member 8 (SHISA8), as a potential key regulatory hub in this process. These findings shed light on the probable molecular mechanisms of sleep disorders in Antarctica and suggest SHISA8 as a novel candidate target for medical intervention in sleep disorders under unique light environments.

PeWRKY20 represses PeMDH1 to modulate malic acid metabolism and flavor formation in postharvest passion fruit

Postharvest events enhance fruit palatability, fragrance and sweetness and reduce sourness. With passion fruit (Passiflora edulis) the underlying molecular events occurring during the postharvest period remain largely unknown. In this study we define how passion fruit flavor alters during the postharvest period using integrated transcriptome and metabolome analyses. Passion fruits were stored under three conditions: room temperature, low temperature, and room temperature with a pre-fumigation with 100 μM methyljasmonate (MeJA). During the postharvest period, organic acid content decreased but sugars and most volatiles increased. While both low temperature and MeJA treatment effectively delayed the aging process, MeJA better maintained fruit flavor. Transcriptomic and network modelling analyses targeted PeWRKY20 was a potential key regulator of the flavor of passion fruit. PeWRKY20 was shown to bind to the Malate Dehydrogenase 1 (PeMDH1) promoter to represses PeMDH1 expression. Transient assays in Nicotiana benthamiana leaves suggested that PeWRKY20 and PeMDH1 function oppositely to regulate the production of malic acid and volatiles, such as heptadecane, dimeththyl phthalate, and L-α-terpineol. Our work unravels a key regulatory hub in postharvest passion fruit development based on an association between malic acid and volatiles.

NRT2.1 mediates the reciprocal regulation of nitrate and NO/SNO in seedling leaves of Fraxinus mandshurica and Betula platyphylla

Nitric oxide (NO) and S-nitrosothiol (SNO) are signal molecules and the products of nitrogen metabolism. Nitrate (NO3−) is the main nitrogen source, and nitrate transporters (NRTs) are responsible for NO3− absorption or transport. However, the interactive effect between NO3−/NRT and NO/SNO in tree plants remains ambiguous. In the present study, 25 mmol L−1 NO3− and 1 mmol L−1 NO donor sodium nitroprusside (SNP) treatment that was conducted for 24 h enhanced NO/SNO and NO3− metabolism, whereas 2.5 mmol L−1 NO3− and 80 μmol L−1 N6022 (a compound that increases SNO content) treatment reduced them in seedling leaves of Fraxinus mandshurica and Betula platyphylla. Among the nine NRT family members examined, the gene expression level of NRT2.1 had a greater response to NO/SNO and NO3− treatment in the seedling leaves of F. mandshurica and B. platyphylla. Meanwhile, FmNRT2.1 mediated NO and SNO production in seedling leaves of F. mandshurica using Agrobacterium-mediated transient transformation. These findings shed light on the reciprocal regulation between NO3− and NO/SNO in seedlings of F. mandshurica and B. platyphylla, and NRT2.1 may act as a key regulatory hub.

Dynamic patterns of gene expressional and regulatory variations in cotton heterosis.

Although the application of heterosis has significantly increased crop yield over the past century, the mechanisms underlying this phenomenon still remain obscure. Here, we applied transcriptome sequencing to unravel the impacts of parental expression differences and transcriptomic reprogramming in cotton heterosis. A high-quality transcriptomic atlas covering 15 developmental stages and tissues was constructed for XZM2, an elite hybrid of upland cotton (Gossypium hirsutum L.), and its parental lines, CRI12 and J8891. This atlas allowed us to identify gene expression differences between the parents and to characterize the transcriptomic reprogramming that occurs in the hybrid. Our analysis revealed abundant gene expression differences between the parents, with pronounced tissue specificity; a total of 1,112 genes exhibited single-parent expression in at least one tissue. It also illuminated transcriptomic reprogramming in the hybrid XZM2, which included both additive and non-additive expression patterns. Coexpression networks between parents and hybrid constructed via weighted gene coexpression network analysis identified modules closely associated with fiber development. In particular, key regulatory hub genes involved in fiber development showed high-parent dominant or over dominant patterns in the hybrid, potentially driving the emergence of heterosis. Finally, high-depth resequencing data was generated and allele-specific expression patterns examined in the hybrid, enabling the dissection of cis- and trans-regulation contributions to the observed expression differences. Parental transcriptional differences and transcriptomic reprogramming in the hybrid, especially the non-additive upregulation of key genes, play an important role in shaping heterosis. Collectively, these findings provide new insights into the molecular basis of heterosis in cotton.

Single-cell total-RNA profiling unveils regulatory hubs of transcription factors

Recent development of RNA velocity uses master equations to establish the kinetics of the life cycle of RNAs from unspliced RNA to spliced RNA (i.e., mature RNA) to degradation. To feed this kinetic analysis, simultaneous measurement of unspliced RNA and spliced RNA in single cells is greatly desired. However, the majority of single-cell RNA-seq chemistry primarily captures mature RNA species to measure gene expressions. Here, we develop a one-step total-RNA chemistry-based single-cell RNA-seq method: snapTotal-seq. We benchmark this method with multiple single-cell RNA-seq assays in their performance in kinetic analysis of cell cycle by RNA velocity. Next, with LASSO regression between transcription factors, we identify the critical regulatory hubs mediating the cell cycle dynamics. We also apply snapTotal-seq to profile the oncogene-induced senescence and identify the key regulatory hubs governing the entry of senescence. Furthermore, from the comparative analysis of unspliced RNA and spliced RNA, we identify a significant portion of genes whose expression changes occur in spliced RNA but not to the same degree in unspliced RNA, indicating these gene expression changes are mainly controlled by post-transcriptional regulation. Overall, we demonstrate that snapTotal-seq can provide enriched information about gene regulation, especially during the transition between cell states.

Current perspectives of lncRNAs in abiotic and biotic stress tolerance in plants.

Abiotic/biotic stresses pose a major threat to agriculture and food security by impacting plant growth, productivity and quality. The discovery of extensive transcription of large RNA transcripts that do not code for proteins, termed long non-coding RNAs (lncRNAs) with sizes larger than 200 nucleotides in length, provides an important new perspective on the centrality of RNA in gene regulation. In plants, lncRNAs are widespread and fulfill multiple biological functions in stress response. In this paper, the research advances on the biological function of lncRNA in plant stress response were summarized, like as Natural Antisense Transcripts (NATs), Competing Endogenous RNAs (ceRNAs) and Chromatin Modification etc. And in plants, lncRNAs act as a key regulatory hub of several phytohormone pathways, integrating abscisic acid (ABA), jasmonate (JA), salicylic acid (SA) and redox signaling in response to many abiotic/biotic stresses. Moreover, conserved sequence motifs and structural motifs enriched within stress-responsive lncRNAs may also be responsible for the stress-responsive functions of lncRNAs, it will provide a new focus and strategy for lncRNA research. Taken together, we highlight the unique role of lncRNAs in integrating plant response to adverse environmental conditions with different aspects of plant growth and development. We envisage that an improved understanding of the mechanisms by which lncRNAs regulate plant stress response may further promote the development of unconventional approaches for breeding stress-resistant crops.

Deciphering the regulatory networks involved in mild and severe salt stress responses in the roots of wild grapevine Vitis vinifera spp. sylvestris.

Transcriptional regulatory networks are pivotal components of plant's response to salt stress. However, plant adaptation strategies varied as a function of stress intensity, which is mainly modulated by climate change. Here, we determined the gene regulatory networks based on transcription factor (TF) TF_gene co-expression, using two transcriptomic data sets generated from the salt-tolerant "Tebaba" roots either treated with 50mM NaCl (mild stress) or 150mM NaCl (severe stress). The analysis of these regulatory networks identified specific TFs as key regulatory hubs as evidenced by their multiple interactions with different target genes related to stress response. Indeed, under mild stress, NAC and bHLH TFs were identified as central hubs regulating nitrogen storage process. Moreover, HSF TFs were revealed as a regulatory hub regulating various aspects of cellular metabolism including flavonoid biosynthesis, protein processing, phenylpropanoid metabolism, galactose metabolism, and heat shock proteins. These processes are essentially linked to short-term acclimatization under mild salt stress. This was further consolidated by the protein-protein interaction (PPI) network analysis showing structural and plant growth adjustment. Conversely, under severe salt stress, dramatic metabolic changes were observed leading to novel TF members including MYB family as regulatory hubs controlling isoflavonoid biosynthesis, oxidative stress response, abscisic acid signaling pathway, and proteolysis. The PPI network analysis also revealed deeper stress defense changes aiming to restore plant metabolic homeostasis when facing severe salt stress. Overall, both the gene co-expression and PPI network provided valuable insights on key transcription factor hubs that can be employed as candidates for future genetic crop engineering programs.

Lipids: A Key Regulatory Hub in Plant Stress Adaptation

The plants exert rapid responses to environmental stresses to adapt with the stress. Plants respond in many ways to different abiotic and biotic stresses. The first cellular component to sense stress signals is cell membrane. Cell membrane is a biological membrane, and its main constituents are Lipids that can sense conditions outside the cell. Remodeling of cellular membrane lipids is one of the critical mechanisms in the plant cells to withstand stresses. Lipids play a critical role in triggering and regulating cellular hormonal signaling cascades. There is a close correlation between ABA-dependent signaling and lipid metabolic pathways to maintain the integrity and the viability of cellular membranes. Phosphatidic acid, lysophospholipid, inositol phosphate, fatty acid, oxylipins, diacylglycerol, and sphingolipid are considered as the signaling molecules. Lipids also act as a stress reliever to lower the negative effects of stress. This review highlights the key regulatory roles of lipids in plant adaptation against the environmental stresses.

Impact of Phospholipase C Gamma 2 Alzheimer's Disease Variants on Microglial Biology and Disease Pathogenesis

AbstractBackgroundAlzheimer’s disease (AD) and other neurodegenerative diseases are typified by a robust microglial‐mediated immune response. Phospholipase C gamma 2 (PLCG2), whose variants confer altered risk for AD, is a critical signaling element for various immune receptors and is a key regulatory hub gene for immune signaling. A functional hypermorphic P522R variant (rs72824905) of PLCG2 has been identified to be protective against AD (OR= 0.68, p=5.83‐10). Significantly, we identified a novel SNP (rs617749044) associated with elevated AD risk (OR=1.164; p=0.047) encoding the PLCG2 M28L variant.MethodTo investigate the impact of PLCG2 AD risk variants on microglial biology and disease pathogenesis, we have generated mice bearing either the M28L risk or the P522R protective PLCG2 variant, all crossed onto the 5XFAD amyloidogenic murine model of AD.ResultHere, we provide comprehensive analysis of PLCG2 action in mouse models of AD. We demonstrate that PLCG2 variants regulate protein‐protein interaction, alter microglial phenotypes in 5XFAD mice, regulate cytokine levels, drive distinct transcriptional phenotypes of microglia, and affect plaque pathology. Our data demonstrate that the M28L variant results in accelerated and exacerbated disease‐related pathology, and conversely, the P522R variant appeared to attenuate disease severity and progression.ConclusionTogether, our finding provides evidence that PLCG2 play an important role in AD pathophysiology, indicating PLCG2 as a potential new therapeutic target for AD.

Reactive oxygen species signalling in plant stress responses.

Reactive oxygen species (ROS) are key signalling molecules that enable cells to rapidly respond to different stimuli. In plants, ROS play a crucial role in abiotic and biotic stress sensing, integration of different environmental signals and activation of stress-response networks, thus contributing to the establishment of defence mechanisms and plant resilience. Recent advances in the study of ROS signalling in plants include the identification of ROS receptors and key regulatory hubs that connect ROS signalling with other important stress-response signal transduction pathways and hormones, as well as new roles for ROS in organelle-to-organelle and cell-to-cell signalling. Our understanding of how ROS are regulated in cells by balancing production, scavenging and transport has also increased. In this Review, we discuss these promising developments and how they might be used to increase plant resilience to environmental stress.

Emerging Roles of Plant DNA-Binding With One Finger Transcription Factors in Various Hormone and Stress Signaling Pathways.

Coordinated transcriptional regulation of stress-responsive genes orchestrated by a complex network of transcription factors (TFs) and the reprogramming of metabolism ensure a plant’s continued growth and survival under adverse environmental conditions (e.g., abiotic stress). DNA-binding with one finger (Dof) proteins, a group of plant-specific TF, were identified as one of several key components of the transcriptional regulatory network involved in abiotic stress responses. In many plant species, Dofs are often activated in response to a wide range of adverse environmental conditions. Dofs play central roles in stress tolerance by regulating the expression of stress-responsive genes via the DOFCORE element or by interacting with other regulatory proteins. Moreover, Dofs act as a key regulatory hub of several phytohormone pathways, integrating abscisic acid, jasmonate, SA and redox signaling in response to many abiotic stresses. Taken together, we highlight a unique role of Dofs in hormone and stress signaling that integrates plant response to adverse environmental conditions with different aspects of plant growth and development.

Transcriptome Meta-Analysis Associated Targeting Hub Genes and Pathways of Drought and Salt Stress Responses in Cotton (Gossypium hirsutum): A Network Biology Approach.

Abiotic stress tolerance is an intricate feature controlled through several genes and networks in the plant system. In abiotic stress, salt, and drought are well known to limit cotton productivity. Transcriptomics meta-analysis has arisen as a robust method to unravel the stress-responsive molecular network in crops. In order to understand drought and salt stress tolerance mechanisms, a meta-analysis of transcriptome studies is crucial. To confront these issues, here, we have given details of genes and networks associated with significant differential expression in response to salt and drought stress. The key regulatory hub genes of drought and salt stress conditions have notable associations with functional drought and salt stress-responsive (DSSR) genes. In the network study, nodulation signaling pathways 2 (NSP2), Dehydration-responsive element1 D (DRE1D), ethylene response factor (ERF61), cycling DOF factor 1 (CDF1), and tubby like protein 3 (TLP3) genes in drought and tubby like protein 1 (TLP1), thaumatin-like proteins (TLP), ethylene-responsive transcription factor ERF109 (EF109), ETS-Related transcription Factor (ELF4), and Arabidopsis thaliana homeodomain leucine-zipper gene (ATHB7) genes in salt showed the significant putative functions and pathways related to providing tolerance against drought and salt stress conditions along with the significant expression values. These outcomes provide potential candidate genes for further in-depth functional studies in cotton, which could be useful for the selection of an improved genotype of Gossypium hirsutum against drought and salt stress conditions.

Plant hormone crosstalk mediated by humic acids

BackgroundThe reliance on chemical inputs to support high yields is the Achilles’ heel of modern crop production. The soil organic matter management is as old as agriculture itself. Recently, the use of soluble humic substances as plant growth promoters has been brought to attention due to their effects on nutrient uptake and water use efficiency. Humic substances applied directly at low concentrations can trigger different molecular, biochemical, and physiological processes in plants. However, how humic substances exert this plethoric regulatory action remains unclear. The objective of this study was to evaluate changes in the transcription level of genes coding cell receptors, phosphatases, synthesis, and function of different plant hormones and transcription factors.Materials and methodsAfter seven days of humic acid treatment, we used RNAseq in maize root seedlings. The level of gene transcription was compared with control plants.ResultsPlant kinase receptors and different phosphatases were regulated by humic acids. Likewise, genes related to plant hormones (auxin, gibberellin, ethylene, cytokinin, abscisic acid, brassinosteroids, jasmonic and salicylic acids) were transcript in differential levels in maize root seedlings as well as the expression of a hundred of transcription factors modifying the signal transduction pathway via alterations of the subsequent gene response.ConclusionWe showed a general mechanism for simultaneously regulating the activity of several hormones where humic acids act as a key regulatory hub in plant responses integrating hormonal signalling and response pathways.

Identification of microRNA and gene interactions through bioinformatic integrative analysis for revealing candidate signatures in prostate cancer

BackgroundProstate cancer (PCa) is a most common diagnosed cancer among males globally. Despite the decreased PCa mortality, increased prevalence of it creates huge burden on the population. MicroRNAs (miRNAs) are class of endogenous, non-coding, single stranded RNAs having ~22–24 bases. They work at the posttranscriptional gene regulation. MiRNAs have been seen in various in-vivo biological processes, including proliferation, apoptosis, migration, invasion, as well as epithelial-mesenchymal transition (EMT). MethodologyTwo miRNA expression datasets GSE76260, GSE60117 and one mRNA expression dataset GSE69223 from GEO (Gene Expression Omnibus) were included in this study for enrichment analysis. We identified total of 255 significant upregulated differentially expressed miRNAs (DEMs) and 339 significant downregulated DEMs from GSE78260 and GSE60117 datasets. 898 significant upregulated differentially expressed genes (DEGs) and 1486 significant downregulated DEGs from GSE69223 datasets in PCa vs normal prostate tissues. ResultsThe Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis for the key DEMs revealed that insulin signaling pathway, MAPK signaling pathway, EMT signaling pathway etc. are the most significant pathways, while KEGG pathway enrichment analysis for the DEGs demonstrated that steroid biosynthesis and focal adhesion are the most significant pathways involved in PCa carcinogenesis. The DEMs including hsa-miR-140-5p, hsa-miR-320b, hsa-miR-369-3p, hsa-miR-450b-5p, hsa-miR-483-3p, hsa-miR-532-3p and hsa-miR-576-5p identified as a key regulatory miRNA. Furthermore, DEGs including EGF, BMP2, FGF2, IGF1, CDH2 identified as the hub genes in the PPI network. Interestingly, key regulator miRNAs were significantly associated with ROC analysis. ConclusionIn this study, these identified key regulatory miRNAs and hub genes may be useful as a diagnostic and prognostic biomarker in PCa, may have contributing role in PCa pathogenesis. Moreover, the identified pathway may be potential therapeutical targets in PCa.

Comparative physiological and transcriptomic analyses reveal key regulatory networks and potential hub genes controlling peanut chilling tolerance.

The unclear molecular mechanism by which peanuts adapt to chilling stress limits progress in molecular breeding for peanut chilling tolerance. Here, the physiological and transcriptional differences between two genotypes with contrasting tolerance under chilling stress were compared. The inhibition of photosynthesis mainly caused by stomatal factors was a common response of peanut seedlings to chilling stress. Chilling-tolerant genotypes could inhibit the accumulation of ROS to adapt to chilling stress, and enhanced activities of CAT and APX were major causes of lower H2O2 content. The results of a conjoint analysis of physiological indices and the RNA-Seq database by WGCNA indicated that the genes in key modules were significantly enriched in pathways related to the oxidation-reduction process. Hub genes encoding RLK, CAT, MYC4, AOS, GST, PP2C, UPL5 and ZFP8 were likely to positively regulate peanut chilling tolerance, but hub genes encoding PAO, NAC2 and NAC72 were likely to negatively regulate peanut chilling tolerance.

Downregulation of miR156-Targeted PvSPL6 in Switchgrass Delays Flowering and Increases Biomass Yield.

MiR156/SQUAMOSA PROMOTER BINDING-LIKEs (SPLs) module is the key regulatory hub of juvenile-to-adult phase transition as a critical flowering regulator. In this study, a miR156-targeted PvSPL6 was identified and characterized in switchgrass (Panicum virgatum L.), a dual-purpose fodder and biofuel crop. Overexpression of PvSPL6 in switchgrass promoted flowering and reduced internode length, internode number, and plant height, whereas downregulation of PvSPL6 delayed flowering and increased internode length, internode number, and plant height. Protein subcellular localization analysis revealed that PvSPL6 localizes to both the plasma membrane and nucleus. We produced transgenic switchgrass plants that overexpressed a PvSPL6-GFP fusion gene, and callus were induced from inflorescences of selected PvSPL6-GFPOE transgenic lines. We found that the PvSPL6-GFP fusion protein accumulated mainly in the nucleus in callus and was present in both the plasma membrane and nucleus in regenerating callus. However, during subsequent development, the signal of the PvSPL6-GFP fusion protein was detected only in the nucleus in the roots and leaves of plantlets. In addition, PvSPL6 protein was rapidly transported from the nucleus to the plasma membrane after exogenous GA3 application, and returned from the plasma membrane to nucleus after treated with the GA3 inhibitor (paclobutrazol). Taken together, our results demonstrate that PvSPL6 is not only an important target that can be used to develop improved cultivars of forage and biofuel crops that show delayed flowering and high biomass yields, but also has the potential to regulate plant regeneration in response to GA3.

Long non-coding RNA ncRuPAR regulates gastric cancer cell proliferation and apoptosis via phosphoinositide 3-kinase/protein kinase B signaling.

Objective: To determine the effect and mechanism of the long non-coding RNA (lncRNA) ncRuPAR (non-protein coding RNA, upstream of coagulation factor II thrombin receptor [F2R]/protease-activated receptor-1 [PAR-1]) in human gastric cancer. Methods: HGC-27-ncRuPAR overexpression and MGC-803-ncRuPAR-RNAi knockdown gastric cancer cell lines were established. We assessed the effect of ncRuPAR on cell proliferation, apoptosis, migration, and invasion using Cell Counting Kit 8, flow cytometry, scratch and transwell assays, respectively. Differentially expressed genes in HGC-27-ncRuPAR overexpression and HGC-27-empty vector cell lines were identified using Affymetrix GeneChip microarray analysis. Ingenuity Pathway Analysis (IPA) of the microarray results was subsequently conducted to identify ncRuPAR-enriched pathways, followed by validation using real time-quantitative PCR (RT-qPCR). As one of the top enriched pathways, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was further examined by western blotting to determine its role in ncRuPAR-mediated regulation of gastric cancer pathogenesis. Results: ncRuPAR inhibited human gastric cancer cell proliferation and induced G1/S phase arrest and apoptosis, but did not affect migration or invasion in vitro. Overexpression of ncRuPAR in vitro was found to inhibit its known target PAR-1, as well as PI3K/Akt signaling. The downstream targets of PI3K/Akt, cyclin D1 was downregulated, but there was no change in expression level of B-cell lymphoma 2 (Bcl-2). Conclusions: We showed that lncRNA-ncRuPAR could inhibit tumor cell proliferation and promote apoptosis of human gastric cancer cells, potentially by inhibiting PAR-1, PI3K/Akt signaling, and cyclin D1. The results suggest a potential role for lncRNAs as key regulatory hubs in GC progression.

Socioecological approach for identifying the determinants of objectively measured physical activity: A prospective study of the UK Biobank

The socioecological approach emphasises that health promotion should focus on a variety of factors that surround individuals simultaneously, yet there is little evidence on how these factors relatively affect physical activity (PA). The main objective was to identify relevant determinants of PA by examining the associations between factors within multilayered socioecological categories and PA. A prospective analysis was conducted with 84,052 participants participating in the accelerometer measurement from the UK Biobank. Time spent in moderate-to-vigorous PA (MVPA) was calculated from participants who wore a wrist-worn accelerometer for seven days; a questionnaire-based self-reported leisure-time physical activity was also assessed. A categorical principal component analysis was conducted to reduce the dimensions of 184 variables. The associations between principal components (PCs) and PA were evaluated using general linear models. A network of PCs was constructed to assess the comprehensive association with PA. PCs related to body composition and chronic diseases were suggested as key determinants of objectively measured MVPA and found to be clustered in the network. PCs related to body composition and socio-economic status were proposed as the key regulatory hubs in the network because they exhibited the highest level of indirect linkages with other components. In the environmental category, PCs related to greenness and air pollution were revealed to be key factors in the self-reported walking for pleasure. Using a socioecological approach, it was discovered that obesity and disease-related factors were the most important determinants, and they had an integrative influence with other factors in different categories.