Omics Analysis of Odorant-Binding Proteins and Cuticle-Enriched SfruOBP18 Confers Multi-Insecticide Tolerance in Spodoptera frugiperda.

Spodoptera frugiperda is a notorious pest that develops a high resistance to many insecticides. Recently, insect odorant-binding proteins (OBPs) have been proven to participate in insecticide resistance. However, the functional evidence supporting the cross-link between OBPs and insecticide resistance remains unexplored. Here, we identified 50 SfruOBPs from the larval transcriptome and genome. Notably, SfruOBP18 was highly expressed in the larval cuticle and could be induced to upregulate its expression by multi-insecticides. Ligand-binding assays revealed that SfruOBP18 bound strongly with four insecticides; RNAi and insecticide bioassay demonstrated that the knockdown of SfruOBP18 did not affect larval survival and development. However, it can significantly increase the larval susceptibility to multi-insecticides, suggesting an uncommon role of SfruOBP18 in multi-insecticide susceptibility. Our study provides a comprehensive understanding of SfruOBPs and furthermore proves that a larval cuticle-enriched OBP can bind with and confer larval tolerance to multi-insecticides. SfruOBP18 could be a new insecticidal target for controlling Lepidoptera pests.

Genome-Wide Identification and Characterization of the GASA Gene Family in Medicago truncatula, and Expression Patterns under Abiotic Stress and Hormone Treatments.

Medicago truncatula is a key model plant for studying legume plants, particularly alfalfa (Medicago sativa), due to its well-defined genetic background. Plant-specific GASA (Gibberellic Acid Stimulated Arabidopsis) genes play various roles in plant growth and development, abiotic stress, and hormone responses. However, limited information is available on GASA research in Medicago. In this study, 26 MtGASAs were identified and analyzed for its structure, evolution, and expressions. Sequence alignments and phylogeny revealed that 26 MtGASAs containing conserved GASA domains were classified into three clades. The chromosomal locations and gene synteny revealed segmental and tandem repetition evolution. Analysis of cis-regulatory elements indicates that family members likely influence various hormone signaling pathways and stress-related mechanisms. Moreover, the RNA-seq and qRT-PCR analyses revealed that 26 MtGASAs were extensively involved in abiotic stresses and hormone responses. Notably, seven MtGASA genes (MtGASA1, 10, 12, 17, 23, 25 and 26) were all dramatically activated by NaCl and Mannitol treatments, and four MtGASAs (MtGASA7, 10, 23 and 24) were significant activated by GA3, PBZ, ABA, and MeJA treatments. Collectively, this study is the first to identify and describe GASA genes in Medicago on a genome-wide scale. The results establish a basis for functional characterization, showing that these proteins are essential in responding to various abiotic stresses and hormonal signals.

Unique Gene Expression Profiles within South Africa Are Associated with Varied Chemotherapeutic Responses in Conventional Osteosarcoma.

BACKGROUND: We determined the predictive gene expression profiles associated with chemo-response in conventional osteosarcomas (COS) within South Africa. MATERIALS AND METHODS: In 28 patients, we performed an RNA extraction, cDNA synthesis, and quantitative analysis using the RT-PCR 2-∆∆CT method to determine the fold change in gene expression alongside GAPDH (housekeeping gene). RESULTS: We observed a significant downregulation in the mRNA expression profiles of ABCB1-p-glycoprotein (p = 0.0007), ABCC3 (p = 0.002), ERCC1 (p = 0.007), p-53 (p = 0.007), and RFC1 (p = 0.003) in the COS patients compared to the healthy donors. Furthermore, ABCB1-p-glycoprotein (p = 0.008) and ABCC3 (p = 0.020) exhibited a significant downregulation in the COS tumour tissues when compared to the healthy donors. In our univariate logistic regression, the predictors of chemotherapeutic response comprised ERCC1 [restricted cubic spline (RCS) knot: OR -0.27; CI -0.504 to -0.032; p = 0.036]; osteoblastic subtype [OR -0.36; CI -0.652 to -0.092; p = 0.026); fibroblastic subtype [OR 0.91; CI 0.569 to 1.248; p < 0.001]; and mixed subtype [OR 0.53; CI 0.232 to 0.032; p = 0.032]. In our multivariable logistic regression, the significant predictors of chemotherapeutic response comprised age [RCS knot: OR -2.5; CI -3.616 to -1.378; p = 0.022]; ABCC3 [RCS knot: OR 0.67; CI 0.407 to 0.936, p = 0.016]; ERCC1 [RCS knot: OR 0.57; CI 0.235 to 0.901; p = 0.044]; RFC1 [RCS knot: OR -1.04; CI -1.592 to -0.487; p = 0.035]; chondroblastic subtype [OR -0.83; CI -1.106 to -0.520; p = 0.012]; and osteoblastic subtype [OR -1.28; CI -1.664 to -0.901; p = 0.007]. CONCLUSIONS: In this South African cohort, we observed the unique gene expression profiles of osteosarcoma tumourigenesis and chemotherapeutic responses. These may serve as prognostication and therapeutic targets. Larger-scale research is needed on the African continent.

Genome-Wide Analysis and Characterization of the SDR Gene Superfamily in Cinnamomum camphora and Identification of Synthase for Eugenol Biosynthesis.

Short-chain dehydrogenase/reductases (SDRs) are the largest NAD(H)-dependent oxidoreductase superfamilies and are involved in diverse metabolisms. This study presents a comprehensive genomic analysis of the SDR superfamily in Cinnamomum camphora, a species that is one of the most significant woody essential oil plants in southern China. We identify a total of 222 CcSDR proteins and classify them into five types based on their cofactor-binding and active sites: 'atypical', 'classic', 'divergent', 'extended', and 'unknown'. Phylogenetic analysis reveals three evolutionary branches within the CcSDR proteins, and further categorization using the SDR-initiative Hidden Markov model resulted in 46 families, with the CcSDR110C, CcSDR108E, and CcSDR460A families being the most populous. Collinearity analysis identified 34 pairs of CcSDR paralogs in C. camphora, 141 pairs of SDR orthologs between C. camphora and Populus trichocarpa, and 59 pairs between C. camphora and Oryza sativa. Expression profile analysis indicates a preference for the expression of 77 CcSDR genes in specific organs such as flowers, bark, twigs, roots, leaves, or fruits. Moreover, 77 genes exhibit differential expression patterns during the four developmental stages of leaves, while 130 genes show variance across the five developmental stages of fruits. Additionally, to explore the biosynthetic mechanism of methyl eugenol, a key component of the leaf essential oil in the methyl eugenol chemotype, this study also identifies eugenol synthase (EGS) within the CcSDR460A family through an integrated strategy. Real-time quantitative PCR analysis demonstrates that the expression of CcEGS in the leaves of the methyl eugenol chemotype is more than fourfold higher compared to other chemotypes. When heterologously expressed in Escherichia coli, it catalyzes the conversion of coniferyl acetate into a mixture predominantly composed of eugenol (71.44%) and isoeugenol (21.35%). These insights pave the way for future research into the functional diversity of CcSDR genes, with a focus on secondary metabolism.

Chromate Affects Gene Expression and DNA Methylation in Long-Term In Vitro Experiments in A549 Cells.

Chromate has been shown to dysregulate epigenetic mechanisms such as DNA methylation, leading to changes in gene expression and genomic instability. However, most in vitro studies are limited to short incubation periods, although chronic exposure may be more relevant for both environmental and occupational exposure. In this study, human adenocarcinoma A549 cells were treated with 1, 2 or 5 µM chromate for 24 h and compared with incubations with 0.2, 0.5 or 1 µM chromate for 1 to 5 weeks. Chromium accumulated in a pronounced time- and concentration-dependent manner after short-term treatment, whereas a plateau of intracellular chromium content was observed after long-term treatment. While short-term treatment induced a G2 arrest of the cell cycle, this effect was not observed after long-term treatment at lower concentrations. The opposite was observed for global DNA methylation: while short-term treatment showed no effect of chromate, significant dose-dependent hypomethylation was observed in the long-term experiments. Time-dependent effects were also observed in a high-throughput RT-qPCR gene expression analysis, particularly in genes related to the inflammatory response and DNA damage response. Taken together, the results suggest specific differences in toxicity profiles when comparing short-term and long-term exposure to chromate in A549 cells.

Extensive immunophenotypic sub-population analysis of StemRegenin1 expanded haematopoietic stem/progenitor cells.

BACKGROUND: Ex vivo haematopoietic stem/progenitor cell (HSPCs) expansion constitutes an important area of research, and has the potential to improve access to umbilical cord blood (UCB) as a source of stem cells for haematopoietic stem cell transplantation (HSCT). The ability to improve stem cell dose and thereby reduce delayed engraftment times, which has plagued the use of UCB as a stem cell source since inception, is a recognised advantage. The extent to which cluster of differentiation (CD)34 sub-populations are affected by expansion with StemRegenin1 (SR1), and whether a particular subtype may account for better engraftment than others, is currently unknown. The purpose of this study was to determine the impact of SR1-induced HSPC expansion on CD34+ immunophenotypic subsets and gene expression profiles. METHODS: UCB-derived CD34+ HSPCs were characterised before (D0) and after expansion (D7) with SR1 using an extensive immunophenotypic panel. In addition, gene expression was assessed and differentially expressed genes were categorised into biological processes. RESULTS: A dose-dependent increase in the number of CD34+ HSPCs was observed with SR1 treatment, and unbiased and extensive HSPC immunophenotyping proved to be a powerful tool in identifying unique sub-populations within the HSPC repertoire. In this regard, we found that SR1 promotes the emergence of HSPC subsets which may aid engraftment post expansion. In addition, we observed that SR1 has a minimal effect on the transcriptome of 7-day expanded CD34+ HSPCs when compared to cells expanded without SR1, with only two genes being downregulated in the former. CONCLUSION: This study revealed that SR1 selects for potentially novel immunophenotypic HSPC subsets post expansion and has a minimal effect on the transcriptome of 7-day expanded HSPCs when compared to vehicle controls. Whether these distinct immunophenotypic sub-populations possess greater engraftment capacity remains to be tested in animal models.

[Influence of Tis108 on GA content and expression of key enzyme GeCYP714A1 involved in GA deactivation of Gastrodia elata].

To investigate the influence of the strigolactone inhibitor Tis108 on the growth of Gastrodia elata, this study treated G. elata tuber with Tis108 solution of 10 µmol·L~(-1) and measured the content of endogenous hormone gibberellin(GA) in the tuber. By using reverse transcription-polymerase chain reaction(RT-PCR) technology, the key enzyme GeCYP714A1 gene involved in GA deactivation was cloned. Bioinformatics analysis on the GeCYP714A1 gene was carried out by using ExPASy, SWISS-MODEL, MEGA, etc., and its expression levels in different parts of G. elata were determined. The results showed that after Tis108 treatment, GA content in G. elata tuber was significantly increased, and the transcription level of the GeCYP714A1 gene was significantly decreased. The full length of the coding region of the GeCYP714A1 gene is 1 173 bp, encoding 390 amino acids. The protein has a molecular weight of 44.85 kDa, a theoretical isoelectric point of 9.83, an instability index of 49.20, an aliphatic index of 89.03, and a grand average of hydropathicity of-0.235, classifying it as an unstable, basic, hydrophilic protein, and the GeCYP714A1 protein was localized in the mitochondria, lacking a signal peptide and a transmembrane structure. Phylogenetic tree analysis revealed that GeCYP714A1 was most closely related to the DcCYP714C2(PKU78454.1) protein from Dendrobium candidum, with a sequence identity of 67.25%. The qRT-PCR analysis of the expression patterns of the GeCYP714A1 gene indicated that GeCYP714A1 had the highest transcription level in G. elata tuber, followed by stem and inflorescence. The study represented that Tis108 inhibited the transcription level of GeCYP714A1 involved in GA deactivation in G. elata tuber, thereby increasing the accumulation of GA and affecting the growth of G. elata tuber. These results provided a basis for further studies of strigolactone regulation of GA signal and tuber development in G. elata.

Exposure of Arabidopsis thaliana Mutants to Genotoxic Stress Provides New Insights for the Involvement of TDP1α and TDP1ß genes in DNA-Damage Response.

Genotoxic stress activates the DNA-damage response (DDR) signalling cascades responsible for maintaining genome integrity. Downstream DNA repair pathways include the tyrosyl-DNA phosphodiesterase 1 (TDP1) enzyme that hydrolyses the phosphodiester bond between the tyrosine of topoisomerase I (TopI) and 3'-phosphate of DNA. The plant TDP1 subfamily contains the canonical TDP1α gene and the TDP1ß gene whose functions are not fully elucidated. The current study proposes to investigate the involvement of TDP1 genes in DDR-related processes by using Arabidopsis thaliana mutants treated with genotoxic agents. The phenotypic and molecular characterization of tdp1α, tdp1ß and tdp1α/ß mutants treated with cisplatin (CIS), curcumin (CUR), NSC120686 (NSC), zeocin (ZEO), and camptothecin (CPT), evidenced that while tdp1ß was highly sensitive to CIS and CPT, tdp1α was more sensitive to NSC. Gene expression analyses showing upregulation of the TDP2 gene in the double mutant indicate the presence of compensatory mechanisms. The downregulation of POL2A gene in the tdp1ß mutant along with the upregulation of the TDP1ß gene in pol2a mutants, together with its sensitivity to replication inhibitors (CIS, CTP), point towards a function of this gene in the response to replication stress. Therefore, this study brings novel information relative to the activity of TDP1 genes in plants.

Comparative transcriptome analysis of whiteflies raised on cotton leaf curl Multan virus-infected cotton plants.

Cotton leaf curl Multan virus (CLCuMuV), a serious viral disease causative agent in cotton plants in South Asia, is transmitted by the Bemisia tabaci cryptic species complex in a persistent circulative manner. A previous study indicated that Asia II-7 whiteflies could transmit CLCuMuV, while Mediterranean (MED) whiteflies failed to transmit CLCuMuV. However, little is known about the genes involved in this process. In this study, Asia II-7 and MED B. tabaci were utilized to determine transcriptomic responses after 48 h of acquisition access periods (AAPs). Result of Illumina sequencing revealed that, 14,213 and 8,986 differentially expressed genes (DEGs) were identified. Furthermore, DEGs related to the immune system and metabolism of Asia II-7 and MED in response to CLCuMuV-infected plants were identified and analyzed using Gene Ontologies (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the number of related DEGs in MED was lower than that of Asia II-7. The most abundant groups of DEGs between both viruliferous and aviruliferous whitefly species were the zf-C2H2 family of transcription factors (TFs). Notably, in comparison to viruliferous MED, Asia II-7 exhibited more DEGs related to cathepsin biosynthesis. Overall, this study provides the basic information for investigating the molecular mechanism of how begomoviruses affect B. tabaci metabolism and immune response either as vector cryptic species or non-vector species.

Genome-wide investigation of the TIFY transcription factors in alfalfa (Medicago sativa L.): identification, analysis, and expression.

BACKGROUND: Alfalfa (Medicago sativa L.) is an essential leguminous forage with high nutrition and strong adaptability. The TIFY family is a plant-specific transcription factor identified in many plants. However, few reports have been reported on the phylogenetic analysis and gene expression profiling of TIFY family genes in alfalfa. RESULT: A total of 84 TIFY genes belonging to 4 categories were identified in alfalfa, including 58 MsJAZs, 18 MsZMLs, 4 MsTIFYs and 4 MsPPDs, respectively. qRT-PCR data from 8 genes in different tissues revealed that most MsTIFY genes were highly expressed in roots. The expression of MsTIFY14 was up-regulated after different times in both thrips-resistant and susceptible alfalfa after thrips feeding, and the expression of the remaining MsTIFYs had a strong correlation with the time of thrips feeding. Different abiotic stresses, including drought, salt, and cold, could induce or inhibit the expression of MsTIFY genes to varying degrees. In addition, the eight genes were all significantly up-regulated by JA and/or SA. Interestingly, MsTIFY77 was induced considerably by all the biotic, abiotic, or plant hormones (JA or SA) except ABA. CONCLUSION: Our study identified members of the TIFY gene family in alfalfa and analyzed their structures and possible functions. It laid the foundation for further research on the molecular functions of TIFYs in alfalfa.

Evaluation of cerebrospinal fluid (CSF) and interstitial fluid (ISF) mouse proteomes for the validation and description of Alzheimer's disease biomarkers.

BACKGROUND: Mass spectrometry (MS)-based cerebrospinal fluid (CSF) proteomics is an important method for discovering biomarkers of neurodegenerative diseases. CSF serves as a reservoir for interstitial fluid (ISF), and extensive communication between the two fluid compartments helps to remove waste products from the brain. NEW METHOD: We performed proteomic analyses of both CSF and ISF fluid compartments using intracerebral microdialysis to validate and detect novel biomarkers of Alzheimer's disease (AD) in APPtg and C57Bl/6J control mice. RESULTS: We identified up to 625 proteins in ISF and 4483 proteins in CSF samples. By comparing the biofluid profiles of APPtg and C57Bl/6J mice, we detected 37 and 108 significantly up- and downregulated candidates, respectively. In ISF, 7 highly regulated proteins, such as Gfap, Aldh1l1, Gstm1, and Txn, have already been implicated in AD progression, whereas in CSF, 9 out of 14 highly regulated proteins, such as Apba2, Syt12, Pgs1 and Vsnl1, have also been validated to be involved in AD pathogenesis. In addition, we also detected new interesting regulated proteins related to the control of synapses and neurotransmission (Kcna2, Cacng3, and Clcn6) whose roles as AD biomarkers should be further investigated. COMPARISON WITH EXISTING METHODS: This newly established combined protocol provides better insight into the mutual communication between ISF and CSF as an analysis of tissue or CSF compartments alone. CONCLUSIONS: The use of multiple fluid compartments, ISF and CSF, for the detection of their biological communication enables better detection of new promising AD biomarkers.

Genome-Wide Identification and Characterization of Maize Long-Chain Acyl-CoA Synthetases and Their Expression Profiles in Different Tissues and in Response to Multiple Abiotic Stresses.

Long-chain acyl-CoA synthetases (LACSs) are essential enzymes that activate free fatty acids to fatty acyl-CoA thioesters, playing key roles in fatty acid (FA) catabolism, lipid synthesis and storage, epidermal wax synthesis, and stress tolerance. Despite their importance, comprehensive information about LACS genes in maize, a primary food crop, remains scarce. In the present work, eleven maize LACS genes were identified and mapped across five chromosomes. Three pairs of segmentally duplicated genes were detected in the maize LACS gene family, which underwent significant purifying selection (Ka/Ks < 1). Subsequently, phylogenetic analysis indicated that ZmLACS genes were divided into four subclasses, as supported by highly conserved motifs and gene structures. On the basis of the PlantCARE database, analysis of the ZmLACS promoter regions revealed various cis-regulatory elements related to tissue-specific expression, hormonal regulation, and abiotic stress response. RT-qPCR analysis showed that ZmLACS genes exhibit tissue-specific expression patterns and respond to diverse abiotic stresses including drought and salt, as well as phytohormone abscisic acid. Furthermore, using the STRING database, several proteins involved in fatty acid and complex lipid synthesis were identified to be the potential interaction partners of ZmLACS proteins, which was also confirmed by the yeast two-hybrid (Y2H) assay, enhancing our understanding of wax biosynthesis and regulatory mechanisms in response to abiotic stresses in maize. These findings provide a comprehensive understanding of ZmLACS genes and offer a theoretical foundation for future research on the biological functions of LACS genes in maize environmental adaptability.

Genome-wide characterization of DELLA gene family in blueberry (Vaccinium darrowii) and their expression profiles in development and response to abiotic stress.

BACKGROUND: The DELLA proteins, a class of GA signaling repressors, belong to the GRAS family of plant-specific nuclear proteins. Members of DELLA gene family encode transcriptional regulators with diverse functions in plant development and abiotic stress responses. To date, DELLAs have been identified in various plant species, such as Arabidopsis thaliana, Malus domestica, Populus trichocarpa, and other land plants. Most information of DELLA family genes was obtained from A. thaliana, whereas little is known about the DELLA gene family in blueberry. RESULTS: In this study, we identified three DELLA genes in blueberry (Vaccinium darrowii, VdDELLA) and provided a complete overview of VdDELLA gene family, describing chromosome localization, protein properties, conserved domain, motif organization, and phylogenetic analysis. Three VdDELLA members, containing two highly conserved DELLA domain and GRAS domain, were distributed across three chromosomes. Additionally, cis-acting elements analysis indicated that VdDELLA genes might play a critical role in blueberry developmental processes, hormone, and stress responses. Expression analysis using quantitative real-time PCR (qRT-PCR) revealed that all of three VdDELLA genes were differentially expressed across various tissues. VdDELLA2 was the most highly expressed VdDELLA in all denoted tissues, with a highest expression in mature fruits. In addition, all of the three VdDELLA genes actively responded to diverse abiotic stresses. Based on qRT-PCR analysis, VdDELLA2 might act as a key regulator in V. darrowii in response to salt stress, whereas VdDELLA1 and VdDELLA2 might play an essential role in cold stress response. Under drought stress, all of three VdDELLA genes were involved in mediating drought response. Furthermore, their transiently co-localization with nuclear markers in A. thaliana protoplasts demonstrated their transcriptional regulator roles. CONCLUSIONS: In this study, three VdDELLA genes were identified in V. darrowii genome. Three VdDELLA genes were closely related to the C. moschata DELLA genes, S. lycopersicum DELLA genes, and M. domestica DELLA genes, respectively, indicating their similar biological functions. Expression analysis indicated that VdDELLA genes were highly efficient in blueberry fruit development. Expression patterns under different stress conditions revealed the differentially expressed VdDELLA genes responding to salt, drought, and cold stress. Overall, these results enrich our understanding of evolutionary relationship and potential functions of VdDELLA genes, which provide valuable information for further studies on genetic improvement of the plant yield and plant resistance.

Genome-wide identification, characterization and expression analysis of the bZIP transcription factors in garlic (Allium sativum L.).

Introduction: The bZIP genes (bZIPs) are essential in numerous biological processes, including development and stress responses. Despite extensive research on bZIPs in many plants, a comprehensive genome-wide analysis of bZIPs in garlic has yet to be undertaken. Methods: In this study, we identified and classified 64 AsbZIP genes (AsbZIPs) into 10 subfamilies. A systematic analysis of the evolutionary characteristics of these AsbZIPs, including chromosome location, gene structure, conserved motifs, and gene duplication, was conducted. Furthermore, we also examined the nucleotide diversity, cis-acting elements, and expression profiles of AsbZIPs in various tissues and under different abiotic stresses and hormone treatments. Results and Discussion: Our findings revealed that gene replication plays a crucial role in the expansion of AsbZIPs, with a minor genetic bottleneck observed during domestication. Moreover, the identification of cis-acting elements suggested potential associations of AsbZIPs with garlic development, hormone, and stress responses. Several AsbZIPs exhibited tissue-preferential and stress/hormone-responsive expression patterns. Additionally, Asa7G01972 and Asa7G01379 were notably differentially expressed under various stresses and hormone treatments. Subsequent yeast two-hybridization and yeast induction experiments validated their interactions with Asa1G01577, a homologue of ABI5, reinforcing their importance in hormone and abiotic stress responses. This study unveiled the characteristics of the AsbZIP superfamily and lays a solid foundation for further functional analysis of AsbZIP in garlic.

Identifying Key Genes and Their Associated Molecular Pathways in Lupus Nephritis-Osteoporosis: An In-Silico Analysis.

Nephritis and osteoporosis are debilitating medical conditions that significantly impact human health and reduce quality of life. To develop potential therapeutic strategies for these disorders necessitates understanding the genetic and molecular mechanisms. Here, we employed bioinformatics techniques purposed to find key genes and associated pathways responsible for nephritis-osteoporosis comorbidity. Six microarray datasets of systemic lupus erythematosus (SLE) and osteoporosis were retrieved from the Gene Expression Omnibus (GEO) database. Post normalization of data sets LIMMA package was utilized for differential expression analysis, among the datasets 44 differentially expressed genes (DEGs) were identified. The identified 44 genes were further analyzed for gene ontology (GO) where it was found that these genes are involved in defense response, organism interactions, and response to external stimuli. In predicting the molecular function, they were involved in several biological processes including binding to lipopolysaccharides and having peptidase and hydrolase activities. Firstly, the identified genes were primarily associated with certain granules such as specific granules and secretory granules in the aspect of cellular components. Enrichment analysis pointed out the potential pathways linked to the immune system, neutrophil degranulation, innate immunity, and immune response to tuberculosis. To examine interactions among DEGs, a complex protein-protein interaction (PPI) network was built, resulting in the identification of seven hub genes, CXCL8, ELANE, LCN2, MMP8, IFIT1, MX1, and ISG15. The study suggests that these elucidated hub genes might have high potential to be exploited as promising biomarkers and therapeutic targets in nephritis-osteoporosis. Taken together, this study provided deeper insights into the genetic and molecular basis for the comorbidity of nephritis and osteoporosis.

Deciphering the molecular landscape of rheumatoid arthritis offers new insights into the stratified treatment for the condition.

Background: For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments. Methods: We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs. Results: Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. Conclusions: The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.

Evaluation of secretome biomarkers in glioblastoma cancer stem cells: A bioinformatics analysis.

BACKGROUND: Glioblastoma (GBM) is a malignant brain tumor that frequently occurs alongside other central nervous system (CNS) conditions. The secretome of GBM cells contains a diverse array of proteins released into the extracellular space, influencing the tumor microenvironment. These proteins can serve as potential biomarkers for GBM due to their involvement in key biological processes, exploring the secretome biomarkers in GBM research represents a cutting-edge strategy with significant potential for advancing diagnostic precision, treatment monitoring, and ultimately improving outcomes for patients with this challenging brain cancer. AIM: This study was aimed to investigate the roles of secretome biomarkers and their pathwayes in GBM through bioinformatics analysis. METHODS AND RESULTS: Using data from the Gene Expression Omnibus and the Cancer Genome Atlas datasets-where both healthy and cancerous samples were analyzed-we used a quantitative analytical framework to identify differentially expressed genes (DEGs) and cell signaling pathways that might be related to GBM. Then, we performed gene ontology studies and hub protein identifications to estimate the roles of these DEGs after finding disease-gene connection networks and signaling pathways. Using the GEPIA Proportional Hazard Model and the Kaplan-Meier estimator, we widened our analysis to identify the important genes that may play a role in both progression and the survival of patients with GBM. In total, 890 DEGs, including 475 and 415 upregulated and downregulated were identified, respectively. Our results revealed that SQLE, DHCR7, delta-1 phospholipase C (PLCD1), and MINPP1 genes are highly expressed, and the Enolase 2 (ENO2) and hexokinase-1 (HK1) genes are low expressions. CONCLUSION: Hence, our findings suggest novel mechanisms that affect the occurrence of GBM development, growth, and/or establishment and may also serve as secretory biomarkers for GBM prognosis and possible targets for therapy. So, continued research in this field may uncover new avenues for therapeutic interventions and contribute to the ongoing efforts to combat GBM effectively.

Association between miRNAs in serum at 10-14 gestational weeks and spontaneous preterm delivery.

INTRODUCTION: Preterm delivery (PTD) is the leading cause of death in children under 5 years of age. Cervical shortening detected by ultrasound can be used to predict PTD, but prediction is not perfect, and complementary diagnostic markers are needed. Recently, specific plasma microribonucleic acid (miRNAs) detected in early second trimester were shown to be associated with spontaneous PTD in high-risk women with a singleton pregnancy. The aim of this study was to explore to what extent these miRNAs are associated with spontaneous PTD and cervical length in a general population. MATERIAL AND METHODS: This study is a nested case-control study within the CERVIX study. The CERVIX study evaluated the ability of cervical length screening with transvaginal ultrasound to identify women at risk of PTD. In the present study, women who delivered spontaneously <34 weeks (n = 61) were compared with a control group of women who delivered at full term (39 + 0 to 40 + 6 gestational weeks, n = 205). Archived serum samples were analyzed with RT-qPCR for miRNA expression levels of let-7a-5p, miR-150-5p, miR-15b-5p, miR-185-5p, miR-191-5p, miR-19b-3p, miR-23a-3p, miR-374a-5p, and miR-93-5p. The mean relative expression was compared between the groups. Sub-analyses were performed for women delivering <32, <30, and <28 weeks vs the full-term group. RESULTS: The analyzed miRNAs were not significantly differentially expressed in women delivering <34 weeks compared to those delivering at full term. MiR-191-5p and miR-93-5p were significantly overexpressed in women who delivered <32 weeks, and further increase in fold change was observed with decreasing gestational age at delivery. The level of miR-15b-5p was significantly higher in women delivering at <30 weeks compared to those delivering at full term. CONCLUSIONS: Our study shows that overexpression of miR-93-5p, miR-15b-5p, and miR-191-5p in serum at early gestation is associated with spontaneous PTD in a general population. Further research is needed to evaluate the potential of these miRNAs as future biomarkers for spontaneous PTD, as well as their pathophysiological role in spontaneous PTD.

Redirecting Tumor Evolution with Nanocompiler Precision for Enhanced Therapeutic Outcomes.

Precisely programming the highly plastic tumor expression profile to render it devoid of drug resistance and metastatic potential presents immense challenges. Here, a transformative nanocompiler designed to reprogram and stabilize the mutable state of tumor cells is introduced. This nanocompiler features a trio of components: 2-deoxy-d-glucose-modified lipid nanoparticles to inhibit glucose uptake, iron oxide nanoparticles to induce oxidative stress, and a deubiquitinase inhibitor to block adaptive protein profile changes in tumor cells. By specifically targeting the hypermetabolic nature of tumors, this approach disrupted their energy production, ultimately fostering a state of vulnerability and impeding their ability to adapt and resist. The results of this study indicate a substantial reduction in tumor growth and metastasis, thus demonstrating the potential of this strategy to manipulate tumor protein expression and fate. This proactive nanocompiler approach promises to steer cancer therapy toward more effective and lasting outcomes.

Insight from expression profiles of FT orthologs in plants: conserved photoperiodic transcriptional regulatory mechanisms.

Floral transition from the vegetative to the reproductive stages is precisely regulated by both environmental and endogenous signals. Among these signals, photoperiod is one of the most important environmental factors for onset of flowering. A florigen, FLOWERING LOCUS T (FT) in Arabidopsis, has thought to be a major hub in the photoperiod-dependent flowering time regulation. Expression levels of FT likely correlates with potence of flowering. Under long days (LD), FT is mainly synthesized in leaves, and FT protein moves to shoot apical meristem (SAM) where it functions and in turns induces flowering. Recently, it has been reported that Arabidopsis grown under natural LD condition flowers earlier than that grown under laboratory LD condition, in which a red (R)/far-red (FR) ratio of light sources determines FT expression levels. Additionally, FT expression profile changes in response to combinatorial effects of FR light and photoperiod. FT orthologs exist in most of plants and functions are thought to be conserved. Although molecular mechanisms underlying photoperiodic transcriptional regulation of FT orthologs have been studied in several plants, such as rice, however, dynamics in expression profiles of FT orthologs have been less spotlighted. This review aims to revisit previously reported but overlooked expression information of FT orthologs from various plant species and classify these genes depending on the expression profiles. Plants, in general, could be classified into three groups depending on their photoperiodic flowering responses. Thus, we discuss relationship between photoperiodic responsiveness and expression of FT orthologs. Additionally, we also highlight the expression profiles of FT orthologs depending on their activities in flowering. Comparative analyses of diverse plant species will help to gain insight into molecular mechanisms for flowering in nature, and this can be utilized in the future for crop engineering to improve yield by controlling flowering time.