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Purpose: To evaluate the response of human peri-implant soft tissue (PIST) to different healing abutment materials 24 hours after positioning by assessing the expression of genes related to the early connective tissue wound healing response. Materials and Methods: The following four materials were used to create experimental abutments that were mounted on implants placed in five patients (four different abutments in each patient): group A--grade 4 titanium (Ti), group B--grade 5 Ti, group C--zirconia (Zr), and group D--polyetheretherketone (PEEK). Before implant placement, a gingival biopsy (control, CT) sample was obtained using a 2-mm-diameter punch (T0). After 24 hours, PIST biopsy samples were collected using a specifically designed custom-made cutting device. Real-time polymerase chain reaction (PCR) was performed to analyze the expression of the following genes: COL-I, COL-III, MMP-1, TIMP-1, TGF-^1, FN, ITGA4, ITGA5, ITGB1, RAC-1, COL-IV, aSMA, IL-6, and CXCL-1. Results: Gene expression analysis showed some differences between CT and the experimental groups; however, no significant differences were detected when comparing the experimental groups. COL-I was significantly downregulated in groups A and C compared to CT. Expression of MMP-1 and TIMP-1 increased in all the experimental groups but to a lesser extent in group A. FN, RAC-1, COL-IV, and aSMA were downregulated, especially in group A, in which CXCL-1 and IL-6 showed the lowest expression. Conclusions:The results of grade 4 Ti and Zr abutments seem to be promising, because a lower expression of genes related to inflammation, myofibroblast activation, and extracellular matrix remodeling was observed when compared with grade 5 Ti and PEEK, without triggering a profibrotic response in the early phases of PIST repair. [ABSTRACT FROM AUTHOR]

Among the biotic stresses, wilt disease severely affects tomato quality and productivity globally. The causal organism of this disease is Fusarium oxysporum f. sp. lycopersici (Fol), which is very well known and has a significant impact on the productivity of other crops as well. Efforts have been made to investigate the effect of plant growth-promoting bacteria (PGPB) on alleviating tomato wilt disease. Four PGPB strains, such as Pseudomonas aeruginosa BHUPSB01 (T1), Pseudomonas putida BHUPSB04 (T2), Paenibacillus polymyxa BHUPSB16 (T3), and Bacillus cereus IESDJP-V4 (T4), were used as inocula to treat Fol- challenged plants. The results revealed that PGPB treatments T1, T2, T3, and T4 were able to decrease the severity of Fusarium wilt in the tomato plants at different levels. Among the treatments, T3 displayed the strongest protective effect, with the lowest disease frequency, which was 15.25%. There were no significant differences observed in parameters such as fruit yield and relative water content in the PGPB-inoculated plants, although T3 and T4 showed minimal electrolyte leakage. Significant changes in chlorophyll fluorescence were also recorded. A lower level of H2O2 and malondialdehyde (MDA) was observed in the T3 and T4 treatments. In addition, proline accumulation was highest in the T3-treated plants. Antioxidative enzyme activities, such as catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), significantly increased in the PGPB-treated plants. Furthermore, the highest phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO) activity was reported in the T3 and T4 plants, respectively. The PGPB-treated plants showed elevated expression of the PAL, PPO, PR3, PR2, SOD, CAT , and PO genes. This study's results reveal that PGPB strains can be utilized as biocontrol agents (BCAs) to enhance tomato resistance against Fusarium wilt. [ABSTRACT FROM AUTHOR]

Purpose: Congenital mesoblastic nephromas (CMN) are histologically classified into classical, cellular, and mixed subtypes. Most cellular CMNs harbor ETV6-NTRK3 gene fusions, and classic and mixed CMNs harbor EGFR internal tandem duplications (EGFR-ITDs). Classic CMNs are considered benign, whereas recurrent or metastatic diseases occur in the cellular subtypes. Direct identification of mutations is desirable for an accurate diagnosis. However, molecular genetic analyses cannot be performed in a number of histopathology laboratories. This study aimed to investigate a surrogate marker for the accurate histological classification of CMN. Methods: Overall, 11 CMN cases diagnosed at our institute were included in this study. Reverse transcription-polymerase chain reaction was performed for the NTRK gene fusion and EGFR-ITDs in all cases. Comprehensive mRNA analysis was performed using the nCounter® Gene Expression Assay. Principal component analysis (PCA) was performed based on the gene expression levels. Immunohistochemical evaluation was conducted for the expression of p-Mek1/2, p-Erk1/2, and EGFR. Results: PCA revealed differences in mutation patterns between the EGFR-ITDs and NTRK fusion tumor groups. Gene ontology analysis of the highly expressed genes in the EGFR-ITDs tumor group revealed enrichment related to the mitogen-activated protein kinase (MAPK) signaling pathway. p-Mek1/2 and p-Erk1/2 immunoreactivity was significantly increased in the EGFR-ITDs tumor group (p = 0.018 and p = 0.017, respectively). EGFR immunoreactivity is not a useful marker for CMN with EGFR-ITD. Conclusion: p-Mek1/2 and p-Erk1/2 immunoreactivity may be useful markers for EGFR-ITDs. Thus, MEK1/2 inhibitors possess the potential to be used as a targeted therapy for CMN with EGFR-ITDs. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the chemoprotective potential of karanjin against 7,12-dimethylbenz(α)anthracene (DMBA)-induced breast cancer. Methodology: Thirty-six female rats were utilized for the study. Breast cancer was induced through a subcutaneous injection of 35 mg/kg DMBA. The animals were allocated to six groups. Three groups were allocated for karanjin (50 mg/kg, 100 mg/kg, and 200 mg/kg), and received daily treatment for 20 weeks (including 2 weeks as pre-treatment). Doxorubicin (4 mg/kg) was administered to the standard control group twice a week for 20 weeks. The disease control (DC) and normal control (NC) groups received daily treatment with saline. After the treatment, oxidative stress parameters, biochemical parameters, and inflammatory parameters were estimated. CCAAT-displacement protein/cut homeobox (CUP/Cux) and scaffold/matrix attachment region binding protein 1 (SMAR1) expression levels were measured through gene expression analysis. Immunohistochemical (IHC) analysis was performed to estimate the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Results: Tumor growth reduced significantly (P-value < 0.01) in karanjin-treated animals compared to the DC group. Karanjin significantly (P-value < 0.01) regulated the levels of oxidative stress parameters, biochemical parameters, and inflammatory parameters compared to the DC group. Karanjin treatment significantly (P-value < 0.001) regulated the expression levels of SMAR1 and CDP/Cux. A notable reduction in the IHC scores was observed for ER, PR, and HER2 expression in karanjin groups. Conclusion: Karanjin demonstrated chemoprotective activity against DMBA-induced breast cancer in animals potentially through modulation of SMAR1 and CDP/Cux gene expression and reduction of ER, PR and HER2 expression levels. [ABSTRACT FROM AUTHOR]

Hymenoscyphus fraxineus, the causal agent of Ash Dieback (ADB), has been introduced to eastern Europe in the 1990s from where it spread causing decline in European ash populations. However, the genetic basis of the molecular response in tolerant and susceptible ash trees to this disease is still largely unknown. We performed RNA-sequencing to study the transcriptomic response to the disease in four ash genotypes (ADB-tolerant FAR3 and FS36, and ADB-susceptible UW1 and UW2), during a time-course of 7, 14, 21, and 28 days post-inoculation, including mock-inoculated trees as control samples for each sampling time point. The analysis yielded 395 and 500 Differentially Expressed Genes (DEGs) along the response for ADB-tolerant FAR3 and FS36, respectively, while ADB-susceptible UW1 and UW2 revealed 194 and 571 DEGs, respectively, with most DEGs found exclusively in just one of the genotypes. DEGs shared between tolerant genotypes FAR3 and FS36, included genes involved in the production of phytoalexins and other secondary metabolites with roles in plant defense. Moreover, we identified an earlier expression of genes involved in both pattern- and effector-triggered immunity (PTI and ETI) in ADB-tolerant genotypes, while in ADB-susceptible genotypes both responses were delayed (late response). Overall, these results revealed different transcriptomic expression patterns not only between ADB-tolerant and ADB-susceptible genotypes, but also within these two groups. This hints to individual responses in the natural tolerance to ADB, possibly revealing diversified strategies across ash genotypes. [ABSTRACT FROM AUTHOR]

The phosphate transporter (PHT) family plays an important role in the uptake and transport of P elements in plants. A total of 158 PbPHTs were identified from the genome of 'duli' (Pyrus betulifolia Bunge) in this study, including 70 PbPHT1s, 2 PbPHT2s, 70 PbPHT3s, 12 PbPHT4s, and 4 PbPHT5s. Among the 158 PHT genes, 150 were localized to 17 'duli' chromosomes. Gene duplication analysis identified 18 tandemly duplicated gene pairs. The promoter analysis showed that there were a large number of cis-acting elements related to phytohormones, growth, development, stress, and light response in PbPHTs. qRT-PCR analysis revealed that most PHT genes in 'duli' were highly expressed in the fruits, flowers, leaves, stems, and roots, and 15 PbPHT genes were responsive to 5 μM, 0.5 mM, 5 mM H2PO4, NaCl, GR24 (synthetic SL analog), GA3 (gibberellin 3), ABA (abscisic acid), and IAA (indole-3-acetic acid). GR24, GA3, IAA, and 5 mM KH2PO4 treatments could increase the concentration, absorption, transport, and distribution of P elements in the rhizomes and leaves of 'duli', but 5 μM KH2PO4, NaCl, and ABA had the opposite effect. This study therefore provides a list of PbPHT genes with substantial roles in abiotic stress response, as well as important information to understand the functional characteristics of PbPHT during 'duli' abiotic stress tolerance, and explores the function of PbPHTs in exogenous hormones, phosphorus, and salt stress in the future. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of plasma treated metal contaminated water, used for irrigation, on plant growth. Zinc (Zn) is a commonly used metal that can enter the environment through industrial processes. It may be released as particles into the atmosphere or discharged as wastewater into waterways or the ground. Exposure to large amounts of zinc, even for a short duration, can seriously impact human health. In this experiment, three different DBD (dielectric barrier discharge) O2 plasma treated zinc contaminated water and a control (tap water) were used, with Arabidopsis thaliana as the model plant. The treatments were: (i) Control, (ii) Zn water, (iii) Zn + O3(30 min), and (iv) Zn + O3(60 min). Arabidopsis plant exhibited maximum growth in the Zn + O3(30 min) treatment. All growth parameters, except leaf area, followed this trend: Zn + O3(30 min) > Control > Zn water > Zn + O3(60 min). Gene expression analysis revealed that reduced metal ion stress and controlled oxidation due to active oxygen species contributed to favorable/improved growth of Arabidopsis in the Zn + O3(30 min) treatment. Therefore, 30 min of DBD O2 plasma treated zinc contaminated water [Zn + O3(30 min)] can mitigate the adverse effects of excess zinc ions and promote the growth of Arabidopsis plants. [ABSTRACT FROM AUTHOR]

Ovarian endometrioma (OE), also known as "chocolate cysts," is a cystic mass that develops in the ovaries due to endometriosis and is a common gynecological condition characterized by the growth of endometrial tissue outside the uterus, leading to symptoms such as dysmenorrhea, pelvic pain, and infertility. However, the precise molecular and cellular mechanisms driving this pathophysiology remain largely unknown, posing challenges for diagnosis and treatment. Here, we employed integrated single-cell transcriptomic profiling of over 52,000 individual cells from endometrial tissues of OE patients and healthy donors and identified twelve major cell populations. We identified notable alterations in cell type-specific proportions and molecular signatures associated with OE. Notably, the activation of IGFBP5+ macrophages with pro-inflammatory properties, NK cell exhaustion, and aberrant proliferation of IQCG+ and KLF2+ epithelium are key features and may be the potential mechanisms underlying the pathogenesis of OE. Collectively, our data contribute to a better understanding of OE at the single cell level and may pave the way for the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Recent studies on integrating multiple omics data highlighted the potential to advance our understanding of the cancer disease process. Computational models based on graph neural networks and attention-based architectures have demonstrated promising results for cancer classification due to their ability to model complex relationships among biological entities. However, challenges related to addressing the high dimensionality and complexity in integrating multi-omics data, as well as in constructing graph structures that effectively capture the interactions between nodes, remain active areas of research. This study evaluates graph neural network architectures for multi-omics (MO) data integration based on graph-convolutional networks (GCN), graph-attention networks (GAT), and graph-transformer networks (GTN). Differential gene expression and LASSO (Least Absolute Shrinkage and Selection Operator) regression are employed for reducing the omics data dimensionality and feature selection; hence, the developed models are referred to as LASSO-MOGCN, LASSO-MOGAT, and LASSO-MOGTN. Graph structures constructed using sample correlation matrices and protein-protein interaction networks are investigated. Experimental validation is performed with a dataset of 8,464 samples from 31 cancer types and normal tissue, comprising messenger-RNA, micro-RNA, and DNA methylation data. The results show that the models integrating multi-omics data outperformed the models trained on single omics data, where LASSO-MOGAT achieved the best overall performance, with an accuracy of 95.9%. The findings also suggest that correlation-based graph structures enhance the models’ ability to identify shared cancer-specific signatures across patients in comparison to protein-protein interaction networks-based graph structures. The code and data used in this study are available in the link (https://github.com/FadiAlharbi2024/Graph_Based_Architecture.git).

Cerebellar information processing is critically shaped by several types of inhibitory interneurons forming various intra-cerebellar feed-forward and feed-back loops. Evidence gathered over the past decades has focused interest on a non-uniform set of cortical inhibitory interneurons distinct from “classical” Golgi, basket or stellate cells, summarily referred to as PLIs (for Purkinje cell layer interneurons). Similarly, cerebellar nuclear inhibitory interneurons have gained increasing attention. Our understanding of the functions of these cells is still fragmentary. For humans, we lack functional data, and even any dependable morphological classification for these cells. Here, I used publicly available single cell based gene expression data to compare inhibitory interneurons from the cerebellar cortex and inhibitory nuclear neurons of humans and mice. Integration of nuclear and cortical cells revealed transcriptomic similarities between subsets of these cells and suggest known characteristics of cortical cell types may be helpful to devise strategies for the further characterization of nuclear inhibitory interneurons. Comparison of human and murine PLIs indicate that these strongly differ by the expression of genes used to characterize these cells in mice. This limits their utility to identify and classify human PLIs, and leaves the question open as to the number and characteristics of non-Golgi inhibitory interneurons resident in the cerebellar granule cell and Purkinje cell layers in humans. [ABSTRACT FROM AUTHOR]

Salt stress inhibits seed germination, plant growth, development and productivity. Ca2+-ATPases play a key role in plant response to environmental stresses. Sugar beet is an important cash crop and one of the main sugar crops in China. However, there are few reports on the study of Ca2+-ATPase gene family in sugar beet. In this study, we analyzed the sugar beet Ca2+-ATPase gene family and the functions of genes in response to salt stress. A total of 21 Ca2+-ATPase genes were identified in the genome. Their physical and chemical properties, chromosome localization, and subcellular localization were predicted by bioinformatics analysis. Additionally, their phylogenetic relationships, structural characteristics, cis-acting elements, and expression patterns in different tissues of sugar beet under salt stress were analyzed. Protein interaction networking indicates that Ca2+-ATPase may play a role in flavonoid biosynthesis and ABA signal transduction. The results help to advance our understanding of the Ca2+-ATPase gene family, providing a scientific base for elucidating the functions of Ca2+-ATPase genes in plant stress responses. [ABSTRACT FROM AUTHOR]

Abstract Lung squamous cell carcinoma (LUSC) is a subtype of non-small cell lung cancer. It has a grim prognosis for patients, primarily because the disease often remains asymptomatic in its early stages. As a result, it is frequently diagnosed at an advanced stage, limiting treatment options. This underscores the importance of studying potential biomarkers and developing personalized treatment strategies. In this study, we used an advanced bioinformatics approach, integrating two authoritative databases, NCBI's GEO and TCGA, to perform a large-scale cross-platform gene expression analysis. To deeply mine the gene expression data of a large number of lung squamous carcinoma samples, we used a screening strategy based on median absolute deviation to select genes that differed significantly in multiple datasets. The expression variations of these genes between normal and cancerous tissues provided us with valuable clues revealing key molecules that may be involved in the disease process. Through rigorous statistical tests, we identified 36 genes that were significantly associated with patient survival, and further constructed a model using Cox proportional risk model containing 11 key genes (MRPL40, GABPB1AS1, PTPN3, SNCA, PYGB, RAP1, VDR, PHPT1, KIAA0100, TBC1D30, CYP7B1) in a risk prediction model. The prediction model not only reflects the strong correlation between gene expression and LUSC prognosis, but also provides clinicians with an effective tool to predict patients' survival prospects. In the future, this model is expected to guide the development of individualized treatment plans, thereby improving the quality of life and overall prognosis of patients.

Abstract Background Heterotrimeric G proteins are crucial signaling molecules involved in cell signaling, plant development, and stress response. However, the genome-wide identification and analysis of G proteins in castor (Ricinus communis L.) have not been researched. Results In this study, RcG-protein genes were identified using a sequence alignment method and analyzed by bioinformatics and expression analysis in response to salt stress. The results showed that a total of 9 G-protein family members were identified in the castor genome, which were classified into three subgroups, with the majority of RcG-proteins showing homology to soybean G-protein members. The promoter regions of all RcG-protein genes contained antioxidant response elements and ABA-responsive elements. Go enrichment analysis displayed that RcG-protein genes were involved in the G protein-coupled receptor signaling pathway, regulation of root development, and response to the bacterium. Real-time PCR showed varying responses of all RcG-protein genes to salt stress. RcGB1 was notably expressed in both roots and leaves under salt treatment, suggesting that it may be an essential gene associated with salt tolerance in the castor. Conclusions This study offers a theoretical framework for exploring G-protein function and presents potential genetic assets for improving crop resilience through genetic enhancement.

Abstract Fish, being highly sensitive to changes in the physico-chemical parameters of water, are good indicators of contamination. Teesta, a prominent northern West Bengal River system, is increasingly contaminated due to anthropogenic activities. This study aims to determine agricultural pesticide contamination and its genotoxic impact on the resident fish, Pethia conchonius, as an experimental organism. Sample water analysis from three riverine sites I, II & III, showed the presence of the insecticides imidacloprid (IMI), chlorpyrifos (CPF), bifenethrin (BF), cypermethrin (CP), difenthiuron, acetamiprid (AC) in the sites II and III only with adjoining agricultural lands. Comet assay revealed a significantly lower % Head DNA (~ 1.2 times), higher %Tail DNA (~ 16 times), and %Tail length (~ 3.1 times) in the gills of Pethia conchonius from sites II and III. About 4 and 10 times increase of micronuclei and other nuclear abnormalities were also noted in the erythrocytes of the fish from sites II and III than I, which was not contaminated. The antioxidant enzymes SOD, CAT, and GST activity and MDA levels were significantly higher (p

Abstract Eccrine sweat glands are essential for thermoregulation. Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder characterized by the absence of sweating, leading to severe complications like heatstroke and skin dryness. The underlying etiology remains unknown, complicating diagnosis and treatment. This study aimed to elucidate the genetic mechanisms of AIGA by analysing the gene expression in eccrine sweat glands using the GSE193125 dataset from the NCBI Gene Expression Omnibus (GEO). This study identified differentially expressed genes (DEGs) (genes that show statistically significant differences in expression levels in AIGA), with JUN and CCN1 significantly downregulated in anhidrotic lesions of AIGA patients. Receiver operating characteristic (ROC) curve demonstrated the accuracy of these genes in classification (JUN = 0.88 and CCN1 = 0.77). Gene and protein interaction networks which are defined as networks of physical interactions between genes and proteins, constructed using GeneMANIA and STRING, revealed substantial physical interactions among them. Gene set enrichment analysis highlighted the neuroinflammatory and estrogen receptor signaling pathways are associated with this condition, suggesting hormonal regulation’s role in the anhidrosis mechanism. Key miRNAs, including hsa-let-7b-5p, hsa-miR-10b-5p, and hsa-miR-124-3p, are associated with the DEGs, underscoring the importance of post-transcriptional and transcriptional regulation. Through the Drug Gene Interaction Database (DGIdb), ciprofibrate is identified as a potential therapeutic agent targeting the JUN gene. Molecular docking confirmed a strong binding affinity between ciprofibrate and JUN, suggesting ciprofibrate could modulate JUN activity and regulate AIGA symptoms. ADMET analysis, which refers to the assessment of absorption, distribution, metabolism, excretion, and toxicity of a drug or compound, is crucial for evaluating its pharmacokinetic and safety profile. The analysis indicated that ciprofibrate has favourable pharmacokinetic properties and a relatively safe toxicity profile. This comprehensive bioinformatics approach, integrating gene expression analysis, miRNA identification, and drug interaction, provides valuable insights into anhidrosis molecular pathology and highlights ciprofibrate’s potential as a targeted therapeutic strategy. Despite limitations, including a small sample size and reliance on computational predictions, this study paves the way for further research and potential therapeutic interventions for AIGA.

Abstract Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune dysregulation, and systemic fibrosis. Research on SSc has been hindered largely by lack of relevant models to study the progressive nature of the disease and to recapitulate the cell plasticity that is observed in this disease context. Generation of models for fibrotic disease using pluripotent stem cells is important for recapitulating the heterogeneity of the fibrotic tissue and are a potential platform for screening anti-fibrotic drugs. We previously reported a novel in-vitro model for fibrosis using induced pluripotent stem cell-derived mesenchymal cells (iSCAR). Here we report the generation of a “scar-like phenotype” when iPSC derived mesenchymal cells are cultured on hydrogel that mimicks a wound healing/scarring response (iSCAR). First, we performed RNA sequencing (RNA-seq) based transcriptome profiling of iSCAR culture at 48 h and 13 days to characterize early and latestage scarring phenotypes. The next generation RNA-seq of these iSCAR culture at different timepoints detected expression 92% of early “scar associated” genes and 85% late “scar associated” genes, respectively. Comparative transcriptomic analysis of a gene level SSc compendium matrix to the iSCAR wound associated model revealed genes common in both data sets. Early scar formation genes showed biological processes of hypoxia (27.5%), vascular development (13.7%) and glycolysis (27.5), while late scar formation showed genes associated with senescence (22.6%). Next we show the effects of two different antifibrotic compounds to validate the utility of the model as a screening tool to study early and late-stagelate-stage fibrosis. An autotaxin inhibitor was used to validate the iSCAR late stage fibrotic model (iSCAR-T) and an antifibrotic tool screening compound of unknown mechanism (EX00015097) was used to study and validate both early (iSCAR-P) and late-stage (iSCAR-T) fibrosis in the iSCAR model.

Background Behaviorally conditioned immune functions are suggested to be regulated by bidirectional interactions between CNS and peripheral immune system via the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system (SNS), and the parasympathetic nervous system (PNS). Since the current knowledge about biochemical pathways triggering conditioned immune enhancement is limited, the aim of this pilot study was gaining more insights into that. Methods Rats were conditioned with camphor smell and poly I:C injection, mimicking a viral infection. Following stimulus re-exposure, animals were sacrificed at different time points, and neural tissues along the HPA axis was analyzed with a rat genome array together with plasma protein using Luminex analysis. Results In the hypothalamus, we observed a strong upregulation of genes related to Wnt/β-catenin signaling (Otx2, Spp1, Fzd6, Zic1), monoaminergic transporter Slc18a2 and opioid-inhibitory G-protein Gpr88 as well as downregulation of dopaminergic receptors, vasoactive intestinal peptide Vip, and pro-melanin-concentrating hormone Pmch. In the pituitary, we recognized mostly upregulation of steroid synthesis in combination with GABAergic, cholinergic and opioid related neurotransmission, in adrenal glands, altered genes showed a pattern of activated metabolism plus upregulation of adrenoceptors Adrb3 and Adra1a. Data obtained from spleen showed a strong upregulation of immunomodulatory genes, chemo-/cytokines and glutamatergic/cholinergic neurotransmission related genes, as also confirmed by increased chemokine and ACTH levels in plasma. Conclusions Our data indicate that in addition to the classic HPA axis, there could be additional pathways as e.g. the cholinergic anti-inflammatory pathway (CAIP), connecting brain and immune system, modulating and finetuning communication between brain and immune system.

Through a comprehensive examination of pyroptosis‐related differential expressed genes (PRDEGs), this work investigates the molecular complexities of spontaneous preterm birth (SPTB), also known as premature delivery, before the due date. Through the process of merging and correcting batch effects in the GSE120480 and GSE73714 datasets, we were able to identify 36 PRDEGs that exhibited significant expression differentiation in SPTB. Through functional enrichment and pathway analysis, their importance in amino acid transport and cytokine receptor interaction has been highlighted. Among the genes that have emerged as crucial, CEBPA, APOA1, and CEP55 have been identified. The relevance of these molecules was demonstrated using experimental knockdowns, which also suggested that they could be used as molecular biomarkers and therapeutic targets for SPTB. [ABSTRACT FROM AUTHOR]

Lung squamous cell carcinoma (LUSC) is a subtype of non-small cell lung cancer. It has a grim prognosis for patients, primarily because the disease often remains asymptomatic in its early stages. As a result, it is frequently diagnosed at an advanced stage, limiting treatment options. This underscores the importance of studying potential biomarkers and developing personalized treatment strategies. In this study, we used an advanced bioinformatics approach, integrating two authoritative databases, NCBI's GEO and TCGA, to perform a large-scale cross-platform gene expression analysis. To deeply mine the gene expression data of a large number of lung squamous carcinoma samples, we used a screening strategy based on median absolute deviation to select genes that differed significantly in multiple datasets. The expression variations of these genes between normal and cancerous tissues provided us with valuable clues revealing key molecules that may be involved in the disease process. Through rigorous statistical tests, we identified 36 genes that were significantly associated with patient survival, and further constructed a model using Cox proportional risk model containing 11 key genes (MRPL40, GABPB1AS1, PTPN3, SNCA, PYGB, RAP1, VDR, PHPT1, KIAA0100, TBC1D30, CYP7B1) in a risk prediction model. The prediction model not only reflects the strong correlation between gene expression and LUSC prognosis, but also provides clinicians with an effective tool to predict patients' survival prospects. In the future, this model is expected to guide the development of individualized treatment plans, thereby improving the quality of life and overall prognosis of patients. [ABSTRACT FROM AUTHOR]

Introduction: Intraductal papillary mucinous neoplasms (IPMNs) are diverse premalignant tumors of the pancreas. They progress stepwise from adenoma to carcinoma and offer an opportunity for intervention prior to malignant transformation into pancreatic ductal adenocarcinoma (PDAC). The current study aimed to identify differentially expressed genes (DEGs) in invasive PDAC‐associated IPMN vs. noninvasive IPMN to understand the potential molecular changes involved in malignant transformation of IPMN into PDAC. Materials and Methods: Archived tissue and data from 12 patients with histologically proven invasive PDAC arising from IPMN specimens were assessed. Gene expression analysis was performed on RNA extracted from macro‐dissected tissue specimens using the NanoString nCounter PanCancer Progression assay. Statistical and pathway analysis was performed using SPSS v28 and Ingenuity Pathway Analysis, respectively. Results: A total of 159 genes had significantly (p < 0.05, q < 0.05) different expression in PDAC arising from IPMN compared with that from IPMN alone (91 overexpressed and 68 underexpressed). Interestingly, 14 of top 10 over‐ and underexpressed genes were predicted to translate secretory proteins, with SignalP scores approaching 1. A number of differential canonical pathways (e.g., LXR/RXR activation pathway, glycolysis I gluconeogenesis I, and hepatic fibrosis) and potential upstream regulators (e.g., TGFB1, THBS2, etc.) were also identified. Conclusion: A differential gene expression profile between PDAC arising from IPMN and IPMN alone was identified. Pathway analysis identified potential mechanisms involved in malignant transformation of IPMN to PDAC. [ABSTRACT FROM AUTHOR]

Heavy and costly use of phosphorus (P) fertiliser is often needed to achieve high crop yields, but only a small amount of applied P fertiliser is available to most crop plants. Hakea prostrata (Proteaceae) is endemic to the P‐impoverished landscape of southwest Australia and has several P‐saving traits. We identified 16 members of the Phosphate Transporter 1 (PHT1) gene family (HpPHT1;1‐HpPHT1;12d) in a long‐read genome assembly of H. prostrata. Based on phylogenetics, sequence structure and expression patterns, we classified HpPHT1;1 as potentially involved in Pi uptake from soil and HpPHT1;8 and HpPHT1;9 as potentially involved in Pi uptake and root‐to‐shoot translocation. Three genes, HpPHT1;4, HpPHT1;6 and HpPHT1;8, lacked regulatory PHR1‐binding sites (P1BS) in the promoter regions. Available expression data for HpPHT1;6 and HpPHT1;8 indicated they are not responsive to changes in P supply, potentially contributing to the high P sensitivity of H. prostrata. We also discovered a Proteaceae‐specific clade of closely‐spaced PHT1 genes that lacked conserved genetic architecture among genera, indicating an evolutionary hot spot within the genome. Overall, the genome assembly of H. prostrata provides a much‐needed foundation for understanding the genetic mechanisms of novel adaptations to low P soils in southwest Australian plants. [ABSTRACT FROM AUTHOR]

SUPPRESSOR OF MAX2 1-LIKE (SMXL) proteins are negative regulators of strigolactone (SL) signal transduction that play an important role in regulating plant branching and responses to abiotic stress. Here, we studied the role of SMXL proteins in pear growth, development, and stress resistance. A total of 18 SMXL members were characterized in 'duli'. All SMXL members were localized to chloroplasts. Chromosome mapping analysis showed that the members of this family were unevenly distributed on 14 chromosomes. Gene fragment replication analysis showed that there were no tandem repeat genes in PbSMXLs, and 12 pairs of homologous genes were fragment duplications. There were 30 pairs of homologous genes between 'duli' and apples, and 17 between 'duli' and Arabidopsis thaliana. Analysis of cis-acting elements showed that there was a large number of photo-effector elements, short-effector elements, hormone-responsive elements, and abiotic stress-responsive elements in the promoter sequences of this family. Analysis of enzyme activity and endogenous SL showed that β-carotenoid isomerase (D27), carotenoid cleavage dioxygenase 7 (CCD7), lateral branch oxidoreductase (LBO) levels, and SL content were higher in 'duli' roots and leaves compared in the control under exogenous GA3 (gibberellin 3), IAA (indole-3-acetic acid), GR24 (synthetic SL analog), and NaCl. Most SMXL genes in 'duli' were highly expressed in branches and axillary lobes, but their expression was low in fruits. qRT-PCR analysis revealed that eight PbSMXL genes were responsive to GA3, PAC (Paclobutrazol), IAA, ABA (abscisic acid), GR24, and Tis108 (SL biosynthesis inhibitor). PbSMXLs responded positively to salt stress. The expression of PbSMXL6 and PbSMXL15 was significantly induced under salt stress. The expression of PbSMXL7, PbSMXL10, and PbSMXL15 was significantly induced by Tis108 treatment. The results of this study enhance our understanding of the role of SMXL genes in the responses to plant growth regulators and salt stress. Our findings will also aid future studies of the functions of SMXL genes in 'duli'. [ABSTRACT FROM AUTHOR]

The oil bean is a high-quality, economically valuable variety of kidney bean (Phaseolus vulgaris L.) that is widely cultivated in Northeast China. However, the prevalence of anthracnose, caused by a combination of factors, including continuous cropping over many years, has led to significant declines in both yield and quality. The mitogen-activated protein kinase (MAPK) cascade is a highly conserved plant cell signaling pathway that plays a pivotal role in plant growth and development, as well as responses to biotic stress. However, its role in the response of P. vulgaris to anthracnose infection has not previously been reported. We identified and characterized thirteen MAPK genes (PvMAPK01–PvMAPK13) in the P. vulgaris genome. These genes were found on eight of the eleven chromosomes of P. vulgaris, and phylogenetic analyses classified them into four previously established subgroups (A–D). Analysis of the cis-acting elements in their promoter regions revealed the presence of multiple elements associated with light, hormone regulation, stress responses, and growth and development. An analysis of intraspecific collinearity revealed that whole-genome and/or segmental duplication, rather than tandem duplication, has been the primary driver of PvMAPK family expansion in P. vulgaris. Transcriptome data revealed that the PvMAPKs differed in their tissue-specific expression patterns, with PvMAPK05 showing particularly high expression in stems and stem tips and PvMAPK07 and PvMAPK11 showing relatively low expression across all tissues. In general, expression of the PvMAPKs was higher in stems, stem tips, and pods than in other tissues and organs, suggesting that they may be particularly important for regulating stem and pod development. Analysis of the expression of PvMAPKs in field-grown plants infected or uninfected with anthracnose revealed that the relative expression levels of PvMAPK05, PvMAPK07, PvMAPK09, and PvMAPK11 exhibited particularly significant changes in response to anthracnose infection across different varieties, suggesting their potential involvement in the anthracnose response of Phaseolus vulgaris. This study reports the fundamental characteristics of the thirteen MAPK genes in P. vulgaris, documents their expression patterns in diverse tissues, and offers preliminary insights into their responses to anthracnose infection, establishing a foundation for subsequent functional validation. [ABSTRACT FROM AUTHOR]

Background: Table grapes suffer from a dramatic deterioration in quality, a reduction in shelf life and commercial value resulting from allivated postharvest respiratory metabolism and excessive energy consumption after harvest. Objective: In this study, effects of hydrogen-rich water (HRW) on berry quality, respiratory metabolism, and energy level were investigated by multi concentration gradient tests (0% (control), 20%, 40%, 60%, 80%, and 100%). Methods: To achieve this goal, by measuring fruit quality, respiratory metabolism, related enzyme activities, energy status, and other related indicators, to study its impact on postharvest fruit quality and further explore the mechanism of maintaining fruit quality after harvest. Results: Compared to the control group, samples treated with HRW exhibited higher fruit firmness, total soluble solids (TSS), and titratable acids (TA), with the most prominent effect observed after treatment with 60% HRW. Compared with the control group, grapes treated with 60% HRW exhibited more effective regulation in the expression of GPI, AOX, SDH1, COX6a, G6DH, 6PGD, NADK, and AGPase gene, which helped maintain normal respiratory metabolism and energy levels in the fruit samples. Conclusions: Our results showed that HRW treatment could potentially maintain the quality and prolong the shelf life of postharvest grapes by regulating gene expression and the activity of key enzymes involved in respiratory and energy metabolisms. [ABSTRACT FROM AUTHOR]

Peanut is one of the widely cultivated oil and economic crops worldwide and has become a major source of oil and protein for humans due to its high oil and protein content. With the increasing global demand for vegetable oil, improving the fatty acid composition and increasing the lipid content of peanut seeds has become a top priority in peanut breeding. Transcriptional regulators can modulate the expression of a series of genes in metabolic pathways related to lipid synthesis, significantly affecting lipid synthesis and metabolism. In this study, two transcription factors, AhWRI1-1 and AhWRI1-2, were cloned from the leaves of Huayu 33. The ORF of AhWRI1-1 was 1101 bp, encoding 366 amino acids, and the ORF of AhWRI1-2 was 1128 bp, encoding 375 amino acids. Bioinformatics analysis revealed that both AhWRI1-1 and AhWRI1-2 contained two AP2/EREBP conserved domains. The expression patterns of AhWRI1-1 and AhWRI1-2 in different tissues were detected by qRT-PCR. The results showed that AhWRI1-1 had the highest expression in seeds, suggesting its involvement in the regulation of fatty acid synthesis and oil accumulation, while AhWRI1-2 had the highest expression in hypocotyls, indicating its role in hypocotyl development. Additionally, the differences in the responses of AhWRI1-1 and AhWRI1-2 to abiotic stresses suggested that these transcription factors may play different roles under such conditions. Transcriptional activation experiments in yeast showed that both Ah- WRI1-1 and AhWRI1-2 possess transcriptional activation activities. This study lays the foundation for future in-depth functional studies of AhWRI1-1 and AhWRI1-2. [ABSTRACT FROM AUTHOR]

Objectives: Hepatocellular carcinoma (HCC) is a considerable global health concern. This study attempts to analyze gene expression data between liver tissues with HCV-related HCC and healthy liver tissues to identify potential biomarkers that contribute to HCC development. Methods: We analyzed RNA sequencing data from liver tissues with HCV-related HCC and healthy liver tissues in this study. We retrieved the dataset from NCBI using the code GSE140845. We performed gene expression analysis using the Limma software package in the R programming language, defining genes as differentially expressed if they had a log2 fold change (log2FC) > 1 and a p > 0.05. We conducted data visualization using scatter plots, UMAP, volcano plots, and mean difference (MD) plots. Results: A total of 20,868 genes were analyzed between the HCV-HCC and healthy liver tissue groups, and 3,303 genes were found to be significantly differentially expressed. Genes such as AKR1B10, MUC13, SLC22A11, and SPINK1 showed upregulation in the HCV-HCC group, whereas CNDP1, IGFALS, PVALB, and CLEC4M showed downregulation. These genes have the potential to serve as biomarkers and play critical roles in understanding the mechanisms of HCC development. Conclusion: This study highlights the differential regulation of genes associated with HCV-HCC, emphasizing their potential roles in the pathogenesis of HCC. Notably, the identified biomarkers hold promise as therapeutic targets. These findings may contribute to personalized medicine approaches and enable the development of novel strategies for the prevention and treatment of HCC. [ABSTRACT FROM AUTHOR]

Leaf color affects the efficiency of photosynthesis, and leaf color mutants are important genetic materials for studying the mechanisms of photosynthesis, chlorophyll biosynthesis, and chloroplast development in rice. In this study, a white-striped leaf mutant, wst1, was obtained from the mutant population of the indica restorer line 'Chuanhui 907' (R907) when treated with 60Co-γ radiation. Compared to the wild-type, the wst1 mutant showed normal leaf color before tillering and white stripes on the leaf and leaf sheaths after tillering. The chlorophyll and carotenoid contents were significantly reduced, and the thylakoids of chloroplasts developed abnormalities in wst1 plants in the tillering stage. The results of agronomic trait analysis showed that the number of effective panicles, plant height, seed setting rate, and 1000-grain weight of the wst1 mutant were significantly lower than those of the wild-type. Genetic analysis revealed that the phenotype of the wst1 mutant is controlled by a pair of recessive nuclear genes. The candidate gene was mapped to a 72 kb region between the InDel markers M6 and M12 on the short arm of chromosome 1 using molecular marker linkage analysis. Candidate genes were sequenced on the interval, and a G base was replaced by A at the 6972nd position on the 16th exon of LOC_Os01g01920, which encoded a previously reported protein containing the HD domain, WSF3/WFSL1, leading to alternative splicing, causing a 104 bp deletion in the coding region, and resulting in mistranslation after the 490 amino acid of the encoded protein translation in wst1. RT-qPCR analysis showed that the expression levels of most genes related to chlorophyll synthesis and chloroplast development were significantly altered in wst1 plants. Our study identified a novel allele of wsf3 and wfsl1 mutant and provided a new genetic resource and theoretical basis for further understanding of the molecular mechanism of WST1 gene regulation of white-striped leaves in rice. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions We aimed to assess the gene expression profiles of nonlesional small bowels in patients with Crohn's disease (CD) to identify its accompanying molecular alterations.We performed RNA sequencing of the uninflamed small bowel tissues obtained from 70 patients with ileal CD and 9 patients with colon cancer (non‐CD controls) during bowel resection. Differentially expressed gene (DEG) analyses were performed using DESeq2. Gene set enrichment, correlation, and cell deconvolution analyses were applied to identify modules and functionally enriched transcriptional signatures of CD.A comparison of CD patients and non‐CD controls revealed that of the 372 DEGs, 49 protein‐coding genes and 5 long non‐coding RNAs overlapped with the inflammatory bowel disease susceptibility loci. The pathways related to immune and inflammatory reactions were upregulated in CD, while metabolic pathways were downregulated in CD. Compared with non‐CD controls, CD patients had significantly higher proportions of immune cells, including plasma cells (P = 1.15 × 10−4), and a lower proportion of epithelial cells (P = 1.12 × 10−4). Co‐upregulated genes (M14 module) and co‐downregulated genes (M9 module) were identified in CD patients. The M14 module was enriched in immune‐related genes and significantly associated with the responses to anti‐tumor necrosis factor (TNF) therapy. The core signature of the M14 module was comprised of six genes and was upregulated in nonresponders to anti‐TNF therapy of five independent cohorts (n = 163), indicating acceptable discrimination ability (area under the receiver operating characteristic curve of 75–86%).The differences in gene expression and cellular composition between CD patients and non‐CD controls imply significant molecular alterations, which are associated with the response to anti‐TNF treatment. [ABSTRACT FROM AUTHOR]

Background: Heterotrimeric G proteins are crucial signaling molecules involved in cell signaling, plant development, and stress response. However, the genome-wide identification and analysis of G proteins in castor (Ricinus communis L.) have not been researched. Results: In this study, RcG-protein genes were identified using a sequence alignment method and analyzed by bioinformatics and expression analysis in response to salt stress. The results showed that a total of 9 G-protein family members were identified in the castor genome, which were classified into three subgroups, with the majority of RcG-proteins showing homology to soybean G-protein members. The promoter regions of all RcG-protein genes contained antioxidant response elements and ABA-responsive elements. Go enrichment analysis displayed that RcG-protein genes were involved in the G protein-coupled receptor signaling pathway, regulation of root development, and response to the bacterium. Real-time PCR showed varying responses of all RcG-protein genes to salt stress. RcGB1 was notably expressed in both roots and leaves under salt treatment, suggesting that it may be an essential gene associated with salt tolerance in the castor. Conclusions: This study offers a theoretical framework for exploring G-protein function and presents potential genetic assets for improving crop resilience through genetic enhancement. [ABSTRACT FROM AUTHOR]

Fish, being highly sensitive to changes in the physico-chemical parameters of water, are good indicators of contamination. Teesta, a prominent northern West Bengal River system, is increasingly contaminated due to anthropogenic activities. This study aims to determine agricultural pesticide contamination and its genotoxic impact on the resident fish, Pethia conchonius, as an experimental organism. Sample water analysis from three riverine sites I, II & III, showed the presence of the insecticides imidacloprid (IMI), chlorpyrifos (CPF), bifenethrin (BF), cypermethrin (CP), difenthiuron, acetamiprid (AC) in the sites II and III only with adjoining agricultural lands. Comet assay revealed a significantly lower % Head DNA (~ 1.2 times), higher %Tail DNA (~ 16 times), and %Tail length (~ 3.1 times) in the gills of Pethia conchonius from sites II and III. About 4 and 10 times increase of micronuclei and other nuclear abnormalities were also noted in the erythrocytes of the fish from sites II and III than I, which was not contaminated. The antioxidant enzymes SOD, CAT, and GST activity and MDA levels were significantly higher (p < 0.05) in the liver samples from sites II and III, while AChE activity was significantly decreased (p < 0.001) in the brain tissues. Moreover, the sod, cat, and gpx expression in the hepatic cells were significantly upregulated compared to the β actin mRNA indicating increased oxidative stress. Increased genomic damage, antioxidant enzyme activity, higher MDA levels, decreased AChE activity in the brain, and the upregulation of hepatic genes strongly suggested the genotoxic effects of the detected insecticides in combination with other contaminants. [ABSTRACT FROM AUTHOR]

High-dimensional gene expression data cause challenges for traditional statistical tools, particularly when dealing with non-linear relationships and outliers. The present study addresses these challenges by employing a generalized correlation coefficient (GCC) that incorporates a flexibility parameter, allowing it to adapt to varying levels of symmetry and asymmetry in the data distribution. This adaptability is crucial for analyzing gene association networks, where the GCC demonstrates advantages over traditional measures such as Kendall, Pearson, and Spearman coefficients. We introduce two novel adaptations of this metric, enhancing its precision and broadening its applicability in the context of complex gene interactions. By applying the GCC to relevance networks, we show how different levels of the flexibility parameter reveal distinct patterns in gene interactions, capturing both linear and non-linear relationships. The maximum likelihood and Spearman-based estimators of the GCC offer a refined approach for disentangling the complexity of biological networks, with potential implications for precision medicine. Our methodology provides a powerful tool for constructing and interpreting relevance networks in biomedicine, supporting advancements in the understanding of biological interactions and healthcare research. [ABSTRACT FROM AUTHOR]

In the current clinical setting, conventional serum biomarkers such as serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) have several lapses in chronic kidney disease (CKD) diagnosis. Diagnosing CKD using non-invasive methods is crucial for implementing prompt therapeutic interventions and preventing disease progression. This study aims to identify the potential diagnostic urinary biomarkers and their correlation with existing renal markers, Scr, eGFR, and proteinuria in diabetic and hypertensive CKD. RNA was extracted from eighty-two urine samples of CKD patients and healthy controls (HC) and reverse transcribed for gene expression analysis using quantitative polymerase chain reactions. The expression of NGAL, MMP9, ANXA3, OLFM4, PI3, and PRMT3 genes was analyzed relative to the reference gene, B2M. Fold changes (FC) in gene expression in diabetic nephropathy (DN), and hypertensive nephropathy (HT) were calculated against HC. Log2 normalized FC was used to determine significance levels and correlation with existing serum markers. NGAL, ANXA3, and OLFM4 exhibited the highest upregulations in DN with mean Log2FC 1.42, 2.66, and 5.87, respectively. A two-fold increase in NGAL FC was observed in early DN than in late DN, suggesting its potential as an early urinary biomarker for DN. PI3 and MMP9 were upregulated in HT patients with higher FC values. PRMT3 showed a significant negative correlation (P<0.05) in HT patients with Scr (r=-0.738) and proteinuria (r=-0.906). The gene panels including ANXA3, OLFM4, and NGAL, and PI3, PRMT3, and MMP9, could have potential diagnostic value in DN and HT, respectively. [ABSTRACT FROM AUTHOR]

Eccrine sweat glands are essential for thermoregulation. Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder characterized by the absence of sweating, leading to severe complications like heatstroke and skin dryness. The underlying etiology remains unknown, complicating diagnosis and treatment. This study aimed to elucidate the genetic mechanisms of AIGA by analysing the gene expression in eccrine sweat glands using the GSE193125 dataset from the NCBI Gene Expression Omnibus (GEO). This study identified differentially expressed genes (DEGs) (genes that show statistically significant differences in expression levels in AIGA), with JUN and CCN1 significantly downregulated in anhidrotic lesions of AIGA patients. Receiver operating characteristic (ROC) curve demonstrated the accuracy of these genes in classification (JUN = 0.88 and CCN1 = 0.77). Gene and protein interaction networks which are defined as networks of physical interactions between genes and proteins, constructed using GeneMANIA and STRING, revealed substantial physical interactions among them. Gene set enrichment analysis highlighted the neuroinflammatory and estrogen receptor signaling pathways are associated with this condition, suggesting hormonal regulation’s role in the anhidrosis mechanism. Key miRNAs, including hsa-let-7b-5p, hsa-miR-10b-5p, and hsa-miR-124-3p, are associated with the DEGs, underscoring the importance of post-transcriptional and transcriptional regulation. Through the Drug Gene Interaction Database (DGIdb), ciprofibrate is identified as a potential therapeutic agent targeting the JUN gene. Molecular docking confirmed a strong binding affinity between ciprofibrate and JUN, suggesting ciprofibrate could modulate JUN activity and regulate AIGA symptoms. ADMET analysis, which refers to the assessment of absorption, distribution, metabolism, excretion, and toxicity of a drug or compound, is crucial for evaluating its pharmacokinetic and safety profile. The analysis indicated that ciprofibrate has favourable pharmacokinetic properties and a relatively safe toxicity profile. This comprehensive bioinformatics approach, integrating gene expression analysis, miRNA identification, and drug interaction, provides valuable insights into anhidrosis molecular pathology and highlights ciprofibrate’s potential as a targeted therapeutic strategy. Despite limitations, including a small sample size and reliance on computational predictions, this study paves the way for further research and potential therapeutic interventions for AIGA.Article Highlights: JUN and CCN1 genes downregulated in anhidrotic lesions of patients with acquired idiopathic generalized anhidrosis. Hormonal regulation may play a role in AIGA, with neuroinflammatory and estrogen pathways possibly involved. Ciprofibrate shows potential as a treatment for AIGA by targeting JUN, supported by drug interaction and docking studies. [ABSTRACT FROM AUTHOR]

The study of the pathogenesis of febrile seizures and their consequences frequently necessitates gene expression analysis. The primary methodology employed for such analysis is reverse transcription with quantitative polymerase chain reaction (RT-qPCR). To ensure the accuracy of data obtained by RT-qPCR, it is crucial to utilize stably expressed reference genes. The objective of this study was to identify the most suitable reference genes for use in the analysis of mRNA production in various brain regions of rats following prolonged neonatal febrile seizures. The expression stability of eight housekeeping genes was evaluated using the online tool RefFinder in the dorsal and ventral hippocampal regions and in the temporal and medial prefrontal cortex of the brain. The Ppia gene exhibited the greatest stability of expression. Conversely, the genes with the least stable expression levels were Actb and Ywhaz; thus, it is not recommended to use them for normalization in a febrile seizure model. Additionally, the majority of housekeeping genes demonstrate age-related, region-specific fluctuations. Therefore, it is crucial to employ the appropriate housekeeping genes for each brain structure under investigation when examining the expression dynamics of genes of interest in a febrile seizure model. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune dysregulation, and systemic fibrosis. Research on SSc has been hindered largely by lack of relevant models to study the progressive nature of the disease and to recapitulate the cell plasticity that is observed in this disease context. Generation of models for fibrotic disease using pluripotent stem cells is important for recapitulating the heterogeneity of the fibrotic tissue and are a potential platform for screening anti-fibrotic drugs. We previously reported a novel in-vitro model for fibrosis using induced pluripotent stem cell-derived mesenchymal cells (iSCAR). Here we report the generation of a "scar-like phenotype" when iPSC derived mesenchymal cells are cultured on hydrogel that mimicks a wound healing/scarring response (iSCAR). First, we performed RNA sequencing (RNA-seq) based transcriptome profiling of iSCAR culture at 48 h and 13 days to characterize early and latestage scarring phenotypes. The next generation RNA-seq of these iSCAR culture at different timepoints detected expression 92% of early "scar associated" genes and 85% late "scar associated" genes, respectively. Comparative transcriptomic analysis of a gene level SSc compendium matrix to the iSCAR wound associated model revealed genes common in both data sets. Early scar formation genes showed biological processes of hypoxia (27.5%), vascular development (13.7%) and glycolysis (27.5), while late scar formation showed genes associated with senescence (22.6%). Next we show the effects of two different antifibrotic compounds to validate the utility of the model as a screening tool to study early and late-stagelate-stage fibrosis. An autotaxin inhibitor was used to validate the iSCAR late stage fibrotic model (iSCAR-T) and an antifibrotic tool screening compound of unknown mechanism (EX00015097) was used to study and validate both early (iSCAR-P) and late-stage (iSCAR-T) fibrosis in the iSCAR model. [ABSTRACT FROM AUTHOR]

Purpose: To perform an extensive exploratory analysis to build a deeper insight into clinically relevant molecular biomarkers in Papillary, Follicular, and Anaplastic thyroid carcinomas (PTC, FTC, ATC). Methods: Thirteen Thyroid Cancer (THCA) datasets incorporating PTC, FTC, and ATC were derived from the Gene Expression Omnibus. Genes differentially expressed (DEGs) between THCA and normal were identified and subjected to GO and KEGG analyses. Multiple topological properties were harnessed and protein-protein interaction (PPI) networks were constructed to identify the hub genes followed by survival analysis and validation. Results: There were 70, 87, and 377 DEGs, and 23, 27, and 53 hub genes for PTC, FTC, and ATC samples, respectively. Survival analysis detected 39 overall and 49 relapse-free survival-relevant hub genes. Six hub genes, BCL2, FN1, ITPR1, LYVE1, NTRK2, TBC1D4, were found common to more than one THCA type. The most significant hub genes found in the study were: BCL2, CD44, DCN, FN1, IRS1, ITPR1, MFAP4, MKI67, NTRK2, PCLO, TGFA. The most enriched and significant GO terms were Melanocyte differentiation for PTC, Extracellular region for FTC, and Extracellular exosome for ATC. Prostate cancer for PTC was the most significantly enriched KEGG pathway. The results were validated using TCGA data. Conclusions: The findings unravel potential biomarkers and therapeutic targets of thyroid carcinomas. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are multipotent, progenitor cells that reside in tissues across the human body, including the periodontal ligament (PDL) and gingiva. They are a promising therapeutic tool for various degenerative and inflammatory diseases. However, different heterogeneity levels caused by tissue-to-tissue and donor-to-donor variability, and even intercellular differences within a given MSCs population, restrict their therapeutic potential. There are considerable efforts to decipher these heterogeneity levels using different "omics" approaches, including single-cell transcriptomics. Previous studies applied this approach to compare MSCs isolated from various tissues of different individuals, but distinguishing between donor-to-donor and tissue-to-tissue variability is still challenging. In this study, MSCs were isolated from the PDL and gingiva of 5 periodontally healthy individuals and cultured in vitro. A total of 3,844 transcriptomes were generated using single-cell mRNA sequencing. Clustering across the 2 different tissues per donor identified PDL- and gingiva-specific and tissue-spanning MSCs subpopulations with unique upregulated gene sets. Gene/pathway enrichment and protein-protein interaction (PPI) network analysis revealed differences restricted to several cellular processes between tissue-specific subpopulations, indicating a limited tissue-of-origin variability in MSCs. Gene expression, pathway enrichment, and PPI network analysis across all donors' PDL- or gingiva-specific subpopulations showed significant but limited donor-to-donor differences. In conclusion, this study demonstrates tissue- and donor-specific variabilities in the transcriptome level of PDL- and gingiva-derived MSCs, which seem restricted to specific cellular processes. Identifying tissue-specific and tissue-spanning subpopulations highlights the intercellular differences in dental tissue–derived MSCs. It could be reasonable to control MSCs at a single-cell level to ensure their properties before transplantation. [ABSTRACT FROM AUTHOR]

The TCP gene family plays pivotal roles in the development and abiotic stress responses of plants; however, no data has been provided for this gene family in Opisthopappus taihangensis. Based on O. taihangensis genome, 14 TCP genes were identified and divided into two classes (I and II). After tandem and segmental duplication/whole-genome duplication (WGD), more loss and less gain events of OtTCPs occurred, which might be related with the underwent purifying selection during the evolution. The conserved motifs and structures of OtTCP genes contained light response, growth and development, hormone response, and stress-related cis-acting elements. Different OtTCP genes, even duplicated gene pairs, could be expressed in different tissues, which implied that OtTCP genes had diverse function. Among OtTCPs, OtTCP4, 9 and 11 of CYC clade (Class II) presented a relative wide expression pattern with no or one intron. The three TCP genes could be regarded as important candidate factors for O. taihangensis in growth, development and stress response. These results provided some clues and references for the further in-depth exploration of O. taihangensis resistance mechanisms, as well as those of other unique eco-environment plants.

Among the biotic stresses, wilt disease severely affects tomato quality and productivity globally. The causal organism of this disease is Fusarium oxysporum f. sp. lycopersici (Fol), which is very well known and has a significant impact on the productivity of other crops as well. Efforts have been made to investigate the effect of plant growth-promoting bacteria (PGPB) on alleviating tomato wilt disease. Four PGPB strains, such as Pseudomonas aeruginosa BHUPSB01 (T1), Pseudomonas putida BHUPSB04 (T2), Paenibacillus polymyxa BHUPSB16 (T3), and Bacillus cereus IESDJP-V4 (T4), were used as inocula to treat Fol-challenged plants. The results revealed that PGPB treatments T1, T2, T3, and T4 were able to decrease the severity of Fusarium wilt in the tomato plants at different levels. Among the treatments, T3 displayed the strongest protective effect, with the lowest disease frequency, which was 15.25%. There were no significant differences observed in parameters such as fruit yield and relative water content in the PGPB-inoculated plants, although T3 and T4 showed minimal electrolyte leakage. Significant changes in chlorophyll fluorescence were also recorded. A lower level of H2O2 and malondialdehyde (MDA) was observed in the T3 and T4 treatments. In addition, proline accumulation was highest in the T3-treated plants. Antioxidative enzyme activities, such as catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), significantly increased in the PGPB-treated plants. Furthermore, the highest phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO) activity was reported in the T3 and T4 plants, respectively. The PGPB-treated plants showed elevated expression of the PAL, PPO, PR3, PR2, SOD, CAT, and PO genes. This study’s results reveal that PGPB strains can be utilized as biocontrol agents (BCAs) to enhance tomato resistance against Fusarium wilt.

Background Behaviorally conditioned immune functions are suggested to be regulated by bidirectional interactions between CNS and peripheral immune system via the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system (SNS), and the parasympathetic nervous system (PNS). Since the current knowledge about biochemical pathways triggering conditioned immune enhancement is limited, the aim of this pilot study was gaining more insights into that. Methods Rats were conditioned with camphor smell and poly I:C injection, mimicking a viral infection. Following stimulus re-exposure, animals were sacrificed at different time points, and neural tissues along the HPA axis was analyzed with a rat genome array together with plasma protein using Luminex analysis. Results In the hypothalamus, we observed a strong upregulation of genes related to Wnt/β-catenin signaling (Otx2, Spp1, Fzd6, Zic1), monoaminergic transporter Slc18a2 and opioid-inhibitory G-protein Gpr88 as well as downregulation of dopaminergic receptors, vasoactive intestinal peptide Vip, and pro-melanin-concentrating hormone Pmch. In the pituitary, we recognized mostly upregulation of steroid synthesis in combination with GABAergic, cholinergic and opioid related neurotransmission, in adrenal glands, altered genes showed a pattern of activated metabolism plus upregulation of adrenoceptors Adrb3 and Adra1a. Data obtained from spleen showed a strong upregulation of immunomodulatory genes, chemo-/cytokines and glutamatergic/cholinergic neurotransmission related genes, as also confirmed by increased chemokine and ACTH levels in plasma. Conclusions Our data indicate that in addition to the classic HPA axis, there could be additional pathways as e.g. the cholinergic anti-inflammatory pathway (CAIP), connecting brain and immune system, modulating and finetuning communication between brain and immune system.

Chromatin is not randomly distributed within the nucleus, but organized in a three-dimensional structure that plays a critical role in genome functions. Сohesin and condensins are conserved multi-subunit protein complexes that participate in mammalian genome organization by extruding chromatin loops. The fine temporal regulation of these complexes is facilitated by a number of other proteins, one of which is microcephalin (Mcph1). Mcph1 prevents condensin II from associating with chromatin through interphase. Loss of Mcph1 induces chromosome hypercondensation; it is not clear to what extent this reorganization affects gene expression. In this study, we generated several mouse embryonic stem cell (mESC) lines with knockout of the Mcph1 gene and analyzed their gene expression profile. Gene Ontology analyses of differentially expressed genes (DEGs) after Mcph1 knockout revealed gene categories related to general metabolism and olfactory receptor function but not to cell cycle control previously described for Mcph1. We did not find a correlation between the DEGs and their frequency of lamina association. Thus, this evidence questions the hypothesis that Mcph1 knockout-mediated chromatin reorganization governs gene expression in mESCs. Among the negative effects of Mcph1 knockout, we observed numerous chromosomal aberrations, including micronucleus formation and chromosome fusion. This confirms the role of Mcph1 in maintaining genome integrity described previously. In our opinion, dysfunction of Mcph1 may be a kind of “Rosetta stone” for deciphering the function of condensin II in the interphase nucleus. Thus, the cell lines with knocked-out Mcph1 can be used to further study the influence of chromatin structural proteins on gene expression.