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Nicotine use produces psychoactive effects, and chronic use is associated with physiological and psychological symptoms of addiction. However, chronic nicotine use is known to decrease food intake and body weight gain, suggesting that nicotine also affects central metabolic and appetite regulation. We recently showed that acute nicotine self-administration in nicotine-dependent animals produces a short-term increase in food intake, contrary to its long-term decrease of feeding behavior. As feeding behavior is regulated by complex neural signaling mechanisms, this study aimed to test the hypothesis that nicotine intake in animals exposed to chronic nicotine may increase activation of pro-feeding regions and decrease activation of pro-satiety regions to produce the acute increase in feeding behavior. FOS immunohistochemistry revealed that acute nicotine intake in nicotine self-administering animals increased activation of the pro-feeding arcuate and lateral hypothalamic nuclei and decreased activation of the pro-satiety parabrachial nucleus. Regional correlational analysis also showed that acute nicotine changes the functional connectivity of the hunger/satiety network. Further dissection of the role of the arcuate nucleus using electrophysiology found that putative POMC neurons in animals given chronic nicotine exhibited decreased firing following acute nicotine application. These brain-wide central signaling changes may contribute to the acute increase in feeding behavior we see in rats after acute nicotine and provide new areas of focus for studying both nicotine addiction and metabolic regulation.

Introduction: Vascular smooth muscle cells are important in intimal hyperplasia. Thrombospondin-1 is a matricellular protein involved in the vascular injury response. Statins are cholesterol lowering drugs that have beneficial cardiovascular effects. Statis have been shown to inhibit smooth muscle migration through the mevalonate pathway. This effect is thought to be mediated by small G protein Ras and Rho turnover which requires many hours. While many patients undergoing treatment for vascular disease are on statins, many are not. Thus immediate pretreatment with statins before surgery may be beneficial. We hypothesized that statins have effects independent of the mevalonate pathway and thus have an immediate effect. Methods: Human vascular smooth muscle cells were pretreated for 20 h (long-term) or 20 min (short-term) with fluvastatin, or mevalonolactone plus fluvastatin. Thrombospondin-1-induced migration, activation of p42/p44 extracellular signal-regulated kinase, c-Src, focal adhesion kinase and PI3 kinase was determined. The effect of fluvastatin on thrombospondin-1-induced expression of THBS1, FOS, HAS2 and TGFB2 was examined. Results: Both treatments inhibited thrombospondin-1-induced chemotaxis back to the control group. Mevalonolactone reversed the long-term statin effect by increasing migration but had no effect on the short-term statin response. p42/p44 extracellular signal-regulated kinase was activated by thrombospondin-1 and both treatments augmented activation. Neither treatment affected c-Src activity, but both inhibited focal adhesion kinase and PI3 kinase activity. Only long-term statin treatment inhibited THBS1 expression while both treatments inhibited FOS and TGFB2 expression. Neither treatment affected HAS2. FOS knockdown inhibited thrombospondin-1-induced HAS2 but not TGFβ2 gene expression. Conclusion: Long-term fluvastatin inhibited thrombospondin-1-induced chemotaxis through the mevalonate pathway while short-term fluvastatin inhibited chemotaxis through an alternate mechanism. Short-term stains have immediate effects independent of the mevalonate pathway. Acute local treatment with statins followed by longer term therapy may limit the vascular response to injury. [ABSTRACT FROM AUTHOR]

Accurate slope stability prediction is of utmost importance to reduce disastrous effects of slope failures and landslides. However, conventional methods of slope stability analysis are complex and challenging, and more importantly, use of these methods in a wide-area slope stability assessment requires a large number of soil property and field investigation data. These complexities and challenges often demand some simplified statistical slope stability analysis models such as by using machine learning (ML) techniques. So, in this research, we develop slope stability prediction models using multiple linear regression (MLR) and artificial neural network (ANN) and classify the slopes as safe or unsafe using random forest (RF) and support vector machine (SVM) methods. For this purpose, a dataset of 4,208 slope cases was created using limit equilibrium-based Slide software. The effectiveness of each model was then evaluated using statistical metrics and validated through roadside slope cases in Nepal, India, Canada, and the UK. In this study, Spencer's method-based ANN model was found to have demonstrated the highest reliability. The findings of this work may contribute to simplified and better decision-making process in slope stability assessment, slope safety enhancement, and sustainability improvement in engineering projects involving soil slopes. [ABSTRACT FROM AUTHOR]

Abstract Aim The present work set out to classify cell subpopulations related to liver metastasis from gastric cancer (GC) and the mechanisms of their interactions with other immune cell subpopulations. Background GC is characterized by a high degree of heterogeneity and liver metastasis. Exploring the mechanism of liver metastasis of GC from the perspective of heterogeneity of the tumor microenvironment (TME) might help improve the efficacy of GC treatment. Objective Based on the cellular subpopulation characteristics of GC with liver metastasis, the regulatory mechanisms contributing to GC progression were analyzed, with special focuses on the roles of signaling pathways, transcription factors (TFs) and ligand–receptor pairs. Methods The GSE163558 dataset was downloaded from the Gene Expression Omnibus (GEO) database to collect single-cell transcriptomic data of GC patients and their metastasis groups for cell clustering and relevant analyses. Differentially expressed genes (DEGs) in the GC and GC liver metastasis groups were screened and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. SCENIC analysis was used to mine TFs that affected cellular subpopulations during liver metastasis from GC. The relative expression levels of TFs in GC were determined using qRT-PCR. Transwell and wound healing assays were utilized to verify the regulation of the TFs on the migration and invasion of GC cells. Interaction network between the cellular subpopulations was developed applying CellChat. Results Single-cell clustering was performed to group six major cell subpopulations, namely, Myeloid cells, B cells, Mast cells, Epithelial cells, Fibroblasts, and TNK cells, among which the number of TNK cells was significantly increased in the GC liver metastasis group. Differentially enriched pathways of TNK cells between GC and GC liver metastasis groups mainly included IL-17 and Pi3k–Akt signaling pathways. TNK cell subsets could be further categorized into CD8 T cells, Exhausted T cells, NK cells, NKT cells, and Treg cells, with the GC liver metastasis group showing significantly more CD8 T cells and NKT cells. FOS and JUNB were the TFs of TNK cell marker genes that contributed to liver metastasis from GC and the invasion and migration of GC cell lines. Significant differences in immune cell communication ligand–receptor pairs existed between the GC and GC liver metastasis groups. Conclusion This study revealed the critical role of TNK cell subsets in GC with liver metastasis applying single-cell transcriptomics analysis. The findings provided an important theoretical basis for developing novel therapies to inhibit liver metastasis from GC.

Abstract This research aimed to investigate the effects of dietary fructooligosaccharides (FOS) on attenuating the Aeromonas hydrophila (A. hydrophila)-induced oxidative stress and apoptosis in blunt snout bream Megalobrama amblycephala. Fish were divided into three groups as follows: C1 (Control), T1 (A. hydrophila), and T2 (A. hydrophila + 4 g/kg FOS). The results showed that the activities of antioxidant enzymes increased, the liver morphology had disorderly arrangement, and extensive cell necrosis occurred because of A. hydrophila-infection. While the dietary FOS improved the above-mentioned liver damage. Additionaly, FOS elevated mRNA levels of pro-apoptotic molecules, including caspase-8 and 9, and down-regulated mRNA levels of the anti-apoptotic molecule Bcl-2, which is triggered by A. hydrophila-infection. The transcriptome analysis showed that the oxidative stress-related DEGs pathways were activated in intestine of blunt snout bream by A. hydrophila-infection. The FOS-added group led to the enrichment of more pathways to health. Further WGCNA co-expression network analysis showed that the screened single genes were clustered into 49 modules. The two modules with the highest association to the five traits (10 hub genes) were chosen to build the network by combining the physiological and biochemical characteristic. In summary, this research offers a foundation for the exploring of A. hydrophila-restoration genes in dietary FOS, and also lays a theoretical foundation for aquaculture in the future.

Background: Antibiotic use has undesirable side-effects on the host, including perturbations of gut microbiota, immunity, and health. Mammalian studies have demonstrated that concomitant/post antibiotic use of pro-, pre-, and synbiotics could re-establish gut microbiota and prevent detrimental host effects. However, studies evaluating similar effects in fish are scanty. This study evaluated the effects of dietary supplementation with a synbiotic mixture on the post-smolt Atlantic salmon gut microbiota, growth performance, and health during antibiotic treatment and subsequent recovery. Fish in five tanks each were fed either a commercial control diet or a synbiotic diet containing Pediococcus acidilactici and fructo-oligosaccharides, for 6 weeks (S1). Then, fish in three tanks per treatment were fed with medicated diets, containing 3500 ppm florfenicol coated onto the control or synbiotic diets, for 2 weeks (S2) and refed with the respective nonmedicated diets for another 3 (S3) and 5 (S4) weeks of recovery period. The fish not subjected to medication were fed the control or synbiotic diets throughout the experimental period. Samples were collected at S1-S4 from both the nonmedicated and medicated fish. Results: Florfenicol decreased the feed intake in control group. It reduced the growth rate in both control and synbiotic groups with lesser reduction in synbiotic group. Florfenicol did not significantly affect observed taxa and Shannon indexes. Bacterial composition before and after medication clustered distinctly in control and clustered together in synbiotic groups. Lactobacillus dominated in control while Lactobacillus and Pediococcus dominated in synbiotic group during medication and recovery. Florfenicol did not significantly influence the immune or stress response marker gene expressions, though the expression patterns differed between diet groups. Florfenicol did not cause inflammation in the distal intestine or change hepatosomatic index. Conclusions: This study highlighted the negative impact of a two-week florfenicol treatment on feed intake and growth performance in Atlantic salmon, with moderate effects on gut microbiota and gene expression. Concomitant use of a synbiotic diet helped to maintain the gut microbial composition and influenced the performance positively and immune gene expressions differently during medication. This study indicates the importance of nutritional interventions through synbiotic supplementation as a possible strategy for managing Atlantic salmon during antibiotic treatment. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC), a prevalent form of primary liver malignancy, arises from liver-specific hepatocytes. Senecio scandens Buch.-Ham(Climbing senecio) is a bitter-tasting plant of the Compositae family with anti-tumor properties. This study aims to identify the molecular targets and pathways through which Climbing senecio regulates HCC. Methods: Active ingredients of Climbing senecio were collected from four online databases and mapped to relevant target databases to obtain predicted targets. After recognizing the key pathways through which Climbing senecio acts in HCC. Gene expression data from GSE54238 Underwent differential expression and weighted gene correlation network analyses to identify HCC-related genes. The "Climbing senecio-Hepatocellular Carcinoma Targets" network was constructed using Cytoscape 3.10.1 software, followed by topology analysis to identify core genes. The expression and distribution of key targets were evaluated, and the differential expression of each key target between normal and diseased samples was calculated. Moreover, single-cell data from the Gene Expression Omnibus (GSE202642) were used to assess the distribution of Climbing senecio's bioactive targets within major HCC clusters. An intersection analysis of these clusters with pharmacological targets and HCC-related genes identified Climbing senecio's primary targets for this disease. Cell communication, receiver operating characteristic (ROC)analysis, survival analysis, immune filtration analysis, and molecular docking studies were conducted for detailed characterization. Results: Eleven components of Climbing senecio were identified, along with 520 relevant targets, 300 differentially expressed genes, and 3765 co-expression module genes associated with HCC. AKR1B1, CA2, FOS, CXCL2, SRC, ABCC1, and PLIN1 were identified within the intersection of HCC-related genes and Climbing senecio targets. TGFβ, IL-1, VEGF, and CXCL were identified as significant factors in the onset and progression of HCC. These findings underscore the anti-HCC potential and mode of action of Climbing senecio, providing insights into multi-targeted treatment approaches for HCC. Conclusions: This study revealed that Climbing senecio may target multiple pathways and genes in the process of regulating HCC and exert potential drug effects through a multi-target mechanism, which provides a new idea for the treatment of HCC. However, the research is predicated on network database analysis and bioinformatics, offering insights into HCC therapeutic potential while emphasizing the need for further validation. [ABSTRACT FROM AUTHOR]

This article deals with the optimization of a French language course of instruction, in hybrid mode, intended for “Arabized” students in the first year of the preparatory classes of the ESTI. The data collected by the survey and observation indicate that students have serious communicative and methodological language needs in French. More than half of those questioned preferred face-to-face. The results also show that by harmoniously combining face-to-face and remote FOS teaching elements, a hybrid course can take advantage of the strengths of each mode, thus offering rich and flexible teaching/learning, taking into account the variety of needs and maximizing educational effectiveness. [ABSTRACT FROM AUTHOR]

The gut microbiome plays a critical role to all animals and humans health. Methods based on ex vivo cultures are time and cost-effective solutions for rapid evaluation of probiotic effects on microbiomes. In this study, we assessed whether the protein secretome from the potential probiotic Enterococcus durans LAB18S grown on fructoligosaccharides (FOS) and galactoligosaccharides (GOS) had specific effects on ex vivo cultured intestinal microbiome obtained from a healthy individual. Metaproteomics was used to evaluate changes in microbial communities of the human intestinal microbiome. Hierarchical clustering analysis revealed 654 differentially abundant proteins from the metaproteome samples, showing that gut microbial protein expression varied on the presence of different E. durans secretomes. Increased amount of Bacteroidetes phylum was observed in treatments with secretomes from E. durans cultures on FOS, GOS and albumin, resulting in a decrease of the Firmicutes to Bacteroidetes (F/B) ratio. The most functionally abundant bacterial taxa were Roseburia, Bacteroides, Alistipes and Faecalibacterium. The results suggest that the secretome of E. durans may have favorable effects on the intestinal microbial composition, stimulating growth and different protein expression of beneficial bacteria. These findings suggest that proteins secreted by E. durans growing on FOS and GOS have different effects on the modulation of gut microbiota functional activities during cultivation. [ABSTRACT FROM AUTHOR]

Underground compressed air energy storage chambers are a promising emerging energy storage technology with strict limitations relating to the stability of the surrounding rock. This study conducted displacement and plastic zone analyses during the excavation and stabilization phases of the chamber utilizing the finite difference method based on engineering data, demonstrating that the stability of salt rock can effectively withstand internal pressures ranging from 0 to 9 MPa, with an average of 15 mm in the Z-axis and 19.23 mm in the X-axis. To further investigate the feasibility of subterranean energy storage reservoirs, the FOS for various surrounding rocks was calculated at different burial depths. These results facilitated a parameter sensitivity analysis on the stability of the surrounding rock of the underground energy storage reservoir. The dynamic reaction of the underground chamber was studied using synthetic seismic wave technology, demonstrating that the seismic capacity of the structure adhered to the code, and the post-seismic displacement remained within the safe range (Z-axis 34 mm, horizontal 19 mm). The results demonstrate the stability analysis method of the chamber and establish a foundation for the extensive implementation of CAES which will contribute to the development of energy storage technology. [ABSTRACT FROM AUTHOR]

Aim: The present work set out to classify cell subpopulations related to liver metastasis from gastric cancer (GC) and the mechanisms of their interactions with other immune cell subpopulations. Background: GC is characterized by a high degree of heterogeneity and liver metastasis. Exploring the mechanism of liver metastasis of GC from the perspective of heterogeneity of the tumor microenvironment (TME) might help improve the efficacy of GC treatment. Objective: Based on the cellular subpopulation characteristics of GC with liver metastasis, the regulatory mechanisms contributing to GC progression were analyzed, with special focuses on the roles of signaling pathways, transcription factors (TFs) and ligand–receptor pairs. Methods: The GSE163558 dataset was downloaded from the Gene Expression Omnibus (GEO) database to collect single-cell transcriptomic data of GC patients and their metastasis groups for cell clustering and relevant analyses. Differentially expressed genes (DEGs) in the GC and GC liver metastasis groups were screened and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. SCENIC analysis was used to mine TFs that affected cellular subpopulations during liver metastasis from GC. The relative expression levels of TFs in GC were determined using qRT-PCR. Transwell and wound healing assays were utilized to verify the regulation of the TFs on the migration and invasion of GC cells. Interaction network between the cellular subpopulations was developed applying CellChat. Results: Single-cell clustering was performed to group six major cell subpopulations, namely, Myeloid cells, B cells, Mast cells, Epithelial cells, Fibroblasts, and TNK cells, among which the number of TNK cells was significantly increased in the GC liver metastasis group. Differentially enriched pathways of TNK cells between GC and GC liver metastasis groups mainly included IL-17 and Pi3k–Akt signaling pathways. TNK cell subsets could be further categorized into CD8 T cells, Exhausted T cells, NK cells, NKT cells, and Treg cells, with the GC liver metastasis group showing significantly more CD8 T cells and NKT cells. FOS and JUNB were the TFs of TNK cell marker genes that contributed to liver metastasis from GC and the invasion and migration of GC cell lines. Significant differences in immune cell communication ligand–receptor pairs existed between the GC and GC liver metastasis groups. Conclusion: This study revealed the critical role of TNK cell subsets in GC with liver metastasis applying single-cell transcriptomics analysis. The findings provided an important theoretical basis for developing novel therapies to inhibit liver metastasis from GC. [ABSTRACT FROM AUTHOR]

Introduction: Different functional domains can be identified along the longitudinal axis of the mammalian hippocampus. We have recently hypothesized that a similar functional gradient may exist along the longitudinal axis of the avian hippocampal formation (HF) as well. If the 2 gradients are homologous, we would expect the caudal HF to be more responsive to acute stress than the rostral HF. Methods: We restrained 8 adult Dekalb White hens in a bag for 30 min under red-light conditions and compared FOS-immunoreactive (FOS-ir) cell densities in different hippocampal subdivisions to control hens. Results: Although we could find no evidence of an activated stress response in the hypothalamic-pituitary-adrenal axis of the restrained birds, we did find a significant increase in FOS-ir cell densities in the rostral HF of the restrained birds compared to controls. Conclusion: We speculate that the HF response is not due to an acute stress response, but instead, it is related to the change in spatial context that was part of taking the birds and restraining them in a different room. We see no activation in the caudal HF. This would be consistent with our hypothesis that the longitudinal axis of the avian HF is homologous to the long axis of the mammalian hippocampus. [ABSTRACT FROM AUTHOR]

This research aimed to investigate the effects of dietary fructooligosaccharides (FOS) on attenuating the Aeromonas hydrophila (A. hydrophila)-induced oxidative stress and apoptosis in blunt snout bream Megalobrama amblycephala. Fish were divided into three groups as follows: C1 (Control), T1 (A. hydrophila), and T2 (A. hydrophila + 4 g/kg FOS). The results showed that the activities of antioxidant enzymes increased, the liver morphology had disorderly arrangement, and extensive cell necrosis occurred because of A. hydrophila-infection. While the dietary FOS improved the above-mentioned liver damage. Additionaly, FOS elevated mRNA levels of pro-apoptotic molecules, including caspase-8 and 9, and down-regulated mRNA levels of the anti-apoptotic molecule Bcl-2, which is triggered by A. hydrophila-infection. The transcriptome analysis showed that the oxidative stress-related DEGs pathways were activated in intestine of blunt snout bream by A. hydrophila-infection. The FOS-added group led to the enrichment of more pathways to health. Further WGCNA co-expression network analysis showed that the screened single genes were clustered into 49 modules. The two modules with the highest association to the five traits (10 hub genes) were chosen to build the network by combining the physiological and biochemical characteristic. In summary, this research offers a foundation for the exploring of A. hydrophila-restoration genes in dietary FOS, and also lays a theoretical foundation for aquaculture in the future. [ABSTRACT FROM AUTHOR]

Minimally processed products are highly convenient, and fresh-cut fruits coated with the synbiotic film have many advantages. This study investigated the film-forming components and preservation ability of Da Xanh pomelo and Thai jackfruit fresh-cut by synbiotic pectin film. The results showed that PA70 film combined with 1.5% FOS (fructooligosaccharides) had the highest number of viable cells of L. plantarum after 30 days of storage at 5 °C. The number of probiotic cells existing on fresh-cut products of Da Xanh pomelo and Thai jackfruit was always high (> 8 log CFU/g) and stable during 10 days of storage. In addition, jackfruit and pomelo fresh-cut preserved with probiotic film also showed probiotic activity in simulated stomach and small intestine medium with the number of probiotic cells (> 6 log CFU/g) and survival cell ratio after 4 h in small intestine medium reached 81.20 ± 0.92% (pomelo) and 82.16 ± 0.94% (Thai jackfruit). [ABSTRACT FROM AUTHOR]

Dendrobine (DDB), an alkaloid isolated from the Chinese herb Dendrobium, has antioxidant and anti-inflammatory effects; however, whether DDB reduces oleic acid (OA)-induced lipid accumulation remains unclear. OA-induced lipid accumulation model of HepG2 cells were treated with DDB. Cellular lipid deposition was assessed by Oil Red O (ORO) staining and triglyceride and total cholesterol detection. RNA-Sequencing (RNA-seq), biological function analysis, and transcription factor (TFs) prediction were combined to identify key TF in the DDB-treated OA model. Finally, the roles of FOS and METTL14 were examined using a DDB-induced lipid accumulation model. DDB inhibited OA-induced lipid accumulation. We identified 895 differentially expressed genes (DEGs) that were mainly enriched in various biological processes of lipid synthesis and transport. Four transcription factors (SOX9, MLXIPL, FOS, and JUN) associated with lipid metabolism and FOS levels in the OA-induced lipid accumulation model after DDB treatment had the greatest changes in expression change. Overexpression of FOS alleviates the inhibitory effect of DDB on OA-induced lipid accumulation. METTL14 is a target gene of FOS, and simultaneous interference with METTL14 in cells with high FOS expression restored the alleviating effect of DDB on lipid accumulation. DDB alleviated OA-induced lipid accumulation by inhibiting the FOS/METTL14 pathway. [ABSTRACT FROM AUTHOR]

ABSTRACT Background The therapeutic management of metastatic hormone‐sensitive prostate cancer (mHSPC) is still based on clinical and pathological parameters due to the lack of biomarkers that may drive tailored treatment. Methods In this non‐randomized, single‐center, retrospective trial, we searched for a genetic signature using the NanoString nCounter PanCancer Pathways Panel on formalin‐fixed paraffin embedded prostate cancer samples belonging to 48 patients with de novo or relapsed mHSPC. Patients were divided into a high‐clinical‐risk group (n = 36) and a low‐clinical‐risk group (n = 12) according to the mean time to metastatic relapse. Results The analysis of Nanostring nCounter Panel data revealed differential expression of 42 genes between high‐clinical‐risk and low‐clinical‐risk groups. All the genes except for NR4A1 and FOS were upregulated in the high‐clinical‐risk group. A general overexpression of apoptosis, PI3K and MAPK pathway‐related genes, including AKT2, was observed in the high‐clinical‐risk group. Conclusion The differential genetic signature identified between the two study groups revealed novel biomarkers in mHSPC, additionally suggesting new therapeutic targets within the hormone sensitive phase, such as AKT2. Further prospective larger cohort studies are needed to assess the prognostic value of our findings and their exact role in prostate cancer progression.

ABSTRACT Dietary fibers influence the composition of the human gut microbiota and directly contribute to its downstream effects on host health. As more research supports the use of glycans as prebiotics for therapeutic applications, the need to identify the gut bacteria that metabolize glycans of interest increases. Fructo-oligosaccharide (FOS) is a common diet-derived glycan that is fermented by the gut microbiota and has been used as a prebiotic. Despite being well studied, we do not yet have a complete picture of all FOS-consuming gut bacterial taxa. To identify new bacterial consumers, we used a short exposure of microbial communities in a stool sample to FOS or galactomannan as the sole carbon source to induce glycan metabolism genes. We then performed metatranscriptomics, paired with whole metagenomic sequencing, and 16S amplicon sequencing. The short incubation was sufficient to cause induction of genes involved in carbohydrate metabolism, like carbohydrate-active enzymes (CAZymes), including glycoside hydrolase family 32 genes, which hydrolyze fructan polysaccharides like FOS and inulin. Interestingly, FOS metabolism transcripts were notably overexpressed in Blautia species not previously reported to be fructan consumers. We therefore validated the ability of different Blautia species to ferment fructans by monitoring their growth and fermentation in defined media. This pulse metatranscriptomics approach is a useful method to find novel consumers of prebiotics and increase our understanding of prebiotic metabolism by CAZymes in the gut microbiota.IMPORTANCEComplex carbohydrates are key contributors to the composition of the human gut microbiota and play an essential role in the microbiota’s effects on host health. Understanding which bacteria consume complex carbohydrates, or glycans, provides a mechanistic link between dietary prebiotics and their beneficial health effects, an essential step for their therapeutic application. Here, we used a pulse metatranscriptomics pipeline to identify bacterial consumers based on glycan metabolism induction in a human stool sample. We identified novel consumers of fructo-oligosaccharide among Blautia species, expanding our understanding of this well-known glycan. Our approach can be applied to identify consumers of understudied glycans and expand our prebiotic repertoire. It can also be used to study prebiotic glycans directly in stool samples in distinct patient populations to help delineate the prebiotic mechanism.

Background: The mechanism by which chondrocyte senescence aggravate OA progression has not yet been well elucidated. The aim of this study was to investigate the chondrocyte senescence related gene biosignatures in OA, and to analyze on the underlying mechanisms of senescence in OA. Materials and methods: We intersected osteoarthritis dataset GSE82107 from GEO database and senescence dataset from CellAge database of human senescence-associated genes based on genetic manipulations experiments plus gene expression profilin, and screened out 4 overlapping genes. The hub genes were verified in vitro and in human OA cartilage tissues by qRT-PCR. We further confirmed the function of mitogen-activated protein kinase 12 (MAPK12) and Fos proto-oncogene (FOS) in OA in vitro and in vivo by qRT-PCR, western blotting, Edu staining, immunofluorescence, SA-β-gal staining, HE, IHC, von frey test, and hot plate. Results: 1458 downregulated and 218 upregulated DEGs were determined from GSE82107, and 279 human senescence-associated genes were downloaded from CellAge database. After intersection assay, we screened out 4 overlapping genes, of which FOS, CYR61 and TNFSF15 were upregulated, MAPK12 was downregulated. The expression of MAPK12 was obviously downregulated, whereas the expression profiles of FOS, CYR61 and TNFSF15 were remarkedly upregulated in H2O2- or IL-1β-stimulated C28/I2 cells, human OA cartilage tissues, and knee cartilage of aging mice. Furthermore, both MAPK12 over-expression and FOS knock-down can promote cell proliferation and cartilage anabolism, inhibit cell senescence and cartilage catabolism, relieve joint pain in H2O2- or IL-1β-stimulated C28/I2 cells and mouse primary chondrocytes, destabilization of the medial meniscus (DMM) mice. Conclusion: This study explored that MAPK12 and FOS are involved in the occurrence and development of OA through modulating chondrocyte senescence. They might be biomarkers of OA chondrocyte senescence, and provides some evidence as subsequent possible therapeutic targets for OA. The translational potential of this article: The translation potential of this article is that we revealed MAPK12 and FOS can effectively alleviate OA by regulating chondrocyte senescence, and thus provided potential therapeutic targets for prevention or treatment of OA in the future.

Introduction: Microbial pathogens invade various human organs, including the oral cavity. Candida albicans (C.a) and Streptococcus mutans (S.m) served respectively as representative oral pathogenic fungi and bacteria to stimulate dental pulp stem cells (DPSCs) and to screen the DPSC subcluster that specifically responded to fungal infection. Methods: DPSCs were obtained from the impacted third molars of six healthy subjects. Then, cells were mixed and divided into three samples, two of which were stimulated with C.a and S.m, respectively; the third sample was exposed to cell medium only (Ctrl). Single-cell mRNA sequencing analysis of treated DPSCs was performed. Results: DPSCs were composed of four major clusters of which one, DPSC.7, exhibited unique changes compared to those of other subclusters. The DPSC.7 cell percentage of the C.a sample was twice those of the Ctrl and S.m samples. DPSC.7 cells expressed genes associated with the response to reactive oxygen species (ROS) response. DPSC.7 subgroup cells established characteristic aggregation under the stimulation of different pathogens in UMAP. The MAPK/ERK1/2 and NF-kB pathways were up-regulated, DUSP1/5/6 expressions were suppressed, FOS synthesis was activated, the immune-related pathway was induced, and the levels of cytokines, including IL-6 and CCL2, were upregulated in DPSC.7 cells when stimulated with C.a. Conclusions: Our study analyzed the cellular and molecular properties of DPSCs infected by oral fungi and bacteria with single-cell RNA sequencing. A subcluster of DPSCs responded specifically to infections with different pathogens, activating the MAPK and NF-kB pathways to induce immune responses via the ROS pathway. This suggests novel treatment strategies for fungal infections. [ABSTRACT FROM AUTHOR]

Osteoblastoma is a benign bone tumor with predominance in those < 20 years of age and rarely occurs in the maxillofacial region. The identification of FOS gene rearrangements in osteoblastomas has been reported, however, a small subset of osteoblastomas do not show FOS gene rearrangements. There are no reports discussing the relationship between age and FOS gene rearrangement in osteoblastomas. We report the case of a 66-year-old female patient with histological features of osteoblastoma in the mandible without FOS gene rearrangement. According to a review of previously reported cases of osteoblastoma, FOS gene rearrangement is significantly less common in patients > 40 years of age (P = 0.041). Osteoblastomas occurring in older adult patients may exhibit pathogeneses different from those of young patients. Further data, including the relationship between age and FOS gene rearrangement, is necessary to clarify the pathogenesis of osteoblastoma. [ABSTRACT FROM AUTHOR]

In Japan, intravenous injection of a 7 % solution of sodium bicarbonate (NaHCO 3) had been originally developed to inhibit motion sickness and then have long been used to treat vertigo. Previously, we reported that Fos-positive neurons appear in the amygdala after hypergravity stimulation in rats. In the present study, we examined whether injection of 7 % NaHCO 3 inhibits hypergravity-induced Fos expression in the neurons in the central nucleus of the amygdala in rats. Rats were exposed to 2 G hypergravity in an animal centrifuge device for 3 h. A solution of 7 % NaHCO 3 at a dose of 4 mM/kg was injected intraperitoneally before 2 G hypergraviy. Fos-positive neurons in the amygdala were stained immunohistochemically. The number of Fos-positive neurons in the central nucleus of the amygdala was significantly increased after 2 G hypergravity in rats that received no drugs or saline, compared to that in rats exposed only to the noise of the centrifuge and received 7 % NaHCO 3 solution. The number of Fos-positive neurons in the central nucleus of the amygdala after 2 G hypergravity was significantly decreased in rats that received 7 % NaHCO 3 solution, compared to that in rats that received no drugs or saline. Since Fos expression is a marker of activated neurons, the present findings suggest that hypergravity activates the amygdala and that administration of 7 % NaHCO 3 suppresses hypergravity-induced activation of the amygdala. Hypergravity disturbs spatial orientation to produce motion sickness and the amygdala is involved in fear response. Recently, Ziemann et al. suggested that fear-evoking stimuli reduce the pH in the amygdala to activate it, leading to induction of fear behavior and that administering HCO 3 − attenuates fear behavior [Cell 2009; 139: 1012–1021]. Therefore, it is possible that hypergravity reduces the pH in the amygdala to activate it, thereby inducing the fear associated with motion sickness and that administration of 7 % NaHCO 3 increases the brain pH thereby suppressing hypergravity-induced activation of the amygdala and inhibiting the fear associated with motion sickness. In patients with vertigo, 7 % NaHCO 3 therapy may increase the brain pH thereby suppressing the activation of the amygdala and inhibiting the fear associated with vertigo to elicit a beneficial clinical effect. [ABSTRACT FROM AUTHOR]

Long non-coding RNA (LncRNA) plays an important role in malignant transformation of cells. This study aimed to explore the role of Lnc-ENST00000535078 in the malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) induced by coal tar pitch extract (CTPE). The malignant transformation model of BEAS-2B cells exposed to CTPE. Cell proliferation was examined by Cell counting kit-8 (CCK-8) assay. Colony formation assay was used to assess the colony of cells. Cell migration and invasion were detected by Transwell analysis. Cell cycle progression and apoptotic status were assessed by flow cytometry. Differentially expressed genes were screened by RNA sequencing. The results showed that Lnc-ENST00000535078 expression was highest in malignantly transformed BEAS-2B cells passaged to the 30th generation. Knockdown of Lnc-ENST00000535078 inhibited the migration, invasion and anti-apoptotic abilities of malignantly transformed BEAS-2B cells. Transcriptome analysis found 608 differential genes. CCND1 and FOS genes were screened out because of their levels were positive correlation with the expression of Lnc-ENST00000535078, which were consistent with the RNA sequencing results. In conclusion, Low expression of Lnc-ENST00000535078 inhibits the migration and invasion of malignant transformed BEAS-2B cells and promotes apoptosis in these cells. Lnc-ENST00000556926 might affect the malignant transformation of cells through the regulation of CCND1 and FOS. This study may provide a potential target for intervention in CTPE-induced lung cancer. [ABSTRACT FROM AUTHOR]

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Abstract This study investigated the influence of bacterial cyclic lipopeptides (LP; surfactins, iturins, fengycins) on microbial interactions. The objective was to investigate whether the presence of bacteria inhibits fungal growth and whether this inhibition is due to the release of bacterial metabolites, particularly LP. Selected endophytic bacterial strains with known plant-growth promoting potential were cultured in the presence of Fusarium oxysporum f.sp. strigae (Fos), which was applied as model fungal organism. The extracellular metabolome of tested bacteria, with a focus on LP, was characterized, and the inhibitory effect of bacterial LP on fungal growth was investigated. The results showed that Bacillus velezensis GB03 and FZB42, as well as B. subtilis BSn5 exhibited the strongest antagonism against Fos. Paraburkholderia phytofirmans PsJN, on the other hand, tended to have a slight, though non-significant growth promotion effect. Crude LP from strains GB03 and FZB42 had the strongest inhibitory effect on Fos, with a significant inhibition of spore germination and damage of the hyphal structure. Liquid chromatography tandem mass spectrometry revealed the production of several variants of iturin, fengycin, and surfactin LP families from strains GB03, FZB42, and BSn5, with varying intensity. Using plate cultures, bacillomycin D fractions were detected in higher abundance in strains GB03, FZB42, and BSn5 in the presence of Fos. Additionally, the presence of Fos in dual plate culture triggered an increase in bacillomycin D production from the Bacillus strains. The study demonstrated the potent antagonistic effect of certain Bacillus strains (i.e., GB03, FZB42, BSn5) on Fos development. Our findings emphasize the crucial role of microbial interactions in shaping the co-existence of microbial assemblages.

This research falls within the domain of French for specific objectives (FOS). We are interested in a particular audience, in this case archivists operating in various professional sectors. We hope, through our investigation, to determine the nature of the training offered in French, for these candidate archivists who follow a university course based, on the whole, on the Arabic language, and this, in order to arrive at an analysis of their language requirements in the professional environment. We will first define their output profile by assessing the objectives and content assigned to the French module. Then, we will examine their entry profile into working life based on semi-structured interviews.

This study investigated the influence of bacterial cyclic lipopeptides (LP; surfactins, iturins, fengycins) on microbial interactions. The objective was to investigate whether the presence of bacteria inhibits fungal growth and whether this inhibition is due to the release of bacterial metabolites, particularly LP. Selected endophytic bacterial strains with known plant-growth promoting potential were cultured in the presence of Fusarium oxysporum f.sp. strigae (Fos), which was applied as model fungal organism. The extracellular metabolome of tested bacteria, with a focus on LP, was characterized, and the inhibitory effect of bacterial LP on fungal growth was investigated. The results showed that Bacillus velezensis GB03 and FZB42, as well as B. subtilis BSn5 exhibited the strongest antagonism against Fos. Paraburkholderia phytofirmans PsJN, on the other hand, tended to have a slight, though non-significant growth promotion effect. Crude LP from strains GB03 and FZB42 had the strongest inhibitory effect on Fos, with a significant inhibition of spore germination and damage of the hyphal structure. Liquid chromatography tandem mass spectrometry revealed the production of several variants of iturin, fengycin, and surfactin LP families from strains GB03, FZB42, and BSn5, with varying intensity. Using plate cultures, bacillomycin D fractions were detected in higher abundance in strains GB03, FZB42, and BSn5 in the presence of Fos. Additionally, the presence of Fos in dual plate culture triggered an increase in bacillomycin D production from the Bacillus strains. The study demonstrated the potent antagonistic effect of certain Bacillus strains (i.e., GB03, FZB42, BSn5) on Fos development. Our findings emphasize the crucial role of microbial interactions in shaping the co-existence of microbial assemblages. [ABSTRACT FROM AUTHOR]

Ischemic fasciitis is a pseudosarcomatous fibroblastic/myofibroblastic proliferation that shares several overlapping morphological features with proliferative fasciitis and proliferative myositis. Prompted by a recent study that demonstrated FOS gene rearrangements in proliferative fasciitis and proliferative myositis, suggesting that these lesions likely represent examples of "transient neoplasia," we examined a cohort of ischemic fasciitis for similar events. Nine cases of ischemic fasciitis were retrieved from our institutional archives for diagnosis verification, immunostaining for FOSB, and fluorescence in situ hybridization using validated FOS and FOSB break-apart probes. Additionally, RNAseq was performed on a subset of cases. In our cohort, eight out of nine cases of ischemic fasciitis were positive for FOSB IHC, but FISH studies were consistently negative for FOSB and FOS gene rearrangements in all cases. Additionally, RNA sequencing did not detect any gene fusions. These findings suggest that the pathogenesis of ischemic fasciitis is distinct from that of proliferative fasciitis and proliferative myositis. [ABSTRACT FROM AUTHOR]

In our previous study, intranuclear cardiac troponin I (cTnI) may function as a co‐factor of Yin Yang 1(YY1). Here, we aimed to explore the role of intranuclear cTnI in ageing hearts. Nuclear translocation of cTnI was demonstrated using Western blot and immunofluorescence. The potential nuclear localization sequences (NLSs) of cTnI were predicted by a web server and then verified in 293T cells by putative NLS‐eGFP‐GST and NLS‐mutant transfection. The ratio of Nuclear cTnI/ Total cTnI (Nu/T) decreased significantly in ageing hearts, accompanied with ATG5‐decline‐related impaired cardiac autophagy. RNA sequencing was performed in cTnI knockout hearts. The differential expressed genes (DEGs) were analysed by overlapping with YY1 ChIP‐sequencing data. cTnI gain and loss experiments in vitro determined those filtered DEGs' expression levels. A strong correlation was found between expression patterns cTnI and FOS. Using ChIP‐q‐PCR, we demonstrated that specific binding DNA sequences of cTnI were enriched in the FOS promoter −299 to −157 region. It was further verified that pcDNA3.1 (−)‐cTnI could increase the promoter activity of FOS by using luciferase report assay. At last, we found that FOS can regulate the ATG5 (autophagy‐related gene 5) gene by using a luciferase report assay. Taken together, our results indicate that decreased intranuclear cTnI in ageing hearts may cause impaired cardiac autophagy through the FOS/ATG5 pathway. [ABSTRACT FROM AUTHOR]