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KEY MESSAGE: Cd induces photosynthetic inhibition and oxidative stress damage in H. citrina, which mobilizes the antioxidant system and regulates the expression of corresponding genes to adapt to Cd and Pb stress. Cd and Pb are heavy metals that cause severe pollution and are highly hazardous to organisms. Physiological measurements and transcriptomic analysis were combined to investigate the effect of 5 mM Cd or Pb on Hemerocallis citrina Baroni. Cd significantly inhibited H. citrina growth, while Pb had a minimal impact. Both Cd and Pb suppressed the expression levels of key chlorophyll synthesis genes, resulting in decreased chlorophyll content. At the same time, Cd accelerated chlorophyll degradation. It reduced the maximum photochemical efficiency of photosystem (PS) II, damaging the oxygen-evolving complex and leading to thylakoid dissociation. In contrast, no such phenomena were observed under Pb stress. Cd also inhibited the Calvin cycle by down-regulating the expression of Rubisco and SBPase genes, ultimately disrupting the photosynthetic process. Cd impacted the light reaction processes by damaging the antenna proteins, PS II and PS I activities, and electron transfer rate, while the impact of Pb was weaker. Cd significantly increased reactive oxygen species and malondialdehyde accumulation, and inhibited the activities of antioxidant enzymes and the expression levels of the corresponding genes. However, H. citrina adapted to Pb stress by the recruitment of antioxidant enzymes and the up-regulation of their corresponding genes. In summary, Cd and Pb inhibited chlorophyll synthesis and hindered the light capture and electron transfer processes, with Cd exerting great toxicity than Pb. These results elucidate the physiological and molecular mechanisms by which H. citrina responds to Cd and Pb stress and provide a solid basis for the potential utilization of H. citrina in the greening of heavy metal-polluted lands.

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With the growing dependence on lithium-ion batteries, there is an urgent need to understand the potential developmental toxicity of LiPF6, a key component of these batteries. Although lithium's toxicity is well-established, the biological toxicity of LiPF6 has been minimally explored. This study leverages the zebrafish model to investigate the developmental impact of LiPF6 exposure. We observed morphological abnormalities, reduced spontaneous movement, and decreased hatching and swim bladder inflation rates in zebrafish embryos, effects that intensified with higher LiPF6 concentrations. Whole-mount in situ hybridization demonstrated that the specific expression of the swim bladder outer mesothelium marker anxa5b was suppressed in the swim bladder region under LiPF6 exposure. Transcriptomic analysis disclosed an upregulation of apoptosis-related gene sets. Acridine orange staining further supported significant induction of apoptosis. These findings underscore the environmental and health risks of LiPF6 exposure and highlight the necessity for improved waste management strategies for lithium-ion batteries.

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Introduction: This study introduces the Supervised Magnitude-Altitude Scoring (SMAS) methodology, a novel machine learning-based approach for analyzing gene expression data from non-human primates (NHPs) infected with Ebola virus (EBOV). By focusing on host-pathogen interactions, this research aims to enhance the understanding and identification of critical biomarkers for Ebola infection. Methods: We utilized a comprehensive dataset of NanoString gene expression profiles from Ebola-infected NHPs. The SMAS system combines gene selection based on both statistical significance and expression changes. Employing linear classifiers such as logistic regression, the method facilitates precise differentiation between RT-qPCR positive and negative NHP samples. Results: The application of SMAS led to the identification of IFI6 and IFI27 as key biomarkers, which demonstrated perfect predictive performance with 100% accuracy and optimal Area Under the Curve (AUC) metrics in classifying various stages of Ebola infection. Additionally, genes including MX1, OAS1, and ISG15 were significantly upregulated, underscoring their vital roles in the immune response to EBOV. Discussion: Gene Ontology (GO) analysis further elucidated the involvement of these genes in critical biological processes and immune response pathways, reinforcing their significance in Ebola pathogenesis. Our findings highlight the efficacy of the SMAS methodology in revealing complex genetic interactions and response mechanisms, which are essential for advancing the development of diagnostic tools and therapeutic strategies. Conclusion: This study provides valuable insights into EBOV pathogenesis, demonstrating the potential of SMAS to enhance the precision of diagnostics and interventions for Ebola and other viral infections.

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Background: Systemic Lupus Erythematosus (SLE) is acknowledged for its significant influence on systemic health. This study sought to explore potential crosstalk genes, pathways, and immune cells in the relationship between SLE and moyamoya disease (MMD). Methods: We obtained data on SLE and MMD from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify common genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these shared genes. Hub genes were further selected through the least absolute shrinkage and selection operator (LASSO) regression, and a receiver operating characteristic (ROC) curve was generated based on the results of this selection. Finally, single-sample Gene Set Enrichment Analysis (ssGSEA) was utilized to assess the infiltration levels of 28 immune cells in the expression profile and their association with the identified hub genes. Results: By intersecting the important module genes from WGCNA with the DEGs, the study highlighted CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P as key crosstalk genes linking SLE and MMD. GO analysis indicated that these shared genes were predominantly enriched in immune system process and immune response. LASSO analysis identified MPZL3 as the optimal shared diagnostic biomarkers for both SLE and MMD. Additionally, the analysis of immune cell infiltration revealed the significant involvement of activation of T and monocytes cells in the pathogenesis of SLE and MMD. Conclusion: This study is pioneering in its use of bioinformatics tools to explore the close genetic relationship between MMD and SLE. The genes CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P have been identified as key crosstalk genes that connect MMD and SLE. Activation of T and monocytes cells-mediated immune responses are proposed to play a significant role in the association between MMD and SLE.

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As Bacillus cereus endospores exist in various vegetables grown in soil, the possibility of contamination in food products with high salt concentrations cannot be ignored. Recent studies revealed that harsh conditions affect the resistance of bacteria; thus, we investigated the developmental aspect of heat resistance of B. cereus after sporulation with high NaCl concentration. RNA sequencing was conducted for transcriptomic changes when B. cereus endospores formed at high salinity, and membrane fluidity and hydrophobicity were measured to verify the transcriptomic analysis. Our data showed that increasing NaCl concentration in sporulation media led to a decrease in heat resistance. Also, endospore hydrophobicity, membrane fluidity, and endospore density decreased with sporulation at higher NaCl concentrations. When the transcript changes of B. cereus sporulated at NaCl concentrations of 0.5 and 7% were analyzed by transcriptome analysis, it was confirmed that the NaCl 7% endospores had significantly lower expression levels (FDR<0.05) of genes related to sporulation stages 3 and 4, which led to a decrease in expression of spore-related genes such as coat proteins and small acid-soluble proteins. Our findings indicated that high NaCl concentrations inhibited sporulation stages 3 and 4, thereby preventing proper cell maturation in the forespores and adequate formation of the coat protein and cortex. This inhibition led to decreased endospore density and hydrophobicity, ultimately resulting in reduced heat resistance.resistanceWe expect that this study will be utilized as a baseline for further studies and enhance sterilization strategies.

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Benzothiadiazole (BTH) regulates grape development, ripening, volatiles, and phenolics. This study used metabolomics and transcriptomics to understand how exogenous BTH affects Chardonnay grapes' maturation and synthesis of isoprenoids. A 0.37 mM BTH solution was sprayed during the swelling and veraison stages, and then the ripe grapes were analyzed. Our results show that BTH application significantly increased levels of important isoprenoids such as free terpinen-4-ol, bound linalool, and 8'-apo-ß-carotenal. Additionally, BTH was found to modulate several signaling pathways, including those involved in ethylene biosynthesis, salicylic acid synthesis, the abscisic acid pathway, and sugar metabolism, by regulating the expression of genes like VvACO4, VvTAR, VvPLD, VvTIP1-1, VvSTKs, VvPK, VvSUC2, VvGST4, and VvSTS. BTH also promoted grapevine resistance by up-regulating the expression of VvHSP20, VvGOLS4, VvOLP, and VvPR-10. Furthermore, BTH affected isoprenoids biosynthesis by regulating the expression of VvTPS35 and VvMYB24. Moreover, 13 hub genes in the MEgreen module were identified as crucial for the biosynthesis of isoprenoids. BTH application during the swelling stage remarkably promoted isoprenoid biosynthesis more effectively than veraison. Our study provides insights into the molecular mechanisms underlying BTH-induced regulation of grape development and offers a promising approach for enhancing the quality and resistance of grapes.

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Acute myeloid leukaemia (AML) is a highly heterogeneous disease, which lead to various findings in transcriptomic research. This study addresses these challenges by integrating 34 datasets, including 26 control groups, 6 prognostic datasets and 2 single-cell RNA sequencing (scRNA-seq) datasets to identify 10,000 AML-related genes (ARGs). We focused on genes with low variability and high consistency and successfully discovered 191 AML signatures (ASs). Leveraging machine learning techniques, specifically the XGBoost model and our custom framework, we classified AML subtypes with both scRNA-seq and bulk RNA-seq data, complementing the ELN2022 classification approach. Our research also identified promising treatments for AML through drug repurposing, with solasonine showing potential efficacy for high-risk AML patients, supported by molecular docking and transcriptomic analyses. To enhance reproducibility and customizability, we developed CSAMLdb, a user-friendly database platform. It facilitates the reuse and personalized analysis of nearly all results obtained in this research, including single-gene prognostics, multi-gene scoring, enrichment analysis, machine learning risk assessment, drug repositioning analysis and literature abstract named entity recognition. CSAMLdb is available at http://www.csamldb.com.

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The impact of contaminants on Copepod sp. and its molecular response is least explored, despite their abundance and dominance among invertebrates in aquatic environments. In the present investigation, Dioithona rigida, a cyclopoid zooplankton, was treated with selenium nanoparticles (SeNPs) to determine the associated biochemical changes, and the chronic exposure effects were recorded using transcriptomic analysis. It was found that, SeNPs were acutely toxic with a lethal dose 50% of 140.9 mg/L. The de novo assembled transcriptome of the copepod comprised 81,814 transcripts, which underwent subsequent annotations to biological processes (23,378), cellular components (21,414), and molecular functions (31,015). Comparison of the expressed transcripts against the treated sample showed that a total of 186 transcript genes were differentially expressed among the D. rigida treatments (control and SeNPs). The significant downregulated genes are coding for DNA repair, DNA-templated DNA replication, DNA integration, oxidoreductase activity and transmembrane transport. Similarly, significant upregulations were observed in protein phosphatase binding and regulation of membrane repolarization. Understanding the impact of SeNPs on copepods is crucial not only for aquatic ecosystem health but also for human health, as these organisms play a key role in marine food webs, ultimately affecting the fish consumed by humans. By elucidating the molecular responses and potential toxicological effects of SeNPs, this study provides key insights for risk assessments and regulatory policies, ensuring the safety of seafood and protecting human health from the unintended consequences of nanoparticle pollution.

The toxicity analysis in Dioithona rigida is the first of its kind as a copepod model for analysis on dietary fixation of metal toxicity at the trophic level. Since this copepod is a major zooplankton fed by fish and crustacean larvae in marine ecosystems, the toxicity analysis on this copepod will give us more insights of the trophic-level food transfer. As far as our knowledge, this is the first study that opted to construct the de novo transcriptomic pipeline for this copepod, treated with selenium nanoparticles. The effectiveness of this work may be further extrapolated to assess the effect of other metal nanoparticles in this model organism. Although the selenium toxicity in marine ecosystem is an established sector, through our combined approach of biochemical analysis and omics approach, the solid framework and comprehensive insight of the selenium toxicity in reproductive fitness and molecular changes has been studied. This study chose to seek a reliable alternative in the sense of new copepod model and omics approach to analyse the relevant metal nanoparticle toxicity in the marine ecosystem.

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Tris (2-chloroethyl) phosphate (TCEP), a commonly used organophosphate flame retardant, has garnered considerable concern owing to its pervasive presence in the environment and its toxic effects on living organisms. The perpetuation of populations and species hinges on successful reproduction, yet research into the mechanisms underlying reproductive toxicity remains scant, particularly in aquatic species. In this work, zebrafish embryos were exposed to TCEP (0, 0.8, 4, 20, and 100 µg/L) for 120 days until sexual maturation, and multiple reproductive endpoints were investigated in male zebrafish. Our results showed that the body weight, body length, and gonadal-somatic index (GSI) were remarkably decreased in all TCEP treatment groups (except GSI in the 0.8 µg/L TCEP-treated group). Long-term exposure to TCEP led to reduced reproductive capacity of male zebrafish, as evidenced by decreased fertilization. Histological observation gave an indication of delayed testicular development and inhibited spermatogenesis under TCEP stress. The content of testosterone (T) was significantly elevated in all TCEP treatment group, whereas 17 ß-estradiol (E2) levels remained stable. Transcriptome analysis revealed a lot of downregulated genes involved in steroid hormone biosynthesis, energy metabolism, and sperm motility, which might account for the imbalance of steroid hormone levels, retarded spermatogenesis and declined fertilization success. Overall, these findings offered a thorough understanding of the mechanisms underlying the male reproductive toxicity caused by TCEP, highlight the risk of TCEP on reproductive health of fish.

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Understanding the brain's mechanisms in individuals with obesity is important for managing body weight. Prior neuroimaging studies extensively investigated alterations in brain structure and function related to body mass index (BMI). However, how the network communication among the large-scale brain networks differs across BMI is underinvestigated. This study used diffusion magnetic resonance imaging of 290 young adults to identify links between BMI and brain network mechanisms. Navigation efficiency, a measure of network routing, was calculated from the structural connectivity computed using diffusion tractography. The sensory and frontoparietal networks indicated positive associations between navigation efficiency and BMI. The neurotransmitter association analysis identified that serotonergic and dopaminergic receptors, as well as opioid and norepinephrine systems, were related to BMI-related alterations in navigation efficiency. The transcriptomic analysis found that genes associated with network routing across BMI overlapped with genes enriched in excitatory and inhibitory neurons, specifically, gene enrichments related to synaptic transmission and neuron projection. Our findings suggest a valuable insight into understanding BMI-related alterations in brain network routing mechanisms and the potential underlying cellular biology, which might be used as a foundation for BMI-based weight management.

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Reactive oxygen species (ROS) and oxidative stress accelerate cellular aging, but their impact on different tissues varies. The cornea, known for its robust antioxidant defense systems, is relatively resistant to age-related diseases like cancer. However, the precise mechanisms by which the cornea maintains ROS homeostasis during aging remain unclear. Through comparative single-cell transcriptomic analysis of the cornea and other tissues in young and old nonhuman primates, we identified that a ZNF281 coding transcriptomic program is specifically activated in cornea during aging. Further investigation revealed that ZNF281 forms a positive feedback loop with FOXO3 to sense elevated levels of ROS and mitigate their effects potentially by regulating the mitochondrial respiratory chain and superoxide dismutase (SOD) expression. Importantly, we observed that overexpression of ZNF281 in MSCs prevented cellular senescence. In summary, these findings open up possibilities for understanding tissue-specific aging and developing new therapies targeting ROS damage.

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Bioconversion of abundant lactose-replete whey permeate to value-added chemicals holds promise for valorization of this expanding food processing waste. Efficient conversion of whey permeate-borne lactose requires adroit microbial engineering to direct carbon to the desired chemical. An engineered strain of Clostridium beijerinckii NCIMB 8052 (C. beijerinckii_mgsA+mgR) that produces 87% more butanol on lactose than the control strain was assessed for global transcriptomic changes. The results revealed broadly contrasting gene expression patterns in C. beijerinckii_mgsA+mgR relative to the control strain. These were characterized by widespread decreases in the abundance of mRNAs of Fe-S proteins in C. beijerinckii_mgsA+mgR, coupled with increased differential expression of lactose uptake and catabolic genes, iron uptake genes, two-component signal transduction and motility genes, and genes involved in the biosynthesis of vitamins B5 and B12, aromatic amino acids (particularly tryptophan), arginine, and pyrimidines. Conversely, the mRNA patterns suggest that the L-aspartate-dependent de novo biosynthesis of NAD as well as biosynthesis of lysine and asparagine and metabolism of glycine and threonine were likely down-regulated. Furthermore, genes involved in cysteine and methionine biosynthesis and metabolism, including cysteine desulfurase-a central player in Fe-S cluster biosynthesis-equally showed reductions in mRNA abundance. Genes involved in biosynthesis of capsular polysaccharides and stress response also showed reduced mRNA abundance in C. beijerinckii_mgsA+mgR. The results suggest that remodeling of cellular and metabolic networks in C. beijerinckii_mgsA+mgR to counter anticipated effects of methylglyoxal production from heterologous expression of methylglyoxal synthase led to enhanced growth and butanol production in C. beijerinckii_mgsA+mgR. IMPORTANCE: Biological production of commodity chemicals from abundant waste streams such as whey permeate represents an opportunity for decarbonizing chemical production. Whey permeate remains a vastly underutilized feedstock for bioproduction purposes. Thus, enhanced understanding of the cellular and metabolic repertoires of lactose-mediated production of chemicals such as butanol promises to identify new targets that can be fine tuned in recombinant and native microbial strains to engender stronger coupling of whey permeate-borne lactose to value-added chemicals. Our results highlight new genetic targets for future engineering of C. beijerinckii for improved butanol production on lactose and ultimately in whey permeate.

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Background: Static tumor features before initiating anti-tumor treatment were insufficient to distinguish responding from non-responding tumors under the selective pressure of immuno-therapy. Herein we investigated the longitudinal dynamics of peripheral blood inflammatory indexes (dPBI) and its value in predicting major pathological response (MPR) in non-small cell lung cancer (NSCLC). Methods: A total of 147 patients with NSCLC who underwent neoadjuvant immunochemotherapy were retrospectively reviewed as training cohort, and 26 NSCLC patients from a phase II trial were included as validation cohort. Peripheral blood inflammatory indexes were collected at baseline and as posttreatment status; their dynamics were calculated as their posttreatment values minus their baseline level. Least absolute shrinkage and selection operator algorithm was utilized to screen out predictors for MPR, and a MPR score was integrated. We constructed a model incorporating this MPR score and clinical predictors for predicting MPR and evaluated its predictive capacity via the area under the curve (AUC) of the receiver operating characteristic and calibration curves. Furthermore, we sought to interpret this MPR score in the context of micro-RNA transcriptomic analysis in plasma exosomes for 12 paired samples (baseline and posttreatment) obtained from the training cohort. Results: Longitudinal dynamics of monocyte-lymphocyte ratio, platelet-to-lymphocyte ratio, platelet-to-albumin ratio, and prognostic nutritional index were screened out as significant indicators for MPR and a MPR score was integrated, which was further identified as an independent predictor of MPR. Then, we constructed a predictive model incorporating MPR score, histology, and differentiated degree, which discriminated MPR and non-MPR patients well in both the training and validation cohorts with an AUC value of 0.803 and 0.817, respectively. Furthermore, micro-RNA transcriptomic analysis revealed the association between our MPR score and immune regulation pathways. A significantly better event-free survival was seen in subpopulations with a high MPR score. Conclusion: Our findings suggested that dPBI reflected responses to neoadjuvant immuno-chemotherapy for NSCLC. The MPR score, a non-invasive biomarker integrating their dynamics, captured the miRNA transcriptomic pattern in the tumor microenvironment and distinguished MPR from non-MPR for neoadjuvant immunochemotherapy, which could support the clinical decisions on the utilization of immune checkpoint inhibitor-based treatments in NSCLC patients.

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Although most cyanobacteria grow in visible light (VL; λ = 400-700 nm), some cyanobacteria can also use far-red light (FRL; λ = 700-800 nm) for oxygenic photosynthesis by performing far-red light photoacclimation. These two types of cyanobacteria can be found in the same environment. However, how they respond to each other remains unknown. Here, we reveal that coculture stresses FRL-using Chlorogloeopsis fritschii PCC 9212 and VL-using Synechocystis sp. PCC 6803. No significant growth difference was found in Synechocystis sp. PCC 6803 between the coculture and the monoculture. Conversely, the growth of Chlorogloeopsis fritschii PCC 9212 was suppressed in VL under coculture. According to transcriptomic analysis, Chlorogloeopsis fritschii PCC 9212 in coculture shows low transcript levels of metabolic activities and high transcript levels of ion transporters, with the differences being more noticeable in VL than in FRL. The transcript levels of stress responses in coculture were likewise higher than in monoculture in Synechocystis sp. PCC 6803 under FRL. The low transcript level of metabolic activities in coculture or the inhibition of cyanobacterial growth indicates a possible negative interaction between these two cyanobacterial strains.IMPORTANCEThe interaction between two cyanobacterial species is the primary focus of this study. One species harvests visible light, while the other can harvest far-red and visible light. Prior research on cyanobacteria interaction concentrated on its interactions with algal, coral, and fungal species. Interactions between cyanobacterial species were, nevertheless, rarely discussed. Thus, we characterized the interaction between two cyanobacterial species, one capable of photosynthesis using far-red light and the other not. Through experimental and bioinformatic approaches, we demonstrate that when one cyanobacterium thrives under optimal light conditions, it stresses the remaining cyanobacterial species. We contribute to an ecological understanding of these two kinds of cyanobacteria distribution patterns. Cyanobacteria that utilize far-red light probably disperse in environments with limited visible light to avoid competition with other cyanobacteria. From a biotechnological standpoint, this study suggests that the simultaneous cultivation of two cyanobacterial species in large-scale cultivation facilities may reduce the overall biomass yield.

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BACKGROUND: Marinesco-Sjögren syndrome (MSS) is an autosomal recessive neuromuscular disorder that arises in early childhood and is characterized by congenital cataracts, myopathy associated with muscle weakness, and degeneration of Purkinje neurons leading to ataxia. About 60% of MSS patients have loss-of-function mutations in the SIL1 gene. Sil1 is an endoplasmic reticulum (ER) protein required for the release of ADP from the master chaperone Bip, which in turn will release the folded proteins. The expression of non-functional Sil1 leads to the accumulation of unfolded proteins in the ER and this triggers the unfolded protein response (UPR). A dysfunctional UPR could be a key element in the pathogenesis of MSS, although our knowledge of the molecular pathology of MSS is still incomplete. METHODS: RNA-Seq transcriptomics was analysed using the String database and the Ingenuity Pathway Analysis platform. Fluorescence confocal microscopy was used to study the remodelling of the extracellular matrix (ECM). Transmission electron microscopy (TEM) was used to reveal the morphology of the ECM in vitro and in mouse tendon. RESULTS: Our transcriptomic analysis, performed on patient-derived fibroblasts, revealed 664 differentially expressed (DE) transcripts. Enrichment analysis of DE genes confirmed that the patient fibroblasts have a membrane trafficking issue. Furthermore, this analysis indicated that the extracellular space/ECM and the cell adhesion machinery, which together account for around 300 transcripts, could be affected in MSS. Functional assays showed that patient fibroblasts have a reduced capacity of ECM remodelling, reduced motility, and slower spreading during adhesion to Petri dishes. TEM micrographs of negative-stained ECM samples from these fibroblasts show differences of filaments in terms of morphology and size. Finally, structural analysis of the myotendinous junction of the soleus muscle and surrounding regions of the Achilles tendon revealed a disorganization of collagen fibres in the mouse model of MSS (woozy). CONCLUSIONS: ECM alterations can affect the proper functioning of several organs, including those damaged in MSS such as the central nervous system, skeletal muscle, bone and lens. On this basis, we propose that aberrant ECM is a key pathological feature of MSS and may help explain most of its clinical manifestations.

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Phenylalanine ammonia lyase (PAL) is a widely studied enzyme in plant biology due to its role in connecting primary metabolism to secondary phenylpropanoid metabolism, significantly influencing plant growth, development, and stress response. Although PAL genes have been extensively studied in various plant species but their exploration in cucumber has been limited. This study successfully identified 11 CsPAL genes in Cucumis sativus (cucumber). These CsPAL genes were categorized based on their conserved sequences revealing patterns through MEME analysis and multiple sequence alignment. Interestingly, cis-elements related to stress were found in the promoter regions of CsPAL genes, indicating their involvement in responding to abiotic stress. Furthermore, these gene's promoters contained components associated with light, development and hormone responsiveness. This suggests that they may have roles in hormone developmental processes. MicroRNAs were identified as a key regulators for the CsPAL genes, playing a crucial role in modulating their expression. This discovery underscores the complex regulatory network involved in the plant's response to various stress conditions. The influence of these microRNAs further highlights the complicated mechanisms that plants use to manage stress. Gene expression patterns were analyzed using RNA-seq data. The significant upregulation of CsPAL9 during HT3h (heat stress for 3 h) and the heightened upregulation of both CsPAL9 and CsPAL7 under HT6h (heat stress for 6 h) in the transcriptome study suggest a potential role for these genes in cucumber's tolerance to heat stress. This comprehensive investigation aims to enhance our understanding of the PAL gene family's versatility, offering valuable insights for advancements in cucumber genetics.

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Cobalt (Co) and Nickel (Ni) are used nowadays in various industrial applications like lithium-ion batteries, raising concerns about their environmental release and public health threats. Both metals are potentially carcinogenic and may cause neurological and cardiovascular dysfunctions, though underlying toxicity mechanisms have to be further elucidated. This study employs untargeted transcriptomics to analyze downstream cellular effects of individual and combined Co and Ni toxicity in human liver carcinoma cells (HepG2). The results reveal a synergistic effect of Co and Ni, leading to significantly higher number of differentially expressed genes (DEGs) compared to individual exposure. There was a clear enrichment of Nrf2 regulated genes linked to pathways such as glycolysis, iron and glutathione metabolism, and sphingolipid metabolism, confirmed by targeted analysis. Co and Ni exposure alone and combined caused nuclear Nrf2 translocation, while only combined exposure significantly affects iron and glutathione metabolism, evidenced by upregulation of HMOX-1 and iron storage protein FTL. Both metals impact sphingolipid metabolism, increasing dihydroceramide levels and decreasing ceramides, sphingosine and lactosylceramides, along with diacylglycerol accumulation. By combining transcriptomics and analytical methods, this study provides valuable insights into molecular mechanisms of Co and Ni toxicity, paving the way for further understanding of metal stress.

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Purpose: Alzheimer's disease (AD) is a common neurodegenerative disease, which can lead to cognitive impairment and dementia. Since AD is tightly associated with aging and cellular senescence, objective of this study was to investigate the association between senescence-related genes and proteins (SRGs and SRPs) and the development of AD. Design: The whole study was based on transcriptomic analysis of control and AD brain tissues and Mendelian randomization (MR) analysis. Methods: For transcriptomic analysis, GSE5281 dataset from GEO database contains the transcriptomic data of human brain tissues (n = 161) from control group and AD patients. The expression of SRGs in control and AD brain tissues were compared by Student's t test. For MR analysis, the instrumental single-nucleotide polymorphisms (SNPs) associated with 110 SRPs were filtered and selected from a large genome-wide association study (GWAS) for plasma proteome. The causality between plasma levels of SRPs and AD was explored using GWAS data of AD from Lambert et al. (17,008 cases and 37,154 controls) and further validated by using data from FinnGen consortium (6,489 patients and 170,489 controls). MR estimate was performed using the inverse-variance weighted (IVW) method and the heterogeneity and pleiotropy of results were tested. Results: Transcriptomic analysis identified 36 up-regulated (including PLAUR) and 8 down-regulated SRGs in AD brain tissues. In addition, the MR results at both discovery and validation stages supported the causality between plasma levels of PLAUR (IVW-p = 3.04E-2, odds ratio [OR] = 1.15), CD55 (IVW-p = 1.56E-3, OR = 0.86), and SERPINE2 (IVW-p = 2.74E-2, OR = 0.91) and the risk of AD. Conclusion: Our findings identified that PLAUR, as an SRG, may take part in the development of AD and found that high plasma levels of PLAUR was associated with increased risk of AD, indicating that this gene was a risk factor for this disease and providing the rationale of existing drugs or new preventative and therapeutic strategies.

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Background: Benign paroxysmal positional vertigo (BPPV) is a common neurological disorder with a high recurrence rate. Type 2 diabetes mellitus (T2DM) is recognized as a risk factor for BPPV recurrence. However, the genomic association between T2DM and BPPV recurrence remains understudied. Methods: Differential gene expression analysis and weighted gene co-expression network analysis were used to identify shared genes between BPPV recurrence and T2DM. The MCC algorithm was employed to select hub genes from the protein-protein interaction network of the shared genes. The predictive efficacy of hub genes for BPPV recurrence and T2DM was assessed using ROC curve analysis. Genemania database was used to identify downstream targets of hub genes. The immune infiltration landscape of BPPV and T2DM was characterized using the CIBERSORT algorithm. Correlation analysis was performed to explore the relationship between hub genes and immune cells. The expression levels of hub genes in patient blood samples were validated using qPCR. Results: Thirteen shared genes were identified and a protein-protein interaction network was constructed for BPPV recurrence and T2DM. Subsequently, four hub genes were selected, and their expression levels effectively predicted the occurrence of BPPV recurrence and T2DM. These hub genes were highly correlated with immune cell infiltration, indicating a common mechanism underlying recurrent BPPV and T2DM. Finally, the upregulation of hub genes in patients with T2DM comorbid with BPPV recurrence was confirmed in blood samples. These hub genes may serve as predictive biomarkers for assessing the recurrence rate in BPPV patients with comorbid T2DM. Conclusion: We proposed shared gene characteristics between BPPV recurrence and T2DM, revealing an immune-mediated inflammatory regulation as a common pathway and identifying four immune-related biomarkers and potential therapeutic targets for T2DM comorbid with recurrent BPPV.

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Bone marrow-mesenchymal stromal cells (BM-MSCs) are key components of the BM niche, where they regulate hematopoietic stem progenitor cell (HSPC) homeostasis by direct contact and secreting soluble factors. BM-MSCs also protect the BM niche from excessive inflammation by releasing anti-inflammatory factors and modulating immune cell activity. Thanks to these properties, BM-MSCs were successfully employed in pre-clinical HSPC transplantation models, increasing the rate of HSPC engraftment, accelerating the hematological reconstitution, and reducing the risk of graft failure. However, their clinical use requires extensive in vitro expansion, potentially altering their biological and functional properties. In this work, we analyzed the transcriptomic profile of human BM-MSCs sorted as CD45-, CD105+, CD73+, and CD90+ cells from the BM aspirates of heathy-donors and corresponding ex-vivo expanded BM-MSCs. We found the expression of immune and inflammatory genes downregulated upon cell culture and selected the transcription factor EGR1 to restore the MSC properties. We overexpressed EGR1 in BM-MSCs and performed in vitro tests to study the functional properties of EGR1-overexpressing BM-MSCs. We concluded that EGR1 increased the MSC response to inflammatory stimuli and immune cell control and potentiated the MSC hematopoietic supportive activity in co-culture assay, suggesting that the EGR1-based reprogramming may improve the BM-MSC clinical use.