Search Results (9,975)

Mollusks, such as bivalves, face increasing threats, such as disease, in aquaculture. Exosomes, widely derived from living cells carrying diverse bioactive molecules, affect the immune response. To overcome these challenges, bivalves utilize exosomal miRNAs as critical regulators of immune responses. This study investigates the role of exosomal miRNAs in modulating immune and metabolic responses in Pinctada fucata martensii following lipopolysaccharide (LPS) stimulation. Exosomes (75–150 nm) were isolated from hemolymph and characterized. High-throughput sequencing identified 30 differentially expressed miRNAs (DEMs) and 1349 differentially expressed genes (DEGs) in LPS-treated oysters, with significant enrichment in TNF, TLR/NF-κB, and metabolic pathways. This study revealed exosomal miRNA-mediated regulation of immune genes (IκBα, TRAF6, IRAK1, and BIRC2/3) and metabolic enzymes (PCK and CYP2J), demonstrating their role in apoptosis, inflammation, and metabolic reprogramming. Network analysis highlighted miRNA–mRNA interactions, including miR-7/IκBα (TNF pathway) and miR-34_5/IRAK1 (TLR pathway). Additionally, exosomal miRNAs (miR-92_2 and novel_mir5) were found to regulate oxidative stress (SOD1) and gluconeogenesis (PCK), linking immune defense with metabolic adaptation. These findings provide novel insights into exosomal miRNA-mediated immune regulation in bivalves, revealing conserved mechanisms with potential implications for molluscan health and disease management. Full article

Background/Objectives: This study systematically investigated the expression characteristics of the ALDOA gene in skeletal muscle cells and its effects on cell proliferation, apoptosis, and differentiation. Methods: We constructed an ALDOA overexpression vector and transfected it into C2C12 cells and porcine skeletal muscle satellite cells. Results: We found that ALDOA exhibited the highest expression in the longissimus dorsi muscle and was primarily localized in the cell nucleus. Overexpression of ALDOA significantly inhibited cell proliferation, induced G0/G1 phase arrest, and downregulated the expression of proliferation-related genes such as CDK2 and Cyclin D1. Concurrently, ALDOA overexpression markedly promoted apoptosis. Regarding differentiation, although ALDOA expression was upregulated during differentiation, its overexpression significantly suppressed the expression of myogenic differentiation-related genes (such as MYOD, MYOG, MEF2C), suggesting a negative regulatory role in differentiation control. Conclusions: This study reveals the multifaceted regulatory functions of ALDOA in skeletal muscle cells, providing experimental evidence for deepening the understanding of its mechanisms in muscle development and regeneration. This study provides the first functional evidence that ALDOA acts as a multifunctional regulator in skeletal muscle cells, negatively governing cell growth and fate decisions by inhibiting proliferation, promoting apoptosis, and impeding myogenic differentiation, thereby extending its role beyond glycolysis to direct governance of cellular processes. This study reveals for the first time that ALDOA possesses dual functions in muscle cells, regulating both metabolism and transcription. Full article

Background/Objective: Larazotide acetate (LA) is a synthetic octapeptide under development as a therapeutic candidate for celiac disease, acting to reduce intestinal permeability and regulate tight junctions (TJs). Although several studies have shown barrier-protective effects, the cellular mechanisms underlying LA’s actions in the intestinal epithelium remain unclear. This study aimed to elucidate the mechanistic roles of LA in maintaining intestinal epithelial integrity during cellular injury. Methods: C2BBe1 and leaky IPEC-J2 cell monolayers were pretreated with 10 mM LA and subjected to anoxia/reoxygenation (A/R) injury. Transepithelial electrical resistance (TEER), TJ protein localization, and phosphorylation of myosin light chain-2 (MLC-2) were analyzed. In addition, RNA sequencing was conducted to identify differentially expressed genes and signaling pathways affected by LA treatment. Results: LA pretreatment significantly increased TEER and preserved TJ protein organization during A/R injury. Transcriptomic analysis revealed enrichment of genes related to barrier regulation, small GTPase signaling, protein phosphorylation, proliferation, and migration. LA pretreatment markedly reduced MLC-2 phosphorylation, likely through modulation of the ROCK pathway, consistent with RNA-seq findings. Moreover, LA enhanced cellular proliferation, validating transcriptomic predictions. Conclusions: LA exerts a protective effect on intestinal epithelial integrity by stabilizing tight junctions, reducing MLC-2 phosphorylation, and promoting epithelial proliferation. These findings highlight a novel mechanism for LA and support its therapeutic potential in treating gastrointestinal disorders associated with “leaky gut” and mucosal injury. Full article

While significant progress has been made in understanding the heterogeneity of Neural Stem Cells (NSCs), our understanding of similar heterogeneity among the more abundant transit amplifying progenitors is lagging. Our work on the neural progenitors (NPs) of the neonatal subventricular zone (SVZ) began over a decade ago, when we used antibodies to the four antigens, CD133, LeX, CD140a, and NG2 to perform Fluorescence-activated cell sorting to classify subsets of the neonatal mouse SVZ as either multi-potential (MP1, MP2, MP3, MP4 and PFMPs), glial-restricted (GRP1, GRP2, and GRP3), or neuron-astrocyte restricted (BNAP). Using RNA sequencing, we have characterized the distinctive molecular fingerprints of four SVZ neural progenitor subtypes and compared their gene expression profiles to those of the NSCs. We performed bioinformatic analyses to provide insights into each NP type’s unique interactome and the transcription factors regulating their development. Overall, we identified 1581 genes upregulated in at least one NP subset compared to the NSCs. Of these genes, 796 genes were upregulated in BNAP/GRP1 compared to NSCs; 653 in GRP2/MP3; 440 in GRP3; and 527 in PFMPs. One gene that emerged from our analysis that can be used to distinguish the NPs from the NSCs is Etv1, also known as Er81. Also notable is that the NSCs downregulated cilia formation genes as they differentiated to become multipotential progenitors. Among the NPs, both PFMP and GRP3 subtypes differentially expressed genes related to neuron and oligodendrocyte development, including Matn4, Lhfpl3 and Olig2. GRP3s uniquely expressed Etv5, a transcription factor known to promote glial cell fate specification, while PFMPs uniquely expressed Lhx6, a transcription factor that regulates interneuron specification. PFMPs also expressed transcripts for olfactory receptors. Unlike the other NPs, the GRP1 and GRP2 NPs upregulated expression of genes for proteins involved in immune function. The present work will serve as an important resource for investigators interested in further defining the transit amplifying progenitors of the mammalian SVZ. Full article

This study investigated the role of miR-144 in mitigating oxidized fish oil (OFO)-induced muscle oxidative stress and quality deterioration in Megalobrama amblycephala. The feeding trial was conducted for 5 weeks, and four experimental diets were formulated, namely NC (fresh fish oil), OF (OFO), OF + ago (OFO and miR-144 agomir), and OF + anta (OFO and miR-144 antagomir). Histological results showed that OFO significantly reduced myofiber density (from 758.00 ± 13.69 to 636.57 ± 13.44 N/mm²) and decreased the percentage of myofibers with diameters > 50 μm (from 53.45% to 38.52%). OFO intake significantly increased the content of malondialdehyde (MDA), protein carbonyl (PC), advanced oxidation protein product (AOPP), and 3-nitrotyrosine (3-NT), and significantly decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity in muscle. OFO treatment significantly up-regulated the expression of inflammatory factors (NF-κB, TNF-α, HO-1, and IL-6), significantly down-regulated NQO1. Moreover, OFO reduced muscle differentiation and maturation by down-regulating the expression of MyoG, MYHC1, and protein synthesis genes (AKT3, TOR, and S6K1), and up-regulating the expression of protein hydrolysis genes (FoxO3a, MuRF1, HSP70, Beclin-1, P62, and ATG8). Moreover, miR-144 agomir exacerbated OFO-induced muscle damage by suppressing Nrf2, whereas miR-144 antagomir mitigated these effects. Silencing miR-144 re-activates Nrf2, alleviating oxidative damage, enhancing protein deposition, and improving muscle quality. These findings suggest that targeting the miR-144/Nrf2 axis could counteract OFO-induced muscle deterioration. Full article

Grain amaranths are recalcitrant to conventional in vitro plant regeneration by organogenesis de novo or through somatic embryogenesis. Consequently, floral organogenesis by these methods, representing the culminating developmental point in angiosperms, is rarely achieved. In the present study, the manipulation of in vitro flowering was explored as part of a strategy designed to overcome grain amaranth’s regeneration recalcitrance. It led to an efficient and reproducible in vitro protocol in which half-longitudinally dissected zygotic embryos generated fully developed Amaranthus hypochondriacus (Ah) plants. The use of high-irradiance illumination with LED lamps with a 3:1 red–blue irradiance ratio was a critical factor, leading to a 70% rate of early flowering events under flowering-inhibiting long-day photoperiod conditions. Contrariwise, no flowering was induced under LED white lights. All in vitro flowering Ah plants yielded viable seeds. To understand the basic molecular mechanisms of the phenomenon observed, gene expression patterns and principal component analysis of key flowering-related genes were analyzed after cultivation in vitro for 4, 8, and 12 weeks under both lighting regimes. These coded for photoreceptors, photomorphogenetic regulators, embryogenic modulators, and flowering activators/repressors. The results highlighted the upregulation of key flowering-regulatory genes, including CONSTANS, FLOWERING LOCUS T, and LEAFY, together with the downregulation of the floral repressor TERMINAL FLOWER1. Ribosome biogenesis- and seed-development-related genes were also differentially expressed, supporting a key role in this process for protein synthesis and embryogenesis. A model is proposed to explain how this light-regulated molecular framework enables in vitro flowering and seed production in Ah plants kept under long-day photoperiods. Full article

Michelia ‘Xin’ is an evergreen rare ornamental tree species that undergoes FBD only once but blooms twice a year. However, the molecular mechanisms controlling its FBD process remain largely unknown. This study characterized the FBD process and delved into the key molecular regulatory mechanisms through transcriptomic and metabolomic analyses of developing flower buds. FBD in Michelia ‘Xin’ was characterized into five stages, including vegetative (T1), floral meristem transition (T2), tepal primordia differentiation (T3), stamen primordia differentiation (T4), and pistil primordia differentiation (T5). Analyses revealed a stage-specific metabolic and transcriptional regulation of FBD, with increasing numbers of differential metabolites and a decreasing number of DEGs from T1 to T5. Most phytohormone and transcription factor-related DEGs were highly induced from T2. The down-regulation of dormancy-associated protein homologs and CONSTANS-LIKE proteins associated with significant induction of flowering-promoting factor, CLAVATA3, trichome birefringence-like, and GRAVITROPIC IN THE LIGHT proteins was essential for the induction and reproductive organs’ development. Porphyrin biosynthesis, chlorophyll a-b binding proteins, DNA replication, flavonoid biosynthesis, and starch and sucrose metabolism were also significantly induced from T2. Key pivotal candidate genes were screened out. Our results provide fundamental resources for dissecting the molecular network regulating FBD and molecular-assisted flowering control in Michelia ‘Xin’. Full article

Metallocarboxypeptidase (MCP) is a crucial protein enzyme involved in food digestion and absorption in animals, which has a potential influence on the differentiation of the trophic niche. Considering that stomatopods have raptorial appendage-specific trophic niches, the present study screened and compared the MCP M14 gene family of three stomatopods (Lysiosquillina maculata, Odontodactylus scyllarus, and Oratosquilla oratoria) with different raptorial appendage morphologies based on full-length transcriptome information. There are 13 and 17 MCP M14 gene family members identified in L. maculata and O. scyllarus, respectively, which are classified as M14A, M14B, and M14D subfamilies. However, 15 MCP M14 family members have been identified in O. oratoria, all belonging to the M14A subfamily. The physicochemical properties, phylogenetic relationships, conserved motifs, and secondary and tertiary structures of the MCP M14 amino acid sequences were also analyzed in the present study. The results revealed that each amino acid sequence had unique physicochemical properties. Ten conserved motifs were further characterized across the MCP M14 amino acid sequences, and the type and number of motifs from the same subfamily remained highly conserved. Meanwhile, we found that most of the MCP M14 gene family members have critical residues (including Zn²⁺ binding sites [His69, Glu72, and His196], substrate-binding residues [Arg124, Arg127, and Arg145], and disulfide bond-forming residues [Cys138 and Cys161]) involved in disulfide bond formation and enzyme activity stabilization. Furthermore, the random coil is the predominant structural feature of the MCP M14 amino acid sequence. In conclusion, these results are undoubtedly valuable for exploring the evolution and regulation mechanisms of the trophic niche in stomatopods. Full article

Background/Objectives: Neurodegenerative diseases (NDs) such as Alzheimer’s (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic Lateral Sclerosis (ALS) are clinically distinct but share overlapping molecular mechanisms. Methods: To identify conserved systemic signatures, we analyzed blood RNA-Seq datasets using Weighted Gene Co-Expression Network Analysis (WGCNA), differential expression, pathway enrichment, and miRNA–mRNA network mapping. Results: Two modules, the red and turquoise, showed strong preservation across diseases. The red module was enriched for cytoskeletal and metabolic regulation, while the turquoise module involved immune, stress-response, and proteostatic pathways. Discussion: Key hub genes, such as HMGCR, ACTR2, MYD88, PTEN, EP300, and regulatory miRNAs like miR-29, miR-132, and miR-146a, formed interconnected networks reflecting shared molecular vulnerabilities. The absence of classical heat shock proteins in preserved blood modules highlights tissue-specific expression differences between blood and neural systems. Several hub genes overlap with known pharmacological targets, suggesting potential in translational relevance. Conclusions: Together, these findings reveal conserved blood-based transcriptional modules that suggest parallel central neurodegenerative processes and may support future biomarker development and possible therapeutic exploration. Full article

Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disorder characterized by progressive demyelination and axonal degeneration within the central nervous system, driven by complex genomic and epigenomic dysregulation. Its pathogenesis involves aberrant DNA methylation patterns at CpG islands of numbers of genes like OLIG1 and OLIG2 disrupting protein expression at myelin with compromised oligodendrocyte differentiation. Furthermore, histone modifications, particularly H3K4me3 and H3K27ac, alter the promoter regions of genes responsible for myelination, affecting myelin synthesis. MS exhibits chromosomal instability and copy number variations in immune-regulatory gene loci, contributing to the elevated expression of genes for pro-inflammatory cytokines (TNF-α, IL-6) and reductions in anti-inflammatory molecules (IL-10, TGF-β1). Vitamin D deficiency correlates with compromised immune regulation through hypermethylation and reduced chromatin accessibility of vitamin D receptor (VDR) dysfunction and is reported to be associated with dopaminergic neuronal loss. Vitamin D supplementation demonstrates therapeutic potential through binding with VDR, which facilitates nuclear translocation and subsequent transcriptional activation of target genes via vitamin D response elements (VDREs), resulting in suppression of NF-κB signalling, enhancement of regulatory T-cell (T_reg) responses due to upregulation of specific genes like FOXP3, downregulation of pro-inflammatory pathways, and potential restoration of the chromatin accessibility of oligodendrocyte-specific gene promoters, which normalizes oligodendrocyte activity. Identification of differentially methylated regions (DMRs) and differentially expressed genes (DEGs) that are in proximity to VDR-mediated gene regulation supports vitamin D supplementation as a promising, economically viable, and sustainable therapeutic strategy for MS. This systematic review integrates clinical evidence and eventual bioinformatical meta-analyses that reference transcriptome and methylome profiling and identify prospective molecular targets that represent potential genetic and epigenetic biomarkers for personalized therapeutic intervention. Full article

Background: The Tibetan Plateau, which is known for its high elevation and low oxygen levels, presents a challenging environment for its inhabitants. To adapt to these hypoxic conditions, species of Schizothoracine, a subfamily of Cyprinidae, have developed unique physiological mechanisms and functions. Transforming growth factor-β (TGF-β) is a multifunctional cytokine involved in the regulation of cell growth, differentiation, apoptosis, and the cellular immune response. However, its specific role in adaptation to hypoxia remains poorly understood. Methods: In this study, we aimed to characterize the TGF-β1 gene in Gymnocypris dobula (Gd) and Schizothorax prenanti (Sp) and to test whether TGF-β1 contributes to hypoxia adaptation in plateau Schizothoracine fish. The predicted protein for Gd-TGF-β1 contains several primary domains, including cwf21 (cdc5 protein 21), GYF (Glycine-Tyrosine-Phenylalanine), FN1 (Fibronectin 1), a conservative domain, and a signal peptide. Results: The results of tissue distribution revealed that the mRNA level of TGF-β1 in brain, heart, muscle, skin, gills, and spleen—which are key tissues involved in oxygen sensing, transport, and physiological adaptation to hypoxic environments—was significantly lower in G. dobula than that in S. prenanti. Western blotting analysis revealed that the expression of activated TGF-β1 in G. dobula was significantly higher than that in S. prenanti. To investigate whether TGF-β1 in G. dobula possesses hypoxic adaptive features, Gd-TGF-β1 and Sp-TGF-β1 were cloned into an expression vector and transfected into 293-T cells, which are widely used due to their ease of culture, high transfectability, and well-characterized properties. We found that the survival rate of cells transfected with Gd-TGF-β1 was significantly higher than that of cells transfected with Sp-TGF-β1 after hypoxia treatment. Conclusions: These findings suggest that G. dobula may promote hypoxic adaptation through the activation and increased expression of TGF-β1. Changes in TGF-β1 expression may play a role in the adaptation of G. dobula to hypoxic conditions. Full article

Mealybugs are high-priority quarantine pests in fresh-produce trade due to cryptic habits, broad host ranges, and market-access risks. Phytosanitary irradiation (PI) provides a non-residual, process-controlled option that is increasingly integrated with modified-atmosphere (MA/MAP) logistics. Because molecular oxygen enhances indirect radiation damage (oxygen enhancement ratio, OER), oxygen limitation may modulate PI outcomes in mealybugs. The Jack Beardsley mealybug (Pseudococcus jackbeardsleyi) has an IPPC-adopted PI treatment of 166 Gy (ISPM 28, PT 45). We exposed adult females to 166 Gy under air and 1% O₂ and generated whole-transcriptome profiles across treatments. Differentially expressed genes and co-differentially expressed genes (co-DEGs) were integrated with protein–protein interaction (PPI) and regulatory networks, and ten hubs were validated by reverse transcription quantitative PCR (RT-qPCR). Hypoxia attenuated irradiation-induced transcriptional disruption. Expression programs shifted toward transport, redox buffering, and immune readiness, while morphogen signaling (Wnt, Hedgehog, BMP) was coherently suppressed; hubs including wg, hh, dpp, and ptc showed stronger down-regulation under hypoxia + irradiation than under irradiation alone. Despite these molecular differences, confirmatory bioassays at 166 Gy under both atmospheres (air and 1% O₂) achieved complete control. These results clarify how oxygen limitation modulates PI responses in a quarantine mealybug while confirming the operational efficacy of the prescribed 166 Gy dose. Practically, they support the current international standard and highlight the value of documenting oxygen atmospheres and managing dose margins when PI is applied within MA/MAP supply chains. Full article

In this study, the differences in gene expression of Stropharia rugosoannulata at different treatment times under high temperature and drought stress were analyzed by transcriptomics. Here, a total of 74,571 transcripts and 16,233 unigenes were identified, with an average assembly length of 3002 bp. A total of 10,248 differentially expressed genes (DEGs) were identified. DEG analysis indicated that the numbers of DEGs under high-temperature stress for 1 d, 2 d, and 3 d were 798, 851, and 1484, respectively. These DEGs were involved in 96 GO functional categories and 69 KEGG metabolic pathways. Meanwhile, the numbers of DEGs under drought stress for 3 d, 6 d, and 9 d were 421, 1072, and 2880, respectively. These DEGs were involved in 108 GO functional categories and 78 KEGG metabolic pathways. Further analysis of the metabolic pathway (ko04011) commonly enriched by DEGs identified 15 candidate genes responding to high-temperature or drought stress. Eight candidate genes were randomly selected for qRT-PCR verification, and the qRT-PCR results were basically consistent with the transcriptome datasets. These findings provide critical candidate genes for understanding the molecular regulation mechanism of S. rugosoannulata in response to high temperature and drought stress and have important reference value for its stress resistance breeding. Full article

Studies have shown that the iron concentration in the peritoneal fluid of women is associated with the severity of endometriosis. Therefore, investigation of iron metabolism-related genes (IM-RGs) in endometriosis holds significant implications for both prevention and therapeutic strategies in affected patients. Differentially expressed IM-RGs (DEIM-RGs) were identified by intersecting IM-RGs with differentially expressed genes derived from GSE86534. Mendelian randomization analysis was employed to determine DEIM-RGs causally associated with endometriosis, with subsequent verification through sensitivity analyses and the Steiger test. Biomarkers associated with IM-RGs in endometriosis were validated using expression data from GSE86534 and GSE105764. Functional annotation, regulatory network construction, and immunological profiling were conducted for these biomarkers. Single-cell RNA sequencing (scRNA-seq) (GSE213216) was utilized to identify distinctively expressed cellular subsets between endometriosis and controls. Experimental validation of biomarker expression was performed via reverse transcription–quantitative polymerase chain reaction (RT-qPCR). BMP6 and SLC48A1, biomarkers indicative of cellular BMP response, were influenced by a medicus variant mutation that inactivated PINK1 in complex I, concurrently enriched by both biomarkers. The lncRNA NEAT1 regulated BMP6 through hsa-mir-22-3p and hsa-mir-124-3p, while SLC48A1 was modulated by hsa-mir-423-5p, hsa-mir-19a-3p, and hsa-mir-19b-3p. Immune profiling revealed a negative correlation between BMP6 and monocytes, whereas SLC48A1 displayed a positive correlation with activated natural killer cells. scRNA-seq analysis identified macrophages and stromal stem cells as pivotal cellular components in endometriosis, exhibiting altered self-communication networks. RT-qPCR confirmed elevated expression of BMP6 and SLC48A1 in endometriosis samples relative to controls. Both BMP6 and SLC48A1 were consistently overexpressed in endometriosis, reinforcing their potential as biomarkers. Moreover, macrophages and stromal stem cells were delineated as key contributors. These findings provide novel insights into therapeutic and preventive approaches for patients with endometriosis. Full article

Congenital hearing loss, frequently resulting from defective hair cells, remains poorly understood due to the incomplete identification of key pathogenic genes. Oncomodulin (OCM) is a kind of calcium-binding protein (CaBP) that regulates diverse cellular processes and is thought to play crucial roles in auditory function. In teleost fish, parvalbumin 8 (pvalb8) and parvalbumin 9 (pvalb9) belong to the oncomodulin lineage and are highly expressed in hair cells. In this study, we first reported the oncomodulin lineage function in fish and identified pvalb8 as an essential regulator of hair cell development. Single-cell RNA sequencing (scRNA-seq) and whole-mount in situ hybridization (WISH) revealed that pvalb8 is highly and specifically expressed in supporting cells and hair cells. Functional loss of pvalb8, achieved via CRISPR/Cas9 knockout or morpholino knockdown, resulted in reduced neuromast size and a significant decrease in neuromast hair cell number, leading to auditory behavioral deficits. In addition, pvalb9 mutants exhibited hair cell defects similar to those observed in pvalb8 mutants, including a significant reduction in hair cell number. Moreover, pvalb8 loss strongly inhibited the proliferation of supporting cells, which likely accounts for the reduced number of differentiated hair cells. The expression levels of Wnt target genes, axin2, ccnd1, and myca, were all significantly reduced in pvalb8 mutants compared to control zebrafish, while activation of the Wnt signaling pathway rescued the hair cell loss observed in pvalb8 mutants, indicating that pvalb8 promotes hair cell development via Wnt-dependent proliferative signaling. These findings highlight pvalb8 as a critical factor in the regulation of auditory hair cell formation and function in zebrafish, offering new insights into the role of oncomodulin lineage in sensory cell development. Full article