Search Results (14,436)

Timely classification of cardiovascular diseases is crucial to improve medical outcomes. Emerging remote patient monitoring systems help achieve this by enabling continuous monitoring of electrocardiogram signals in home environments. However, these systems struggle with unique challenges like missing genuine medical emergencies, rising energy demands, scalability challenges, handling vast medical databases, data processing delays, and safeguarding patient records. To overcome these challenges, we propose a single framework with three main phases: (a) an embedded hardware-driven K-Nearest Neighbor (KNN)-assisted real-time ECG monitoring and classification method; (b) a differentiated communication strategy (DCS) formed with a priority-based ECG data packaging framework and multi-layered security protocols; and (c) a multi-level blockchain network (MLBN) architecture armed with adaptive security mechanisms and real-time cross-chain medical data communication bridges. Simulations are conducted using the ECG signals (1000 fragments) dataset and the Ganache Ethereum development framework. The classification accuracies obtained for patient urgent categories U1 to U5 are 91.43%, 95.71%, 94.23%, 90.00%, and 91.43%, respectively. The performance evaluation results of the KNN-guided classification method, along with DCS and MLBN simulation results obtained from average gas consumption analysis, confirms reliability and viability of our framework, while also revolutionizing remote patient monitoring technology and addressing critical challenges in existing systems. Full article

Milk-derived exosomes (MDEs) are bioactive nanocarriers rich in microRNAs (miRNAs) that play critical roles in post-transcriptional regulation during neonatal development and immune adaptation. However, the dynamic changes in miRNA expression across lactation stages and their biological functions remain insufficiently explored. We hypothesized that the miRNA cargo of buffalo MDEs exhibits temporal specificity, thereby dynamically matching the immune requirements of the neonatal calves. Therefore, the present study aimed to systematically characterize the miRNA expression profiles of MDEs derived from colostrum, transitional milk, and mature milk. MDEs were isolated, purified using differential ultracentrifugation, and characterized via transmission electron microscopy, Western blotting, and nanoparticle-tracking analysis. A total of 370 miRNAs were identified in the MDEs, with 220 (59.5%) co-expressed across colostrum, transitional milk, and mature milk. Comparative analysis revealed that colostrum MDEs exhibited the greatest miRNA diversity. Expression patterns of miRNAs showed distinct stage-specific clustering as lactation progressed. Compared to mature milk, 100 differentially expressed miRNAs (DE-miRNAs) were identified in colostrum MDEs, including 39 upregulated and 61 downregulated miRNAs. Bioinformatics analyses indicated that predicted target genes were associated with transmembrane transport, immune response, cell development, and apoptosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis identified pathways involved in immune regulation, inflammation, and apoptosis. Moreover, macrophages incubated with buffalo colostrum MDEs showed upregulation of proliferation-related genes and downregulation of pro-inflammatory factors, suggesting an anti-inflammatory effect through activation of the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) signaling pathway. These findings offer new insights into miRNA profiles of buffalo MDEs across the early postpartum transition and provide a preliminary basis for exploring immunomodulatory potential of buffalo MDEs. Full article

Due to its high efficiency and safety, oocyte vitrification finds broad application in many fields of life sciences, such as clinical assisted reproduction and conservation of animal genetic resources. However, vitrification may cause cellular damage and reduce the quality of oocytes and their cumulus cells (CCs), which could be closely related to disorders in lipid metabolism. At present, the impact of vitrification upon the lipid profile of oocytes and CCs has not been systematically elucidated. In this study, we used porcine germinal vesicle cumulus–oocyte complexes (COCs) as a model to analyze their lipid characteristics after vitrification and in vitro maturation (IVM), utilizing untargeted lipid metabolomics. Our results showed that an overall count of 37 down-regulated and 8 up-regulated differential lipids was identified in the vitrified oocytes. Pathway analysis confirmed the enrichment in glycerophospholipid metabolism and fat digestion and absorption, etc. Combined with transcriptomic analysis, three enriched pathways were revealed, including the AMPK signaling pathway, metabolic pathways, and fatty acid elongation. On the other hand, a total of four down-regulated and eight up-regulated differential lipids were detected in the vitrified CCs. Pathway enrichment implicated autophagy, glycerophospholipid metabolism, etc. A joint analysis of metabolomic and transcriptomic data revealed four enrichment pathways, including cholesterol metabolism, fat digestion and absorption, regulation of lipolysis in adipocytes, and metabolic pathways. Notably, the supplementation of lysophosphatidylcholine during IVM attenuated oxidative stress, enhanced mitochondrial activity, and enhanced the viability and embryonic development of cryopreserved porcine oocytes. The results indicate that vitrification alters lipids in oocytes and CCs, and the supplementation of lipids plays a role in improving the quality of vitrified oocytes. Full article

Nephrocalcinosis, defined as the deposition of calcium salts within the renal parenchyma, represents a radiologic and pathologic endpoint shared by a broad spectrum of metabolic and monogenic disorders. Advances in genomic medicine have identified more than 30 genes involved in tubular transport, mineral and acid–base homeostasis, oxalate metabolism, mitochondrial function, ciliary signaling, and nephron development, reframing nephrocalcinosis as a heterogeneous manifestation of discrete molecular defects rather than a single disease entity. Despite this diversity, these conditions converge on common physicochemical pathways of tubular supersaturation, crystal nucleation, growth, and intrarenal retention. These processes are amplified by the intrinsic vulnerability of the renal medulla—characterized by hyperosmolality, hypoxia, and slow tubular flow—and by epithelial injury, loss of crystallization inhibitors, and impaired ciliary signaling. Distinct genotype–phenotype signatures, including age at onset, biochemical profiles, and extrarenal manifestations, provide important diagnostic clues and help differentiate major monogenic entities. The increasing availability of targeted gene panels, whole-exome sequencing, and whole-genome sequencing has substantially improved diagnostic yield, particularly in pediatric populations. Molecular diagnosis now directly informs therapeutic decision-making and long-term management, enabling a shift toward precision nephrology. This narrative review integrates genetic, mechanistic, and clinical perspectives to illustrate how molecular diagnosis reshapes the evaluation, prognosis, and treatment of nephrocalcinosis. Full article

Breast carcinoma is a major cause of cancer-related mortality among women worldwide. Identifying novel molecular targets remains essential, particularly for aggressive triple-negative breast cancer (TNBC). Leucine-rich alpha-2-glycoprotein 1 (LRG1) has been linked to tumor progression and angiogenesis, but its molecular mechanisms in breast cancer are poorly defined. We evaluated the effects of recombinant human LRG1 (rhLRG1) on cell viability and migration in MDA-MB-231 TNBC cells and performed transcriptomic profiling followed by functional enrichment analyses using GenArise, Cytoscape, and R-based tools. RhLRG1 treatment significantly increased cell viability and migration. Transcriptomic analysis revealed activation of key oncogenic cascades, including the PI3K/AKT, MAPK, and RAS signaling pathways. Hub-gene analysis identified upregulated genes involved in proliferation (NRAS, STAT5B, IGF2), angiogenesis (PGF, ANGPT2), and apoptosis (CASP8, BAD), whereas downregulated genes were associated with apoptotic resistance (BCL2, MCL1) and adhesion (LAMB1, ITGB4). Functional enrichment highlighted LRG1’s role in the bioinformatic analysis of differentially expressed genes that were obtained from microarray assays. LRG1 remodels the tumor microenvironment by promoting proliferation, angiogenesis, and apoptotic sensitivity while repressing resistance-related genes. These findings position LRG1 as a potential diagnostic biomarker and therapeutic target for advanced breast carcinoma. Full article

Epigenetic regulation plays a central role in modulating plant immune responses and interactions with beneficial microbes. In this study, we investigated the contribution of RNA-directed DNA methylation (RdDM) components—DCL3; AGO9; DCL1; and the de novo DNA methyltransferases CMT3, DRM1, and DRM2—to the interaction between Arabidopsis thaliana, Trichoderma atroviride, and foliar pathogens. We show that DCL3 and AGO9 differentially regulate basal and inducible immunity, negatively affecting resistance to the necrotrophic fungus Botrytis cinerea, while promoting defense against the hemibiotrophic bacterium Pseudomonas syringae pv. tomato DC3000. Transcriptional analyses revealed that RdDM components modulate the balance between jasmonic acid/ethylene (JA/ET) and salicylic acid (SA) signaling pathways, influencing the amplitude and coordination of defense responses. In addition, DCL3 and DCL1 appear to be required for the full expression of T. atroviride-mediated systemic resistance, whereas AGO9 and DNA methyltransferases contribute to efficient root colonization. Notably, mutants in these pathways displayed enhanced basal resistance but impaired responsiveness to beneficial microbial signals, revealing a trade-off between constitutive defense activation and inducible systemic protection. Consistent with this, alterations in RdDM components were also associated with changes in plant growth dynamics under specific conditions, supporting a role for epigenetic regulation in coordinating growth–defense trade-offs. Together, our findings support a model in which epigenetic regulation controls defense responsiveness, enabling plants to balance immune activation, growth and compatibility toward beneficial microbes. Full article

The capacity of the brain to adapt to experience has long been associated with synaptic plasticity; however, recent evidence demonstrates that experience-driven neural activity also modulates white matter organization through dynamic regulation of oligodendrocyte lineage cells and myelination. Activity-dependent myelination has emerged as a complementary form of neuroplasticity that contributes to circuit efficiency, temporal coordination, and cognitive function. This review aims to examine the neurobiological mechanisms linking cognitive stimulation and activity-dependent neuronal signaling with oligodendroglial dynamics and adaptive myelination. A narrative review of experimental and translational studies was conducted, focusing on evidence from animal models and human research exploring neuron–oligodendroglia interactions, neurotransmitter-mediated signaling, learning paradigms, physical exercise, and neuromodulatory interventions relevant to myelination and brain plasticity. Accumulating evidence indicates that cognitive stimulation, learning, and physical activity modulate neuronal firing patterns and neurotransmitter release, influencing oligodendrocyte precursor cell proliferation, differentiation, and myelin remodeling. Neurotransmitters such as glutamate, GABA, dopamine, and acetylcholine play key roles in neuron–oligodendroglia communication, largely through calcium-dependent intracellular signaling pathways. These mechanisms have been associated with experience-dependent circuit refinement across motor, cognitive, and stress-related paradigms. Rather than implying direct clinical effects, this review highlights oligodendroglial plasticity as a biologically plausible substrate through which cognitive and behavioral experiences may influence adaptive myelination and white matter integrity. Understanding these mechanisms provides a conceptual framework for future research exploring non-pharmacological approaches to modulate brain plasticity at the level of myelin. Full article

The accumulated ammonia within the recirculating aquaculture systems threaten fish health, while little is known about the influences during early fish ontogeny. Using larval and juvenile yellow catfish (Pelteobagrus fulvidraco) as a model, a comprehensive experiment exposing fish to varying total ammonia nitrogen concentrations (0, 10, 20 mg/L for larvae; 0, 25, 125 mg/L for juveniles) was conducted to evaluate the effects on gill transcriptome and microbiota along with the serotonergic regulation. First, the serotonin (5-HT) signal, which controls oxygen chemoreception and ventilation, was mainly detected in the surface of the body of the larvae, and then shifted to gill filaments of juveniles, showing a transition from cutaneous to branchial respiration. Both larval and juvenile yellow catfish exhibited reduced survival, damaged gill structure, and elevated 5-HT expression after ammonia exposure, as well as upregulated tph1b, slc6a4b, scgn and lama5 expression with the increased ammonia concentration, indicating the effects on respiratory function via serotonergic regulation. Further transcriptome analysis was conducted in juveniles to identify the differentially expressed genes (DEGs) and thus, to illustrate more detailed responses after ammonia exposure; KEGG enrichment analysis of DEGs indicated the coping strategy shifted from metabolic buffering to metabolic elimination via glutamine synthesis with the increased ammonia level. The qRT-PCR experiment also identified the increased expression of genes involved in the urea cycle—such as ass1, asl and glula—with the increased ammonia level. Considering the potential contributary role of microbiome to gill health, 16S sequencing was conducted on the gill in the control and the 125 mg/L ammonia-exposed group. Ammonia exposure at 125 mg/L induced significant variation in Simpson index and a marked decline in β diversity. Notably, the abundance of opportunistic pathogens such as Pseudomonadota increased, while the abundance of Deinococcota and Deinococcus—which were renowned for exceptional stress resistance capacity—decreased after ammonia exposure. Thus ammonia exposure disrupts the transcriptomic and microecological balance within gill mucosa, which may elevate the risk of pathogenic infection. Overall, our study provided the first evidence of serotonergic regulation on early fish respiration during ammonia exposure, and also offered new theoretical insights into the involvement of microorganisms in ammonia toxicity. Full article

Short-chain fatty acids (SCFAs) are key biomarkers of gut microbiota activity; however, routine quantification in fecal samples relies largely on chromatography, which is instrument-intensive and throughput-limited chromatography techniques. Herein, we present a rapid machine-learning-assisted electroanalysis platform for SCFAs profiling that integrates a disposable three-electrode planar gold chip with voltammetric fingerprinting and artificial neural network (ANN)-based signal decoupling. To generate orthogonal chemical information and improve the discrimination of structurally similar species, a dual pretreatment strategy combining acid-catalyzed esterification and alkaline dissociation was employed prior to electrochemical analyses. Differential pulse voltammetry (DPV) and cyclic voltammetry (CV) were employed to acquire high-dimensional fingerprints, from which current-, potential-, and area-based descriptors were extracted using a cross-information feature strategy. A hierarchical modeling framework improved total SCFAs prediction by incorporating ANN-predicted propionate and butyrate concentrations as auxiliary inputs. While linear calibration was achievable in standard mixtures, direct linear models performed poorly in real fecal matrices due to strong sample-dependent matrix interference. In contrast, the ANN captured nonlinear relationships among multifeature inputs and suppressed matrix effects. Validation against gas chromatography–mass spectrometry in an independent fecal test cohort (n = 30) demonstrated excellent agreement and low prediction errors, with mean absolute error/root mean square error values of 0.063/0.072 mM (propionic acid), 0.029/0.034 mM (butyric acid), and 0.135/0.202 mM (total SCFAs). The DPV/CV acquisition requires only minutes per sample, whereas pretreatment takes 1~3 h depending on the target route but can be performed in parallel for batch processing; thus, overall throughput is determined mainly by batch pretreatment rather than per-sample instrument time. This electrochemical–ANN workflow provides a portable, high-throughput alternative to chromatography for fecal SCFAs profiling in clinical screening and microbiome research. Full article

Jasmonate ZIM-domain (JAZ) proteins, as core negative regulatory factors of the jasmonic acid (JA) signaling pathway, play a key role in the growth and development of plants and the response to biotic and abiotic stress. In this study, 11 flax JAZ members were identified, all of which contain a ZIM domain and a Jas domain. LuJAZs comprise 3–16 exons, encoding 187–808 amino acids (aa) with molecular weights ranging from 20.24 to 88.76 kDa and isoelectric points (PI) of 5.68–9.77. They are all hydrophilic proteins located in the nucleus. These 11 LuJAZ genes are divided into five subfamilies and are unevenly distributed on chromosomes. Transcriptome and qRT-PCR analyses revealed that six LuJAZ genes, including LUSG00004384, LUSG00030782, LUSG00016742, LUSG00004390, LUSG00010997, and LUSG00029783, are significantly induced by JA. The protein–protein interaction (PPI) prediction and analysis of differential expression genes (DEGs) suggest that the MYC2 gene (LUSG00028070) may play a role in the JA-induced response. This study provides a theoretical basis for further exploring the function of the JAZ family in flax. Full article

Citrus genomes as storehouses of genetic information of immense commercial utility remain untapped for the improvement of fruit quality traits and other production-related stresses. With the rapid expansion of transcriptomic datasets, integrative meta-analysis has further aided in uncovering interspecies molecular mechanisms associated with fruit quality development. In this study, we performed a cross-project RNA-Seq meta-analysis, integrating multiple publicly available BioProjects encompassing diverse citrus species, viz., Citrus sinensis, C. reticulata, C. maxima, C. clementina, C. japonica, and C. papeda, known to dominate the morphogenetic evolution of the citrus industry. High-throughput RNA-Seq data were processed using various bioinformatics tools. A total of 15 interspecies comparisons identified 676 unique DEGs, enriched in pathways related to secondary juice yield and processing quality traits. We also established that domestication aided in metabolism, oxidative stress responses, phenylpropanoid and flavonoid biosynthesis, and hormone-mediated signaling. Multivariate analyses (PCA and heatmap visualization) highlighted distinct yet overlapping expression patterns across these citrus species. By combining differential expression, co-expression network analysis and QTL-GWAS integration, we identified 19 high-confidence candidate genes responsible for transcriptomic variation associated with measurable fruit quality traits. Genes such as LOC102612823 and LOC102607495, which co-localized with seed number QTLs on chromosome 1, represented strong candidates regulating reproductive development and seed formation, the traits that directly influence fruit texture and market acceptability. Genes linked to juice content QTLs, including LOC102611137 and LOC102612553 on chromosome 5, suggested their roles in metabolic regulations behind juice accumulation. These loci provided definitive breeding clues for enhancing the reshaping of citrus fruit transcriptomes while retaining key ancestral regulatory components. Full article

Bone marrow(BM) is the primary site of hematopoiesis, supporting the self-renewal and differentiation of hematopoietic stem cells (HSCs). Its function depends on a highly complex microenvironment composed of stromal cells, vascular networks, extracellular matrix components, and dynamic biophysical signals. Traditional two-dimensional culture systems and animal models fail to adequately recapitulate the spatial architecture and dynamic regulatory processes of the human bone marrow niche, thereby limiting in-depth investigations into hematopoietic regulatory mechanisms, disease pathogenesis, and drug-induced bone marrow toxicity. In recent years, advances in microphysiological systems (MPS) have provided novel engineering approaches for the in vitro reconstruction of the bone marrow microenvironment. This review systematically summarizes current construction strategies for bone marrow MPS, including three-dimensional self-organized bone marrow organoids and microfluidic bone marrow-on-a-chip platforms. Particular attention is given to the roles of key cellular components, biomaterial scaffolds, vascularized architectures, and dynamic perfusion systems in biomimetic bone marrow engineering. In addition, we discuss strategies for constructing more complex models, such as vascular niches, vascularized bone tissue constructs, and bone metastasis models. Bone marrow MPS more faithfully recapitulate the hematopoietic microenvironment and provide a physiologically relevant in vitro platform for hematopoietic research, disease modeling, and drug evaluation, thereby supporting future advances in precision and regenerative medicine. Full article

Dendritic cells (DCs) integrate innate immune sensing with adaptive immune priming through coordinated transcriptional programs that regulate antiviral defense, inflammatory signaling, and antigen presentation. However, the hierarchical organization and interdependence of these pathways following stimulation remain incompletely defined. Here, we performed an in silico re-analysis with full reproducibility of publicly available RNA-sequencing data (GSE108526) to characterize the temporal architecture and associations of immune transcriptional modules in human dendritic cells at 6 h and 16 h following innate immune activation. Principal component analysis revealed stimulation status as the dominant source of transcriptomic variance. Differential expression analysis confirmed robust induction of interferon-stimulated genes (ISGs) alongside modulation of inflammatory mediators and antigen presentation-associated genes. Module-level quantification showed that interferon signaling constituted the primary early transcriptional axis, whereas inflammatory cytokine programs displayed moderate induction and antigen presentation-associated genes exhibited distinct temporal dynamics. Association analysis demonstrated strong relationships between CIITA and downstream MHC class II genes, supporting coordinated antigen presentation regulation, while relationships between interferon and inflammatory modules were positive but non-proportional, indicating partial modular independence. Collectively, these findings reveal a structured yet non-uniform transcriptional organization in stimulated human dendritic cells, characterized by dominant interferon responses accompanied by context-dependent inflammatory activation and differentially associated antigen presentation programs. This integrative framework provides a reproducible systems-level approach for dissecting immune transcriptional architecture in human dendritic cell activation. Full article

Background/Objectives: Patient-derived mesenchymal stem cells (MSCs) represent a promising avenue for myocardial regeneration, yet therapeutic application remains limited by inconsistent differentiation capacity and the absence of standardized cardiogenic induction protocols. This study demonstrates a proof-of-concept for guiding patient-specific bone marrow MSCs toward a functional cardiomyocyte phenotype using paracrine signals from differentiating iPSC-derived cardiomyocytes (iPSC-CMs). Materials and Methods: MSCs were maintained in conditioned medium from a concurrent, validated iPSC-CM differentiation protocol, with evaluation via immunocytochemistry, optical mapping, and whole-cell patch-clamp recordings. Results: Differentiated MSCs acquired organized sarcomeric architecture with cross-striations and displayed spontaneous calcium oscillations with decay kinetics matching source iPSC-CMs (CaT50 ≈ 283 ms vs. 301 ms). In co-culture, MSC-derived cells exhibited synchronized calcium dynamics with iPSC-CMs, confirming functional coupling, while patch-clamp detected hallmark cardiac ion currents (INa, ICa,L, and IKv). Morphologically, MSC-CMs displayed more mature, elongated rod-like shapes. Conclusions: Although current densities indicate partial immaturity, their reproducible detection validates successful cardiomyogenic commitment. This “parallel differentiation” platform eliminates donor-specific protocol tuning, providing a streamlined, paracrine-mediated approach to generate autologous cardiomyocyte-like cells for disease modeling, pharmacological testing, and future regenerative applications. Full article

Soybean (Glycine max L.) is an important agricultural crop for human food and animal feed. Soybean yield is severely constrained by abiotic stresses such as salinity and drought, which affect large proportions of arable and irrigated lands worldwide. This necessitates the development of new soybean varieties tolerant to these stress factors. Mutation breeding is an effective approach to improve the stress tolerance of plants due to increased genetic diversity. In this study, two gamma-induced salinity and drought-tolerant soybean mutants (SM1 and SM3-1) were compared with the parental line S04-05 using GO and KEGG pathway enrichment analyses. GO enrichment analyses revealed extensive differential gene expression in the mutant lines under stress conditions, with significant enrichment of pathways related to photosynthesis, hormone signaling, carbohydrate metabolism, and flavonoid and isoflavonoid biosynthesis. Genotype-specific analyses indicated that the SM3-1 mutant exhibited a dynamic regulatory response associated with maintaining the photosynthetic apparatus and chloroplast homeostasis under stress, whereas the SM1 mutant showed an adaptation strategy based on metabolite-mediated osmotic adjustment and ROS scavenging. Compared to the parental variety S04-05, the mutants showed distinct metabolic regulation in phenylpropanoid/isoflavone metabolism, with upregulation of many isoflavone biosynthesis genes under salinity, drought, and untreated conditions, indicating a key and sustained role of this pathway in stress tolerance. Most SNPs identified in the isoflavone biosynthesis pathway consist of moderate-impact and modifier variations. These findings suggest that gamma mutagenesis and subsequent selection processes allow for the development of novel genetic variants that operate through different physiological and metabolic mechanisms but exhibit similar levels of tolerance. In this respect, the study reveals that mutation breeding is a potentially sustainable and effective breeding strategy for increasing abiotic stress tolerance in soybeans. Full article