Bacterial extracellular vesicles (BEVs) are increasingly proposed as materials for skin-directed cosmetics, yet rapid adoption of "exosome" terminology has outpaced clarity on their origin, composition, and manufacturing quality. This review argues that the value of BEVs depends on scientific discipline rather than marketing appeal, and that they are promising because they are biologically potent, not because they are intrinsically benign. We retain BEVs as the scientific umbrella term for vesicles released by bacteria and we propose the term microbiome-derived vesicles (MDVs) as the consumer-facing designation for qualified commensal BEVs - a surface term that avoids the difficulty of "bacterial" while its definition preserves bacterial provenance. We develop a three-axis framework for BEV identity that integrates compositional analysis, producer-strain genomics, and functional or safety profiling, and we position whole-genome sequencing (WGS) as decisive for source qualification and mechanistic interpretation but insufficient to prove the efficacy of a purified preparation. Building on this framework, we summarize isolation, purification, and analytical characterization requirements; interpret current skin-efficacy evidence in light of its methodological limits; and discuss formulation, cosmetic application, regulatory positioning, and manufacturable quality. We conclude that transparent bacterial provenance, reproducible preparation, and evidence proportionate to the claims made are prerequisites for evaluating commensal BEVs, described for skin applications as MDVs, as a scientifically defined cosmetic platform.
Roundabout guidance receptor 1 (ROBO1) is critical for various processes essential to mammalian development. However, its role in postnatal development and growth remains poorly understood, primarily due to perinatal lethality in knockout models. Robo1 knockout mice on a mixed B6/129S genetic background survive into adulthood and exhibit previously unreported abnormalities across multiple organs. These mice display stunted growth and organ-specific defects, including enlarged lung alveoli, premature hair graying, and diminished subcutaneous fat. Notably, these mice have a reduced lifespan. At 23 days of age, corresponding to the beginning of early puberty in mice, Robo1 knockout mice show significantly reduced plasma levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), paralleling decreased expression in the pituitary gland and liver, respectively, compared to wild-type littermates. These findings suggest that ROBO1 contributes to the postnatal development and functional maintenance of multiple organs, with associated modulation of the GH/IGF-1 axis, potentially influencing survival. Further studies with larger cohorts are warranted to elucidate the broader implications of ROBO1 deficiency, particularly in relation to human developmental disorders such as growth hormone deficiencies. Germline loss of ROBO1 results in stunted postnatal growth and reduced survival in mice. ROBO1-deficient mice undergo aberrant development of various organs, including pituitary gland, skin, and lungs. ROBO1 loss impairs the GH/IGF-1 axis during early puberty in mice.
Climate change poses a growing threat to chickpea production through abiotic stresses such as drought, heat, and salinity. Understanding the molecular stress response of chickpea is critical for improving resilience and minimizing yield loss. To identify robust, stress-responsive differentially expressed genes (DEGs) in chickpea under abiotic stress (drought, salt, and salinity) by comparing three complementary large-scale RNA-seq data analytical approaches. This study employed three complementary approaches, traditional meta-analysis, conventional statistical testing, and unsupervised machine learning, on publicly available chickpea RNA-seq data to identify robust differentially expressed genes (DEGs) under drought, salt, and salinity stress. Available RNA-seq datasets were integrated regardless of variety, tissue type, or geographical origin. The HDBSCAN clustering algorithm was optimized through distance metric evaluation and grid search hyperparameter tuning, with Euclidean distance optimal for drought and salinity and Manhattan distance for salt stress. Standard deviation-based feature engineering on the top 3,000 most variable genes yielded the most stress-specific DEGs, with high fold enrichments for cytochrome P450, phenylpropanoid biosynthesis, and heme binding under drought. For salt and salinity stress, limited sample availability constrained the feature space, reducing HDBSCAN clustering resolution and DEG specificity demonstrating that ML performance scales markedly with sample size and feature richness, where DESeq2 showed comparatively greater robustness. For the drought dataset spanning 11 bioprojects, Limma-voom and DESeq2 with bioproject correction both returned non-specific housekeeping enrichment, in direct contrast to the stress-specific signal recovered by HDBSCAN, empirically demonstrating the superior biological specificity of unsupervised ML-based outlier detection in heterogeneous multi-bioproject data. Compared to HN-score meta-analysis, HDBSCAN demonstrated superior stress specificity by leveraging complex high-dimensional expression patterns, offering a powerful and scalable strategy for stress-responsive gene identification in chickpea and other crops.
Citrus is the most widely cultivated fruit crop with the highest yield worldwide, and postharvest losses caused by Penicillium digitatum account for 90
Breast cancer is a biologically heterogeneous disease, and reliable non-invasive biomarkers are needed to improve early detection and clinical risk stratification. MicroRNAs (miRNAs) represent promising diagnostic candidates due to their regulatory roles in tumor-associated gene expression. In this study, an integrative analysis of miRNA and mRNA expression profiles was performed using paired tumor and normal samples from the TCGA-BRCA cohort to identify diagnostically relevant miRNAs. Differential expression analysis and receiver operating characteristic (ROC) curve analysis were used to identify miRNAs with high discriminatory capacity. Priority was given to candidates showing strong inverse correlation with predicted target genes. A logistic regression model was developed for internal validation using a held-out test set, and exploratory clinical serum analysis was conducted using qRT-PCR on serum samples from breast cancer patients and healthy controls. Multiple upregulated miRNAs with strong discriminatory capacity (AUC values > 0.90) were identified. Among these, hsa-miR-200a was prioritized based on consistently high diagnostic accuracy and a strong inverse correlation with its predicted target gene, TNS1. hsa-miR-200a expression was elevated across pathological stages and molecular subtypes, whereas TNS1 expression was progressively reduced. The logistic regression model achieved an accuracy of 92.9
The mutton snapper (Lutjanus analis) is a reef fish commonly found in tropical waters of the Western Atlantic Ocean. Genomic studies of this species are needed to support conservation efforts and breeding programs. Here, we report the development of a chromosome-scale reference assembly for the mutton snapper and conduct an initial comparative genomic analysis with other lutjanids. The genome of one mutton snapper specimen was sequenced using PAC-Bio HiFi long reads and Illumina short reads. Contigs and scaffolds were assembled in the Flye pipeline and anchored using Hi-C proximity guided assembly. Gene prediction and functional annotations were obtained in AUGUSTUS and eggNOG-mapper, respectively. The mutton snapper genome was compared to those of other lutjanids to infer gene family evolution and chromosome synteny conservation. Assembly and polishing yielded 946 contigs and 926 scaffolds (N50 of 3.16 Mb, complete BUSCO score 98.1
Microalgae rapidly adjust their chloroplast physiology in response to environmental stress, and these adaptive responses are closely associated with cellular fitness and metabolic performance. However, conventional assessments of stress adaptation primarily rely on growth characteristics, pigment accumulation, or physiological measurements, which often require extended cultivation periods and may not capture early molecular responses. In this study, we introduce a digital PCR (dPCR)-based platform for rapid assessment of chloroplast stress adaptation in microalgae. The platform quantifies the chloroplast-to-nuclear genome copy number ratio (C/N ratio) using multiplex dPCR and utilizes this metric as a molecular indicator of chloroplast acclimation. As a proof-of-concept, the assay was applied to the halotolerant microalga Dunaliella salina cultivated under different salinity stress conditions. Distinct temporal changes in the C/N ratio were observed across salinity treatments, indicating dynamic chloroplast genome remodeling during stress adaptation. The assay enabled sensitive detection of chloroplast responses at early cultivation stages, prior to the appearance of clear phenotypic differences. These findings demonstrate that chloroplast-to-nuclear genome quantification by dPCR provides a rapid and reproducible approach for monitoring chloroplast stress adaptation in microalgae. The proposed platform offers a practical molecular tool for strain evaluation, cultivation optimization, and stress-response studies, and may support future applications in microalgal biotechnology and industrial production systems.
Soybean [Glycine max (L.) Merrill] is one of the most widely cultivated crops worldwide. Its seeds contain about 40
Diabetic nephropathy (DN), a major diabetic microvascular complication, is the primary cause of end-stage renal disease worldwide. It is characterized by mesangial cell fibrosis and chronic inflammation, which current treatments cannot completely reverse. Baicalein, a major flavonoid from Scutellaria baicalensis Georgi, has anti-inflammatory and antifibrotic activities, but its role and mechanism in high glucose (HG)-induced mesangial cell injury (a key DN feature) remain unclear. This study investigated baicalein’s effects on rat glomerular mesangial cells (HBZY-1) and validated key findings in human primary glomerular mesangial cells. CCK-8 assay identified 10–20 μM as baicalein’s non-cytotoxic range (cell viability ≥ 90
BackgroundIn Xenopus laevis, multiciliated cells (MCCs) in epidermis produce coordinated motile cilia to promote fluid flow across epithelial surfaces. In a previous study, it has been reported that Bmp signaling negatively regulates the multiciliated cell formation. However, Bmp signaling is required for the early ectodermal patterning and epidermal specification.ObjectiveIn the present study, the requirement of Bmp signaling was examined in ectoderm specification including multiciliogenesis of epidermis. Inhibition of Bmp signaling using a dominant-negative Bmp receptor (Dnbr) decreased MCC formation both in animal cap explants and whole embryos.MethodsDifferentially expressed MCC-associated transcripts were confirmed by transcriptome and RT-qPCR analysis of Bmp-inhibited and control animal cap explants. The promoters of multicilia-associated genes including mcidas, foxj1, deup1 and ccno were cloned to examine how Bmp signaling regulated MCC gene expression.ResultsDnbr-injected embryos consistently showed the reduced promoter activity. However, a direct target gene of Bmp signaling ventx1.1 restored MCC gene expression and promoter activity as well as epidermal marker expression in Dnbr-injected embryos.ConclusionTogether, the results support a model in which early BMP/Ventx1.1 axis positively modulates epidermal multiciliogenesis at least in part by establishing epidermal competence through ventx1.1 associated transcriptional programs.
Pulmonary arterial hypertension (PAH) is a hemodynamic disorder that can progress to right heart failure and result in death. This study investigated the molecular mechanisms underlying the onset and progression of PAH to identify potential therapeutic targets. Peripheral blood samples from PAH patients were analyzed to assess serum levels of DKK1 and CKAP4, as well as NF-κB pathway activation. Supernatants from hypoxia-treated pulmonary artery endothelial cells (PAECs), plasmid-transfected cells, and SC75741-treated cells were used to modulate pulmonary artery smooth muscle cells (PASMCs). RT-qPCR, Western blot, and ELISA were employed to quantify DKK1 and CKAP4 expression and evaluate NF-κB pathway activation in PASMCs. EdU staining and CCK-8 viability assay were performed to assess cell proliferation, while DCFH-DA staining and ELISA were used to measure ROS, SOD, and MDA levels. DKK1 and CKAP4 expression were positively correlated, and both were upregulated with increasing pulmonary artery systolic pressure (PASP) in PAH patients. The supernatant from hypoxia-exposed PAECs induced NF-κB pathway activation, cell proliferation, and oxidative stress in PASMCs, effects that were inhibited by siDKK1, siCKAP4, and SC75741. Hypoxia stimulated PAECs to secrete DKK1, which in turn upregulated CKAP4 expression and activated the NF-κB pathway in PASMCs, promoting cell proliferation and oxidative stress.
Adenophora taquetii is an endemic species of Jeju Island, Republic of Korea, and has medicinal and ornamental value. However, genomic resources for this species, particularly the chloroplast genome data, remain limited. We sequenced, assembled, and characterized the complete chloroplast genome of A. taquetii and compared it with those of other Adenophora species. Whole-genome sequencing data were generated using an Illumina HiSeq platform. Raw reads were preprocessed using Trimmomatic, mapped with BWA-MEM, and used for chloroplast genome assembly with NOVOPlasty, Fast-Plast, and GetOrganelle. Genome annotation was performed using GeSeq, comparative analysis was conducted using mVISTA in LAGAN mode, simple sequence repeats (SSRs) were identified using MISA, single-nucleotide polymorphism (SNP) matrices were generated using SAMtools, and phylogenetic analysis was performed using maximum likelihood and Bayesian inference based on aligned complete chloroplast genome sequences. The chloroplast genome of A. taquetii was 161,772 bp long and exhibited the typical quadripartite structure of angiosperm chloroplast genomes, comprising a large single-copy (LSC) region (113,770 bp), a small single-copy (SSC) region (27,738 bp), and two inverted repeat (IR) regions (10,132 bp each). Comparative analysis revealed substantial variation in chloroplast genome size among related species, ranging from 157,851 bp in A. stricta to 218,673 bp in A. verticillata. In total, 143 genes were annotated in A. taquetii, including 96 protein-coding, 38 tRNA, and 9 rRNA genes. In addition, 25 SSRs and 1,161 SNPs were identified, and phylogenetic analysis supported a close relationship between A. taquetii and A. stricta. The complete chloroplast genome of A. taquetii provides a useful genomic resource for comparative chloroplast genomics, species identification, and phylogenetic studies within the genus Adenophora.
Diabetes mellitus (DM) is a chronic metabolic disorder that carries the risk of severe complications, such as cardiovascular disease, renal impairment, and an increased susceptibility to Alzheimer's disease. Considering these significant health implications, it is crucial to deepen our understanding of this condition. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, play a critical role in various biological processes and, when dysregulated, can contribute to the development of diseases such as diabetes mellitus. This study aimed to investigate the association between type 2 diabetes mellitus (T2DM) and specific miRNA polymorphisms (miR-125a C > T, miR-152 C > T, miR-938 G > A, and miR-491 G > A) in a Korean population. We examined the distribution of miRNA polymorphisms through genotyping in 238 T2DM patients and 343 healthy controls using polymerase chain reaction-restriction fragment length polymorphism technique. Our findings indicate that the miR-938 GA genotype and its dominant model were significantly associated with an elevated risk of T2DM. Moreover, specific combinations of genetic variations were linked to either an increased or decreased risk of developing T2DM. These results suggest that miRNA polymorphisms may influence an individual’s genetic susceptibility to T2DM and offer potential therapeutic targets and diagnostic tools.
BackgroundClear cell renal cell carcinoma (ccRCC) exhibits significant metabolic alterations. Protein succinylation, a metabolite-induced post-translational modification, plays a vital role in cellular metabolism and tumor biology.ObjectiveTo characterize the succinylation-associated transcriptional signature and its clinical relevance in ccRCC.MethodsWe developed a succinylation-associated transcriptional score based on a literature-curated 20-gene panel using the TCGA-KIRC RNA-seq dataset, with prognostic validation in two independent cohorts (E-MTAB-1980 and CPTAC). The tumor immune microenvironment was analyzed via ESTIMATE, CIBERSORT, and ssGSEA. Cellular localization of the score was investigated using single-cell and spatial transcriptomics. Functional enrichment, drug response analyses, and qPCR validation were also performed.ResultsTumor tissues demonstrated significantly reduced succinylation-associated transcriptional scores compared to normal counterparts, with higher scores correlating with improved clinical outcomes. Multivariate analyses supported the independent prognostic value of the succinylation-associated transcriptional score for overall survival in the TCGA and validation datasets. Interestingly, low-score tumors exhibited a transcriptionally "immune-hot" phenotype, characterized by enhanced immune cell infiltration and elevated immune checkpoint expression. Single-cell and spatial transcriptomic analyses suggested that tumor cells primarily contributed to the succinylation-associated transcriptional score. Functional assessments revealed that high scores were associated with oxidative phosphorylation and fatty acid metabolism, while low scores correlated with pro-tumorigenic signaling pathways. Computational drug sensitivity analysis identified exploratory associations that may inform future therapy stratification based on succinylation profiles.ConclusionThe succinylation-associated transcriptional score represents a promising biomarker candidate in ccRCC, showing associations with prognosis and key metabolic-immune features. Our study underscores the role of succinylation in ccRCC biology and provides a framework for metabolic subtyping that may inform future biological and clinical stratification studies.
Sodium (NaCl) is essential for neuronal excitability, muscle contraction, and osmotic balance, yet excessive intake causes cellular stress and dehydration, requiring tight homeostatic control. Drosophila melanogaster provides a genetically tractable system to dissect salt sensing and regulation. To summarize current understanding of concentration-dependent salt taste coding and systemic sodium homeostasis in flies. This review integrates genetic, behavioral, electrophysiological, and physiological studies describing (1) peripheral taste receptor neurons mediating differential responses to low- versus high-salt, (2) neural circuits for appetitive versus aversive behaviors, (3) state-dependent plasticity of salt preference, and (4) post-prandial ion balancing in the gut and malpighian tubules. Flies exhibit a biphasic behavioral response to salt: low concentrations promote feeding, whereas high concentrations induce aversion. Distinct classes of gustatory receptor neurons encode these opposing valences. Salt preference is further modulated by internal physiological state, integrating sensory detection with systemic ion balance. Coordinated sensory, neural, and excretory mechanisms govern ionic homeostasis in Drosophila melanogaster, thereby providing an evolutionarily conserved framework for investigating sodium balance across species.
BackgroundMammary tumor is one of the most prevalent cancers in female companion dogs. Current chemotherapeutic treatments are often limited by high toxicity and financial burden, highlighting the need for safer and more accessible therapeutic alternatives.ObjectiveThis study aimed to evaluate the anticancer potential of the methanol extract of Polytrichastrum alpinum, a moss species native to Antarctica, in mammary tumor cell lines derived from companion dogs.MethodsTwo canine mammary tumor cell lines, MGT316 and MGT612, were treated with various concentrations of Polytrichastrum alpinum methanol extract. Cell viability, colony-forming ability, cell cycle distribution, apoptosis, migration, and invasion were assessed. Cytotoxic effects on normal canine epithelial cells were also evaluated to compare responses between tumor and non-tumorigenic cells.ResultsPolytrichastrum alpinum methanol extract significantly reduced cell viability and colony-forming ability in a dose-dependent manner. It induced G0/G1 cell cycle arrest and promoted apoptosis in both tumor cell lines. Additionally, the extract effectively inhibited cell migration and invasion. Notably, minimal cytotoxic effects were observed in normal canine epithelial cells, indicating differential sensitivity between tumor and non-tumorigenic cells.ConclusionThese findings demonstrate that Polytrichastrum alpinum methanol extract exerts antiproliferative, pro-apoptotic, and anti-invasive effects on mammary tumor cells of companion dogs, indicating its potential as a natural therapeutic agent. Furthermore, given the relevance of canine mammary tumors as a comparative model, this study may provide valuable translational insights for human breast cancer research within a One Health framework.
Cymbidium goeringii is one of the most widely cultivated and traded ornamental orchids in East Asia. Due to its high horticultural value and phenotypic variability, accurate cultivar identification is essential but challenging, as their flowers bloom only briefly in spring. We have developed a forensic tool for rapid and exact cultivar discrimination by applying 12 simple sequence repeat (SSR) profiles in C. goeringii. This study was performed to establish an expanded SSR dataset for cultivar identification and phylogenetics in C. goeringii. We examined a total of 6,051 samples from 269 cultivars, including 92 Korean cultivars with ≥ 10 samples each. Among these, representative combined genotypes (CG1) were determined, and their frequencies (CG1
Despite the substantial progress in drug discovery and precision therapeutics, the predictive power of current ocular safety assessments remains limited owing to the lack of human experimental models. Conventional two-dimensional cell cultures lack the complex laminar organization, multicellular interactions, and functional electrophysiological properties of the human retina. Additionally, animal models frequently exhibit species-specific differences in retinal development, metabolism, and stress responses that hinder translational accuracy. Human induced pluripotent stem cell-derived retinal organoids are transformative microphysiological platforms that recapitulate key aspects of the human retinal architecture, including photoreceptor differentiation, synaptic connectivity, and neuronal functionality within a three-dimensional and human-derived context. In addition to structural resemblance, these systems enable multidimensional and mechanism-related toxicity assessments of oxidative stress, mitochondrial dysfunction, lysosomal impairment, ferroptotic signaling, synaptic dysregulation, and adaptive cytoprotective pathways. Therefore, retinal organoids can be incorporated into quantitative and regulatory toxicological frameworks using concentration–response modeling, benchmark dose derivation, and adverse outcome pathway mapping. Notably, these models identify the reactive oxygen species-mitochondria-lysosome axis as a central vulnerability hub that mechanistically links diverse exposure modalities, including small-molecule drugs, biologics, gene therapies, and nanomaterials, to photoreceptor degeneration. Ongoing advances in maturation, vascular-like integration, microfluidic coupling, and interline reproducibility have further enhanced their translational value. Collectively, retinal organoids are redefining ocular safety assessments by shifting the paradigm from hazard identification to predictive, mechanism-based, and human toxicology.
BACKGROUND:Mutations in isocitrate dehydrogenase 1 (IDH1) are hallmark features of diffuse gliomas and drive extensive metabolic and epigenetic reprogramming through accumulation of the oncometabolite 2-hydroxyglutarate (2-HG). However, the downstream transcriptional programs and chromatin-based mechanisms linking mutant IDH1 to oncogenic signaling remain incompletely understood. OBJECTIVE:This study aimed to define transcriptional changes associated with the IDH1 R132H mutation and to determine how epigenetic mechanisms influence KRAS-associated gene expression. METHODS:We analyzed transcriptomic data from the TCGA-LGG cohort and public RNA-seq datasets to identify differentially expressed genes and enriched pathways. Key findings were validated using qRT-PCR in cellular models expressing IDH1 R132H. To assess epigenetic regulation, we performed knockdown experiments targeting the H3K36 methyltransferases SETD2 and SMYD5. RESULTS:Integrated transcriptomic analyses revealed consistent enrichment of KRAS signaling-related gene signatures in IDH1 R132H tumors and cell models. qRT-PCR validation confirmed altered expression of key KRAS-associated genes involved in immune response, extracellular matrix remodeling, and tumor-related processes. Notably, the knockdown of SETD2 or SMYD5 significantly reduced the expression of these genes, indicating that H3K36 methylation-associated chromatin regulation contributes to their transcriptional activation. CONCLUSION:These findings demonstrate that mutant IDH1 promotes KRAS-associated transcriptional programs, at least in part, through epigenetic mechanisms involving H3K36 methylation-dependent chromatin regulation in glioma.
