The glymphatic system and meningeal lymphatic vessels: from physiology to pathophysiology, with insights into visualization.

CCN5 overexpression suppresses trophoblast HTR-8/SVneo cell proliferation, migration, invasion, and epithelial-mesenchymal transition.

Single-cell transcriptomics uncovers immune remodeling in heart failure complicated by myocarditis

SUMMARYTransporters are transmembrane proteins that mediate the selective translocation of metabolites, ions, and drugs across biological membranes. Their activity is essential for cellular communication, nutrition, detoxification, homeostasis, and responses to stress. Despite their fundamental biological and biomedical importance, particularly their involvement in genetic diseases and multidrug resistance in microbes and cancer cells, transporters remained relatively understudied until recently. This was largely due to the technical challenges of isolating and functionally characterizing these dynamic proteins, whose structure, function, and cellular expression continuously depends on specific interactions with membrane lipids. Nevertheless, since the mid-1960s, several transporters have been identified and extensively characterized at the genetic and physiological levels in model microorganisms, including fungi. In this review, we trace the 60-year research journey of UapA, a uric acid-xanthine transporter from the filamentous fungus Aspergillus nidulans (Ascomycota). The UapA story spans from early classical genetic analyses to the recent determination of its high-resolution structure. We describe the development of genetic, molecular, and cellular tools and how these enabled the functional dissection of UapA and were subsequently used for other A. nidulans transporters, including studies on cellular expression and turnover regulation. We additionally highlight up-to-date structural approaches that refined our knowledge on the transport mechanism, how substrate specificity is determined, and on membrane trafficking pathways underlying biogenesis and endocytosis of UapA and other transporters. The concepts developed through 60 years of persistent work on UapA have established important paradigms relevant to fungal physiology that have proven to be broadly applicable to understanding transporter-linked processes in other eukaryotic organisms.

Microglial HMGB2 mediates neuroinflammation and brain damage in Cx3cr1-creERT2 epileptic mice through astrocyte-derived CCL2.

An extracellular, optogenetic antibody platform for stimulus-gated antigen recognition and modulation of cell behavior.

Vaccination is critical for controlling infectious diseases; however, assessing efficacy solely through neutralizing antibody titers oversimplifies immune protection. The cellular and molecular mechanisms driving variable vaccine-induced immune responses remain underexplored, limiting comprehensive vaccine evaluation. Using single-cell sequencing, we profiled and compared cellular dynamic, transcriptomic profiles, the immune repertoire, and cellular communication in vaccine recipients with high and low antibody titers after Ad5-nCoV booster vaccination, using peripheral blood mononuclear cell samples collected from a cohort of 144 participants. Cellular profiling revealed no significant changes in most immune cell subsets. However, high responders exhibited increased cytotoxic CD8+ lymphocytes and natural killer T cells, with reduced CD8+ mucosal-associated invariant T cells. This group showed up-regulated immune and effector genes, down-regulated proinflammatory genes, and elevated inhibitory gene expression in clonal natural killer cells, accompanied by enhanced CD8+ T-cell clonal expansion. In addition, the variable and joining (VJ) gene usage of B and T cells in the high-response group showed biased patterns, with preferential expression of IGLJ3, IGKJ3, IGHV3-33, and IGHJ4 in B cells and TRAV27, TRAJ33, TRBV9, and TRBJ2-7 in T cells. Cell communication also indicated balanced proinflammatory and anti-inflammatory cytokine expression in high responders. These findings elucidate the cellular and molecular mechanisms underlying robust immune responses to the Ad5-nCoV booster, highlighting the critical role of cellular immunity. By integrating humoral and cellular insights, this study offers a new perspective of comprehensive framework for evaluating vaccine efficacy.

Cardiovascular diseases remain the leading cause of mortality worldwide, highlighting the urgent need for more effective therapeutic strategies. Despite substantial advances in conventional biomaterials, their limited ability to support functional integration and dynamically interact with the biological microenvironment continues to hinder therapeutic outcomes. Native cardiovascular tissues rely on tightly regulated bioelectrical signaling to coordinate cellular communication, tissue homeostasis, and functional repair. Consequently, recreating these bioelectrical cues has emerged as a key design principle in cardiovascular tissue engineering. Electroactive biomaterials have gained increasing attention as a promising platform to address this challenge by enabling electrical modulation of cellular behavior and tissue function. In this review, we summarize the intrinsic bioelectrical properties of cardiovascular tissues and discuss the roles of electrical stimulation in regulating disease-relevant cellular responses. We further highlight recent advances in the development of conductive, piezoelectric, and other electroactive biomaterials for cardiovascular tissue engineering applications. Finally, we critically discuss the major challenges and future opportunities in the field, including tissue-specific responses, stimulation parameter optimization, long-term safety, and clinical translation. Collectively, electroactive biomaterials represent a promising and rapidly evolving frontier for the development of dynamic, responsive, and next-generation therapies for cardiovascular diseases.

Medicinal plants have long served as important sources of therapeutic agents owing to their diverse bioactive constituents and multi-target pharmacological properties. In particular, plant-derived compounds have attracted increasing attention for the management of chronic inflammatory and metabolic diseases, including atherosclerosis. However, the molecular mechanisms by which medicinal plants modulate the cellular heterogeneity and intercellular communication networks within atherosclerotic plaques remain insufficiently understood. Despite the widespread implementation of lipid-lowering therapy, the persistence of residual inflammatory risk, driven by immunometabolic network dysregulation, remains a cardinal therapeutic challenge in atherosclerosis (AS) management. While Perilla frutescens exhibits well-documented anti-inflammatory properties, the precise molecular targeting within the atherosclerotic plaque microenvironment and the regulatory mechanisms governing intercellular communication networks remain poorly elucidated. To address this gap, we established a multi-scale integrative computational framework synergizing network pharmacology, human atherosclerotic plaque single-cell transcriptomic (scRNA-seq) profiling, and ensemble machine learning algorithms (LASSO and random forest) for systematic identification of robust therapeutic targets. Subsequently, molecular docking coupled with 100-ns all-atom molecular dynamics (MD) simulations validated the binding affinity and thermodynamic stability of drug–target complexes. The study successfully analyzed the cellular heterogeneity lineage of plaques and identified a core feature set of 10 genes including HIF1A, PPARG and ITGB1, which specifically mapped the differentiation trajectory of macrophages to foam cells. External validation in an independent cohort demonstrated superior diagnostic performance of this signature (AUC = 0.996). Cellular communication network dissection revealed the foam cell-driven SPP1–ITGB1 signaling axis as a pivotal conduit orchestrating inflammatory crosstalk. Molecular docking demonstrated pronounced binding affinity between luteolin, the principal bioactive constituent of Perilla frutescens, and ITGB1 (binding energy: − 8.9 kcal/mol). MD simulations further corroborated the efficacy of luteolin in stabilizing ITGB1 conformation via a "conformational-locking" mechanism (RMSD equilibration within 0.10–0.20 nm), thereby abrogating pathological cell adhesion signaling transduction. Collectively, this study provides a high-resolution molecular atlas of Perilla frutescens-mediated AS intervention, systematically elucidating the mechanistic paradigm whereby luteolin attenuates vascular inflammation through targeted disruption of the SPP1–ITGB1 communication axis. These findings underscore the therapeutic targeting of cell adhesion receptors as a translationally promising strategy for mitigating residual inflammatory risk in AS.Graphical abstract

Nanoplastics perturb extracellular vesicle-mediated communication in the in vitro and ex vivo bone marrow microenvironment of multiple myeloma.

High resolution spatial transcriptomics identifies insufficient radiofrequency ablation induces hepatocellular carcinoma progression via CEBPD / CXCL2 axis.

Single-nuclei transcriptomics provides insights into cellular heterogeneity and communications in the glacial relict Hucho bleekeri under heat exposure.

BackgroundDiabetic cardiomyopathy (DCM) is a diabetes-related myocardial disorder causing fibrosis, hypertrophy, and progressive diastolic and systolic dysfunction. This study aims to explore how metabolic, inflammatory, and fibrotic mechanisms in non-cardiomyocytes drive DCM to reveal new therapeutic targets.MethodsSingle-cell RNA sequencing (scRNA-seq) was performed to investigate the role of non-cardiomyocytes in DCM, enabling the identification of cell types, gene expression dynamics, and intercellular communication networks in patients with type 2 diabetes. The scRNA-seq data were obtained from the GEO to investigate cell-type-specific contributions and heterogeneity across tissues. Metabolic pathway scores were calculated using scMetabolism. Moreover, cell trajectory analysis and cellular communication studies were performed to examine shared and disease-specific cell populations in diabetes and cardiomyopathy. CCK-8, colony formation, Transwell migration and invasion assays were preformed to explore the function of PTPRC in HUVECs.ResultsUsing SingleR annotation, we identified eight distinct cell types, with NK cells and smooth muscle cells representing the shared cell populations across both diseases. Cell trajectory analysis revealed three distinct branches based on gene expression over pseudotime, and the top differentially expressed genes in each cell type clustering into six categories. Metabolic pathway analysis predicted that epithelial cells, macrophages, and neurons as the most metabolically active across multiple pathways, highlighting metabolic heterogeneity among patient samples. Additionally, four key signaling pathways associated with NK cells and smooth muscle cells were predicted to emphasize the divergence in gene expression across cell types. PTPRC is implicated in diabetes and cardiomyopathy and functions as a positive regulator of HUVEC viability, clonogenic growth, migration, and invasion.ConclusionThis study demonstrates significant heterogeneity among non-cardiomyocytes in patients with diabetes and cardiomyopathy, highlighting the need for targeted therapeutic interventions to address these differences.

Cellular communication network (CCN) proteins are key matricellular regulators of cartilage development, yet their species‐specific roles and network‐level context remain unclear. This study integrated bulk RNA sequencing from chicken and mouse embryonic limb bud micromass cultures and human mesenchymal stem cell chondrogenesis with co‐expression, protein–protein interaction, and ortholog analyses to construct CCN‐centered regulatory networks across models. CCN1 and CCN2 emerged as dominant, conserved hubs enriched in collagen‐containing extracellular matrix, cartilage development, and growth factor signaling modules, whereas CCN3–CCN6 showed lower context‐dependent expression and connectivity. Functional and ortholog analyses revealed moderate pathway conservation, with high conservation of IGF, EGFR, and HIF‐1 signaling, but reduced overlap in hypoxia and mechanosensing/Hippo categories, indicating species‐specific tuning of environmental sensing. A focused ortholog screen identified multifunctional conserved hubs, including COL2A1, TGFBR1, SMAD3, RUNX2, HIF1A, IGF1, SPP1, and CD44. Single‐cell RNA‐seq meta‐analysis of human iPSC‐derived chondrogenesis and embryonic limb datasets showed CCN1/2 expression and homologous network activity peaking in mesenchymal and early chondrocyte populations, consistent with model‐dependent persistence into hypertrophic and ossification stages in vivo. Overall, this work defines a conserved CCN1/2‐centered axis integrating extracellular matrix formation with growth factor and mechanical cues, providing a framework for model selection and CCN‐targeted cartilage regeneration strategies.

Anticipating mesenchymal stem cell quantification: CD63-Expressing small extracellular vesicles in cord blood serum: A proof of concept study.

Development of anti-CD4-1/CD8β monoclonal antibodies and spatiotemporal immune profiling of response to live attenuated IHNV in rainbow trout (Oncorhynchus mykiss).

Always on the move: Mapping spatiotemporal interactome with proximity labeling in mammalian cells.

Protein secretion is a fundamental biological process essential for cellular communication, matrix remodeling, and overall homeostasis across all domains of life. While the classical endoplasmic reticulum (ER)-to-Golgi pathway has long been recognized as the primary route for eukaryotic protein export, decades of research reveal that numerous cytosolic and membrane proteins bypass this canonical route. This alternative paradigm, termed unconventional protein secretion (UcPS), encompasses direct transmembrane translocation, vesicle-mediated release, and Golgi-bypass mechanisms. Simultaneously, prokaryotes utilize highly specialized secretion machineries to deliver effector proteins. Despite these established frameworks, the precise molecular regulation, cargo sorting mechanisms, and dynamic crosstalk between these diverse pathways remain incompletely understood. Here, we comprehensively review the molecular mechanisms of UcPS and prokaryotic secretion systems, synthesizing their evolutionary adaptations and operational frameworks. By mapping nonvesicular pores, extracellular vesicles intermediates, and complex bacterial nanomachine assemblies, we delineate how cells rapidly mobilize proteins under stress. Furthermore, we highlight the dual role of these pathways in driving physiological adaptation versus fueling pathological dissemination. Abnormalities in these secretory nodes are now recognized as primary drivers of neurodegeneration, inflammatory disorders, and cancer metastasis. Consequently, manipulating UcPS mechanisms offers promising, multidimensional therapeutic opportunities for future medicine.

Encoding chemical cues through compartmentalized signal packaging.

Tributyltin (TBT) is a widespread marine contaminant that affects the development and reproduction of marine invertebrates; however, its molecular impacts on early embryonic development remain poorly understood. In this study, we investigated the effects of environmental concentrations of TBT on the miRNA expression profiles of the marine gastropod Tritia mutabilis during intracapsular embryogenesis. Embryos were exposed for 10days to low (10-12M) and high (10-10M) concentrations of TBT, and the differential expression of miRNAs was assessed by high-throughput sequencing. Obtained results revealed a significant modulation of several miRNAs across treatments, with a set of 11 miRNAs responding to both low and high TBT concentrations, while miR-486-5p and miR-183-5p were specifically modulated under the low TBT concentration, and miR-263b, miR-184, and miR-100-5p were exclusive to the highest concentration. Pathway analyses identified a range of biological processes affected, including nervous system development, cellular functions such as proliferation and cell growth, signal transduction, cellular component assembly and cell-cell interactions. Notably, several pathways were highly enriched (i.e., ≥100 regulated target genes) under both conditions, including focal adhesion, Ras signaling, regulation of actin cytoskeleton, Rap1 signaling, cAMP signaling, calcium signaling, and cGMP-PKG signaling pathways, highlighting the vulnerability of developmental and cellular communication networks, and further supported by the expression analysis of the corresponding miRNA-regulated target genes. These findings demonstrate that TBT contributes to the developmental abnormalities of marine gastropod embryos by modulating miRNA-mediated control of gene transcription. Our results contribute to advancing the understanding of miRNAs' potential utility as biomarkers for environmental monitoring.