Coloured and variegated leaves are common in shade-tolerant ornamentals. However, it remains unclear whether their photosynthetic performance is determined mainly by pigment abundance or by the organisation of chloroplasts and thylakoids. We tested this in three Epipremnum aureum phenotypes ('Neon', 'Golden' and 'Jade') that share a genetic background but contrast in leaf colour, chloroplast density and thylakoid membrane abundance. Plants were grown in a greenhouse and assessed by hyperspectral and thermal imaging, infrared gas exchange analysis, chlorophyll a fluorescence measurements, and structural, ultrastructural and biochemical analyses. Traits were integrated by principal component analysis, with the quantum yield of CO2 assimilation per absorbed photon (αCO2,abs) as the response variable. 'Neon' leaves had high specific leaf area and approximately 55% lower maximum Rubisco carboxylation (VcMAX) and electron transport capacity (JMAX) than 'Jade', as well as reduced chloroplast and thylakoid abundance and warmer canopies, despite carotenoid enrichment. JIP-test parameters and fluorescence light-response curves showed high absorption and dissipation per PSII reaction centre, elevated excitation pressure, modest non-photochemical quenching (NPQ), low αCO2,abs, small carbohydrate pools and low intrinsic water-use efficiency. 'Jade' leaves developed thick mesophyll with dense chloroplast populations, extensive thylakoid networks, highest NPQ, cool canopies and large carbohydrate reserves, whereas 'Golden' leaves combined thin laminae and intermediate chloroplast-thylakoid organisation with early light saturation of CO2 assimilation and the highest intrinsic water-use efficiency. Principal component analysis revealed a structural axis of chloroplast and thylakoid organisation that better predicted αCO2,abs, net carbon gain and canopy temperature than pigment abundance. In variegated E. aureum, 'photon economy' is therefore governed primarily by chloroplast and thylakoid membrane organisation and abundance rather than by carotenoid accumulation.

Background: Tumor-derived small extracellular vesicles (sEV), which we call TEX, carry a cargo of molecules that resembles the producer tumor cells. Circulating freely in body fluids, TEX potentially serve as a liquid tumor biopsy. TEX horizontally transfer their cargo to various recipient cells, imparting to them pro-tumor activity. Mechanisms of TEX-driven reprogramming might involve nucleic acids, especially double-stranded (ds)DNA. Methods: TEX isolated from supernatants of human tumor cells were identified as sEV, based on their size, endocytic origin and morphology. TEX treated with DNase/RNase cocktail were examined by transmission and cryo-electron microscopy and tested for biologic activity. DNA was extracted from enzyme-treated TEX, quantified by Qubit and analyzed for fragment sizes. The presence of genomic DNA in TEX was confirmed by PCR, and sequencing of the TP53 gene fragment for a mutational signature was performed. Results: Enzymatic and microscopic studies of TEX showed that nucleic acids are present in the biocorona on the outer surface. Their removal interfered with the biocorona integrity. A short TEX exposure to DNase/RNase altered their morphology without impairing vesicle functions; longer treatments induced TEX re-organization into smaller membrane-bound vesicles. The TEX lumen contained long fragments of protected genomic DNA with a mutational signature reflecting that of the tumor. Conclusions: Nucleic acids present on the TEX surface support the vesicular integrity. The TEX lumen contains membrane-protected large (ds)DNA fragments with the mutational signature of the parent tumor. The presence of surface and luminal nucleic acids in TEX, and especially their mutational signature, suggests that TEX may serve as highly promising cancer-specific biomarkers.

Despite the growing interest in brain structural plasticity and the substantial body of knowledge that has accumulated over recent decades, some issues remain poorly defined, leading to confusion in the interpretation of results. In addition to stem cell-driven neurogenesis in adult neurogenic niches (adult neurogenesis), neuronal precursors in a state of arrested maturation have also been described, representing a form of neurogenesis without division based on so-called "immature" or late-maturing neurons. These processes occur in different brain regions yet share certain molecular markers and temporal windows. Recent advances in comparative neuroplasticity have further complicated our understanding. Studies reveal a reduction in adult neurogenesis in the olfactory bulb and hippocampus of large-brained, gyrencephalic mammals compared with small-brained species such as rodents. Conversely, a higher prevalence of immature neurons has been reported in the neocortex and amygdala of larger-brained mammals. It is becoming evident that evolutionary trade-offs took place in distinct plastic processes, resulting in the predominance of certain forms in particular species, while others coexist and share overlapping markers. Regardless of the approach employed (neuroanatomical, immunocytochemical, phylogenetic, or transcriptional), current evidence indicates substantial heterogeneity in cell types with different origins and fates across diverse mammalian species. These patterns appear to be sculpted by evolutionary pressures yet unified by shared transient maturational states.

Mitochondria comprise ~1/3rd of the volume of an adult ventricular cardiomyocyte. The gene Immt encodes the Mic60/Mitofilin protein that is hypothesized to organize the mitochondrial contact site and cristae organization system (MICOS) complex that generates mitochondrial cristae junctions between the inner and outer membranes. To investigate the function of the Immt gene in the mouse heart, we generated and characterized mice in which this gene was specifically deleted in the mouse heart using a loxP-targeted allele (Immtfl/fl) and either the constitutive heart-specific Myh6-Cre transgene or the conditional Myh6-MerCreMer transgene, each of which showed lethality in several weeks. Hearts from these mice showed progressive hypertrophic cardiomyopathy and failure with lost contractility and lung edema. At the ultrastructural level, hearts from these mice showed extreme abnormalities in mitochondrial architecture characterized by lost cristae junctions, stacking of the inner mitochondrial membranes, mitophagy and areas with complete absence of mitochondria. Analysis of mitochondria showed loss of the MICOS complex of proteins as well as loss of mitochondrial membrane potential (Δψ) and increased expression of mitophagy proteins and mitochondrial biogenesis transcription factors. Hearts from these mice also showed widespread cardiomyocyte necrosis and induction of the universal mitochondrial stress response at the mRNA level, as well as major alterations in cardiac metabolites, suggesting greater use of glucose, ketones and amino acids. We conclude that the Immt gene is required for cardiac mitochondrial structure and function, although the ensuing mitochondrial stress response provides molecular clues as to how the heart can compensate metabolically and maintain viability for weeks after mitochondria are absent or unfunctional.

Genome editing has emerged as a transformative approach for understanding and treating retinal degenerative diseases. Combining this technology with pluripotent stem cells provides an ideal platform for modeling human development and disease, and investigating emerging therapeutic strategies ultimately aimed towards in vivo correction. This approach enables both functional studies to understand retinal degeneration and the early development of targeted therapies for inherited disease. This review offers a comprehensive overview of genome-editing techniques and the ability to create new clinically relevant models to understand human disease in retinal research, focusing on the use of the CRISPR-Cas9 system in induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), as well as highlighting recent advancements in base and prime editing. Gene editing in various retinal diseases is discussed in context of studies focusing on disease modeling or developing therapeutic strategies. Continued refinement of these techniques will be essential for advancing translational applications in retinal disease treatment.

Retromer is an evolutionarily conserved protein complex first identified in budding yeast. It was originally described for its essential role in endosome-to-Golgi retrieval of lysosomal hydrolase receptors. Retromer is now known to mediate trafficking of many endosomal cargoes. The mammalian retromer is constituted by a core heterotrimer encoded by the vacuolar protein sorting (VPS) gene products VPS26, VPS35, and VPS29. To mediate cargo recognition and endosomal sorting into various pathways, this trimer can cooperate with phosphoinositide-binding sorting nexin family members. Defective retromer functioning has been associated with alterations in cellular homeostasis, leading to disease. To gain insights into how it may mediate these broad processes, a proteomic strategy in polarized Madin-Darby canine kidney cells was devised to identify retromer-interacting proteins. Subsequent validation of one of the candidates, i.e., cytokeratin 19, led to the unexpected finding that retromer localizes to the pericentriolar region in dividing cells and subsequently translocates to the midbody during cytokinesis. Retromer was found interacting with CK19, and its antisense depletion led to delocalization from CK19. Subcellular fractionation and live cell monitoring of depleted cells provided evidence of a role by retromer in post-metaphase progression and in epithelial cell migration, thereby connecting retromer with key processes of cellular dynamics.

Skeletal muscle regeneration declines with age despite the persistence of satellite cells (muscle stem cells, MuSCs), suggesting that regenerative impairment reflects functional dysregulation rather than MuSC depletion. Increasing evidence identifies early MuSC activation during the immediate post-injury period as a stress-sensitive, rate-limiting transition that is particularly vulnerable in aged muscle. Aged MuSCs exhibit elevated stress responses and reduced membrane remodeling capacity, accompanied by weakened activation-associated transcriptional induction. In contrast, proliferative and differentiation programs remain largely intact once activation is successfully initiated. These findings underscore that impaired coordination during early activation contributes to long-term regenerative decline in aging. Within this framework, MG53 (tripartite motif-containing protein 72, TRIM72), a muscle-enriched TRIM family E3 ubiquitin ligase originally identified as a mediator of sarcolemmal membrane repair, may also function as a stress-responsive regulator that stabilizes the early activation environment. Rather than directly determining cell fate, MG53 is proposed to facilitate activation by mitigating stress-associated membrane disruption and maintaining programmatic coordination under age-related physiological constraints. Most mechanistic evidence derives from rodent models, and direct validation in human aging muscle remains limited. These observations suggest that targeting early activation, rather than simply increasing proliferation, may better preserve regenerative capacity in aging skeletal muscle.

Stem cell therapy represents an intrinsic part of regenerative medicine, with expanding applications in orthopedic and musculoskeletal research. Although studies span from small-animal models to early-phase clinical trials, the field remains fragmented, with wide variation in stem cell types, delivery methods, and target tissues. A consolidated overview is needed to inform future directions and bridge the gap between preclinical promise and clinical application. This scoping review synthesized evidence from 500 preclinical and clinical studies, identified through systematic searches and screened in accordance with PRISMA-ScR guidelines. Data were extracted on stem cell type and source, delivery approach, targeted tissue and organ, and disease indication. We found that autologous bone marrow-derived mesenchymal stem cells were the most used, with adipose- and perinatal-derived cells gaining prominence in recent years. Small-animal models such as rats and rabbits predominated, while large-animal and human studies focused mainly on knee osteoarthritis. Intra-articular injection was the principal delivery method across both preclinical and clinical settings. By mapping prevailing practices and emerging trends, this review provides a comprehensive reference for researchers, clinicians, and regulatory stakeholders. It highlights translational pathways, identifies critical gaps, and offers evidence to guide the design of safe, effective, and scalable regenerative therapies in orthopedics.

Aquaporins (AQPs) are a family of small integral membrane proteins that mediate the selective transport of water and, in some cases, small solutes such as glycerol and hydrogen peroxide. In the skin, distinct AQP isoforms are expressed throughout the epidermis, dermis, and hypodermis, where they play key roles in maintaining hydration, regulating keratinocyte and fibroblast proliferation, modulating inflammatory responses, and preserving overall tissue integrity. Increasing evidence indicates that aberrant AQP expression or function contributes to skin carcinogenesis, influencing tumor initiation, local invasion, metastasis, and responses to microenvironmental stress. Alterations in specific AQP isoforms have been associated with both major classes of cutaneous malignancies-non-melanoma skin cancers (NMSC), including basal cell carcinoma and squamous cell carcinoma, as well as malignant melanoma (MM)-yet their mechanistic contributions remain incompletely understood. This review synthesizes current knowledge on the involvement of each AQP isoform in skin cancer pathogenesis and progression, integrating findings from molecular, cellular, and in vivo studies. By clarifying the diverse roles of AQPs in cutaneous malignancies, this work aims to support the development of targeted interventions and guide future research in this rapidly evolving field.

Prostate cancer (PCa) is the most general cancer in men and is often linked with distant metastasis in its later stages. The caffeic acid (CA) derivative, N-(4-methoxyphenyl)methylcaffeamide (MPMCA), demonstrates superior liver-protective effects compared to CA. Nevertheless, the functions of MPMCA on prostate cancer metastasis remain unclear. Here, we demonstrate that MPMCA blocks migration and invasion in prostate cancer cells without affecting cell viability. By suppressing the production of mesenchymal markers Vimentin, N-cadherin and β-catenin and upregulating the production of the epithelial marker Zonula Occludens-1 (ZO-1), MPMCA also controls Epithelial-Mesenchymal Transition (EMT). The Phosphoinositide 3-kinase (PI3K), Protein kinase B (AKT) and mechanistic target of rapamycin (mTOR) pathway has been documented to regulate MPMCA-inhibited cell motility. Transfection with Snail and Slug cDNA reverses MPMCA's suppression of EMT, migration, and invasion in prostate cancer cells. Importantly, our in vivo data indicates that MPMCA reduces Snail and Slug expression and prostate cancer metastasis. Our evidence suggests that MPMCA is a novel therapeutic candidate for treating metastatic prostate cancer.