Search Results (1,277)

Endothelial dysfunction underlies many cardiovascular and metabolic diseases. Lysosomal storage disorders, particularly sphingolipidoses, cause intracellular accumulation of specific sphingolipids due to inherited enzyme defects. This review focuses on Gaucher, Niemann–Pick (types A, B, A/B) and Fabry diseases, selected because they exhibit clinically significant cardiovascular manifestations and each accumulates a distinct sphingolipid—glucocerebroside, sphingomyelin, or globotriaosylceramide—allowing comparative analysis of how different metabolic defects converge on similar endothelial phenotypes. We summarize current knowledge on how substrate accumulation disrupts the ceramide/sphingosine-1-phosphate (S1P) rheostat, affecting NO synthase, vascular permeability, inflammation, angiogenesis, autophagy and cell death. Common and disease-specific changes in endothelial morphology and barrier function are discussed. Importantly, direct experimental evidence for endothelial involvement in Gaucher and Niemann–Pick diseases remains scarce; most mechanistic insights derive from non-endothelial cell models, highlighting a significant gap that underscores the need for targeted endothelial studies. Deficiencies of GBA1, SMPD1, and GLA each modulate S1P and ceramide production through distinct pathways, yet all three conditions share similar functional endothelial alterations driven by disrupted sphingolipid homeostasis. Understanding these common mechanisms opens new perspectives for diagnostic biomarkers and therapeutic strategies aimed at restoring sphingolipid balance in the endothelium, though further research is required to validate these findings in endothelial-specific contexts. Full article

This study presents a computational and experimental aerodynamic characterisation of a full-scale 5.5 m diameter, six-sail horizontal-axis windmill of the traditional Cretan Lasithi type, equipped with flexible woven polyester sails that act as a passive load-control mechanism. Seventeen operating points spanning wind speeds of 2.3–18.3 m/s were simulated in OpenFOAM using a transient sliding-mesh Arbitrary Mesh Interface formulation with the k–ω SST turbulence closure on a 2.3 million cell grid, selected on the basis of a four-level grid convergence study. CFD simulations identify three distinct aerodynamic regimes: a drag-dominated high-TSR regime (λ > 2.1), a mixed lift–drag working range with peak loading near λ ≈ 1.4–1.5, and a deep-stall regime in which boundary-layer separation propagates from root to tip as λ falls below 1.0. Field measurements conducted at the Energy Systems Synthesis Lab of the Hellenic Mediterranean University in compliance with IEC 61400-12-1:2005(E) confirm that rotor speed stabilises passively at 55–58 RPM above 13 m/s without any active control mechanism; CFD predictions agree with measured power output within 8–12% across the 2–13 m/s attached-flow envelope. The combined evidence indicates that passive overspeed self-regulation is driven by aeroelastic sail deformation, reducing effective disc solidity at high wind speeds, a mechanism that rigid-geometry CFD correctly identifies in trend but cannot quantify in magnitude. The primary limitation of the present work is the rigid-sail assumption of the CFD model, which requires a two-way coupled fluid–structure interaction extension as a future step. Full article

Recent studies have identified microRNAs (miRNAs) in honey, opening a new and promising area of nutrition research. In this view, pasteurized and unpasteurized samples of Eucalyptus, Orange Blossom, Chestnut, and Sulla honeys were analyzed using manual and semi-automated RNA extraction methods. Semi-automated extraction yielded significantly higher RNA amounts than manual methods, while pasteurization selectively affected miRNA presence, depending on the type of honey. The panel of conserved miRNAs monitored was let-7a-5p, miR-1-3p, miR-7-5p, miR-10a-5p, miR-33a-5p, miR-34a-5p, miR-92a-3p, miR-125b-5p and miR-133a-3p, across honey varieties and in their extracellular vesicles with structures approximately 200 nm in diameter that retain four miRNAs in all honey types, miR-1-3p, miR-34a-5p, miR-92a-3p, and miR-133a-3p. Bioinformatic analyses of validated miRNA targets revealed enrichment in pathways related to cytoskeletal organization, transcriptional regulation, protein stability, and immune system processes, with Reactome categories clustering around signal transduction, protein metabolism, and immune interactions. Cell–type–specific enrichment suggested that gastric isthmus progenitor cells, stromal cells, and immune subsets could be potential targets, implying roles in epithelial renewal, immune modulation, and wound healing. Overall, these findings enhance our understanding of honey as a source of conserved miRNAs in extracellular vesicles, highlighting its potential as a natural carrier that protects miRNAs from degradation. This study offers new insights into the health-promoting properties of honey, warranting further preclinical studies. Full article

Sensitive skin is characterized by hypersensitivity to normal stimuli, and objective diagnostic tools and treatments are still limited. Currently, cosmetics for sensitive skin are developed through the exclusion of known irritants rather than investigation into the underlying mechanisms of sensitivity. In this study, we developed an integrated pipeline combining transcriptome analysis via microneedle-based skin sampling (MISSM), bioinformatics, in vitro validation, and clinical assessment to identify sensitive skin-associated inflammatory biomarkers and cosmetic ingredients that regulate them. Candidate biomarkers and matched cosmetic ingredients were identified from transcriptomic data and validated in lactic acid-stimulated HaCaT and human dermal fibroblasts via qRT-PCR. A prototype emulsion was developed and evaluated in a 4-week open-label pilot clinical trial with longitudinal molecular monitoring via MISSM. After lactic acid stimulation, sensitive skin-associated biomarkers (MCOLN1, CYR61, PMAIP1, PTGS2, and HMGB2) were significantly upregulated in both cell types, and cosmetic ingredients that regulate these biomarkers were confirmed in vitro. The emulsion prototype demonstrated hypoallergenicity in a primary irritation test. In the pilot clinical trial, target biomarker expression was significantly reduced in MISSM-derived samples, with improvements in skin hydration, barrier function, redness, and sensory reactivity also observed. This integrated pipeline will enable the discovery of inflammatory biomarker-regulating cosmetic ingredients, with potential applicability to various inflammatory skin conditions. Full article

This study evaluates the effect of decorative ceramic screen printing on the optical and photovoltaic performance of glass covers intended for building-integrated photovoltaics (BIPV). Nine ceramic-printed glass samples with different colors and optical densities were compared with a 4 mm Optiwhite reference glass and a bare silicon solar cell. The samples were characterized by UV-VIS-NIR spectrophotometry, energy-dispersive X-ray spectroscopy (EDS), and electrical measurements under simulated AM 1.5G irradiation at 1000 W/m². The optical results showed that the Optiwhite reference provided the highest transmittance, whereas the printed samples exhibited lower transmission, typically in the range of 60–80% in the visible region, depending on the coating type. Among the decorative variants, sample 1 showed the highest transparency, while sample 6 exhibited the lowest transmittance. The spectral behavior of the coated glasses indicates that the ceramic layers modify the photon flux reaching the solar cell through wavelength-dependent absorption and scattering effects. The photovoltaic measurements confirmed a clear relationship between decorative coating and electrical performance. Relative to the Optiwhite-covered reference cell, the printed samples showed power losses ranging from approximately 17% to 32%, with sample 1 achieving the highest maximum power among the decorative variants at 1.41 W, and sample 4 the lowest at 1.16 W. The main electrical effect of the ceramic coatings was a reduction in short-circuit current, whereas the open-circuit voltage remained nearly constant across the tested samples. EDS analysis identified the presence of ceramic-layer constituents associated with silica-, zinc-, titanium-, iron-, cobalt-, aluminum-, and fluorine-containing compounds, supporting the interpretation of vitrified decorative coatings formed during high-temperature processing. Overall, the results demonstrate that decorative ceramic printing can provide a practical compromise between architectural appearance and photovoltaic output when the optical density of the coating is appropriately controlled. Full article

Cells operate as open thermodynamic systems where energy transformations and transport processes occur across membranes, exhibiting distinct thermo-electro-biochemical behaviours in healthy versus diseased states. Living organisms generate waste heat due to internal irreversibility, which dissipates into the environment and serves as an observable flow of information. By analysing this heat loss and its changes under external influences, new insights into cellular behaviour can be gained. This paper highlights recent advances in this thermodynamic approach, which frames living systems as black boxes, focusing on their input–output dynamics and introducing the emerging field of bioengineering thermodynamics. A key challenge in applying extremely low-frequency electromagnetic fields (ELF-EMF) to proliferative disorders has been the empirical selection of effective field parameters. To address this, we employed a bio-thermodynamic engineering model to calculate the ELF frequency that maximizes mean entropy changes based on cellular biophysical parameters. This entropy change corresponds to a metabolic shift that reduces cell proliferation. Experimental validation was performed on six human cancer cell lines, where proliferation rates served as indicators confirming the model’s predictions. For the first time, this approach enabled the calculation and experimental validation of ELF frequencies selectively effective on different cell types, demonstrating a promising method for targeted therapeutic applications. Full article

Battery formation is important for ensuring the quality and service life of cells in lithium-ion battery (LIB) production. During the formation process, fault cells, such as low open-circuit voltage cells, are screened offline after the charging stage since, in most formation protocols, the online screening process is absent. This can lead to energy waste and extend the rework cycle of the fault cells in the LIB formation process. To address this problem, this paper considers the online fault cell screening problem, the formation pre-screening, in the LIB formation process as a classification task and proposes a data-driven model based on incomplete time-series data for formation pre-screening. First, the proposed model transforms segments of the incomplete charging voltage curve (ICVC) of the LIB as tokens, which is a more compact and less redundant data representation of the ICVC. Then, the attention-based feature encoder, Transformer encoder (TE), captures the dependency between tokens to extract features for the formation pre-screening. Finally, a task-specified decoder, feature enhance decoder (FED), is used to screen out fault cells online. The effectiveness of the proposed model is verified using real-world production data collected from a specific type of 18,650 lithium-ion cell under one formation protocol. The results on the investigated industrial dataset show that the proposed model achieves an accuracy of 98.73% and a miss rate of 1.92% during formation pre-screening, which is a 2.49% improvement in accuracy and an 8.98% decrease in miss rate compared with the deep residual network baseline. These results demonstrate the feasibility of using incomplete formation-stage voltage curves for online fault-cell pre-screening, which has the potential to reduce unnecessary charging and rework time in LIB production. Full article

Morse-type tapers at the head–stem junction in total hip replacements (THRs) provide many benefits to permit a successful surgical outcome. However, with the introduction of modular tapered devices comes complications associated with fluid ingress and motion at the interface that can cause fretting corrosion, which has been implicated in clinical failure. Increased surface roughness amplitude (R_a) and angular mismatch to ensure taper contact closer to the equator of the femoral head are design features introduced for use with ceramic heads but have been adopted by metal head couples. While increased surface roughness amplitude has been found to contribute to fretting corrosion, there is a distinct lack of systematic studies investigating the interactions between angular mismatch and R_a. This study measured the fretting corrosion and motion response of clinically representative samples, in part reference to ASTM F1875, when subjected to uniaxial incremental dynamic loading. The fretting corrosion response was measured in situ with an integrated three electrode electrochemical cell. Motion at the head–neck interface was measured with a bespoke motion measurement solution based on eddy-current principles which uses four sensors to allow motion to be fully characterised in three dimensions. Key findings from this study included a 5–10-fold increase in current measured in the increased roughness amplitude samples, suggesting an increased susceptibility to fretting corrosion without a corresponding increase in motion. The distal samples engaged around the opening of the taper interface and presented the lowest current measurements but most off-axis subsidence. Findings from this study indicate that optimisation of the taper interfaces in THR, in terms of fretting corrosion and motion, can be made and can be assessed using short-term preclinical tests. Full article

The type VI secretion system (T6SS) is a contact-dependent, contractile multiprotein complex widely distributed among Gram-negative bacteria. It mediates the translocation of effector proteins into bacterial competitors and eukaryotic host cells, promoting environmental fitness and contributing to virulence. In Salmonella, five pathogenicity islands encoding T6SSs (SPI-6, SPI-19, SPI-20, SPI-21, and SPI-22) have been described, along with an expanding repertoire of associated effector proteins. However, their global diversity and distribution remain incompletely resolved due to limited genomic sampling. To address this, we analyzed a curated dataset of 490 Salmonella genomes representing 45 serotypes. T6SS regions were identified using SecreT6, revealing that SPI-6 is widely distributed, whereas SPI-19, SPI-20, and SPI-21 are restricted to a subset of serotypes. SPI-20 and SPI-21 were exclusively found in S. enterica subsp. arizonae and diarizonae, while SPI-22 was absent from all analyzed genomes. All open reading frames within T6SS clusters were then analyzed for effector prediction and functional annotation. This approach recovered 32 out of 45 previously described T6SS effectors and identified several novel candidates. These included a cytidine deaminase with predicted DNase activity in SPI-6: two candidate nuclease effectors in SPI-19 with DNase and RNase activities, and four putative effectors in SPI-21, including enzymes with predicted peptidoglycan hydrolase activity, a potential inhibitor of eukaryotic ATPases, and a membrane pore-forming toxin. Additionally, a putative phospholipase effector was identified within a VgrG-associated genomic island in a subset of S. enterica subsp. diarizonae isolates. Collectively, these findings expand the known repertoire of Salmonella T6SS effector proteins and highlight their functional diversity. Full article

Ensuring global food security under accelerating climate change requires transformative approaches to crop improvement that extend beyond the limits of traditional breeding and gene editing. While domestication and modern agriculture have delivered substantial gains in productivity, these advances often came at the cost of genetic diversity, stress resilience, and developmental plasticity. Plants, however, inherently exhibit remarkable flexibility in their morphology and development, as evidenced by the vast diversity of organ shapes, cell types, and adaptive responses that have evolved across lineages. This natural design space provides a foundation for reimagining plant architecture using synthetic biology. Recent advances in plant synthetic biology, including programmable transcription factors, CRISPR-based regulatory systems, synthetic gene circuits, orthogonal signalling pathways, and plant artificial chromosomes, now enable precise, modular, and environmentally responsive manipulation of developmental processes. These tools allow researchers to rewire hormone pathways, tune quantitative gene expression, integrate multiple environmental signals, and create novel regulatory modules that operate independently of endogenous networks. Beyond understanding plant development, these capabilities open avenues for engineering crops with dynamic architectures, enhanced plasticity, and improved resilience to complex and fluctuating stresses. In this review, we synthesise insights from natural diversity, developmental biology, and synthetic regulatory engineering to outline how plant architecture can be rationally redesigned. We argue that integrating synthetic biology with modern breeding and modelling frameworks will be essential for generating the next generation of programmable crops; i.e., varieties capable of sustaining productivity and stability in an era of unprecedented environmental and geopolitical changes. Full article

Eicosanoids and their receptors act as key regulators of inflammation, calcium homeostasis, mitochondrial function, and cardiomyocyte survival, thereby contributing to the onset and progression of cardiac dysfunction. This review aims to summarize the evidence to underscore the pivotal role of eicosanoids and their receptors in the pathophysiology of cardiomyopathy, analysing the potential protective activity of traditional and natural compounds to counteract cardiovascular disease onset and progression. Among eicosanoid receptors, prostaglandin E2 receptor 3 (EP3), prostaglandin E2 receptor 4 (EP4), chemoattractant receptor expressed on type 2 helper T cells (CRTH2), and thromboxane prostanoid (TP) emerge as critical modulators with distinct and often opposing effects on cardiac physiology. While EP3 and CRTH2 are predominantly associated with detrimental outcomes such as impaired contractility and enhanced apoptosis, EP4 signalling consistently demonstrates cardioprotective properties, including improved calcium handling and preservation of mitochondrial integrity. These findings highlight the therapeutic potential of selectively targeting eicosanoid receptor pathways to mitigate cardiac remodelling and dysfunction. In parallel, increasing attention has been directed toward natural bioactive compounds as complementary strategies for cardioprotection. Polyphenols, flavonoids, carotenoids, and other nutraceuticals exert beneficial effects through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, often intersecting with eicosanoid signalling pathways. Their ability to modulate oxidative stress and inflammatory responses suggests a promising role in preventing or attenuating cardiomyopathy, particularly in metabolic and drug-induced contexts. Future research should focus on well-designed clinical trials, a deeper characterization of receptor-specific signalling networks, and the development of targeted therapies that combine pharmacological and nutraceutical approaches. Overall, a better understanding of eicosanoid-mediated mechanisms may open new ways for cardiomyopathy prevention and treatment, ultimately improving patient outcomes and reducing the burden of cardiovascular disease. Full article

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness driven by elevated intraocular pressure from compromised aqueous outflow. While genome-wide association studies have identified numerous risk loci, specific candidate proteins and their cellular mechanisms remain elusive. We employed a multi-omics framework integrating UK Biobank plasma proteomics (N = 53,022) and large-scale POAG GWAS summary statistics. We performed a Proteome-Wide Association Study, Mendelian Randomization, and Bayesian colocalization to infer causality. Identified candidates were mapped to human and mouse ocular scRNA-seq atlases to characterize cell-type specificity, followed by druggability assessments. We prioritized five putative causal proteins, with SEL1L and TFPI demonstrating the strongest evidence. Cross-species scRNA-seq revealed that SEL1L and SERPINF1 are robustly expressed in the trabecular meshwork (TM), particularly the juxtacanalicular tissue, implicating them in outflow resistance. Conversely, TFPI and SLC9A3R2 localize to Schlemm’s canal endothelium, suggesting a role in modulating barrier function. Pathway analyses highlighted endoplasmic reticulum protein processing and coagulation cascades. This study maps putative causal POAG proteins to conventional outflow pathway cells, highlighting SEL1L as a novel target for TM homeostasis and TFPI for drug repurposing, thereby providing data-driven hypotheses to facilitate precision glaucoma therapeutics. Full article

Retinal neurovascular unit (RNVU) dysfunction underlies major blinding and neurodegenerative conditions including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal ischemia–reperfusion (RIR) injury, and Alzheimer’s disease (AD)-associated retinopathy. Within the RNVU, calcium ions coordinate neurotransmission, glial activation, vascular tone, and blood–retinal barrier maintenance, and calcium dysregulation is emerging as a unifying pathogenic hub across these conditions. Although upstream triggers differ, including mechanical stress in glaucoma, hyperglycemia in DR, oxidative damage in AMD, ischemic energy failure in RIR, and amyloid-β–driven endoplasmic reticulum stress in AD, all converge on disruption of intracellular calcium homeostasis, producing shared downstream consequences including excitotoxic injury of retinal ganglion cells (RGCs), Müller cell reactive gliosis, and pericyte hypercontraction. Broad-spectrum calcium channel blockade has shown limited clinical success, underscoring the need for cell-type-specific and pathway-selective approaches. This review therefore catalogs key interventional nodes, including transient receptor potential (TRP) channel antagonists, T-type calcium channel inhibitors, calcium/calmodulin-dependent protein kinase II (CaMKII) suppressors, and mitochondrial permeability transition pore (mPTP) inhibitors, and discusses how precision targeting of these pathways may restore RNVU homeostasis and open a therapeutic window into central nervous system (CNS) degenerative disorders. Full article

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a frequent and severe complication of open-heart surgery. Although oxidative/inflammatory mechanisms are known to contribute to its pathophysiology, the circulating factors involved are poorly understood. In this preliminary investigation, we evaluated the effects of plasma from patients undergoing cardiac surgery on endothelial and renal tubular cells at anesthesia induction (T0) and 48 h after surgery (T1). Plasma levels of thiobarbituric acid-reactive substances (TBARSs), glutathione (GSH), and nitric oxide (NO) were measured in parallel. At T0, patient plasma showed increased TBARSs and reduced GSH and NO levels, consistent with oxidative imbalance, and induced cellular injury. In both cell types, plasma exposure reduced cell viability and mitochondrial membrane potential, while it increased oxidant release. Endothelial cells also showed decreased NO production, whereas renal tubular displayed increased apoptotic markers and reduced anti-aging factors. At T1, these alterations were further aggravated only in patients who developed CSA-AKI, whose plasma caused more severe endothelial and tubular damage. These findings support the presence of circulating injurious factors in cardiac surgery patient plasma that may contribute to CSA-AKI pathogenesis and help identify patients at risk before irreversible kidney damage develops. Full article

Once written off as nothing more than a waste product of glycolysis, lactic acid is now seen as a key signaling molecule that operates across a wide range of physiological and pathological processes, from immune regulation and tumor metabolism to neural function. But its role goes beyond energy metabolism and cell signaling. Recent studies have uncovered a new type of post-translational modification called histone lactylation, in which lactate itself provides the lactoyl group attached to lysine residues on histones. This modification directly ties a cell’s metabolic state to the epigenetic control of gene expression. For example, histone lactylation helps shift macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype by fine-tuning gene transcription. In this review, we walk through the discovery and biochemical foundation of histone lactylation; discuss the likely writer and eraser enzymes that manage its dynamic changes; and highlight recent advances in understanding the role of this modification in inflammation, tumorigenesis, neurological disorders, and interactions with gut microbes. We also lay out key unanswered questions and consider why targeting protein lactylation might open up new therapeutic possibilities. Full article