Search Results (627)

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. Full article

This work experimentally investigates the behavior of a new indoor air conditioning system based on the application of Peltier cells in a Horizontal Air–Ground Heat Exchanger (HAGHE). To this end, a laboratory-scale prototype focusing exclusively on the terminal section of the system was developed and tested under controlled conditions. A series of configurations was tested, each representing an evolution of the previous one. The results highlight the strong dependence of system performance on airflow velocity, applied voltage, and heat dissipation effectiveness, demonstrating both the potential and the critical limitations of the proposed configurations. The most promising results were obtained in the advanced (fourth and fifth) configurations, yielding average temperature increases of approximately +1.9 °C on the hot flow and decreases ranging from −1.0 °C to −1.7 °C on the cold flow at moderate total voltages (40–50 V) and higher airflow velocities (0.5–0.6 m/s). In line with the principles of the circular economy, the prototype was constructed using recycled materials, including plastic pipes and Peltier cells recovered from discarded devices. Full article

Solar cell installations are most often located in places where there is abundant open space. It is however more difficult to place solar cells in urban environments due to space constraints and suboptimal light conditions. One potential solution is to create three-dimensional structures covered with solar cell modules having a relatively small physical footprint (e.g., with a shape such as a tower), creating a three-dimensional (3D) solar cell installation (sometimes called ‘power towers’). To explore this, we fabricate physical models of 3D towers covered with solar cells (here referred to as 3DPV towers) and test them in a model urban environment. A number of different 3DPV designs are explored and are benchmarked against solar cells that are placed flat on the ground or inclined at 30° to the horizontal. When normalised by their physical footprint area, we find that 3DPV towers can produce as much as 3.05 times as much power in an ‘urban environment’ as the power generated by a conventionally sited solar cell that is inclined at 30°. Significantly, we also show that light scattered from nearby buildings can enhance the power collected by 3DPV towers by up to 29%. These findings indicate that 3DPV towers present a promising opportunity to generate solar power in complex urban environments. Full article

Multiple myeloma (MM) is a clonal plasma cell neoplasm characterized by autonomous immunoglobulin overproduction. Despite associations between serum metabolites and MM, causal mechanisms remain unclear. Here, we employed bidirectional Mendelian randomization (MR) using 452 serum metabolites to elucidate causal associations with MM risk. The inverse variance-weighted (IVW) method was prioritized, complemented by MR-Egger and weighted median (WM) analyses to address horizontal pleiotropy. Sensitivity analyses—including Cochran’s Q test, MR-Egger intercept evaluation, and leave-one-out (LOO) robustness checks—confirmed result stability. Pathway enrichment was performed using MetaboAnalyst 6.0. RNA-seq data were integrated to identify transcriptional regulators and signaling pathways mediating serum metabolite-driven MM. Among 21 metabolites significantly associated with MM, 8 exhibited protective inverse correlations, while 13 showed risk-enhancing effects. Sensitivity analyses further confirmed the validity of the observed relationships, while bidirectional MR confirmed no reverse causality. Pathway enrichment highlighted valine/leucine/isoleucine biosynthesis and biotin metabolism as pivotal pathways. Integrating transcriptomic data revealed 11 overlapping genes enriched in metal ion transmembrane transporter activity and glycosaminoglycan biosynthesis—chondroitin sulfate/dermatan sulfate. This study established a causal relationship between specific serum metabolites and MM and revealed that key genes may affect the development of MM through metabolic-epigenetic crosstalk, providing preliminary insights into potential therapeutic targets. Full article

Craniofacial development is orchestrated by a finely regulated interplay of numerous genes and signaling pathways. Palatogenesis proceeds through a complex, stepwise process, in which endogenous mechanical stresses within tissues have been implicated. However, the impact of exogenous fluidic flow mechanical stress derived from maternal movement on palatal development remains unclear. In this study, we investigated the effect of exogenous fluidic flow mechanical stress on palatal morphogenesis, focusing on the horizontal outgrowth of palatal shelves after elevation. Palatal tissues dissected from mouse embryos were subjected to organ culture with or without mechanical loading (loaded and unloaded groups, respectively). Stress magnitude was quantified by calculating wave energy, and morphometric and molecular analyses were performed. Compared with the unloaded group, palatal shelves in the loaded group showed significant increases in thickness and volume, accompanied by enhanced cell proliferation, nuclear translocation of YAP and β-catenin, and upregulation of the osteogenic markers Osterix and Osteocalcin. No significant difference in apoptosis was observed. These findings indicate that exogenous mechanical stress promotes cell proliferation and osteogenic differentiation through the Hippo and WNT/β-catenin pathways in palate explants. Our results suggest that moderate maternal movement-induced mechanical stress contributes to normal palatogenesis, providing new insights into the mechanisms underlying cleft palate. Full article

The global challenge of antimicrobial resistance (AMR) has been framed primarily in terms of genetic resistance mechanisms. Nevertheless, bacteria can also survive antimicrobial stress through phenotypic plasticity, resulting in transient, non-genetic states such as tolerance, persistence, and population-level resilience. These phenotypic states complicate diagnostic efforts, diminish antibiotic efficacy, and contribute to the chronic nature of infections even in the absence of heritable resistance. This review evaluates phenotypic plasticity as a significant yet underrecognized factor in AMR, with a focus on responses to oxidative and photodynamic stress. Key manifestations of plasticity are discussed, including morphological and metabolic remodeling such as filamentation, small-colony variants, and metabolic rewiring, as well as envelope- and biofilm-associated heterogeneity and regulatory flexibility mediated by gene networks and horizontal regulatory transfer. The review highlights plastic responses elicited by reactive oxygen species-mediated stress and antimicrobial photodynamic inactivation, where single-cell heterogeneity, biofilm and mucus barriers, and light-dependent cues influence bacterial survival. Case studies are presented to demonstrate how photodynamic strategies can induce transient protective states and act synergistically with antibiotics, revealing mechanisms of action that extend beyond conventional single-target therapeutic models. Drawing on evidence from single-cell analyses, biofilm ecology, and experimental evolution, this review establishes phenotypic plasticity as a central element in the chemical biology of AMR. Enhanced understanding of plasticity is essential for advancing diagnostics, informing the development of adjuvant therapies, and predicting bacterial responses to novel antimicrobial interventions. Full article

Composite integrative and conjugative elements (ICEs) frequently mediate the co-transfer of multiple antibiotic resistance genes during horizontal gene transfer, but their formation mechanisms remain unclear. This study investigated the site-specific integration of Tn1806 into ICESa2603-family ICEs in Streptococcus agalactiae by conjugation experiments. PCR screening of 161 S. agalactiae clinical isolates identified potential Tn1806-like ICE carriers; whole-genome sequencing was performed to further characterize the macrolide-resistance isolates from this group. PCR detection resulted in 24 carrying Tn1806-like ICEs being found, five of which were macrolide-resistant. Genomic analysis for these five revealed distinct Tn1806-like ICEs (ICESag16, ICESag57, ICESag139, ICESag167, and ICESag220), three of which were found nested within another ICE (ICESpy009, an ICESa2603-family ICE). Conjugation experiments confirmed ICESag167 could integrate into the snf2 (methyltransferase containing a SNF2 helicase domain) of ICESpy009 in recipient cells, generating a composite ICE. Re-conjugation verified the transferability of composite ICE at low frequencies (8.63 × 10⁻⁸), during which some nested ICESag167 were excised and transferred independently. This work provides first experimental evidence supporting Tn1806 nesting within another ICE as a mechanism for resistance accumulation and mobile element evolution in S. agalactiae. The spread of such composite ICEs may confer multiple forms of resistance to new hosts, challenging infection treatment and raising public health concerns. Full article

Extracellular vesicles (EVs) are membrane-bound nanoparticles released by almost all cell types into the extracellular space, acting as important mediators of intercellular communication by transferring proteins, lipids, and nucleic acids horizontally. EVs are generally classified into small EVs (<200 nm), medium/large EVs (>200 nm), microvesicles, and apoptotic bodies, with current classification methods focusing on physical properties, molecular composition, and cellular origin, as detailed in the MISEV2023 guidelines. EVs are highly promising for diagnostic and therapeutic applications due to their intrinsic biocompatibility, stability in biological fluids, capacity to carry diverse molecular cargo, and potential for drug delivery and functionalization to enable targeted delivery and tissue repair. This narrative review discusses the emerging roles of EVs across various medical fields, including obstetrics and gynecology, ophthalmology, otorhinolaryngology, urology, oncology, orthopedics, neurology, immunology, wound healing, chronic pain management, dermatology, and cardiology. In each discipline, EVs show potential as biomarkers for diagnosing physiological or pathological conditions and as carriers for targeted drug delivery and regenerative treatments. Exosomes, a major type of small EVs, have especially attracted attention as versatile nanocarriers for precision medicine. However, translation into clinical practice requires addressing key pitfalls, including the standardization of isolation and characterization protocols, dose definition, GMP-compliant large-scale production, and regulatory approval. Ongoing interdisciplinary collaboration across disciplines and thorough clinical testing will be essential to unlock the full biomedical potential of EVs and establish them as transformative tools in personalized healthcare. Full article

Baroclinic wave resonance, particularly Rossby waves, has attracted great interest in ocean and atmospheric physics since the 1970s. Research on Rossby wave resonance covers a wide variety of phenomena that can be unified when focusing on quasi-stationary Rossby waves traveling at the interface of two stratified fluids. This assumes a clear differentiation of the pycnocline, where the density varies strongly vertically. In the atmosphere, such stationary Rossby waves are observable at the tropopause, at the interface between the polar jet and the ascending air column at the meeting of the polar and Ferrel cell circulation, or between the subtropical jet and the descending air column at the meeting of the Ferrel and Hadley cell circulation. The movement of these air columns varies according to the declination of the sun. In oceans, quasi-stationary Rossby waves are observable in the tropics, at mid-latitudes, and around the subtropical gyres (i.e., the gyral Rossby waves GRWs) due to the buoyant properties of warm waters originating from tropical oceans, transported to high latitudes by western boundary currents. The thermocline oscillation results from solar irradiance variations induced by the sun’s declination, as well as solar and orbital cycles. It is governed by the forced, linear, inviscid shallow water equations on the β-plane (or β-cone for GRWs), namely the momentum, continuity, and potential vorticity equations. The coupling of multi-frequency wave systems occurs in exchange zones. The quasi-stationary Rossby waves and the associated zonal/polar and meridional/radial geostrophic currents modify the geostrophy of the basin. Here, it is shown that the ubiquity of resonant forcing in (sub)harmonic modes of Rossby waves in stratified media results from two properties: (1) the natural period of Rossby wave systems tunes to the forcing period, (2) the restoring forces between the different multi-frequency Rossby waves assimilated to inertial Caldirola–Kanai (CK) oscillators are all the stronger when the imbalance between the Coriolis force and the horizontal pressure gradients in the exchange zones is significant. According to the CK equations, this resonance mode ensures the sustainability of the wave systems despite the variability of the forcing periods. The resonant forcing of quasi-stationary Rossby waves is at the origin of climate variations, as well-known as El Niño, glacial–interglacial cycles or extreme events generated by cold drops or, conversely, heat waves. This approach attempts to provide some new avenues for addressing climate and weather issues. Full article

The increasing demand for air travel has intensified the need for more efficient air traffic management (ATM) solutions. One of the key challenges in this domain is the optimal sectorization of airspace to ensure balanced controller workload and operational efficiency. Traditional airspace sectors, typically static and based on historical flow patterns, often fail to adapt to evolving traffic complexity, resulting in imbalanced workload distribution and reduced system performance. This study introduces a novel methodology for optimizing ATC sector geometries based on air traffic complexity indicators, aiming to enhance the balance of operational workload across sectors. The proposed optimization is formulated in the horizontal plane using a two-dimensional cell-based airspace representation. A graph-partitioning optimization model with spatial and operational constraints is applied, along with a refinement step using adjacent-cell pairs to improve geometric coherence. Tested on real data from Madrid North ACC, the model achieved significant complexity balancing while preserving sector shapes in a real-world case study based on a Spanish ACC. This work provides a methodological basis to support static and dynamic airspace design and has the potential to enhance ATC efficiency through data-driven optimization. Full article

Orthodontic force magnitude influences angiogenesis during orthodontic tooth movement (OTM); however, the role of senescent cells remains largely unclear. This study investigated the localization of senescent cells and their expression of vascular endothelial growth factor (VEGF) during angiogenesis using a rat horizontal OTM model with different force magnitudes. Nickel–titanium coil springs exerting 60 g or 180 g of orthodontic force were applied to the maxillary first molar of 15-week-old male Sprague–Dawley rats; untreated rats served as controls. Tooth movement was evaluated by stereomicroscopy and micro-computed tomography. Senescent cells (p21, p16) and angiogenesis (CD31 and VEGF) were evaluated by multiplex immunofluorescence. Tooth movement was observed under both the 60 g and 180 g conditions. The 60 g group showed increased cellularity, vascular density, and VEGF expression, suggesting an optimal mechanical force. In contrast, the 180 g group reduced cellularity and angiogenesis, consistent with excessive force. Senescent cells were more abundant in the 60 g group, with over 40% expressing VEGF. These findings suggest that force magnitude influences the presence of VEGF⁺ senescent cells, which may be associated with the angiogenic process in OTM. This work provides insights into the mechanisms underlying optimal force in orthodontic treatment. Full article

In this study, copper–carbon material composites, Cu/CM (where CM is reduced graphene oxide (rGO), graphitic carbon nitride (g-C₃N₄), their mixture, and N-doped reduced graphene oxide (N-rGO)), were prepared using a simple method of chemical reduction of copper cations in the presence of CM related to molecular-level mixing methods. Additionally, copper cations from its oxides present in the composites were reduced in an electrochemical cell by depositing them on the surface of a horizontally positioned cathode. The structure and morphology of the Cu/CM composites were studied using electron microscopy and X-ray diffraction analysis. The thermal stability and elemental analysis were determined for the carbon materials. The resulting Cu/CM composites were used as electrocatalysts in the electrohydrogenation of the aromatic ketone, acetophenone. Cu/rGO and Cu/N-rGO composites with a 1:1 ratio exhibited catalytic activity in this process, increasing the rate of APh hydrogenation and its degree of conversion with the selective formation of a single product, methyl phenyl carbinol (or 1-phenylethanol), compared to the electrochemical reduction of APh on a cathode without a catalyst. The Cu/N-rGO composite demonstrated the highest electrocatalytic activity. Full article

The study establishes a comprehensive mathematical modeling framework for solar-driven hydrogen production by integrating a triple-diode photovoltaic (PV) model, an alkaline electrolyzer, and a hydrogen turbine (H₂T), subsequently using hybrid power utilization to optimize hydrogen output. The Triple-Diode Model (TDM) accurately reproduces the electrical performance of a 144-cell photovoltaic module under standard test conditions (STC), enabling precise calculations of hourly maximum power point outputs based on real-world conditions of global horizontal irradiance and ambient temperature. The photovoltaic system produced 1.07 MWh during the summer months (May to September 2025), which was sent straight to the alkaline electrolyzer. The electrolyzer, using Specific Energy Consumption (SEC)-based formulations and Faraday’s law, produced 22.6 kg of green hydrogen and used around 203 L of water. The generated hydrogen was later utilized to power a hydrogen turbine (H₂T), producing 414.6 kWh, which was then integrated with photovoltaic power to create a hybrid renewable energy source. This hybrid design increased hydrogen production to 31.4 kg, indicating a substantial improvement in renewable hydrogen output. All photovoltaic, electrolyzer, and turbine models were integrated into a cohesive MATLAB R2024b framework, allowing for an exhaustive depiction of system dynamics. The findings validate that the amalgamation of H₂T with photovoltaic-driven electrolysis may significantly improve both renewable energy and hydrogen production. This research aligns with Saudi Vision 2030 and global clean-energy initiatives, including the Paris Agreement, to tackle climate change and its negative impacts. An integrated green hydrogen system, informed by this study’s findings, could significantly improve energy sustainability, strengthen production reliability, and augment hydrogen output, fully aligning with economical, technical, and environmental objectives. Full article

This study presents an integrated, low-cost system for measuring extremely small displacements in Ionic Polymer–Metal Composite (IPMC) actuators operating in aqueous environments. A custom optical setup was developed, combining a glass tank, a tubular microscope with a 10× achromatic objective, a digital USB camera and uniform LED backlighting, enabling side-view imaging of the actuator with high contrast. The microscopy system achieves a spatial sampling of 0.536 μm/pixel on the horizontal axis and 0.518 μm/pixel on the vertical axis, while lens distortion is limited to a maximum edge deviation of +0.015 μm/pixel (≈+2.8%), ensuring consistent geometric magnification across the field of view. On the image-processing side, a predictive grid-based tracking algorithm is introduced to localize the free tip of the IPMC. The method combines edge detection, Harris corners and a constant-length geometric constraint with an adaptive search over selected grid cells. On 1920 × 1080-pixel frames, the proposed algorithm achieves a mean processing time of about 10 ms per frame and a frame-level detection accuracy of approximately 99% (98.3–99.4% depending on the allowed search radius) for actuation frequencies below 2 Hz, enabling real-time monitoring at 30 fps. In parallel, dedicated electronic circuitry for supply and load monitoring provides overvoltage, undervoltage, open-circuit and short-circuit detection in 100 injected fault events, all faults were detected and no spurious triggers over 3 h of nominal operation. The proposed microscopy and tracking framework offer a compact, reproducible and high-resolution alternative to laser-based or Digital Image Correlation techniques for IPMC displacement characterization and can be extended to other micro-displacement sensing applications in submerged or challenging environments. Full article

This study proposes a novel four-pointed-star-shaped honeycomb structure having zero Poisson’s ratio, designed to overcome the stress concentration inherent in traditional point-to-point connected star-shaped honeycombs.By introducing a horizontal connecting wall at cell junctions, the new configuration achieves a more uniform stress distribution and enhanced structural stability. An analytical model for the in-plane equivalent elastic modulus was derived using homogenization theory and the energy method. The model, along with the structure’s zero Poisson’s ratio characteristic, was validated through finite element simulations and experimental compression tests. The simulations predicted an equivalent elastic modulus of 51.71 MPa (Y-direction) and 74.67 MPa (X-direction), which aligned closely with the experimental measurements of 56.61 MPa and 60.50 MPa, respectively. The experimental Poisson’s ratio was maintained near zero (v = 0.02). Parametric analysis further revealed that the in-plane equivalent elastic modulus decreases with increases in the wall angle, horizontal wall length, and wall thickness. This work demonstrates a successful structural optimization strategy that improves both mechanical performance and manufacturability for zero Poisson’s ratio honeycomb applications. Full article