Search Results (3,496)

Insects achieve millisecond sensor–motor loops with tiny sensors, compact neural circuits, and powerful actuators, embodying the principles of Edge AI. We present a comprehensive architectural blueprint translating insect neurobiology into a hardware–software stack: a latency-first control hierarchy that partitions tasks between a fast, dedicated Reflex Tier and a slower, robust Policy Tier, with explicit WCET envelopes and freedom-from-interference boundaries. This architecture is realized through a neuromorphic Reflex Island utilizing spintronic primitives, specifically MRAM synapses (for non-volatile, innate memory) and spin-torque nano-oscillator (STNO) reservoirs (for temporal processing), to enable instant-on, memory-centric reflexes. Furthermore, we formalize the biological governance mechanisms, demonstrating that, unlike conventional ICEs and miniturbines that exhibit narrow best-efficiency islands, insects utilize active thermoregulation and DGC (Discontinuous Gas Exchange) to maintain nearly constant energy efficiency across a broad operational load by actively managing their thermal set-point, which we map into thermal-debt and burst-budget controllers. We instantiate this integrated bio-inspired model in an insect-like IFEVS thruster, a solar cargo e-bike with a neuromorphic safety shell, and other safety-critical edge systems, providing concrete efficiency comparisons, latency, energy budgets, and safety-case hooks that support certification and adoption across autonomous domains. Full article

The Lunar Gateway is a planned small space station that will orbit the Moon and serve as a central hub for NASA’s Artemis program to return humans to the lunar surface and to prepare for Mars missions. This work presents a hybrid optimization strategy for designing minimum-fuel transfers from an Earth orbit to a Lunar Near-Rectilinear Halo Orbit. The corresponding optimal control problem—crucial for missions to NASA’s Lunar Gateway—is characterized by a high-dimensional, non-convex solution space due to the multi-body gravitational environment. To tackle this challenge, a two-stage hybrid optimization scheme is employed. The first stage uses a Genetic Algorithm heuristic as a global search strategy, to identify promising feasible trajectory solutions. Subsequently, the initial solution guess (or guesses) produced by GA are improved by a local optimizer based on a Sequential Quadratic Programming method: from a suitable initial guess, SQP rapidly converges to a high-precision feasible solution. The proposed methodology is applied to a representative cargo mission case study, demonstrating its efficiency. Our numerical results confirm that the hybrid optimization strategy can reliably generate mission-grade quality trajectories that satisfy stringent constraints while minimizing propellant consumption. Our analysis validates the combined GA-SQP optimization approach as a robust and efficient tool for space mission design in the cislunar environment. Full article

It is challenging to manoeuvre large deck cargo barges within the confined, congested port waters, especially when berthing and unberthing at a U-shaped basin. To investigate the safety operation of those ships under these complex circumstances, the research employs an integrated methodology to enhance safety. Ship manoeuvring simulations were first conducted to determine the critical environmental limits (including wind, current, and wave thresholds) under which safe operations are feasible. Subsequently, for safe mooring, Computational Fluid Dynamics (CFD) simulations were applied to analyse the hydrodynamic forces acting on the barge while berthed. These CFD results were crucial for determining the optimal mooring configuration (number, type, and arrangement of lines) required to sustain the environmental loads. The combined insights from manoeuvring simulations and CFD analysis provide a comprehensive framework for port planners and mariners, which will substantially improve the operational safety of large deck cargo barges utilising U-shaped berths in busy and spatially constrained port areas. Full article

Extracellular vesicles (EVs) from human body fluids are valuable tools for biomarker discovery and for exploring the mechanisms underlying various pathologies, including infectious diseases. The translation of EV research into clinical practice is however hindered by the variability in EV pre-clinical investigations. Therefore, standardisation of analytical procedures and reporting policies is essential. Human serum is a key biological matrix for biomarker discovery and is commonly stored within biobanks. Here, we investigated different strategies for EV enrichment from small volumes of biobanked serum and evaluated their impact on EVs’ downstream analyses. EVs were obtained from 250 μL of biobanked serum using ultracentrifugation (UC), size-exclusion chromatography-based methods (ExoSpin-ES, qEV1-35 nm, and qEV1-70 nm), or ExoRNeasy (ER). The resulting EVs were subsequently characterised for morphology, concentration, surface phenotype, and multi-omics profiles. All methods successfully enriched small EVs expressing tetraspanins on their surface, although at different concentrations. The most efficient method for proteomics analyses was qEV1-70 nm, followed by ES, which was more susceptible to contamination by serum proteins. EV-miRNA cargo was effectively profiled in UC-, ES-, and ER-EVs, with the latter providing the broadest miRNA coverage. Our results support the feasibility of using biobanked serum for EV-based research and further highlight the importance of selecting appropriate EV enrichment methods, since they influence both miRNA and protein cargo characterisation. Full article

Side flaps are critical structural components of flat freight wagons, directly affecting cargo safety during transportation and playing an essential role in loading and unloading operations. Over the years, their reliability has been well established, with standardized designs available in UIC technical datasheets. Despite this standardization, the introduction of newly manufactured or redesigned components necessitates technological validation through Finite Element Method (FEM) simulations and/or physical testing. This requirement holds irrespective of whether the component in question adheres to existing standards or is a novel development. This study presents the creation and application of computational models for the structural sizing and strength assessment of side flaps for flat wagons. The models are verified through a series of physical tests conducted by a research team at the Technical University of Sofia. Full article

Extracellular vesicle (EV)-based therapies have emerged as promising, cell-free approaches for dental tissue regeneration. This narrative review integrates mechanistic insights, therapeutic efficacy data, and safety and delivery considerations from in vitro and in vivo studies to elucidate the molecular mechanisms by which EVs, particularly those from dental pulp stem cells (DPSCs) and mesenchymal stem cells (MSCs), drive regenerative processes via key signalling axes (PI3K/Akt, MAPK, BMP/Smad, and Hedgehog). Preclinical studies demonstrate that unmodified and engineered EVs enhance odontogenic differentiation, angiogenesis, bone repair, and immunomodulation in models of pulp regeneration, alveolar bone defects, osteonecrosis, and periodontitis. Isolation and purification methodologies were also evaluated, comparing ultracentrifugation, size-exclusion chromatography, and density-cushion approaches, and discussing how protocol variations affect EV purity, dosing metrics, and functional reproducibility. Early-phase clinical evaluations report only low-grade transient adverse events, underscoring a generally favourable safety profile. Despite these encouraging results, significant challenges remain: heterogeneity in EV cargo composition, lack of standardised potency assays, and incomplete long-term safety data. The review highlights the urgent need for rigorous, harmonised regulatory frameworks and robust quality control measures to ensure that EV-based modalities can be translated into safe, effective, and reproducible therapies in regenerative dentistry. Full article

This article describes the possibilities of using universal flat wagons to transport long cargoes and suggests measures for upgrading them, which involve the installation of superstructures on the load-bearing structures to keep the cargo from overturning. The study was conducted using the flat wagon model 13-401. Several options for implementing such superstructures have been considered. The load-bearing structure of the flat wagon was modeled as a rod system. The most rational option for upgrading was evaluated by assessing the force factors acting in the structure under the influence of external loads. According to the chosen upgrade option, a spatial model of the bearing structure of the flat wagon was built, and its strength was calculated using the finite element method. The proposed option was found to be appropriate. The results of the research can be used to improve the efficiency of transportation of long cargoes by universal flat wagons. Full article

In this study, using global liner shipping schedules, UNCTAD’s Port Liner Shipping Connectivity Index and Liner Shipping Bilateral Connectivity Index, together with bilateral trade-value data for 2022–2024, we construct a multilayer weighted port-to-port network that explicitly embeds port-level cargo-handling and service organisation capabilities, as well as demand-side routing pressure, into node and edge weights. Building on this network, we apply CONCOR-based structural-equivalence analysis to delineate functionally homogeneous port clusters, and adopt a structural role identification framework that combines multi-indicator connectivity metrics with Rank-Sum Ratio–entropy weighting and Probit-based binning to classify ports into high-efficiency core, bridge-control, and free-form bridge roles, thereby tracing the reconfiguration of cluster-level functional structures before and after the Red Sea crisis. Empirically, the clustering identifies four persistent communities—the Intertropical Maritime Hub Corridor (IMHC), Pacific Rim Mega-Port Agglomeration (PRMPA), Southern Commodity Export Gateway (SCEG), and Euro-Asian Intermodal Chokepoints (EAIC)—and reveals a marked spatial and functional reorganisation between 2022 and 2024. IMHC expands from 96 to 113 ports and SCEG from 33 to 56, whereas EAIC contracts from 27 to 10 nodes as gateway functions are reallocated across clusters, and the combined share of bridge-control and free-form bridge ports increases from 9.6% to 15.5% of all nodes, demonstrating a thicker functional backbone under rerouting pressures. Spatially, IMHC extends from a Mediterranean-centred configuration into tropical, trans-equatorial routes; PRMPA consolidates its role as the densest trans-Pacific belt; SCEG evolves from a commodity-based export gateway into a cross-regional Southern Hemisphere hub; and EAIC reorients from an Atlantic-dominated structure towards Eurasian corridors and emerging bypass routes. Functionally, Singapore, Rotterdam, and Shanghai remain dominant high-efficiency cores, while several Mediterranean and Red Sea ports (e.g., Jeddah, Alexandria) lose centrality as East and Southeast Asian nodes gain prominence; bridge-control functions are increasingly taken up by European and East Asian hubs (e.g., Antwerp, Hamburg, Busan, Kobe), acting as secondary transshipment buffers; and free-form bridge ports such as Manila, Haiphong, and Genoa strengthen their roles as elastic connectors that enhance intra-cluster cohesion and provide redundancy for inter-cluster rerouting. Overall, these patterns show that resilience under the Red Sea crisis is expressed through the cluster-level rebalancing of core–control–bridge roles, suggesting that port managers should prioritise parallel gateways, short-sea and coastal buffers, and sea–land intermodality within clusters when designing capacity expansion, hinterland access, and rerouting strategies. Full article

While drug-eluting cardiovascular devices, including drug-eluting stents and drug-coated balloons, have significantly reduced restenosis rates, they remain limited by delayed vascular healing, chronic inflammation, and late adverse events. These limitations reflect a fundamental mismatch between current device pharmacology, which relies on nonselective antiproliferative drugs, and the highly coordinated, cell-specific programs that orchestrate vascular repair. Extracellular vesicles (EVs), nanometer-scale membrane-bound particles secreted by virtually all cell types, provide a biologically evolved platform for intercellular communication and cargo delivery. In the cardiovascular system, EVs regulate endothelial regeneration, smooth muscle cell phenotype, extracellular matrix remodeling, and macrophage polarization through precisely orchestrated combinations of miRNA, proteins, and lipids. Here, we synthesize mechanistic insights into EV biogenesis, cargo selection, recruitment, and functional effects in vascular healing and inflammation and translate these into a formal framework for EV-inspired device engineering. We discuss how EV-based or EV-mimetic coatings can be designed to sense the local microenvironment, deliver encoded biological “instruction sets,” and function within ECM-mimetic scaffolds to couple local stent healing with systemic tissue repair. Finally, we outline the manufacturing, regulatory, and clinical trial issues that must be addressed for EV-inspired cardiovascular devices to transition from proof of concept to clinical reality. By shifting the focus from pharmacological suppression to biological regulation of healing, EV-based strategies offer a path to resolve the long-standing tradeoff between restenosis prevention and durable vascular healing. Full article

Glaucoma is a leading cause of irreversible blindness worldwide, with its asymptomatic progression highlighting the urgent need for early, minimally invasive biomarkers. Exosomes derived from the aqueous humor (AH) have emerged as promising candidates, as they carry proteins, nucleic acids, and lipids that reflect the physiological and pathological state of ocular tissues such as the trabecular meshwork and ciliary body. However, their low abundance, nanoscale size, and the limited volume of AH complicate detection and characterization. Conventional methods, including Western blotting, PCR or mass spectrometry, are labor-intensive, time-consuming, and often incompatible with microliter-scale samples. Electrochemical biosensors offer a highly sensitive, rapid, and low-volume alternative, enabling the detection of exosomal surface markers and internal cargos such as microRNAs, proteins, and lipids. Recent advances in nanomaterial-enhanced electrodes, microfluidic integration, enzyme- and nanozyme-mediated signal amplification, and ratiometric detection strategies have significantly improved sensitivity, selectivity, and multiplexing capabilities. While most studies focus on blood or serum, these platforms hold great potential for AH-derived exosome analysis, supporting early-stage glaucoma diagnosis, monitoring of disease progression, and evaluation of therapeutic responses. Continued development of miniaturized, point-of-care electrochemical biosensors could facilitate clinically viable, noninvasive exosome-based diagnostics for glaucoma. Full article

Cancer immunotherapy increasingly relies on nucleic acid-based vaccines, yet achieving efficient and safe delivery remains a critical limitation. Polyplexes—electrostatic complexes of cationic polymers and nucleic acids—have emerged as versatile carriers offering greater chemical tunability and multivalent targeting capacity compared to lipid nanoparticles, with lower immunogenicity than viral vectors. This review summarizes key design principles governing polyplex performance, including polymer chemistry, architecture, and assembly route—emphasizing microfluidic fabrication for improved size control and reproducibility. Mechanistically, effective systems support stepwise delivery: tumor targeting, cellular uptake, endosomal escape (via proton-sponge, membrane fusion, or photochemical disruption), and compartment-specific cargo release. We discuss therapeutic applications spanning plasmid DNA, siRNA, miRNA, mRNA, and CRISPR-based editing, highlighting preclinical data across multiple tumor types and early clinical evidence of on-target knockdown in human cancers. Particular attention is given to physiological barriers and engineering strategies—including size-switching systems, charge-reversal polymers, and tumor-penetrating peptides—that improve intratumoral distribution. However, significant challenges persist, including cationic toxicity, protein corona formation, manufacturing variability, and limited clinical responses to date. Current evidence supports polyplexes as a modular platform complementary to lipid nanoparticles in selected oncology indications, though realizing this potential requires continued optimization alongside rigorous translational development. Full article

Immunogenic cell death (ICD) is a subtype of regulated cell death characterized by the spatiotemporally coordinated emission of damage-associated molecular patterns (DAMPs), such as calreticulin (CALR), ATP, and high-mobility group box-1 (HMGB1), which collectively prime tumor-specific T-cell responses. Autophagy, a lysosome-dependent catabolic process, is increasingly recognized as a key modifier of antitumor immunity and the tumor microenvironment (TME). In preclinical models, autophagy can not only promote ICD by sustaining endoplasmic reticulum (ER) stress, eukaryotic translation initiation factor-2α (eIF2α) phosphorylation, and secretory pathways, but it can also limit ICD by degrading DAMPs, antigenic cargo, and major histocompatibility complex (MHC) molecules. The net outcome is highly context-dependent and determined by the tumor type, the nature and intensity of the stress, and the level at which autophagy is modulated. Herein, we summarize how autophagy affects the three canonical ICD-associated DAMPs, highlight solid-tumor models in which autophagy supports ICD, and contrast them with systems wherein autophagy inhibition is required for immunogenicity. We then focus on hematological malignancies, especially multiple myeloma, where recent reports implicate the autophagy-related protein GABARAP in bortezomib-induced ICD. Finally, we discuss the translational implications, including rational combinations of autophagy modulators with ICD-inducing chemotherapies, targeted drugs, and cellular immunotherapies, and outline the remaining challenges for safely harnessing the autophagy–ICD axis in the clinical setting. Full article

Diabetic wounds remain chronically non-healing due to impaired angiogenesis, persistent inflammation, and defective extracellular matrix remodelling. In recent years, stem cell-derived exosomes have emerged as a potent cell-free regenerative strategy capable of recapitulating the therapeutic benefits of mesenchymal stem cells while avoiding risks associated with direct cell transplantation. This review critically evaluates the preclinical evidence supporting the use of exosomes derived from adipose tissue, bone marrow, umbilical cord, and induced pluripotent stem cells for diabetic wound repair. These exosomes deliver bioactive cargos such as microRNAs, proteins, lipids, and cytokines that modulate key signalling pathways, including Phosphatidylinositol 3-kinase/Protein kinase (PI3K/Akt), Nuclear factor kappa B (NF-κB), Mitogen-activated protein kinase (MAPK), Transforming growth factor-beta (TGF-β/Smad), and Hypoxia inducible factor-1α/Vascular endothelial growth factor (HIF-1α/VEGF), thereby promoting angiogenesis, accelerating fibroblast and keratinocyte proliferation, facilitating re-epithelialization, and restoring immune balance through M2 macrophage polarization. A central focus of this review is the recent advances in exosome-based delivery systems, including hydrogels, microneedles, 3D scaffolds, and decellularized extracellular matrix composites, which significantly enhance exosome stability, retention, and targeted release at wound sites. Comparative insights between stem cell therapy and exosome therapy highlight the superior safety, scalability, and regulatory advantages of exosome-based approaches. We also summarize progress in exosome engineering, manufacturing, quality control, and ongoing clinical investigations, along with challenges related to standardization, dosage, and translational readiness. Collectively, this review provides a comprehensive mechanistic and translational framework that positions stem cell-derived exosomes as a next-generation, cell-free regenerative strategy with the potential to overcome current therapeutic limitations and redefine clinical management of diabetic wound healing. Full article

Abdominal aortic aneurysm (AAA) is a life-threatening disease. Although AAA is generally asymptomatic, the mortality rate remains very high once rupture occurs, even with successful treatment. The pathophysiology of AAA involves inflammatory cell infiltration, smooth muscle cell apoptosis, and extracellular matrix degradation. However, there are various unclear aspects of pathophysiology due to cellular heterogeneity and multifactorial disease. Moreover, there are no blood biomarkers or available pharmacological drugs for AAA. Extracellular vesicles (EVs) are lipid bilayer particles released from every type of cell for intercellular communication. EVs include proteins, DNA, RNA (mRNA, microRNA), and lipids. EV cargos are delivered to recipient cells and modulate their biological effects. Although fewer studies have investigated EVs in AAA than in other cardiovascular diseases with similar molecular mechanisms, recent research indicates that EVs play a significant role in AAA development. Further research on EVs and AAA will contribute to the elucidation of AAA pathophysiology and the development of novel pharmacological drugs. In this review, we summarize the EV-associated pathophysiology, EV-based biomarkers, and EV-based treatment strategies in AAA. We also discuss the prospects for EVs research in AAA. Full article

Emerging research indicates that neuronal activity is maintained by an architectural system of protons in a multi-scale fashion. Proton architecture is formed when organelles (such as mitochondria, endoplasmic reticulum, lysosomes, synaptic vesicles, etc.) are coupled together to produce dynamic energy domains. Techniques have been developed to visualize protons in neurons; recent advances include near-atomic structural imaging of organelle interfaces using cryo-tomography and nanoscale resolution imaging of organelle interfaces and proton tracking using ultra-fast spectroscopy. Results of these studies indicate that protons in neurons do not diffuse randomly throughout the neuron but instead exist in organized geometric configurations. The cristae of mitochondrial cells create oscillating proton micro-domains that are influenced by the curvature of the cristae, hydrogen bonding between molecules, and localized changes in dielectric properties that result in time-patterned proton signals that can be used to determine the metabolic load of the cell and the redox state of its mitochondria. These proton patterns also communicate to the rest of the cell via hydrated aligned proton-conductive pathways at the mitochon-dria-endoplasmic reticulum junctions, through acidic lipid regions, and through nano-tethered contact sites between mitochondria and other organelles, which are typically spaced approximately 10–25 nm apart. Other proton architectures exist in lysosomes, endosomes, and synaptic vesicles. In each of these organelles, the V-ATPase generates steep concentration gradients across their membranes, controlling the rate of cargo removal from the lumen of the organelle, recycling receptors from the surface of the membrane, and loading neurotransmitters into the vesicles. Recent super-resolution pH mapping has indicated that populations of synaptic vesicles contain significant heterogeneity in the amount of protons they contain, thereby influencing the amount of neurotransmitter released per vesicle, the probability of vesicle release, and the degree of post-synaptic receptor protonation. Additionally, proton gradients in each organelle interact with the cytoskeleton: the protonation status of actin and microtubules influences filament stiffness, protein–protein interactions, and organelle movement, resulting in the formation of localized spatial structures that may possess some type of computational significance. At multiple scales, it appears that neurons integrate the proton micro-domains with mechanical tension fields, dielectric nanodomains, and phase-state transitions to form distributed computing elements whose behavior is determined by the integration of energy flow, organelle geometry, and the organization of soft materials. Alterations to the proton landscape in neurons (e.g., due to alterations in cristae structure, drift in luminal pH, disruption in the hydration-structure of the cell, or imbalance in the protonation of cytoskeletal components) could disrupt the intracellular signaling network well before the onset of measurable electrical or biochemical pathologies. This article will summarize evidence indicating that proton–organelle interaction provides a previously unknown source of energetic substrate for neural computation. Using an integrated approach combining nanoscale proton energy, organelle interface geometry, cytoskeletal mechanics, and AI-based multiscale models, this article outlines current principles and unresolved questions related to the subject area as well as possible new approaches to early detection and precise intervention of pathological conditions related to altered intracellular energy flow. Full article