Search Results (4,503)

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

Background/Objectives: Conventional workflows, peripheral blood smears, and bone marrow assessment supplemented by LDI-PCR, molecular cytogenetics, and array-CGH, are expert-driven in the face of biological and imaging variability. Methods: We propose an AI pipeline that integrates convolutional neural networks (CNNs) and transfer learning-based models with two explainable AI (XAI) approaches, LIME and Grad-Cam, to deliver both high diagnostic accuracy and transparent rationale. Seven public sources were curated into a unified benchmark (66,550 images) covering ALL, AML, CLL, CML, and healthy controls; images were standardized, ROI-cropped, and split with stratification (80/10/10). We fine-tuned multiple backbones (DenseNet-121, MobileNetV2, VGG16, InceptionV3, ResNet50, Xception, and a custom CNN) and evaluated the accuracy and F1-score, benchmarking against the recent literature. Results: On the five-class task (ALL/AML/CLL/CML/Healthy), MobileNetV2 achieved 97.9% accuracy/F1, with DenseNet-121 reaching 97.66% F1. On ALL subtypes (Benign, Early, Pre, Pro) and across tasks, DenseNet121 and MobileNetV2 were the most reliable, achieving state-of-the-art accuracy with the strongest, nucleus-centric explanations. Conclusions: XAI analyses (LIME, Grad-CAM) consistently localized leukemic nuclei and other cell-intrinsic morphology, aligning saliency with clinical cues and model performance. Compared with baselines, our approach matched or exceeded accuracy while providing stronger, corroborated interpretability on a substantially larger and more diverse dataset. Full article

The global cancer burden continues to increase worldwide. Among the various treatment options, radiotherapy (RT), which employs high-energy ionizing radiation to destroy cancer cells, is one of the primary modalities for cancer. However, increasing the absorbed dose to the target volume also increases the risk of damage to surrounding healthy tissues. This radiation-induced toxicity to normal tissues limits the desirable dosage that can be delivered to the tumor, thereby constraining the effectiveness of radiation therapy in achieving tumor control. FLASH radiotherapy (FLASH-RT) has emerged as a promising technique due to its biological advantages. FLASH-RT involves the delivery of radiation at an ultra-high dose rate (≥40 Gy/s). Unlike conventional RT, FLASH-RT achieves comparable tumor control rates while significantly reducing damage to surrounding normal tissues, a phenomenon known as the FLASH effect. Although the mechanism behind the FLASH effect is not fully understood, this approach shows considerable promise for future cancer treatment. The development of specialized treatment planning systems (TPS) becomes imperative to facilitate the clinical implementation of FLASH-RT from experimental studies. These systems must account for the unique characteristics of FLASH-RT, including ultra-high dose rate delivery and its distinctive radiobiological effects. Critical reassessment and optimization of treatment planning protocols are essential to fully leverage the therapeutic potential of the FLASH effect. This review examines key considerations for the TPS development of electron and proton FLASH-RT, including electron and proton FLASH techniques, biological models, crucial beam parameters, and dosimetry, providing essential insights for optimizing TPS and advancing the clinical implementation of this promising therapeutic modality. Full article

Autoimmune diseases arise from the loss of antigen-specific tolerance, leading to chronic inflammation and tissue damage. Peptide-based therapeutics provide a precise strategy to restore immune balance by targeting autoreactive lymphocytes and antigen-presenting cells in tolerogenic contexts. These therapies induce regulatory T cells, modulate APC phenotypes, and can interfere with proinflammatory signaling. Advances in delivery technologies, including nanoparticles, lipid nanoparticles, hydrogels, and conjugates, improve peptide stability, co-deliver tolerogenic cues, and enable targeted antigen presentation. mRNA lipid nanoparticle platforms permit in situ expression of peptides or immunomodulatory molecules. Preclinical studies in models of type 1 diabetes, multiple sclerosis, and lupus demonstrate robust antigen-specific tolerance, while early-phase clinical trials show safety and mechanistic engagement. Insights from approved peptide therapies in allergy and other fields underscore the importance of epitope selection, delivery context, and biomarker-guided development. Collectively, these strategies suggest that rationally formulated, precisely targeted peptide therapeutics hold promise for achieving durable immune tolerance in autoimmune disease. Full article

Reducing CO₂ emissions in transport requires sustainable alternatives such as fuel cell electric vehicles. A critical challenge is the efficient and safe storage and fast refueling of hydrogen at 70 MPa. This study proposes a practical design-support tool to optimize hydrogen storage systems for heavy-duty vehicles with capacities up to 100 kg. A customizable, dynamic Matlab-Simulink model was developed, including all components from dispenser to onboard tanks, enabling evaluation of multiple design options. The aim is to provide clear guidelines to ensure fast, safe, and complete refueling compliant with SAE J2601-5 limits. Simulations showed Type III tanks deliver the best performance. The fastest refueling (~10 min) was achieved with shorter pipes, larger diameters and low temperatures (20 °C ambient, −40 °C dispenser), while Average Pressure Ramp Rate was maximized up to 9 MPa/min (220 g/s of hydrogen from the dispenser) without exceeding SAE limits for pressure and temperature. Full article

Bacterial carbonic anhydrases (CAs) are essential for intracellular pH regulation, bicarbonate homeostasis, and energy metabolism, making them attractive antimicrobial targets. Here, building on evidence that acetazolamide (AZA) delivered via hyaluronic acid–palmitate (HA-PA) nanocarriers impairs Escherichia coli growth and its glucose uptake, we investigated the physiological roles of β- and γ-class CAs using sulphonamide inhibitors with distinct selectivity encapsulated in HA-PA nanomicelles to ensure intracellular delivery. AZA, a potent dual β/γ-CA inhibitor, ethoxzolamide (EZA), a selective β-CA inhibitor, and hydrochlorothiazide (HCT), a weaker inhibitor of both classes, were tested for effects on bacterial physiology. The nanoparticles reduced growth in a dose- and class-dependent manner, with AZA exerting the strongest activity, EZA intermediate inhibition, and HCT only modest effects at higher concentrations. Early metabolic responses assessed via intracellular ATP after three hours of exposure revealed an unexpected and reproducible ATP increase for all inhibitors relative to untreated cells, suggesting reduced ATP consumption in bicarbonate-dependent pathways. These findings provide indirect yet compelling evidence that β- and γ-class CAs influence bacterial energy homeostasis and support the rationale for CA inhibition as an antimicrobial strategy, while highlighting HA-PA carriers as effective systems for delivering CA inhibitors intracellularly and enhancing their functional activity in bacterial cells. Full article

Metal nanoparticles (NP) are increasingly used in biomedical applications. Among them, silver NPs (AgNPs) are used as active components in antibacterial coatings for wound dressings, medical devices, implants, cosmetics, textiles, and food packaging. On the other hand, AgNPs can be toxic to humans, depending on the dose and route of exposure, as agents delivering silver to cells. The cysteine residues are the primary molecular targets in such exposures, due to the high affinity of Ag⁺ ions to thiol groups. The Endothelial monocyte-activating polypeptide II (EMAP II), a cleaved C-terminal peptide of the intracellular aminoacyl-tRNA synthetase multifunctional protein AIMP1, contains five cysteines exposed at its surface. This prompted the question of whether they can be targeted by Ag⁺ ions present at the AgNPs surface or released from AgNPs in the course of oxidative metabolism of the cell. We explored the interactions between recombinant EMAP II, tRNA, and AgNPs using UV-Vis and fluorescence spectroscopy, providing insight into the effects of AgNPs dissolution kinetics on interaction EMAP II with tRNA. In addition, the EMAP II fragments binding to intact AgNPs were established by heteronuclear ¹H-¹⁵N HSQC spectra utilizing a paramagnetic probe. Structural analysis of the EMAP II reveal that the 3D structure of protein was destabilized (partially denatured) by the binding of Ag⁺ ions released from AgNPs at the most exposed cysteines. Surprisingly, this effect enhanced tRNA affinity to EMAP II, lowering its $K_d$. The course of the EMAP II/tRNA/AgNP reaction was also modulated by other factors, such as the presence of Mg²⁺ ions and TCEP, a thiol-group protector used to mimic the reducing conditions of the cell. Full article

Copper (Cu) is an essential element required by all living cells, where it supports critical enzymatic and signaling functions. In cancer, this balance is often disrupted, creating vulnerabilities that can be therapeutically exploited. Changes in Cu availability have been shown to influence key immunoregulatory pathways, including those involved in inflammation, cell death, and immune evasion. Notably, Cu can drive expression of programmed death ligand 1 (PD-L1), contributing to immunosuppression, while also promoting immunogenic cell death, which stimulates adaptive immune responses. These dual effects highlight the complexity and therapeutic potential of Cu-based interventions, particularly in the context of immune modulation and toxicity. This review argues that Cu-based nanomedicines can selectively deliver high concentrations of bioactive Cu to tumor cells, inducing cell death and triggering adaptive immune responses. We summarize current knowledge on Cu’s roles in cancer and immunity, emphasizing recent insights into how these intersect through Cu-mediated modulation of anticancer immune pathways. Finally, we explore the clinical potential of Cu-based nanomedicines to convert immunologically “cold” tumors into “hot” ones, thereby improving responses to immunotherapy. Realizing this potential will depend on the thoughtful integration of Cu delivery approaches with existing immunotherapeutic strategies. Full article

Poly(ethylene oxide) (PEO)-based solid polymer electrolytes typically suffer from limited ionic conductivity at near-room temperature and often require inorganic reinforcement. Halide solid-state electrolytes such as Li₃InCl₆ (LIC) offer fast Li⁺ transport but are moisture-sensitive and typically require pressure-assisted densification. Here, we fabricate a flexible LIC–PEO composite electrolyte via slurry casting in acetonitrile with a small amount of LiPF₆ additive. The free-standing membrane delivers an ionic conductivity of 1.19 mS cm⁻¹ at 35 °C and an electrochemical stability window up to 5.15 V. Compared with pristine LIC, the composite shows improved moisture tolerance, and its conductivity can be recovered by mild heating after exposure. The electrolyte enables stable Li|LIC–PEO|Li cycling for >620 h and supports Li|LIC–PEO|NCM111 cells with capacity retentions of 84.2% after 300 cycles at 0.2 C and 80.6% after 150 cycles at 1.2 C (35 °C). Structural and surface analyses (XRD, SEM/EDX, XPS) elucidate the composite microstructure and interfacial chemistry. Full article

In situ preparation routes have become central to advancing lead sulfide (PbS) quantum dots (QDs) for solar-energy conversion, owing to their ability to create strongly coupled QD/oxide interfaces that are difficult to achieve with ex situ colloidal methods, along with their simplicity and potential for low-cost, scalable processing. This review systematically examines the fundamental mechanisms, processing levers, and device implications of the dominant in situ approaches successive ionic layer adsorption and reaction (SILAR), voltage-assisted SILAR (V-SILAR), and chemical bath deposition (CBD). These methods enable conformal QD nucleation within mesoporous scaffolds, improved electronic coupling, and scalable low-temperature fabrication, forming the materials foundation for high-performance PbS-based architectures. We further discuss how these in situ strategies translate into enhanced solar-energy applications, including quantum-dot-sensitized solar cells (QDSSCs) and photoelectrochemical (PEC) hydrogen production, highlighting recent advances in interfacial passivation, scaffold optimization, and bias-assisted growth that collectively suppress recombination and boost photocurrent utilization. Representative device metrics reported in recent studies indicate that in-situ-grown PbS quantum dots can deliver photocurrent densities on the order of ~5 mA cm⁻² at applied potentials around 1.23 V versus RHE in photoelectrochemical systems, while PbS-based quantum-dot-sensitized solar cells typically achieve power conversion efficiencies in the range of ~4–10%, depending on interface engineering and device architecture. These performances are commonly associated with conformal PbS loading within mesoporous scaffolds and quantum-dot sizes in the few-nanometer regime, underscoring the critical role of morphology and interfacial control in charge transport and recombination. Recent studies indicate that performance improvements in PbS-based solar-energy devices are primarily governed by interfacial charge-transfer kinetics and recombination suppression rather than QD loading alone, with hybrid heterostructures and inorganic passivation layers playing a key role in modifying band offsets and surface trap densities at the PbS/oxide interface. Remaining challenges are associated with defect-mediated recombination, transport limitations in densely loaded porous scaffolds, and long-term chemical stability, which must be addressed to enable scalable and durable PbS-based photovoltaic and photoelectrochemical technologies. 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

This work advances a 6G-ready, micro-granular SDN fabric that unifies high-performance edge data planes with intent-driven, multi-domain orchestration and cloud offloading. First, edge and cell-site whiteboxes are upgraded with Smart Network Interface Cards and embedded AI accelerators, enabling line-rate processing of data flows and on-box learning/inference directly in the data plane. This pushes functions such as traffic classification, telemetry, and anomaly mitigation to the point of ingress, reducing latency and backhaul load. Second, an SDN controller, i.e., ETSI TeraFlowSDN, is extended to deliver multi-domain SDN orchestration with native lifecycle management (LCM) for whitebox Network Operating Systems—covering onboarding, configuration-drift control, rolling upgrades/rollbacks, and policy-guarded compliance—so operators can reliably manage heterogeneous edge fleets at scale. Third, the SDN controller incorporates a new NFV-O client that seamlessly offloads network services—such as ML pipelines or NOS components—to telco clouds via an NFV orchestrator (e.g., ETSI Open Source MANO), enabling elastic placement and scale-out across the edge–cloud continuum. Together, these contributions deliver an open, programmable platform that couples in-situ acceleration with closed-loop, intent-based orchestration and elastic cloud resources, targeting demonstrable gains in end-to-end latency, throughput, operational agility, and energy efficiency for emerging 6G services. Full article

Preterm infants in neonatal intensive care units (NICUs) experience impaired neurodevelopment and dysregulated stress responses, partly due to a lack of tactile stimulation. Although massage therapy offers proven therapeutic benefits by stimulating C-tactile afferents through (gentle) dynamic touch, existing methods are limited by clinical staff variability and resource constraints. This work presents a compact soft-pneumatic actuator array (SPAA) utilizing four nylon–TPU actuators (modules) connected in series or in parallel to perform a sequential actuation; this array is designed to deliver safe, shear-free, and massage-like normal compression tailored for preterm infants. Actuator performance was characterized using a load-cell and a pressure sensor under different preloads (10–30 g), establishing operating internal pressures of 20–50 kPa, which produced target force ranges between 0.1 and 0.3 N. Two SPAA architectures were evaluated: (i) parallel manifold with branch resistances and (ii) series chain with graded outlet resistances, using passive fluidic sequencing for controlled activation. The series configuration achieved repeatable sequential actuation with programmable delays, essential for mimicking therapeutic massage patterns. These results demonstrate that passive soft-pneumatic sequencing can reliably deliver dynamic tactile stimuli within neurophysiological and safety constraints, laying the groundwork for standardized, automated neonatal massage therapy in NICUs. Full article

Decarbonizing industry, improving urban sustainability, and expanding clean energy use are key global priorities. This study presents a techno-economic analysis (TEA) and life-cycle assessment (LCA) of green hydrogen (GH₂) production via water electrolysis for low-carbon applications in the Central Asian region, with Uzbekistan considered as a representative case study. Solar PV and wind power are used as renewable electricity sources for a 44 MW electrolyzer. The assessment also incorporates recent advances in alkaline water electrolyzers (AWE) enhanced with metal–organic framework (MOF) materials, reflecting improvements in efficiency and hydrogen output. The LCA, performed using SimaPro, evaluates the global warming potential (GWP) across the full hydrogen production chain. Results show that the MOF-enhanced AWE system achieves a lower levelized cost of hydrogen (LCOH) at 5.18 $/kg H₂, compared with 5.90 $/kg H₂ for conventional AWE, with electricity procurement remaining the dominant cost driver. Environmentally, green hydrogen pathways reduce GWP by 80–83% relative to steam methane reforming (SMR), with AWE–MOF delivering the lowest footprint at 1.97 kg CO₂/kg H₂. In transport applications, fuel cell vehicles powered by hydrogen derived from AWE–MOF emit 89% less CO₂ per 100 km than diesel vehicles and 83% less than using SMR-based hydrogen, demonstrating the substantial climate benefits of advanced electrolysis. Overall, the findings confirm that MOF-integrated AWE offers a strong balance of economic viability and environmental performance. The study highlights green hydrogen’s strategic role in the Central Asian region, represented by Uzbekistan’s energy transition, and provides evidence-based insights for guiding low-carbon hydrogen deployment. Full article