Transcutaneous prosthetic systems, which directly connect an external limb prosthesis to the skeleton, offer substantial biomechanical and clinical advantages over conventional socket-based devices. By eliminating the soft tissue loading inherent to the socket interfaces, these systems enable improved load transfer, comfort, and more natural sensory feedback through direct skeletal attachment. However, their widespread clinical adoption remains limited by complications at the skin-implant interface, including infection, marsupialization, and epithelial down-growth.Advances in surface engineering, particularly nanoscale modifications, have demonstrated a critical capacity to both promote host cell adhesion and direct macrophage polarization, thereby addressing epithelial sealing and chronic inflammation. Bioactive coatings incorporating extracellular matrix proteins or adhesion peptides have been designed to replicate dermal-epidermal interactions and reinforce epithelial anchorage. In parallel, antimicrobial strategies employing antibiotics, peptides, or metal-based coatings have been developed to counteract bacterial colonization of the stoma. Moreover, cell-based therapies using fibroblasts and mesenchymal stem cells have shown promise in supporting dermal integration and modulating local inflammation. Despite these advances, durable and infection-resistant skin-implant integration remains unresolved, indicating that long-term clinical success will require integrated, multifunctional interfaces capable of simultaneously supporting soft-tissue sealing, infection control, immunomodulation and mechanical stability. The development of transcutaneous prostheses designed to enhance skin-implant integration in lower-limb amputees holds substantial translational promises, with implications that extend from individual patient outcomes to broader healthcare systems and biomedical innovation pipelines. Although osseointegrated prosthetic systems have demonstrated improved mobility and enhanced comfort, compared with traditional socket-based devices, their widespread clinical adoption remains limited by complications at the percutaneous interface. Addressing these challenges through bio-hybrid interface creates a realistic pathway toward an infection-resistant and durable skin attachment.From a translational perspective, this strategy is gaining increasing interests due to its practical feasibility: several of its core elements, including surface-modified titanium, antimicrobial coatings, and bioactive agents, are supported by existing regulatory pathways. This enables stepwise innovation within well-defined approval frameworks without the need to create entirely new regulatory categories.Next-generation implants could build upon clinically accepted materials while incorporating advanced surface functionalities that promote epithelial sealing, dermal integration, and controlled immune modulation. Smart, bioresponsive surfaces capable of releasing antimicrobial or anti-inflammatory agents in response to bacterial colonization further strengthen the clinical value proposition by directly addressing infection risk, one of the primary causes of implant failure and revision surgery. Reducing these complications, improving the biological seal at the skin-implant junction, is not merely a solution to a complication: it is an initial enabling technology for the next generation of smart prostheses, that would integrate sensors and neural communication systems, and decrease long-term healthcare costs associated with hospitalizations, antibiotic therapy, and surgical revisions, thereby reducing the overall cost of healthcare system.Successful clinical translation will depend on multidisciplinary collaboration, robust preclinical modelling of the skin interface, and carefully designed clinical trials that evaluate both biological integration and functional outcomes. Enhanced skin-implant integration could shift transcutaneous prostheses from a niche intervention to a broadly adopted standard of care, redefining long-term rehabilitation strategies for individuals living with limb loss.
Atrial fibrillation (AF) frequently requires rhythm control with electrical cardioversion, with approximately 10%-20% of patients undergoing electrical cardioversion annually. Despite its widespread use, cardioversion failure remains common, and clinical practice varies considerably with respect to shock energy, pad positioning, and defibrillator technology. Commonly used biphasic defibrillators differ in not only maximum energy output but also proprietary waveform characteristics and impedance-compensation algorithms, factors that may independently influence cardioversion success. To date, these devices have not been compared directly in a randomized clinical trial.The maximum energy shocks trial is a single-centre, prospective, randomized, single-blinded controlled study comparing 2 widely used external defibrillators: the Physio-Control LIFEPAK 20 (Physio Control, location), capable of delivering up to 360 J, and the ZOLL Medical R-Series (ZOLL Medical, Chelmsford, MA), with a maximum programmable energy of 200 J. Rather than isolating shock energy alone, the trial evaluates real-world device performance, recognizing that waveform design and adaptive algorithms differ among manufacturers. We hypothesize that the 360-J-capable defibrillator will be associated with a higher rate of successful cardioversion when used within a standardized stepwise protocol.Adults (aged ≥ 18 years) with persistent AF scheduled for elective cardioversion are randomized in a single-blinded fashion. The primary outcome is successful cardioversion, defined as restoration of sinus rhythm with at least 2 consecutive sinus or atrial-paced beats. A total of 356 patients will be enrolled to assess superiority.This trial represents the first randomized comparison of real-world defibrillator system performance in AF cardioversion and will help inform future cardioversion protocols and defibrillator selection. NCT06556667. La fibrillation auriculaire (FA) nécessite fréquemment un contrôle du rythme cardiaque par cardioversion électrique (CVE), environ 10 à 20 % des patients bénéficiant d'une CVE chaque année. Malgré son utilisation répandue, l'échec de la cardioversion reste fréquent et la pratique clinique varie considérablement en ce qui concerne l'énergie du choc appliqué, le positionnement des électrodes et la technologie des défibrillateurs. Les défibrillateurs biphasiques couramment utilisés diffèrent non seulement par leur puissance maximale délivrable, mais aussi par les caractéristiques propriétaires de leurs formes d'onde et leurs algorithmes de compensation d'impédance, facteurs qui peuvent influencer indépendamment le succès de la cardioversion. À ce jour, ces appareils n'ont pas fait l'objet de comparaison directe dans le cadre d'un essai clinique randomisé.L'essai MAXSHOCK (chocs à énergie maximale) est une étude prospective, randomisée, en simple aveugle, monocentrique, qui compare deux défibrillateurs externes largement utilisés : le Physio-Control® LIFEPAK 20, capable de délivrer jusqu'à 360 joules, et le Zoll® Medical R-Series, avec une énergie maximale programmable de 200 joules. Plutôt que d'isoler uniquement l'énergie du choc, l'essai évalue les performances réelles des appareils, en reconnaissant que la conception des formes d'onde et les algorithmes adaptatifs diffèrent d'un fabricant à l'autre. Nous émettons l'hypothèse que le défibrillateur capable de délivrer jusqu'à 360 J sera associé à un taux plus élevé de cardioversion réussie lorsqu'il sera utilisé dans le cadre d'un protocole standardisé par paliers.Les adultes (≥ 18 ans) présentant une FA persistante et devant subir une cardioversion élective sont randomisés selon un schéma en simple aveugle. Le critère d'évaluation principal est la réussite de la cardioversion, définie comme le rétablissement du rythme sinusal avec au moins deux battements sinusaux ou auriculaires consécutifs. Au total, 356 patients seront recrutés pour évaluer la supériorité.Cet essai représente la première comparaison randomisée des performances réelles des systèmes de défibrillation dans la cardioversion de la FA et contribuera à éclairer les futurs protocoles de cardioversion et le choix des défibrillateurs. NCT06556667.
Vehicle-road wear microplastics (VRWMPs) are microplastic-sized polymer-containing particles generated from the vehicle-road system, including tire-road wear particles (TRWPs) as the dominant composite class and other polymer-bearing wear debris (e.g., road marking wear). Their complex chemical composition and wide particle size distribution pose potential ecological risks. However, their impacts on ecosystems have long been overlooked because overlapping terminology (e.g., TRWP versus broader non-exhaust emissions) and nonstandardized characterization methods hinder cross-study comparability, while a tire-centered research focus and limited field monitoring obscure the contribution of pavement materials and realistic exposure scenarios. Existing studies largely emphasize tire-derived contributions, while the role of pavement materials remains underrepresented, resulting in an incomplete understanding of VRWMP formation mechanisms. In addition, limited long-term and systematic monitoring data constrain current knowledge of VRWMP migration, transformation, and environmental risks. From a road engineering perspective, this review synthesizes the full lifecycle of VRWMP, from generation to environmental fate. It focuses on formation mechanisms, preparation and characterization methods, migration, and transformation processes within roadway systems, and associated ecological and human health effects. Evidence indicates that VRWMP generation is jointly controlled by tire characteristics and pavement materials, yet a standardized characterization framework is still lacking. The migration and transformation of VRWMP are difficult to model due to data scarcity and pronounced regional variability related to geography, climate, and traffic conditions. Soil and aquatic environments represent major sinks, and exposure pathways such as inhalation may induce adverse biological effects, including oxidative stress and DNA damage. With the increasing complexity of pavement materials, establishing full-chain control of VRWMP, from generation to environmental fate, is becoming an urgent research priority. This review provides a scientific basis for advancing cleaner and more sustainable transportation infrastructure.
Water distribution systems (WDSs) must simultaneously satisfy consumer demand, maintain adequate pressure, and keep storage levels within operational bounds; objectives that require active adjustment of pump operations in response to changing conditions. This study introduces a framework that computes pump commands directly from measured operational data, eliminating the need for hydraulic model construction or calibration. The approach is validated across both levels of WDS control: at the device level, using the quadruple-tank process (QTP) as a laboratory-scale hydraulic benchmark in simulation, physical hardware, and real-time execution; and at the operational level, on a small-scale WDS under time-varying consumer demands. Across all case studies, the controller maintains tank levels and junction pressures within prescribed service bounds with mean absolute percentage errors below 4%, while using only 200 data samples. This is over 99% less data required by model predictive control (MPC). On the studied small-scale WDS, the controller achieves uninterrupted demand satisfaction, safe storage levels, and adequate junction pressures while reducing computational cost by 90% compared to a typical MPC. These results demonstrate the potential of data-driven, model-free approaches as a practical and data-efficient alternative for real-time control (RTC) of modern WDSs.
Developing soft matter systems with programmability, multifunctional integration, and environmental adaptability represents a critical challenge in soft robotics and smart materials. Herein, we propose a versatile framework for constructing active and programmable shape-morphing soft matter systems based on addressable actuation and strain-constraint mechanisms. Using liquid crystal elastomers (LCEs) and conductive constraint strips serving simultaneously as geometric constraints and localized Joule heaters, this framework circumvents complex microstructural manipulation, enabling addressable electrothermal actuation and deterministic 2D-to-3D morphological transformation. Combined with the established analytical model, we propose an inverse design strategy capable of reconstructing complex target surfaces featuring spatially non-uniform curvatures. To demonstrate its integration capability, we incorporate shape memory polymers (SMPs) and crack-based sensors via a thermally decoupled design to construct a proprioceptive lockable soft robotic system (PLSRS), exhibiting zero-energy shape retention and real-time proprioception. Finally, we validate this system by deploying the PLSRS in a flapping-wing robot, where a 1D convolutional neural network (1D-CNN) optimized via the grey wolf optimizer (GWO) deciphers aeroelastic signals to estimate wind speed and trigger autonomous adaptive wing regulation. This work successfully fuses physical intelligence with computational intelligence, providing a versatile platform for next-generation adaptive soft robots.
1,3-Butanediol (1,3-BDO) is widely used in consumer and industrial products; however, its microbial degradation remains poorly understood. Here, we dissect the catabolic and regulatory mechanisms of (R)-1,3-BDO utilization in Pseudomonas putida KT2440 and develop (R)-1,3-BDO-responsive transcriptional biosensors. Transcriptomics and qRT-PCR revealed strong induction of the ped gene cluster, which oxidizes (R)-1,3-BDO to (R)-3-hydroxybutyrate [(R)-3-HB], and of the LysR-regulated operon PP_2047-2051, which channels (R)-3-HB toward acetoacetate and acetyl-CoA. Gene deletion and enzyme assays identified pedE and PP_2049 as essential for (R)-1,3-BDO catabolism, with PP_2049 playing a more critical role than the canonical β-hydroxybutyrate dehydrogenase HbdH (PP_3073). Regulatory analysis showed that PedR1 directly activates catabolic genes independently of PedR2-challenging the widely accepted indirect-only model-while PedS1 proved dispensable, implying an alternative sensor kinase. Promoter-GFP fusions demonstrated that full activation of the pedE promoter requires both PedR1 and the PedS2-PedR2 two-component system, whereas the pedS2R2 promoter requires only PedR1 and functions in both native and heterologous hosts, including Escherichia coli. These results define the genetic and regulatory architecture of (R)-1,3-BDO degradation in P. putida and establish pedE- and pedS2R2-based promoters as (R)-1,3-BDO-responsive biosensors. 1,3-Butanediol is an increasingly prevalent industrial chemical whose environmental fate depends on microbial degradation. Understanding how microorganisms sense and metabolize this compound is therefore essential for both environmental microbiology and biotechnology. This study clarifies the genetic and regulatory basis of (R)-1,3-BDO catabolism in Pseudomonas putida, identifying key enzymes and transcriptional regulators that control its utilization. By coupling pathway elucidation with promoter characterization, this work enables the development of (R)-1,3-BDO-responsive biosensors that function in both native and heterologous hosts. These insights are important for understanding the environmental fate of 1,3-BDO and designing inducible regulatory systems for biotechnological applications.
Pesticide mixtures are prevalent in aquatic systems within agricultural regions, but their transport and removal mechanisms in the presence of submerged macrophytes remain unclear. This study investigated changes in water quality, plant physiology, epiphytic microbial communities, and pesticide distribution in wetland substrates during 56 days of repeated exposure to a mixture of 12 pesticides at environmental (0.5 and 1 μg/L) and high (5 and 10 μg/L) concentrations. The average removal rates of total pesticides ranged from 58.61% to 75.52% and decreased with increasing pesticide addition and exposure time. Bioconcentration factors in plants were significantly higher than sediment-water partition coefficients for all pesticides. Notably, triazole pesticides (paclobutrazol, tebuconazole and hexaconazole) tended to accumulate in the system compared to neonicotinoid insecticides (dinotefuran, imidacloprid, and thiamethoxam). Pesticide addition reduced nutrient removal efficiency and induced oxidative damage in V. natans leaves. A total of 3, 14, and 17 biomarkers were identified in Con, PG1, and PG10, respectively, suggesting that PG1 and PG10 disturbed the epiphytic bacterial community. Co-occurrence network analysis revealed potential associations between pesticide residues and epiphytic bacterial taxa in PG10. PICRUSt2-based functional prediction indicated that compared to control, the predicted potential for xenobiotics biodegradation and metabolism was higher in PG1, whereas predicted genes related to starch and hemicellulose decomposition increased and denitrification-related predicted genes decreased in PG10. These data highlight that V. natans can accumulate pesticides and survive repeated pesticide exposure during the 56-day experiment, although high concentration pesticides had adverse effects on V. natans-epiphytic bacterial community.
Brain organoids have progressed from simple three-dimensional neuroepithelial aggregates to increasingly sophisticated systems that recapitulate key aspects of human neurodevelopment and disease. Despite rapid biological advances, their translational potential remains constrained by challenges in maturation, vascular integration, reproducibility, and scalable standardization. Recent innovations, including microfluidic perfusion platforms, synthetic extracellular matrices, vascularization strategies, and modular assembloid assembly, illustrate a shift from descriptive modeling to functionally integrated and experimentally controllable neural systems. However, increasing biological complexity introduces ethical and regulatory considerations that must be incorporated into translational research frameworks. These advances provide new opportunities to investigate human-specific developmental mechanisms and bridge the gap between in vitro modeling and in vivo neurobiology. Future progress will depend on balancing two complementary objectives: enhancing biological fidelity and improving experimental utility through increasingly controllable and design-driven organoid platforms with defined architecture, functionality, and reproducibility. In this context, brain organoids are emerging as bioengineered neural tissue systems that share important conceptual and technological foundations with next-generation artificial organ technologies. Continued advances in bioengineering, standardization, and systems-level integration are essential to maximize their translational impact on disease modeling, therapeutic testing, and regenerative neuroscience.
Uric acid (UA) is a clinically relevant urinary biomarker for assessing the risk of urolithiasis, but portable electrochemical platforms require wide dynamic range, robust bio-electronic interfacing, and validation with real samples. In this study, we present a Complementary Metal-Oxide-Semiconductor (CMOS) potentiostatic amperometric readout circuit and a portable sensing platform for urinary UA measurement. The proposed circuit is designed to work with both two- and three-electrode electrochemical configurations and uses separate amplifier loops for electrode bias control and current readout to improve stability and linearity during measurement. Fabricated in a 0.18-μm CMOS process, the readout integrated circuit occupies an active area of 102 μm × 195 μm and operates from a 3.3 V supply while maintaining an oxidation potential of approximately 0.7 V at the sensing interface. DC simulation was performed to evaluate the current detection capability of the architecture. Fabricated silicon measurements were conducted to validate circuit operation, and the system was evaluated using UA assays and fresh urine samples under controlled dilution. The readout circuit was further implemented within a portable multi-parameter urine sensing platform that supports concurrent measurement of UA, pH- and calcium-related signals, and conductivity with microcontroller-based digitization. DC simulation indicates that the proposed architecture can theoretically support a current detection range from 150 pA to 160 μA (>5 decades) with less than 2% current replication error under nominal conditions. Fabricated silicon measurements validate stable potentiostatic operation and linear electrochemical response within the experimentally evaluated UA concentration range (20-500 ppm), demonstrating a functional electrochemical interface of the readout circuit. The multi-decade current capability therefore represents a simulation-supported design potential of the architecture, while the experimental validation focuses on the sensing range of the implemented UA assay. When evaluated using fresh urine samples under controlled dilution, the system exhibits a clear linear relationship between readout current and UA concentration over a relevant range of 20-500 ppm, with measurement differences typically within 10 ppm and less than 5% compared with an adjusted commercial analyzer. Together, these results demonstrate a compact and robust electrochemical readout solution that supports flexible sensor integration and provides a practical foundation for portable, multi-biomarker urine analysis and future data-driven monitoring of urolithiasis risk.
ToBRFV is a major threat to tomato and pepper crops because it spreads quickly and survives for a long time in the environment. Since there are few ways to control it after infection, early detection before symptoms are visible is crucial. Yet, only limited public datasets are available for this research. We present one of the first openly accessible, longitudinal multispectral image dataset dedicated to ToBRFV detection. In this study, two tomato cultivars and two pepper cultivars, all of which are commercially important and widely cultivated in greenhouses, were selected. Using these plants ensures that the dataset reflects real-world agricultural practices and captures variability across commercially grown types. Both healthy and ToBRFV-inoculated plants from each cultivar were included in the imaging process. All plants were cultivated under fully controlled greenhouse conditions in Adana Province, Türkiye. Healthy and infected tomato plants were grown in two separate greenhouses to prevent cross-contamination. Imaging was conducted over a 29-day period using Red-Green-Blue (RGB) and Visible Near Infrared (VNIR) cameras, including narrowband captures at 800 nm and 1000 nm, from multiple viewing angles. Infection status was confirmed via Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) analysis at multiple time points. The dataset is organized into four clean, labelled subsets and released under a CC BY 4.0 license. This resource provides unique opportunities for developing and benchmarking computer vision and machine learning approaches for pre-symptomatic plant disease detection, spectral feature analysis, and integration into precision agriculture systems. By combining controlled experimental design, spectral diversity, and open access, it establishes a robust foundation for cross-disciplinary research in plant pathology, agricultural engineering, and artificial intelligence.
Strokes such as acute ischemic stroke require vascular access for endovascular thrombectomy. To navigate the small and complex cerebral vessels with multiple branches, clinicians use guidewires or catheters with pre-shaped tips. However, complex procedures still face the problem of increased X-ray exposure for both clinicians and patients. Engineering technologies such as robotic guidewires and catheters are being applied to neurovascular procedures to make them faster and more effective. The technology presented in this study involves Collaborative Robotic (Cobot) guidewires that can be steered by magnetic fields to effectively enter the target vessel and navigate complex blood vessels. The Cobot guidewire can be steered according to the direction of the magnetic field because its tip contains a permanent magnet and a magnetic polymer. The magnetic field for steering the Cobot guidewire can be controlled and generated by electromagnetic control systems (ECS). In this study, the performance of neurovascular procedures using the Cobot guidewire and manual guidewire is compared in both phantom and swine models. Based on various parameters, the Cobot guidewire demonstrates superior performance in neurovascular procedures compared to the manual guidewire. Favorable procedure time and navigation efficiency suggest that a magnetically assisted Cobot guidewire is potentially feasible for neurovascular interventions.
Chemically similar metal(loid)s exploit nutrient transport systems and destabilize integrated metal-homeostasis networks, triggering redox imbalance, transcriptional reprogramming, and multiscale regulatory responses that ultimately determine plant adaptation or toxicity. Plant growth depends on the homeostasis of mineral nutrients, but it is short in heterogeneous soils where required elements are found together with chemically similar harmful metal(loid)s. The divalent ionic and coordination properties of Cd-Zn and Ni-Fe are similar, while the arsenate-phosphate interactions are structurally analogous oxyanion mimicry systems. Cd-Zn, Ni-Fe, and As-P have broad-substrate transport systems with partially overlapping ion-recognition properties, notably under nutrient-limiting conditions. Although it is widely recognized that transporter promiscuity exists in a systemic manner. The overall systemic effects, such as metal homeostasis, redox signaling, activity of the organelles, transcriptional regulation, and whole-plant ion balance between tissues and cellular compartments of its action, are not yet clearly understood. We are stating that chemically similar metal stress signifies the destabilization of an integrated homeostatic network and not just limitation of transporters. Substantial overlap exists in conserved transporter families (ZIP, NRAMP, PHT, IRT, HMA), which are triggered by nutritional deprivation to induce high-affinity transporter families, which stimulates the uptake of both essential and simultaneously detrimental metals. Competitive metal entry causes disruption of the cytosolic and organellar redox balance, leading to the production of ROS, which results in transcriptional reprogramming, turnover of transporters, metal redistribution, and calcium-, kinase-, and hormone-mediated signaling. In addition to uptake, intracellular regulatory mechanisms act to control metal partitioning, including thiol chelation, vacuolar sequestration, metallochaperone activity, organelle-specific redistribution, and transporter dynamics. Root exudation and plant-microbe interactions are some of the rhizospheric activities that cause further speciation of the metals before they can enter the membrane. We suggest a multiscale model, in which coordinated regulatory reprogramming during co-exposure is the basis for adaptive resistance, and failure of metal homeostasis, and redox-feedback regulation is the basis for toxicity. Chemical mimicry can therefore be considered a systemic limitation of the productivity of plants.
Distributed drive electric vehicles (DDEVs) show great potential in electric vehicle applications owing to their high transmission efficiency and precise driving control. Nevertheless, existing stability control methods suffer from insufficient proactivity and limited real-time regulation capability, making them unable to guarantee satisfactory longitudinal stability performance under complex operating conditions. To address this issue, this paper presents a vehicle state estimation and longitudinal stability control system for complex driving scenarios. A LiDAR-IMU fusion scheme is developed, which combines the adaptive unscented Kalman filter (AUKF) and time-series analysis (TSA) to improve state estimation accuracy. Furthermore, a multi-model model predictive control (MPC) framework is established to classify driving conditions and generate integrated control commands through weighted fusion, so as to achieve optimized longitudinal stability and smooth mode switching. The main novelty of this work lies in the integration of predictive state estimation and scenario-classified weighted-fusion multi-model MPC, which differs from conventional switching MPC and gain-scheduled MPC by avoiding abrupt mode switching and explicitly considering model differences under typical DDEV operating conditions. Both simulation and hardware-in-the-loop (HIL) results validate that the proposed system effectively enhances longitudinal stability and control performance under complex conditions. The root-mean-square error (RMSE) of yaw rate estimation is reduced to 0.111 deg/s, and the control accuracy is improved by 21.7% compared with the conventional MPC method. This work lays a solid theoretical basis for the application of distributed drive electric vehicles.
Osteosarcoma remains a major treatment challenge, especially for patients with recurrent, refractory or metastatic diseases. Adoptive cell therapy (ACT), including CAR-T cells, TCR engineered T cells, CAR-NK cells and macrophage based cell therapy, provides a promising strategy for redirecting immune effector cells to fight osteosarcoma. However, clinical translation has been limited by antigen heterogeneity, on-target/off-tumor toxicity, insufficient tumor trafficking, poor persistence, functional exhaustion, and the immunosuppressive tumor microenvironment. This mini review discusses emerging innovations designed to overcome these safety and efficacy barriers. First, engineering strategies such as multi-antigen recognition, logic-gated CAR systems, suicide switches, transient CAR expression, armored cytokine circuits, checkpoint-resistant designs, and chemokine receptor modification may improve precision, controllability, and durability. Second, vaccination approaches may serve as programmable amplifiers of ACT by promoting in vivo expansion, immune memory, antigen spreading, and local inflammatory priming. Third, tumor microenvironment remodeling through stromal modulation, vascular normalization, myeloid reprogramming, checkpoint blockade, and metabolic intervention may convert osteosarcoma into a more permissive niche for cellular therapy. Collectively, next-generation ACT for osteosarcoma will likely require modular, biomarker-guided combinations that integrate cellular engineering, vaccine-based boosting, and microenvironmental remodeling to achieve safer and more durable antitumor responses.
Halide-based solid electrolytes (HSEs) have garnered substantial interest for all-solid-state batteries (ASSBs) due to their wide electrochemical windows, moderate-to-high room-temperature ionic conductivity, and enhanced air stability over traditional sulfide and oxide-based SEs. This review consolidates recent advances in HSEs, focusing on the link between structure, compositions, and materials properties that influence the transport of lithium-ion (Li-ion) and post-lithium-ion (P-Li-ion) and their stability at the interface. Based on the chemistry of their central metal, HSEs are divided into five classes; key factors influencing ionic conductivity are examined. Nevertheless, despite these benefits, many challenges remain, including interfacial instability, the trade-off between ionic conductivity and electrochemical stability, mechanical challenges, and material costs. The main synthesis methods, mechanochemical, co-melting, and wet-chemical, are investigated for phase formation, scalability, and defect control. The link between synthesis, microstructure, and device-level performance metrics, including critical current density, area-specific resistance, and cycle life, is examined. The strategies, involving bilayer and dual-electrolyte design as well as interface engineering, are analyzed to reduce interfacial resistance and dendrite growth. The applications of HSE in Li-ion and P-Li-ion systems are examined. This review offers a detailed framework and delineates potential research paths to advance scalable, high-performance HSEs for next-generation ASSBs.
Melatonin is a pleiotropic hormone with well-documented antioxidant, anti-inflammatory, neuroprotective, and immunomodulatory properties, making it a promising candidate for the treatment of diverse diseases including neurodegenerative disorders, cardiovascular diseases, cancer, and sleep disturbances. However, its clinical translation has been hampered by several biopharmaceutical limitations, including poor aqueous solubility, extensive hepatic first-pass metabolism, rapid systemic clearance, and low oral bioavailability. Additionally, physiological barriers such as the blood-brain barrier, stratum corneum, and mucosal epithelia restrict its accumulation at target sites. In recent years, nanotechnology-based drug delivery systems have emerged as powerful tools to overcome these challenges. This review provides a comprehensive overview of advanced melatonin nanocarriers with a focus on their design principles, formulation strategies, and therapeutic applications. A central theme of this review is the integration of carrier design with biological barrier circumvention and administration routes-elucidating how specific nanocarrier platforms address the shortcomings of conventional immediate- and prolonged-release melatonin formulations through spatial and temporal control over drug distribution. We summarize recent preclinical progress in melatonin nanocarriers for a wide range of disease models, including Alzheimer's disease, Parkinson's disease, myocardial infarction, retinal degeneration and glaucoma, depression, and various cancers, with emphasis on the relationship between administration routes and therapeutic outcomes. Finally, critical challenges in clinical translation are addressed, including large-scale manufacturing, long-term toxicity evaluation, regulatory considerations, and the development of chronotherapy-compatible delivery systems. By integrating insights from materials science, pharmaceutics, and nanomedicine, this review aims to provide a rational framework for the future design and clinical application of melatonin-based nanotherapeutics.
The formalin-inactivated Coxiella burnetii virulent phase I vaccine (PIV) has been shown to be more protective than the avirulent phase II vaccine (PIIV) against virulent C. burnetii challenge in animal models. However, the cellular and molecular mechanisms underlying the differential ability of PIV and PIIV to induce protective immunity remain unclear. PIV and PIIV were generated from axenic (ACCM-D) cultures and administered to mice using single or multiple immunization regimens. Protective efficacy was evaluated following challenge with virulent C. burnetii. Humoral immune responses were assessed by measuring phase I-specific IgM and IgG antibodies. Bulk RNA sequencing and flow cytometry were used to compare immune responses in PIV- and PIIV-vaccinated mice. The role of neutrophils in vaccine-mediated protection was examined through neutrophil depletion prior to challenge. Regardless of single or multiple immunizations, PIV and PIIV generated from axenic (ACCM-D) cultures retained their differential protective efficacies, with PIV providing robust protection but PIIV did not. PIV elicited earlier phase I-specific IgM responses and sustained higher IgG responses compared to PIIV, indicating differences in immunogenicity. Cellular and transcriptomic analyses revealed that PIV induced a prolonged neutrophil response in the spleen, accompanied by upregulation of genes involved in neutrophil degranulation, metal sequestration, and TLR-dependent innate immune pathways. In contrast, the neutrophil response induced by PIIV was transient and did not persist into later stages of vaccination. Depletion of neutrophils in PIV-vaccinated mice prior to challenge significantly reduced the protective efficacy of PIV. These findings demonstrate that PIV-induced protection against C. burnetii infection is partially dependent on sustained neutrophil activation. This study provides novel evidence that modulation of neutrophil-mediated effector functions plays a critical role in PIV-mediated protective immunity.
Tamoxifen is widely used to activate Cre-ERT2/LoxP transgenic systems for cell- and time-specific gene recombination. However, its regional and long-term effects on the adult murine skeleton are not well defined. Here we sought to identify immediate and long-term regional effects of short-term tamoxifen treatment on gene recombination and cortical and trabecular bone structure in young adult 10kbDmp1-Cre-ERT2 mice, which targets gene recombination primarily to osteoblasts and osteocytes. Tamoxifen was administered by four 20mg/kg bolus injections to 12-week-old mice of both sexes. In cortical bone, tamoxifen induced persistent recombination in osteocytes (detected by Ai9.tdTomato labelling), which was region- and sex-dependent: female metaphyseal cortex showed the highest labelling (in ∼80% of osteocytes) that remained for 12 weeks. However, diaphyseal cortex and males showed less osteocyte labelling (∼60%). In trabecular bone of male and female mice, labelling was observed in ∼90% of osteocytes and in ∼60% of bone surface cells at 14 weeks of age but both substantially after a further twelve weeks, particularly in females. In both sexes, tamoxifen transiently accelerated longitudinal bone growth, increased trabecular bone mass, and increased metaphyseal cortical porosity while suppressing radial growth. Bone structure largely normalised by 26 weeks, but the osteocyte lacunocanalicular network remained disordered. This indicates that (i) 10kbDmp1-Cre-ERT2-induced recombination is not uniform through the skeleton or between sexes, and (ii) short-term tamoxifen administration has both transient and persistent effects on bone structure. Investigators using any tamoxifen-inducible system should test recombination in each site and sex, and control for tamoxifen's effects on skeletal structure.
Extracellular vesicles (EVs) derived from parasites have emerged as a critical frontier for understanding pathogenic mechanisms and developing novel control strategies. This bibliometric analysis systematically examines 365 original research articles published between 2015 and 2025 using CiteSpace to map the intellectual structure, collaborative networks, and evolving research hotspots of this field. Global publication output exhibits a sustained upward trend, with China, the United States, Brazil, Spain, and Australia as the leading contributors. Notably, Spain demonstrates the highest centrality in international collaboration networks, functioning as a key hub. Author co-authorship analysis reveals a relatively sparse network density, with Ana Claudia Torrecilhas, Alex Loukas, and Antonio Marcilla among the most prolific contributors. Keyword clustering using the log-likelihood ratio algorithm identifies three predominant research domains: protozoan parasites (encompassing Plasmodium, Trypanosoma, Leishmania, and Toxoplasma), trematode parasites (including Schistosoma and Fasciola), and cellular/molecular mechanisms of immunomodulation. Timeline analysis documents a decisive paradigm shift from morphological description and cargo cataloguing toward mechanistic dissection of host-parasite crosstalk, with increasing emphasis on translational applications in diagnostics, vaccine development, and drug delivery. Burst detection analysis reveals sustained citation bursts for methodological standardization guidelines, reflecting the community's recognition of persistent challenges in EV isolation and characterization. This technology-driven, interdisciplinary field provides robust evidence for future priority setting, international collaboration, and resource allocation.
A prescribed-time time varying formation control of second-order multi-agent systems with DoS attacks is proposed in this article. Firstly, a prescribed-time control law is proposed under time-triggered scenario when the agents are affected with DoS attacks. This is further extended to the self-triggered scenario under DoS attacks. An undirected graph and time varying formation is considered in developing the control law. Rigorous mathematical proof is given to validate the control law. Simulation results in both time-triggered and self-triggered scenario under DoS attacks is presented to highlight the effectiveness of the approach in this article. Comparison results are also shown the bandwidth efficiency of the proposed approach.