Search Results (307)

Solar radio bursts at very low frequencies are key phenomena in the Sun–Earth space environment, providing crucial diagnostics of the acceleration and propagation of solar wind, coronal mass ejection (CME), and non-thermal energetic particles and serving as important indicators for space weather forecasting. To meet the demand for rapid screening of burst events in large-scale observational datasets, we present an end-to-end automatic detection and evaluation framework tailored for Type III bursts, built upon long-term radio dynamic spectra from STEREO-A/SWAVES. We formulate radio burst detection as a one-dimensional interval localization task along the time axis and, in view of the scarcity of annotated samples, cast it as a few-shot object detection task. Building upon the Faster R-CNN architecture with a ResNet50-FPN backbone, we propose the Meta-FSOD framework, which adopts an episodic training paradigm to construct support–query episode pairs. The framework incorporates a metric-guided prototype learning branch to semantically align and calibrate region-of-interest (RoI) features via class prototypes, and integrates a dynamic Beta-Gating mechanism coupled with Soft-NMS to effectively suppress false positives while preserving high-recall performance. Experimental results demonstrate that, despite being trained on a significantly smaller dataset than comparable studies, Meta-FSOD achieves competitive performance, closely matching that of conventional supervised model. The proposed framework exhibits strong cross-temporal generalization capabilities and holds considerable potential for engineering applications in deep space exploration missions. Full article

This study presents a distribution-optimized mesostructure estimation method for statistically modeling near-surface aggregate size distributions in concrete by optimizing the spatial arrangement of polydisperse spherical aggregates with respect to formwork boundaries. The approach is based on minimizing the deviation between a generated cumulative aggregate volume function and an idealized linear target function corresponding to a constant area fraction along the specimen depth. To enable efficient computation for systems containing a large number of aggregates, grain size groups derived from the grading curve are represented using symmetric Beta distributions, allowing each group to be described by a single shape parameter. The resulting optimization problem is solved using a derivative-free Powell algorithm. The method inherently captures wall effects, leading to a migration of smaller aggregates toward the specimen boundaries to compensate for the geometric constraints of bigger aggregates. Experimental validation was performed for a single concrete mixture and specimen geometry by determining the depth-dependent mean bulk density of a concrete cube using incremental surface grinding combined with high-resolution 3D laser scanning. The optimized mesostructure shows strong agreement with measured density profiles for the investigated specimen. While the validation is limited to a single mixture and geometry, the results indicate that the proposed method is a computationally efficient approach for incorporating wall effects into mesoscale concrete models. Furthermore, increasing aggregate volume fractions intensify the near-surface accumulation of fine particles. Full article

Radiopharmaceutical therapy (RPT) has emerged as a transformative modality in oncology, particularly for patients with metastatic or inoperable tumors. By leveraging molecularly targeted carriers conjugated to cytotoxic radionuclides, RPT enables precise delivery of ionizing radiation to tumor sites while minimizing off-target effects. Central to this approach are alpha (α) and beta (β) particle-emitting radionuclides. This review aims to provide a comprehensive overview of all clinically relevant alpha and beta emitters and incorporates the most recent advances from 2017–2025, offering a comprehensive and up-to-date perspective. Alpha and beta emitters hold significant promises for the future, especially in nuclear medicine, energy, and environmental monitoring. Medically, these emitters are at the forefront of targeted radiotherapy, offering new hope for cancer treatment. Alpha emitters such as Actinium-225 and Radium-223 are gaining attention for their high linear energy transfer, which allows them to effectively kill cancer cells while minimizing damage to surrounding healthy tissues. Beta emitters, including Lutetium-177 and Iodine-131, are already widely used for treating thyroid cancer, neuroendocrine tumors, and prostate cancer. They offer a longer range in tissue penetration than alpha particles, making them suitable for larger or more diffuse tumors. Alpha and beta emitters hold tremendous promise in targeted radiotherapy. However, current research is limited by an incomplete understanding of resistance pathways, insufficient long-term safety and efficacy data, and underdeveloped personalized treatment frameworks. As production technologies improve and safety protocols advance, these emitters will likely play an even more prominent role in both health care and scientific innovation. Full article

Background/Objectives: Poor oral bioavailability and limited intestinal permeation restrict the clinical translation of phytochemicals for colorectal cancer (CRC) therapy. The present preliminary study explored the development of a nanoparticle-based combinatorial formulation of resveratrol (Resv), acetyl-11-keto-β-boswellic acid (AKBA), and quercetin (Quer), to improve intestinal permeation and anti-cancer efficacy. Methods: A triple phytochemical nano formulation (designated as 3X) was developed and evaluated for morphology, particle size, zeta potential, encapsulation efficiency, and in vitro pharmaceutical characteristics. Safety was evaluated using in vitro cytotoxicity assays, while anticancer efficacy and apoptotic potential were preliminarily evaluated in Caco-2 CRC cell lines. Gene expression analysis was performed to examine the modulation of inflammation and cancer-related markers. Results: The 3X formulation exhibited a particle size of 198.5 nm with a polydispersity index of 0.492 and a zeta potential of −32.7, indicating good nanoscale stability. The encapsulation efficiencies were 90% for AKBA, 80% for Resv, and 75% for Quer. In vitro permeation studies demonstrated a controlled release mechanism. The formulation showed minimal hemolysis (3%) and had acceptable in vitro safety. The IC50 of the formulation was found to be 365 µg in the cytotoxicity assay. Treatment with the 3X nanoformulation significantly modulated anti-inflammatory and cancer-related gene expression in Caco2 cells, evidenced by downregulation of TGFβ (Transforming Growth Factor-beta) and COX-2 (cyclooxygenase-2), and upregulation of TNFα (Tumor necrosis factor-alpha) and nitric oxide (NO) and reduced IL-1β (Interleukins-1 beta) expression compared with control cells. Conclusions: The findings demonstrate that the developed 3X nano formulation exhibits favorable permeation characteristics and exerts anticancer activity against CRC. Based on preliminary findings, the formulation represents a promising phytochemical-based combination strategy for CRC, warranting further in vivo studies to validate its efficacy and elucidate the underlying molecular mechanisms. Full article

Coronaviruses are worldwide-distributed RNA viruses with zoonotic potential and the ability to jump from one host species to another, including humans. Even after the COVID-19 pandemic, the search for new, biologically active substances with anti-coronavirus activity continues to be a critical milestone for human health protection. In the framework of a complex engineering strategy, we cultivated the microalgal species Scenedesmus acutus in two different innovative types of flat-plate photobioreactors (PBR1 and K1) for CO₂ utilization and biomass production with special features. Isolated extracts from the microalgal biomass of each one were compared for their anti-coronavirus potential. The design of both PBRs allows a hydrodynamic regime to achieve best fluid flow distribution in their sections, therefore providing the optimal so-called flashing light effect. Of course, this is achieved under well-controlled operational conditions. A strain of beta coronavirus 1 (BCoV, bovine coronavirus) replicated in MDBK cells was used as an in vitro model for the evaluation of the antiviral activity of both extracts. The cell viability, number of survived BCoV particles, and cytopathic effect were evaluated after pre-incubation of the virus with the extracts or direct treatment. The extracts’ samples exhibited evident antiviral activity—extract 1 (from PBR1) in concentrations ≥ 200 µg/mL and extract 2 (from K1) in concentrations ≥150 µg/mL. The ddPCR result revealed significant diminishment of the BCoV particles in samples treated with higher concentrations of the extracts. The phytochemical analysis for certain main groups of compounds (flavonoids, polyphenols, carotenoids, and lipids) showed some differences for both extracts, which could be a possible reason for the observed difference in the antiviral activity. In conclusion, the innovative PBRs are a good platform for studying microalgal growth kinetics by applying different stress conditions from hydrodynamics and mass transfer subsystems. Both extracts showed promising potential for the isolation of metabolites with antiviral activity against BCoV and could be an object for future pharmacological investigations. Full article

The blood–brain barrier (BBB) is a major obstacle to the development of brain-targeted drug delivery systems, restricting greater than 98% of small molecules (<500 Da) and virtually all large-molecule drugs from entering the brain tissues from the bloodstream, resulting in suboptimal drug doses and therapeutic failure in the treatment of Alzheimer’s disease (AD). However, the advent of nanotechnology has provided significant solutions to the BBB challenges, enabling particle size reduction, enhanced drug solubility, reduced premature drug degradation, extended and sustained drug release, enhanced drug transport across the BBB, increased drug target specificity and enhanced therapeutic efficacy. In corollary, a library of brain-targeted surface-functionalized nanotherapeutics has been widely reported in the current literature. These promising in vitro, in vivo and pre-clinical results from the existing literature provide quantitative evidence for the relative clinical utility of each of the techniques, indicating remarkable capacity for brain-targeted carrier systems; many of them are still being tested in human clinical trials. However, despite the recorded research successes in drug transport across the BBB, there are currently no clinically proven medications that can slow or reverse the progression of AD because most of the novel therapeutics have not been successful during the clinical trials. Therefore, the main option for the treatment of AD is symptomatic treatment using cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. Although these therapies help to alleviate symptoms of AD and improve patients’ quality of life, they neither slow the progression of disease nor cure it. Thus, an effective disease-modifying therapy for the treatment of AD is an unmet clinical need. It is apparent that a deeper understanding of the structural complexity and controlling dynamic functions of the BBB in tandem with a comprehensive elucidation of AD pathogenesis are crucial to the development of novel nanocarriers for the effective treatment of AD. Therefore, this narrative review describes the contextual analysis of several promising strategies that enhance brain-targeted drug delivery across the BBB in AD treatment and recent research efforts on two major AD biomarkers that have revolutionized AD diagnosis, amyloid-beta plaques and phosphorylated tau protein tangle, as potential targets in AD drug development. This has led to the Food and Drug Administration (FDA)’s approval of two intravenous (IV) anti-amyloid monoclonal antibodies, Lecanemab (Leqembi^®) and Donanemab (Kisunla^®), which were developed based on the Aβ cascade hypothesis for the treatment of early AD. This review also discusses the recent shift in the Aβ cascade hypothesis to Aβ oligomer (conformer), a soluble intermediate of Aβ, which is the most toxic mediator of AD and could be the most potent drug target in the future for a more accurate and effective drug development model for the treatment of AD. Furthermore, various promising nanoparticle-based drug carriers (therapeutic nanoparticles) that were developed from intensive research are discussed, including their clinical utility, challenges and prospects in the treatment of AD. Overall, it suffices to state that the advent of nanotechnology provided several innovative techniques for overcoming the BBB and improving drug delivery to the brain; however, their long-term biosafety is a relevant concern. Full article

A comb model with periodic potential in side branches is introduced. A comb model is a model of geometrically constrained diffusion, such that the diffusion process along the comb’s main axis (backbone) is coupled to the diffusion process in fingers, the side branches of the comb. Here, we consider a generalized version of this complex process by enabling a periodic potential function in the fingers. We aim to understand how the potential function added affects the asymptotic transport scalings in the backbone. A set of exact results pertaining to the generalized model is obtained. It is shown that the relaxation process in fingers leads directly to the occurrence of a non-equilibrium stationary state (NESS) in comb geometry, provided that the total energy is zero. Also, it is shown that the spatial distribution of the probability density in proximity to NESS is given by the Mathieu distribution with zero energy. The latter distribution is found to be the direct result of relaxation towards stationarity of the Mathieu eigenspectrum. It is suggested that the generalized model can characterize anisotropic particle dispersion in beta-plane atmospheric (alternatively, electrostatic drift-wave plasma) turbulence and the subsequent formation of layered structures, zonal flows, and staircases. In this regard, the inherent interconnection between combs and staircases is discussed in some detail. Full article

Requirements for novel effective antiviral agents against SARS-CoV-2 emphasizes the importance of robust in vitro screening platforms. We developed a test system based on spike-pseudotyped lentiviruses, carrying either luc+ or EGFP reporter genes as a payload, and a human non-small cell lung carcinoma (NSCLC) cell line, overexpressing ACE2 (H1299-hACE2). The cell origin makes our system resemble lung epithelium infection. Transmission electron microscopy confirmed that the spike glycoproteins on the pseudotyped lentiviral particles resemble native SARS-CoV-2 spike glycoproteins, thus validating their use in inhibitor screening. H1299-hACE2 cells showed significantly higher infection rate (p < 0.005) with spike-pseudotyped lentiviruses compared to parental H1299 cells, as determined by luciferase and fluorescence assays. The susceptibility of the stable H1299-hACE2 cell line to a broad panel of SARS-CoV-2 variants (Wuhan, Beta, Delta, Omicron) was assessed here for the first time in a unified experimental setting. Infection of H1299-hACE2 cells with SARS-CoV-2 induced cell fusion and syncytium formation with subsequent cell death. The developed pseudovirus-based assay was further used for assessment of the antiviral properties of derivatives of 1,7,7-trimethyl-[2.2.1]-bicycloheptane-potential spike protein inhibitors, which possess moderate activity against lentiviral particles. The H1299-hACE2/spike-pseudotyped lentivirus assay is, therefore, a reliable, high-efficiency platform for screening spike-mediated entry inhibitors. The cell line obtained during the development of the platform can be used to isolate and study new variants of SARS-CoV-2. Full article

Background: In nuclear medicine, numerous cancer types are treated via internal irradiation with radiopharmaceuticals, including low-LET (linear energy transfer) beta-emitting radionuclides like Lu-177. In most cases, such treatments lead to low-dose exposure of organ systems with β-irradiation, which induces only few isolated DSBs (double-strand breaks) in the nuclei of hit cells, the most threatening DNA damage type. That damaging effect contrasts with the clustering of DNA damage and DSBs in nuclei traversed by high-LET particles (α particles, ions, etc.). Methods: After in-solution β-irradiation for 1 h with Lu-177 leading to an absorbed dose of about 100 mGy, we investigated the spatial nano-organization of chromatin at DSB damage sites, of repair proteins and of heterochromatin marks via single-molecule localization microscopy (SMLM) in PBMCs. For evaluation, mathematical approaches were used (Ripley distance frequency statistics, DBScan clustering, persistent homology and similarity measurements). Results: We analyzed, at the nanoscale, the distribution of the DNA damage response (DDR) proteins γH2AX, 53BP1, MRE11 and pATM in the chromatin regions surrounding a DSB. Furthermore, local changes in spatial H3K9me3 heterochromatin organization were analyzed relative to γH2AX distribution. SMLM measurements of the different fluorescent molecule tags revealed characteristic clustering of the DDR markers around one or two damage foci per PBMC cell nucleus. Ripley distance histograms suggested the concentration of MRE11 molecules inside γH2AX-clusters, while 53BP1 was present throughout the entire γH2AX clusters. Persistent homology comparisons for 53BP1, MRE11 and γH2AX by Jaccard index calculation revealed significant topological similarities for each of these markers. Since the heterochromatin organization of cell nuclei determines the identity of cell nuclei and correlates to genome activity, it also influences DNA repair. Therefore, the histone H3 tri methyl mark H3K9me3 was analyzed for its topology. In contrast to typical results obtained through photon irradiation, where γH2AX and H3K9me3 markers were well separated, the results obtained here also showed a close spatial proximity (“co-localization”) in many cases (minimum distance of markers = marker size), even with the strictest co-localization distance threshold (20 nm) for γH2AX and H3K9me3. The data support the results from the literature where only one DSB induced by low-dose low LET irradiation (<100 mGy) can remain without heterochromatin relaxation for subsequent repair. Full article

Spray freeze-drying (SFD) is a novel technique for formulating dry powders, particularly for pulmonary drug delivery via dry powder inhalers (DPIs). Despite their low density and excellent aerodynamic properties, such powders are affected by high cohesiveness due to their surface properties. Sugars such as mannitol (MAN), trehalose, raffinose, and sucrose are commonly used in SFD. MAN is widely employed due to its high MAN—ice eutectic temperature—at which MAN and water (ice) form a stable eutectic mixture—and its crystallinity. However, crystallinity can impact the microparticles’ (MPs) cohesiveness, since MAN exhibits distinct polymorphs (α, β, δ) with peculiar properties. This study provides valuable insights for the development of DPI formulations by ensuring precise control over MAN polymorphism, ultimately enhancing formulation stability and performance. We introduced, for the first time, an intermediate freezing (IF) step within the SFD process to modulate MAN polymorphism, demonstrating its synergy with optimised storage temperature conditions. Furthermore, polyvinylpyrrolidone, 2-hydroxypropyl beta cyclodextrin, dextran, and polysorbate 80 were employed as polymorphism-controlling agents for MAN, contributing to the development of stable formulations with reduced particle cohesion and improved storage stability at room temperature. For the first time, this study shows that MAN polymorphism in SFD can be controlled to drive dry powder inhaler performance. Full article

Bioaerosols are a major source of airborne microbial contamination in intensive poultry production systems. Their concentration and community structure can profoundly influence animal health, public health, and the overall safety of the farming environment. However, the dynamic characteristics of bacterial aerosols in enclosed poultry houses during winter remain insufficiently studied. Using Taihang chickens as a model, this study investigated three key production stages—brooding (15 days), growing (60 days), and laying (150 days)—under winter cage-rearing conditions. A six-stage Andersen sampler was employed alongside culture-dependent enumeration and 16S rRNA high-throughput sequencing to analyze variations in bacterial aerosol concentration, particle size distribution, and community succession patterns. The results revealed a significant increase in the concentration of culturable airborne bacteria with bird age, rising from 8.98 × 10³ colony-forming unit (CFU)/m³ to 2.89 × 10⁴ CFU/m³ (p < 0.001). The particle size distribution progressively shifted from larger, settleable particles (≥4.7 μm) toward smaller, respirable particles (<4.7 μm). Microbial sequencing indicated a continuous increase in bacterial alpha diversity across the three stages (Chao1 and Shannon indices, p < 0.05), while beta diversity exhibited stage-specific clustering, reflecting clear differences in community assembly. The composition of dominant bacterial genera transitioned from potentially pathogenic taxa such as Acinetobacter and Corynebacterium during the brooding stage to a greater abundance of beneficial genera, including Bacteroides, Lactobacillus, and Ruminococcus, in later stages. This shift suggests a potential ecological link between aerosolized bacterial communities and host development, possibly related to the aerosolization of gut microbiota. Notably, several zoonotic bacterial species were detected in the poultry house air, indicating potential public health and occupational exposure risks under winter confinement conditions. This study is the first to elucidate the ecological succession patterns of airborne bacterial aerosols in Taihang chicken houses across different growth stages during winter. The findings provide a scientific basis for optimizing winter ventilation strategies, implementing stage-specific environmental controls, and reducing pathogen transmission and occupational hazards. Full article

Microbial communities play a crucial role in coastal ecosystem function, yet their seasonal and spatial dynamics in response to environmental change remain underexplored in tropical and subtropical regions. This yearlong study investigated microbial composition in water, sinking particles, and sediments along an inshore–offshore gradient influenced by the Caloosahatchee River Estuary in southwest Florida. The region has been altered by rapid coastal development and was struck by Hurricane Ian in September 2022. Environmental parameters exhibited significant spatiotemporal variation, shaping microbial beta diversity in all habitats. Sediment communities showed the greatest hurricane-induced disruption but returned to pre-disturbance conditions within six months. Dominant microbial classes included Alphaproteobacteria, Bacteroidia, and Gammaproteobacteria. Biogeochemical cycling taxa displayed strong habitat specificity, such as Desulfobulbia which dominated sinking particles, Desulfobacteria which was abundant in sediments, and Nitrosomonadaceae and Nitrosopumilaceae which were key nitrifiers in water and sediments, respectively. Particle–sediment taxonomic overlap suggests resuspension processes. Several inshore microbial indicators were consistently present across microbial habitats, especially at estuarine sites, suggesting the estuary as a microbial diversity reservoir for the coastal zone. These results highlight the value of long-term microbial monitoring to understand ecosystem change and resilience in dynamic coastal environments. Full article

Nowadays, growing evidence indicates that plant-derived nanovesicles cross biological barriers between species, including humans, and deliver therapeutic molecules that influence gene expression, affecting various processes such as inflammation, oxidative stress, and cancer. For these reasons, plant-derived nanovesicles are gaining attention as a valuable substitute for mammalian exosomes as they offer benefits such as reduced immunogenicity, enhanced bioavailability, and the inclusion of beneficial plant metabolites. However, the development of affordable plant-derived nanovesicle-based therapies requires a robust characterization of their molecular structure and cargo, which in turn depends on obtaining sufficient quantities of homogeneous nanovesicle populations. In this study, we used an advanced purification platform combining ultrafiltration and anion exchange chromatography to isolate highly pure plant-derived nanovesicles from a new source, Beta vulgaris L. These particles were characterized in terms of size, charge, and morphology, and their molecular content was analyzed by omic technologies, including proteomics, lipidomics, and miRNomics. Their ability to promote wound healing and reduce inflammation was demonstrated in vitro using human cells. Furthermore, bioinformatic analysis linking the microRNA profile with potential human target genes provides insights into the biochemical pathways that underlie the bioactivity of nanovesicles. Full article

The traditional method used in the production of inactivated vaccines is chemical inactivation using beta-propiolactone or formaldehyde. An alternative method is inactivation by irradiation. Virus inactivation is often accompanied by a change in particle shape, which can negatively affect the preservation of antigens and immunogenicity. Therefore, determining the shape and structure of the viral particle after inactivation is an important step in the development of antiviral vaccines. The poliovirus strain Sabin 2 was inactivated with a dose of 30.5 ± 0.5 kGy. in a pulsed linear electron accelerator with a power of 15 kW and electron energy of 10 MeV. Samples inactivated with beta-propiolactone or formaldehyde were used for comparison. All types of inactivation resulted in D-antigen recovery as determined by enzyme-linked immunosorbent assay. There was no statistical difference between D-antigen recovery in irradiated samples and those inactivated chemically. The shape and structure of the inactivated poliovirus particles were studied using atomic force and electron microscopy. After inactivation with beta-propiolactone or formaldehyde, a change in the native icosahedral shape was observed, with many particles appearing flattened. Specific sorption of antibodies showed that the antigen is mainly preserved in intact capsids for all type of inactivation. However, in the case of inactivation with formaldehyde and accelerated electrons, a significant number of fragments measuring 10–20 nm in height were present. Their proportion was 38 ± 2% and 17 ± 2% for inactivation with accelerated electrons and formaldehyde, respectively. The proportion of bound fragments during inactivation with beta-propiolactone was less than 1%. Full article

3D printing of beta titanium alloys for biomedical applications is currently in great demand, both for material reasons and for the possibility of producing very complex replacements, often directly tailored to the patient. Gyroidal and similar structures are ideal for biomedical replacements but their manufacturing require specific additive technology and post-processing like annealing or etching. The aim of this work is to determine the mechanical properties of Ti25Nb4Ta8Sn alloy which overcomes Ti6Al4V in biomedical applications. The results showed that Ti6Al4V exhibited a significantly higher ultimate tensile strength (up to 1200 MPa) compared with the beta titanium alloy Ti25Nb4Ta8Sn (up to 360 MPa), while the latter demonstrated a substantially lower elastic modulus (∼40–50 GPa), beneficial for biomedical applications. Annealing improved strength and reduced internal stresses in both alloys, while etching effectively removed residual powder but slightly decreased mechanical integrity. These findings provide a quantitative basis for optimizing printing and post-processing parameters of beta titanium alloys for implant design. The properties will be used for future numerical simulations of implants made from Ti25Nb4Ta8Sn alloy based on discrete particle grid models. Full article