Search Results (452)

The rapid growth of Distributed Energy Resources (DERs) exerts significant pressure on distribution network margins, requiring predictive and safe coordination. This paper presents a closed-loop framework combining a topology-aware Spatio-Temporal Transformer (STT) for multi-horizon forecasting, a cooperative multi-agent reinforcement learning (MARL) controller under Centralized Training and Decentralized Execution (CTDE), and a real-time safety layer that enforces feeder limits via sensitivity-based quadratic programming. Evaluations on three SimBench feeders, with OLTC/capacitor hybrid control and a stress protocol amplifying peak demand and mid-day PV generation, show that the method reduces tail violations by 31% and 56% at the 99th percentile voltage deviation, and lowers branch overload rates by 71% and 90% compared to baselines. It mitigates tail violations and discrete switching while ensuring real-time feasibility and cost efficiency, outperforming rule-based, optimization, MPC, and learning baselines. Stress maps reveal robustness envelopes and identify MV–LV bottlenecks; ablation studies show that diffusion-based priors and coordination contribute to performance gains. The paper also provides convergence analysis and a suboptimality decomposition, offering a practical pathway to scalable, safe, and interpretable DER coordination. Full article

Pomme fruits are propagated vegetatively, thereby facilitating frequent viral transmission. The causative agent of apple rubbery wood disease, apple rubbery wood virus 2 (ARWV2), can infect apple and pear. The branches of ARWV2-infected, symptomatic trees are flexible due to the decreased lignification of the xylem. In this research, we reanalysed our small RNA (sRNA) HTS datasets to survey the presence of ARWV2 in Hungary. Validation of HTS using RT-PCR revealed infection in several cultivars. The following RT-PCR-based survey revealed the infection of 17 trees, including not only apple, but also pears, one quince, and a rootstock, without showing any rubbery wood symptoms. Analysis of the sRNA datasets allowed us to profile the sRNA pattern of ARWV2-infected and non-infected trees, and characterise the differential expression pattern of vsiRNAs, sRNAs, and miRNAs targeting the lignin biosynthetic pathway. The results confirmed that the gene-expression changes in the genes that regulate lignification cannot be directly correlated with the presence of the virus, which can explain its frequent latent presence. The variable titre and sequence of the virus, and mixed-infection status of the trees, make its reliable diagnostics challenging, which could be achieved as a result of further research. Full article

Atherosclerosis (AS) currently lacks fully effective treatments. This study investigated the natural compound hesperidin as a potential therapy. Apolipoprotein E knockout (ApoE^−/−) mice were used as a model of atherosclerosis; we found that hesperidin treatment improved physiological and metabolic health, reduced plaque formation, and decreased systemic inflammation and oxidative stress. Hesperidin also reshaped gut microbiota, increasing beneficial bacteria (Verrucomicrobia and Bacteroidota) and significantly lowering fecal levels of branched-chain amino acids (BCAAs: valine, leucine, and isoleucine) by 27.4%, 50.1%, and 40.8%, respectively. These changes were linked to specific microbial shifts. We conclude that hesperidin alleviates atherosclerosis likely by modulating the gut microbiota–BCAA–host axis, identifying it as a promising dietary intervention or therapeutic agent. Full article

Accurate depth image inpainting in complex urban environments remains a critical challenge due to occlusions, reflections, and sensor limitations, which often result in significant data loss. We propose a hybrid deep learning framework that explicitly combines local and global modelling through Convolutional Neural Networks (CNNs) and Transformer modules. The model employs a multi-branch parallel architecture, where the CNN branch captures fine-grained local textures and edges, while the Transformer branch models global semantic structures and long-range dependencies. We introduce an optimized attention mechanism, Agent Attention, which differs from existing efficient/linear attention methods by using learnable proxy tokens tailored for urban scene categories (e.g., façades, sky, ground). A content-guided dynamic fusion module adaptively combines multi-scale features to enhance structural alignment and texture recovery. The frame-work is trained with a composite loss function incorporating pixel accuracy, perceptual similarity, adversarial realism, and structural consistency. Extensive experiments on the Paris StreetView dataset demonstrate that the proposed method achieves state-of-the-art performance, outperforming existing approaches in PSNR, SSIM, and LPIPS metrics. The study highlights the potential of multi-scale modeling for urban depth inpainting and discusses challenges in real-world deployment, ethical considerations, and future directions for multimodal integration. Full article

Bacillus anthracis is the etiological agent of the zoonotic disease anthrax. The pathogen has colonized many regions of all inhabited continents. Increasing evidence points to a strong contribution of anthropogenic activities (trade) in this almost global spread. This article contributes further genomic data from 21 B. anthracis strains, including 19 isolated in Germany, aiming to support and detail the human role in anthrax dispersal. The newly sequenced genomes belong to the B. anthracis lineage predominant in China. This lineage is remarkable because of its phylogenetic structure. A polytomy with nine branches radiating from a central node was identified by whole-genome single-nucleotide polymorphism (wgSNP) analysis. Strains from Germany populate two among the nine branches. Detailed analysis of the polytomy indicates that it most likely emerged in China. We propose that the polytomy is the result of the import of contaminated animal products in a limited spatiotemporal frame, followed by the distribution of these products to different locations within China, where new B. anthracis lineages then became independently established. Currently available data point to Bengal as a likely geographic source of the original contamination, and the history of trade exchanges between Bengal and China agrees with the early fifteenth century as a likely time period. The subsequent exports to Germany would have occurred during the 19th century according to German trade history. Notably, Germany has been experiencing localized anthrax outbreaks from this trade heritage up into the 21st century. Full article

We present a hybrid partial differential equation-agent-based model (PDE-ABM). In our framework, tumor cells secrete tumor angiogenic factor (TAF), while endothelial cells chemotactically migrate and branch in response. Reaction–diffusion PDEs for TAF, oxygen, and cytotoxic drug are coupled to discrete stochastic dynamics of tumor cells and endothelial tip cells, ensuring multiscale integration. Motivated by observed perfusion heterogeneity in tumors and its pharmacokinetic consequences, we conduct a linear stability analysis for a reduced endothelial–TAF reaction–diffusion subsystem and derive an explicit finite-domain threshold for Turing instability. We demonstrate that bidirectional coupling, where endothelial cells both chemotactically migrate along TAF gradients and secrete TAF, is necessary and sufficient to generate spatially periodic vascular clusters and inter-cluster hypoxic regions. These emergent patterns produce heterogeneous drug penetration and resistant niches. Our results identify TAF clearance, chemotactic sensitivity, and endothelial motility as effective levers to homogenize perfusion. The model is two-dimensional and employs simplified kinetics, and we outline necessary extensions to three dimensions and saturable kinetics required for quantitative calibration. The study links reaction–diffusion mechanisms with clinical principles and suggests actionable strategies to mitigate resistance by targeting endothelial–TAF feedback. Full article

Background/Objectives: Trophoblast cell surface antigen 2 (Trop2), a transmembrane glycoprotein overexpressed in a broad spectrum of epithelial malignancies but minimally expressed in normal tissues, has emerged as a clinically relevant prognostic biomarker and therapeutic target, particularly in breast cancer. This study aims to develop an enhanced way of targeting Trop2 expression in tumors and blocking it using extracellular vesicles (EVs) bioengineered to express a nanobody sequence against Trop2 (NB60 E). Methods: Here, a plasmid construct was designed to express the Trop2 sequence, NB60, flanked with HA tag and myc epitope and a PDGFR transmembrane domain in the C-terminal region, and was transfected into HEK293T cells for EVs isolation. The potency of NB60 E to knock down Trop2 in letrozole-resistant breast cancer cells (LTLT-Ca and MDA-MB-468 cells) was initially investigated. Thereafter, the effects of NB60 E on the cell viability and downstream signaling pathway of Trop2 via MTT assay and Western blotting were determined. Lastly, we also examined whether NB60 E treatment in Jurkat T cells affects IL-6, TNF-α, and IL-2 cytokine production by enzyme-linked immunosorbent assay (ELISA). Results: Results revealed treatment with NB60 E significantly reduced surface Trop2 expression across both cell lines by 23.5 ± 1.5% in MDA-MB-468, and 61.5 ± 1.5% in LTLT-Ca, relative to the HEK293T-derived control EVs (HEK293T E). NB60 E treatment resulted in a marked reduction in LTLT-Ca cell viability by 52.8 ± 0.9% at 48 h post-treatment. This was accompanied by downregulation of key oncogenic signaling molecules: phosphorylated ERK1/2 (p-ERK 1/2) decreased by 30 ± 4%, cyclin D1 by 67 ± 11%, phosphorylated STAT3 (p-STAT3) by 71.8 ± 1.6%, and vimentin by 40.8 ± 1.4%. ELISA analysis revealed significant decreases in IL-6 (−57.5 ± 1.5%, 7.4 ± 0.35 pg/mL) and TNF-α (−32.1 ± 0.3%, 6.1 ± 1.2 pg/mL) levels, coordinated by an increase in IL-2 secretion (22.1 ± 2.7%, 49.2 ± 1.1 pg/mL). Quantitative analysis showed marked reductions in the number of nodes (−45 ± 4.4%), junctions (−55 ± 3.5%), and branch points (−38 ± 1.2%), indicating suppression of angiogenic capacity. In vivo experiment using near-infrared Cy7 imaging demonstrated rapid and tumor-selective accumulation of NB60 E within 4 h post-administration, followed by efficient systemic clearance by 24 h. The in vivo results demonstrate the effectiveness of NB60 E in targeting Trop2-enriched tumors while being efficiently cleared from the system, thus minimizing off-target interactions with normal cells. Lastly, Trop2 expression in LTLT-Ca tumor xenografts revealed a significant reduction of 41.0 ± 4% following NB60 E treatment, confirming efficient targeted delivery. Conclusions: We present a first-in-field NB60 E-grafted EV therapy that precisely homes to Trop2-enriched breast cancers, silences multiple growth-and-invasion pathways, blocks angiogenesis, and rewires cytokine crosstalk, achieving potent antitumor effects with self-clearing, biomimetic carriers. Our results here show promising potential for the use of NB60 E as anti-cancer agents, not only for letrozole-resistant breast cancer but also for other Trop2-expressing cancers. Full article

UV-C radiation has emerged as a germicidal agent against pathogens, particularly following the COVID-19 pandemic. While UV-C effectively reduces cross-contamination in hospitals, it induces photodegradation in polymer devices, potentially damaging and posing risks to patient safety. Therefore, it is crucial to detect the effects of UV-C photodegradation on early stages, as well as the effects of prolonged UV-C exposure. In this study, we investigated the UV-C photodegradation (254 nm, 471 kJ/mol) of isotactic polypropylene homopolymer (PP), commonly used in medication packaging. The impact of UV-C on PP was evaluated through rheology and infrared spectroscopy. Surface energy was measured by the contact angles formed by drops of water and diiodomethane. The effects of photodegradation on the polymer’s morphology were examined using scanning electron microscopy, and the melting temperature and crystallinity by differential scanning calorimetry. Lastly, the effect of UV-C on molecular mobility was studied using ¹H Time Domain Nuclear Magnetic Resonance (¹H TD-NMR). These techniques proved to be valuable tools for identifying the early stages of UV-C photodegradation, and ¹H TD-NMR was a sensitive method to identify the chain branching as a photodegradation product. This study highlights the impact of UV-C on PP photodegradation and hence the importance of understanding UV-C-induced degradation. Full article

Macroalgal polysaccharides represent a diverse group of structurally complex biopolymers with significant potential in biomedicine and functional food applications. This review provides a comprehensive examination of their structural features, biological activities, and molecular targets, with an emphasis on precision applications. Key polysaccharides such as alginates, carrageenans, fucoidans, ulvans, and laminarans are highlighted, focusing on their unique chemical backbones, degrees of sulfation, and branching patterns that underlie their bioactivity. Special attention is given to their roles in modulating inflammation, oxidative stress, apoptosis, gut microbiota, and metabolic pathways. Comparative assessment of extraction strategies, structure–function relationships, and bioactivity data highlights the importance of tailoring polysaccharide processing methods to preserve bioefficacy. Emerging insights from computational modelling and receptor-binding studies reveal promising interactions with immune and apoptotic signalling cascades, suggesting new therapeutic opportunities. Finally, the review outlines challenges related to standardisation, scalability, and regulatory approval, while proposing avenues for future research toward clinical translation and industrial innovation. By integrating structural biology, pharmacology, and nutraceutical sciences, this work underscores the potential of macroalgal polysaccharides as precision agents in health-promoting formulations and next-generation functional foods. Full article

Currently, resin polymer anchoring agents are widely used for bolting support in coal mine roadways to anchor the bolts to the surrounding rock mass. However, due to the relatively low strength of the resin anchoring agent itself, the required anchoring length tends to be excessively long. Based on this, this paper proposes the use of resin concrete as a replacement for resin. Compared to resin anchoring agents, resin concrete offers greater mechanical interlocking force with anchor rods, which can reduce the theoretical anchoring length. To systematically investigate the influence of factors such as the diameter and anchorage length of Glass Fiber-Reinforced Polymer (GFRP) bolt on the bond behavior between GFRP bolts and resin concrete, 33 standard pull-out tests were designed and conducted in accordance with the CSA S807-19 standard. Taking the 18 mm-diameter bolt as an example, when the bond lengths were 2D, 3D, 4D, and 5D, the average bond strengths were 41.32 MPa, 39.18 MPa, 38.84 MPa, and 37.44 MPa, respectively. This represents a decrease of 5.18%, 6.00%, and 9.39% for each subsequent increase in bond length. The results indicate that the bond strength between GFRP anchors and resin decreases as the anchorage length increases. Due to the shear lag effect, the average bond strength also decreases with increasing anchor diameter. Taking a 5D (where D is the anchor diameter) anchorage length as a reference, the average bond strengths for anchor diameters of 18 mm, 20 mm, 22 mm, and 24 mm were 37.44 MPa, 33.97 MPa, 32.18 MPa, and 31.50 MPa, respectively. The corresponding reductions compared to the 18 mm diameter case were 9.27%, 14.05%, and 15.87%. Based on the experimental results, this paper proposes a bond–slip constitutive model between the bolt and resin concrete, which consists of a rising branch, a descending branch, and a residual branch. A differential equation relating shear stress to displacement was established, and the functions describing the variation in displacement, normal stress, and shear stress along the position were solved for the ascending branch. Although an analytical solution for the differential equation of the descending branch was not obtained, it will not affect the subsequent derivation of the theoretical anchorage length for the GFRP bolt–resin concrete system, as structural components in practical engineering are not permitted to undergo excessive bond-slip. Full article

Background/Objectives: Plant growth-promoting rhizobacteria (PGPR) have demonstrated potential for enhancing plant growth; existing research inadequately characterizes the metabolic underpinnings of PGPR-induced plant phenotypes. Methods: A deeper investigation into the impact of PGPR on plant metabolic pathways is crucial for a comprehensive understanding of their growth-promoting mechanisms and for the development of more effective biofertilizers and plant protection strategies. Results: To clarify the core metabolic pathways targeted by PGPR strains, we selected alfalfa as the research object, employed two Pseudomonas combinations, and utilized a broad-targeted metabolomics approach to investigate the metabolic characteristics of alfalfa roots. Through the analysis of primary and secondary metabolites, a total of 2694 metabolites were identified, among which lipids were the main nutrients during the growth of alfalfa. The L-citrulline and L-arginine contents were significantly upregulated, thereby affecting nitrogen metabolism and ultimately promoting plant growth. In addition, different branches of the isoflavonoid biosynthesis pathway showed differential regulation, indicating their close relationship with plant growth promotion. Conclusions: This study provides a new perspective for a deeper understanding of the molecular mechanisms by which PGPR promotes plant growth and lays a theoretical foundation for the future development of PGPR-based agricultural biological agents. Full article

Hydrogels are hydrophilic biocompatible polymers that can be used as a drug delivery material in different medical branches, including vital pulp therapy. The aim of this study is to characterize the physical and biological properties of the newly developed formula as a candidate direct pulp-capping material. The hydrogel composite was prepared from natural and synthetic origins (polyvinyl alcohol (PVA), hyaluronic acid (HA), and sodium alginate (SA)) with the incorporation of bioactive Moringa. Different formulas of hydrogel containing different concentrations were evaluated for physicochemical (FTIR, XRD, SEM, degradation, and swelling), mechanical (viscosity, folding endurance, film thickness), and biological (antioxidant, antibacterial, and cytotoxicity) properties. FTIR and XRD confirmed successful incorporation and partial cross-linking between moringa and hydrogel compounds. At low concentrations of moringa, the hydrogel formula showed integrity, scavenging activity, and homogeneity. The moringa-loaded films showed concentration-dependent antioxidant and antibacterial properties, especially at higher concentrations, with acceptable cytocompatibility. The low concentration of moringa (0.5%) may be considered a promising candidate as a novel pulp-capping agent supporting tissue healing and regeneration. Full article

Polysaccharides derived from green algae have garnered significant attention owing to their distinctive structural characteristics and biological activities. In particular, sulfated polysaccharides from these algae represent a promising frontier in the discovery of novel therapeutic agents. In this present study, a sulfated galactan from Caulerpa taxifolia, designated SGC, was obtained by dilute alkali extraction and chromatographic purification. On the basis of chemical and spectroscopic analyses, the backbone of SGC was constituted by a backbone of →3)-β-d-Galp-(1→ with sulfate substitution at the C-2 and a branch on C-6. The side chains contained →6)-β-d-Galp(2SO₄)-(1→, →6)-β-d-Galp(3OMe)-(1→ and →3)-β-d-Galp(4,6-Pyr)-(1→ units. SGC possessed strong hypoglycemic activity in vitro, as evaluated by an assay of α-amylase inhibition. The anti-diabetic activity of SGC in vivo was further investigated using T2DM mice induced by high-fat diet combined with streptozotocin. The results indicated that SGC markedly restored body weight, reduced fasting blood glucose and possessed a significant glucose-regulating effect. Furthermore, SGC effectively increased insulin sensitivity and mitigated insulin resistance. Additionally, SGC effectively regulated lipid metabolism and alleviated oxidative stress. Notably, SGC ameliorated liver and pancreas damage induced by high-fat diet combined with streptozotocin. The investigation demonstrates that SGC is a unique sulfated galactan and has potential as a novel anti-diabetic agent. Full article

In response to the escalating plastic pollution crisis, the development of high-performance biodegradable materials is critical. Poly(butylene succinate) (PBS) is an important biodegradable polymer as it possesses excellent biodegradability and processability. But it suffers from limitations such as low mechanical strength, poor thermal stability, and high production costs. In this study, taxus residue (TF), a waste by-product, was utilized as a reinforcing filler to reduce PBS costs while enhancing its overall performance. To address the interfacial incompatibility between TF and PBS, branched PBS (T-PBS) was introduced as a compatibilizer. The TF was surface-modified via alkali treatment and silane coupling (KH550), and a series of PBS/TF/T-PBS composites with varying T-PBS viscosity grades were prepared by melt blending. The compatibilization mechanism of T-PBS and its influence on the composite structure, crystallization behavior, thermal stability, rheological, and mechanical properties were systematically investigated. Results show that the branched structure significantly enhanced T-PBS melt strength and reactivity. The introduction of T-PBS effectively improved interfacial compatibility between TF and PBS matrix, reducing phase separation and interfacial defects. Compared to uncompatibilized PBS/TF composites, those with appropriately viscous T-PBS exhibited improved tensile strength (increased by 19.7%) and elongation at break (increased by 78.8%), while flexural strength was also maintained at an enhanced level. The branched points acted as nucleating agents, increasing the onset temperature and degree of crystallinity. In the high-temperature region, the synergistic barrier effect from TF and char residue improved thermal stability (T_85% reached 408.19 °C). Rheological analysis revealed enhanced viscosity and elasticity of the system. This study provides a promising strategy and theoretical foundation for the high-value utilization of taxus waste and the development of high-performance biodegradable PBS-based composites. Full article

In recent years, symptoms of Twig Cankers and Shoot Blight (TCSB) have re-emerged in several Italian peach orchards, particularly within key production areas of the Emilia-Romagna region. The fungal pathogen Diaporthe amygdali is recognized as the primary causal agent of TCSB, leading to the rapid desiccation of shoots, flowers, leaves, and branches, often accompanied by resin exudation from cankers that appear in late winter or early spring. Given Italy’s position as the second-largest peach producer in Europe, ensuring sustainable yields and high fruit quality necessitates a deeper understanding of D. amygdali biology and the development of effective diagnostic and management tools. This study employed a hybrid whole-genome sequencing strategy, combining Illumina short-read and PacBio long-read technologies, to generate the first high-quality genome assembly of D. amygdali isolated from peach. The genome analysis revealed candidate virulence genes and other factors involved in pathogenicity, deepening our understanding of the infection strategies employed by D. amygdali. These findings may support the potential development of sustainable, effective strategies against TCSB, ultimately supporting resilient peach production in Italy and beyond. Full article