Search Results (8,382)

Mesenchymal stem cells (MSCs) are multipotent cells that have the ability to mediate cellular repair through a combination of soluble paracrine factors, as well as bioactive cargo packaged within extracellular vesicles (EVs). Although MSC-derived EVs have been widely investigated for their regenerative potential, progress toward translational evaluation has been limited in part by challenges in scalable and reproducible manufacturing. We recently reported that human telomerase reverse transcriptase (hTERT)-immortalized MSCs reproducibly produce EVs that retain key characteristics of EVs derived from primary MSCs. Building on this work, three-dimensional (3D) culture systems have emerged as promising platforms for large-scale manufacturing. In this study, we compared the yield, molecular composition, and functional activity of EVs produced from hTERT-immortalized MSCs cultured in either a fixed-bed bioreactor or conventional two-dimensional (2D) flasks. Our data demonstrate that bioreactor culture results in increased EV yield as compared to an equivalent production from 2D cultures. Molecular analyses indicated that bioreactor-derived EVs were associated with a broader spectrum of cargo and were enriched with molecules that may contribute to enhanced reparative function. Importantly, bioreactor-derived EVs also exerted a more pronounced effect in cellular repair assays in vitro. Collectively, these results highlight the potential of fixed-bed bioreactors as scalable platforms for EV production, offering higher yields while preserving molecular composition and functional activity. This approach represents an important step toward achieving the reproducible, high-quality EV production required for research and future translational applications. Full article

Factor XII (FXII) is a central mediator at the intersection of coagulation, fibrinolysis, inflammation, and immunity. It is activated upon contact with negatively charged surfaces, triggering the intrinsic coagulation pathway and driving thrombus formation and stabilization. Beyond clotting, FXII contributes to activation of the kallikrein–kinin system, generation of bradykinin, and modulation of inflammatory and immune responses. Congenital FXII deficiency does not increase bleeding risk, highlighting its unique role and making FXII inhibition an attractive strategy for anticoagulation and immune modulation with a potentially superior safety profile. Preclinical studies provide compelling evidence for this concept. In models of ischemic stroke and traumatic brain injury, FXII blockade significantly reduced infarct volume, improved neurological outcomes, and attenuated neuroinflammation without increasing hemorrhage. Similarly, in extracorporeal circulation and vascular stent implantation, FXII inhibition prevented thrombus formation and reduced fibrin deposition, achieving effects comparable to heparin but with markedly lower bleeding risk. Several classes of FXII inhibitors are currently in development, including antisense oligonucleotides, peptides, recombinant proteins, and monoclonal antibodies. Among them, Ixodes ricinus contact phase inhibitor (Ir-CPI) and recombinant human albumin-fused Infestin-4 (rHA-Infestin-4) have demonstrated strong antithrombotic efficacy in animal models. Most notably, garadacimab, a monoclonal anti-FXIIa antibody, has completed phase 3 trials and received regulatory approval for hereditary angioedema (HAE) prophylaxis, where it markedly reduces attack frequency with a favorable safety profile. This review summarizes current knowledge on FXII biology and evaluates its translational potential as a novel target for anticoagulant and anti-inflammatory therapies. Full article

Biomimetics in dental restorative materials has gradually shifted from simply copying the appearance of natural teeth to better understanding how those tissues actually behave. Instead of focusing only on aesthetics, there is now more attention on how enamel and dentin function in real conditions, how they respond to stress, interact with their surroundings, and change over time. Because of this, newer materials are no longer just passive fillers; they are being designed to reflect aspects of natural tooth structure, composition, and behavior within the oral environment. This review brings together key ideas in this area, recent developments, and the challenges that remain. One issue that often comes up is how terms like bioinspired, biomimetic, and bioactive are used. They are sometimes treated as if they mean the same thing, but in practice, they point to different goals or levels of complexity in material design. For instance, some studies focus on creating more organized composite structures or mimicking natural mineralization processes, while others focus on antibacterial surfaces or peptide-based approaches that may support remineralization. There is also growing interest in materials that respond to environmental changes, such as shifts in pH or the early stages of wear. Even with promising laboratory results, these materials are not yet widely used in everyday clinical practice. Several issues continue to slow their adoption, including unclear terminology, limited availability of testing models that reflect real oral conditions, and a lack of long-term clinical data. Part of the challenge lies in the lack of consistent terminology, which can make it harder to compare findings across studies. Manufacturing challenges also remain, particularly when scaling up more complex systems. Moving forward, progress will depend on closer collaboration across disciplines, including materials science, oral biology, microbiology, and digital manufacturing. Such efforts will be important for developing restorative materials that behave more like natural tissues and perform reliably over time inside the mouth. Full article

To address the challenges of narrow genetic backgrounds and low phenotypic selection efficiency in tomato breeding, comparative genomics was applied. Based on the genomic sequences of five tomato varieties (‘Micro-Tom’, ‘Moneymaker’, ‘M82’, ‘Heinz 1706’, and ‘LA2093’), a total of 285,796 InDel loci were preliminarily identified. Based on these loci, a total of 255 pairs of molecular markers were developed. Subsequently, based on InDel length, polymorphism, and electrophoretic performance, 63 InDel markers with stable amplification, clear polymorphic bands, and coverage across all 12 chromosomes were rigorously selected. These markers were subsequently used to analyze the genetic diversity of 52 tomato germplasm resources. The polymorphism information content (PIC) values of the markers ranged from 0.074 to 0.402, with an average of 0.2804. Cluster analysis based on InDel genotyping data divided the 52 germplasm samples into four distinct groups with significant genetic differentiation, which was validated in conjunction with previously collected phenotypic data from the 52 tomato germplasm resources. Furthermore, a set of core InDel primer combinations (24 pairs) was selected to construct unique DNA fingerprint profiles for each germplasm group. Overall, the InDel markers developed in this study provide an efficient tool for evaluating genetic diversity in tomato germplasm and offer a reliable molecular basis for germplasm identification, heterosis prediction, and marker-assisted breeding, thereby facilitating the development of improved tomato cultivars. Full article

Understanding how viruses engage host cell surfaces is fundamental to infection biology and therapeutic development. While vaccines remain central to prevention, recent global crises have emphasized the need for complementary antiviral strategies that can be mobilized rapidly against both known and emerging pathogens. In this context, artificial intelligence (AI) systems for biomolecular structure prediction, culminating in AlphaFold 3, are reshaping what is experimentally and conceptually achievable. Here, we present “Interactys-AI”, a framework designed to exploit AI-based structural modeling to systematically map virus–host protein–protein interactions (PPIs) and connect them to actionable drug repurposing opportunities. Beyond a technical workflow, Interactys-AI reflects a broader transformation toward predictive and anticipatory antiviral discovery. We describe the conceptual foundations of the platform, its implementation, and its application to influenza A H5N1 hemagglutinin. We further discuss how structural AI may redefine preparedness strategies, highlight current limitations, and outline future directions toward real-time therapeutic hypothesis generation. Full article

Atypical teratoid rhabdoid tumor (AT/RT) is a rare, highly aggressive embryonal central nervous system malignancy occurring predominately in infants and toddlers. Spinal AT/RT (spAT/RT) cases are even more limited, and as a result, little is known regarding prognostic factors and optimal treatment regimens. Molecularly, AT/RT is divided into three groups: AT/RT-SHH, AT/RT-TYR and AT/RT-MYC. spAT/RT is predominantly of the MYC subtype. Additionally, a third of patients with AT/RT have a germline Rhabdoid Tumor Predisposition Syndrome (RTPS) that increases the likelihood of developing additional rhabdoid tumors, including renal rhabdoid tumors. Due to the rarity of these tumors, there is a lack of consensus on treatment strategies to be employed. This review paper details the published literature on spAT/RT, with particular emphasis on the recent advances in understanding the biology of these aggressive tumors and currently available therapeutic options, and highlights the challenges associated with the management of this extremely rare condition. Full article

Micro air vehicles (MAVs) operating at low Reynolds numbers face aerodynamic and structural challenges that differ significantly from those encountered by conventional aircrafts. Nature provides effective solutions to these constraints, as insects, birds, and bats demonstrate highly efficient flight through integrated interactions between morphology, kinematics, and unsteady aerodynamic mechanisms. This review examines how biological flight principles can inform the design of next-generation MAVs. The study first analyzes biological flight strategies across insects, birds, and bats, with emphasis on scaling laws and physiological adaptations relevant to small-scale flight. It then reviews key unsteady aerodynamic phenomena governing low-Reynolds-number flight, including leading-edge vortex stability, wing–wake interactions, tandem-wing effects, and ground influence, as well as current modeling approaches ranging from quasi-steady methods to high-fidelity Navier–Stokes simulations. Building on these principles, the paper discusses biomimetic design strategies for MAV wings, structural–aerodynamic coupling, and actuation technologies used to replicate flapping flight. Existing MAV demonstrators inspired by biological flyers are analyzed, including concepts relevant to planetary exploration environments. Finally, the review identifies current technological limitations and research gaps in materials, actuation, aerodynamic modeling, and system integration. By synthesizing insights from biology and engineering, this work highlights key directions for the development of efficient, adaptable biomimetic MAV platforms capable of operating in complex environments. Full article

Growing evidence suggests that chronic kidney disease (CKD) profoundly disrupts gut microbiome and its activity. This study explores how CKD affects colon microbial metabolism, focusing on (1) the representativeness of fecal metabolomics, (2) saccharolytic and proteolytic fermentation metabolites, and (3) the gut microbiome’s role in the partitioning of tryptophan in its metabolic pathways. Tryptophan’s main metabolic pathways include the indolic and the kynurenine pathways, which lead, respectively, to the formation of indoxyl sulfate and kynurenine, both contributing to uremic toxicity. Using a rat model of CKD, we evaluated whether fecal concentrations of microbial compounds, on which most studies are based, reflect the colonic concentrations in contact with the gut mucosa. Thus, we quantified the concentration and content of amino acids, indole, p-cresol, and also short-chain fatty acids, in different colon sections. We demonstrated that CKD promotes increased proteolytic fermentation and an augmented tryptophan partitioning into both the indolic and kynurenine pathways. Depletion of the indolic pathway obtained upon antibiotic treatment leads to a further enhancement of the kynurenine pathway. Full article

Titanium dioxide (TiO₂) has evolved from a conventional photocatalyst into a sophisticated nano-platform that bridges environmental sustainability and biomedicine. This paper proposes a unified interfacial redox design framework that links the electronic-structure engineering of the TiO₂ with the spatial control of its reactive oxygen species (ROS). In the environmental sector, we highlight advances in photocatalytic detoxification, such as the cleavage of organophosphates via Ag-modified TiO₂, driven by doping and metal–support interactions. In the biomedical domain, TiO₂ is framed as an active bio-interface capable of coordinative protein binding. We specifically examine the “moonlighting” protein dihydrolipoamide dehydrogenase (DLDH) as a model for stable, oriented biofunctionalization. By integrating RGD-targeting motifs, these hybrid systems enable integrin-directed, localized photodynamic effects. We further address critical toxicological considerations, emphasizing that TiO₂ behavior is context-dependent and governed by particle size, crystallinity, and surface state. By synthesizing insights from catalysis and redox biology, this manuscript outlines principles for the rational design of safer, application-specific TiO₂ technologies. This convergence supports a transition from non-selective oxidation toward predictable, spatially confined redox outcomes in both complex environmental matrices and physiological systems. This review outlines key mechanistic insights and proposes design principles for controlled and context-dependent TiO₂ activity. Full article

Understanding how geometry governs interfacial contact and material removal is central to designing efficient bioinspired surface systems. Gastropod radular teeth form natural arrays of microscale cutting elements optimized for repeated interaction with compliant and semi-rigid substrates, yet experimentally validated shape–performance relationships remain limited. Here, we isolate geometric effects on interfacial mechanics using stereolithography-printed biomimetic tooth arrays inspired by the taenioglossan radula of the hard-substrate grazer Spekia zonata. Two morphologically distinct tooth types (central and marginal) were systematically varied in cusp and stylus geometry (four variants each), while array configuration, material, and boundary conditions were kept constant. Tooth stiffness was quantified in bending tests as load-induced height reduction. Interfacial performance was assessed using a controlled pull-through assay in agarose substrates of two stiffness levels (0.4% and 0.8%), with continuous force recording and measurement of removed mass. Marginal-tooth geometries were stiffer and consistently removed more substrate than central variants. Although work increased substantially in stiffer gels, removal did not scale proportionally and declined for central teeth, revealing a decoupling between mechanical input and yield. Performance correlated with active engagement rather than work alone, indicating geometry-limited contact regimes. These findings establish geometry-controlled stiffness and engagement as key parameters for efficient abrasive interfaces. Full article

Targeted therapies are reshaping oncology by enabling treatment selection based on actionable molecular alterations, improving precision, and reducing unnecessary toxicity. This review provides an up-to-date overview of current targeted treatment modalities and the medicinal chemistry principles that support their discovery and optimization. We synthesize evidence on small-molecule and biologic strategies spanning receptor and non-receptor kinases and their major signaling axes (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), apoptosis regulation (BCL-2 family), DNA repair via poly(ADP-ribose) polymerase (PARP) inhibition, and epigenetic or metabolic targets including histone deacetylases (HDACs), bromodomain and extra-terminal proteins (BET), and mutant isocitrate dehydrogenases (IDH1/2). Across these areas, we summarize recurrent resistance mechanisms and the rationale for combination or sequential approaches. Biologic targeted therapy is discussed in parallel, including immune checkpoint blockade, antibody–drug conjugates, bispecific antibodies (BsAb), and cell therapies such as chimeric antigen receptor T cells, with emphasis on biomarker-guided patient stratification. Finally, we outline emerging directions beyond canonical nodes, including modulation of the p53-MDM2/MDM4 axis, ferroptosis control through AIFM2/FSP1, and innate immune pathways such as CD47-SIRPa and the stimulator of interferon genes (STING). Overall, the field is shifting from single-target inhibition toward integrated strategies that combine precise molecular targeting with an understanding of signaling network dynamics, resistance evolution, and therapeutic vulnerabilities. Full article

Streptococcus mutans (S. mutans), one of the main etiological pathogens of dental caries, forms dental plaque biofilms that drive tooth decay. Although bacterial membrane vesicles (MVs) are increasingly recognized as modulators of biofilm biology, little is known about MVs generated by S. mutans. The objective of this study is to investigate the role of S. mutans-derived MVs in the development of S. mutans biofilms formed under static conditions in plates or confocal dishes. Transmission electron microscopy and nanoparticle tracking analysis revealed that the MVs were cup-shaped with bilayered membranes and averaged 80.49 $\pm$ 32.24 nm in diameter. The addition of ≥5 µg/mL MVs enhanced biofilm formation during the initial adhesion stage (0 to 6 h), as demonstrated by crystal violet staining and XTT assays. Confocal laser scanning microscopy and scanning electron microscopy confirmed the incorporation of PKH26-labeled MVs into S. mutans biofilms and showed that supplemental MVs increased bacterial viability and extracellular polysaccharide biomass. Furthermore, RT-qPCR analysis revealed upregulated expression of genes related to adhesion and quorum-sensing systems in MV-treated biofilms. In conclusion, these findings indicate that S. muants MVs are integral biofilm components that promote biofilm establishment at the early stage of biofilm formation. Full article

Coffee production, particularly in shade-grown farms, plays a crucial role in the livelihoods of Mexican farmers. Shade-grown coffee systems are also recognised for supporting biodiversity and enhancing carbon capture. Nevertheless, the geographical heterogeneity of Mexico makes the selection of tree species in these agroforestry systems challenging. This study develops region-specific priority lists to conserve biodiversity, improve carbon capture, and support the livelihoods of producers across nine coffee-growing regions within the state of Chiapas. We identified the tree species distributed in each region using an extensive dataset from the Global Biodiversity Information Facility and a novel approach that enhanced spatial resolution of the prioritisation process, despite biases in collection efforts. A set of 23 criteria, including conservation status, carbon content, and documented uses by local communities, was compiled from databases and literature reviews and used to calculate a priority score for each species. Based on these scores, a list of 20 recommended species was generated for each region. However, additional participatory validation is needed to translate these lists into practice. A similarity analysis revealed that geographically proximate regions shared similar species composition. Overall, this study provides a transparent framework for regionally tailored shade-tree selection to inform conservation and restoration planning in coffee agroforestry landscapes. Full article

This paper develops an intelligent Enhanced Starfish Optimization (ESFO) algorithm for optimizing a secure wireless communication infrastructure. The Starfish Optimization (SFO) algorithm is inspired by starfish biology, using the integrated modeling of the arm-based exploration, preying, and regeneration behaviors of starfish. To further enhance the exploitation capability of the standard Starfish Optimization (SFO), the proposed Enhanced Starfish Optimization (ESFO) integrates a fitness-based interacting mechanism within the exploitation phase. This innovative modification improves local search accuracy, preserves population diversity, and mitigates premature convergence without introducing additional control parameters. Moreover, the proposed Enhanced Starfish Optimization (ESFO) is designed for secure wireless transmission, which is considered one of the main topics in next-generation wireless network infrastructure. The investigated network addresses the use of Simultaneously Transmitting and Reflecting RIS (STAR-RIS) in the security of the physical layer. This implemented STAR-RIS has a coupled phase shift to create reflected and transmission links, unlike traditional Reconfigurable Intelligent Surface (RIS). In this regard, we create a safe beamforming architecture that optimizes both Base Station (BS) precoding vectors and STAR-RIS transmission/reflection coefficients. In order to validate the efficiency of the proposed Enhanced Starfish Optimization (ESFO) algorithm, it is compared to several benchmark optimizers such as standard Starfish Optimization (SFO), Dhole Optimizer (DO), Neural Network Algorithm (NNA), Crocodile Ambush Optimization Algorithm (CAOA), and white shark Optimizer (WSO). These comparisons include several scenarios based on the transmitted power threshold which is varied in the range of 20 to 70 dBm with step of 5 dBm. The simulation results show that the proposed Enhanced Star Fish Optimization (ESFO) algorithm consistently outperforms existing benchmark approaches. This study supports future intelligent communication infrastructures in terms of secrecy and achievable rates over a range of transmit power levels. In particular, ESFO improves performance by up to 20–25% while converging 40–50% faster than traditional optimization algorithms, demonstrating its usefulness and resilience in STAR-RIS-assisted secure communication systems. The suggested ESFO-enabled architecture outperforms standard RIS-based systems in terms of secrecy capacity, according to numerical studies, and low-resolution STAR-RIS phase-shifters are sufficient to ensure robust secrecy performance. Full article

Background: Uterine sarcomas are rare but highly aggressive mesenchymal malignancies associated with poor survival. Preoperative differentiation from benign leiomyomas remains a critical oncologic challenge, frequently resulting in unexpected postoperative diagnoses and potential tumour dissemination during morcellation. Reliable, accessible biomarkers to support preoperative risk assessment are lacking. This study evaluated whether CRP, a systemic inflammatory marker implicated in tumour biology, could aid in the preoperative identification of uterine sarcoma. Methods: This retrospective single-centre study included 39 patients with histologically confirmed uterine sarcoma and 39 patients with leiomyoma treated between 2010 and 2021. Preoperative serum CRP levels were compared between groups. As data were non-normally distributed, the Mann–Whitney U test was used for comparisons, and Spearman’s rank correlation was applied for association analyses. Results: Patients with sarcoma were significantly older than controls (56.2 ± 12.9 vs. 39.2 ± 6.7 years, p < 0.0001). Preoperative CRP levels were significantly higher in sarcoma patients compared with leiomyoma patients (26.4 ± 46.8 mg/L vs. 0.4 ± 1.6 mg/L; p < 0.001). Elevated CRP (>5 mg/L) was observed in 53.8% of sarcoma cases versus 2.6% of controls. Undifferentiated sarcomas demonstrated the highest CRP levels. CRP levels were not significantly associated with tumour aggressiveness. A moderate negative correlation between age and preoperative CRP was identified (r = −0.476, p = 0.029). Receiver operating characteristic analysis demonstrated a moderate discriminatory ability of preoperative CRP for differentiating uterine sarcoma from leiomyoma (AUC 0.751, 95% CI 0.668–0.834). Conclusions: Elevated preoperative CRP levels are significantly associated with uterine sarcoma and may enhance oncologic risk stratification prior to surgery. Integration of CRP into multimodal preoperative assessment algorithms could improve surgical planning and reduce the risk of inadvertent tumour dissemination. Prospective multicentre studies are required to validate its diagnostic performance and define clinically relevant cut-off values. Full article