Search Results (12,653)

Background: Triple−negative breast cancer (TNBC) remains among the most aggressive and therapeutically unresponsive subtypes due to the absence of ER, PR, and HER2 targets. Casein Kinase II (CK2), a pleiotropic serine/threonine kinase overexpressed in TNBC, represents a compelling target for rational drug design. Methods: Here, we present an AI−integrated benchmarking framework combining virtual drug discovery, molecular dynamics simulations, machine learning−driven QSAR modeling, and quantum−mechanical electronic structure analysis to identify potent CK2 inhibitors from natural product chemical space. Results: A validated XP docking protocol (ROC–AUC = 0.748) screened ~480,000 compounds, yielding seven hits, with superior binding to the reference inhibitor CX−4945. Among these, Anastatin B, 3,4,8,9,10−pentahydroxy−dibenzo−[b,d]pyran−6−one, Rhein, and aloe emodin acetate exhibited highly favorable docking scores (−11.6 to −13.1 kcal mol⁻¹) and stable 200 ns binding dynamics, reflected by RMSD ≤ 2 Å and compact Rg trajectories. MM−PBSA/MM−GBSA analyses confirmed robust thermodynamic stability, while DFT−derived HOMO–LUMO gaps (3.8–4.3 eV) suggested optimal electronic reactivity for kinase inhibition. Machine learning QSAR models demonstrated strong predictive performance, with the best stacking models achieving test R² ≈ 0.69 and consistent cross−validation performance (CV R² ≈ 0.66–0.69), supporting reliable prediction of pIC₅₀ values and prioritization of top−ranked scaffolds. Conclusions: Collectively, this integrative framework bridges AI−based learning and biophysical validation, establishing a reproducible paradigm for de novo CK2 inhibitor discovery in TNBC. Full article

Solar interfacial evaporation is promising for freshwater production, yet thermodynamic energy limits and mass transfer attenuation in high-salinity environments restrict practical applications. To address these challenges, a 3D high-efficiency evaporator is developed by cross-linking a hydrophilic composite gel onto a macroporous sponge scaffold. This spatially decoupled architecture enables fundamental water-state regulation and efficient environmental heat harvesting. Specifically, hydrophilic functional groups in the gel network reduce the equivalent enthalpy of vaporization of water to 1181.8 J g⁻¹. Simultaneously, the 3D columnar structure induces a sidewall cold sink effect to extract additional ambient thermal energy. Through this synergy, the PCPH delivers a remarkable apparent evaporation rate of 8.59 kg m⁻² h⁻¹ under one standard sun. Furthermore, interconnected macropores within the sponge establish excellent convective pathways for rapid ion diffusion. Consequently, the device operated continuously for 8 h in a 10 wt% NaCl solution without significant blockage and decreased key metal ion concentrations in 3.5 wt% simulated seawater by 4 to 5 orders of magnitude. The purified water fully satisfies World Health Organization standards. This study offers an innovative strategy to surpass conventional photothermal bottlenecks and design highly durable water treatment materials. Full article

Adipogenesis is a critical factor in causing obesity, which is a global health problem associated with metabolic disorders, such as insulin resistance and cardiovascular diseases. Natural compounds with anti-adipogenic activity may represent potential approaches for modulating adipocyte function. However, despite increasing interest in natural products, the anti-adipogenic potential of acridone alkaloids, particularly prenylated derivatives, remains largely unexplored. This study examined the effects of N-methylatalaphylline (NMA), a prenylated acridone alkaloid, on adipocyte differentiation, lipid accumulation, and glucose uptake. NMA exhibited anti-adipogenesis, particularly toward preadipocytes, and significantly reduced lipid accumulation in murine 3T3-L1 and human PCS-210-010 adipocytes at nontoxic doses (1.5–6 µM). At 3–6 µM, NMA downregulated adipogenic regulators, including PPARγ, C/EBPα, and SREBP1, along with adipogenic effectors, such as FABP4, adiponectin, LPL, PLIN1, and FAS. Mechanistic studies indicated that NMA treatment was associated with reduced phosphorylation of AKT, ERK, and p38, accompanied by cell-cycle arrest and inhibition of mitotic clonal expansion. Meanwhile, activation of AMPK-ACC signaling, which may contribute to suppression of adipogenesis and reduced glucose uptake, was observed in differentiated 3T3-L1 cells after treatment with 6 µM NMA for 48 h. Additionally, molecular docking and molecular dynamics simulations suggested potential interaction between NMA and ERK1, supported by hydrogen bonding and hydrophobic contacts. Overall, these findings suggest that NMA exerts anti-adipogenic effects in vitro by modulating adipocyte proliferation, differentiation, and lipid metabolism. These findings highlight NMA as a promising acridone alkaloid scaffold for anti-adiposity applications, warranting further in vivo validation. Full article

Cutaneous T-cell lymphoma (CTCL), primarily mycosis fungoides (MF) and Sézary syndrome (SS), has long been characterized as a neoplasm of mature memory T cells, based on monoclonal T-cell receptor (TCR) rearrangements and tissue-resident memory (TRM)/central memory (TCM) T-cell phenotypes. This review synthesizes converging population-genetic, multi-omic, and single-cell evidence to argue that this characterization is incomplete and that a progenitor-based model better accounts for the full spectrum of disease biology. We present evidence that initiating mutations arise in hematopoietic stem or early lymphoid progenitor survive thymic selection, and diversify after TCR assembly, resulting in branched evolution across both blood and skin. In SS, paired analyses reveal > 200 shared variants between CD34⁺ progenitors and Sézary cells, as well as signal-joint T-cell receptor excision circle (sjTREC) positivity, providing direct progenitor-level evidence. In MF, convergent signals, multiple malignant clonotypes per lesion, greater blood–skin than skin–skin clonotype overlap, and compartment-specific CNV subclones, implicate hematogenous seeding and reseeding. Population-scale lymphoid clonal hematopoiesis and lymphoid-pattern mosaic chromosomal alterations define a compatible antecedent state. Spatial single-cell atlases and trajectory analyses map site-conditioned programs in skin, including Th2-skewed cytokines, microbial responses, and UV signatures, that select and expand subclones and explain inter- and intra-patient heterogeneity. This framework reconciles mature immunophenotypes with upstream initiation and clarifies why compartment-focused therapies often reshape rather than eradicate disease. It yields testable predictions and actionable implications: trials should pair multicompartment cytoreduction with strategies that attenuate progenitor-derived reservoirs, restore immune balance, and repair skin barrier dysfunction. A progenitor-initiated, niche-adapted model provides a coherent scaffold for more durable control in CTCL. Full article

This exploratory study examines how complex non-linear television narratives support viewers’ cognitive processing through embedded compensatory mechanisms. Using Season 1 of the Netflix series Dark as a case study, we conducted a quantitative content analysis examining temporal structure across 10 episodes. The series presents interconnected timelines (1953, 1986, 2019), creating substantial cognitive demands for viewers. Statistical analyses revealed a significant negative correlation (r = −0.745, p < 0.05) between spatial fragmentation (number of locations) and scene duration, suggesting systematic compensatory editing strategies. Despite high temporal complexity, the narrative maintains a hierarchical timeline structure with 2019 serving as the primary temporal anchor (59% of screen time). These preliminary findings suggest that complex storytelling incorporates built-in cognitive scaffolding mechanisms that may facilitate comprehension despite exceeding traditional working memory constraints. The study contributes to understanding how narrative design can support distributed cognition and has implications for theories of cognitive load and multimedia learning. Full article

The inflammatory response possesses a central role in human pathophysiology, regulating the tissue microenvironment and cell signaling. Inflammation occurs either as a symptom of homeostasis disturbance or as a driver for determining cell fate. In this context, cells recruit secreted cytokines, chemokines and intracellular mediators, in cooperation with their surrounding cellular components, to integrate inflammatory stimuli. The extracellular matrix (ECM) acts as a scaffold for shaping tissue structure and simultaneously undergoes continuous remodeling to provide a dynamic network for intercellular communication. Serglycin (SRGN) is the only known intracellular and extracellular proteoglycan, implicated in the formation of secretory vesicles and ECM reorganization. The regulatory roles of SRGN in the bioavailability of secreted factors, as well as SRGN pleiotropic interactions within the ECM, as well as with cell surface receptors, have emerged to beessential for inflammatory diseases and tumor progression. Its overexpression and excessive secretion, alongside its contribution to cell signaling, highlight the potential diagnostic and therapeutic aspects of SRGN in human diseases. Full article

Dehydrothyrsiferol (DT), a brominated oxasqualenoid from the red alga Laurencia viridis, represents a compelling example of this framework. This review establishes DT as a model Smart Secondary Metabolite based on the convergence of a unique molecular architecture of rigid stereogroups connected by flexible bonds; a high metabolic yield (0.42% w/w of crude extract); potent selective bioactivity against kinetoplastids and drug-resistant tumors; multi-target modulation of protein phosphatase 2A (PP2A) and cell-surface integrins; and distinctive chemotaxonomic relevance within Macaronesian communities. Its biosynthesis proceeds through stereocontrolled epoxide-opening cascades, generating an evolutionarily refined scaffold. Ecologically, DT operates as a multifunctional shield, providing antifouling protection and deterring herbivory. Pharmacologically, it acts as a selective signaling modulator, triggering integrin-mediated cell death (IMD) in resistant cancer cells and inducing mitochondrial collapse in protozoa. In vivo studies in murine models of cutaneous leishmaniasis have demonstrated an 87% reduction in lesion size, reinforcing its promise as a lead structure. Full article

Soft tissue reconstruction often requires biomaterials that provide temporary mechanical support while permitting vascular integration and tissue remodeling. In reconstructive breast surgery, these demands converge within a uniquely challenging environment characterized by large surface areas, variable perfusion, frequent exposure to radiation, and reliance on prosthetic implants. Consequently, breast reconstruction serves as a clinically relevant model for evaluating the performance and limitations of soft tissue scaffolds. Acellular dermal matrices (ADMs) were introduced to provide biologically derived reinforcement capable of host integration and neovascularization. Although ADM has transformed implant-based reconstruction, clinical experience has revealed important limitations, including variability in mechanical properties, inconsistent vascularization, susceptibility to fibrosis, and suboptimal performance in compromised tissue beds. These challenges have driven increasing interest in synthetic polymer scaffolds engineered for reproducible mechanics, controlled degradation, and scalable manufacturing. This narrative review examines the evolution from ADM to synthetic and hybrid scaffold systems in breast reconstruction. We discuss how scaffold architecture, thickness, porosity, and degradation kinetics influence angiogenesis, immune response, and mechanical load transfer during healing. Hybrid strategies that incorporate selective bioactivity within synthetic frameworks are also explored, highlighting their translational promise and current limitations. These principles are particularly relevant in implant-based breast reconstruction, where scaffold performance directly influences complication rates, implant stability, and long-term outcomes. Collectively, breast reconstruction serves as a rigorous translational model demonstrating that optimal soft tissue scaffolds must balance vascular permissiveness, mechanical reliability, and predictable resorption to optimize reconstructive success and guide future biomaterial innovation. Full article

Background/Objectives: The rapid emergence of antimicrobial resistance (AMR) is driven not only by antibiotic selective pressure but also by bacterial adaptive responses that enhance genetic diversification under stress. The SOS response, regulated by the RecA-LexA axis, plays a central role in coordinating DNA repair, mutagenesis, and phenotypic adaptation. Targeting this pathway represents a promising strategy to limit bacterial adaptability without directly affecting viability. This study aimed to evaluate benzoxaborole-based compounds as potential inhibitors of the LexA regulatory pathway. Methods: A drug repurposing approach was employed to investigate the benzoxaborole scaffold and the clinically approved derivatives tavaborole and crisaborole. Biochemical assays were used to assess LexA autocleavage in a RecA-dependent co-protease system. Molecular docking analyses were performed to evaluate compound binding within the LexA catalytic site. Microbiological assays were conducted to examine the effects on antibiotic-induced filamentation and biofilm formation under different growth conditions. Results: Selected benzoxaboroles inhibited LexA autocleavage, with tavaborole showing the strongest inhibitory profile in the biochemical assay. Docking analyses supported these findings, indicating stable binding within the LexA catalytic site near the catalytic serine residue. At the cellular level, tavaborole and benzoxaborole significantly reduced levofloxacin-induced filamentation at sub-inhibitory concentrations. Both compounds also decreased biofilm formation under nutrient-limited conditions, while no significant effects were observed on preformed biofilms. Crisaborole showed limited cellular activity despite measurable biochemical effects. Conclusions: These findings identify benzoxaboroles as modulators of the LexA-dependent SOS response and support the potential repurposing of clinically approved compounds as adjuvants to limit bacterial adaptive responses associated with antimicrobial resistance. Full article

Solution electrospinning (SES) and melt electrowriting (MEW) are complementary fiber-based fabrication platforms extensively investigated in tissue engineering. SES generates fibers typically ranging from the nanometer to the low-micrometer scale, producing fibrous networks that mimic the native extracellular matrix (ECM) and support key cellular functions. MEW, by contrast, operates solvent-free and enables precise, layer-by-layer deposition of microfibers with well-controlled geometry, conferring the mechanical integrity and open-pore architecture that SES constructs inherently lack. Despite growing interest, the body of peer-reviewed literature reporting original hybrid SES–MEW fabrication and biological outcome data remains limited, with no comprehensive cross-tissue synthesis available to date. This narrative review examines the current state of SES–MEW hybrid strategies across five tissue engineering targets selected for their clinical relevance: skin, vascular grafts, bone, cartilage, cardiac valves, and skeletal muscle. For each application, the architectural rationale, the fabrication approach, and the in vitro and in vivo biological outcomes are discussed in an integrated manner, with attention to how the spatial organization of nano- and microfibers translates into tissue-specific functional responses. A comparative analysis across tissue types highlights both the versatility of hybrid constructs and their persistent limitations, including suture retention values that remain below clinically accepted thresholds in vascular applications, incomplete cellular infiltration through dense nanofibrous layers, and the absence of validated, reproducible scale-up protocols compatible with clinical-grade manufacturing. The review concludes by identifying the most critical open questions in the field, encompassing process standardization, regulatory classification, and the emerging role of machine learning in closed-loop MEW process optimization. This work aims to provide an evidence-based perspective on the current state of hybrid SES–MEW scaffold engineering and the key translational gaps limiting clinical application. Full article

Electrical stimulation enhances functionality and accelerates maturation in biofabricated tissues, which are particularly important for muscle tissue engineering applications. Accordingly, there is demand for 3D-printable electrically conductive cytocompatible scaffolds that enable patient-specific geometries and localized electrical stimulation, as well as incorporate further maturation-promoting geometrical cues. Filament-based scaffolds from fused filament fabrication could overcome current limitations in geometric freedom, size and partially cytotoxic additives. In this study, biodegradable polylactic acid (PLA)-based conductive filaments incorporating graphene nanoplatelets (GNPs) or carbon nanofibers (CNFs) were developed via melt-mixing extrusion to possibly enable the electrical functionalization of muscle scaffolds. A two-stage process combining twin-screw and single-screw extrusion was preferred to allow for higher filler incorporation. Filament morphology, printability, electrical conductivity, and cytocompatibility were systematically evaluated. Homogeneous filaments containing up to 16 wt.% GNPs or 3.6 wt.% CNFs were successfully produced and processed by fused filament fabrication into scaffold geometries supporting myoblast orientation. Electrical conductivity was measured above 16 wt.% GNPs, with up to 2.7 µS/m, with printed constructs capable of connecting a circuit. GNP-based filaments were cytocompatible, supporting myoblast attachment and elongated morphology. An adjustable electrical stimulation setup demonstrated improved muscle maturation and contractile responses of C2C12 myoblasts, highlighting biodegradable conductive filaments’ potential for electrically active muscle tissue scaffolds. Full article

With global cancer cases projected to reach 35 million by 2050 and drug resistance to existing chemotherapeutic drugs remaining a significant threat in cancer therapy, accounting for up to 90% of chemotherapy failures, the search for novel anticancer compounds continues to be increasingly important. This systematic review (2021–2025) examined the role of thiazoles and 4-thiazolidinones/thiazolidinediones as popular scaffolds in existing anticancer drug design. While researchers continue to focus on well-established molecular targets, such as EGFR, VEGFR-2, and tubulin, there is a notable difference regarding other preferred choices for thiazoles and 4-thiazolidinones/thiazolidinediones. Among analyzed mechanisms of anticancer activity notably favored for thiazoles was the inhibition of serine/threonine protein kinases (CDK-2, BRAF^V600E), while for 4-thiazolidinones/thiazolidinediones more studied were ROS generation and PPARγ activation. Furthermore, less-researched mechanisms of anticancer activity with no FDA-approved drugs such as PTP1B, SIRT2, PKM2, eIF4E, CA XI and XII inhibition for thiazole derivatives and pan-PIM kinase and BAG3 protein inhibition for 4-thiazolidinones/thiazolidinediones were evaluated as well. Notable was the popularity of the multi-targeting approach for modern drug design, with ~30% reporting two or more targets for their compounds. Despite these advancements, the review identified critical gaps in ADMET evaluations, safety analyzing against normal human cells and the lack of mechanistic studies connecting the targeted protein and the compounds anticancer effects. Full article

This paper presents a modular system architecture and an automated signal processing pipeline designed to quantify neurophysiological relaxation responses to fragrance using consumer-grade wearable electroencephalography (EEG). By integrating real-time data streaming via Open Sound Control (OSC) with a high-performance backend, the platform enables objective assessment of olfactory stimuli through a reproducible Sleep Readiness Index (SRI) derived from spectral power shifts. To mitigate the signal quality constraints inherent in portable hardware, the framework utilizes a robust suite of engineering controls, including zero-phase filtering and automated artifact rejection, ensuring data integrity across short-window trials. Validation through construct-level analysis of public sleep datasets and synthetic sensitivity testing confirms the index’s directional reliability, while runtime benchmarking demonstrates sub-millisecond compute times suitable for interactive wellness applications. Ultimately, this framework provides a transparent, auditable engineering scaffold that replaces subjective self-reports with a standardized, within-session proxy metric for comparative fragrance evaluation. Full article

Diabetic wounds are a common and severe complication of diabetes mellitus, characterized by delayed healing due to persistent inflammation, impaired angiogenesis, and cellular dysfunction. Conventional therapeutic approaches remain limited in efficacy. In recent years, exosomes have attracted considerable attention in wound healing and regenerative medicine because of their crucial role in intercellular communication and tissue repair. However, rapid clearance of exosomes in vivo greatly limits their therapeutic efficacy. To address this critical limitation, we engineered a decellularized extracellular matrix (dECM)-based hydrogel system functionalized with exosomes derived from skin-derived precursor cells (SKPs). This biomimetic scaffold was designed to serve as a local exosome-delivery platform at the wound site, with the aim of improving exosome utilization and augmenting their regenerative effects. Comprehensive in vitro characterization demonstrated that the exosome-loaded composite hydrogels exhibited robust pro-angiogenic activity, as evidenced by enhanced endothelial cell proliferation, migration, and tube formation. Moreover, the hydrogels displayed significant antibacterial effects against wound-relevant pathogens and potent reactive oxygen species (ROS)-scavenging capacity, thereby mitigating oxidative damage. Notably, the composite hydrogels also promoted the phenotypic polarization of macrophages toward the pro-regenerative M2 phenotype. In parallel, in vivo studies using a streptozotocin-induced diabetic rat wound model confirmed that treatment with the composite hydrogels significantly accelerated wound closure rates compared to control groups. Histological and immunohistochemical analyses revealed enhanced angiogenesis, as evidenced by increased CD31-positive microvessel density, as well as improved collagen deposition, re-epithelialization, and an attenuated local inflammatory microenvironment characterized by reduced pro-inflammatory cytokine expression and elevated M2 macrophage infiltration. Collectively, the SKPs exosome-loaded dECM based composite hydrogels developed in this study represent a potential therapeutic strategy for the treatment of diabetic wounds. Full article

Decellularized extracellular matrix (dECM) scaffolds derived from xenogeneic tissues represent promising biomaterials for tissue engineering. In this study, dECM scaffolds were developed and characterized from four ovine tissues—skin, tunica vaginalis, fascia lata, and pericardium—using a detergent-based decellularization protocol to evaluate decellularization efficiency and extracellular matrix (ECM) preservation. Decellularization was performed using a sequential detergent-based protocol with sodium dodecyl sulfate and Triton X-100. Decellularization efficacy and matrix preservation were evaluated through gross examination, histological analysis, scanning electron microscopy (SEM), and residual DNA quantification. Gross inspection revealed increased translucency and reduced pigmentation in decellularized tissues compared with native counterparts, indicating effective cellular removal while maintaining overall tissue architecture. Histological assessment confirmed the complete absence of nuclear and cytoplasmic material, alongside preservation of collagen-rich extracellular matrix organization. SEM analysis demonstrated well-maintained ultrastructural features, including aligned collagen fibers and porous ECM architecture, with complete removal of epithelial and stromal cellular elements. Quantitative analysis revealed approximately 94% reduction in residual DNA content across all decellularized tissues compared with native controls. This study demonstrated that the employed detergent-based protocol reliably produces structurally preserved, acellular scaffolds from multiple ovine tissues. The resulting biomaterials exhibit structural characteristics that support their potential use in tissue engineering applications, pending further functional validation. Full article