Search Results (445)

Stem cells, with their self-renewal and multi-lineage differentiation potential, hold promise for tissue repair and intractable diseases treatment. Yet clinical translation of stem cell therapies has long been hindered by insufficient scalable stem cell manufacturing, stemness loss and functional decline in 2D expansion, and poor post-transplantation cell retention, unregulated fate control. Programmable microcarriers (MCs) paired with 3D dynamic culture offer an emerging strategy to address these bottlenecks and enable stem cell fate regulation. In this review, we systematically review advanced MC fabrication strategies for stem cell fate regulation, comparing features of emerging technologies (microfluidics, electrospraying, in-air microfluidics, integrated in situ functionalization) and their implications for programmable MC control and scalable manufacturing. We analyze how MCs modulate stem cell behaviors (adhesion, proliferation, stemness maintenance, differentiation) via synergistic static physicochemical cues and dynamic stimuli-responsive properties. We map the latest advances in functionalized MC-mediated stem cell therapy across osteochondral defects, autoimmune, skin, ophthalmic and neurodegenerative diseases. Finally, we pinpoint unresolved challenges for clinical translation of MC–stem cell system and outline key future research directions. This review offers a systematic roadmap for advancing programmable MC fabrication, clinical-grade stem cell biomanufacturing, and precise cell therapy development. Full article

Bone defects from trauma, tumour resection, infection, and degenerative disease remain a major clinical burden, and autografts face limitations of supply and donor-site morbidity. Three-dimensional (3D) printing offers a route to patient-specific, architecturally defined bone scaffolds, while biopolymers from natural sources provide biodegradability, biocompatibility, and extracellular matrix-mimicking cues consistent with sustainable, green biomaterials science. This review synthesises recent progress in 3D printing of biopolymer-based scaffolds for bone tissue engineering. We first examine the principal feedstocks—alginate, gelatin and gelatin methacryloyl, collagen, chitosan, silk fibroin, cellulose, and microbial polyesters—and their preparation, crosslinking chemistry, and printability. We then compare extrusion, light-based, and indirect printing technologies and the process–property relationships governing resolution, mechanical competence, and cell viability. Composite and functionalisation strategies, including biopolymer–bioceramic hybrids and controlled delivery of growth factors and antimicrobial agents, are analysed as routes to osteoinduction, vascularisation, and infection control. Finally, we evaluate translational performance in preclinical models and outline central challenges of vascularisation, mechanical–degradation matching, scalability, and regulatory standardisation. Biopolymer 3D printing is positioned as a ve rsatile, sustainable platform whose clinical maturation depends on integrated material, structural, and biological design. Full article

Soil microbial carbon use efficiency (CUE) is a pivotal determinant of soil carbon sequestration, yet how forest quality gradients regulate CUE through the interplay of mineral-microbial interactions in subtropical conifer ecosystems remains poorly understood. To address this, we examined the CUE response and its drivers across a forest quality gradient (high-quality to poor-quality stands) in subtropical coniferous forests in China. Soil mineral composition (including soil texture and the contents of Fe₂O₃, CaO, and MgO), physicochemical properties, microbial community diversity, and CUE were quantified. The results showed that CUE decreased by 2.7%, from 0.533 in high-quality stands to 0.519 in low-quality stands. Concurrently, soil organic carbon (SOC), nutrient availability, and microbial diversity exhibited consistent declining trends along the forest quality gradient. The CUE showed a significant positive correlation with SOC (r > 0.90, p < 0.001). Structural equation modeling and random forest revealed that microbial diversity was the most dominant correlated factor of CUE (the total effects on CUE = 0.932), followed by SOC. However, soil minerals indirectly influenced CUE via SOC. These findings highlight microbial diversity as the dominant observed correlate of CUE across forest quality gradients. This study not only deepens the understanding of the microbial mechanisms underlying soil carbon dynamics in subtropical forests but also provides key scientific basis for ecological restoration of poor-quality forests and nature-based climate solutions. Full article

Polyurethane synthetic leather is a widely used covering material in automotive interiors, and its surface coating characteristics directly determine the occupant experience. However, the underlying mechanisms by which these characteristics influence visuo-tactile perception in the context of new energy vehicles (NEVs) require further investigation. In this study, a composite experimental matrix was constructed by combining surface textures with distinct roughness gradients and representative colors extracted via data mining within the HSV color space. Targeting these two surface coating characteristics—color and texture—systematic evaluations were conducted across three independent perception stages: purely visual, purely tactile, and combined visuo-tactile. Eye-tracking metrics, specifically pupil diameter and total fixation duration, were extracted and cross-analyzed alongside multidimensional subjective evaluations. The results indicate that surface texture exerts a significant main effect on both perceived tactile softness and pleasantness, whereas the impact of color variation is remarkably weak. Furthermore, highly complex surface textures lead to prolonged fixation durations, reflecting increased exploratory interest and the high perceptual salience of intricate details rather than mere cognitive workload. Moreover, significant differences in pupil diameter were observed across texture conditions, potentially reflecting the combined influence of low-level image properties and higher-order texture perception. Concurrently, an interference effect of visual features on tactile perception was observed; specifically, the introduction of visual cues (encompassing color and texture) significantly diminished the pleasantness experienced during tactile interaction. These findings elucidate the intrinsic connections between surface coating characteristics and users’ visuo-tactile perception, offering important theoretical guidance and practical implications for optimizing the surface design of automotive polyurethane synthetic leather and enhancing the overall occupant experience. Full article

Cardiovascular diseases remain the leading cause of mortality worldwide, highlighting the urgent need for more effective therapeutic strategies. Despite substantial advances in conventional biomaterials, their limited ability to support functional integration and dynamically interact with the biological microenvironment continues to hinder therapeutic outcomes. Native cardiovascular tissues rely on tightly regulated bioelectrical signaling to coordinate cellular communication, tissue homeostasis, and functional repair. Consequently, recreating these bioelectrical cues has emerged as a key design principle in cardiovascular tissue engineering. Electroactive biomaterials have gained increasing attention as a promising platform to address this challenge by enabling electrical modulation of cellular behavior and tissue function. In this review, we summarize the intrinsic bioelectrical properties of cardiovascular tissues and discuss the roles of electrical stimulation in regulating disease-relevant cellular responses. We further highlight recent advances in the development of conductive, piezoelectric, and other electroactive biomaterials for cardiovascular tissue engineering applications. Finally, we critically discuss the major challenges and future opportunities in the field, including tissue-specific responses, stimulation parameter optimization, long-term safety, and clinical translation. Collectively, electroactive biomaterials represent a promising and rapidly evolving frontier for the development of dynamic, responsive, and next-generation therapies for cardiovascular diseases. Full article

Light is a critical environmental cue regulating development and quality in edible fungi, yet the effects of dynamic light regimes (for example, transitions from white to blue light) remain poorly understood. We systematically investigated how white-light pretreatment duration (0, 4, 8, or 12 h) and two blue-light regimes—B6 (6 h blue followed by white until harvest) and Bc (continuous blue until harvest)—affect fruiting-body development, yield, color, textural properties, and nutritional quality of Pleurotus pulmonarius. The experiment was conducted at a single commercial production facility in Zhejiang Province, China, using the commercial strain P. pulmonarius (cultivar ‘Jinxiu’). Two-way ANOVA revealed significant interactions between white-light pretreatment and blue-light regime for cap a* value (red-green), cap width, cap hardness and chewiness, stipe hardness, number of fruiting bodies, and several nutrient components. All dynamic light regimes reduced cap L* value (lightness) and b* value (yellow-blue); continuous blue (Bc) produced a darker cap. Yield responses to blue-light duration depended on pretreatment: without white pretreatment, Bc outperformed B6, whereas with 4–12 h white pretreatment B6 produced higher yields. Relative to the control (CK), all dynamic regimes significantly increased total free amino acids and essential amino acids. Except for W4B6 and W12B6, all other treatments significantly increased crude protein; total soluble sugar, crude fat, and crude fiber decreased in most treatments compared to CK. These results indicate that an optimized transition from white to blue light can synergistically improve the color, nutritional quality and yield of P. pulmonarius. The W8Bc regime (8 h white pretreatment followed by continuous blue until harvest) produced the highest cap chewiness (21.65 N·mm) and free amino acid content (3110.44 μg·g⁻¹), the darkest cap color, and the top comprehensive score in the entropy-weighted TOPSIS evaluation, despite ranking second in yield and high-quality rate. Under the conditions tested (single cultivar ‘Jinxiu’ at one production base), we recommend the W8Bc light regime as suitable for industrial cultivation of Pleurotus pulmonarius. However, it should be noted that these findings cannot be generalized to the entire species without further validation across multiple strains and multiple locations. Full article

Nitrogen (N) fertilization is a fundamental agronomic practice that governs crop productivity, yet its effects on the molecular composition and chemical stability of soil organic carbon (SOC) remain poorly understood, especially in cereal–legume intercropping systems. Traditional studies have focused on total SOC stocks rather than molecular-level changes, and the mechanistic pathway linking N addition to SOC functional group transformation remains unclear. This study addressed these critical gaps by investigating how graded N addition (0, 180, 270, and 360 kg N ha⁻¹) reshapes SOC chemistry in a subtropical soybean–maize intercropping system. Soil physicochemical properties, inorganic N pools, N-transformation enzyme activities (urease, nitrate reductase, and glutaminase), microbial biomass indices, labile organic carbon fractions (particulate, mineral-associated, and dissolved organic carbon), and SOC functional groups characterized by Fourier transform infrared (FTIR) spectroscopy were quantified across a two-year field experiment (2024–2025). Results showed that increasing N rates significantly elevated nitrate nitrogen (NO₃⁻-N) accumulation while depressing soil pH. Nitrogen-transformation enzymes, especially nitrate reductase and glutaminase, responded strongly and positively to the N gradient. Microbial biomass carbon (MBC) and nitrogen (MBN) increased with moderate N input but exhibited saturation or decline at 360 kg N ha⁻¹, accompanied by reduced microbial carbon use efficiency (CUE) and a lower MBC/MBN ratio. Among labile carbon fractions, dissolved organic carbon (DOC) was the most responsive pool, increasing markedly with N addition and correlating strongly with NO₃⁻-N. FTIR analysis revealed that N addition shifted SOC functional group composition toward chemically recalcitrant structures: the relative abundances of aromatic C=C and carbonyl C=O groups increased significantly, whereas labile C–O groups declined. Random forest modelling identified C=C, NO₃⁻-N, and DOC as the three most influential predictors of SOC chemical composition. Structural equation modelling (SEM) demonstrated a sequential mechanistic pathway: N fertilization increased NO₃⁻-N, which stimulated glutaminase activity and enhanced DOC, ultimately promoting C=C/C=O stabilization and explaining 91.3% of the variance in SOC aromaticity. These findings reveal that N addition does not merely augment SOC quantity but fundamentally transforms its molecular architecture toward greater chemical stability through a nitrate-mediated, enzyme–labile carbon coupling mechanism. This study provides a novel spectroscopic–mechanistic framework for understanding carbon–nitrogen interactions in intercropping agroecosystems and informs precision N management strategies aimed at simultaneous crop production and long-term soil carbon sequestration. Full article

Spanish Differential Object Marking (DOM) is conditioned by well-known local properties of the direct object, but also by clause- and discourse-level factors. In this study, we examine whether these factors are also available as potential learning cues in child-directed speech (CDS). We analyzed longitudinal naturalistic CDS from two monolingual and three bilingual (heritage) Spanish-learning children, manually extracting transitive clauses and coding DOM presence alongside discourse specificity, verb class, coreferential pronoun (clitic doubling), relative animacy, and DO placement, plus two local cues for comparison. Regression analyses revealed that a wider range of local and global factors conditioned DOM in monolingual than in bilingual CDS. The potential informativeness of these factors as learning cues was quantified using Competition Model measures of availability, reliability, and validity. In monolingual CDS, local cues (+human, pronominal/proper name DOs) were highly reliable, and two global cues (clitic doubling and relative animacy) showed moderate reliability. Whereas discourse specificity and verb class were highly available, they were comparatively unreliable. Validity values were uniformly low; although several global cues matched or exceeded local cues in validity, this pattern largely reflected their greater availability rather than higher reliability. In bilingual CDS, reliability and validity were reduced across nearly all cues, with little differentiation among cues. These findings suggest that Spanish-learning children encounter potentially usable utterance- and discourse-level evidence for DOM in CDS, but that the robustness of this evidence is markedly weaker in bilingual input. Full article

Numerous surface modification strategies, particularly nanoengineering approaches, have been explored to tailor the physicochemical and topographical properties of titanium surfaces in order to enhance osteogenic responses at the implant interface. In this study, we propose an alkaline ozonation strategy as a novel approach to generate nanostructured TiO₂ layers on Ti-6Al-4V alloy surfaces. Titanium discs were treated in a 6 M KOH solution under continuous bubbling of ozone, allowing the formation of reactive oxygen species (ROS) responsible for oxidative surface restructuring. Scanning electron microscopy (SEM) revealed the formation of a homogeneous three-dimensional TiO₂ nanonetwork composed of intertwined nanofibers. X-ray photoelectron spectroscopy (XPS) confirmed the oxidative reconstruction of the Ti alloy surface. The fraction of Ti⁴⁺ species characteristic of TiO₂ increased markedly from 44.2 at% to 92.2 at%, accompanied by a strong reduction in Ti⁰ (from 40.2 at% to 5.8 at%) and Ti³⁺ (from 15.7 at% to 2.1 at%). Concomitantly, lattice oxygen associated with Ti–O–Ti bonding increased from 48 at% to 78 at% as deduced from the O 1s signal, while the surface carbon content decreased from 48 at% to 18 at%. The modification induced a pronounced increase in surface hydrophilicity, with the water contact angle decreasing from 85° to 32° and the surface free energy increasing from 40.8 mJ/m² to 69.8 mJ/m². In vitro studies demonstrated good cytocompatibility and enhanced osteogenic differentiation of human mesenchymal stem cells, with twice as much alkaline phosphatase activity after 14 days and mineralization of the extracellular matrix after 28 days than those on TCPS, and also significantly higher than those on the nonmodified Ti alloy control. These findings indicate that the generated three-dimensional TiO₂ nanonetwork acts as a surface-confined nanoscaffold providing nanoscale cues that promote osteogenic cell responses on titanium implant surfaces. Full article

Large rotator cuff tendon injuries pose a dual clinical challenge: poor inherent healing capacity and high mechanical demands. To address this, we have developed a bifunctional scaffold that combines a slow-degrading, mechanically robust polyurethane core coated with tendon-derived extracellular matrix (ECM) extract to provide both structural support and regenerative cues. In a rabbit model of supraspinatus tendon injury, this ECM-polyurethane scaffold facilitated healing of critical-sized defects, resulting in aligned, tendon-like tissue with improved biomechanical properties. This study further explored the tendon healing mechanisms of the ECM-polyurethane scaffold in a rabbit model of large supraspinatus tendon injury using transcriptomic and qPCR analyses. At one month post-surgery, while both ECM-coated and uncoated polyurethane scaffolds initially provoked similar inflammatory responses when compared to healthy tendon, their healing pathways diverged significantly. The control polyurethane scaffold activated pathways associated with adipose tissue development, a non-functional outcome, whereas the ECM-coated scaffold actively directed healing toward tendon regeneration. These results demonstrate that the ECM coating is the critical factor driving divergent healing responses in polyurethane scaffolds, even though their underlying biomechanical properties are similar. This underscores the importance of combining biomechanical reinforcement with biologically active regenerative signals for effective regeneration of tendon and other load-bearing tissues. Full article

Dental pulp tissue contains mesenchymal stem/progenitor cells that possess high proliferative potential for self-renewal. They are neural-crest derived cells and exhibit multi-lineage differentiation properties. These progenitor stem cells are now recognized as being vital to the dentin regeneration process following injury. Understanding the molecular mechanisms that mediate the differentiation of adult stem cells into odontoblasts and their use in the repair of the dentin–pulp complex is of significant interest in regenerative dental medicine. Dentin Phosphophoryn (DPP), synthesized and processed predominantly by the odontoblasts, functions both as a structural and signaling protein. We had previously demonstrated that DPP activates NF-κB and promotes Wnt5a expression in dental pulp stem cells. In this context, we observed that DPP can activate TAZ, a biologically potent transcriptional coactivator which serves as a downstream element of the NF-κB signaling cascade. Furthermore, binding of NF-κB p65 subunit to the TAZ promoter was facilitated by DPP stimulation, and their interaction was confirmed by ChIP analysis. In addition, DPP-dependent activation of the TAZ/TEAD reporter was confirmed by luciferase activity in DPSCs. Co-immunoprecipitation analysis confirmed the in vivo interaction between TAZ and β-catenin with DPP stimulation. This regulatory complex facilitated TAZ to bind to the conserved TEAD binding motifs of key gene targets involved in odontogenic differentiation such as RUNX2, OSX, OCN, ALP, BMP4, and WNT5A. Some of these genes also contain binding sites for the TCF/LEF transcription factors that interact with the Wnt effector, β-catenin. Activation of TAZ and β-catenin resulted in the upregulation of odontoblast gene expression and reduced expression in the presence of the TAZ–TEAD protein complex inhibitor. Using mandibles of DSPP KO and WT mice, we confirmed reduced TAZ and β-catenin protein levels in the dental pulp cells and in the odontoblasts of DSPP KO mice when compared with WT. Thus, DPP, an extracellular matrix protein, provides biological cues to activate the TAZ signaling pathway that can stimulate the terminal differentiation of DPSCs into functional odontoblasts. Full article

Bone grafting remains limited, and the strategies to design even more structurally complex scaffolds—able to reproduce the hierarchical architecture of bone extracellular matrix—are rapidly growing. In this study, we report the fabrication of a hierarchically structured scaffold produced by layering poly(ε-caprolactone)/gelatin (PCL/Gt) or poly(lactic acid)/gelatin (PLA/Gt) electrospun nanofibers via coaxial electrospinning onto 3D-printed poly(lactic acid) (PLA) scaffolds via fused deposition modeling (FDM). After the printing process, PLA disks (10 × 1 mm, 20% infill, ~80% porosity, pore size ~1.57 mm) were coated with core/shell (PCL/Gt, PLA/Gt) fibers to investigate the in vitro interfacial response of osteoblasts in comparison with monocomponent fibrous coatings (PCL, PLA, Gt). SEM and TEM confirmed that core/shell fibers exhibited bead-free morphologies, with a significant reduction in fiber diameter (≈287–316 nm) and higher interfibrillar porosity compared to monocomponent fibers. FTIR and thermogravimetric analyses indicated the presence of hydrogen bonding between the polyester and gelatin, and the absence of residual solvent after deposition. At the same time, water contact angle measurements confirmed an increase in hydrophilic properties from 80–86° to 120° ascribable to the presence of gelatin. Accordingly, in vitro response of human fetal osteoblasts (hFOB 1.19) exhibited an evident improvement in the case of Gt-based fibrous coatings (i.e., PCL/Gt and PLA/Gt) in terms of early adhesion (4–24 h) and metabolic activity from 3 to 21 days, cell spreading into star-shaped morphologies, formation of extracellular matrix, and mineral phase deposition. In more detail, a remarkable increase in alkaline phosphatase activity was observed in Gt-based coaxial coatings from day 7 onward, with the highest values recorded for PLA/Gt. Overall, we demonstrated that the Gt-based coaxial fibrous coating provided a mix of topological and biochemical cues that synergistically promoted key osteoblast activities at the interface, supporting the regeneration of new bone tissue in highly tailored 3D-printed scaffolds, thus suggesting a promising strategy for personalized regenerative medicine. Full article

Smart contract auditing remains challenging because vulnerabilities often emerge only under complex execution conditions, cross-transaction interactions, and environment-dependent assumptions. Existing analysis techniques, including static analysis, symbolic execution, fuzzing, and recent LLM-assisted approaches, each provide useful but incomplete coverage, and monolithic auditing pipelines often struggle to balance search breadth, reproducibility, and reporting reliability. This paper presents SEMA, a self-evolving multi-agent auditing framework for smart contracts that formulates auditing as a resource-bounded discovery of concrete counterexamples under replay-certified reporting semantics. SEMA combines heterogeneous specialized agents, an orchestrator, a shared artifact-centric knowledge base, and a replay-based referee. During auditing, agents generate and consume reusable artifacts, such as candidate invariants, refuted hypotheses, transaction templates, and coverage cues, allowing the shared search state to evolve across rounds without modifying the analyzers themselves. To ensure reporting reliability, findings are accepted only when the referee can replay the candidate scenario under a pinned execution configuration and confirm violation of an executable security property. We further evaluate SEMA on an annotated smart contract benchmark under a fixed 300 s budget per contract. The full system achieves 0.9469 instance recall, 0.9441 success rate, and 0.9445 macro-average category recall on the retained executable subset, outperforming both symbolic-only and fuzzing-only baselines, as well as multi-agent ablations that disable dynamic knowledge evolution or cross-agent artifact reuse. Full article

Road intersection crashes remain a major contributor to injuries due to complex conflict patterns and multimodal interactions. Among the factors influencing intersection safety, inadequate intersection sight distance (ISD) attributed to roadside sight obstructions can limit drivers’ ability to respond to conflicting movements, potentially affecting crash injury outcomes. Despite its importance, visual obstruction has rarely been examined as a distinct context in traffic crash injury severity modeling. This study investigates crash injury severity at visually obstructed intersections using an ordinal probit modeling framework applied to 951 intersection crashes documented with sight obstruction as a contributing factor in Wyoming over the period 2014 through 2023. Crash data were analyzed to identify the effects of driver behavior, vehicle characteristics, roadway geometry, environmental conditions, and traffic control on ordered injury severity outcomes ranging from property damage only (PDO) to fatal and serious injury. Nonparametric bootstrap resampling with 1000 iterations was employed to assess parameter stability and construct empirical confidence intervals. Average marginal effects were estimated to quantify the change in probability of each injury severity level associated with key predictors. The results indicate that alcohol involvement produces the largest severity shift, reducing the probability of PDO outcomes by 51.2 percentage points while increasing the probability of fatal and serious injury by 34.2 percentage points. Hillcrest grade locations increase fatal and serious injury risk by 14.4 percentage points, while adverse road surface conditions, including snowy, icy, and wet pavements, consistently reduce fatal and serious injury probability by 12.5 to 15.1 percentage points, reflecting behavioral adaptation to visually salient hazard cues. Bootstrap validation confirms strong parameter stability across all estimates, with 94% of parameters showing bootstrap standard errors within 25% of their asymptotic counterparts. By formally establishing visually obstructed intersections as a dedicated severity modeling context and integrating systematic bootstrap validation, this study contributes both substantive and methodological insights to support evidence-based prioritization of intersection safety improvements. Full article

This study isolated and characterized Lactiplantibacillus plantarum WYP from naturally fermented pineapple peel residues. The strain exhibited a potent in vitro histamine degradation rate of 78.63% and demonstrated multiple probiotic properties, including acid and bile salt tolerance, simulated gastrointestinal fluid resistance, antimicrobial activity against foodborne pathogens, and in vitro cholesterol-lowering ability. Whole-genome sequencing revealed a 3.34 Mb circular genome encoding 3200 genes. Genomic analysis elucidated a multidimensional “Prevention–Promotion–Utilization” (PPU) strategy for histamine regulation: prevention via the absence of histidine decarboxylase (hdc) genes; promotion of degradation via multicopper oxidase (e.g., cueO) and amine oxidase systems; and utilization through downstream aldehyde metabolism and redox homeostasis genes. Safety assessments confirmed the strain’s non-hemolytic nature, absence of harmful metabolite production, and no detectable risk of acquired antibiotic resistance gene transfer. The integration of phenotypic and genomic evidence positions LPWYP as a promising probiotic candidate for mitigating biogenic amines in fermented foods. Full article