Search Results (328)

Craniosynostosis is a congenital bone developmental condition characterized by the premature ossification of calvarial sutures, leading to restricted skull expansion and potential neurological complications. Although little is known about the signaling that governs this accelerated fusion, our research group has previously identified a stiffness-dependent upregulation of osteogenic genes in cells derived from fused sutures, highlighting the role of mechanotransduction in disease progression. Building on these findings, the present study describes the development of a unique patient-derived three-dimensional (3D) tissue-engineering (TE) model of non-syndromic craniosynostosis (NS-CS) to investigate how extracellular matrix (ECM) composition and biochemical cues regulate ossification timing and patterns. Cells isolated from clinically relevant tissues, surgically obtained from patent and prematurely fused calvarial sutures of pediatric NS-CS patients, were characterized and cultured under both two-dimensional (2D) and 3D suture-mimicking conditions. Comparative analysis revealed differences in cellular responsiveness between cells isolated from fused and patent sutures across the different experimental conditions, with cells from fused sutures consistently exhibiting higher expression of osteogenic markers. Notably, the elevated expression of osteogenic and chondrogenic markers suggested the possible involvement of endochondral-like ossification mechanisms during the pathological process of suture fusion. This patient-derived model was designed to recapitulate biophysical and biochemical features of the extracellular matrix of healthy and pathological sutures, serving as a tool for future research, helping us to understand the underlying mechanisms behind the pathophysiology of craniosynostosis. Full article

Since its inception in 2017, temporal interference stimulation (TIS) has attracted increasing attention as a novel neuromodulation approach with the potential to non-invasively target deep brain structures. As the field moves from initial biophysical validation toward broader experimental and translational applications, a macroscopic understanding of its developmental trajectory and thematic evolution is needed. In this study, we systematically mapped the scientific landscape of TIS research using bibliometric methods to characterize its knowledge structure, core themes, and emerging frontiers. The analysis shows that TIS research has expanded rapidly from foundational animal studies and biophysical mechanism validation toward computational head modeling, individualized electric field optimization, and early human applications. Current research is increasingly focused on cross-species scaling, stimulation dosimetry, comparative advantages over other neuromodulation techniques, precise targeting strategies, and potential physiological risks such as high-frequency conduction block. Overall, TIS is evolving from an exploratory biophysical concept into a promising but technically and physiologically complex neuromodulation tool. Overcoming current engineering and translational barriers, particularly through individualized modeling, rigorous optimization, and well-designed human studies, will be essential for establishing TIS as a reliable therapeutic intervention. Full article

In vitro maturation (IVM) is a critical step affecting the efficiency of bovine in vitro embryo production; however, oxidative stress during in vitro culture can impair oocyte quality and subsequent developmental competence. This study investigated the effects of cysteine supplementation on bovine oocyte IVM, redox homeostasis, mitochondrial status, and transcriptomic changes. Bovine cumulus-oocyte complexes were cultured in IVM medium supplemented with 0, 25, 50, 75, 100, or 125 μM cysteine, and 75 μM was identified as the optimal concentration. Compared with the control group, 75 μM cysteine increased the first polar body extrusion rate from approximately 78% to 81% and improved the fertilization/cleavage rate from approximately 74% to 82%. It also significantly increased the proportions of 2-cell, 4-cell, and 8-cell embryos, whereas morula and blastocyst rates were not significantly affected. At the cellular level, 75 μM cysteine significantly reduced ROS levels and increased GSH content, as indicated by changes in relative fluorescence intensity. JC-1 staining showed that the JC-1 monomer signal decreased from approximately 16.0 to 13.5, whereas the JC-1 aggregate signal increased from approximately 13.2 to 14.8, indicating improved mitochondrial membrane potential status. In addition, lipid droplet fluorescence intensity increased from approximately 11.8 to 13.4, mitochondrial fluorescence intensity increased from approximately 6.0 to 7.0, and cytoskeletal fluorescence intensity showed no significant difference between groups. Smart-seq2 transcriptomic analysis identified 1935 differentially expressed genes, including 1778 upregulated and 157 downregulated genes, which were mainly enriched in translation, ribosomal structural components, RNA binding, oxidative phosphorylation, and metabolism-related pathways. qRT-PCR further confirmed the upregulation of key genes, including NDUFS2, VDAC3, ANXA2, MTHFD1L, and SCD. Overall, 75 μM cysteine improves bovine oocyte IVM quality by enhancing antioxidant capacity, improving mitochondrial membrane potential, increasing lipid-derived energy substrate storage, and regulating genes related to energy metabolism and developmental competence. Full article

Cultivated-meat production relies on robust animal cell-line engineering, scalable tissue-engineering strategies, and clearly defined regulatory standards. This review examines the developmental pipeline from primary tissue biopsy to large-scale expansion and regulatory evaluation, focusing on stable and safe immortalized cell platforms. We compare muscle satellite cells, mesenchymal stromal/adipogenic progenitors and induced pluripotent stem cells, highlighting trade-offs among proliferative capacity, lineage commitment, genomic stability, and food-safety considerations. We then analyze immortalization strategies, including spontaneous senescence bypass, telomerase reactivation and CRISPR-based checkpoint modulation, highlighting their impact on genomic stability and food-safety risks. Recent advances in serum-free media, extracellular matrix-mimetic biomaterials and staged co-culture protocols have enabled centimeter-scale tissues with improved texture and marbling; however, cost, reproducibility and scalability remain bottlenecks. Integrating multi-omics surveillance with life-cycle assessment reveals that environmental benefits (land, water and antibiotic reduction) are attainable only when energy inputs and growth-factor sourcing are optimized. Finally, we examine regulatory frameworks that distinguish food-grade immortalized cells from pharmaceutical substrates and genetically modified crops. By integrating cell biology, animal biotechnology, and bioprocess engineering, this review identifies technical priorities for advancing cultivated meat from laboratory development to industrial implementation, positioning genomic monitoring as an essential framework for assessing biological stability, functional predictability, and food-production suitability. Full article

Alternative splicing (AS) is a major post-transcriptional regulatory mechanism that greatly expands transcriptomic and proteomic diversity in plants. Recent studies have demonstrated that AS dynamically regulates gene expression during plant development and under diverse environmental conditions through isoform-specific modulation of transcript stability, translation efficiency, protein localization, and signaling pathways. In this review, we summarize recent advances in understanding the roles of AS in plant development and abiotic stress responses. Mechanistically, splice site selection is regulated through coordinated interactions among cis-regulatory elements, RNA-binding proteins, RNA secondary structures, transcriptional kinetics, chromatin organization, and spliceosomal dynamics. AS plays critical roles in various developmental processes, including seed germination, vegetative growth, flowering transition, and senescence, while also contributing to plant adaptation to abiotic stresses such as osmotic, temperature, and oxidative stresses. Particular emphasis is placed on the diverse regulatory outcomes of AS, including isoform-specific protein functions, AS-coupled nonsense-mediated decay, transcript stability control, and context-dependent isoform switching. We further discuss the varying levels of experimental evidence supporting reported AS events, ranging from transcriptome-wide observations to genetically and biochemically validated isoform functions. Moreover, recent advances in long-read sequencing, single-cell transcriptomics, proteogenomics, and genome-engineering technologies are accelerating the functional characterization of splice isoforms and uncovering the complexity of AS-mediated regulatory networks. Collectively, these advances highlight AS as a central mechanism coordinating plant developmental plasticity and environmental adaptation. Full article

Anthocyanin-rich dark pigmentation is increasingly recognized as more than a simple consequence of flavonoid accumulation. Here, we define the anthocyanin-driven dark phenotype (ADP) as a coordinated stress-responsive state characterized by intense anthocyanin accumulation coupled with cellular and regulatory reprogramming. Recent studies show that reactive oxygen species, sugar signaling, temperature stress, and hormonal crosstalk converge on MYB–bHLH–WD40-centered regulatory networks that integrate pigment biosynthesis with vacuolar organization, transport activity, and stress adaptation. Epigenetic remodeling, chromatin dynamics, and post-transcriptional regulation further influence pigment intensity and persistence. Importantly, ADPs do not represent an alternative biosynthetic pathway or merely pigment abundance, but instead reflect a systems-level regulatory state governed by coordinated transcriptional, hormonal, and epigenetic control of the canonical anthocyanin machinery. However, several important questions remain unresolved, including how plants retain phenotypic stability under various environmental and developmental settings, whether ADPs contribute to long-term stress memory, and how anthocyanin accumulation is balanced with growth and energy expenditures. To translate ADP-associated features into crop development techniques, these gaps must be filled. We also emphasize spatial omics and CRISPR-based engineering as new methods for analyzing and modifying stress-resilient phenotypes. Full article

This study designed, developed, and evaluated a combined egg incubator and hatchery system to enhance poultry breeding efficiency, reliability, and ergonomic operation. Utilizing a developmental research design, the project addressed challenges in traditional incubation and hatching processes, including inconsistent temperature and humidity control, inadequate ventilation, frequent power interruptions, limited access to affordable materials and technical expertise, insufficient safety mechanisms, and a lack of multifunctional capability. Data were collected from 30 experts in agricultural engineering and poultry technology to evaluate design, construction, material availability, functionality, usability, safety, modularity, and ergonomics. Findings revealed the system was highly efficient, safe, and user-centered, improving hatch rates and operator comfort. Full article

Neuroblastoma (NB), the most common extracranial solid tumor of childhood, exemplifies one of the most formidable paradigms of tumor immune evasion (TIME) in pediatric oncology. Despite significant advances in multimodal therapy and the clinical integration of immunotherapeutic strategies, high-risk NB (HR-NB) remains largely refractory to durable immune control. This failure reflects not an absence of immune engagement, but the presence of a highly evolved and developmentally wired immune escape architecture. In this review, we synthesize emerging insights from single-cell, multi-omics, and functional studies to define how developmental lineage, cellular plasticity, metabolic rewiring, epigenetic regulation, and therapy-induced adaptation converge to engineer immune blindness in NB. We discuss how NB’s neural crest origin establishes a baseline of low immunogenicity, which is subsequently reinforced through coordinated suppression of antigen presentation, dominance of immune checkpoint signaling, and profound dysfunction of cytotoxic T and natural killer cells within an immunosuppressive tumor microenvironment. Central to this process is tumor-intrinsic plasticity, whereby lineage instability and dedifferentiation, exacerbated by therapeutic pressure, embed immune silence as a stable tumor state. We highlight evidence positioning RD3 as a master upstream regulator linking cellular identity to immune visibility, governing antigen presentation, innate immune sensing, checkpoint expression, and cytotoxic lymphocyte engagement. Beyond tumor-intrinsic mechanisms, we examine the roles of immunosuppressive myeloid populations, tumor-derived exosomes, metabolic stress, hypoxia, and ferroptosis-associated pathways in reinforcing immune paralysis. Finally, we outline emerging therapeutic strategies aimed at dismantling this architecture, including combinatorial checkpoint blockade, metabolic and epigenetic reprogramming, exosome-targeted interventions, and next-generation immune engineering platforms. Together, this review reframes TIME in NB as a programmable, developmentally rooted process and provides a mechanistic roadmap for restoring immune competence and therapeutic susceptibility in HR disease. Full article

Hydrogel-based sensors have emerged as transformative soft-sensing platforms, featuring tissue-matched compliance, high water content, stimuli responsiveness, and chemical tunability, properties which are unachievable with conventional rigid sensors. Despite substantial advances, the existing reviews focus on individual polymer categories, discrete transduction mechanisms, or targeted standalone applications, failing to establish an integrated pipeline from material design to final sensing performance. This review fills these crucial gaps by systematically correlating polymer chemistry, crosslinking tactics, and fabrication protocols with the selection of transduction mechanisms and resultant sensing performance across biomedical and environmental fields. We conduct a critical assessment of natural and synthetic polymers together with chemical, physical, and hybrid composite crosslinking methodologies. Multiple sensing modalities, including piezoresistive, capacitive, thermogalvanic, electrochemical, colorimetric, ratiometric fluorescence, and piezoionic sensing are elaborated alongside representative quantitative performance parameters. Emerging platforms, including self-powered thermogalvanic sensors, SERS-integrated biosensors, and MXene/MOF composites, are highlighted as underexplored frontiers. In addition, persistent bottlenecks including dehydration-derived signal drift, inferior long-term operational stability, unsatisfactory target selectivity, and obstacles toward large-scale manufacturability are rigorously analyzed. Ultimately, this review constructs a holistic unified framework bridging polymer molecular design, fabrication engineering, signal transduction, and practical end-use applications, laying a clear developmental roadmap for next-generation flexible and smart hydrogel-based sensing systems. Full article

Predictive Maintenance Digital Twin (PdMDT) is an emerging cyber-physical technology with potential to revolutionise industrial maintenance. Despite this gradual prominence, the foundational infrastructure required to stage-by-stage develop the technology is lacking. Researchers have developed reference architecture (RA), information and functional requirements and the Model Based Systems Engineering (MBSE) for systematic development. These interventions have not addressed the stage- by-stage systematic development of PdMDT. Other gaps like the conflation of PdMDT with Predictive Maintenance (PdM), lack of formal definition of the PdMDT, inconsistent nomenclature, and partial and non-scalable implementations continue to define the field. In this research, these gaps are addressed through a systematic literature review which reveal the quality of aggregated studies from three databases—IEEE Digital Explore, Scopus, and the Web of Science, and a comparative and critical analysis of PdM and PdMDT from which several gaps in literature are discovered. The Primary contribution of this investigation is the development of a 9-stage life-cycle developmental framework for the PdMDT which necessitated the clarification of the inconsistent PdMDT terminologies, clarification of the various PdMDT implementations and a formal definition for PdMDT. All these interventions are necessary for the realisation of PdMDT at an industrial scale. Full article

With the increasing prevalence of pirated software, reverse engineering is regarded as a key technology. Reverse engineering enables the reconstruction of compiled code into a high-level language, revealing its functions and characteristics. We analyzed existing research results on software reverse engineering with a focus on the main methods, application scope, and emerging trends of combining reverse engineering with ML. The practical application of reverse engineering in intellectual property rights protection was examined by comparing it with existing methods, such as code obfuscation and anti-analysis mechanisms. Finally, this paper proposes future research directions, emphasizing the ethical and developmental aspects of reverse engineering, as well as the importance of AI. Full article

In situ hybridization (ISH) has undergone a rapid evolution from a low-throughput histological staining technique to a diverse family of modern methods for sensitive, specific and multiplexed molecular detection in intact cells and tissues, and to a cornerstone technology for image-based spatial transcriptomics. This transformation has been driven by advances in probe design, signal amplification, cyclic imaging, combinatorial barcoding, automated fluidics and computational decoding, which together allow RNA molecules to be measured within preserved cellular and tissue architecture. In this review, we examine the molecular and engineering principles that underlie modern ISH methods and their extension into ISH-based spatial profiling, with emphasis on hybridization chain reaction, branched-DNA amplification, SABER-FISH, rolling-circle-amplification-based approaches, seqFISH, MERFISH, RAEFISH and selected commercial implementations. We discuss how sensitivity, specificity, tissue compatibility, optical crowding, imaging burden, cost, reproducibility and computational uncertainty shape the practical use of each method. Sequencing-based spatial capture platforms are not reviewed comprehensively, but are considered where comparative benchmarks help clarify trade-offs in spatial resolution, transcriptome breadth, tissue area or analytical interpretation. We also consider how recent benchmarking and standardization efforts are beginning to define quantitative criteria for comparing platforms, and how advances in segmentation, barcode decoding, spatial integration and cell–cell communication analysis convert raw images into biological insight. Finally, we highlight applications in targeted transcript detection, tissue-based validation, neuroscience, cancer, developmental biology, non-model organisms and spatial functional genomics, where modern ISH methods and ISH-based spatial profiling provide information that bulk and dissociated single-cell approaches cannot capture. Together, these developments trace how ISH has expanded from targeted molecular visualization into a broad methodological framework for in situ detection and spatially resolved transcriptomic analysis. Full article

Ensuring global food security under accelerating climate change requires transformative approaches to crop improvement that extend beyond the limits of traditional breeding and gene editing. While domestication and modern agriculture have delivered substantial gains in productivity, these advances often came at the cost of genetic diversity, stress resilience, and developmental plasticity. Plants, however, inherently exhibit remarkable flexibility in their morphology and development, as evidenced by the vast diversity of organ shapes, cell types, and adaptive responses that have evolved across lineages. This natural design space provides a foundation for reimagining plant architecture using synthetic biology. Recent advances in plant synthetic biology, including programmable transcription factors, CRISPR-based regulatory systems, synthetic gene circuits, orthogonal signalling pathways, and plant artificial chromosomes, now enable precise, modular, and environmentally responsive manipulation of developmental processes. These tools allow researchers to rewire hormone pathways, tune quantitative gene expression, integrate multiple environmental signals, and create novel regulatory modules that operate independently of endogenous networks. Beyond understanding plant development, these capabilities open avenues for engineering crops with dynamic architectures, enhanced plasticity, and improved resilience to complex and fluctuating stresses. In this review, we synthesise insights from natural diversity, developmental biology, and synthetic regulatory engineering to outline how plant architecture can be rationally redesigned. We argue that integrating synthetic biology with modern breeding and modelling frameworks will be essential for generating the next generation of programmable crops; i.e., varieties capable of sustaining productivity and stability in an era of unprecedented environmental and geopolitical changes. Full article

The expansion of floriculture into climatic transition regions requires precise tools to mitigate thermo-hydric risks. Gladiolus (Gladiolus × grandiflorus Hort.) is sensitive to temperature extremes, requiring strategic planning of planting schedules and heat stress mitigation. The objective in this study was to evaluate the PhenoGlad model for its ability to simulate developmental stages and heat stress damage in eight gladiolus cultivars across multiple environments and planting dates in the state of Mato Grosso do Sul, Midwest Brazil. Field experiments were conducted in five municipalities during the autumn, winter, and spring growing seasons. Model performance was evaluated by starting the simulation at planting or at emergence, using the statistics root mean square error (RMSE), bias index (BIAS), Willmott’s index of agreement (d), and the correlation coefficient (r). Simulations starting at emergence reduced the error in predicting the timing of developmental stages (from 5.34 to 3.16 days). For leaf development, the model was highly accurate, with an RMSE lower than one leaf for different planting dates, sites, and cultivars. Furthermore, the model accurately predicted extreme heat stress events (daily maximum temperatures > 34 °C associated with low relative humidity), which resulted in severe damage and inhibition of reproductive development in the field. In conclusion, the PhenoGlad model is a robust decision-support system and agricultural engineering tool for production scheduling and climate loss mitigation in tropical floriculture. Full article

Nitrate functions as both a nutrient and a signaling molecule in plants, initiating genome-wide transcriptional reprogramming and systemic developmental adjustments. Traditionally, plasma membrane nitrate sensing and nuclear transcriptional responses have been considered independent processes linked through linear transduction pathways. However, recent findings reveal that the dual-affinity nitrate transceptor NRT1.1 (NPF6.3) and the transcription factor NLP7 form an integrated signaling nexus—the Nitrate transporter 1.1 (NRT1.1)-NIN-like protein 7 (NLP7) nexus. This review examines the coupling mechanisms, including Ca²⁺-dependent phosphorylation cascades, nucleocytoplasmic shuttling, and a recently discovered MAPK amplification branch. We further explore the nexus’s conserved and diversified functions across crop species, and propose a three-tier rational design framework for reprogramming nitrate responses to enhance nitrogen use efficiency. By bridging structural biology and synthetic biology, this integrative perspective transitions crop improvement from empirical selection to structure-guided design, offering a roadmap for predictive crop engineering. Full article