Search Results (1,086)

In drug-induced liver injury (DILI) prediction field, animal models and in vitro cell models are most commonly used. However, animal models require long experimental timelines and may exhibit species-specific differences compared with humans, whereas conventional two-dimensional (2D) cell culture models lack cell-to-cell and cell-to-extracellular matrix (ECM) interaction. Liver organoid models and liver organ-on-a-chip can better simulate the human liver microenvironment; however, the construction of liver organoids requires a long cycle and high costs, while liver organ-on-a-chip systems demand specialized equipment and professional technicians. Herein, we selected the human C3A cell line, characterized by its low cost and facile culture conditions to establish an in vitro three-dimensional (3D) liver model. Briefly, C3A cells were embedded in Matrigel and cultured for 7 days to allow model maturation. Compared with their 2D-cultured cell model, the established 3D model exhibited elevated mRNA expression levels of drug-metabolizing cytochrome P450 enzymes (CYPs). Moreover, the model displayed robust expression of key hepatic biomarkers, as well as bile duct biomarkers. To evaluate the model’s applicability for DILI prediction, we performed toxicity assessments using a panel of six well-characterized hepatotoxicants and three non-hepatotoxic compounds. Notably, the 3D C3A model achieved a sensitivity of 83.3%, specificity of 100%, and overall accuracy of 88.9%. Furthermore, treatment of this model with chlorpromazine, a well-characterized cholangiotoxic agent, resulted in suppressed expression of the bile duct biomarker cytokeratin 19 (CK19) and bile salt export pump (BSEP), accompanied by impaired bile acid transport capacity. Taken together, this study provided a simple, low-cost, easy to culture, and more readily scalable 3D hepatic model in comparison with conventional 2D primary human hepatocyte (PHHs) models and other advanced 3D liver models. Notably, the model displayed dual hepatic and biliary characteristics, supporting predictions of both DILI and drug-induced bile duct injury. It provided a promising in vitro platform for assessing drug-induced hepatobiliary toxicity, with potential to reduce reliance on animal experiments and accelerate early-stage screening of novel pharmaceutical candidates. Full article

Background: Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy with limited therapeutic options and poor prognosis. The increasing complexity of molecular stratification and treatment selection has stimulated interest in computational and biological modeling approaches for precision oncology. Objective. This narrative review aims to provide a comprehensive overview of digital twins (DTs), DT-enabling computational models, and biological twins (BTs) in CCA, discussing their applications, limitations, and potential integration within hybrid precision medicine frameworks. Methods: A narrative literature review was conducted. To inform the twin-focused sections, a structured PubMed search was performed using predefined keywords related to CCA and twin-related technologies, including organoids, xenografts, organ-on-chip systems. Particular attention was devoted to recent studies addressing computational modeling, patient-derived experimental systems, and translational applications. Results: DT development in CCA is supported by an ecosystem of DT-enabling technologies, including radiomics, artificial intelligence, multi-omics integration, and simulation-based models. However, fully realized medical DTs remain unavailable. BTs, including patient-derived organoids, xenografts, and microfluidic platforms, enable functional validation of therapeutic hypotheses but face challenges related to scalability, standardization, and clinical feasibility. Emerging hybrid DT-BT frameworks seek to combine computational prediction with biological validation through iterative feedback loops, potentially improving patient stratification and treatment personalization. Conclusions: DTs and BTs represent complementary components of an evolving precision oncology ecosystem in CCA. Although technical, biological, regulatory, and implementation challenges remain, the convergence of computational models, longitudinal molecular monitoring, and patient-derived systems may facilitate clinically actionable hybrid twin frameworks. Successful translation will require both technological innovation and healthcare-system improvements to precision medicine access. Full article

This study investigated the effects of apple, oak, and mesquite wood chip types on the physicochemical properties, VOC profiles, and sensory characteristics of brined smoked goat meat. Boneless muscles were brined in 1% NaCl and randomly assigned to a non-smoked control group or three wood chip-smoked groups. All smoked groups showed significantly lower TBARS values than the control (p < 0.05), indicating improved oxidative stability, whereas pH, cooking loss, and Warner–Bratzler shear force did not differ significantly among groups, indicating that fundamental textural properties were preserved. Notably, mesquite- and oak-smoked meats exhibited significantly higher abundances of key smoke-derived phenolic compounds—including guaiacol, phenol, o-cresol (2-methylphenol), and 2-methoxy-5-methylphenol—and sulfur-containing compounds such as carbon disulfide and hexathiane, which correlated with reduced off-flavor scores and significant improvements in smoke flavor and overall acceptability compared to the control and apple-smoked groups (p < 0.05). These findings demonstrate that smoking goat meat with mesquite or oak wood chips is an effective processing strategy to mask the perception of species-specific off-flavor and enhance overall sensory acceptability. Full article

For decades, soilless media have been used as a growing medium in horticultural production, but issues with sustainability and the climate impact of some components, like peat moss, have driven the industry to search for alternative products or fillers that are more environmentally viable. Utility mulch, a byproduct of tree trimming companies, is an organic mulch containing various components of a tree, including ground and chipped wood, and is often available for free. Thus, this study aimed to evaluate whether utility mulch can be an economically and ecologically viable soilless media filler for growing petunia (Petunia Juss.) ‘Multiflora Prostrate’ and begonia (Begonia L.) ‘Viking XL Red On Chocolate’ plants in a greenhouse. The experiment was conducted in a split-plot design with two replications. The rate of mulch was considered the main plot and the type of mulch as the sub-plot. Utility mulch was divided into three types: fresh, aged, and decomposed, and was applied at rates of 10%, 20%, 30%, 40%, and 50% v/v, while 100% soilless media was used as a control. For growth media properties, decomposed mulch showed a greater bulk density and water-holding capacity compared to the control, while fresh and aged mulch showed reduced values for both properties. The highest air porosity values (30.2–31.2%) were observed in media with fresh mulch at a 30 to 50% rate. For begonia, up to 20% of any of the different mulch treatments showed similar plant growth (height, width, SPAD, number of flowers) as the control. Shoot dry weight was found to be the greatest with the control but presented similar results when measured with 10% of fresh and decomposed mulch, while water use efficiency was only greater with the control. For petunia, only 10% of any type of mulch showed similar growth and performance as the control, except for the number of flowers. The number of flowers was reduced at all rates of mulch in petunia. Greater rates of fresh and aged mulch reduced nitrate content in the media, while the pH increased with all types of mulch. For phosphorus, a greater rate of aged and decomposed mulch showed the lowest value compared to the control for petunia, whereas in begonia, decomposed mulch showed the lowest P content, which might be associated with the higher substrate pH level. This study suggests that as much as 20% of the different-aged mulches for begonia and 10% for petunia could be used as a cheap substrate replacement in soilless media. Full article

Background/Objectives: Epilepsy remains a major neurological disorder, with approximately one-third of patients continuing to experience pharmacoresistant seizures despite the availability of numerous antiseizure medications (ASMs). While current therapies primarily target neuronal hyperexcitability through modulation of ion channels and neurotransmitter systems, increasing evidence suggests that epileptogenesis arises from multiscale interactions involving molecular, cellular, circuit, network, neuroinflammatory, and neurovascular mechanisms. Although therapeutic strategies have diversified, this expanded mechanistic understanding has not yet been fully incorporated into therapeutic development and evaluation. This review integrates current knowledge of multiscale epilepsy pathophysiology with recent therapeutic advances and emerging experimental platforms. Methods: This narrative review synthesized literature identified primarily through PubMed and Google Scholar searches through January 2026, supplemented by targeted updates of therapeutic development and regulatory status through July 2026. Particular emphasis was placed on ion channel modulators, synaptic and neuromodulatory therapies, neuroinflammatory interventions, precision genetic approaches, and human-relevant experimental platforms, including induced pluripotent stem cell (iPSC)-derived models, brain organoids, multi-electrode arrays (MEAs), organ-on-a-chip systems, multi-omics technologies, and artificial intelligence (AI)-based analytical frameworks. Results: Current and emerging therapies target increasingly diverse molecular, circuit, neuromodulatory, and neuroinflammatory mechanisms. However, drug resistance remains multifactorial, and the long-term effects of therapeutic interventions on network remodeling, neuro-glial interactions, and sustained clinical response remain incompletely understood. NAMs provide complementary capabilities for patient-specific disease modeling, functional network phenotyping, neurovascular modeling, and the integration of molecular, electrophysiological, and computational data across biological scales. Conclusions: Epilepsy is increasingly recognized as a multiscale network disorder rather than solely a condition of neuronal hyperexcitability. The coordinated use of complementary human-relevant platforms may help incorporate multiscale mechanistic insights into therapeutic development and evaluation, narrow persistent translational gaps, and support more predictive and mechanism-informed treatment strategies. Full article

Biomimetic structures are now a major topic of research, as natural systems achieve high performance through hierarchical organization, multifunctional interfaces, and scale-bridging design principles. Nanofabrication provides a powerful approach to recapitulate biological architectures from the nanoscale to the macroscale, allowing accurate control of the surface chemistry, geometry, transport, mechanics and function. Recent work demonstrates that this approach is especially critical for bionic devices and systems, including biosensors, drug delivery platforms, tissue-engineered constructs, organ-on-chip systems, soft robots, and biohybrid devices. The aim of this review is to provide a systematic overview on how nanofabrication allows the construction of biomimetic structures, with emphasis on bio-templating and replication of natural structures, applications of nanofabrication in bionic devices and systems, and cross-scale biomimetics. Full article

Palm-vein recognition is an attractive biometric modality for secure access control because its subcutaneous vascular patterns are difficult to observe and reproduce externally. However, existing studies optimize the recognition algorithm and the hardware accelerator in isolation, and rarely satisfy the on-chip memory and energy constraints of edge devices. This paper presents a hardware-aware co-design of a lightweight FPGA accelerator for palm-vein recognition, in which the network is shaped by the cost structure of the target fabric and the inference engine is organized around the resulting layer shapes. On the algorithm side, a hardware-aware neural architecture search with deployment cost terms is combined with divisor-aligned structured pruning and INT8 quantization-aware training. Structured pruning reduces the model parameters to 0.32 M and the MACs to 87.2 M while preserving recognition accuracy. On the hardware side, a task-specific design space exploration selects a $14\times 12$ systolic array and an output-stationary dataflow that keeps all feature maps and weights on chip and reduces the modeled buffer-access count by 34.6% relative to the best alternative stationary dataflow. Implemented on a Xilinx Zynq-7100 at 100 MHz, the deployed INT8 checkpoint attains an accuracy of 99.50%, with a PL inference latency of 33.03 ms and an energy efficiency of 33.27 FPS/W. Full article

Cyclic adenosine monophosphate and cyclic guanosine monophosphate are key regulators of cellular physiology and tissue homeostasis. Conventional experimental models have provided fundamental insights into cyclic nucleotide pathways; however, they often fail to fully recapitulate essential features of in vivo systems. Two-dimensional cell cultures lack spatial organization, while animal models incompletely capture cell–cell interactions and the dynamic microenvironment shaping signaling processes. In recent years, advanced three-dimensional and microengineered systems have emerged as tools to bridge this gap. In this review, we discuss how three-dimensional and organ-on-chip systems are transforming the study of cyclic nucleotide signaling by enabling reconstruction of tissue architecture and signaling niches. Spheroids and organoids provide robust models to investigate compartmentalized signaling and intercellular communication. Complementarily, microfluidic organ-on-chip devices introduce controlled mechanical cues, perfusion, and tissue interfaces, enabling real-time monitoring of signaling dynamics. We highlight recent advances in microphysiological systems for investigating the spatial and temporal dynamics of cyclic adenosine monophosphate and cyclic guanosine monophosphate signaling, including biosensors, live-cell imaging, and genome editing. We further discuss applications in physiological and pathological contexts, including metabolic, cardiovascular and cancer diseases, and outline current challenges and future perspectives for integrating three-dimensional and organ-on-chip technologies. Full article

The development of patient-derived organoids (PDOs) has substantially advanced the study of gastrointestinal diseases by providing three-dimensional human models that faithfully recapitulate the structural, molecular, and functional characteristics of native tissues. Unlike conventional two-dimensional cultures and animal models, intestinal organoids preserve epithelial architecture, cellular heterogeneity, and patient-specific genetic features, enabling more physiologically relevant investigations of gastrointestinal physiology and disease. Recent technological advances, including co-culture systems, organoid-derived monolayers, and organ-on-chip platforms, have further expanded their ability to model epithelial interactions with immune cells, stromal components, and the gut microbiota. These developments have facilitated mechanistic studies of epithelial barrier function, host–microbiota communication, microbial metabolites, and endocrine signaling, while also supporting translational applications in inflammatory bowel disease, infectious disorders, inherited gastrointestinal diseases, and gastrointestinal cancers. Moreover, patient-derived organoids have emerged as promising platforms for drug screening, biomarker discovery, precision medicine, and regenerative therapies. Despite these advances, several challenges remain, including limited representation of the native tissue microenvironment, lack of standardized culture protocols, scalability, and regulatory issues that currently restrict routine clinical implementation. This review summarizes recent progress in gastrointestinal organoid technology, highlighting current applications, emerging experimental platforms, and future perspectives for integrating organoid-based models into translational research and personalized medicine. Full article

Intestinal stem cells (ISCs) are essential for maintaining intestinal homeostasis and repairing injury, and have garnered extensive attention in recent years. ISC research has not only advanced our understanding of intestinal physiology but also revealed pathological roles of ISCs in diseases and facilitated the identification of potential targeted therapies. This review aims to comprehensively present the current state of ISC research. It elaborates on the multi-level regulatory mechanisms governing ISCs, including niche cells, signaling pathways, gut microbiota, extracellular matrix, and epigenetic regulation. It further summarizes the involvement of ISCs in colorectal cancer, inflammatory bowel disease, radiation-induced intestinal injury, and short bowel syndrome, as well as their application in organoid technology. Finally, this review highlights future directions, including dissecting how distinct cellular states and microenvironments dynamically regulate ISC function, and the integration of cutting-edge technologies like microfluidic organ-on-a-chip and gene editing technologies to accelerate the translation of basic discoveries into clinical practice, thereby providing a valuable reference for researchers in the field. Full article

The human placenta is a temporary organ structured to optimize exchange between the maternal and fetal circulatory systems. Its fetal component consists of highly branched chorionic villi, which are anchored to the maternal uterine wall and project into the intervillous space. The outer surface of these villi is lined by a multinucleated, continuous layer called the syncytiotrophoblast, which is supported by an underlying layer of proliferative cytotrophoblast cells and the invasive extravillous trophoblast (EVT). This cellular bilayer forms a selective barrier that directly bathes in maternal blood, allowing for the efficient transfer of oxygen and nutrients while structurally preventing the direct mixing of maternal and fetal blood cells. Human placental studies have been stymied by ethical and accessibility constraints. Stem cell biology has now revolutionized the capacity to model human placental development, in particular with the derivation of human trophoblast stem cells (hTSCs) and organoids. Authentic, self-renewing human trophoblast stem cells (hTSCs) were first derived not from pluripotent stem cells but from primary tissue—first-trimester villous cytotrophoblasts and blastocysts. Derivation from human pluripotent stem cells (PSCs) followed only subsequently, along two principal routes: conversion of naive PSCs, which retain extraembryonic competence, and induction from primed PSCs, as well as by direct reprogramming of somatic cells to induced hTSCs. An important advance underlying these improvements is the mapping of a global reprogramming roadmap. Multi-omic and lineage-tracing experiments have mapped the stepwise transcriptional and epigenetic conversions of fibroblasts to hTSCs, including sequential chromatin reconfiguration, trophoblast gene network activation, and repression of somatic signatures. These results identify major regulatory bottlenecks and intermediate states, improving reprogramming fidelity. The derivation of stem-cell-based trophoblast organoids now enables complex modeling of placental architecture, function, and disease susceptibility in vitro. These organoids accurately recapitulate placental barrier functions and immunological features, allowing for examinations of maternal–fetal health, pregnancy disorders, and placental infection response to viruses like cytomegalovirus and SARS-CoV-2. Looking ahead, the integration of reprogramming and organoid technologies will propel patient-specific and tailor-made models for personalized diagnostics, drug screening, and mechanism studies. As we unravel the molecular ballet of trophoblast induction, such discoveries have the potential to bridge basic translational gaps in reproductive biology and maternal–fetal medicine. Full article

Cancer is the second leading cause of death worldwide, and tumor heterogeneity remains a major obstacle to effective therapy. In vitro reconstruction of the tumor microenvironment (TME) is particularly challenging because of its complexity, dynamic nature, and spatial heterogeneity, which limits the predictive value of conventional models for anticancer drug evaluation. Traditional Chinese medicine (TCM) has attracted increasing attention in cancer therapy owing to its multi-component, multi-target, and multi-pathway therapeutic characteristics. However, the complexity of TCM formulations and the diversity of their bioactive constituents make their pharmacological mechanisms difficult to elucidate using conventional experimental models. Microfluidic tumor microenvironment-on-a-chip (TME-on-a-chip) platforms integrate engineered cell culture with dynamic perfusion systems to recapitulate key structural, biochemical, and cellular features of the TME, thus providing a more physiologically relevant platform for anticancer research. With advantages such as low sample consumption, precise spatiotemporal control, multicellular co-culture, and real-time monitoring, these platforms provide a promising strategy for evaluating the efficacy and microenvironment-dependent effects of TCM-derived compounds and formulations. In this review, we summarize recent advances in the construction of TME-on-a-chip models, including multicellular organization, extracellular matrix simulation, vascularization, and immune microenvironment reconstruction, and discuss how these systems can be applied to key questions in TCM-based anticancer research. We further analyze current technical and methodological challenges that limit their broader adoption in TCM research and highlight future directions for promoting mechanism-driven and precision-oriented development of TCM in cancer therapy. Full article

The escalating accumulation of microplastics (MPs) in marine ecosystems presents a critical environmental crisis. However, current monitoring efforts rely heavily on labor-intensive, contamination-prone, and time-consuming laboratory analyses. While these conventional off-chip methods provide high accuracy, they inherently lack the throughput and autonomy required for continuous, real-time oceanic surveillance. To bridge this technological gap, microfluidic technologies (Lab-on-a-Chip) provide a viable route towards miniaturized, reagent-free in situ detection with reduced sample volumes and continuous operation capability. This review examines the transition from benchtop to field-deployable platforms and organizes the available microfluidic approaches for MP analysis into a structured overview. We examine on-chip sample manipulation and complementary separation techniques, such as acoustophoresis, dielectrophoresis, and optical tweezers, which are essential for isolating target particles from complex environmental matrices and overcoming intrinsic microfluidic challenges. Following sample preparation, we provide a comprehensive evaluation of state-of-the-art optical and spectroscopic identification methods optimized for continuous flow detection. Finally, we address current analytical limitations and discuss how the integration of machine learning with dynamic spectral libraries could enable autonomous, field-deployed monitoring networks for long-term MP surveillance. Full article

Cancer metabolism is a dynamic and context-dependent process shaped by both tumor-intrinsic programs and microenvironmental cues. Capturing this complexity remains a major challenge, which limits the translation of metabolic insights into clinically actionable strategies. Patient-derived tumor organoids, together with emerging engineered platforms such as organ-on-chip systems, vascularized assembloids, and bioprinted tumor models, have opened new avenues for investigating tumor metabolism in physiologically relevant settings. These models enable the study of metabolic heterogeneity across tumor types, disease stages, and treatment conditions while preserving clinically relevant tumor features. Importantly, they provide functional platforms for ex vivo metabolic profiling, identification of metabolic vulnerabilities, and prediction of therapeutic responses. In this review, we discuss recent advances in the use of patient-derived and engineered 3D tumor models to characterize context-dependent metabolic states and treatment-induced metabolic rewiring. We first review technologies currently available to interrogate metabolism in these systems, including optical metabolic imaging, spatial metabolomics, isotope tracing, and bioenergetic profiling. We then discuss how 3D tumor models are used to investigate metabolic interactions within the tumor microenvironment (TME), including stromal and immune crosstalk, acidosis, nutrient availability, and circadian regulation. Finally, we critically examine current limitations, particularly the insufficient physiological relevance of standard organoid culture conditions for metabolic studies, and discuss how advanced engineering approaches and computational modeling may contribute to metabolism-driven functional precision oncology. Full article

Preimplantation embryo development requires a tightly regulated microenvironment that is not fully reproduced by conventional static culture. We developed a polydimethylsiloxane-based microfluidic embryo co-culture platform integrating compartmentalized architecture with dynamic perfusion to simulate physiological conditions. The study included two stages. First, NIH/3T3 mouse fibroblasts were evaluated as helper cells under three culture conditions after transition to embryo culture medium. Helper-cell viability in the dynamic chip was 84.72%, compared with 71.91% after manual medium replacement in 24-well plates and 94.27% in the 24-well control group. Second, mouse embryos were cultured under four conditions: conventional 24-well plates, static microfluidic chip culture with co-culture, dynamic microfluidic chips without co-culture, and dynamic microfluidic chip co-culture. Blastocyst formation rates were 100.0% (9/9), 0.0% (0/6), 33.3% (3/9), and 55.5% (5/9), respectively. Because no inferential statistical analysis was performed, these proportions are interpreted descriptively. Nevertheless, the blastocyst formation in the microfluidic co-culture group supports the technical feasibility of integrating dynamic perfusion and helper-cell co-culture within a single platform. Further optimization and validation are required. This platform provides a foundation for future development of advanced embryo culture technologies including patient-specific endometrial co-culture systems in assisted reproduction, disease modeling, or drug development. Full article