Search Results (188)

Kidney organoids, as three-dimensional microstructures derived from human pluripotent stem cells or adult stem cells, precisely simulate the cellular heterogeneity, spatial conformation, and some physiological functions of human kidney units in vitro. Kidney organoids are three-dimensional microstructures derived from human pluripotent stem cells (hPSCs). They precisely simulate the cellular heterogeneity, spatial conformation, and key physiological functions of human kidney units in vitro. This technology, by replicating the interaction network between the glomerulus and renal tubules, provides an unprecedented window for observing the dynamic development and pathological processes of human kidneys. This technology replicates the interaction network between the glomerulus and renal tubules. It thereby provides an unprecedented window into human kidney development and disease. Based on the strong similarity between organoids and native organs, as well as the human genetic information they carry, both iPSC-derived and patient-specific organoids have demonstrated significant value in kidney disease modeling, drug toxicity testing, and the development of regenerative treatment strategies. This review systematically elucidates the key advancements in the field of kidney organoids, including optimized strategies for stem cell-directed differentiation, innovations in culture systems driven by biomaterials engineering, technological breakthroughs in disease model construction, and applications of organoids in drug screening platforms and regenerative medicine. Additionally, it analyzes translational challenges such as the lack of vascularization, insufficient functional maturity, and obstacles in standardized production. These insights will deepen the understanding of kidney pathological mechanisms and propel organoid technology towards substantial clinical therapeutic applications. This review summarizes how convergent technologies in stem cell biology and bioengineering aim to bridge this functional gap. We examine the use of advanced organoids in disease modeling and drug discovery. We also highlight their current limitations. Our focus is on the core translational bottlenecks: vascularization, long-term maturation, and scalable production. Overcoming these hurdles is essential to transform kidney organoids from a research tool into a platform for precision medicine and regenerative therapy. Full article

Efficient in vitro regeneration remains a major constraint in the genetic transformation, genome editing, and molecular breeding of wheat (Triticum aestivum L.), largely due to strong genotype-dependent recalcitrance and limited activation of developmental programs required for somatic embryogenesis. Plant regeneration relies on extensive transcriptional reprogramming and epigenetic remodeling orchestrated by morphogenic regulators that modulate meristem identity, as well as cellular pluri- and totipotency. In this review, we synthesize current molecular knowledge on key transcription factors (BBM, WUS/WUS2, GRF-GIF, WOX, LAX1, SERK, WIND1/ERF115) and signaling peptides (CLE/CLV-WUS module, phytosulfokine/PSK) that regulate embryogenic competence in monocot cereals, with emphasis on their orthologs and functional relevance in wheat. We highlight how controlled expression of these morphogenic genes, promoter engineering, and transient or excisable induction systems can significantly enhance regeneration capacity, reduce chimerism in CRISPR-Cas-edited plants, and facilitate genotype-independent transformation. We also discuss epigenetic and metabolic constraints underlying wheat recalcitrance and their potential modulation to improve culture responsiveness. By integrating evidence from wheat, rice, maize, and barley, we outline conserved gene-regulatory networks that reinitiate totipotency and propose strategies to accelerate doubled haploid production and speed-breeding pipelines. Collectively, morphogenic factors emerge as central molecular tools for overcoming regeneration bottlenecks and enabling next-generation wheat improvement. The objective of this review is to synthesize and critically evaluate current molecular knowledge on morphogenic regulators controlling in vitro regeneration in wheat (Triticum aestivum L.), with particular emphasis on their roles in genetic transformation and genome editing. Full article

Glioblastoma multiforme (GBM) is characterized by aggressive growth, extensive vascularization, high metabolic malleability, and a striking capacity for therapy resistance. Current treatments involve surgical resection and concomitant radiation therapy and chemotherapy, prolonging survival times marginally due to the therapy resistance that is built up by the tumor cells. A growing body of research has identified exosomes as critical enablers of therapy resistance. These nanoscale vesicles enable GBM cells to disseminate oncogenic proteins, nucleic acids, and lipids that collectively promote angiogenesis, maintain autophagy under metabolic pressure, and suppress apoptosis. As interest grows in targeting tumor communication networks, exosome-based therapeutic strategies have emerged as promising avenues for improving therapeutic outcomes in GBM. This review integrates current insights into two complementary therapeutic strategies: inhibiting exosome biogenesis and secretion, and engineering exosomes as precision vehicles for the delivery of anti-tumor molecular cargo. Key molecular regulators of exosome formation—including the endosomal sorting complex required for transport (ESCRT) machinery, tumor susceptibility gene 101 (TSG101) protein, ceramide-driven pathways, and Rab GTPases—govern the sorting and release of factors that enhance GBM survival. Targeting these pathways through pharmacological or genetic means has shown promise in suppressing angiogenic signaling, disrupting autophagic flux via modulation of autophagy-related gene (ATG) proteins, and sensitizing tumor cells to apoptosis by destabilizing mitochondria and associated survival networks. In parallel, advances in exosome engineering—encompassing siRNA loading, miRNA enrichment, and small-molecule drug packaging—offer new routes for delivering therapeutic agents across the blood–brain barrier with high cellular specificity. Engineered exosomes carrying anti-angiogenic, autophagy-inhibiting, or pro-apoptotic molecules can reprogram the tumor microenvironment and activate both the intrinsic mitochondrial and extrinsic ligand-mediated apoptotic pathways. Collectively, current evidence underscores the potential of strategically modulating endogenous exosome biogenesis and harnessing exogenous engineered therapeutic exosomes to interrupt the angiogenic and autophagic circuits that underpin therapy resistance, ultimately leading to the induction of apoptotic cell death in GBM. Full article

Perioperative pain remains a major clinical challenge, with many surgical patients experiencing inadequate analgesia and progression to chronic postsurgical pain. Conventional opioid-centered strategies are limited by narrow therapeutic windows, systemic toxicity, tolerance, opioid-induced hyperalgesia, and poor efficacy in neuroimmune-driven pain states. Advances in molecular neuroscience and biomedical engineering have catalyzed the development of nonpharmacologic analgesic technologies that modulate pain pathways through biophysical rather than receptor–ligand mechanisms. This narrative review synthesizes emerging nonpharmacologic analgesic platforms relevant to anesthesiology, integrating molecular, cellular, and systems-level mechanisms with clinical evidence. It examines how peripheral sensitization, spinal dorsal horn plasticity, glial and neuroimmune activation, and supraspinal network dysfunction create ideal targets for device-based interventions. Electrical neuromodulation strategies, including peripheral and central techniques, are discussed alongside temperature-based, photonic, and focused-energy modalities. These include cryoneurolysis, radiofrequency techniques, photobiomodulation, and low-intensity focused ultrasound. Clinical integration within enhanced recovery pathways, patient selection, workflow considerations, and limitations of the current human evidence base are reviewed. While many of these technologies are established in chronic pain management, this review emphasizes available human perioperative data and discusses how chronic pain evidence informs perioperative translation within opioid-sparing multimodal anesthesia care. Collectively, these technologies support a mechanism-based, systems-level approach to pain modulation, with perioperative relevance varying by modality and strength of available human evidence. Full article

Soil salinity is a major constraint on global crop production, disrupting photosynthesis, ion homeostasis, and growth. Beyond the roles of classic osmoprotectants and antioxidant enzymes, flavonoids have emerged as versatile mediators of salt stress tolerance at the interface of redox control, hormone signaling, and developmental plasticity. This review summarizes current evidence on how salinity remodels flavonoid biosynthesis, regulation, and function from cellular to whole-plant scales. We first outline the phenylpropanoid–flavonoid pathway, with emphasis on transcriptional control by MYB, bHLH, and NAC factors and their integration with ABA, JA, and auxin signaling. We then discussed how post-synthetic modifications such as glycosylation and methylation adjust flavonoid stability, compartmentation, and activity under salt stress. Functional sections highlight roles of flavonoids in ROS scavenging, Na⁺/K⁺ homeostasis, membrane integrity, and the modulation of ABA/MAPK/Ca²⁺ cascades and noncoding RNA networks. Spatial aspects, including root–shoot communication and rhizosphere microbiota recruitment, are also considered. Based on this synthesis, we propose a flavonoid-centered stress network (FCSN), in which specific flavonoids function as key nodes that connect metabolic flux with hormonal crosstalk and stress signaling pathways. We argue that reconceptualizing flavonoids as central stress network regulators, rather than generic antioxidants, provides a basis for metabolic engineering, bio-stimulant design, and breeding strategies aimed at improving crop performance on saline soils. Full article

This study investigates the adaptive mechanisms that enable a single wild barley (Hordeum spontaneum) accession to withstand extreme salinity. Salt stress reshapes plant metabolism and gene expression, offering targets for breeding salt-tolerant cereals. A time-course RNA-Seq experiment was conducted on leaves exposed to 500 mM NaCl, followed by differential expression and functional annotations to characterize transcriptomic responses. Transcriptomic profiling identified 140 dynamically upregulated genes distributed across 19 interconnected metabolic pathways, with phased activation of oxidative phosphorylation, nitrogen assimilation, lipid remodeling, and glutathione metabolism. Central metabolic nodes, including acetyl-CoA, hexadecanoyl-CoA, and ubiquinone, coordinated bioenergetic output, membrane stabilization, and redox homeostasis. Ribose-5-phosphate and ribulose-5-phosphate linked glycolysis and the pentose phosphate pathway, supplying NADPH for antioxidant defense and nucleotide repair, while riboflavin derived from Ru5P enhanced flavoprotein activity. In parallel, glucose and fructose-6-phosphate supported osmotic adjustment and glycolytic flux, and increased sterol and cuticular lipid biosynthesis, including cholesterol-like compounds, reinforced membrane integrity and calcium signaling. Glutathione and N-acetyl-glutamate together mitigated oxidative stress and modulated polyamine metabolism, strengthening cellular resilience under salt stress. These findings outline a coordinated network of metabolic and redox pathways that can guide the engineering of salt-tolerant cereals for sustainable production in saline agroecosystems. Full article

Heavy metal (HM) contamination threatens environmental sustainability, food safety, and agricultural productivity worldwide. HM toxicity adversely affects plant growth, reducing germination rates by 20–50%, impairing seedling establishment, and inhibiting shoot and root development by 30–60% in various crops. HM disrupts key physiological processes, including photosynthesis, stomatal regulation, membrane integrity, nutrient uptake, and enzymatic and nonenzymatic antioxidant activities. These disruptions largely result from oxidative stress, caused by the excessive accumulation of reactive oxygen species, which damage cellular components. To counteract HM toxicity, plants deploy a complex defense network involving antioxidant enzymes, metal chelation by phytochelatins and metallothioneins, vacuolar sequestration, and symbiotic interactions with arbuscular mycorrhizal fungi, which can retain 40–70% of metals in roots and reduce translocation to shoots. At the molecular level, MAPK (Mitogen-Activated Protein Kinase) signaling pathways, transcription factors (e.g., WRKY, MYB, bZIP, and NAC), and phytohormonal crosstalk regulate the expression of stress-responsive genes expression to enhance HM stress tolerance. Advances in nanotechnology offer promising strategies for the remediation of HM-contaminated soils and water sources (HM remediation); engineered and biogenic nanoparticles (e.g., ZnO, Fe₃O₄) improve metal immobilization, reduce bioavailability, and enhance plant growth by 15–35% under HM stresses, although excessive doses may induce phytotoxicity. Future applications of nanotechnology in HM remediation should consider nanoparticle transformation (e.g., dissolution and agglomeration) and environmentally relevant concentrations to ensure efficacy and minimize phytotoxicity. Integrating phytoremediation with nanoparticle-enabled strategies provides a sustainable approach for HM remediation. This review emphasizes the need for a multidisciplinary framework linking plant science, biotechnology, and nanoscience to advance HM remediation and safeguard agricultural productivity. Full article

The escalating frequency and severity of drought events pose significant threats to agricultural productivity and food security. Drought stress not only restricts crop growth and yields but also destabilizes agricultural ecosystems. Over evolutionary timescales, plants have developed intricate adaptive strategies, encompassing drought escape (accelerated phenology), avoidance (water-conserving morphology) and tolerance (cellular protection), which involve complex biological mechanisms spanning molecular signaling, metabolic reprogramming and organ morphological remodeling. To mitigate drought risks, breeding drought-tolerant and water-efficient crops is imperative. Currently, drought resistance breeding is undergoing a paradigm shift, transitioning from traditional phenotypic selection toward genomics-assisted selection, molecular design and artificial intelligence (AI)-driven predictive modeling. This review provides a comprehensive analysis of drought stress response mechanisms in crops, integrating three key dimensions: physiological/biochemical adaptations, hormonal signaling networks and morphological/structural modifications. Furthermore, it critically evaluates recent advances in genetic improvement approaches for drought resistance, such as marker-assisted selection, transgenic technology and gene editing. It also explores the integration of multi-omics data and AI to enhance precision molecular breeding and overcome the inherent trade-off between drought resistance and yield potential. By synthesizing advancements in molecular breeding and smart agriculture, this work provides a roadmap for developing climate-resilient crops optimized through synergistic trait engineering and intelligent environmental sensing. Full article

This study investigates the spatiotemporal changes in land use and land cover (LULC) in the Kağıthane basin, Istanbul, a region experiencing rapid urban growth, to assess its environmental sustainability. Sentinel-1 and Sentinel-2 satellite images processed on the Google Earth Engine (GEE) platform were used for 2017, 2020, and 2023. Optical data from Sentinel-2, after atmospheric and geometric corrections, combined with co- and cross-polarized radar backscatter from Sentinel-1, supported land cover classification. Additionally, 14 spectral indices, including the Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI), and Urban Index (UI), enhanced discrimination between classes. To estimate LULC projections for 2035, 2050, 2065, 2080, and 2095, the Modules for Land Use Change Evaluation (MOLUSCE) model was used, which integrates artificial neural networks with a cellular automata framework. Six driving variables, roads, streams, topographic parameters (elevation, slope, and aspect), and population density, were incorporated into multiple scenarios. Model performance was evaluated using overall accuracy, Kappa statistics, and confusion matrices, yielding strong results (91.88% accuracy; Kappa = 0.84). The simulations indicate a significant decline in forest cover and barren lands, while vegetation and built-up areas are projected to grow steadily, raising concerns about long-term urban sustainability. Water bodies are projected to remain relatively stable. Under these changes, future direct carbon emissions were estimated using carbon emission coefficients by land class. Indirect carbon emissions were estimated based on natural gas and electricity consumption data. Considering both direct and indirect emissions, the results indicate a decrease in carbon emissions from 2023 to 2035, followed by an increase of up to 13% between 2035 and 2095. These findings emphasize the importance of combining multi-sensor remote sensing data with spatially explicit modeling to accurately assess land use changes in rapidly urbanizing basins. The study emphasizes the critical need to adopt sustainability measures that address changes in carbon emissions and guide future urban planning towards a more sustainable path. Full article

Microalgae of the genus Nannochloropsis are known for their ability to accumulate large amounts of lipids, particularly triacylglycerides (TAGs), when exposed to nitrogen-limiting conditions. This trait makes them promising candidates for biofuel production. While previous studies have used transcriptomics and metabolomics to explore how these organisms respond to nutrient stress, the role of post-translational modifications—especially protein phosphorylation—remains poorly understood. To address this gap, we conducted a comprehensive analysis of protein phosphorylation events in Nannochloropsis oceanica under both nitrogen-replete and nitrogen-depleted conditions over a time-course experiment. Using mass spectrometry-based phosphoproteomics, we identified 1371 phosphorylation sites across 884 proteins. Temporal clustering of these phosphorylation events revealed two distinct regulatory phases: an early response aimed at conserving nitrogen resources, and a later phase that promotes lipid accumulation. Notably, we identified 11 phosphorylated proteins associated with the Target of Rapamycin (TOR) signaling pathway, suggesting that this conserved regulatory network plays a key role in coordinating the cellular response to nitrogen deficiency. By integrating our phosphoproteomic result with previously published transcriptomic and metabolomic datasets, we provide a more complete view of how N. oceanica adapts to nitrogen stress at the molecular level. This systems-level approach highlights the importance of protein phosphorylation in regulating metabolic shifts and offers new insights into engineering strategies for enhancing lipid production in microalgae. Full article

Human airways maintain homeostasis through intricate cellular interactomes combining secretome-mediated signalling and mechanotransduction feedback loops. This review presents the first unified map of bidirectional mechanobiology–secretome interactions between airway epithelial cells (AECs), smooth muscle cells (ASMCs), and chondrocytes. We unify a novel three-component regulatory architecture: epithelium functioning as environmental activators, smooth muscle as mechanical actuators, and cartilage as calcium-dependent regulators. Critical mechanotransduction pathways, particularly YAP/TAZ signalling and TRPV4 channels, directly couple matrix stiffness to cytokine release, creating a closed-loop feedback system. During development, ASM-driven FGF-10 signalling and peristaltic contractions orchestrate cartilage formation and epithelial differentiation through mechanically guided morphogenesis. In disease states, these homeostatic circuits become pathologically dysregulated; asthma and COPD exhibit feed-forward stiffness traps where increased matrix rigidity triggers YAP/TAZ-mediated hypercontractility, perpetuating further remodelling. Aberrant mechanotransduction drives smooth muscle hyperplasia, cartilage degradation, and epithelial dysfunction through sustained inflammatory cascades. This system-level understanding of airway cellular networks provides mechanistic frameworks for targeted therapeutic interventions and tissue engineering strategies that incorporate essential mechanobiological signalling requirements. Full article

Plants continuously face multiple abiotic stresses, including drought, salinity, heat, cold, and heavy metal, that challenge cellular homeostasis and threaten global crop productivity. Recent research reveals that these stress responses are not isolated but interconnected through shared hormonal, redox, and transcriptional networks. This review provides an integrative synthesis of current advances in stress signaling, emphasizing how perception, transduction, and memory layers are hierarchically organized across distinct stress types. We outline key regulatory hubs—such as ABA-centered hormonal crosstalk, chloroplast-nucleus redox communication, and epigenetic priming—that coordinate systemic tolerance. Furthermore, we highlight emerging evidence for stress-specific modules that operate under combined stresses (e.g., drought–heat, salinity–cold), providing a unified framework for understanding how plants integrate multi-dimensional signals. This synthesis offers a conceptual perspective linking signaling architecture to adaptive outcomes, aiming to inform future strategies for engineering multi-stress-resilient crops. Full article

The process of aging is fundamentally driven by genomic instability and the accumulation of DNA damage, which progressively impair cellular and tissue function. In order to counteract these challenges, cells rely on the DNA damage response (DDR), a multilayered signaling and repair network that preserves genomic integrity and sustains homeostasis. Within this framework, nucleases and helicases have pivotal and complementary roles by remodeling aberrant DNA structures, generating accessible repair intermediates, and determining whether a cell achieves faithful repair, undergoes apoptosis, or enters senescence. Defects in these enzymes are exemplified in human progeroid syndromes, where inherited mutations lead to premature aging phenotypes. This phenomenon is also replicated in genetically engineered mouse models that exhibit tissue degeneration, stem cell exhaustion, and metabolic dysfunction. Beyond their canonical repair functions, helicases and nucleases also interface with the epigenome, as DNA damage-induced chromatin remodeling alters enzyme accessibility, disrupts transcriptional regulation, and drives progressive epigenetic drift and chronic inflammatory signaling. Moreover, their dysfunction accelerates the exhaustion of adult stem cell populations, such as hematopoietic, neural, and mesenchymal stem cells. As a result, tissue regeneration is undermined, establishing a self-perpetuating cycle of senescence, impaired repair, and organismal aging. Current research is focused on developing therapeutic strategies that target the DDR–aging axis on several fronts: by directly modulating repair pathways, by regulating the downstream consequences of senescence, or by preventing DNA damage from accumulating upstream. Taken together, evidence from human disease, animal models, molecular studies, and pharmacological interventions demonstrates that nucleases and helicases are not only essential for genome maintenance but also decisive in shaping aging trajectories. This provides valuable knowledge into how molecular repair pathways influence organismal longevity and age-related diseases. Full article

In response to growing clinical demands for more targeted and effective immunotherapies to treat cancer, biomaterial-based strategies have emerged as powerful tools for locally regulating immune responses. Among these, hydrogels, a class of biocompatible and tunable polymeric networks, are increasingly being leveraged for their high versatility and adaptability for creating tailored immune environments. By enabling controlled delivery of immune cues and direct cellular engineering, hydrogels utilized in vivo can precisely regulate both innate and adaptive immune responses while minimizing systemic toxicity. In this review, we outline essential hydrogel design features necessary for in vivo functionality including injectability, degradation kinetics, and immune-specific functionalization. Building on these principles, we explore how hydrogels have been employed to enhance T cell activation and dendritic cell maturation and guide macrophage reprogramming. Beyond cellular modulation, we further examine the use of hydrogels for cytokine and immunoregulatory agent delivery, tumor microenvironment remodeling, and the creation of tertiary-like lymphoid structures. Finally, we review recently completed and ongoing clinical trials of hydrogels in the cancer immunotherapy space. Together, these insights underscore the growing potential of in vivo hydrogel systems as immuno-interactive platforms capable of reshaping immune responses across diverse disease contexts. Full article

Accurate forecasting of cellular traffic in non-stationary environments remains a formidable challenge, as real-world traffic patterns dynamically evolve, emerge, and vanish over time. To tackle this, we propose a novel meta-learning framework, GMM-SCM-DCM, which features a Dynamic Component Management (DCM) mechanism. This framework employs a Gaussian Mixture Model (GMM) for probabilistic meta-feature representation. The core innovation, the DCM mechanism, enables online structural evolution of the meta-learner by dynamically splitting, merging, or pruning Gaussian components based on a bimodal similarity metric, ensuring sustained alignment with shifting data distributions. A Single-Component Mechanism (SCM) is utilized for precise base learner initialisation. To ensure a rigorous and realistic validation, we reconstructed the Telecom Italia Milan dataset by applying unsupervised clustering and meta-feature engineering to identify and label four distinct functional zones: residential, commercial, mixed use, and crucially, non-stationary areas. This curated dataset provides a critical testbed for non-stationary forecasting. Comprehensive experiments demonstrate that our model significantly outperforms traditional methods and meta-learning baselines, achieving a 9.3% reduction in MAE and approximately 70% faster convergence. The model’s superiority is further confirmed through extensive ablation studies, robustness tests across base learners and data scales, and successful cross-dataset validation on the Shanghai Telecom dataset, showcasing its exceptional generalization capability and practical utility for real-world network management. Full article