Search Results (167)

Viral oncolysis is considered a promising cancer treatment method because of its good tolerability and durable anti-tumor effects. Compared with other oncolytic viruses, Newcastle disease virus (NDV) has some distinct advantages. As an RNA virus, NDV does not recombine with the host genome, making it safer compared with DNA viruses and retroviruses; NDV can induce syncytium formation, allowing the virus to spread among cells without exposure to host neutralizing antibodies; and its genome adheres to the hexamer genetic code rule (genome length as a multiple of six nucleotides), ensuring accurate replication, low recombination rates, and high genetic stability. Although wild-type NDV has a killing effect on various tumor cells, its oncolytic effect and working mechanism are diverse, increasing the complexity of generating engineered oncolytic viruses with NDV. This study aims to employ whole-genome CRISPR-Cas9 knockout screening and RNA sequencing to identify putative key regulatory factors involved in the interaction between NDV and human colon cancer HCT116 cells and map their global interaction networks. The results suggests that NDV infection disrupts cellular homeostasis, thereby exerting oncolytic effects by inhibiting cell metabolism and proliferation. Meanwhile, the antiviral immune response triggered by NDV infection, along with the activation of anti-apoptotic signaling pathways, may be responsible for the limited oncolytic efficacy of NDV against HCT116 cells. These findings not only enhance our understanding of the oncolytic mechanism of NDV against colonic carcinoma but also provide potential strategies and targets for the development of NDV-based engineered oncolytic viruses. Full article

Rapid urbanization and industrial development have significantly altered land use and cover across the globe, intensifying urban thermal environments and exacerbating the urban heat island (UHI) effect. Gujranwala, Pakistan, represents an industrial growth that has driven substantial land use/land cover (LULC) changes and temperature increases; however, the directional and distance-based patterns of these changes remain unquantified. Therefore, this study is conducted to examine spatiotemporal changes in LULC and variations in the Urban Thermal Field Variation Index (UTFVI) between 2001 and 2021 and to project future scenarios for 2031 and 2041 using (1) Earth Observation Indices (EOIs) with machine learning (ML) classifiers (Random Forest) for precise LULC mapping through the Google Earth Engine (GEE) platform, (2) Cellular Automata–Artificial Neural Networks (CA-ANNs) for future scenario projection, and (3) Gradient Directional Analysis (GDA) to quantify directional (16-axis) and distance-based (concentric zones) patterns of urban expansion and thermal variation from 2001–2021. The study revealed significant LULC changes, with built-up areas expanding by 7.5% from 2001 to 2021, especially in the east, northeast, and southeast directions within a 20 km radius. Due to urban encroachment, vegetation and cropland decreased by 1.47% and 1.83%, respectively. The urban thermal environment worsened, with the highest land surface temperature (LST) rising from 41 °C in 2001 to 55 °C in 2021. Additionally, the UTFVI showed expanding areas under the ‘strong’ and ‘strongest’ categories, increasing from 30.58% in 2001 to 33.42% in 2041. Directional analysis highlighted severe thermal stress in the southern and southwestern areas linked to industrial activities and urban sprawl. This integrated approach provides a template for analyzing urban thermal environments in developing cities, supporting targeted mitigation strategies through direction- and distance-specific planning interventions to mitigate UHI impacts. Full article

Bacterial structures formed from the outer membrane and the periplasm components carry biomolecules to expel cellular material and interact with other cells. These outer membrane vesicles (OMVs) can encapsulate bioactive content, which confers OMVs with high potential as alternative drug delivery vehicles or as a platform for novel vaccine development. Single-gene mutants derived from Escherichia coli JC8031 were engineered to further enhance OMV production based on metabolic network modelling and in silico gene knockout design (ΔpoxB, ΔsgbE, ΔgmhA, and ΔallD). Mutants were experimentally obtained by genome editing using CRISPR-Cas9 and tested for OMVs recovery observing an enhanced OMV production in all of them. Lipidomic analysis through LC-ESI-QTOF-MS was performed for OMVs obtained from each engineered strain and compared to the wild-type E. coli JC8031 strain. The lipid profile of OMVs from the wild-type E. coli JC8031 did not change significantly confirmed by multivariate statistical analysis when compared to the mutant strains. The obtained results suggest that the vesicle production can be further improved while the obtained vesicles are not altered in their composition, allowing further study for stability and integrity for use in therapeutic settings. Full article

Despite significant advances in understanding neuronal development, a fully quantitative framework that integrates intracellular mechanisms with environmental cues during axonal growth remains incomplete. Here, we present a unified biophysical model that captures key mechanochemical processes governing axonal extension on micropatterned substrates. In these environments, axons preferentially align with the pattern direction, form bundles, and advance at constant speed. The model integrates four core components: (i) actin–adhesion traction coupling, (ii) lateral inhibition between neighboring axons, (iii) tubulin transport from soma to growth cone, and (iv) orientation dynamics guided by substrate anisotropy. Dynamical systems analysis reveals that a saddle–node bifurcation in the actin adhesion subsystem drives a transition to a high-traction motile state, while traction feedback shifts a pitchfork bifurcation in the signaling loop, promoting symmetry breaking and robust alignment. An exact linear solution in the tubulin transport subsystem functions as a built-in speed regulator, ensuring stable elongation rates. Simulations using experimentally inferred parameters accurately reproduce elongation speed, alignment variance, and bundle spacing. The model provides explicit design rules for enhancing axonal alignment through modulation of substrate stiffness and adhesion dynamics. By identifying key control parameters, this work enables rational design of biomaterials for neural repair and engineered tissue systems. Full article

Indonesia faces significant challenges in meeting food security targets due to rapid agricultural land loss, with approximately 1.22 million hectares of rice fields converted between 1990 and 2022. Therefore, this study developed a prediction model for the loss of rice fields by 2030, incorporating land productivity attributes, specifically rice cropping intensity/RCI, using geospatial technology—a novel method with a resolution of approximately 10 m for quantifying ecosystem service (ES) impacts. Land use/land cover data from Landsat images (2013, 2020, 2024) were classified using the Random Forest algorithm on Google Earth Engine. The prediction model was developed using a Multi-Layer Perceptron Neural Network and Markov Cellular Automata (MLP-NN Markov-CA) algorithms. Additionally, time series Sentinel-1A satellite imagery was processed using K-means and a hierarchical clustering analysis to map rice fields and their RCI. The validation process confirmed high model robustness, with an MLP-NN Markov-CA accuracy and Kappa coefficient of 83.90% and 0.91, respectively. The present study, which was conducted in Indramayu Regency (West Java), predicted that 1602.73 hectares of paddy fields would be lost within 2020–2030, specifically 980.54 hectares (61.18%) and 622.19 hectares (38.82%) with 2 RCI and 1 RCI, respectively. This land conversion directly threatens ES, resulting in a projected loss of 83,697.95 tons of rice production, which indicates a critical degradation of service provisioning. The findings provide actionable insights for land use planning to reduce agricultural land conversion while outlining the urgency of safeguarding ES values. The adopted method is applicable to regions with similar characteristics. Full article

Electrically conductive hydrogels are gaining attention owing to their applications in biosensing, cellular interfaces, and tissue engineering. However, conventional hydrogels often lack adequate electrical conductivities. Here, we present two novel conductive alginate-based hydrogels designed for extrusion-based 3D bioprinting: (i) covalently synthesized alginate–polypyrrole (alginate–PPy) via EDC/NHS-mediated conjugation with 3-aminopropyl pyrrole, and (ii) nanoparticle-reinforced alginate blended with polypyrrole nanoparticles (alginate@PPy-NP). Both systems exhibited shear-thinning behavior, tunable viscoelasticity, and excellent printability. Alginate@PPy-NP demonstrated superior compressive strength and shape fidelity, whereas alginate–PPy showed enhanced elastic moduli (G′/G″), reflecting a more uniform gel network. Electrical conductivity increased with increasing pyrrole content in both formulations. Optimization of the composition and printing conditions enabled the fabrication of fibroblast-laden constructs with high structural integrity. This work highlights the potential of alginate–polypyrrole hydrogels as customizable, conductive bioinks for 3D bioprinting in regenerative medicine. Full article

Effective bone tissue regeneration remains pivotal in implant dentistry, particularly for edentulous patients with compromised alveolar bone due to atrophy and sinus pneumatization. Biomaterials are essential for promoting regenerative processes by supporting cellular recruitment, vascularization, and osteogenesis. This study presents the development and characterization of a novel lithography-printed ceramic β-TCP scaffold, with a macro/micro-porous lattice, engineered to optimize osteoconduction and mechanical stability. Morphological, structural, and biomechanical assessments confirmed a reproducible microarchitecture with suitable porosity and load-bearing capacity. The scaffold was also employed for maxillary sinus augmentation, with postoperative evaluation using micro computed tomography, synchrotron imaging, histology, and Fourier Transform Infrared Imaging analysis, demonstrating active bone regeneration, scaffold resorption, and formation of mineralized tissue. Advanced imaging supported by deep learning tools revealed a well-organized osteocyte network and high-quality bone, underscoring the scaffold’s biocompatibility and osteoconductive efficacy. These findings support the application of these 3D-printed β-TCP scaffolds in regenerative dental medicine, facilitating tissue regeneration in complex jawbone deficiencies. Full article

Both biochemical cues and the electrophysiological microenvironment play a pivotal role in influencing cell behaviors. In this study, collagen/polypyrrole biomimetic electroactive composite coatings with a fiber network structure were constructed on the surface of titanium substrates by hot alkali treatment and stepwise electrochemical deposition. Materialistic characterization and electrochemical performance tests demonstrated that the titanium electrodes modified with collagen/polypyrrole composite coatings exhibited the surface morphology of a collagen film layer, and their electroactivity was significantly enhanced. Cellular experiments demonstrated that the collagen in the composite coatings could provide good biomimetic biochemical cues as a main extracellular matrix component, which have a substantial effect in promoting cell adhesion, proliferation, and osteogenic differentiation. Furthermore, under exogenous electrical signals, the polypyrrole coating has the capacity to facilitate an appropriate electrophysiological microenvironment, thereby promoting osteogenic differentiation. The collagen/polypyrrole composite coating exhibited a better effect in promoting osteogenic differentiation among all samples by simultaneously providing the appropriate biochemical cues and electrophysiological microenvironments. This work demonstrates the feasibility of synergistic pro-osteogenesis by biochemical cues and an electrophysiological microenvironment, which is instructive for the field of bone tissue engineering. Full article

Mechanical forces are increasingly recognised as fundamental regulators of cellular function, complementing classical biochemical cues to direct development, tissue homeostasis, and disease progression. Cells detect external and internal forces via mechanosensor proteins and adapt their cytoskeletal architecture, leading to changes in cell behaviour. Biomaterials and biodevices come to the aid of tailoring biomaterials’ properties in terms of chemical/physical properties and, by emulating dynamical forces, e.g., shear stress and cell swelling, they may enlighten mechanobiological processes. Additionally, emerging technologies expand the experimental toolkit for probing mechanobiological phenomena in complex, customisable settings. Central to these processes are mechanotransducer proteins and membrane–organelle networks that convert mechanical deformation into biochemical signals, orchestrating downstream transcriptional and post-translational modifications. This review highlights how through bridging material engineering and cellular mechanics, mechanobiology provides a unified framework to understand how physical forces shape tissues and drive pathologies. The continued integration of advanced biomaterials, dynamic biodevices, and multiscale analytical methods promises to uncover new mechanistic insights and inform the development of mechanotherapeutic strategies. Full article

Polyamines play a pivotal role in regulating the growth and metabolic adaptation of microalgae, yet their integrative regulatory roles remain underexplored. This review advances a comprehensive perspective of microalgae growth, integrating polyamine dynamics, amino acid metabolism, and redox balance. Polyamines (putrescine, spermidine, and spermine) biology in microalgae, particularly Chlamydomonas reinhardtii, is reviewed, exploring their critical function in modulating cell cycle progression, enzymatic activity, and stress responses through nucleic acid stabilization, protein synthesis regulation, and post-translational modifications. This review explores how the exogenous supplementation of polyamines modifies their intracellular dynamics, affecting growth phases and metabolic transitions, highlighting the complex regulation of internal pools of these molecules. Comparative analyses with Chlorella ohadii and Scenedesmus obliquus indicated species-specific responses to polyamine fluctuations, linking putrescine and spermine levels to important tunable metabolic shifts and fast growth phenotypes in phototrophic conditions. The integration of multi-omic approaches and computational modeling has already provided novel insights into polyamine-mediated growth regulation, highlighting their potential in optimizing microalgae biomass production for biotechnological applications. In addition, genomic-based modeling approaches have revealed target genes and cellular compartments as bottlenecks for the enhancement of microalgae growth, including mitochondria and transporters. System-based analyses have evidenced the overlap of the polyamines biosynthetic pathway with amino acids (especially arginine) metabolism and Nitric Oxide (NO) generation. Further association of the H₂O₂ production with polyamines metabolism reveals novel insights into microalgae growth, combining the role of the H₂O₂/NO rate regulation with the appropriate balance of the mitochondria and chloroplast functionality. System-level analysis of cell growth metabolism would, therefore, be beneficial to the understanding of the regulatory networks governing this phenotype, fostering metabolic engineering strategies to enhance growth, stress resilience, and lipid accumulation in microalgae. This review consolidates current knowledge and proposes future research directions to unravel the complex interplay of polyamines in microalgal physiology, opening new paths for the optimization of biomass production and biotechnological applications. Full article

We explored the effects of altering expression levels of the sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA) ion-transporting enzymes on key T lymphocyte signaling functions. In these studies, we have taken advantage of the Jurkat T cell line which provides a T lymphocyte model cell phenotype with a well-characterized T cell receptor (TCR)-activated signaling pathway, as well as offering a cellular system with a good understanding of the SERCA expression profile. These studies have been prompted by a strong imperative to gain a better understanding of the complex roles SERCA Ca²⁺ pumps play in the integrated TCR-activated signaling network, particularly given the central role of SERCA functions in regulating essential endoplasmic reticulum (ER) integrity. We find in this study that altering SERCA expression can significantly reconfigure ER Ca²⁺ stores, increasing or decreasing Ca²⁺ storage capacity depending on upregulation or downregulation of SERCA expression, and these effects are also associated with substantial changes in agonist-induced Ca²⁺ release and influx patterns. Not surprisingly, these fundamental changes in TCR-regulated Ca²⁺ signaling properties are associated with major alterations in T lymphocyte functions including regulation of growth patterns, cytokine secretion and energy utilization. Our study also describes additional evidence revealing intriguing functional distinctions between the major SERCA isoform-regulated Ca²⁺ stores in T lymphocytes. Our work thus serves to reinforce increasing efforts to target the SERCA pumps as a potential profitable strategy to produce novel engineered T lymphocytes in the rapidly growing field of T-cell immunotherapy Full article

The intraosseous environment is a dynamic and intricate system integral to bone health, encompassing vascular, cellular, and biochemical interactions that drive key processes such as hematopoiesis, bone remodeling, and systemic mineral regulation. This review examines the structural composition of the bone matrix, the diverse cellular landscape, and the interconnected vascular and nervous networks, highlighting their roles in preserving bone function and responding to pathological changes. Recent studies reveal regulatory mechanisms involving oxygen tension, ionic balance, signaling molecules, and mechanotransduction pathways that shape bone metabolism and its adaptation to mechanical forces. Insights into the bone microenvironment’s metabolic shifts in cancer and its interaction with inflammation underscore its pivotal role in disease progression and therapeutic innovation. Additionally, advances in imaging techniques and biomaterials fuel progress in bone regeneration and understanding its microenvironment. Exploring the intricate physiochemical dynamics and regulatory networks within the intraosseous system unlocks potential clinical applications in bone diseases, tissue engineering, and systemic metabolic disorders. This comprehensive review bridges fundamental science with translational research, offering insights into the complex yet essential intraosseous environment. Full article

Research findings reveal that thermal environments precisely regulate the skeletal system through a triple regulation of “structural morphology-cellular dynamics-molecular mechanisms”: At the tissue morphology level, moderate heat exposure can promote increased bone density and longitudinal growth, as well as improved fracture load and yield point, but may negatively affect geometric shape and cortical bone thickness. Continuous high-temperature exposure harms bone structure, manifested as changes in biomechanical characteristics such as decreased toughness and rigidity. At the cellular level, thermal environments directly affect the proliferation/apoptosis balance of osteoblasts and osteoclasts, and by regulating osteocyte network activity and bone marrow mesenchymal stem cell fate decisions, these four cell populations form temperature-dependent metabolic regulatory circuits. At the molecular dimension, heat stress can activate the release of neural factors such as CGRP and NPY, which possess dual regulatory functions promoting both bone formation and resorption; simultaneously achieving coordinated regulation of angiogenesis and fat inhibition through VEGF and TGFβ. The thermal environment–bone regulatory mechanisms revealed in this study have important translational value: they not only provide theoretical basis for biomechanical protection strategies for high-temperature workers and athletes, but also offer innovative entry points for analyzing the pathological mechanisms of heat stroke secondary bone injury and osteoporosis through heat stress-related signaling pathways, while establishing a theoretical foundation for the development of temperature-responsive functionalized biomaterials in bone tissue engineering. Full article

The extracellular matrix (ECM) is a dynamic network providing mechanical and biochemical cues that regulate cellular behavior. ECM stiffness critically influences fibroblasts, the primary ECM producers, particularly in inflammation and fibrosis. This review explores the role of ECM stiffness in fibroblast-driven inflammation and tissue remodeling, focusing on the physicochemical and biological mechanisms involved. Engineered materials, hydrogels, and polydimethylsiloxane (PDMS) are highlighted for replicating tissue-specific stiffness, enabling precise control over cell–matrix interactions. The surface functionalization of substrate materials, including collagen, polydopamine, and fibronectin, enhances bioactivity and fibroblast adhesion. Key mechanotransduction pathways, such as integrin signaling and YAP/TAZ activation, are related to regulating fibroblast behaviors and inflammatory responses. The role of fibroblasts in driving chronic inflammatory diseases emphasizes their therapeutic potentials. Advances in ECM-modifying strategies, including tunable biomaterials and hydrogel-based therapies, are explored for applications in tissue engineering, drug delivery, anti-inflammatory treatments, and diagnostic tools for the accurate diagnosis and prognosis of ECM stiffness-related inflammatory diseases. This review integrates mechanobiology with biomedical innovations, providing a comprehensive prognosis of fibroblast responses to ECM stiffness and outlining future directions for targeted therapies. Full article

Plants face an array of environmental stresses, including both abiotic and biotic stresses. These stresses significantly impact plant lifespan and reduce agricultural crop productivity. Abiotic stresses, such as ultraviolet (UV) radiation, high and low temperatures, salinity, drought, floods, heavy metal toxicity, etc., contribute to widespread crop losses globally. On the other hand, biotic stresses, such as those caused by insects, fungi, and weeds, further exacerbate these challenges. These stressors can hinder plant systems at various levels, including molecular, cellular, and development processes. To overcome these challenges, multi-omics computational approaches offer a significant tool for characterizing the plant’s biomolecular pool, which is crucial for maintaining homeostasis and signaling response to environmental changes. Integrating multiple layers of omics data, such as proteomics, metabolomics, ionomics, interactomics, and phenomics, simplifies the study of plant resistance mechanisms. This comprehensive approach enables the development of regulatory networks and pathway maps, identifying potential targets for improving resistance through genetic engineering or breeding strategies. This review highlights the valuable insights from integrating multi-omics approaches to unravel plant stress responses to both biotic and abiotic factors. By decoding gene regulation and transcriptional networks, these techniques reveal critical mechanisms underlying stress tolerance. Furthermore, the role of secondary metabolites in bio-based products in enhancing plant stress mitigation is discussed. Genome editing tools offer promising strategies for improving plant resilience, as evidenced by successful case studies combating various stressors. On the whole, this review extensively discusses an advanced multi-omics approach that aids in understanding the molecular basis of resistance and developing novel strategies to improve crops’ or organisms’ resilience to abiotic and biotic stresses. Full article