Search Results (7,298)

The global antibiotic resistance crisis raises concerns about antibiotic use, and alternative strategies are urgently needed. In this context, host defense peptides (HDPs) have rapidly gained interest. However, one of the main obstacles is their production strategy. Chemical synthesis is the most widely used, although it is not scalable and has sequence limitations. A possible alternative is recombinant production, but the strategies used so far have limited efficiency. In this study, we aim to compare the activity and main characteristics of different HDPs produced by both chemical synthesis and by recombinant production, using an approach based on tetramers to ameliorate the production process. The results obtained showed that the production of HDPs as tetrameric peptides by recombinant production in Lactococcus lactis enhanced the peptide activity, with HDPs being much more active in terms of antimicrobial activity, more structurally stable, and nanostructured. Thus, the recombinant strategy described herein, fusing four repetitions of the same peptide, can become a real alternative to produce highly active HDPs through a scalable production process. Full article

Feline calicivirus (FCV) is a highly contagious pathogen widely circulating in cat populations. FCV has been shown to be able to evade the host immune response through different mechanisms. As a result, following the acute phase of infection, some cats remain persistently infected or experience reinfection cycles with variants of the same strain or with distinct field FCVs. These animals may become asymptomatic carriers, assuming a critical role in virus transmission and posing a significant risk to susceptible cats, particularly in high-density settings. Typical clinical signs of FCV infection include upper respiratory tract disease, oral ulcerations, salivation, and gingivostomatitis. In some cases, FCV infection has also been linked to a range of other clinical manifestations, including severe virulent systemic disease with high mortality rates. Indeed, FCV diversity and evolution have led to the emergence of new genetic, antigenic, and phenotypic variants, challenging disease control. This review provides a comprehensive synthesis of FCV, including its molecular biology, epidemiology, pathogenesis and clinical manifestations. Additionally, the role of vaccination and direct prophylaxis is critically evaluated. An integrated approach is essential to mitigate FCV transmission and disease burden in feline populations. Full article

The incidence of pancreatic ductal adenocarcinoma (PDAC) is continuing to rise globally, while overall survival continues to be poor. Margin-negative (R0) surgical resection is essential to improve patient outcomes. With increasing understanding of the importance of anatomy and biology to establishing the resectability of PDAC, neoadjuvant therapy (NAT) has emerged as an important strategy to achieve an R0 resection, particularly for those with borderline resectable (BR-PDAC) and locally advanced disease (LA-PDAC). However, despite the multiple randomised controlled trials (RCTs) published in recent years, the optimum regime has yet to be fully established. The role of neoadjuvant chemoradiation therapy (CRT) remains controversial, possibly allowing for improved local disease control at a potential cost of interrupting systemic treatment. The emergence of stereotactic ablative radiotherapy (SABR), in place of conventional radiation therapy, improves patient tolerance of NAT and may improve local tumour control for patients with PDAC during limited fractions, minimising systemic therapy interruption. A particular niche for SABR may be as part of NAT for LA-PDAC, potentially converting a minority of patients with favourable biology to allow for resection. While pancreaticoduodenectomy can be technically challenging following NAT, there is no difference in the rate of major morbidity or mortality post operatively. Indeed, post-operative pancreatic fistula (POPF) rates may be lower following NAT. Overall, however, evidence for SABR in a neoadjuvant setting for BR- and LA-PDAC remains sparse. Full article

This article introduces two enhanced techniques: the Natural Transform Iterative Method (NTIM) and the Optimal Auxiliary Function Method (OAFM). These approaches provide a close approximation for solving fractional-order Navier–Stokes equations, which are widely employed in domains such as biology, ecology, and applied sciences. By comparing the solutions derived from these methods to exact solutions, it is clear that they provide accurate and efficient outcomes. These findings highlight the straightforward yet effective use of these methodologies in modeling engineering systems. Navier–Stokes equations have numerous practical uses, including analyzing fluid flow in pipelines and channels, predicting weather patterns, and constructing aircraft and vehicles. Full article

Accurate and sensitive detection of protein biomarkers is critical for advancing in vitro diagnostics (IVD), yet conventional enzyme-linked immunosorbent assays (ELISA) often fall short in terms of sensitivity compared to nucleic acid-based tests. Bridging this sensitivity gap is essential for improving diagnostic accuracy, particularly in diseases where protein levels better reflect disease progression than nucleic acid biomarkers. In this review, we present strategies developed to enhance the sensitivity of ELISA, structured according to the sequential steps of the assay workflow. Beginning with surface modifications, we then discuss the methodologies to improve mixing and washing efficiency, followed by a summary of recent advances in signal generation and amplification techniques. In particular, we highlight the emerging role of cell-free synthetic biology in augmenting ELISA sensitivity. Recent developments such as expression immunoassays, CRISPR-linked immunoassays (CLISA), and T7 RNA polymerase–linked immunosensing assays (TLISA) demonstrate how programmable nucleic acid and protein synthesis systems can be integrated into ELISA workflows to surpass the present sensitivity, affordability, and accessibility. By combining synthetic biology-driven amplification and signal generation mechanisms with traditional immunoassay formats, ELISA is poised to evolve into a highly modular and adaptable diagnostic platform, representing a significant step toward the next generation of highly sensitive and programmable immunoassays. Full article

This paper analyzes a mathematical model to investigate the complex interactions between tumor cells, immune cells (natural killer (NK) cells and CD8+ cytotoxic T lymphocytes (CTLs)) and chemotherapy. The primary objectives are to analyze tumor–immune interactions without and under treatment, identify critical thresholds for tumor eradication, and evaluate how chemotherapy parameters influence therapeutic outcomes. The model integrates NK cells and CTLs as effector cells, combining their dynamics linearly for simplicity. Tumor growth follows a logistic function, while immune–tumor interactions are modeled using a Hill function for fractional cell death. Stability and bifurcation analysis are employed to identify equilibria (tumor-free, high-tumor, and a novel middle steady state), bistability regimes, and critical parameter thresholds. Numerical simulations use experimentally validated parameter values from the literature. This mathematical analysis provides a framework for assessing the efficacy of chemotherapy by examining the dynamic interplay between tumor biology and treatment parameters. Our findings reveal that treatment outcomes are sensitive to the balance between the immune system’s biological parameters and chemotherapy-specific factors. The model highlights scenarios where chemotherapy may fail due to bistability and identifies critical thresholds for successful tumor eradication. These insights can guide clinical decision making in dosing strategies and suggest combination therapies such as immunotherapy–chemotherapy synergies to shift the system toward favorable equilibria. Full article

The liver is a vital organ responsible for a broad range of metabolic functions, including glucose and lipid metabolism, detoxification, and protein synthesis. Its structural complexity, characterized by hexagonal hepatic lobules composed of diverse parenchymal and non-parenchymal cell types, supports its broad spectrum of physiological activities. Traditional in vitro liver models have contributed significantly to our understanding of hepatic biology and the development of therapies for liver-related diseases. However, static culture systems fail to replicate the dynamic in vivo microenvironment, particularly the continuous blood flow and shear stress that are critical for maintaining hepatocyte function and metabolic zonation. Recent advances in microphysiological systems (MPS) incorporating dynamic fluid flow have addressed these limitations by providing more physiologically relevant platforms for modeling liver function. These systems offer improved fidelity for applications in drug screening, toxicity testing, and disease modeling. Furthermore, the integration of liver MPS with other organ models in multi-organ-on-chip platforms has enabled the investigation of inter-organ crosstalk, enhancing the translational potential of in vitro systems. This review summarizes recent progress in the development of dynamic liver MPS, highlights their biomedical applications, and discusses future directions for creating more comprehensive and predictive in vitro models. Full article

In controlled environment agriculture (CEA), supplementary lighting, particularly light-emitting diode (LED) technology, is essential for optimizing plant growth and development. Among the spectral components, blue light (400–500 nm) plays an important role in affecting plant morphogenesis, photosynthesis, and key physiological processes. However, species-specific guidelines for optimizing blue light parameters such as intensity, duration, and spectral ratios remain insufficiently developed. Furthermore, plant spectral requirements shift across developmental stages, highlighting distinct blue light management strategies for each phase. This review synthesizes existing knowledge on the impacts of blue light on morphological adaptation, photosynthetic efficiency, flowering, and secondary metabolism, with an emphasis on differential responses across diverse plant species. We emphasize the need for growth-stage-specific lighting protocols and scalable strategies applicable to commercial CEA systems. Interdisciplinary collaboration, integrating molecular biology, genomics, and horticultural engineering, is necessary to enhance understanding of blue light-driven regulatory networks, optimize photoreceptor responses, and facilitate systematic validation of adaptive lighting approaches, ultimately advancing sustainable horticulture and next-generation CEA innovations. Full article

Traditional medicinal plants are valued for their therapeutic potential, yet the full spectrum of their bioactive compounds often remains underexplored. Recent advances in multiomics technologies, including metabolomics, proteomics, and transcriptomics, combined with in vitro culture systems and elicitor-based strategies, have revolutionized our ability to characterize and enhance the production of valuable secondary metabolites. This review synthesizes current findings on the integration of these approaches to help us understand phytochemical pathways optimising bioactive compound yields. We explore how metabolomic profiling links chemical diversity with antioxidant and antimicrobial activities, how proteomic insights reveal regulatory mechanisms activated during elicitation, and how in vitro systems enable controlled manipulation of metabolic outputs. Both biotic and abiotic elicitors, such as methyl jasmonate and salicylic acid, are discussed as key triggers of phytochemical defense pathways. Further, we examine the potential of multiomics-informed metabolic engineering and synthetic biology to scale production and discover novel compounds. By aligning traditional ethnobotanical knowledge with modern biotechnology, this integrative framework offers a powerful avenue to unlock the pharmacological potential of medicinal plants for sustainable and innovative therapeutic development. Full article

Exposure to chronic stress creates vulnerability to drug misuse and presents a barrier to sustained recovery for many individuals experiencing substance use disorders (SUDs). Preclinical literature demonstrates that stress modulates psychostimulant intake and seeking, yet there are wide gaps in our understanding of the specific mechanisms by which stress promotes brain changes that may govern addiction-related behaviors. Recent data suggest that microglia, innate immune cells in the central nervous system, are highly responsive to chronic stressors, and several mechanistic links have been explored highlighting the critical role microglia play in stress-related brain adaptation. Importantly, psychostimulants may engage similar microglial machinery, which opens the door for investigation into how microglia may be involved in shaping motivation for psychostimulants, especially in the context of stress exposure. The aims of this review are threefold: 1. Offer a brief overview of microglial biology in the adult brain. 2. Review current methods of interrogating microglial function with a focus on morphometric analyses. 3. Highlight preclinical research describing how microglia contribute to brain changes following chronic stress and/or psychostimulant exposure. Ultimately, this review serves to prime investigators studying the intersection of stress and SUDs to consider the relevant impacts of microglial actions. Full article

Modern oncology increasingly relies on personalized strategies that aim to customize medical interventions, using both tumor biology and clinical features to enhance efficacy and minimize adverse effects. In recent years, precision medicine has been implemented as part of systemic therapies; however, its integration into radiation therapy (RT) is still a work in progress. Conventional RT treatment plans are based on the Linear Quadratic (LQ) model and utilize standardized alpha and beta ratios (α/β), which ignore the high variability in terms of treatment response between and within patients. Recent advances in radiobiology, as well as general medical technologies, have also driven a shift toward more tailored approaches, including in RT. This review provides an overview of current knowledge and future perspectives for the personalization of RT, highlighting the role of tumor and patient-specific biomarkers, advanced imaging techniques, and novel therapeutic approaches. As an alternative to conventional RT modalities, hadron therapy and Flash RT are discussed as innovative approaches with the potential to improve tumor targeting while sparing normal tissues. Furthermore, the synergistic combination of RT with immunotherapy is discussed as a potential strategy to support antitumor immune responses and overcome resistance. By integrating biological insights, technological innovation, and clinical expertise, personalized radiation therapy may significantly advance the precision oncology paradigm. Full article

Climate change poses significant challenges to temperate rice production, particularly affecting grain quality and market acceptance. This review synthesizes current knowledge of climate-induced quality changes, with a focus on the Australian rice industry as a case study with comparisons to other temperate regions. Environmental stressors such as extreme temperatures, variable rainfall, elevated CO₂, and salinity disrupt biochemical pathways during grain development, altering physicochemical, textural, and aromatic traits. Different rice classes exhibit distinct vulnerabilities: medium-grain japonica varieties show reduced amylose under heat stress, aromatic varieties experience disrupted aroma synthesis under drought, and long-grain types suffer kernel damage under combined stresses. Temperature is a key driver, with quality deterioration occurring above 35 °C and below 15 °C. Systems biology analyses reveal complex signalling networks underpinning these stress responses, although experimental validation remains limited. The Australian industry has responded by developing cold-tolerant cultivars, precision agriculture, and water-saving practices, yet projected climate variability demands more integrated strategies. Priorities include breeding for stress-resilient quality traits, refining water management, and deploying advanced phenotyping tools. Emerging technologies like hyperspectral imaging and machine learning offer promise for rapid quality assessment and adaptive management. Sustaining high-quality rice in temperate zones requires innovation linking physiology with practical adaptation. Full article

Elite soccer places significant neuromuscular and metabolic stress on athletes, leading to elevated production of reactive oxygen and nitrogen species (RONS), particularly in skeletal muscle, where intense contractile activity and increased oxygen flux drive oxidative processes. These reactive species play a dual role in skeletal muscle, supporting adaptive signaling at controlled levels while causing oxidative damage when poorly regulated. This paper presents an integrated synthesis of current knowledge on redox biology in elite soccer players, focusing on the origins and regulation of RONS, the functions of enzymatic and non-enzymatic antioxidant systems, and how both RONS and antioxidant responses influence muscle performance, fatigue, recovery, and long-term physiological adaptation. Drawing on studies conducted between 2000 and 2025, the discussion underscores the seasonal fluctuations in oxidative stress, individual variability in redox responses, and the potential adverse effects of unsystematic antioxidant supplementation. The analysis also emphasizes the value of using biomarker-guided, periodized antioxidant interventions tailored to training demands. Future directions include longitudinal tracking and the use of AI-assisted monitoring to enable personalized strategies for maintaining redox balance and optimizing performance in elite sport. Full article

Pediatric high-grade gliomas (pHGGs), particularly diffuse midline gliomas (DMGs), are among the most lethal brain tumors due to poor survival and resistance to therapies. DMGs possess a distinct genetic profile, primarily driven by hallmark mutations such as H3K27M, ACVR1, and PDGFRA mutations/amplifications and TP53 inactivation, all of which contribute to tumor biology and therapeutic resistance. Developing physiologically relevant preclinical models that replicate both tumor biology and the tumor microenvironment (TME) is critical for advancing effective treatments. This review highlights recent progress in in vitro, ex vivo, and in vivo models, including patient-derived brain organoids, genetically engineered mouse models (GEMMs), and region-specific midline organoids incorporating SHH, BMP, and FGF2/8/19 signaling to model pontine gliomas. Key genetic alterations can now be introduced using lipofectamine-mediated transfection, PiggyBac plasmid systems, and CRISPR-Cas9, allowing the precise study of tumor initiation, progression, and therapy resistance. These models enable the investigation of TME interactions, including immune responses, neuronal infiltration, and therapeutic vulnerabilities. Future advancements involve developing immune-competent organoids, integrating vascularized networks, and applying multi-omics platforms like single-cell RNA sequencing and spatial transcriptomics to dissect tumor heterogeneity and lineage-specific vulnerabilities. These innovative approaches aim to enhance drug screening, identify new therapeutic targets, and accelerate personalized treatments for pediatric gliomas. Full article

Transmembrane channel-like (TMC) proteins are essential for hearing and balance; however, the molecular mechanisms that regulate their proper folding and membrane targeting remain poorly understood. Here, we establish Caenorhabditis elegans as a genetically tractable model to dissect TMC-1 trafficking by combining CRISPR knock-in strains, super-resolution microscopy, and genome-wide forward genetic screening. We show that TMC-1 robustly localizes to the plasma membrane in both neurons and muscle cells and identify a conserved valine (V803) in transmembrane domain 9 (TM9) as critical for its biogenesis and trafficking. Structural analyses guided by AlphaMissense and AlphaFold uncover two evolutionarily conserved functional hotspots, one in the extracellular loop adjacent to TM9 and the other in the TMC signature motif, which are interconnected by an evolutionarily conserved disulfide bond. Disrupting this bond in worm TMC-1 abolishes its cell-surface localization and destabilizes the mechanotransduction channel complex. Together, these findings provide a structural framework for interpreting deafness-causing mutations in human TMC1 and highlight disulfide-bond-linked hotspots as key molecular determinants of TMC protein biogenesis and trafficking. Full article