Search Results (503)

Microalgae, with their unparalleled capabilities for sunlight-driven growth, CO₂ fixation, and synthesis of diverse high-value compounds, represent sustainable cell factories for a circular bioeconomy. However, industrial deployment has been hindered by biological constraints and the inadequacy of conventional genetic tools. The advent of CRISPR-Cas systems initially provided precise gene editing via targeted DNA cleavage. This review argues that the true transformative potential lies in moving decisively beyond cutting to harness CRISPR as a versatile synthetic biology “Swiss Army Knife”. We synthesize the rapid evolution of CRISPR-derived tools—including transcriptional modulators (CRISPRa/i), epigenome editors, base/prime editors, multiplexed systems, and biosensor-integrated logic gates—and their revolutionary applications in microalgal engineering. These tools enable tunable gene expression, stable epigenetic reprogramming, DSB-free nucleotide-level precision editing, coordinated rewiring of complex metabolic networks, and dynamic, autonomous control in response to environmental cues. We critically evaluate their deployment to enhance photosynthesis, boost lipid/biofuel production, engineer high-value compound pathways (carotenoids, PUFAs, proteins), improve stress resilience, and optimize carbon utilization. Persistent challenges—species-specific tool optimization, delivery efficiency, genetic stability, scalability, and biosafety—are analyzed, alongside emerging solutions and future directions integrating AI, automation, and multi-omics. The strategic integration of this CRISPR toolkit unlocks the potential to engineer robust, high-productivity microalgal cell factories, finally realizing their promise as sustainable platforms for next-generation biomanufacturing. Full article

Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling of TnP-treated larvae following tail fin amputation revealed 558 differentially expressed genes (DEGs), categorized into four functional networks: (1) drug-metabolizing enzymes (cyp3a65, cyp1a) and transporters (SLC/ABC families), where TnP alters xenobiotic processing through Phase I/II modulation; (2) cellular trafficking and immune regulation, with upregulated myosin genes (myhb/mylz3) enhancing wound repair and tlr5-cdc42 signaling fine-tuning inflammation; (3) proteolytic cascades (c6ast4, prss1) coupled to autophagy (ulk1a, atg2a) and metabolic rewiring (g6pca.1-tg axis); and (4) melanogenesis-circadian networks (pmela/dct-fbxl3l) linked to ubiquitin-mediated protein turnover. Key findings highlight TnP’s unique coordination of rapid (protease activation) and sustained (metabolic adaptation) responses, enabled by short network path lengths (1.6–2.1 edges). Hub genes, such as nr1i2 (pxr), ppara, and bcl6aa/b, mediate crosstalk between these systems, while potential risks—including muscle hypercontractility (myhb overexpression) or cardiovascular effects (ace2-ppp3ccb)—underscore the need for targeted delivery. The zebrafish model validated TnP-conserved mechanisms with human relevance, particularly in drug metabolism and tissue repair. TnP’s ability to synchronize extracellular matrix remodeling, immune resolution, and metabolic homeostasis supports its development for the treatment of fibrosis, metabolic disorders, and inflammatory conditions. Conclusions: Future work should focus on optimizing tissue-specific delivery and assessing genetic variability to advance clinical translation. This system-level analysis positions TnP as a model example for next-generation multi-pathway therapeutics. Full article

As the scale of shipboard power systems expands, their vulnerability becomes increasingly prominent. Identifying vulnerable points in ship power grids is essential for enhancing system stability, optimizing overall performance, and ensuring safe navigation. To address this issue, this paper proposes an algorithm based on fuzzy local dimension and topology (FLDT). The algorithm distinguishes contributions from nodes at different radii and within the same radius to a central node using fuzzy sets, and then derives the final importance value of each node by combining the local dimension and topology. Experimental results on nine datasets demonstrate that the FLDT algorithm outperforms degree centrality (DC), closeness centrality (CC), local dimension (LD), fuzzy local dimension (FLD), local link similarity (LLS), and mixed degree decomposition (MDD) algorithms in three metrics: network efficiency (NE), largest connected component (LCC), and monotonicity. Furthermore, in a ship power grid experiment, when 40% of the most important nodes were removed, FLDT caused a network efficiency drop of 99.78% and reduced the LCC to 2.17%, significantly outperforming traditional methods. Additional experiments under topological perturbations—including edge addition, removal, and rewiring—also show that FLDT maintains superior performance, highlighting its robustness to structural changes. This indicates that the FLDT algorithm is more effective in identifying and evaluating vulnerable points and distinguishing nodes with varying levels of importance. Full article

Mitochondria, pivotal organelles in cellular metabolism and energy production, have emerged as critical players in the pathogenesis of cancer. This review outlines the progress in mitochondrial profiling through mass spectrometry-based metabolomics and its applications in cancer research. We provide unprecedented insights into the mitochondrial metabolic rewiring that fuels tumorigenesis, metastasis, and therapeutic resistance. The purpose of this review is to provide a comprehensive guide for the implementation of mitochondrial metabolomics, integrating advanced methodologies—including isolation, detection, and data integration—with insights into cancer-specific metabolic rewiring. We first summarize current methodologies for mitochondrial sample collection and pretreatment. Furthermore, we then discuss the recent advancements in mass spectrometry-based methodologies that facilitate the detailed profiling of mitochondrial metabolites, unveiling significant metabolic reprogramming associated with tumorigenesis. We emphasize how recent technological advancements have addressed longstanding challenges in the field and explore the role of mitochondrial metabolism-driven cancer development and progression for novel drug discovery and translational research applications in cancer. Collectively, this review delineates emerging opportunities for therapeutic discovery and aims to establish a foundation for future investigations into the therapeutic modulation of mitochondrial pathways in cancer, thereby paving the way for innovative diagnostic and therapeutic approaches targeting mitochondrial pathways. Full article

The worldwide agriculture industry is facing increasing problems due to rapid population increase and increasingly unfavorable weather patterns. In order to reach the projected food production targets, which are essential for guaranteeing global food security, innovative and sustainable agricultural methods must be adopted. Conventional approaches, including traditional breeding procedures, often cannot handle the complex and simultaneous effects of biotic pressures such as pest infestations, disease attacks, and nutritional imbalances, as well as abiotic stresses including heat, salt, drought, and heavy metal toxicity. Applying phytohormonal approaches, particularly those involving hormonal crosstalk, presents a viable way to increase crop resilience in this context. Abscisic acid (ABA), gibberellins (GAs), auxin, cytokinins, salicylic acid (SA), jasmonic acid (JA), ethylene, and GA are among the plant hormones that control plant stress responses. In order to precisely respond to a range of environmental stimuli, these hormones allow plants to control gene expression, signal transduction, and physiological adaptation through intricate networks of antagonistic and constructive interactions. This review focuses on how the principal hormonal signaling pathways (in particular, ABA-ET, ABA-JA, JA-SA, and ABA-auxin) intricately interact and how they affect the plant stress response. For example, ABA-driven drought tolerance controls immunological responses and stomatal behavior through antagonistic interactions with ET and SA, while using SnRK2 kinases to activate genes that react to stress. Similarly, the transcription factor MYC2 is an essential node in ABA–JA crosstalk and mediates the integration of defense and drought signals. Plants’ complex hormonal crosstalk networks are an example of a precisely calibrated regulatory system that strikes a balance between growth and abiotic stress adaptation. ABA, JA, SA, ethylene, auxin, cytokinin, GA, and BR are examples of central nodes that interact dynamically and context-specifically to modify signal transduction, rewire gene expression, and change physiological outcomes. To engineer stress-resilient crops in the face of shifting environmental challenges, a systems-level view of these pathways is provided by a combination of enrichment analyses and STRING-based interaction mapping. These hormonal interactions are directly related to the United Nations Sustainable Development Goals (SDGs), particularly SDGs 2 (Zero Hunger), 12 (Responsible Consumption and Production), and 13 (Climate Action). This review emphasizes the potential of biotechnologies to use hormone signaling to improve agricultural performance and sustainability by uncovering the molecular foundations of hormonal crosstalk. Increasing our understanding of these pathways presents a strategic opportunity to increase crop resilience, reduce environmental degradation, and secure food systems in the face of increasing climate unpredictability. Full article

Colorectal cancer (CRC) remains a leading cause of cancer morbidity and mortality worldwide, especially in older adults where frailty complicates treatment outcomes. Multimodal prehabilitation—comprising nutritional support, physical exercise, and psychological interventions—has emerged as a promising strategy to enhance patients’ resilience before CRC surgery. Clinical studies demonstrate that prehabilitation significantly reduces postoperative complications, shortens hospital stays, and improves functional recovery. Nutritional interventions focus on counteracting malnutrition and sarcopenia through tailored dietary counseling, protein supplementation, and immunonutrients like arginine and glutamine. Physical exercise enhances cardiorespiratory fitness and muscle strength while modulating immune and metabolic pathways critical for surgical recovery. Psychological support reduces anxiety and depression, promoting mental resilience that correlates with better postoperative outcomes. Despite clear clinical benefits, the molecular mechanisms underlying prehabilitation’s effects—such as inflammation modulation, immune activation, and metabolic rewiring—remain poorly understood. This review addresses this knowledge gap by exploring potential biological pathways influenced by prehabilitation, aiming to guide more targeted, personalized approaches in CRC patient management. Advancing molecular insights may optimize prehabilitation protocols and improve survival and quality of life for CRC patients undergoing surgery. Full article

Background: Antibiotics at sub-inhibitory concentrations can rewire bacterial regulatory networks, impacting virulence. Objective: The way that exposure to selected antibiotics (ciprofloxacin, amikacin, azithromycin, ceftazidime, and meropenem) below their minimum inhibitory concentration (sub-MIC) modulates the physiology of Pseudomonas aeruginosa is examined in this study using growth-phase-resolved analysis. Methods: Standard P. aeruginosa strain cultures were exposed to ¼ and ½ MIC to determine the growth kinetics under antibiotic stress. The study measured protease and pyocyanin production and the expression level of important quorum sensing and virulence genes (lasI/R, rhlI/R, pqsR/A, and phzA) at different growth phases. Results: Meropenem produced the most noticeable growth suppression at ½ MIC. Sub-MIC antibiotics did not completely stop growth, but caused distinct, dose-dependent changes. Azithromycin eliminated protease activity in all phases and had a biphasic effect on pyocyanin. Ciprofloxacin consistently inhibited both pyocyanin and protease in all phases. The effects of amikacin varied by phase and dose, while β-lactams markedly increased pyocyanin production during the log phase. In contrast to the plateau phase, when expression was often downregulated or unchanged, most quorum-sensing- and virulence-associated genes showed significant upregulation during the death phase under sub-MIC exposure. Conclusions: These findings indicate that sub-MIC antibiotics act as biochemical signal modulators, preserving stress-adapted sub-populations that, in late growth phases, activate quorum sensing and stress tolerance pathways. Full article

Lactate, once regarded as a metabolic byproduct, is now recognized as a critical immunometabolic regulator that shapes immune responses in both physiological and pathological contexts. This review examines how lactate accumulation occurs across diverse disease settings, including cancer, sepsis, and diabetes, through mechanisms such as hypoxia, mitochondrial dysfunction, and pharmacologic intervention. We then explore how lactate modulates immunity via four integrated mechanisms: transporter-mediated flux, receptor signaling (e.g., GPR81), context-dependent metabolic rewiring, and histone/protein lactylation. Particular emphasis is placed on the dichotomous effects of endogenous versus exogenous lactate, with the former supporting glycolytic effector functions and the latter reprogramming immune cells toward regulatory phenotypes via redox shifts and epigenetic remodeling. The review also highlights how the directionality of lactate transport, and the metabolic readiness of the cell determine, whether lactate sustains inflammation or promotes resolution. After analyzing emerging data across immune cell subsets and disease contexts, we propose that lactate serves as a dynamic rheostat that integrates environmental cues with intracellular metabolic and epigenetic programming. Understanding these context-dependent mechanisms is essential for the rational design of lactate-targeted immunotherapies that aim to modulate immune responses without disrupting systemic homeostasis. Full article

Ginseng rusty root symptoms (GRSs) compromise the yield and quality of Panax ginseng. While transcriptomic analyses have demonstrated extensive remodeling of stress signaling networks, the post-transcriptional defense circuitry remains obscure. We profiled alternative splicing (AS) in three phloem tissues, the healthy phloem (AG), the non-reddened phloem neighboring lesions (BG), and the reddened lesion core (CG), to delineate AS reprogramming during GRS progression. The frequency of AS was sharply elevated in CG, with intron retention predominating. Extensive gains and losses of splice events indicate large-scale rewiring of the splice network. Overlapping differentially alternative spliced genes (DAGs) identified in both CG vs AG and CG vs BG contrasts were significantly enriched for RNA–spliceosome assembly and stress–response pathways, revealing a conserved post-transcriptional response associated with lesion formation. Integrative analysis of differentially expressed genes uncovered 671 loci under dual regulation; functional classification categorized these genes in receptor-like kinase signaling and chromatin-remodeling modules, underscoring the synergy between AS and transcriptional control. Moreover, the B subgenome disproportionately contributed stress-responsive transcripts in diseased tissue, suggesting an adaptive, subgenome-biased strategy. These findings demonstrate that dynamic AS remodeling and subgenome expression bias jointly orchestrate ginseng defense against GRS and provide a framework for breeding disease-resilient crops. Full article

Pancreatic cancer is one of the most lethal malignancies, in part due to its profound metabolic adaptability, which underlies drug resistance and therapeutic failure. This study explores the metabolic rewiring associated with resistance to treatment using a systems metabolomics approach. Exposure to the redox-disrupting agent erastin revealed key metabolic vulnerabilities but failed to produce lasting growth suppression. Combinatorial treatments with methotrexate or alpelisib significantly impaired proliferation and triggered marked metabolic shifts. Systems-level analyses identified serine metabolism as a central adaptive pathway in resilient cells. Metabolic tracing and gene expression profiling showed increased de novo serine biosynthesis and uptake, supporting redox homeostasis, biosynthetic activity, and epigenetic regulation. Notably, cells that resumed growth after drug withdrawal exhibited transcriptional reprogramming involving serine-driven pathways, along with elevated expression of genes linked to survival, proliferation, and migration. These findings establish serine metabolism as a functional biomarker of metabolic plasticity and adaptive resilience in pancreatic cancer, suggesting that targeting this adaptive axis may enhance therapeutic efficacy. Full article

Eukaryotic cells generate ATP primarily via oxidative and substrate-level phosphorylation. Despite the superior efficiency of oxidative phosphorylation, eukaryotic cells often use both pathways as aerobic glycolysis, even in the presence of oxygen. However, its role in cell survival remains poorly understood. Objectives: In this study, aerobic glycolysis was compared between the Warburg effect in breast cancer cells (MCF7) and the Crabtree effect in a laboratory strain of Saccharomyces cerevisiae (S288C). Methods: The metabolic adaptations of MCF7 and S288C cells were compared following treatment with electron transport chain inhibitors, including FCCP, antimycin A, and oligomycin. Results: MCF7 and S288C cells exhibited strikingly similar metabolic rewiring toward substrate-level phosphorylation upon inhibitor treatment, suggesting that mitochondrial oxidative phosphorylation and cytosolic substrate-level phosphorylation communicate through a common mechanism. Measurement of mitochondrial membrane potential (MMP) and ATP concentrations further indicated that cytosolic ATP was transported into the mitochondria under conditions of reduced electron transport chain activity. This ATP was likely utilized in the reverse mode of H⁺/ATPase to maintain MMP, which contributed to the avoidance of programmed cell death. Conclusions: These results suggest that the ATP supply to mitochondria plays a conserved role in aerobic glycolysis in yeast and mammalian cancer cells. This mechanism likely contributes to cell survival under conditions of fluctuating oxygen availability. Full article

Cancer is hallmarked by uncontrolled cell proliferation and enhanced cell survival, driven by a complex interplay of factors—including genetic and epigenetic changes—that disrupt metabolic and signaling pathways and impair organelle function. While the roles of mitochondria and the endoplasmic reticulum in cancer are widely recognized, emerging research is now drawing attention to the involvement of peroxisomes in tumor biology. Peroxisomes are essential for lipid metabolism, including fatty acid α- and β-oxidation, the synthesis of docosahexaenoic acid, bile acids, and ether lipids, as well as maintaining redox balance. Despite their critical functions, the role of peroxisomes in oncogenesis remains inadequately explored. Prostate cancer (PCa), the second most common cancer in men worldwide, exhibits a unique metabolic profile compared to other solid tumors. In contrast to the glycolysis-driven Warburg effect, primary PCa relies primarily on lipogenesis and oxidative phosphorylation. Peroxisomes are intricately involved in the metabolic adaptations of PCa, influencing both disease progression and therapy resistance. Key alterations in peroxisomal activity in PCa include the increased oxidation of branched-chain fatty acids, upregulation of α-methylacyl coenzyme A racemase (a prominent PCa biomarker), and downregulation of 1-alkyl-glycerone-3-phosphate synthase and catalase. This review critically examines the role of peroxisomes in PCa metabolism, progression, and therapeutic response, exploring their potential as biomarkers and targets for therapy. We also consider their relationship with androgen receptor signaling. A deeper understanding of peroxisome biology in PCa could pave the way for new therapies to improve patient outcomes. Full article

The increasing global demand for energy and the urgent need to mitigate climate change have driven the search for sustainable alternatives to fossil fuels, with biofuels emerging as a promising solution. However, the low yields and inefficiencies in biofuel production processes necessitate advanced strategies to enhance their commercial viability. Metabolic engineering has become a pivotal tool in optimizing microbial pathways to improve biofuel production, addressing these challenges through innovative genetic and synthetic biology approaches. This review highlights the role of metabolic engineering in enhancing biofuel production by focusing on microbial engineering for lignocellulosic biomass utilization, strategies to overcome inhibitor effects, and pathway optimization for biofuels like n-butanol and iso-butanol. It also explores the production of advanced biofuels from fatty acid and isoprenoid pathways, emphasizing the use of model organisms such as Escherichia coli and Saccharomyces cerevisiae. Key insights include the application of CRISPR/Cas9 and multiplex automated genome engineering for precise genetic modifications, as well as metabolic flux analysis to optimize pathway efficiency. Additionally, the review discusses synthetic biology methodologies to rewire metabolic networks and improve biofuel yields, providing a comprehensive overview of current advancements and their implications for industrial-scale production. Full article

Yeast genetic improvement is entering a transformative phase, driven by the integration of artificial intelligence (AI), big data analytics, and synthetic microbial communities with conventional methods such as sexual breeding and random mutagenesis. These advancements have substantially expanded the potential for innovative re-engineering of yeast, ranging from single-strain cultures to complex polymicrobial consortia. This review compares traditional genetic manipulation techniques with cutting-edge approaches, highlighting recent breakthroughs in their application to beer and wine fermentation. Among the innovative strategies, adaptive laboratory evolution (ALE) stands out as a non-GMO method capable of rewiring complex fitness-related phenotypes through iterative selection. In contrast, GMO-based synthetic biology approaches, including the most recent developments in CRISPR/Cas9 technologies, enable efficient and scalable genome editing, including multiplexed modifications. These innovations are expected to accelerate product development, reduce costs, and enhance the environmental sustainability of brewing and winemaking. However, despite their technological potential, GMO-based strategies continue to face significant regulatory and market challenges, which limit their widespread adoption in the fermentation industry. Full article

Circadian rhythms govern cellular metabolism, redox balance, and endocrine signaling in numerous tissues. However, chronic disturbance of these biological rhythms, mediated by modern lifestyle factors including shift work, sleep irregularity, and prolonged light exposure, has been increasingly associated with oxidative stress, metabolic dysregulation, and the pathogenesis of chronic diseases. This review discusses recent mechanistic advances that link circadian misalignment with tissue-specific metabolic reprogramming and impaired proteostasis, focusing on metabolic inflammation and associated pathologies. Emerging work reveals a close interdependence between the circadian clock and proteasome-mediated protein turnover and highlights this interplay’s importance in maintaining redox homeostasis. Furthermore, circadian modulation of the activity of the inflammasome complex is suggested to represent an important, but largely unexplored, risk factor in the pathobiology of both malignancy and metabolic syndrome. Recently, researchers have proposed them as novel endocrine regulators of systemic energy balance and inflammation, with a focus on their circadian regulation. In addition, the emerging domains of chrono-epigenetics and tissue-specific programming of the clock pathways may serve to usher in novel therapies through precision medicine. Moving ahead, circadian-based therapeutic approaches, including time-restricted feeding, chronopharmacology, and metabolic rewiring, have high potential for re-establishing physiological domain homeostasis linked to metabolic inflammation pathologies. Elucidating this reciprocal relationship between circadian biology and cellular stress pathways may one day facilitate the generation of precise interventions aiming to alleviate the health burden associated with circadian disruption. Full article