Search Results (2,126)

In oleaginous yeast submerged fermentation, dissolved oxygen (DO) regulates both metabolism and cell morphology. Under oxygen limitation, Trichosporon cutaneum transitions from yeast-form to hyphae-form; the yeast-form morphology is more suitable for lipid production. This study enhanced oxygen transfer via reactor engineering to maintain yeast morphology and improve lipid productivity. Three strategies were assessed: increased agitation/aeration, enriched air supply, and microporous ceramic membrane gas distributor (MCMGD). Fermentation kinetics were analyzed alongside computational fluid dynamics (CFD) simulations of volumetric mass transfer coefficient (k_La), gas holdup, bubble diameter, and flow fields. Conventional strategies only partially alleviated oxygen limitation (maximum 4.47 g/L lipid). Enriched air improved lipid content but induced early myceliation. The MCMGD (1.0 vvm, 150 rpm) shortened fermentation from 150 h to 60 h, achieving 12.06 g/L lipid (49.16% content)—a 2.16-fold lipid concentration increase. Mechanistically, it generated smaller bubbles (1.47 mm vs. 2.54 mm) and higher k_La (0.012 s⁻¹ vs. 0.0055 s⁻¹). CFD revealed improved axial flow, reduced dead zones, and uniform gas holdup, suppressing yeast-to-hyphae shift. By enhancing mass transfer under low shear, the MCMGD ensures adequate oxygenation, maintains productive morphology, and significantly improves lipid production—offering a promising strategy for industrial application. Full article

Increasing evidence suggests pancreatic cancer develops within a host–microbe ecosystem in which microbial communities across anatomical niches interact with tumour biology, immune regulation, metabolism, and therapeutic response. This review examines pancreatic cancer through the lens of humans as holobionts, integrating evidence from the oral, gut, biliary, and intratumoural microbiomes. Epidemiological and sequencing studies demonstrate consistent microbial alterations across these niches in pancreatic cancer, including oral dysbiosis associated with periodontal pathogens, gut microbial shifts toward pro-inflammatory taxa, disease-specific biliary microbial signatures, and the presence of distinct intratumoural microbial communities. Mechanistic studies indicate that intestinal barrier disruption, microbial translocation, immune and metabolite signalling can influence tumour immune architecture, macrophage polarisation, T-cell infiltration, oncogenic signalling pathways, and chemotherapeutic metabolism, particularly inactivation by tumour-associated bacteria. Microbiome-driven shifts in immunometabolism can reprogramme immune-cell metabolic pathways, impairing effective T-cell activation, promoting tumour-supportive macrophage phenotypes. Emerging therapeutic strategies aim to modulate the microbiome–tumour axis, including dietary interventions, probiotics and immunonutrition, faecal microbiota transplantation, engineered microbial therapies, and microbiome-informed antibiotic strategies. While pre-clinical findings are compelling and early-phase clinical studies suggest feasibility, most evidence remains associative and heterogeneous across cohorts and methodologies. Understanding pancreatic cancer as a multi-site ecological system may help explain inter-patient variability in disease progression and treatment response. This could usher in a new era for therapeutic manipulation where future progress will depend on longitudinal, multi-omic, and interventional studies to determine whether microbiome-targeted strategies can produce clinically meaningful improvements in pancreatic cancer outcomes. Full article

Genetically modified (GM) lactic acid bacteria (LAB) are gaining attention as tools for innovation in the food sector, health applications, and industrial processes. LAB have long been used safely due to their GRAS/QPS status, making them suitable for improving fermentation and synthesizing specific and beneficial metabolites. Advances in genomics and gene editing have significantly expanded the available tools, ranging from classical mutagenesis to site-specific recombination, homologous recombination in non-coding regions, CRISPR-based systems, and food-grade chromosomal integration. These approaches enable the insertion of desired genes and the development of engineered strains with tailored functionalities. GM-LAB are also being studied as live delivery systems for therapeutic molecules, including cytokines, hormones, antimicrobial peptides, and vaccine antigens. Engineered strains of Lactococcus lactis and Lactobacillus spp. have yielded promising outcomes in applications such as mucosal immunization, modulation of inflammatory and metabolic responses, and inhibition of pathogenic microorganisms, including multidrug-resistant bacteria. From an industrial perspective, several studies highlight their potential for cost-effective recombinant protein production and the synthesis of high-value metabolites through fermentation. However, within the European Union, their use is subject to stringent regulatory oversight, requiring comprehensive molecular and environmental risk assessments, careful evaluation of horizontal gene transfer, and a preference for markerless chromosomal integrations. Despite these constraints, GM-LAB offer significant potential to improve food quality, sustainability, and human health. Full article

Translating preclinical findings into effective clinical cancer immunotherapies remains a major challenge, mainly because conventional in vitro and animal models often fail to capture the complexity, dynamics, and species-specific features of human immune responses. Organ-on-a-chip (OoC) technologies that combine engineered tissue architectures with precisely controlled microfluidic transport provide human-relevant microphysiological platforms for mechanistic studies of immune–tumor interactions and evaluation of therapeutic efficacy and immunotoxicity under defined microenvironmental conditions. However, immune responses involve time-dependent and interconnected processes, including immune cell trafficking, cytokine programs, metabolic shifts, and cytolysis, that are not adequately resolved by static or endpoint assays. Engineering immune-competent OoC systems therefore requires coordinated design of platform architectures, immune cell incorporation strategies, and integrated measurement workflows capable of capturing dynamic and state-dependent responses. In this review, we summarize engineering strategies for building immune-competent OoC platforms for cancer immunotherapy, focusing on platform architectures, immune cell incorporation methods, and fit-for-purpose assay workflows. Emphasis is placed on embedded sensing modalities (e.g., cytokine, oxygen, and impedance readouts) that provide valuable kinetic and state-variable data. Finally, we discuss key translational challenges, including reproducibility, standardization, and benchmarking, and outline near-term priorities to accelerate the adoption of immune-competent OoC systems in immunotherapy research and development. Full article

Microbial lipids have emerged as a promising sustainable alternative to plant- and petroleum-derived oils, with applications spanning biofuels, oleochemicals, nutraceuticals, and specialty materials. Significant advances in metabolic engineering and strain development have increased lipid production capacity across diverse microorganisms. Numerous reviews have summarized the biological and metabolic advances in this field, highlighting significant progress in metabolic engineering and strain development that has increased lipid production capacity across diverse microorganisms. However, translating these gains into economically viable industrial processes remains a major challenge. This review examines process engineering strategies for microbial lipid production across the full bioprocessing pipeline, from laboratory-scale strain evolution to industrial-scale operation. We discuss recent developments in adaptive laboratory evolution, systems-guided strain optimization, and robustness engineering, emphasizing their implications for process performance. Key bioprocess parameters—including substrate selection, nutrient limitation strategies, reactor design, oxygen transfer, and process control—are critically evaluated for their impact on lipid yield, productivity, and scalability. Furthermore, downstream processing considerations and techno-economic constraints are analyzed in the context of large-scale implementation. By integrating strain-level innovations with process engineering principles, this review highlights current bottlenecks, emerging solutions, and future directions for achieving efficient and scalable microbial lipid biomanufacturing. Full article

Probiotics, live microorganisms that confer health benefits when administered in adequate amounts, are increasingly recognized as modulators of interconnected microbiome–host networks that extend beyond gastrointestinal function. This review synthesizes evidence on classical probiotic roles in maintaining gut homeostasis, immune regulation, and infection prevention, while integrating emerging systemic effects across the gut–brain, gut–skin, gut–oral, and metabolic axes. Rather than presenting isolated outcomes, we adopt a systems-level framework that links probiotic actions to shared mechanisms, including microbial metabolite signaling (e.g., SCFAs), competitive exclusion of pathobionts, barrier reinforcement, and immune–neuroendocrine pathway modulation. We further discuss translational advances that enable rational probiotic design, including targeted delivery platforms (encapsulation and protective matrices), engineered/next-generation strains, and postbiotic-inspired strategies, alongside sustainability considerations and regulatory/labeling challenges. Finally, we outline future directions emphasizing precision microbiome-centered interventions, synthetic biology, and AI-assisted multi-omics analysis to support strain- and context-specific probiotic strategies. Collectively, this review provides an integrated, systems-oriented synthesis to guide future research and accelerate safe clinical and industrial applications of probiotics. Full article

The progression of chronic bone diseases is intricately linked to dysregulated macrophage polarisation. However, a comprehensive understanding of the complex interplay between macrophage polarisation and metabolic reprogramming in the context of bone disorders remains elusive. Thus, this review conducted a systematic search of major databases, including PubMed, using combinations of keywords such as “macrophage polarisation,” “immunometabolism,” “metabolic reprogramming,” and “chronic bone diseases” (including “osteoporosis,” “osteoarthritis,” and “periodontitis”). Inclusion criteria prioritised original research published within the last five years to capture recent advances. Diverging from previous reviews constrained by the classical M1/M2 dichotomy, this article aims to delineate the heterogeneity and functional plasticity of macrophages within the bone microenvironment, emphasising metabolic reprogramming as a central mechanism driving the dynamic behaviour of macrophages across various skeletal pathologies. Furthermore, this review highlights the pivotal roles of specific metabolites—such as succinate, itaconate, and citrate—within the osseous microenvironment, underscoring their influence on macrophage phenotypic transitions and the regulation of bone metabolic homeostasis. Finally, this article envisages innovative therapeutic strategies targeting the “metabolism–immunity axis,” encompassing the design of nano-delivery systems to modulate macrophage metabolism, the utilisation of engineered extracellular vesicles, the development of immunometabolism-modulating biomaterials, and the exploration of naturally occurring bioactive molecules. Based on these findings, the present work proposes the “metabolism–immunity–skeleton” axis as a theoretical framework, thereby establishing a robust foundation for the development of precision metabolic immunotherapy tailored to a spectrum of chronic bone diseases. Full article

Vascularization remains a central challenge in thick tissue engineering. Building on our prior demonstration that carbonate buffer concentration governs multi-channel collagen gel (MCCG) architecture and perfusion culture performance, this study aimed to establish non-contact, orthogonal control of pore size and density in riboflavin-sensitized Type I collagen hydrogels via UV irradiation intensity and preparation temperature. UV intensity was modulated by varying the source-to-sample distance (25–52 mm); preparation temperature was set at 5, 25, or 40 °C; gelation kinetics were quantified using a vial-tilt assay. Pore area fraction ranged from 0.9% to 8.6% and Young’s modulus from 16 to 49 kPa depending on UV dose. Higher preparation temperatures accelerated gelation and produced smaller, more densely distributed pores, consistent with kinetically arrested phase separation. NIH/3T3 fibroblasts cultured on intermediate- and low-intensity UV scaffolds achieved >80% confluency by Day 7, with three-dimensional tissue-like organization and directionally aligned cellular bundles within large pores; cell metabolic activity, assessed by CCK-8 assay, remained consistently high throughout the culture period. These results demonstrate that UV irradiation intensity and preparation temperature are independently tunable, non-contact parameters for reproducible fabrication of collagen scaffolds with tunable vascular-like pore networks, complementing and extending the chemical (buffer concentration) design space of MCCG-based perfusion culture systems. Full article

Producing single-cell protein (SCP) from syngas-derived ethanol and acetate offers a sustainable solution to global protein shortages, yet microbial utilization mechanisms for these mixtures remain underexplored. This study establishes a systematic bioconversion strategy using Cyberlindnera jadinii TU389. To mitigate acetaldehyde accumulation during ethanol metabolism, we engineered the strain TU546 to overexpress acylating acetaldehyde dehydrogenase (ADA6). TU546 achieved a maximum biomass of 46.7 g/L and a protein yield of 21.69 g/L, representing enhancements of 28.16% and 23.02% over the wild-type, respectively. Transcriptomic analysis revealed extensive metabolic reprogramming. In the C2 assimilation pathway, upregulated aldehyde dehydrogenase and acetyl-CoA Synthetase 1 accelerated acetate conversion to acetyl-CoA, while downregulated pyruvate decarboxylase and alcohol dehydrogenase minimized carbon flux loss. The upregulation of tricarboxylic acid cycle enzymes, the glyoxylate shunt, and acyl-coA oxidase improved carbon skeleton retention. Moreover, the upregulation of transaminases and N-acetylglutamate synthase, synergized with intensified cell proliferation signaling, redirected amino acid metabolism toward a synthesis-enhanced and degradation-controlled paradigm. This synergistic regulatory network drives the high-efficiency bioconversion of ethanol and acetate into SCP, establishing a molecular mechanistic foundation for the valorization of syngas-derived C2 substrates in biological macromolecule production. Full article

The broad substrate specificity of enzymes, while advantageous for catalytic diversity, often leads to undesired side reactions and reduced product yields in engineered metabolic pathways. To address this challenge, we developed a programmable protein scaffold based on a self-assembled γPFD-SpyCatcher hydrogel for the in vivo co-immobilization of SpyTag-cyclized cascade enzymes, enabling the co-immobilization of cascade enzymes in a spatially organized manner. Enzymes with broad substrate specificities were linearly fused with SpyTags, facilitating their spatial organization on the nanoscaffold within engineered E. coli to ensure directed catalytic flux. Using this strategy, the yields of pinene and caffeoyl-CoA were enhanced by 5.8-fold (reaching 94.5 mg/L) and 2.4-fold (reaching 78.6 mg/L), respectively, compared to free enzyme systems. This work establishes an effective approach to mitigate the limitations posed by broad enzyme specificity and demonstrates its potential for applications in synthetic biology and industrial biotechnology. Full article

Cancer therapies are increasingly reliant on immunotherapeutic interventions; however, the persistent emergence of primary, adaptive, and acquired resistance severely limits durable clinical efficacy. Circular RNAs (circRNAs), distinguished by their extreme structural stability and covalently closed loops, have recently been established as potent orchestrators of this immune evasion. This review systematically synthesizes current advancements detailing how circRNAs undermine anti-tumor immunity across diverse malignancies. Specifically, we delineate their critical roles in post-transcriptionally upregulating immune checkpoint molecules (e.g., PD-L1), mediating intercellular immunosuppression via exosomal transfer, and metabolically reprogramming the tumor microenvironment to drive CD8+ T-cell exhaustion and macrophage polarization. Ultimately, we conclude that translating these molecular insights into clinical practice is paramount. Beyond serving as predictive biomarkers, engineering circRNA-targeted therapies and exploiting tumor-specific circRNAs to develop novel anti-tumor vaccines represent essential, paradigm-shifting strategies to definitively overcome immune checkpoint inhibitor resistance. Full article

Background/Objectives: The growing prevalence of obesity necessitates innovative gut-targeted material strategies to modulate diet-associated metabolic dysfunction. This study investigates a spray-dried konjac glucomannan–montmorillonite (KGM-MMT) hybrid designed to integrate fermentable polysaccharide properties with luminal lipid-adsorptive clay functions within a single micro-engineered formulation. Methods: In HFD-fed mice treated for 42 days with 2% w/w KGM-MMT, cumulative body weight gain was attenuated by 7.6%, with an AUC of 5094 ± 52.95, compared to 5513 ± 81.35 in HFD controls (p < 0.0001). Results: Serum IL-6 concentrations were reduced by 97% (p = 0.0002), while blood glucose decreased by 46% (p < 0.0001); these effects were greater than those observed with MMT (24%, p = 0.0271) and KGM (16%, ns). Gut microbiota profiling demonstrated a significant 6.2-log₂-fold increase in Lactobacillaceae (p = 0.023) and a 2.4-log₂-fold increase in Enterococcaceae (p = 0.015) following KGM-MMT treatment. Functional shifts inferred from 16S rRNA gene-based prediction indicated a 1.9-fold increase in short-chain fatty acid-related pathways and a 5.4-fold increase in bile acid deconjugation pathways. Conclusions: Although the KGM-MMT hybrid did not consistently outperform its individual components across all endpoints, it consolidated complementary KGM- and MMT-associated effects within a single dosage form. These findings support spray-dried KGM-MMT as a gut-targeted biomaterial strategy that integrates multiple luminal and microbiota-associated functions within a single formulation. Future studies should define dose–response relationships, validate microbiota-derived functional predictions using higher-resolution approaches, and assess durability and safety under longer-term exposure. Full article

Docosahexaenoic acid (DHA) is an essential ω-3 polyunsaturated fatty acid (PUFA) with high nutritional and pharmaceutical value. The marine protist Aurantiochytrium is a promising industrial DHA producer; however, its DHA biosynthesis via the PUFA synthase pathway co-produces ω-6 docosapentaenoic acid (DPA), limiting DHA purity. Here, we introduced an ω-3 desaturase from Phytophthora infestans (Pin-O3D) into Aurantiochytrium sp. SD116. Functional validation in an Escherichia coli system co-expressing the native PUFA synthase confirmed that Pin-O3D converts DPA to DHA, shifting the DHA/DPA ratio from 1:1 to 2:1. Pin-O3D was then integrated into the fatty acid synthase (FAS) locus, simultaneously attenuating FAS activity and enabling heterologous gene expression. The engineered strain ΔFAS-Pin-O3D exhibited significantly (p < 0.0001 in t-test) increased DHA content (55.2% of total fatty acids) and DHA/DPA ratio (5.91) in shake flasks, with no negative impact on biomass or lipid accumulation. Fed-batch fermentation confirmed the scalability of this strategy, achieving a >20% increase in DHA/DPA ratio. This study demonstrates that combining heterologous ω-3 desaturase expression with FAS attenuation is an effective approach for optimizing PUFA profiles in Aurantiochytrium. Full article

Major depressive disorder (MDD) affects over 330 million people globally, yet up to 30% of patients fail initial pharmacotherapy due to genetic variability in drug metabolism. This narrative review synthesizes evidence on pharmacogenomic (PGx) guided approaches for MDD, emphasizing their integration with POC diagnostics and engineering solutions. Approximately 40–50% of patients carry actionable variants in CYP2C19 or CYP2D6, which govern the metabolism of selective serotonin reuptake inhibitors. Landmark trials (GUIDED, PRIME Care, GAPP-MDD) and meta-analyses demonstrate that PGx-informed prescribing modestly but significantly improves remission and response rates, particularly in treatment-resistant depression. Established guidelines from CPIC and the Dutch Pharmacogenetics Working Group provide actionable recommendations for CYP2D6 and CYP2C19 phenotypes. Emerging POC platforms, including Genomadix Cube and Genedrive, now deliver CYP2C19 results within one hour, supporting rapid clinical decisions. However, psychiatric-specific implementation data remain limited compared to cardiology; current POC devices lack multi-gene capabilities, and most studies underrepresent diverse populations. Persistent barriers include variable reimbursement, limited clinician education, and fragmented electronic health record integration. Future directions include pre-emptive genotyping, expanded multi-gene panels, and embedded clinical decision support. With continued engineering innovation and rigorous validation, PGx-guided care holds promise for reducing the trial-and-error burden and advancing precision psychiatry. Full article

Plant metabolism is essential for coordinating growth, development, and defense under changing environmental conditions. Plants continuously adjust their metabolic pathways to balance resource allocation between growth and immune responses. Under stress, metabolic reprogramming redirects energy and resources toward the production of defense compounds and activation of immune signaling pathways. These changes involve complex interactions among primary metabolism, specialised metabolites, and regulatory networks, including calcium signaling, reactive oxygen species, and phytohormones. Advances in metabolomics and multi-omics technologies have improved understanding of the metabolic control of plant immunity; however, knowledge remains fragmented, and an integrated framework linking metabolism, development, and defense is still emerging. This review examines plant immunometabolism by highlighting the dynamic relationships between metabolic networks and immune functions during development and stress. It discusses pathways that influence growth, stress-induced metabolic shifts linked to defense, and how signaling interacts with metabolism. Progress in metabolomics, transcriptomics, proteomics, and computational modeling that supports systems-level analysis of plant metabolism is also summarized. In addition, potential applications in agriculture and biotechnology, including metabolic engineering, genome editing, and metabolomics-based breeding, are considered in relation to crop resilience. By integrating metabolism, signaling, and systems biology, this review provides a broad perspective on how metabolic reprogramming shapes the growth–defense trade-off in plants and outlines future directions for developing climate-resilient crops. Full article