Search Results (774)

Peptide therapeutics occupy a unique position between small organic compounds and large protein biomolecules, combining high specificity, strong pharmacological efficacy, and favourable safety profiles. Consequently, they have emerged as important therapeutic agents for a wide range of diseases, including metabolic and oncological disorders. However, oral administration of peptide drugs remains a major challenge due to extensive enzymatic degradation, low intestinal permeability, mucus entrapment, and presystemic metabolism within the gastrointestinal tract. This review provides a comprehensive overview of contemporary strategies for improving oral peptide delivery, with special emphasis on emerging pharmaceutical formulation technologies, bioinspired delivery systems and ingestible device-assisted approaches. A qualitative literature search was conducted using major scientific databases and included relevant publications available up to May 2026. The analysis identified the main barriers responsible for low oral bioavailability of peptide drugs, as well as promising approaches to overcoming these obstacles, including peptide modification, enzyme inhibition, permeation enhancement, mucolytic strategies, and advanced carrier systems. Special attention is given to multifunctional carrier systems, ingestible medical devices and bile acid-inspired technologies as emerging directions in oral peptide delivery. The convergence of pharmaceutical sciences, bioinspired formulation strategies and biomedical engineering is expected to accelerate the clinical translation of oral peptide formulations and enable their therapeutic potential to be fully exploited. Full article

Tropane alkaloids (TA) constitute a class of plant specialized metabolites with important pharmaceutical applications, including the anticholinergic agents hyoscyamine and scopolamine and the local anesthetic cocaine. Over the past decade, advances in genomics, structural biology, and synthetic biology have substantially revised our understanding of TA biosynthesis, leading to the identification of numerous key biosynthetic enzymes and evolutionary mechanisms. This review comprehensively summarizes current knowledge of TA biosynthesis from precursor formation to structurally diverse end products. We describe the pathway from putrescine to tropinone, the stereoselective metabolic branching mediated by Tropinone Reductases, and the downstream biosynthesis of medicinal tropane alkaloids, calystegines, and cocaine. Particular emphasis is placed on recent discoveries concerning catalytic mechanisms, structural determinants of substrate specificity, metabolic compartmentalization, and the convergent evolution of TA biosynthesis in Solanaceae and Erythroxylaceae. We further integrate advances in genomics, evolutionary biology, and metabolic engineering to highlight emerging strategies for microbial production and pathway redesign. By providing a comprehensive synthesis of recent progress and critical perspectives on unresolved questions, this review offers an updated framework for understanding TA biosynthesis and supports future research in plant specialized metabolism, synthetic biology, and natural product engineering. Full article

Nicotinamide adenine dinucleotide (NAD⁺) is a fundamental metabolic cofactor and signaling molecule that supports redox reactions, DNA repair, chromatin regulation, stress adaptation, inflammation, and neuronal maintenance. Age-associated NAD⁺ decline has been implicated in brain aging and neurodegenerative disorders, but the causal node and limiting compartment differ across tissues and disease states. Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT-1) catalyzes the final step in NAD⁺ biosynthesis and represents the major nuclear isoform of the mammalian NMNAT family. Direct human genetic evidence establishes NMNAT-1 as a causal gene in inherited retinal degeneration, whereas evidence linking endogenous NMNAT-1 to broader brain aging or sporadic neurodegeneration is mainly convergent preclinical, preliminary, or indirect. Beyond NAD⁺ synthesis, biochemical and Drosophila studies suggest possible chaperone-like and proteostasis-supporting functions, but a separable NAD⁺-independent function of endogenous mammalian NMNAT-1 has not yet been established in vivo. Here, we review the molecular structure, localization, and regulation of NMNAT-1, emphasizing calibrated distinctions among catalytic nuclear NAD⁺ supply, engineered axonal protection, pathway-adjacent NAD⁺ interventions, and putative non-catalytic protection. We further discuss how NMNAT-1 dysfunction may contribute to aging-associated genomic instability, neuroinflammation, synaptic impairment, retinal degeneration, selected neurodegenerative models, and glioma biology. Finally, we evaluate therapeutic strategies targeting NMNAT-1 and NAD⁺ pathways, noting that no human trial has yet established efficacy for an NMNAT-1-directed neurological therapy. A compartment-aware and evidence-stratified view is therefore essential for translating NMNAT-1 biology into interventions for age-related neural disease. Full article

Polyphosphate (PolyP) is an inorganic polymer composed of orthophosphate units linked by high-energy phosphate anhydride bonds, widely found in various organisms from bacteria to mammals. In recent years, PolyP has attracted widespread attention in the field of bone tissue engineering due to its unique biological characteristics, possessing both osteoinductive activity and metabolic energy supply functions. This article systematically reviews the molecular structure, physicochemical properties, and multiple mechanisms by which PolyP promotes osteogenic differentiation, as well as biomaterial design strategies based on PolyP. PolyP can synergistically promote osteogenic differentiation through multiple mechanisms, including by acting as a phosphate donor, providing metabolic energy, regulating signaling pathways such as Wnt/β-catenin, and modulating the osteoprotegerin/receptor activator of nuclear factor κB ligand (OPG/RANKL) balance. In terms of material design, PolyP can form nano/microparticles with metal ions such as Ca²⁺, Sr²⁺, and Mg²⁺ and can also be compounded with polymers to construct various forms such as hydrogels, bone cement, and three-dimensional (3D)-printed scaffolds. Preclinical studies have shown that PolyP-incorporated materials exhibit excellent osteogenic performance and biocompatibility in bone defect repair, and preliminary clinical studies have also confirmed its feasibility. This article aims to provide a comprehensive overview of the current applications of PolyP-incorporated materials and delineate future directions, challenges, and necessary pathways for their clinical translation. Full article

During high-concentration ethanol fermentation, Saccharomyces cerevisiae often faces multiple stresses, such as high osmotic pressure, ethanol toxicity, and nutrient limitation. These factors collectively limited the production of ethanol. To identify novel targets related to fermentation performance, we employed SHPERM- bCGHR strategy (a marker free allele replacement strategy based on comparative genomics and homologous recombination). We replaced the endogenous PHO4 of the high-producing strain MF01 with the PHO4 allele from MC15, thereby constructing a novel engineered strain MF01-PHO4. Under low-phosphate conditions, compared with the wildtype strain, the PHO5/11/12 genes and ribosomal protein genes showed significant upregulation in MF01-PHO4. These changes were associated with enhanced phosphorus uptake and protein synthesis. Under high phosphate conditions, the PHO4 expression and glycolytic enzyme gene expression in MF01-PHO4 were both lower than MF01, indicating that the substitution of the PHO4 allele may be associated with the coordinated changes in phosphate signal-mediated carbon phosphorus metabolism. This study identifies PHO4 as a promising candidate target for improving high concentration ethanol fermentation efficiency. These findings provide a framework to understand the phosphate-dependent regulatory effects of PHO4 allelic variation and offer a transferable strategy for strain improvement. Full article

Background/Objectives: The aim of the present study was to investigate the mechanisms in Parkinson’s disease (PD), a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons, aggregation of α-synuclein, mitochondrial dysfunction, oxidative stress, neuroinflammation, gut dysbiosis, and blood–brain barrier (BBB) impairment. Although there are several approved therapies that have been developed, their aqueous solubility, oral bioavailability, first-pass metabolism, and inability to penetrate the BBB make them less effective over time. This review is intended to critically analyze the potential of self-nanoemulsifying drug delivery systems (SNEDDSs) as a pathogenesis-related approach to enhance the delivery and therapeutic activity of repurposed drugs and conventional drugs for PD. Methods: A comprehensive literature search was conducted to address the pathogenic mechanisms of PD, the deficiencies of current pharmacotherapy, recent developments in SNEDDS formulation strategies and their application in improving oral bioavailability, lymphatic transport, BBB penetration and targeted brain delivery. A special focus was dedicated to drug repurposing, functionalized SNEDDSs, PEGylation, and gut–brain axis modulation. Results: SNEDDSs significantly enhance the water solubility, stability, intestinal absorption and systemic exposure of poorly water-soluble therapeutic agents and, to a certain extent, lymphatic uptake to avoid first-pass metabolism. These systems include improved brain delivery, decreased pharmacokinetic variability, and prolonged drug levels within the therapeutic range. Moreover, SNEDDSs can be used to deliver multiple molecules that are found to be neuroprotective, antioxidant, anti-inflammatory and probiotic, all at once, which can act on multiple pathogenic mechanisms associated with PD. Functionalized and PEGylated SNEDDSs add further to formulation stability, extend systemic circulation and increase efficiency of brain targeting. Conclusions: SNEDDSs are a promising translational nanomedicine platform for enhancing the effectiveness of conventional and repurposed therapeutics in PD, which address key pharmacokinetic and biological challenges. The next generation of oral therapies with targeted surface engineering, precision drug repurposing and clinical validation will be expected to bring about a faster advancement of drugs that can alter the course of disease rather than giving only symptomatic relief. Full article

The liver is an immunologically distinctive organ. Portal blood continuously delivers gut-derived antigens and microbial products, requiring hepatic immunity to balance surveillance with restraint. In hepatocellular carcinoma (HCC), this physiology is commonly overlaid by chronic injury, inflammation, and fibrosis, so the background liver forms part of the disease context in which the tumor microenvironment (TME) develops. This review synthesizes how cellular architecture, tumor-intrinsic programs, and structural, metabolic, and microbial conditions interact to shape immune evasion and heterogeneity. HCC provides the principal evidence base, with intrahepatic cholangiocarcinoma (iCCA) used as a structured, biologically distinct comparator. We organize therapies by the microenvironmental barriers they are intended to modify and distinguish established clinical efficacy from evidence that the proposed mechanisms mediate treatment benefit. Single-cell and spatial studies have resolved cellular states and spatial arrangements, including onco-fetal endothelial–myeloid neighborhoods and a macrophage–fibroblast boundary band separating lymphocyte-rich stroma from malignant tissue. These patterns operate within fibrotic and metabolically altered tissue and vary by etiology, spatial context, and tumor type. Vascular endothelial growth factor blockade with immune checkpoint inhibition and dual checkpoint blockade are established first-line options in advanced HCC. Chemo-immunotherapy is established in biliary tract cancer, and IDH1 inhibition has established efficacy in IDH1-mutant cholangiocarcinoma. Myeloid- and stroma-directed strategies, natural-product approaches, and engineered-cell therapies remain preclinical or early clinical. None of the pivotal trials tested whether the proposed microenvironmental mechanism mediated treatment benefit. The liver TME informs treatment selection without yet determining it. Full article

Medicinal plants remain one of the most important sources of therapeutically relevant compounds for pharmaceutical, nutraceutical, and biotechnological applications. However, the naturally low abundance of many specialized metabolites, considerable phytochemical variability, and increasing environmental pressures continue to limit the sustainable exploitation of plant-derived bioactive compounds. This review summarizes current strategies aimed at identifying, understanding, and enhancing the production of medicinally valuable metabolites while highlighting both biological limitations and emerging technological opportunities. Particular attention is given to the interplay between primary and secondary metabolism and its role in determining biosynthetic efficiency in both natural and engineered systems. Beyond discussing established methodologies, this review adopts a broader perspective by incorporating less frequently addressed aspects, including the influence of climate change on metabolite production, the application of bioinformatics-supported approaches to improve bioprospecting efficiency, and the growing role of nanoparticles as elicitors in plant biotechnology. These topics are considered alongside advances in tissue culture technologies, metabolic engineering, molecular approaches, and systems-level analyses aimed at improving metabolite yield and production stability. Current evidence suggests that no single technological framework is sufficient to address the complexity of medicinal plant metabolism. Hence, rather than presenting individual technologies as isolated solutions to specific biosynthetic bottlenecks, this review emphasizes that medicinal plant metabolism should be considered a highly interconnected system in which environmental, molecular, and physiological factors collectively determine production outcomes. Full article

With the increasing environmental concerns about carbon dioxide emissions and the pressing demand for sustainable resources, photosynthetic microorganisms have gained considerable attention as alternative platforms for the environmentally friendly production of fuels and chemicals. These organisms function as green cell factories capable of directly converting carbon dioxide into organic carbon metabolites using solar energy, offering a promising platform for more sustainable biomanufacturing. Among these organisms, cyanobacteria, and particularly Synechocystis sp. PCC 6803, have emerged as particularly attractive hosts due to their relatively simple cellular organization, efficient photosynthetic metabolism, and amenability to genetic manipulation. In addition to rational metabolic engineering approaches, Adaptive Laboratory Evolution (ALE) has recently been proposed as a powerful strategy to improve Synechocystis strain robustness, enhance tolerance to environmental and metabolic stresses, and optimize cellular performance under specific growth conditions. By selecting beneficial spontaneous mutations over successive generations, ALE could complement genetic engineering strategies and further expand the potential of cyanobacterial platforms for efficient and sustainable bioproduction. Full article

Plant diseases impose major constraints on global crop productivity and pose a major threat to food security. Here, we review transcription factors (TFs) as central orchestrators of plant defense, consolidating recent advances in how these regulators connect pathogen perception to immune signaling, transcriptional reprogramming, and durable defense responses. Initially, we combined a literature-based synthesis with a natural language processing (NLP) analysis of 1647 PubMed abstracts published between 2021 and 2026 to map dominant and underexplored TF families associated with plant immunity. WRKY, MYB, AP2/ERF, bHLH/MYC, and NAC dominated the recent literature, whereas families such as NF-Y, Trihelix, PLATZ, TCP, and GRAS represent emerging regulatory actors. Across these and other families, TFs integrate pattern- and effector-triggered immunity, hormone crosstalk, chromatin dynamics, non-coding RNA regulation, post-translational modifications, and metabolic remodeling, in addition to cell-type-specific expression. Further evidence indicates that pathogens frequently manipulate TFs to weaken host defense, underscoring their central position in plant molecular physiology and plant-pathogen coevolution. The data emphasize that TF function is context-dependent and influenced by multilayered regulation, cell type, pathogen lifestyle, and host genetic background. This review provides a framework for understanding TFs in plant immune control and highlights TF-centered strategies for engineering durable crop resistance, along with future challenges. Full article

With the ever-growing population and increasing demand for food, cultivated meat (CM) represents a potentially sustainable alternative source of protein. However, one of the critical challenges is ensuring that the nutritional value of CM is comparable to that of conventional meat. In light of this, this scoping review aimed to systematically map the existing evidence from in vitro studies and identify potential nutritional fortification methods for CM. Literature searches were conducted in PubMed, Embase, and Web of Science from inception to December 2025, supplemented by a hand search in January 2026. Studies were included if they were in vitro studies related to cultivated food that applied a fortification strategy or treatment to improve the nutritional value or food functionality and reported the relevant outcomes. Extracted data (e.g., fortification methods, cell lines, study results) were synthesized descriptively. Seven studies were eligible for inclusion. Three fortification strategies were identified, including metabolic engineering, product reformulation, and nutrient-enriched cell culture medium. Reported outcomes varied among the included studies and included changes in nutritional value, food functionality, and cellular functionality of CM. However, most studies used cell models that are primarily intended for research purposes rather than food production or human consumption, which may limit their relevance to commercial CM products. In conclusion, this review identified preliminary fortification approaches that may modify the nutritional value, food functionality, or cellular functionality of CM. However, further investigation is needed to determine their effects on the nutritional composition of the resulting cell biomass or final CM product. Full article

The growing demand for sustainable and nutritionally optimized protein sources has positioned edible insects as promising platforms for next-generation food and feed systems. Although insect composition varies with diet, the deliberate engineering of their nutritional profiles through controlled dietary and microbiome modulation remains insufficiently characterized. This review proposes an integrative framework in which edible insects are conceptualized as programmable biological systems whose biochemical composition can be tailored through diet–microbiome interactions. Current evidence is critically synthesized to elucidate how dietary inputs, including agro-industrial by-products and algal biomass, reshape gut microbial communities and metabolic pathways in key species such as Hermetia illucens, Tenebrio molitor, and Acheta domesticus. Emphasis is placed on engineering lipid metabolism and fatty acid composition because of their relevance to human nutrition, animal nutrition, and the development of functional food and feed products. By integrating insights from insect physiology, microbiology, and nutritional biochemistry, this work outlines strategies for precision feeding and microbiome-guided interventions aimed at optimizing insect-derived biomass. Key knowledge gaps and technical limitations are also identified, highlighting the need to transition from empirical approaches toward predictive, systems-based nutritional engineering. Collectively, this review highlights the transition from empirical feeding strategies toward predictive, systems-based approaches for designing customized insect biomass within sustainable circular bioeconomy frameworks. Full article

Biotic stresses (pest feeding, pathogenic fungal/bacterial/viral infection) and diverse abiotic stresses (extreme temperature, drought, waterlogging, saline–alkali soil, heavy metal pollution, nutrient deficiency, UV-B, ozone) severely restrict crop growth and global agricultural yield. Lipids act as core membrane structural constituents and vital secondary signaling messengers, executing multi-layered adaptive balancing functions during cell-type interactive stress acclimation, rather than uniform whole-plant lipid responses. They sustain membrane structural integrity across distinct cell populations, serve as synthetic precursors of bioactive signaling molecules, and trigger cascaded transcriptional and metabolic reprogramming upon environmental stimuli to rebalance physiological status among different cell types. This review systematically summarizes cell-type interactive lipid-mediated plant defense and acclimation balance mechanisms across biotic and abiotic stress contexts. We elaborate the biological functions of fatty acids, phospholipids, galactolipids, sphingolipids and their derivatives (jasmonate, salicylic acid, phosphatidic acid, oxylipin) in stress signal transduction and antioxidant defense and strictly distinguish two categories of lipid changes under all stress types: active adaptive lipid remodeling and passive stress-induced lipid oxidative damage. Key contents include stress-triggered cell-type-specific membrane lipid remodeling, the hierarchical transcriptional regulatory network mediated by WRI1, LEC1, PHR, MADS and other transcription factors governing oil metabolism, as well as crosstalk between lipid metabolism and compartmentalized reactive oxygen species (reactive oxygen species (ROS)) signaling. We further compare conserved lipid-regulatory modules and species-specific divergent responses across model plants and economic oilseed crops, integrating state-of-the-art targeted/untargeted lipidomics, single-cell spatial lipidomics and multi-omics joint breeding strategies to improve multi-stress tolerance in oilseed crops. By consolidating global research progress up to 2025, including the two latest 2026 cross-species meta-analysis reviews, this review provides systematic theoretical support and operable multi-level technical frameworks for genetic engineering targeting conserved lipid pathways to breed stress-resilient high-oil crop germplasm, and highlights reliable lipid stress biomarker screening as a promising translational research direction. Full article

Marine macroalgae represent abundant, renewable reservoirs of structurally unique bioactive compounds, such as sulfated polysaccharides, phlorotannins, and carotenoids, with immense potential for sustainable functional foods. However, their industrial exploitation is severely bottlenecked by complex, repeat-rich genomes, recalcitrant genetic transformation tools, and environmental cultivation variability. Synthesizing evidence from 180 high-quality studies spanning from 1961 to 2026, this review provides a comprehensive synthesis of how artificial intelligence (AI) and synthetic biology may contribute to overcoming these challenges. We highlight key advances across the bioengineering pipeline, including the application of metabolic engineering strategies for enhancing valuable compound production in engineered algal systems. For example, a CrtYB-based metabolic engineering approach achieved β-carotene accumulation of 22.8 mg/g in the microalga Chlamydomonas reinhardtii, providing important insights for future metabolic engineering of marine macroalgae. In addition, AI-assisted approaches show promising potential for enzyme discovery, metabolic pathway prediction, and multi-omics-guided optimization of bioactive compound production. We further discuss critical downstream challenges, including the low gastrointestinal absorption (~14%) and extensive metabolic transformation of seaweed-derived phenolic compounds, as well as the potential application of AI-integrated physiological modeling for improving bioavailability prediction and safety assessment. This review provides a pioneering, data-driven synthesis of how the convergence of AI and synthetic biology is overcoming these roadblocks. Moving beyond generic descriptions, we highlight key empirical milestones across the bioengineering pipeline, including multi-fold yield enhancements in target pigments (up to 22.8 mg/g) and the AI-driven discovery of novel polysaccharide-degrading enzymes. Furthermore, we confront critical downstream challenges, specifically addressing the characteristically low (~14%) gastrointestinal absorption bottleneck and extensive metabolic biotransformation of seaweed phenolics. We demonstrate that integrating digital twins with reinforcement learning-driven physiologically based pharmacokinetic (PB-PK) modeling can compress the R&D cycles of these seaweed functional ingredients by over 60%. Unlike previous reviews that treat these technologies as independent entities, this article proposes a macroalgae-focused approach that delivers a unique, macroalgae-specific computational and experimental framework, providing a future roadmap toward intelligent smart marine biotechnology and sustainable development to drive the global blue bioeconomy. Full article

Engineered mesenchymal stem cells (MSCs) have emerged as promising therapeutic platforms for healthspan-relevant applications. As agents of tissue repair and modulators of biological aging, MSCs have been widely studied for their capacity to enhance regeneration, restore immune homeostasis, and reduce chronic inflammation associated with age-related decline. This review examines emerging bioengineering strategies designed to overcome key age-related limitations in MSC homing, survival, and paracrine signaling, which have historically constrained their in vivo efficacy. We discuss major engineering approaches, including genetic modification, surface engineering, metabolic reprogramming, and preconditioning, with particular attention to their contributions to longevity-focused applications. Preclinical studies have demonstrated that engineered MSCs and their extracellular vesicles (EVs) yield measurable improvements in therapeutic performance. Reported benefits include prolonged persistence in inflamed tissues, partial reversal of senescence-associated phenotypes, and modulation of pro-aging inflammatory pathways. While MSC-derived EVs may offer potential safety advantages and could reduce certain risks associated with live-cell administration, this remains to be confirmed in well-controlled clinical studies, and significant challenges persist in terms of manufacturing scalability, cargo consistency, and process standardization. The current literature, which is predominantly preclinical, supports the potential of engineered MSC platforms to improve healthspan-relevant outcomes; direct evidence of healthspan extension in humans is not yet available. However, successful clinical translation will require a standardized manufacturing process to ensure therapeutic safety, reproducibility, and efficacy in age-related conditions. Full article