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Keywords = synthetic biology

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19 pages, 4839 KB  
Article
Juvenile Hormone Analogues Reduce the Expression of a Fatty Acid-Binding Protein Involved in Lipid Accumulation in the Migratory Locust Locusta migratoria
by Tian Miao, Zige Wang, Min Peng, Jinchao Chen, Dengbo Li and Yuemin Ma
Insects 2026, 17(7), 664; https://doi.org/10.3390/insects17070664 (registering DOI) - 25 Jun 2026
Abstract
Juvenile hormone (JH) analog insecticides are widely used in pest management because of their ability to disrupt insect growth and metamorphosis; however, the molecular mechanisms linking endocrine disruption to metabolic dysregulation remain incompletely understood. In addition to their established roles in diapause and [...] Read more.
Juvenile hormone (JH) analog insecticides are widely used in pest management because of their ability to disrupt insect growth and metamorphosis; however, the molecular mechanisms linking endocrine disruption to metabolic dysregulation remain incompletely understood. In addition to their established roles in diapause and developmental regulation, JH signaling pathways have also been implicated in carbohydrate and lipid metabolism. In the present study, we investigated the effects of two JH analogs, pyriproxyfen and hydroprene, on the migratory locust, Locusta migratoria, with particular emphasis on lipid metabolic regulation and the function of midgut-enriched fatty acid-binding protein gene (Mg-FABP). Bioassays were performed to evaluate insecticidal activity, and transcriptomic analyses were conducted to identify differentially expressed genes associated with endocrine signaling and lipid metabolism. Functional characterization of Mg-FABP was further performed using RNA interference (RNAi) and Oil Red O staining assays. In addition, the tertiary structure of LmMg-FABP was predicted using AlphaFold 3, and molecular docking analyses were carried out to investigate its interactions with fatty acid ligands. Both pyriproxyfen and hydroprene caused approximately 70% mortality in locust nymphs and induced significant transcriptional changes in pathways related to hormone signaling and lipid metabolism. Transcriptomic analysis revealed pronounced downregulation of Mg-FABP following JH analog exposure. RNAi-mediated silencing of Mg-FABP significantly reduced lipid droplet accumulation in the fat body, indicating that Mg-FABP plays an essential role in lipid transport and metabolic homeostasis in L. migratoria. Structural analyses further demonstrated that LmMg-FABP possesses a conserved tertiary structure highly similar to FABP homologs from other insect species. Molecular docking identified key amino acid residues involved in fatty acid binding and suggested that hydrophobic interactions are critical for ligand stabilization within the binding cavity. Collectively, our findings demonstrate that pyriproxyfen and hydroprene disrupt insect development not only through endocrine imbalance but also through perturbation of Mg-FABP-associated lipid metabolic pathways. This study provides new mechanistic insight into the coordinated interaction between hormonal signaling and lipid metabolism during JH analog exposure and identifies FABP-mediated lipid transport as a potential molecular target for the development of more selective insect growth regulators. Full article
(This article belongs to the Section Insect Physiology, Reproduction and Development)
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36 pages, 5410 KB  
Review
Artificial Intelligence in Bacteriophage Science: A Comprehensive Narrative Review of Applications, Challenges, and Translational Opportunities
by Jamil Allen G. Fortaleza, Kevin Smith P. Cabuhat, Herminiño C. Lagunzad, Warren B. Panizales, Jowi Tsidkenu Pili Cruz, Joel G. Matamis, Jose Edwardo R. Mamaat, Amelda C. Libres, Rich Milton R. Dulay and Jose Jurel M. Nuevo
Antibiotics 2026, 15(7), 635; https://doi.org/10.3390/antibiotics15070635 (registering DOI) - 25 Jun 2026
Abstract
Antimicrobial resistance and persistent biofilm-associated infections have renewed interest in bacteriophages as alternatives or complements to conventional antibiotics. However, broader therapeutic adoption remains constrained by slow phage discovery, incomplete genome characterization, narrow host range, complex therapeutic matching, and manufacturing variability. Artificial intelligence (AI) [...] Read more.
Antimicrobial resistance and persistent biofilm-associated infections have renewed interest in bacteriophages as alternatives or complements to conventional antibiotics. However, broader therapeutic adoption remains constrained by slow phage discovery, incomplete genome characterization, narrow host range, complex therapeutic matching, and manufacturing variability. Artificial intelligence (AI) offers computational approaches that may help address several of these limitations. This comprehensive narrative review discusses current AI applications across the bacteriophage pipeline, including metagenomic phage discovery, genome annotation, phage–host interaction prediction, personalized phage selection, cocktail optimization, and phage–antibiotic combination design. The review also examines AI-assisted synthetic biology approaches, including receptor-binding protein redesign, CRISPR-enabled engineering, generative genome design, and biosafety screening, as well as emerging applications in bioprocess optimization, yield prediction, purification analytics, quality assurance, and supply-chain management. Current evidence suggests that AI may accelerate phage identification, improve host-range prediction, support therapeutic optimization, and strengthen manufacturing consistency, potentially facilitating the transition of phage therapy from individualized rescue interventions toward more scalable antimicrobial platforms. Nevertheless, major limitations remain, including fragmented, taxonomically biased datasets; limited external validation; restricted interpretability; privacy concerns; biosafety oversight; and evolving regulatory frameworks. Future progress will depend on standardized datasets, multimodal validation, scalable manufacturing systems, experimental and clinical verification, and coordinated regulatory development. Full article
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25 pages, 2140 KB  
Review
Recombinant Alphaherpesvirus Vectors in Veterinary Vaccinology: Platforms, Applications, and Translational Challenges
by Ali Mazloum, Sofya G. Feoktistova, Veronika Ledyaeva, Gava Khulkhachiev, Olga N. Mityaeva and Pavel Yu Volchkov
Int. J. Mol. Sci. 2026, 27(13), 5686; https://doi.org/10.3390/ijms27135686 (registering DOI) - 24 Jun 2026
Abstract
Animal infectious diseases impose severe economic burdens on livestock industries, threaten wildlife populations, and compromise food security. Although vaccination remains the cornerstone of disease prevention, conventional vaccine platforms are often constrained by safety, efficacy, or manufacturing scalability. This narrative review provides a comprehensive [...] Read more.
Animal infectious diseases impose severe economic burdens on livestock industries, threaten wildlife populations, and compromise food security. Although vaccination remains the cornerstone of disease prevention, conventional vaccine platforms are often constrained by safety, efficacy, or manufacturing scalability. This narrative review provides a comprehensive analysis of the state of the art in herpesvirus-vectored vaccines for veterinary applications, focusing on five well-characterized alphaherpesviruses: Bovine herpesvirus type 1 (BoHV-1), Pseudorabies virus (PRV), Marek’s disease virus (MDV), Equine herpesvirus type 1 (EHV-1), and Duck enteritis virus (DEV). The intrinsic characteristics of herpesviruses, including large, stable genomes; the capacity for foreign gene insertion; broad host tropism; and the ability to elicit robust humoral and cellular immunity, are examined, and their performance is compared with that of traditional vaccine platforms. Key advances in vectored vaccine development are highlighted, from proof-of-concept studies to the creation of advanced multivalent constructs. These approaches demonstrate protective efficacy against a range of significant animal pathogens, including foot-and-mouth disease virus, porcine reproductive and respiratory syndrome virus, avian influenza virus, infectious bursal disease virus, and West Nile virus. The literature was identified through systematic searches of PubMed, Google Scholar, and Web of Science (1990–2026), followed by title/abstract screening and reference chaining. Future directions in vector engineering, mucosal delivery, and synthetic biology approaches are considered. Herpesvirus-vectored vaccines represent a versatile platform for enhancing animal health, supporting sustainable agriculture, and mitigating zoonotic risks. Full article
(This article belongs to the Special Issue Recent Advances in Herpesviruses (2nd Edition))
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25 pages, 1841 KB  
Review
Advances in AI-Guided CRISPR-Cas9 Engineering Strategies for Microbial Biotechnology
by Javier Alejandro Delgado-Nungaray, Dulce Alitzel Pérez-Ponce, Luis Joel Figueroa-Yáñez, Eire Reynaga-Delgado, Mario Alberto García-Ramírez and Orfil Gonzalez-Reynoso
J. Genome Biotechnol. Genet. 2026, 1(2), 10; https://doi.org/10.3390/jgbg1020010 (registering DOI) - 24 Jun 2026
Abstract
CRISPR-Cas9 has transformed microbial biotechnology by enabling precise genome modifications; however, achieving high editing efficiency remains a challenge due to multiple determinants, including on-target specificity, off-target events, PAM sequence, sgRNA scaffold composition, and RNA secondary structure. Our review foresees how artificial intelligence (AI) [...] Read more.
CRISPR-Cas9 has transformed microbial biotechnology by enabling precise genome modifications; however, achieving high editing efficiency remains a challenge due to multiple determinants, including on-target specificity, off-target events, PAM sequence, sgRNA scaffold composition, and RNA secondary structure. Our review foresees how artificial intelligence (AI) can address those challenges by enabling automated identification as well as highly active guide RNA (gRNA) optimisation. We highlight the influence of a data-driven training strategy that is focused on high-quality, diverse, and accurately labelled microbial datasets—mainly, given the limitations of models derived from mammalian systems that are not directly transferable to microbial organisms. Moreover, we discuss the key role of FAIR (Findable, Accessible, Interoperable, and Reusable) data principles and centralised, curated CRISPR-Cas databases as foundational elements for developing robust and predictive frameworks. Emerging directions are also explored, including generative AI approaches capable of supporting automated experimental planning. By considering the potential dual use of such technologies, the review further addresses bioethical considerations and regulatory frameworks necessary to ensure responsible genome engineering as a milestone, as well as the implementation of safeguards against misuse, particularly in pathogenic microorganisms. Furthermore, the convergence of standardised experimental data, specialised microbial datasets, and advanced AI architectures is paving the way to transform microbial biotechnology by accelerating metabolic engineering and synthetic biology applications. Full article
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17 pages, 1587 KB  
Review
From Gene to Protein: Advances and Challenges in Microbial Production of Immunoglobulins
by Xinhui Pang, Xin Song, Yongjun Xia, Guangqiang Wang, Xinxin Liu, Zhiqiang Xiong and Lianzhong Ai
Fermentation 2026, 12(6), 296; https://doi.org/10.3390/fermentation12060296 (registering DOI) - 22 Jun 2026
Viewed by 143
Abstract
Immunoglobulins exhibit important biological functions, including the neutralization of cytotoxins, enhancement of phagocytic activity, and activation of the complement system, which have driven their widespread application in both the food and pharmaceutical industries. Due to their low cost and short production cycles, microbial [...] Read more.
Immunoglobulins exhibit important biological functions, including the neutralization of cytotoxins, enhancement of phagocytic activity, and activation of the complement system, which have driven their widespread application in both the food and pharmaceutical industries. Due to their low cost and short production cycles, microbial expression systems such as bacteria and yeast have been increasingly developed in recent years for immunoglobulin production. However, microbial systems face considerable challenges in ensuring proper protein folding, accurate chain assembly, and the soluble expression of full-length immunoglobulins. Recent optimization strategies have focused on host engineering (e.g., modulating secretion pathways and chaperone proteins), the coordinated regulation of expression elements (e.g., optimizing the light-to-heavy chain ratio), and regulation of fermentation processes. In addition to summarizing the above strategies, this review discusses the progress made in expressing both full-length immunoglobulins and antibody fragments across different microbial hosts, analyzes the advantages and limitations of each system, and explores potential future directions, aiming to provide a reference for the efficient heterologous expression of immunoglobulins. Full article
(This article belongs to the Section Microbial Metabolism, Physiology & Genetics)
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10 pages, 223 KB  
Review
Generative AI and Language Models in Human Genetics and Health: From Variant Interpretation to Clinical Decision Support
by Yael Pinchevsky Itan and Yuval Itan
Genes 2026, 17(6), 723; https://doi.org/10.3390/genes17060723 (registering DOI) - 22 Jun 2026
Viewed by 142
Abstract
Generative artificial intelligence (AI) is transforming biological and medical research and data analysis. Beyond analyzing existing information, these models can learn complex patterns and generate new data such as realistic protein sequences, genetic variants, or clinical notes. In molecular biology, language-like sequence models [...] Read more.
Generative artificial intelligence (AI) is transforming biological and medical research and data analysis. Beyond analyzing existing information, these models can learn complex patterns and generate new data such as realistic protein sequences, genetic variants, or clinical notes. In molecular biology, language-like sequence models can read and generate DNA, RNA, and amino acid sequences to predict genetic variant effects, design new proteins, and explore molecular functions. In medicine, large language models (LLMs) trained on biomedical literature and electronic health records (EHRs) can summarize clinical findings, identify patterns, and provide decision support for clinicians and healthcare providers. Additionally, synthetic data generation can help protect patient privacy and augment existing disease datasets. While these advances make tasks that were previously impractical possible at scale, they also carry major risks, including producing convincing but incorrect results, reflecting hidden biases in the training data, and underperforming when real-world conditions change. Full article
(This article belongs to the Section Technologies and Resources for Genetics)
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26 pages, 374 KB  
Review
Microalgae as Novel Food Resources: Technological Breakthroughs, Application Bottlenecks, and Future Pathways
by Xiaomei Zhang, Weixian Chen and Hui Chen
Foods 2026, 15(12), 2241; https://doi.org/10.3390/foods15122241 (registering DOI) - 22 Jun 2026
Viewed by 234
Abstract
Global population growth and the demand for sustainable food systems have pushed microalgae into the spotlight as promising novel food resources. They are rich in protein, omega-3 fatty acids, and bioactive pigments including astaxanthin and phycocyanin. Unlike conventional farming, microalgae cultivation can be [...] Read more.
Global population growth and the demand for sustainable food systems have pushed microalgae into the spotlight as promising novel food resources. They are rich in protein, omega-3 fatty acids, and bioactive pigments including astaxanthin and phycocyanin. Unlike conventional farming, microalgae cultivation can be conducted on non-arable land and may reduce direct competition with conventional food crops for land resources, depending on the production system used. Regulatory progress in China, the European Union (EU), and the United States has resulted in the authorization or approval of several microalgal species and microalgae-derived ingredients for specific food and nutritional applications, including dietary supplements, infant nutrition products, and alternative protein ingredients. Despite these advances, broader commercial adoption remains constrained by several challenges, such as off-flavors and the dark green color, high production costs from closed photobioreactors and energy-intensive downstream purification, fragmented regulatory frameworks across jurisdictions and limited long-term data on bioavailability, allergenicity, safety, and dose–response relationships for some emerging strains. This review focuses on microalgae as novel food resources, covering regulatory approvals, strain selection, high-value utilization, and market translation, synthesizes evidence on nutritional evaluation, application scenarios, and global regulatory differences, analyzes key bottlenecks, and proposes pathways to bridge fundamental research with industrial practice. It also highlights unresolved knowledge gaps to guide future research and policy. Full article
21 pages, 3911 KB  
Article
Time-Resolved Whole-Transcriptome Analysis Suggests Candidate Non-Coding RNA Regulatory Networks Associated with PBAN-Induced Pheromone Biosynthesis in Ostrinia furnacalis
by Hanbo Zhao, Lei Liu, Bin Yang and Guirong Wang
Insects 2026, 17(6), 652; https://doi.org/10.3390/insects17060652 (registering DOI) - 20 Jun 2026
Viewed by 183
Abstract
The biosynthesis of sex pheromones in lepidopteran pheromone glands is tightly regulated by pheromone biosynthesis-activating neuropeptide (PBAN) signaling; yet the contribution of non-coding RNA-mediated post-transcriptional regulation remains largely unclear. This study aimed to characterize temporal transcriptomic changes, candidate non-coding RNA-mediated regulatory associations, and [...] Read more.
The biosynthesis of sex pheromones in lepidopteran pheromone glands is tightly regulated by pheromone biosynthesis-activating neuropeptide (PBAN) signaling; yet the contribution of non-coding RNA-mediated post-transcriptional regulation remains largely unclear. This study aimed to characterize temporal transcriptomic changes, candidate non-coding RNA-mediated regulatory associations, and temporal molecular dynamics underlying transcriptional remodeling after PBAN treatment in Ostrinia furnacalis. First, we performed comprehensive whole-transcriptome sequencing (WTS) on 18 biologically independent samples collected at six time points (0, 20, 40, 60, 90, and 120 min) after PBAN injection. Then, we systematically identified and quantified the dynamic expression patterns of differentially expressed (DE) mRNAs, miRNAs, lncRNAs, and circRNAs in response to PBAN stimulation. By integratively analyzing these multidimensional omics datasets and inferring sequence-based interaction relationships, we inferred a dynamic candidate competing endogenous RNA (ceRNA) like regulatory network. The candidate ceRNA network anchored four core node genes: the PBAN receptor (PBANR), the rate-limiting enzyme acetyl-CoA carboxylase (ACC), and the terminal biosynthetic enzymes desaturase (DES) and fatty acyl-CoA reductase (FAR). The qRT-PCR results further support the temporal expression pattern of key genes during the PBAN response, suggesting that this network can provide a valuable resource for further functional studies. Full article
(This article belongs to the Special Issue Insect Transcriptomics)
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3 pages, 161 KB  
Editorial
Editorial for the Special Issue “Advances in Metabolic Engineering of Industrial Microorganisms”
by Shuobo Shi
Microorganisms 2026, 14(6), 1368; https://doi.org/10.3390/microorganisms14061368 (registering DOI) - 20 Jun 2026
Viewed by 137
Abstract
The past decade has witnessed transformative progress in metabolic engineering, driven by the convergence of synthetic biology, CRISPR-based genome editing, systems biology, and high-throughput omics technologies [...] Full article
(This article belongs to the Special Issue Advances in Metabolic Engineering of Industrial Microorganisms)
46 pages, 1662 KB  
Review
Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression
by Jessica Walshe and Sushanta Kumar Saha
Curr. Issues Mol. Biol. 2026, 48(6), 638; https://doi.org/10.3390/cimb48060638 (registering DOI) - 19 Jun 2026
Viewed by 195
Abstract
Cyanobacteria are increasingly recognised as photosynthetic chassis for sustainable metabolic engineering because oxygenic photosynthesis generates ATP and NADPH via the photosynthetic electron transport chain, which drive CO2 fixation through the Calvin–Benson–Bassham cycle into carbon intermediates that can be redirected toward engineered heterologous [...] Read more.
Cyanobacteria are increasingly recognised as photosynthetic chassis for sustainable metabolic engineering because oxygenic photosynthesis generates ATP and NADPH via the photosynthetic electron transport chain, which drive CO2 fixation through the Calvin–Benson–Bassham cycle into carbon intermediates that can be redirected toward engineered heterologous pathways. Their genetic tractability, CO2-fixing capacity, ecological adaptability, and relatively simple cellular organisation make them attractive platforms for developing low-carbon biotechnological processes. This review explores recent progress in engineering cyanobacteria for heterologous pathway construction, critically evaluating genetic tools including transformation methods, genome integration strategies, promoter systems, and CRISPR-based editing, with specific emphasis on challenges of direct relevance to phototrophic chassis: host–pathway metabolic compatibility, precursor supply, cofactor balancing between photosynthetic output and heterologous pathway demand, and achieving genetic stability in polyploid cyanobacterial genomes. The review also addresses key limitations with mechanistic context: metabolic burden from multi-gene pathway expression reduces growth rate and selects against producing cells; polyploidy delays complete chromosomal segregation of engineered constructs; slow photoautotrophic growth constrains volumetric productivity; native regulatory networks resist carbon flux redirection; and cultivation constraints—including light attenuation in dense cultures and mismatches between photosynthetic ATP/NADPH supply and heterologous pathway demand—further limit achievable yields. Full article
(This article belongs to the Special Issue Latest Review Papers in Molecular Plant Science 2026)
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15 pages, 3249 KB  
Article
Engineering a Fungal Non-Reducing Polyketide Synthase with an Apparently Inactive Product-Template Domain Reveals Insights into the Catalytic Reprogramming
by Ruya Yin, Yifei Qin, Xingrui Liang, Ziqi Zhai, Mengwei Zhang, Dan Xu, Ligang Zhou and Daowan Lai
Int. J. Mol. Sci. 2026, 27(12), 5534; https://doi.org/10.3390/ijms27125534 (registering DOI) - 18 Jun 2026
Viewed by 134
Abstract
Fungal iterative non-reducing polyketide synthases (NR-PKS) contain a unique product template (PT) domain for aromatic cyclization. Among them, some NR-PKSs, such as the sorbicillin NR-PKS (SorB), have an apparently inactive PT. It is unknown what role such PT plays in NR-PKS programming. In [...] Read more.
Fungal iterative non-reducing polyketide synthases (NR-PKS) contain a unique product template (PT) domain for aromatic cyclization. Among them, some NR-PKSs, such as the sorbicillin NR-PKS (SorB), have an apparently inactive PT. It is unknown what role such PT plays in NR-PKS programming. In this study, the PT domain of SorB was first dissected and engineered. Removal of the PT domain from SorB did not change the product profile, but the yield decreased. Meanwhile, a significantly lower transcriptional level of the ketoacyl synthase (KS) domain was observed in the knockout mutant (UvSorB∆PT). Phylogenetic tree analysis and multiple sequence alignments revealed this PT belongs to group I (C2–C7, monocyclic ring), and mutations were found at catalytic dyad sites when compared with functional fungal PTs. However, mutating these residues back to the conserved ones did not give rise to products corresponding to a functional PT, but rendered the NR-PKS unproductive. Likewise, removal of the C-methyltransferase (CMT) domain from SorB destroyed the polyketide production. Furthermore, in an attempt to alter the methylation pattern, mutations of the key substrate-binding sites of the CMT domain were made. Site-directed mutations of the C-MT led to cessation of the polyketide production. This reveals CMT is vulnerable to engineering in a collaborating NR-PKS (SorB). These results provide additional insights for catalytic reprogramming in fungal NR-PKS. Full article
(This article belongs to the Special Issue Microbial Enzymes: Molecular Structure and Mechanism)
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25 pages, 1088 KB  
Review
Adaptive Chemistry: Secondary Metabolites as Tools for Engineering Crops Under Extreme Climate Stress
by Rodica D. Catana, Raluca A. Mihai, Ramiro Fernando Vivanco Gonzaga, Ana-Maria Morosanu, Mirela M. Moldoveanu, Anush Kosakyan and Larisa I. Florescu
Agronomy 2026, 16(12), 1196; https://doi.org/10.3390/agronomy16121196 - 18 Jun 2026
Viewed by 255
Abstract
Extreme climatic conditions often intensify abiotic stress factors (such as drought, salinity, heat stress, ultraviolet radiation, and soil degradation), and are increasingly limiting crop productivity and threatening global food security. Secondary metabolites (SMs), traditionally viewed as defense compounds, are now recognized as key [...] Read more.
Extreme climatic conditions often intensify abiotic stress factors (such as drought, salinity, heat stress, ultraviolet radiation, and soil degradation), and are increasingly limiting crop productivity and threatening global food security. Secondary metabolites (SMs), traditionally viewed as defense compounds, are now recognized as key regulators of plant adaptation to environmental stress. This review synthesizes recent advances in understanding the role of SMs as biochemical targets for improving crop resilience to climate extremes. By integrating evidence from multi-omics studies, artificial-intelligence-driven analyses, and functional genomics, we examine how stress-specific metabolic signatures and regulatory networks can be exploited for crop improvement. We further discuss the application of genome editing, synthetic biology, and metabolomics-assisted breeding to modulate the SM pathways to enhance stress tolerance. Selected case studies highlight the contribution of flavonoids, alkaloids, and terpenoids to stress adaptation in major and underutilized crops grown under salinity, drought, and low-temperature conditions. Despite significant progress, challenges remain, including metabolic trade-offs between stress tolerance and yield, regulatory constraints, and public acceptance of genetically engineered crops. By linking molecular mechanisms with applied strategies, this review provides a conceptual framework for leveraging secondary metabolism in climate-resilient agriculture and identifies key gaps to guide future research and innovation. Full article
(This article belongs to the Special Issue Beyond Survival: Engineering Crops for Extreme Climate Adaptation)
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18 pages, 3102 KB  
Review
Metabolic Pathways and Molecular Regulatory Mechanisms of Nervonic Acid Biosynthesis in Malania oleifera
by Qijiang Xu, Chengyu Jiang, Mingyou Dong, Lusheng Liao, Guangfu Pang, Zhiyong Xing, Siyue Qi and Bo Zhou
Int. J. Mol. Sci. 2026, 27(12), 5507; https://doi.org/10.3390/ijms27125507 - 18 Jun 2026
Viewed by 120
Abstract
Nervonic acid (NA, C24:1 Δ15) is a vital extra-long-chain monounsaturated fatty acid essential for neural development, myelin sheath formation, and neurological health. As the most abundant natural source of NA, Malania oleifera Chun & S.K.Lee has become a key model for studying NA [...] Read more.
Nervonic acid (NA, C24:1 Δ15) is a vital extra-long-chain monounsaturated fatty acid essential for neural development, myelin sheath formation, and neurological health. As the most abundant natural source of NA, Malania oleifera Chun & S.K.Lee has become a key model for studying NA biosynthesis and regulation. This review systematically summarizes the metabolic pathways of nervonic acid biosynthesis in M. oleifera, including plastidial de novo fatty acid synthesis, endoplasmic reticulum (ER)-based very-long-chain fatty acid elongation, and Δ15 desaturation. We focus on the catalytic mechanisms and rate-limiting roles of the elongase complex (KCS, KCR, HCD, ECR) and Δ15 desaturase. Additionally, we integrate recent multi-omics data to analyze key enzyme KCS gene families, their phylogenetic relationships, and syntenic distribution patterns. Furthermore, transcriptional regulatory networks (MYB, bZIP, WRI1, ABI3, FUS3) and epigenetic regulation underlying NA accumulation are also discussed. Finally, we highlight advances, challenges, and prospects in metabolic engineering and synthetic biology for sustainable NA production. This review provides a theoretical basis for the conservation, molecular breeding, and biotechnological utilization of M. oleifera. Full article
(This article belongs to the Section Molecular Plant Sciences)
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28 pages, 5437 KB  
Review
Targeting the Human Gut Microbiota—Between Conventional Therapy and Precision Genetic Engineering
by Naomi-Adina Ciurea, Laura Mahdi, Annarita Graziani, Agostino Di Ciaula, Piero Portincasa and Mohamad Khalil
Nutrients 2026, 18(12), 1958; https://doi.org/10.3390/nu18121958 (registering DOI) - 17 Jun 2026
Viewed by 327
Abstract
The gut microbiota is increasingly examined as a therapeutic target because it contributes to epithelial barrier integrity, microbial metabolite production, bile acid transformation, immune regulation, and communication between the gut and distant organs. This structured narrative review synthesizes evidence on microbiota involvement in [...] Read more.
The gut microbiota is increasingly examined as a therapeutic target because it contributes to epithelial barrier integrity, microbial metabolite production, bile acid transformation, immune regulation, and communication between the gut and distant organs. This structured narrative review synthesizes evidence on microbiota involvement in metabolic, gastrointestinal, hepatic, cancer, and neuroimmune conditions, including MASLD/MASH, inflammatory bowel disease, irritable bowel syndrome, obesity, type 2 diabetes, hypertension, colorectal cancer, Parkinson’s disease, and autism spectrum disorder. Across these conditions, microbiome findings are biologically plausible but heterogeneous. Many associations are shaped by diet, geography, medication exposure, host genetics, disease stage, sampling methods, and analytical pipelines. Microbial alterations should therefore be interpreted as context-dependent signals and candidate modifiers rather than universal causal markers. Conventional microbiota targeted strategies include diet, physical activity, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. These approaches are clinically familiar, but their effects are often broad, host specific, strain dependent, and difficult to assign to one mechanism. Fecal microbiota transplantation has the clearest clinical role in recurrent Clostridioides difficile infection, while evidence for most other indications remains inconsistent. Engineered microbial therapeutics offer greater experimental precision through signal sensing, payload delivery, metabolic modulation, and genetic circuit design. However, most evidence remains preclinical or early translational. Progress requires stronger human trials, standardized methods, mechanistic validation, safety monitoring, ecological containment, transparent reporting, and proportionate regulation. Full article
(This article belongs to the Special Issue Polyphenols in Gut–Liver Homeostasis)
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28 pages, 7751 KB  
Article
Mild Heat Stimulating and Microenvironment Reprogramming Hydrogel for Accelerating Diabetic Wound Healing
by Xueting Xiao, Yannan Liu, Dan Li, Lebin Wang, Zirui Hu, Xinliang Xing, Yali Ding, Xurun Wang, Ruifan Zhang, Jing Yang and Xiaoxuan Ma
Gels 2026, 12(6), 542; https://doi.org/10.3390/gels12060542 - 17 Jun 2026
Viewed by 226
Abstract
Diabetic wounds are characterized by persistent hyperglycemia, excessive ROS accumulation, sustained inflammation, and impaired angiogenesis, yet current treatments remain suboptimal. To address these challenges, we developed a mild heat stimulating and microenvironment reprogramming hydrogel (termed C-4-N) via a green synthetic strategy. L-Arginine (L-Arg) [...] Read more.
Diabetic wounds are characterized by persistent hyperglycemia, excessive ROS accumulation, sustained inflammation, and impaired angiogenesis, yet current treatments remain suboptimal. To address these challenges, we developed a mild heat stimulating and microenvironment reprogramming hydrogel (termed C-4-N) via a green synthetic strategy. L-Arginine (L-Arg) triggered the spontaneous self-polymerization of protocatechuic aldehyde (PA) into poly (protocatechuic aldehyde) (PPA) nanoparticles, onto which ginsenoside Compound K (CK) was subsequently loaded, yielding CK/L-Arg/PPA nanoparticles. These nanoparticles were then uniformly embedded into a dynamic disulfide network composed of α-lipoic acid (LA)-modified chitosan (CS-LA) and 4-arm-PEG-SH under UV irradiation without toxic photo-initiators, forming the C-4-N hydrogel. The C-4-N hydrogel reprogrammed the diabetic wound microenvironment through three synergistic mechanisms, lowering blood glucose and scavenging ROS via the coordinated actions of LA, CK and PPA, promoting M1-to-M2 macrophage polarization via downregulation of pro-inflammatory cytokines (TNF-α, IL-6) and upregulation of anti-inflammatory cytokines (IL-10, TGF-β1), further amplified by mild photothermal stimulation of 40–43 °C. In a diabetic rat model, the C-4-N hydrogel achieved a near-complete wound closure rate of 99.49 ± 0.10% on day 13 upon mild photothermal stimulation, accompanied by enhanced re-epithelialization, organized collagen deposition, vascular maturation, and systemic glucose regulation. In summary, this green synthesized, mild heat-stimulating hydrogel establishes a synergistic microenvironment reprogramming paradigm for chronic diabetic wound managements. Full article
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