Search Results (617)

In the last twenty years, an increasing volume of research has characterized lipids as dynamic signaling molecules that play essential roles in various physiological and pathological processes, especially concerning chronic diseases such as cardiovascular disorders, diabetes, liver disease, neurodegeneration, cancer, obesity, diabetic and chronic kidney diseases and atherosclerosis. Dysregulation of lipid synthesis and storage, lipolysis, fatty acid oxidation, lipid signaling pathways, and organelle-specific lipid modifications, including mitochondrial phospholipid remodeling and endoplasmic reticulum stress induced by saturated fatty acids, are recognized as contributors to the initiation and progression of this pathogenesis. Concurrently with the increasing comprehension of lipid metabolism, the last decade has seen progress in the understanding of genome control, especially with non-coding RNAs (ncRNAs). MicroRNAs, long non-coding RNAs, and circular RNAs, as ncRNAs, are essential modulators of gene expression at the epigenetic, transcriptional, and post-transcriptional levels that affect a number of lipid metabolism-related processes, such as fatty acid synthesis and oxidation, cholesterol homeostasis, and lipid droplet dynamics. Therapeutically, ncRNAs hold considerable promise owing to their tissue specificity and modularity, with antisense oligonucleotides and CRISPR-based editing currently under preclinical evaluation. In this context, we review recent studies exploring the interplay between ncRNAs and the regulatory networks governing lipid metabolism, and how disruptions in these networks contribute to chronic disease. This emerging paradigm underscores the role of ncRNA–lipid metabolism interactions as central nodes in metabolic and inflammatory pathways, highlighting the need for a holistic approach to therapeutic targeting. Full article

Cucumis sativus L. is a globally important vegetable crop that occupies a significant position in protected agriculture due to its high nutritional value, short cultivation cycle, and considerable economic benefits. As a cold-sensitive plant, however, cucumber is highly susceptible to low-temperature stress. which can severely inhibit growth and development, hinder seed germination, and reduce photosynthetic efficiency. Under low-temperature stress, cucumber plants typically incur damage to cellular membrane structures, experience an accumulation of reactive oxygen species (ROS), exhibit a disruption in hormonal homeostasis, and suffer from the inhibition of pivotal metabolic pathways. In response, cucumber plants activate an array of resistance mechanisms, encompassing osmotic adjustment, reinforcement of the antioxidant system, and modulation of cold-responsive gene expression. This review summarizes the physiological and molecular mechanisms underlying cucumber’s response to low-temperature stress, aiming to provide effective strategies for improving abiotic stress resistance. The main findings are as follows: (1) Low-temperature stress damages cucumber cell membranes, suppresses photosynthesis and respiration, suppresses water and nutrient uptake/transport, and suppresses growth retardation. (2) Cucumber counters these adverse effects by orchestrating the accumulation of osmoregulators (e.g., soluble sugars, proline), activating activation defenses (e.g., SOD, CAT), and rebalancing its phytohormone network (e.g., ABA, GA, SA, ethylene). (3) At the molecular level, cucumber activates low-temperature-responsive genes (e.g., COR, GoIS) through transcription factors such as CBF, MYB, and WRKY, thereby enhancing cold tolerance. (4) Application of exogenous protectants (e.g., hydrogen sulfide, melatonin, oligosaccharides) significantly improves cucumber’s low-temperature tolerance by modulating the antioxidant system, promoting osmoregulatory substances accumulation, and regulating hormone signaling pathways. Future research should focus on elucidating the molecular regulatory network in cucumber under low-temperature stress and developing gene editing with multi-omics techniques to advance the development of cold-resistant cultivars and cultivation practices. This study offers a scientific foundation for research on cucumber cold tolerance and proposes potential solutions to agricultural challenges in the context of global climate change. Full article

Recent technological breakthroughs have enabled multidimensional phenotyping, with unprecedented single-cell resolution and genome-wide coverage, across multiple osteoarthritis (OA)-relevant tissues, such as articular cartilage, synovium, infrapatellar fat pad, and subchondral bone. The majority of the single nucleotide variations (SNVs) that have been associated with OA are located in non-protein coding regions and confer risk for disease by altering the expression level, instead of the amino acid sequence of the gene product. These data have shaped the concept of OA as a polygenic disease, where genetic factors disrupt the chromatin landscape in disease-relevant cells, leading to aberrant expression of effector genes. Pharmacologic manipulation of the OA-driving epigenetic landscape has recently emerged as an attractive path for the development of disease-modifying drugs. Novel clustered regulatory interspaced short palindromic repeats (CRISPR)-based technologies provide opportunities for precise epigenetic editing at the desired genomic regions and may allow a targeted transcriptional regulation of disease-relevant genes in disease-relevant cells. The aim of the present narrative review is to summarize the emerging data on the role of epigenetic factors and chromatin structure as calibrators of the risk for developing OA and to discuss the opportunities and challenges arising from the use of chromatin landscape to guide drug discovery. Full article

The genus Quercus is an ecological keystone and economically vital component of Northern Hemisphere forests. While genomic studies have advanced our understanding of its nuclear and chloroplast genomes, the mitochondrial genomes of oaks remain less explored due to their complex evolutionary dynamics, which include extreme size variation, frequent rearrangements, and recurrent horizontal gene transfer. This study presents the assembly, annotation, and comparative analysis of mitogenomes from three closely related Asian oaks—Q. engleriana, Q. kongshanensis, and Q. tungmaiensis—using PacBio HiFi sequencing. The assemblies revealed distinct structural organizations: the Q. engleriana and Q. kongshanensis mitogenomes each comprised one circular contig and one linear contig, whereas the Q. tungmaiensis mitogenome comprised one circular contig and two linear contigs. Comparative analyses revealed variations in codon usage bias, simple sequence repeats, and predicted RNA editing sites. Notably, RNA editing in rps12 was uniquely observed in Q. kongshanensis. Mitochondrial targeting of plastid transcripts constituted 1.39%, 1.79%, and 2.24% of the mitogenomes, respectively. Phylogenetic reconstruction based on mitochondrial PCGs robustly resolved Q. kongshanensis and Q. tungmaiensis as sister species, with all three forming a distinct clade separate from other Quercus species. This study provides comprehensive mitogenomic resources essential for elucidating Quercus evolutionary biology and supporting germplasm development. Full article

Chrysanthemum morifolium Ramat. is a major ornamental crop that suffers from diverse fungal, bacterial, viral, and insect pests, causing significant yield and quality losses. Between 2015 and 2025, rapid progress in molecular biology, genomics, and ecological regulation has advanced both fundamental research and applied control strategies. Multi-locus sequencing, multiplex PCR, and next-generation sequencing refined the identification of fungal and bacterial pathogens, while functional studies of WRKY, MYB, and NAC transcription factors revealed key resistance modules. Hormone-mediated signaling pathways, particularly those of salicylic acid, jasmonic acid, and abscisic acid, were shown to play central roles in host defense. Despite these advances, durable genetic resistance against bacterial pathogens and broad-spectrum defense against viruses remains limited. Novel technologies, including virus-free propagation, RNA interference, and spray-induced gene silencing, have shown promising outcomes. For insect pests, studies clarified the damage and virus-vectoring roles of aphids and thrips, and resistance traits linked to trichomes, terpenoids, and lignin have been identified. Biocontrol agents such as Trichoderma spp., Bacillus spp., predatory mites, and entomopathogenic fungi have also demonstrated efficacy. Future efforts should integrate molecular breeding, genome editing, RNA-based tools, and microbiome management to achieve sustainable chrysanthemum protection. Full article

Knowledge graphs (KGs) represent a promising approach for detecting and correcting errors in automated audio and video transcripts. Yet the lack of accessible tools leaves human reviewers with limited support, as KG construction from media data often depends on advanced programming or natural language processing expertise. We present the Custom LLM Automated Relationship Extractor (CLARE), a system that lowers this barrier by combining context-aware relation extraction with an interface for transcript correction and KG refinement. Users import time-synchronized media, correct transcripts through linked playback, and generate an editable, searchable KG from the revised text. CLARE supports over 150 large language models (LLMs) and embedding models, including local options suitable for privacy-sensitive data. We evaluated CLARE on the Measure of Information in Nodes and Edges (MINE) benchmark, which pairs articles with ground-truth facts. With minimal parameter tuning, CLARE achieved 82.1% mean fact accuracy, exceeding Knowledge Graph Generation (KGGen, 64.8%) and Graph Retrieval-Augmented Generation (GraphRAG, 48.3%). We further assessed interactive refinement by revisiting the twenty-five lowest-scoring graphs for fifteen minutes each and found that the fact accuracy rose by an average of 22.7%. These findings show that CLARE both outperforms prior methods and enables efficient user-driven improvements. By streamlining ingestion, correction, and filtering, CLARE makes KG construction more accessible for researchers working with unstructured data. Full article

Plants have evolved a complex, multilayered immune system that integrates molecular recognition, signaling pathways, epigenetic regulation, and small RNA-mediated control. Recent studies have shown that DNA-level regulatory mechanisms, such as RNA-directed DNA methylation (RdDM), histone modifications, and chromatin remodeling, are critical for modulating immune gene expression, allowing for rapid and accurate pathogen-defense responses. The epigenetic landscape not only maintains immunological homeostasis but also promotes stress-responsive transcription via stable chromatin modifications. These changes contribute to immunological priming, a process in which earlier exposure to pathogens or abiotic stress causes a heightened state of preparedness for future encounters. Small RNAs, including siRNAs, miRNAs, and phasiRNAs, are essential for gene silencing before and after transcription, fine-tuning immune responses, and inhibiting negative regulators. These RNA molecules interact closely with chromatin features, influencing histone acetylation/methylation (e.g., H3K4me3, H3K27me3) and guiding DNA methylation patterns. Epigenetically encoded immune memory can be stable across multiple generations, resulting in the transgenerational inheritance of stress resilience. Such memory effects have been observed in rice, tomato, maize, and Arabidopsis. This review summarizes new findings on short RNA biology, chromatin-level immunological control, and epigenetic memory in plant defense. Emerging technologies, such as ATAC-seq (Assay for Transposase-Accessible Chromatin using Sequencing), ChIP-seq (Chromatin Immunoprecipitation followed by Sequencing), bisulfite sequencing, and CRISPR/dCas9-based epigenome editing, are helping researchers comprehend these pathways. These developments hold an opportunity for establishing epigenetic breeding strategies that target the production of non-GMO, stress-resistant crops for sustainable agriculture. Full article

Secondary metabolites, including alkaloids, flavonoids, and tannins, are crucial for human health, agriculture, and ecosystem functioning. Their synthesis is often species-specific, influenced by both genetic and environmental factors. The increasing demand for these compounds across various industries highlights the need for advancements in plant breeding and biotechnological approaches. Transcription activator-like effector nucleases (TALENs) have emerged as a powerful tool for precise genome editing, offering significant potential for enhancing the synthesis of secondary metabolites in plants. However, while plant genome editing technologies have advanced significantly, the application of TALENs in improving secondary metabolite production and expanding genetic diversity remains underexplored. Therefore, this review aims to provide a comprehensive analysis of TALEN-mediated genome editing in plants, focusing on their role in enhancing secondary metabolite biosynthetic pathways and improving genetic diversity. The mechanisms underlying TALENs are examined, including their ability to target specific genes involved in the synthesis of bioactive compounds, highlighting comparisons with other genome editing tools such as CRISPR/Cas9. This review further highlights key applications in medicinal plants, particularly the modification of pathways responsible for alkaloids, flavonoids, terpenoids, and phenolic compounds. Furthermore, the role of TALENs in inducing genetic variation, improving stress tolerance, and facilitating hybridization in plant breeding programs is highlighted. Recent advances, challenges, and limitations associated with using TALENs for enhancing secondary metabolite production are critically evaluated. In this review, gaps in current research are identified, particularly regarding the integration of TALENs with multi-omics technologies and synthetic biology approaches. The findings suggest that while underutilized, TALENs offer sustainable strategies for producing high-value secondary metabolites in medicinal plants. Future research should focus on optimizing TALEN systems for commercial applications and integrating them with advanced biotechnological platforms to enhance the yield and resilience of medicinal plants. Full article

Repairing the central nervous system (CNS) remains one of the most difficult obstacles to overcome in translational neurosciences. This is due to intrinsic growth inhibitors, extracellular matrix issues, the glial scar–form barrier, chronic neuroinflammation, and epigenetic silencing. The purpose of this review is to bring together findings from recent developments in genome editing and computational approaches, which center around the possible convergence of clustered regularly interspaced short palindromic repeats (CRISPR) platforms and artificial intelligence (AI), towards precision neuroregeneration. We wished to outline possible ways in which CRISPR-based systems, including but not limited to Cas9 and Cas12 nucleases, RNA-targeting Cas13, base and prime editors, and transcriptional regulators such as CRISPRa/i, can be applied to potentially reactivate axon-growth programs, alter inhibitory extracellular signaling, reprogram or lineage transform glia to functional neurons, and block oncogenic pathways in glioblastoma. In addition, we wanted to highlight how AI approaches, such as single-cell multi-omics, radiogenomic prediction, development of digital twins, and design of adaptive clinical trials, will increasingly be positioned to act as system-level architects that allow translation of complex datasets into predictive and actionable therapeutic approaches. We examine convergence consumers in spinal cord injury and adaptive neuro-oncology and discuss expanse consumers in ischemic stroke, Alzheimer’s disease, Parkinson’s disease, and rare neurogenetic syndromes. Finally, we discuss the ethical and regulatory landscape around beyond off-target editing and genomic stability of CRISPR, algorithmic bias, explainability, and equitable access to advanced neurotherapies. Our intent was not to provide a comprehensive inventory of possibilities but rather to provide a conceptual tool where CRISPR acts as a molecular manipulator and AI as a computational integrator, converging to create pathways towards precision neuroregeneration, personalized medicine, and adaptive neurotherapeutics that are ethically sound. Full article

Nitrogen (N) is the primary macronutrient that supports global agriculture. The Haber–Bosch process revolutionized the use of synthetic N fertilizers, enabling significant increases in crop yield. However, N losses from fertilization led to negative impacts on the environment. Improving crops’ N use efficiency (NUE) has been constrained by the limited understanding of N uptake and assimilation mechanisms, and the role of plant–microbe interactions. Among biological approaches, N fixation by cover crops and rhizobia symbioses represents a cornerstone strategy for improving NUE. The adoption of plant growth-promoting bacteria and arbuscular mycorrhizal fungi may enhance N acquisition by increasing root surface, modulating phytohormone levels, and facilitating nutrient transfer. Advances in plant molecular biology have identified key players and regulators of NUE (enzymes, transporters, and N-responsive transcription factors), which enhance N uptake and assimilation. Emerging biotechnological strategies include de novo domestication by genome editing of crop wild relatives to combine NUE traits and stress resilience back into domesticated cultivars. Additionally, novel fertilizers with controlled nutrient release and microbe-mediated nutrient mobilization, hold promise for synchronizing N availability with plant demand, reducing losses, and increasing NUE. Together, these strategies form a multidimensional framework to enhance NUE, mitigate environmental impacts, and facilitate the transition towards more sustainable agricultural systems. Full article

Gene editing enables a better understanding of protein functions. The genome of the protozoan parasite Entamoeba histolytica contains a 4500 bp DNA fragment comprising the ehcp112, ehadh, and ehrabb genes, which together form the V1 virulence locus. Studying these genes has been challenging due to the lack of suitable methodologies. Here, we report the first in vitro and in vivo knockout in E. histolytica (ehcp112 gene) using a modified CRISPR-Cas9 strategy and explore its effects on the other V1 locus genes. Confocal and transmission electron microscopy were used to detect the RNP pathway formed by the Cas9 enzyme and the crRNA–tracrRNA complex, from their entry into the trophozoites until their arrival at the nucleus and heterochromatin. Scanning electron microscopy revealed that the mutant cells (EhCP112-KO) were smaller, with fewer pseudopodia and plasma membrane depressions. DNA sequencing and RT-qPCR assays identified a four-base deletion in the ehcp112 gene in the mutant trophozoites. Western blot assays of EhCP112-KO extracts revealed the absence of the EhCP112 protein. While the EhCP112-KO lysates digested gelatin more efficiently than the HM1:IMSS extracts, their secreted products showed poor enzymatic activity. The ehcp112 knockout also affected the transcription of the ehadh and ehrabb genes, probably due to their genomic position. In conclusion, the implementation of the CRISPR-Cas9 strategy in E. histolytica evidenced the coordinated expression of the ehcp112 gene and the other members of the V1 locus. Full article

The document is an updated review, starting from the Special Issue “Molecular Breeding for Abiotic Stress Tolerance in Crops” published in the Int. J. Mol. Sci. It reviews molecular breeding strategies to enhance abiotic stress tolerance in crops, addressing challenges like drought, salinity, temperature extremes, and waterlogging, which threaten global food security. Climate change intensifies these stresses, making it critical to develop resilient crop varieties. Plants adapt to stress through mechanisms such as hormonal regulation (e.g., ABA, ethylene), antioxidant defense (e.g., SOD, CAT), osmotic adjustment (e.g., proline accumulation), and gene expression regulation via transcription factors like MYB and WRKY. Advanced tools, such as CRISPR/Cas9 genome editing, enable precise modifications of stress-related genes, improving tolerance without compromising yield. Examples include rice (OsRR22, OsDST) and wheat (TaERF3, TaHKT1;5). Epigenetic regulation, including DNA methylation and histone modifications, also plays a role in stress adaptation. Specific studies focused on polyamine seed priming for improved germination and stress resistance, cadmium detoxification mechanisms, and genome-wide association studies (GWAS) to identify genetic markers for salt tolerance and yield. Research on salinity tolerance in wheat emphasizes sodium exclusion and tissue tolerance mechanisms. Future perspectives focus on genetic engineering, molecular markers, epigenetic studies, and functional validation to address environmental stress challenges, including the use of AI and machine learning to manage the large amount of data. The review underscores the importance of translating molecular findings into practical applications to ensure sustainable crop production under changing climates. Full article

The growing demand for sustainable alternatives to petroleum-based plastics has driven interest in bio-based packaging derived from renewable plant biomass. Cellulose, the most abundant biopolymer on Earth, provides high tensile strength, water resistance, and biodegradability, making it a key raw material for eco-friendly packaging. However, its extraction and processing are hindered by lignin, a complex polymer that adds structural rigidity but reduces cellulose accessibility. Recent research has identified plant microRNAs (miRNAs) as powerful post-transcriptional regulators capable of modifying cell wall composition by simultaneously targeting multiple genes involved in lignin biosynthesis, cellulose synthesis, and secondary cell wall formation. By fine-tuning specific miRNAs, it is possible to increase cellulose yield, reduce lignin content, and enhance overall biomass productivity without severely compromising plant growth or stress tolerance. This review summarizes the roles of major plant miRNAs in biomass regulation and outlines biotechnological strategies such as transgenic overexpression, target mimicry, artificial miRNAs (amiRNAs), and CRISPR-based editing for improving bio-based packaging feedstocks. Harnessing miRNA-mediated gene regulation offers a promising pathway toward producing high-quality biomass with optimized cellulose–lignin ratios, enabling more efficient, cost-effective, and sustainable packaging material production. Full article

Rice (Oryza sativa), particularly the japonica subspecies, is a vital global food source but often suffers from short grain length and heat sensitivity, highlighting the need for genetic improvement. This study employed CRISPR/Cas9 technology to investigate the effects of Grain Size3 (GS3) gene editing in the japonica cultivar, ‘Nipponbare’. Successful GS3 editing increased grain size across stable T₃ and T₄ generations. Importantly, different GS3-edited lines, even when all targeted within exon 1, resulted in varied effects on grain length and other yield components. Transcriptomic analyses revealed unique gene expression profiles for each edited line, highlighting the fact that subtle GS3 mutations trigger diverse transcriptional cascades. While common differentially expressed genes (DEGs) were enriched in ethylene signaling and chitinase activity, line-specific KEGG analyses showed distinct pathway enrichments. Crucially, the CR-L5 line exhibited significantly enhanced heat tolerance at heading stage. Under high-temperature stress, CR-L5 maintained a higher relative seed setting rate and a 15% greater grain yield than the wild type. This enhanced thermotolerance in CR-L5 correlated with differing expressions of several wax biosynthesis and chitinase-related genes. Our study provides evidence that specific gs3 mutations can confer enhanced reproductive-stage thermotolerance, offering a strategy for breeding climate-resilient japonica rice with improved grain quality and yield under stress. Full article

Non-coding RNAs (ncRNAs) are critical regulators of gene expression, taking part in the modulation of multiple biological functions across a range of cell types. Initially dismissed as transcriptional noise, ncRNAs are now recognized for their significant roles in key cellular mechanisms, including differentiation, apoptosis, and proliferation, as well as their profound implications for the pathogenesis of numerous human diseases. Due to their remarkable stability, tissue-specific expression patterns, and abundance in body fluids, ncRNAs hold significant promise as non-invasive biomarkers for diagnosis, prognosis, and therapeutic monitoring. Furthermore, advances in RNA-targeted therapeutics have introduced novel strategies to modulate ncRNA activity, although challenges related to delivery efficiency, specificity, and clinical validation remain. This review comprehensively summarizes the classification, biogenesis, and molecular functions of ncRNAs, elucidates their involvement in health and disease, and evaluates their potential as clinical biomarkers and therapeutic targets. Additionally, it discusses the emerging technologies for RNA manipulation, including CRISPR-based RNA editing, that can advance ncRNA research and revolutionize ncRNA-based therapeutics. Full article