Search Results (729)

The year 2025 marks two significant milestones for aflatoxin research: 65 years since aflatoxin was first identified in 1960, and 50 years of focused research on preharvest aflatoxin contamination since it was first recognized in 1975. Studies in the 1970s revealed that A. flavus could infect crops like maize and produce aflatoxin in the field before harvest and made it possible to investigate the potential genetic resistance in crops to mitigate the issues. Tremendous efforts have been made to learn about the process and regulation of aflatoxin production along with interactions between A. flavus and host plants as influenced by environmental factors. This has allowed for the breeding of more resistant crops and investigations into the underlying genetic and genomic components of resistance mechanisms in crops like maize and peanut. However, despite decades of studies, many questions remain. One established “dogma” is that drought stress, especially when combined with high temperatures, is the single greatest contributing factor to preharvest aflatoxin contamination and is a perennial risk faced throughout the major agricultural production regions of the world. Although there are many reviews summarizing the decades’ long wealth of information about A. flavus, aflatoxin biosynthesis, management and host plant resistance, there are few reports that put the spotlight on why aflatoxin contamination is exacerbated by drought stress, which places plants under severe physiological stress and weakens immune systems. Therefore, here we will focus on three major areas of research in maize: the “living embryo” theory and host resistance mechanisms, the “Key Largo hypothesis” and the causes of drought-exacerbated aflatoxin contamination, and recent advancements in CRISPR-based genome editing for enhancing drought tolerance and increasing plant immune responses. This will highlight key breakthroughs and future prospects for the continuing development of superior crop germplasm and cultivars and for mitigating aflatoxin contamination in food and feed supply chains. Full article

Gene therapy represents a transformative frontier in ophthalmology, offering the potential to address inherited and acquired retinal diseases at their genetic origin rather than through symptomatic management. By introducing exogenous genetic material to restore or modulate gene expression, gene therapy aims to preserve or even restore vision in patients with mutations that disrupt normal retinal function. The eye’s small, compartmentalized structure, relative immune privilege, and direct accessibility through subretinal or intravitreal routes make it an ideal target for localized delivery with minimal systemic exposure. The approval of voretigene neparvovec-rzyl for RPE65-mediated retinal dystrophy marked a pivotal milestone, establishing proof of concept for durable and safe gene replacement therapy. Looking ahead, continued refinements in vector design, CRISPR-based editing strategies, and delivery platforms are expected to expand the therapeutic reach of gene therapy beyond monogenic disorders. With multiple early-phase clinical trials underway for inherited and acquired retinal diseases, the coming decade is poised to bring broader applicability, improved durability, and more accessible gene-based treatments across the spectrum of retinal pathology. Full article

This article aims to point out new perspectives opened by genomics and epigenomics in skin rejuvenation strategies which target the main hallmarks of the ageing. In this respect, this article presents a concise overview on: the clinical relevance of the most important clocks and biomarkers used in skin anti-ageing strategy evaluation, the fundamentals, the main illustrating examples preclinically and clinically tested, the critical insights on knowledge gaps and future research perspectives concerning the most relevant skin anti-ageing and rejuvenation strategies based on novel epigenomic and genomic acquisitions. Thus the review dedicates distinct sections to: senolytics and senomorphics targeting senescent skin cells and their senescent-associated phenotype; strategies targeting genomic instability and telomere attrition by stimulation of the deoxyribonucleic acid (DNA) repair enzymes and proteins essential for telomeres’ recovery and stability; regenerative medicine based on mesenchymal stem cells or cell-free products in order to restore skin-resided stem cells; genetically and chemically induced skin epigenetic partial reprogramming by using transcription factors or epigenetic small molecule agents, respectively; small molecule modulators of DNA methylases, histone deacetylases, telomerases, DNA repair enzymes or of sirtuins; modulators of micro ribonucleic acid (miRNA) and long-non-coding ribonucleic acid (HOTAIR’s modulators) assisted or not by CRISPR-gene editing technology (CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats); modulators of the most relevant altered nutrient-sensing pathways in skin ageing; as well as antioxidants and nanozymes to address mitochondrial dysfunctions and oxidative stress. In addition, some approaches targeting skin inflammageing, altered skin proteostasis, (macro)autophagy and intercellular connections, or skin microbiome, are very briefly discussed. The review also offers a comparative analysis among the newer genomic/epigenomic-based skin anti-ageing strategies vs. classical skin rejuvenation treatments from various perspectives: efficacy, safety, mechanism of action, evidence level in preclinical and clinical data and regulatory status, price range, current limitations. In these regards, a concise overview on senolytic/senomorphic agents, topical nutrigenomic pathways’ modulators and DNA repair enzymes, epigenetic small molecules agents, microRNAs and HOTAIRS’s modulators, is illustrated in comparison to classical approaches such as tretinoin and peptide-based cosmeceuticals, topical serum with growth factors, intense pulsed light, laser and microneedling combinations, chemical peels, botulinum toxin injections, dermal fillers. Finally, the review emphasizes the future research directions in order to accelerate the clinical translation of the (epi)genomic-advanced knowledge towards personalization of the skin anti-ageing strategies by integration of individual genomic and epigenomic profiles to customize/tailor skin rejuvenation therapies. Full article

Immunotherapy represents a groundbreaking approach for treating colorectal cancer (CRC), harnessing the body’s own immune system to target tumour cells more precisely than conventional chemotherapy. Immune checkpoint inhibitors, such as antibodies against PD-1, PD-L1, or CTLA-4, have shown remarkable efficacy in certain patients, leading to durable responses and improved survival. However, the majority of CRC cases have limited benefit from a single agent checkpoint blockade. There is a growing need to identify biomarkers that will improve the selection of patients who will best respond to therapy, as well as new targets to sensitise cancers to an immune checkpoint blockade. Unfortunately, the search for reliable biomarkers has been limited by our incomplete understanding of how immunotherapies modify the already complex immune response to cancer. Revolutionary techniques, such as genome-wide CRISPR/Cas9 screening combined with the appropriate validation systems such as in vivo mouse models and/or 3D organoid co-culture systems, are being used to address this knowledge gap. This review will focus on the use of immunotherapies in CRC, discuss why most CRC patients do not respond, and highlight in vitro, in vivo, and novel techniques for discovery of new targets for combination treatment. Full article

Nucleic acid-based gene interfering and editing molecules, such as antisense oligonucleotides, ribozymes, small interfering RNAs (siRNAs), and CRISPR-Cas9-associated guide RNAs, are promising gene-targeting agents for therapeutic applications. Cancer’s heterogeneous and diverse nature demands gene-silencing technologies that are both specific and adaptable. RNase P ribozymes, called M1GS RNAs, are engineered constructs that link the catalytic M1 RNA from bacterial RNase P to a programmable guide sequence. This guide sequence directs the M1GS ribozyme to base-pair with a target RNA, inducing it to fold into a structure resembling pre-tRNA. Catalytic activity can be enhanced through in vitro selection strategies. In this review, we will discuss the application of M1GS ribozymes in targeting cancer-associated RNAs, focusing on the BCR-ABL transcript in leukemia, the internal ribosome entry site (IRES) of hepatitis C virus (HCV), and the replication and transcription activator (RTA) of Kaposi’s sarcoma-associated herpesvirus (KSHV). Together, these examples highlight the versatility of M1GS ribozymes across both viral and cellular oncogenic targets, underscoring their potential as a flexible synthetic biology platform for cancer therapy. Full article

This study presents the complete assembly and analysis of the mitochondrial genome (mitogenome) of Medicago lupulina L. var. vulgaris Koch, cultivar-population VIK32, line MlS-1, which forms an effective symbiosis not only with arbuscular mycorrhiza but also with the root nodule bacteria Sinorhizobium meliloti. The assembly, generated using a hybrid sequencing approach, revealed sequences of putative horizontal origin. These include a highly conserved open reading frame (ORF), orf279, encoding a protein structurally homologous to maturase K, yet bearing remote similarity to bacterial reverse transcriptases and CRISPR-associated proteins. We also identified sequences homologous to mitovirus RNA-dependent RNA polymerases and a fragment of the chloroplast 23S ribosomal RNA (rRNA), suggesting historical gene transfers from viruses and plastids. This work establishes a foundation for investigating the role of mitochondrial genome variation in key plant’s phenotypic traits, such as the enhanced responsiveness to arbuscular mycorrhiza observed in this agronomically valuable line. Full article

Human exposure to Di(2-ethylhexyl) Phthalate (DEHP) occurs through ingestion of contaminated food. Yet, the effects of DEHP on gastrointestinal toxicity at the cellular level are poorly understood and studies conducted to date have used malignant cell lines, limiting our understanding of molecular signaling in intestinal epithelia of otherwise healthy individuals. The objective of our study was to use a non-transformed, colonic epithelial cell line (Young Adult Mouse Colonocytes; YAMCs) to characterize the in vitro effects of DEHP on non-malignant colonic epithelia. A 72 h DEHP exposure significantly reduced cell number and proliferation while short-term exposure increased: cellular apoptosis, BAX expression, Reactive Oxygen Species (ROS) production, gene expression linked to oxidative stress (NRF2, GCLC, HO-1, CHOP). Antioxidant pretreatment prior to DEHP exposure attenuated the phthalate’s apoptotic effect, suggesting a link between oxidative stress and apoptosis. Using YAMCs with a CRISPR-deleted Aryl Hydrocarbon Receptor (AhR) we further showed that the apoptotic and pro-oxidative effects of the phthalate are partially mediated through AhR. In conclusion, we have demonstrated that DEHP-induced toxicity in non-malignant colonocytes is due to ROS-induced oxidative stress and subsequently, apoptosis. We have further demonstrated that these effects are partly mediated by the AhR, a mechanism that deserves further investigation. Future studies should build on these findings by (a) characterizing the specific mechanisms linking ROS production to apoptosis demonstrated in our model of exposure, (b) measuring the dynamics of the receptor following DEHP exposure and (c) examining these effects over a longer exposure period. Full article

The epidemic of infectious diseases, such as influenza A, has imposed a severe health burden on the population. Early detection, diagnosis, reporting, isolation, and treatment are crucial for the prevention, control, and management of infectious diseases. Nucleic acid testing represents a vital approach for the rapid diagnosis of pathogenic microorganism types. However, current nucleic acid detection methods face notable bottlenecks: traditional CRISPR fluorescence assays require time-consuming pre-amplification of target nucleic acids, while existing carbon-nanotube field-effect transistor (FET)-based platforms, though amplification-free, often necessitate complex chip surface modification and probe immobilization, and suffer from non-reusable chips, all limiting their utility in point-of-care testing (POCT) and large-scale screening. This study reports a CRISPR-based amplification-free RNA detection platform (CRISPR-FET) for the rapid identification of influenza A virus. The CRISPR-FET platform described herein enables the detection of viral RNA without amplification within 20 min, with a limit of detection as low as 1 copy/μL. Secondly, a reporter RNA conjugated with gold particles is used to achieve signal amplification in FET detection; meanwhile, the method eliminates probe immobilization, thereby omitting this step and simplifying chip modification to reduce complex work-flows and pre-treatment costs. The chip’s reusability further enhances cost-effectiveness. Additionally, streptavidin-modified magnetic bead adsorption minimizes background errors from excessive reporter RNA and non-target nucleic acids. Finally, validation with 24 clinical samples confirmed the platform’s efficacy. By integrating rapidity, simplicity, and high sensitivity, alongside cost advantages from reusable chips, this CRISPR-FET platform meets the critical need for early influenza A diagnosis and holds promise for advancing POCT and large-scale epidemiological screening. Full article

Cronobacter sakazakii is a foodborne pathogen of major concern due to its link with severe neonatal infections through powdered infant formula (PIF). However, its genomic epidemiology in Bangladesh remains uncharacterized. We report the first whole-genome analysis of three isolates from PIF. Two isolates (S41_PIFM and S44_RUTF) belonged to ST83, a lineage repeatedly associated with neonatal meningitis, septicemia, and persistence in PIF production environments, while the third (S43_TF) represented ST789, a recently described and rare lineage of unknown pathogenic potential. Pan-genome and comparative analyses identified 39 virulence determinants, 19 antimicrobial-resistance genes, and diverse mobile genetic elements. ST83 isolates harbored plasmid replicons IncFII(pCTU2) and pESA2, while the ST789 isolate carried insertion sequence ISKpn34, indicating horizontal gene transfer potential. All strains encoded I-E CRISPR-Cas systems. The detection of globally recognized high-risk ST83 clones alongside the novel ST789 lineage highlights emerging public health risks. This study provides the first genomic insights into C. sakazakii in Bangladesh and underscores the urgent need for genomic surveillance and strengthened food safety monitoring to protect infant health in low- and middle-income countries. Full article

Background: Lung adenocarcinoma (LUAD) presents a significant clinical challenge due to its high heterogeneity and limited treatment efficacy, creating an urgent need for reliable prognostic biomarkers and novel therapeutic targets. Integrating functional genomic vulnerabilities with patient multi-omics data offers a promising approach. Methods: We identified genes essential for LUAD cell proliferation from genome-scale CRISPR-Cas9 screening data (DepMap). These were integrated with transcriptomic data from the TCGA-LUAD cohort to select candidate genes. A prognostic risk-score model was constructed using LASSO and multivariate Cox regression analyses and validated in independent GEO datasets. We analyzed the model’s association with clinical features, signaling pathways, tumor immune microenvironment, and drug sensitivity. The predictive value for immunotherapy response was assessed using a real-world cohort. The core gene SPC25 was further validated through in vitro and in vivo experiments and single-cell RNA-seq analysis. Results: A robust 7-gene risk-score model was established. This model effectively stratified patient prognosis in training and validation sets and was an independent prognostic factor. A high-risk score correlated with advanced tumor stage and an immunosuppressive microenvironment. High expression of the signature genes predicted poor immunotherapy response. Functional experiments confirmed that SPC25 knockdown significantly inhibited LUAD cell proliferation, migration, and colony formation. Critically, in vivo xenograft experiments demonstrated that SPC25 depletion markedly suppressed tumor growth. Single-cell sequencing revealed high SPC25 expression in tumor cells and specific immunosuppressive T-cell subsets. Conclusions: We developed a potent prognostic model for LUAD and validated SPC25 as a key oncogene and promising therapeutic target. Full article

Inherited retinal degenerations (IRDs), driven by pathogenic mutations, often involve primary dysfunction of the retinal pigment epithelium (RPE)—a pathogenic feature shared with atrophic age-related macular degeneration (aAMD), despite aAMD’s multifactorial etiology. Prominin-1 (Prom1), traditionally linked to photoreceptor pathology, has an unclear role in RPE homeostasis. We assessed Prom1 expression in C57BL/6J mouse retina sections and RPE flat mounts using immunohistochemistry and generated Prom1-knockout (KO) mouse RPE cells via CRISPR/Cas9. Bulk RNA sequencing with DESeq2 and gene set enrichment analysis (GSEA) revealed Prom1-regulated pathways. Prom1-KO cells exhibited upregulation of Grem1, Slc7a11, Serpine2, Il1r1, and IL33 and downregulation of Ablim1, Cldn2, IGFBP-2, BMP3, and OGN. Hallmark pathway interrogation identified reduced expression of PINK1 (mitophagy) and MerTK (phagocytosis), implicating defects in mitochondrial quality control and outer segment clearance. Enrichment analysis revealed activation of E2F/MYC targets, mTORC1 signaling, oxidative phosphorylation, and TNFα/NF-κB signaling, alongside suppression of apical junctions, bile acid metabolism, and Epithelial-Mesenchymal Transition (EMT) pathways. These findings suggest Prom1 safeguards RPE integrity by modulating stress responses, mitochondrial turnover, phagocytosis, metabolism, and junctional stability. Our study uncovers Prom1-dependent signaling networks, providing mechanistic insights into RPE degeneration relevant to both IRD and aAMD, and highlights potential therapeutic targets for preserving retinal health. Full article

Alzheimer’s disease (AD), the leading cause of dementia, is defined by two pathological hallmarks, amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles—both now structurally resolved at near-atomic precision thanks to cryo-EM. Despite decades of research, effective disease-modifying therapies remain elusive, underscoring the need for innovative interdisciplinary approaches. This review synthesizes recent advances in structural biology and nanotechnology, highlighting their synergistic potential in revolutionizing AD diagnosis and treatment. Cryo-EM and NMR have revolutionized our understanding of Aβ/tau polymorphs, revealing structural vulnerabilities ripe for therapeutic targeting—yet clinical translation remains bottlenecked by the blood–brain barrier (BBB). Concurrently, nanotechnology offers groundbreaking tools, including nanoparticle-based drug delivery systems for blood–brain barrier (BBB) penetration, quantum dot biosensors for early Aβ detection, and CRISPR-nano platforms for APOE4 gene editing. We discuss how integrating these disciplines addresses critical challenges in AD management—from early biomarker detection to precision therapeutics—and outline future directions for translating these innovations into clinical practice. Full article

The convergence of agricultural biotechnology and artificial intelligence is reshaping modern crop improvement. Despite a surge of studies integrating artificial intelligence and biotechnology, the rapidly expanding literature on intelligent crop breeding remains fragmented across molecular, phenotypic, and computational dimensions. Existing reviews often rely on traditional bibliometric or narrative approaches that fail to capture the deep semantic evolution of research themes. To address this gap, this study employs the BERTopic model to systematically analyze 1867 articles (1995–2025, WoS Core Collection), mapping the thematic landscape and temporal evolution of intelligent crop breeding and revealing how methodological and application-oriented domains have co-evolved over time. Eight core topics emerge, i.e., (T0) genomic prediction and genotype–environment modeling; (T1) UAV remote sensing and multimodal phenotyping; (T2) stress-tolerant breeding and root phenotypes; (T3) ear/pod counting with deep learning; (T4) grain trait representation and evaluation; (T5) CRISPR and genome editing; (T6) spike structure recognition and 3D modeling; and (T7) maize tassel detection and developmental staging. Topic-evolution analyses indicate a co-development pattern, where genomic prediction provides a stable methodological backbone, while phenomics (UAV/multimodal imaging, organ-level detection, and 3D reconstruction) propels application-oriented advances. Attention dynamics reveal increasing momentum in image-based counting (T3), grain quality traits (T4), and CRISPR-enabled editing (T5), alongside a plateau in traditional mainstays (T0, T1) and mild cooling in root phenotyping under abiotic stress (T2). Quality stratification (citation quartiles, Q1–Q4) shows high-impact concentration in T0/T1 and a growing tail of application-driven work across T3–T7. Journal analysis reveals a complementary publication ecosystem: Frontiers in Plant Science and Plant Methods anchor cross-disciplinary dissemination; Remote Sensing and Computers and Electronics in Agriculture host engineering-centric phenomics; genetics/breeding journals sustain T0/T2; and molecular journals curate T5. These findings provide an integrated overview of methods, applications, and publication venues, offering practical guidance for research planning, cross-field collaboration, and translational innovation in intelligent crop breeding. Full article

The domesticated silkworm, Bombyx mori, is a highly valued biodiversity and economic asset, acclaimed for its silk production, besides making important contributions to various scientific disciplines. However, the sericulture industry faces ongoing threats from bacterial and viral infections, which severely impact silkworm health and silk yield. This review provides a comprehensive overview of the innate immune response of B. mori against bacterial and viral pathogens, emphasizing the fundamental molecular and cellular defense mechanisms. We explore the humoral and cellular immune response using antimicrobial peptides (AMPs), pattern recognition receptors (PRRs) like peptidoglycan recognition protein (PGRP), and glucan recognition protein (GRP), which activate canonical signaling pathways. The review further highlights the molecular mechanisms underlying the silkworm’s defense against viruses, incorporating RNA interference (RNAi), apoptosis, and distinct signaling pathways such as Toll and Imd, JAK/STAT, and STING. We also discussed the viral suppression strategies and modulation of host metabolism during infection. Furthermore, the review explores the recent use of CRISPR-Cas gene editing to enhance disease resistance, presenting a promising avenue for mitigating pathogen-induced losses in sericulture. By elucidating these mechanisms, the work provides a synthesis that is critical in terms of developing particular interventions and developing more resistant silkworm strains to ensure that the industry of sericulture becomes viable and productive. Full article

Background: Pseudomonas aeruginosa infection is a major driver of morbidity and mortality in cystic fibrosis (CF), yet disease severity varies widely among people with CF (pwCF). This clinical heterogeneity suggests the involvement of host genetic modifiers beyond CFTR. We previously identified sphingosine 1-phosphate receptor 1 (S1PR1) as a candidate gene associated with susceptibility to P. aeruginosa. Here, we investigated its role in modulating airway epithelial responses to infection. Methods: Using CRISPR/Cas9, we generated S1PR1-knockout bronchial epithelial cells with (IB3-1) and without (C38) CFTR mutations. We assessed cell viability, cytotoxicity, and interleukin-8 secretion following exposure to P. aeruginosa exoproducts. S1PR1 protein expression was evaluated in lung tissue from pwCF and non-CF individuals using immunohistochemistry. Results: S1PR1-mutant cells produced truncated, non-functional peptides. In CFTR-mutant cells, S1PR1 loss reduced viability, increased cytotoxicity, and significantly enhanced interleukin-8 production in response to P. aeruginosa exoproducts. These effects were not observed in CFTR-competent cells. Notably, S1PR1 protein levels were markedly lower in lung tissue from pwCF compared to non-CF individuals. Conclusions: S1PR1 deficiency exacerbates epithelial damage and inflammatory responses to P. aeruginosa in CF models. These findings highlight S1PR1 as a potential contributor to infection severity and a promising target for therapeutic strategies in pwCF. Full article