Search Results (1,238)

Plant architecture is a crucial agronomic trait significantly impacting soybean (Glycine max) yield. Traditional breeding has made some progress in optimizing soybean architecture, but it is limited in precision and efficiency. The Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein (CRISPR/Cas) system, a revolutionary gene-editing technology, provides unprecedented opportunities for plant genetic improvement. This review outlines CRISPR’s development and applications in crop improvement, focusing specifically on progress regulating soybean architecture traits affecting yield, such as node number, internode length, branching, and leaf morphology. It also discusses the technical challenges for CRISPR technology in enhancing soybean architecture, including that the regulatory network of soybean plant architecture is complex and the development of multi-omics platforms helps gene mining. The application of CRISPR enables precise the regulation of gene expression through promoter editing. Meanwhile, it is also faced with technical challenges such as the editing of homologous genes caused by genome polyploidy, the efficiency of editing tools and off-target effects, and low transformation efficiency. New delivery systems such as virus-induced genome editing bring hope for solving some of these problems. The review emphasizes the great potential of CRISPR technology in breeding next-generation soybean varieties with optimized architecture to boost yield potential. Full article

This study focuses on the development and evaluation of automatic speech recognition (ASR) systems for Kazakh child speech, an underexplored domain in both linguistic and computational research. A specialized acoustic corpus was constructed for children aged 2 to 8 years, incorporating age-related vocabulary stratification and gender variation to capture phonetic and prosodic diversity. The data were collected from three sources: a custom-designed Telegram bot, high-quality Dictaphone recordings, and naturalistic speech samples recorded in home and preschool environments. Four ASR models, Whisper, DeepSpeech, ESPnet, and Vosk, were evaluated. Whisper, ESPnet, and DeepSpeech were fine-tuned on the curated corpus, while Vosk was applied in its standard pretrained configuration. Performance was measured using five evaluation metrics: Word Error Rate (WER), BLEU, Translation Edit Rate (TER), Character Similarity Rate (CSRF2), and Accuracy. The results indicate that ESPnet achieved the highest accuracy (32%) and the lowest WER (0.242) for sentences, while Whisper performed well in semantically rich utterances (Accuracy = 33%; WER = 0.416). Vosk demonstrated the best performance on short words (Accuracy = 68%) and yielded the highest BLEU score (0.600) for short words. DeepSpeech showed moderate improvements in accuracy, particularly for short words (Accuracy = 60%), but faced challenges with longer utterances, achieving an Accuracy of 25% for sentences. These findings emphasize the critical importance of age-appropriate corpora and domain-specific adaptation when developing ASR systems for low-resource child speech, particularly in educational and therapeutic contexts. Full article

Systemic light-chain (AL) amyloidosis is a challenging, complex and heterogeneous disease. AL amyloidosis is classified under the category of plasma cell neoplasms and other diseases with paraproteins in the fifth edition of the World Health Organization classification of lymphoid tumors. Epidemiological information is limited, largely due to its low incidence and the lack of a global network of population-based specific registries. Despite recent advances, AL amyloidosis is still considered an incurable disease. The presence of a precursor disease, particularly monoclonal gammopathy of uncertain significance, is the main consolidated risk factor. Limited knowledge about other risk factors precludes the possibility of establishing preventive measures. A relevant percentage of AL amyloidosis patients fulfill the current diagnostic criteria of multiple myeloma. Incidence should be evaluated in the setting of population-based studies. On the one hand, incidence shows a slightly increasing pattern. On the other hand, survival is progressively increasing. Consequently, prevalence is also rising. Early mortality, commonly associated with advanced heart involvement, remains a serious drawback to improve the outcome. Epidemiology represents the first level of heterogeneity in AL amyloidosis. Both genomic and clinical epidemiological research in systemic AL amyloidosis have a crucial role in the global strategy to combat this multifaceted disease. Full article

Human induced pluripotent stem cells (iPSCs) can be genetically engineered to evade host immune recognition, rendering them hypoimmunogenic and suitable as “universal donor” cells for allogeneic transplantation. Such modifications enable the development of off-the-shelf iPSC-derived therapeutics that are immediately available for clinical use without the need for patient-specific derivation or immunosuppression. This review focuses on recent developments in strategies for generating hypoimmunogenic human iPSCs, with particular emphasis on their applications in central nervous system (CNS) cell therapy and repair. We assess immunomodulatory factors based on their immune functions and potential roles in CNS development and disease, with the goal of identifying strategies to use these factors either individually, in combination, or alongside gene editing to reduce immune rejection without compromising neurogenesis or tissue repair. Full article

Background: Centella asiatica, a medicinally important species that is rich in bioactive compounds, lacks a characterized mitochondrial genome, despite nuclear and chloroplast assemblies. We sequenced and annotated its mitochondrial genome to elucidate its genetic foundations and evolutionary mechanisms. Methods: Assembly using Illumina short-reads and Nanopore long-reads was used to characterize the mitochondrial genome. Analyses included structural characterization, codon usage bias, repetitive sequences, horizontal gene transfer (HGT), collinearity, and phylogeny. The resulting tissue-specific (root, stem, and leaf) long non-coding RNA (lncRNA) profiles identified RNA editing sites. Results: The complete mitochondrial genome (249,777 bp, 45.5% GC) comprises three circular contigs encoding 51 genes (33 protein-coding, 15 tRNA, and 3 rRNA). Comparative genomics revealed synteny with the Apiaceae family of plants and evidence of HGT. Phylogenetic analysis resolved taxonomic relationships within Apiales. We predicted that 547 RNA editing sites would be identified in its protein-coding genes. Tissue profiling identified 725 (root), 711 (stem), and 668 (leaf) editing sites, with >71% concordance to predictions. RNA editing-generated cryptic promoters/terminators occur in mitochondrial core function genes (e.g., ATP synthase, cytochrome c reductase/oxidase, ribosome large subunit, and cytochrome c biogenesis), exhibiting a lower frequency in the leaves compared to the roots and stems. Conclusions: We provide the first complete mitochondrial genome assembly for C. asiatica, delineating its complex structure, tissue-modulated RNA editing, and evolutionary trajectory. This high-quality genomic resource establishes a foundation for molecular evolutionary studies and enhances the genomic toolkit for this pharmacologically significant species. Full article

Background/Objectives: Messenger RNA (mRNA) modifications regulate key steps in gene expression, including splicing, translation, and stability. Despite over 300 known RNA modifications, the relatively small subset occurring in mRNA remains understudied compared with tRNA and rRNA. This review aims to systematically evaluate 15 known naturally occurring mRNA-specific modifications, rank them by publication frequency, and highlight emerging frontiers in epitranscriptomics, including discovering new naturally occurring mRNA modifications and environmental RNA (eRNA) epitranscriptomics. Methods: We conducted a structured literature review of PubMed-indexed publications to rank mRNA modifications by citation prevalence. Key modifications such as m⁶A, m⁵C, Ψ, and m¹A were analyzed in terms of enzymatic machinery (“writers,” “erasers,” and “readers”), molecular functions, and physiological relevance. We also reviewed technological advances, with a focus on nanopore sequencing for detection of RNA modifications in native and environmental contexts. Results: The modification m⁶A was identified as the most studied mRNA modification, followed by Ψ, m⁵C, and A-to-I editing (inosine). These modifications influence diverse mRNA processes, including translation efficiency, localization, and immune evasion. Cap-specific modifications such as Cap0, Cap1, and Cap2 were also described, highlighting their role in transcript stability and innate immune regulation. Advances in nanopore sequencing have enabled direct detection of RNA modifications and offer promise for eRNA (environmental RNA) surveys. The potential for nanopore sequencing of many other of the 335 known RNA modifications in the MODOMICS database using existing nanopore technologies is also discussed. Conclusions: mRNA modifications represent a critical, yet incompletely mapped, layer of gene regulation. Continued research—especially using nanopore and machine learning technologies—will help uncover their full biological significance. Exploration of eRNA and identifying new mRNA modifications will redefine our understanding of RNA biology. Full article

Multidrug resistance (MDR) remains a formidable barrier to successful cancer treatment, driven by mechanisms such as efflux pump overexpression, enhanced DNA repair, evasion of apoptosis and the protective characteristics of the tumour microenvironment. Nanoparticle-based delivery systems have emerged as promising platforms capable of addressing these challenges by enhancing intracellular drug accumulation, enabling targeted delivery and facilitating stimuli-responsive and controlled release. This review provides a comprehensive overview of the molecular and cellular mechanisms underlying MDR and critically examines recent advances in nanoparticle strategies developed to overcome it. Various nanoparticle designs are analysed in terms of their structural and functional features, including surface modifications, active targeting ligands and responsiveness to tumour-specific cues. Particular emphasis is placed on the co-delivery of chemotherapeutic agents with gene regulators, such as siRNA, and the use of nanoparticles to deliver CRISPR/Cas9 gene editing tools as a means of re-sensitising resistant cancer cells. While significant progress has been made in preclinical settings, challenges such as tumour heterogeneity, limited clinical translation and immune clearance remain. Future directions include the integration of precision nanomedicine, scalable manufacturing and non-viral genome editing platforms. Collectively, nanoparticle-based drug delivery systems offer a multifaceted approach to combat MDR and hold great promise for improving therapeutic outcomes in resistant cancers. Full article

Retinitis pigmentosa is a group of inherited retinal dystrophies characterized by progressive photoreceptor cell loss leading to irreversible vision loss. Affecting approximately 1 in 4000 individuals worldwide, retinitis pigmentosa exhibits significant genetic heterogeneity, with mutations in genes such as RHO, PRPF31, RPE65, USH2A, and NR2E3, which contribute to its diverse clinical presentation. This review outlines the genetic basis of retinitis pigmentosa and explores cutting-edge gene-based therapeutic strategies. Luxturna (voretigene neparvovec-rzyl), the first FDA-approved gene therapy targeting RPE65 mutations, represents a milestone in precision ophthalmology, while OCU400 is a gene-independent therapy that uses a modified NR2E3 construct to modulate retinal homeostasis across different RP genotypes. Additionally, CRISPR–Cas genome-editing technologies offer future potential for the personalized correction of specific mutations, though concerns about off-target effects and delivery challenges remain. The article also highlights MCO-010, a novel optogenetic therapy that bypasses defective phototransduction pathways, showing promise for patients regardless of their genetic profile. Moreover, QR-1123, a mutation-specific antisense oligonucleotide targeting the P23H variant in the RHO gene, is under clinical investigation for autosomal dominant RP and has shown encouraging preclinical results in reducing toxic protein accumulation and preserving photoreceptors. SPVN06, another promising candidate, is a mutation-agnostic gene therapy delivering RdCVF and RdCVFL via AAV to support cone viability and delay degeneration, currently being evaluated in a multicenter Phase I/II trial for patients with various rod–cone dystrophies. Collectively, these advances illustrate the transition from symptom management toward targeted, mutation-specific therapies, marking a major advancement in the treatment of RP and inherited retinal diseases. Full article

This review synthesizes advances in livestock genomics by examining the interplay between candidate genes, molecular markers (MMs), signatures of selection (SSs), and quantitative trait loci (QTLs) in shaping economically vital traits across livestock species. By integrating advances in genomics, bioinformatics, and precision breeding, the study elucidates genetic mechanisms underlying productivity, reproduction, meat quality, milk yield, fibre characteristics, disease resistance, and climate resilience traits pivotal to meeting the projected 70% surge in global animal product demand by 2050. A critical synthesis of 1455 peer-reviewed studies reveals that targeted genetic markers (e.g., SNPs, Indels) and QTL regions (e.g., IGF2 for muscle development, DGAT1 for milk composition) enable precise selection for superior phenotypes. SSs, identified through genome-wide scans and haplotype-based analyses, provide insights into domestication history, adaptive evolution, and breed-specific traits, such as heat tolerance in tropical cattle or parasite resistance in sheep. Functional candidate genes, including leptin (LEP) for feed efficiency and myostatin (MSTN) for double-muscling, are highlighted as drivers of genetic gain in breeding programs. The review underscores the transformative role of high-throughput sequencing, genome-wide association studies (GWASs), and CRISPR-based editing in accelerating trait discovery and validation. However, challenges persist, such as gene interactions, genotype–environment interactions, and ethical concerns over genetic diversity loss. By advocating for a multidisciplinary framework that merges genomic data with phenomics, metabolomics, and advanced biostatistics, this work serves as a guide for researchers, breeders, and policymakers. For example, incorporating DGAT1 markers into dairy cattle programs could elevate milk fat content by 15-20%, directly improving farm profitability. The current analysis underscores the need to harmonize high-yield breeding with ethical practices, such as conserving heat-tolerant cattle breeds, like Sahiwal. Full article

Chemotherapy remains a cornerstone in the treatment of esophageal cancer (EC), yet chemoresistance remains a critical challenge, leading to poor outcomes and limited therapeutic success. Mitochondrial DNA (mtDNA) has emerged as a pivotal player in mediating these responses, influencing cellular metabolism, oxidative stress regulation, and apoptotic pathways. This review provides a comprehensive overview of the mechanisms by which mtDNA alterations, including mutations and copy number variations, drive chemoresistance in EC. Specific focus is given to the role of mtDNA in metabolic reprogramming, including its contribution to the Warburg effect and lipid metabolism, as well as its impact on epithelial–mesenchymal transition (EMT) and mitochondrial bioenergetics. Recent advances in targeting mitochondrial pathways through novel therapeutic agents, such as metformin and mitoquinone, and innovative approaches like CRISPR/Cas9 gene editing, are also discussed. These interventions highlight the potential for overcoming chemoresistance and improving patient outcomes. By integrating mitochondrial diagnostics with personalized treatment strategies, we propose a roadmap for future research that bridges basic mitochondrial biology with translational applications in oncology. The insights offered in this review emphasize the critical need for continued exploration of mtDNA-targeted therapies to address the unmet needs in EC management and other diseases associated with mitochondria. Full article

This article presents a spatial analysis of projects selected by city residents and implemented in five successive editions (2015–2019) of the participatory budgeting in Częstochowa, Poland. The study examines the relationship between the type of hard projects (small investments in public infrastructure and landscaping) and the pre-existing characteristics of the land use of each district. Kernel density estimation and Spearman correlation analysis were used. The highest spatial density occurred in projects related to the modernization of roads and sidewalks, recreation, and greenery, indicating a relatively high number of proposals within or near residential areas. Key correlations included the following: (1) greenery projects were more common in districts lacking green areas; (2) recreational infrastructure was more frequently chosen in areas with significant water features; (3) street furniture projects were mostly selected in districts with sparse development, scattered buildings, and postindustrial sites; (4) educational infrastructure was often chosen in low-density, but developing districts. The selected projects often reflect local deficits in specific land use or public infrastructure, but also stress the predestination of the recreational use of waterside areas. Full article

Lactic acid bacteria (LAB) are central to food, feed, and health biotechnology, yet their genomes have long resisted rapid, precise manipulation. This review charts the evolution of LAB genome-editing strategies from labor-intensive RecA-dependent double-crossovers to state-of-the-art CRISPR and CRISPR-associated transposase systems. Native homologous recombination, transposon mutagenesis, and phage-derived recombineering opened the door to targeted gene disruption, but low efficiencies and marker footprints limited throughput. Recent phage RecT/RecE-mediated recombineering and CRISPR/Cas counter-selection now enable scar-less point edits, seamless deletions, and multi-kilobase insertions at efficiencies approaching model organisms. Endogenous Cas9 systems, dCas-based CRISPR interference, and CRISPR-guided transposases further extend the toolbox, allowing multiplex knockouts, precise single-base mutations, conditional knockdowns, and payloads up to 10 kb. The remaining hurdles include strain-specific barriers, reliance on selection markers for large edits, and the limited host-range of recombinases. Nevertheless, convergence of phage enzymes, CRISPR counter-selection and high-throughput oligo recombineering is rapidly transforming LAB into versatile chassis for cell-factory and therapeutic applications. Full article

Microalgae, with their unparalleled capabilities for sunlight-driven growth, CO₂ fixation, and synthesis of diverse high-value compounds, represent sustainable cell factories for a circular bioeconomy. However, industrial deployment has been hindered by biological constraints and the inadequacy of conventional genetic tools. The advent of CRISPR-Cas systems initially provided precise gene editing via targeted DNA cleavage. This review argues that the true transformative potential lies in moving decisively beyond cutting to harness CRISPR as a versatile synthetic biology “Swiss Army Knife”. We synthesize the rapid evolution of CRISPR-derived tools—including transcriptional modulators (CRISPRa/i), epigenome editors, base/prime editors, multiplexed systems, and biosensor-integrated logic gates—and their revolutionary applications in microalgal engineering. These tools enable tunable gene expression, stable epigenetic reprogramming, DSB-free nucleotide-level precision editing, coordinated rewiring of complex metabolic networks, and dynamic, autonomous control in response to environmental cues. We critically evaluate their deployment to enhance photosynthesis, boost lipid/biofuel production, engineer high-value compound pathways (carotenoids, PUFAs, proteins), improve stress resilience, and optimize carbon utilization. Persistent challenges—species-specific tool optimization, delivery efficiency, genetic stability, scalability, and biosafety—are analyzed, alongside emerging solutions and future directions integrating AI, automation, and multi-omics. The strategic integration of this CRISPR toolkit unlocks the potential to engineer robust, high-productivity microalgal cell factories, finally realizing their promise as sustainable platforms for next-generation biomanufacturing. Full article

Rice seed storage proteins (SSPs) play a critical role in determining the nutritional quality, cooking properties, and digestibility of rice. To enhance seed quality, CRISPR/Cas9 genome editing was applied to modify SSP composition by targeting genes encoding 13 kDa prolamins and type A glutelins. Three CRISPR/Cas9 constructs were designed: one specific to the 13 kDa prolamin subfamily and two targeting conserved GluA glutelin regions. Edited T₀ and T₁ lines were generated and analyzed using InDel analysis, SDS-PAGE, Bradford assay, and RP-HPLC. Insertions were more frequent than deletions, accounting for 56% and 74% of mutations in prolamin and glutelin genes, respectively. Editing efficiency varied between sgRNAs. All lines with altered protein profiles contained InDels in target genes. SDS-PAGE confirmed the absence or reduction in bands corresponding to 13 kDa prolamins or GluA subunits, showing consistent profiles among lines carrying the same construct. Quantification revealed significant shifts in SSP composition, including increased albumin and globulin content. Prolamin-deficient lines showed reduced prolamins, while GluA-deficient lines exhibited increased prolamins. Total protein content was significantly elevated in all edited lines, suggesting enrichment in lysine-rich fractions. These findings demonstrate that CRISPR/Cas9-mediated editing of SSP genes can effectively reconfigure the rice protein profile and enhance its nutritional value. Full article

Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT). Key histone modifiers, including KLF5, EZH2, and the demethylases KDM4/6, regulate osteoclastogenic signaling pathways and the transition between metastatic dormancy and reactivation. Simultaneously, SWI/SNF chromatin remodelers such as BRG1 and BRM reconfigure enhancer–promoter interactions that promote bone tropism. Non-coding RNAs, including miRNAs, lncRNAs, and circRNAs (e.g., miR-34a, NORAD, circIKBKB), circulate via exosomes to modulate the RANKL/OPG axis, thereby conditioning the bone microenvironment and fostering the formation of a pre-metastatic niche. These mechanistic insights have accelerated the development of epigenetic therapies. DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling. Inhibitors targeting EZH2, BET proteins, and KDM1A are now advancing through early-phase clinical trials, often in combination with bisphosphonates or immune checkpoint inhibitors. Moreover, novel approaches such as CRISPR/dCas9-based epigenome editing and RNA-targeted therapies offer locus-specific reprogramming potential. Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases. Full article