Search Results (10,136)

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical and chemotherapeutic approaches, the presence of metastatic or recurrent disease is still detrimental to the patient’s outcome. Major advances in understanding the molecular mechanisms of OS are needed to substantially improve outcomes for patients being treated for OS. This review integrates new data on the molecular biology, pathophysiology, and immune landscape of OS, as well as introducing salient areas of tumorigenesis underpinning these findings, such as chromothripsis; kataegis; cancer stem cell dynamics; and updated genetic, epigenetic, and glycosylation modifiers. In addition, we review promising biomarkers, diagnostic platforms, and treatments, including immunotherapy, targeted small molecule inhibitors, and nanomedicine. Using genomic techniques, we have defined OS for its significant genomic instability due to TP53 and RB1 mutations, chromosomal rearrangements, and aberrant glycosylation. The TME is also characterized as immunosuppressive and populated by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, ultimately inhibiting immune checkpoint inhibitors. Emerging fields such as glycomics and epigenetics, as well as stem cell biology, have defined promising biomarkers and targets. Preclinical studies have identified that glycan-directed CAR therapies could be possible, as well as metabolic inhibitors and 3D tumor models, which presented some preclinical success and could allow for tumoral specificity and enhanced efficacy. OS is a biologically and clinically complex disease; however, advances in exploring the molecular and immunologic landscape of OS present new opportunities in biomarkers and the development of new treatment options with adjunctive care. Successful treatments in the future will require personalized, multi-targeted approaches to account for tumor heterogeneity and immune evasion. This will help us turn the corner in providing improved outcomes for patients with this resilient malignancy. Full article

Telomeres are protective DNA sequences located at chromosome ends, essential to maintaining genomic stability. This narrative review examines how maternal lifestyle factors during pregnancy influence fetal telomere length (TL). Positive associations have been identified between offspring’s TL and maternal consumption of nutrients such as vitamins C and D, folate, and magnesium. Additionally, adherence to a Mediterranean diet and regular physical activity during pregnancy are correlated with increased placental TL, supporting fetal genomic integrity. Conversely, maternal dietary patterns high in carbohydrates, fats, or alcohol, as well as exposure to triclosan and sleep-disordered breathing, negatively correlate with offspring’s TL. Maternal infections may also shorten TL through heightened inflammation and oxidative stress. However, evidence regarding the impact of other lifestyle factors—including maternal stress, smoking, caffeine intake, polyunsaturated fatty acid consumption, obesity, and sleep quality—remains inconsistent. Given that shorter telomere length has been associated with cardiovascular, pulmonary, and neurodegenerative diseases, as well as certain types of cancer, these findings highlight the vital importance of maternal health during pregnancy in order to prevent potential adverse effects on the fetus. Further studies are required to elucidate the precise timing, intensity, and interplay of these influences, enabling targeted prenatal interventions to enhance offspring health outcomes. Full article

Rubus magurensis Wolanin, M. Nobis & Oklej. (Rosaceae), a new species from the Northern Carpathians, described and illustrated here, is a tetraploid (2n = 28) belonging to the subgenus Rubus series Micantes. Among the most characteristic features of this species are first-year stems that are almost glabrous, leaflets most often arched downward, and inflorescences leafy to the apex with a few simple oval leaves in the upper part, which make this species easy to recognise. This species resembles R. tabanimontanus Figert, from which it differs in having smaller primocane prickles, digitate to subpedate leaves, larger flowers, and inflorescences leafy to the apex. Rubus magurensis is currently known from 11 populations located in southeastern Poland (7 ATPOL 2 × 2 km units). Most of them were found in the central part of the Low Beskid Mts., with two populations located in the northwestern part of the Strzyżów Foothills. Full article

Gastrodia elata Blume is an important medicinal orchid, yet its large-scale cultivation is increasingly threatened by fungal diseases. The 4-coumarate–CoA ligase (4CL) gene family directs a key step in phenylpropanoid metabolism and plant defence, but its composition and function in G. elata have not been investigated. We mined the G. elata genome for 4CL homologues, mapped their chromosomal locations, and analysed their gene structures, conserved motifs, phylogenetic relationships, promoter cis-elements and codon usage bias. Publicly available transcriptomes were used to examine tissue-specific expression and responses to fungal infection. Subcellular localisation of selected proteins was verified by transient expression in Arabidopsis protoplasts. Fourteen Ge4CL genes were identified and grouped into three clades. Two members, Ge4CL2 and Ge4CL5, were strongly upregulated in tubers challenged with fungal pathogens. Ge4CL2 localised to the nucleus, whereas Ge4CL5 localised to both the nucleus and the cytoplasm. Codon usage analysis suggested that Escherichia coli and Oryza sativa are suitable heterologous hosts for Ge4CL expression. This study provides the first genome-wide catalogue of 4CL genes in G. elata and suggests that Ge4CL2 and Ge4CL5 may participate in antifungal defence, although functional confirmation is still required. The dataset furnishes a foundation for functional characterisation and the molecular breeding of disease-resistant G. elata cultivars. Full article

Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a higher incidence and mortality rate, with left-sided (distal) CRC predominating, while females are more frequently diagnosed with right-sided (proximal) tumors, which tend to be more aggressive and less responsive to conventional chemotherapy. Genetic disparities, including microsatellite instability and X-chromosome tumor suppressor genes, contribute to sex-specific differences in tumor progression and treatment response. Immune variations also influence disease outcomes, with females exhibiting stronger immune surveillance but higher exhaustion markers. Lifestyle factors such as body mass index (BMI), smoking, and hormonal influences further modulate CRC risk. While males are more vulnerable to obesity-related CRC, central obesity (waist-to-hip ratio) emerges as a stronger predictor in females. Additionally, smoking increases CRC risk differentially by tumor location. These findings underscore the importance of sex-specific approaches in CRC prevention, screening, and treatment, advocating for personalized medicine strategies tailored to gender-based biological and clinical distinctions. Full article

More than 5.9 million plant germplasm accessions currently conserved in over 850 national genebanks worldwide will accumulate deleterious mutations over long-term conservation. However, little is known about how mutations accumulate in germplasm under long-term conservation. An attempt was made using seed-based RNA-Seq analysis to identify and characterize deleterious genetic variants in 190 diverse soybean accessions that were conserved since 1972 and were regenerated up to 10 cycles. The analysis identified 588 deleterious variants, which were widely distributed across 20 soybean chromosomes, mostly present in 10 or fewer samples, associated with diverse biological processes, and largely predicted to be weakly and mildly detrimental. Significant differences in estimates of three mutation burdens (total, heterozygous, and homozygous) were found among the samples, including sample groups representing different countries of origin. Total and heterozygous mutation burden estimates were found to increase significantly with the number of conservation years since accession acquisition and the number of germplasm regenerations, but homozygous mutation burden estimates were not correlated with these two conservation-related accession features. Total mutation burden estimates were negatively correlated with expressed gene counts and RNA integrity numbers (RINs) and marginally positively associated with averaged gene expression levels. Correlations were also found among expressed gene count, averaged gene expression level, and RIN value. No significant differences were detected between seed-based and leaf-based estimates of total mutation burden, expressed gene count, averaged expression level, and RIN. These findings provide the first empirical evidence that total mutation burden increased primarily through the accumulation of heterozygous, rather than homozygous, deleterious mutations over successive soybean germplasm regenerations. This insight is useful for conducting informative assessments of deleterious mutation accumulation and enhancing the management and conservation of plant germplasm. Full article

Seed oil represents a key trait in soybeans, which holds substantial economic significance, contributing to roughly 60% of global oilseed production. This research employed genome-wide association mapping to identify genetic loci associated with oil content in soybean seeds. A panel comprising 341 soybean accessions, primarily sourced from Northeast China, was assessed for seed oil content at Heilongjiang Province in three replications over two growing seasons (2021 and 2023) and underwent genotyping via whole-genome resequencing, resulting in 1,048,576 high-quality SNP markers. Phenotypic analysis indicated notable variation in oil content, ranging from 11.00% to 21.77%, with an average increase of 1.73% to 2.28% across all growing regions between 2021 and 2023. A genome-wide association study (GWAS) analysis revealed 119 significant single-nucleotide polymorphism (SNP) loci associated with oil content, with a prominent cluster of 77 SNPs located on chromosome 8. Candidate gene analysis identified four key genes potentially implicated in oil content regulation, selected based on proximity to significant SNPs (≤10 kb) and functional annotation related to lipid metabolism and signal transduction. Notably, Glyma.08G123500, encoding a receptor-like kinase involved in signal transduction, contained multiple significant SNPs with PROVEAN scores ranging from deleterious (−1.633) to neutral (0.933), indicating complex functional impacts on protein function. Additional candidate genes include Glyma.08G110000 (hydroxycinnamoyl-CoA transferase), Glyma.08G117400 (PPR repeat protein), and Glyma.08G117600 (WD40 repeat protein), each showing distinct expression patterns and functional roles. Some SNP clusters were associated with increased oil content, while others correlated with decreased oil content, indicating complex genetic regulation of this trait. The findings provide molecular markers with potential for marker-assisted selection (MAS) in breeding programs aimed at increasing soybean oil content and enhancing our understanding of the genetic architecture governing this critical agricultural trait. Full article

Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic malignancy defined by the uncontrolled proliferation of lymphoid precursors. Accurate diagnosis and effective therapeutic strategies hinge on a comprehensive understanding of the genetic and molecular landscape of ALL. This review synthesizes the latest updates in cytogenetic and molecular classifications, emphasizing the 2022 World Health Organization (WHO) and International Consensus Classification (ICC) revisions. Key chromosomal alterations such as BCR::ABL1 and ETV6::RUNX1 and emerging subtypes including Ph-like ALL, DUX4, and MEF2D rearrangements are examined for their prognostic significance. Furthermore, we assess novel diagnostic tools, notably next-generation sequencing (NGS) and optical genome mapping (OGM). While NGS excels at identifying point mutations and small indels, OGM offers high-resolution structural variant detection with 100% sensitivity in multiple validation studies. These advancements enhance our grasp of leukemogenesis and pave the way for precision medicine in both B- and T-cell ALL. Ultimately, integrating these innovations into routine diagnostics is crucial for personalized patient management and improving clinical outcomes. Full article

Background/Objectives: This study examines how seasonality, pollution, and sample type (water and sediment) influence the presence and distribution of antibiotic resistance genes (ARGs), with a focus on antibiotic resistance genes (ARGs) located on plasmids (the complete set of plasmid-derived sequences, including ARGs) in a tropical urban river. Methods: Samples were collected from three sites along a pollution gradient in the Virilla River, Costa Rica, during three seasonal campaigns (wet 2021, dry 2022, and wet 2022). ARGs in water and sediment were quantified by qPCR, and metagenomic sequencing was applied to analyze chromosomal and plasmid-associated resistance profiles in sediments. Tobit and linear regression models, along with multivariate ordination, were used to assess spatial and seasonal trends. Results: During the wet season of 2021, the abundance of antibiotic resistance genes (ARGs) such as sul-1, intI-1, and tetA in water samples decreased significantly, likely due to dilution, while intI-1 and tetQ increased in sediments, suggesting particle-bound accumulation. In the wet season 2022, intI-1 remained low in water, qnrS increased, and sediments showed significant increases in tetQ, tetA, and qnrS, along with decreases in sul-1 and sul-2. Metagenomic analysis revealed spatial differences in plasmid-associated ARGs, with the highest abundance at the most polluted site (Site 3). Bacterial taxa also showed spatial differences, with greater plasmidome diversity and a higher representation of potential pathogens in the most contaminated site. Conclusions: Seasonality and pollution gradients jointly shape ARG dynamics in this tropical river. Plasmid-mediated resistance responds rapidly to environmental change and is enriched at polluted sites, while sediments serve as long-term reservoirs. These findings support the use of plasmid-based monitoring for antimicrobial resistance surveillance in aquatic systems. Full article

Down syndrome (DS), stemming from the triplication of human chromosome 21, results in intellectual disability, with early mid-life onset of Alzheimer’s disease (AD) pathology. Early interventions to reduce cognitive impairments and neuropathology are lacking. One modality, maternal choline supplementation (MCS), has shown beneficial effects on behavior and gene expression in neurodevelopmental and neurodegenerative disorders, including trisomic mice. Loss of basal forebrain cholinergic neurons (BFCNs) and other DS/AD relevant hallmarks were observed in a well-established trisomic model (Ts65Dn, Ts). MCS attenuates these endophenotypes with beneficial behavioral effects in trisomic offspring. We postulate MCS ameliorates dysregulated cellular mechanisms within vulnerable BFCNs, with attenuation driven by novel gene expression. Here, choline acetyltransferase immunohistochemical labeling identified BFCNs in the medial septal/ventral diagonal band nuclei of the basal forebrain in Ts and normal disomic (2N) offspring at ~11 months of age from dams exposed to MCS or normal choline during the perinatal period. BFCNs (~500 per mouse) were microisolated and processed for RNA-sequencing. Bioinformatic assessment elucidated differentially expressed genes (DEGs) and pathway alterations in the context of genotype (Ts, 2N) and maternal diet (MCS, normal choline). MCS attenuated select dysregulated DEGs and relevant pathways in aged BFCNs. Trisomic MCS-responsive improvements included pathways such as cognitive impairment and nicotinamide adenine dinucleotide signaling, among others, indicative of increased behavioral and bioenergetic fitness. Although MCS does not eliminate the DS/AD phenotype, early choline delivery provides long-lasting benefits to aged trisomic BFCNs, indicating that MCS prolongs neuronal health in the context of DS/AD. Full article

Cancer is a major global health issue, with rising incidence rates highlighting the urgent need for more effective treatments. Despite advances in cancer therapy, challenges such as adverse effects and limitations of existing treatments remain. Immunotherapy, which harnesses the body’s immune system to target cancer cells, offers promising solutions. Gamma delta (γδ) T cells are noteworthy due to their potent ability to kill various cancer cells without needing conventional antigen presentation. Recent studies have focused on the role of γδ T cells in α-galactosylceramide (α-GalCer)-mediated immunity, opening new possibilities for cancer immunotherapy. We engineered humanized T cell receptor (HuTCR)-T1 γδ mice by replacing mouse sequences with human counterparts. This study investigates the cytotoxic activity of humanized γδ T cells against several human cancer cell lines (A431, HT-29, K562, and Daudi) in vitro, aiming to elucidate mechanisms underlying their anticancer efficacy. Human cancer cells were co-cultured with humanized γδ T cells, with and without α-GalCer, for 24 h. The humanized γδ T cells showed enhanced cytotoxicity across all tested cancer cell lines compared to wild-type γδ T cells. Additionally, γδ T cells from HuTCR-T1 mice exhibited higher levels of anticancer cytokines (IFN-γ, TNF-α, and IL-17) and Granzyme B, indicating their potential as potent mediators of anticancer immune responses. Blocking γδ T cells’ cytotoxicity confirmed their γδ-mediated function. These findings represent a significant step in preclinical development of γδ T cell-based cancer immunotherapies, providing insights into their mechanisms of action, optimization of therapeutic strategies, and identification of predictive biomarkers for clinical application. Full article

Background/Objectives: Late embryogenesis abundant (LEA) proteins regulate stress responses and contribute significantly to plant stress tolerance. As a model species for stress resistance studies, foxtail millet (Setaria italica) lacks comprehensive characterization of its LEA gene family. This study aimed to comprehensively identify SiLEA genes in foxtail millet and elucidate their functional roles and tissue-specific expression patterns. Methods: Genome-wide identification of SiLEA genes was conducted, followed by phylogenetic reconstruction, cis-acting element analysis of promoters, synteny analysis, and expression profiling. Results: Ninety-four SiLEA genes were identified and classified into nine structurally distinct subfamilies, which are unevenly distributed across all nine chromosomes. Phylogenetic analysis showed closer clustering of SiLEA genes with sorghum and rice orthologs than with Arabidopsis thaliana AtLEA genes. Synteny analysis indicated the LEA gene family expansion through tandem and segmental duplication. Promoter cis-element analysis linked SiLEA genes to plant growth regulation, stress responses, and hormone signaling. Transcriptome analysis revealed tissue-specific expression patterns among SiLEA members, while RT-qPCR verified ABA-induced transcriptional regulation of SiLEA genes. Conclusions: This study identified 94 SiLEA genes grouped into nine subfamilies with distinct spatial expression profiles. ABA treatment notably upregulated SiASR-2, SiASR-5, and SiASR-6 in both shoots and roots. Full article

Artificial gynogenesis is an essential technique for aquaculture breeding. Fertile offspring of the WuLi carp (Cyprinus carpio var. Quanzhounensis, 2n = 100, WLC) were successfully produced via gynogenesis using ultraviolet-irradiated sperm from the blunt snout bream (Megalobrama amblycephala, 2n = 48, BSB). As anticipated, gonadal section examination confirmed that all gynogenetic WuLi carp (2n = 100, GWB) were female. To investigate whether paternal DNA fragments from BSB were integrated into the GWB genome, comparative analyses of morphological traits, DNA content, chromosomal numbers, 5S rDNA sequences, microsatellite DNA markers, fluorescence in situ hybridization (FISH), growth performance and nutritional composition were systematically conducted between GWB and maternal WLC. The results revealed pronounced maternal inheritance patterns across morphological characteristics, DNA quantification, chromosomal configurations, 5S rDNA sequences and FISH signals, while microsatellite detection unequivocally confirmed paternal BSB DNA fragment integration into the GWB genome. Remarkably, GWB demonstrated significantly superior growth performance and elevated unsaturated fatty acid content relative to the maternal line. This approach not only addressed germplasm degradation in WLC but also provided valuable theoretical foundations for breeding programs in this commercially significant species. Full article

Human colorectal cancer (CRC) encompasses tumors affecting a segment of the large intestine (colon) and rectum. It is the third most commonly diagnosed malignancy and the second leading cause of cancer deaths worldwide. It is a multifactorial disease, whose carcinogenesis process involves genetic and epigenetic alterations in oncogenes and tumor suppressor genes, including genes related to DNA repair. The pathogenic mechanisms are described based on the pathways of chromosomal instability, microsatellite instability, and CpG island methylator phenotype. When detected early, CRC is potentially curable, and its treatment is based on the pathological characteristics of the tumor and factors related to the patient, as well as on drug efficacy and toxicity studies. Therefore, the aim of this study was to review the pathogenesis and molecular subtypes of CRC and to describe the main targets of disease-directed therapy used in patients refractory to current treatments. Full article

Telomeres are terminal regions of chromosomes that protect and stabilize chromosome structures. Telomeres are usually composed of specific DNA repeats (motifs) that are maintained by telomerase and a complex of specific proteins. Telomeric DNA sequences are generally highly conserved throughout the evolution of different groups of eukaryotes. The most common motif in insects is TTAGG, but it is not universal, including in the large order Hemiptera. In particular, several derived telomeric motifs were identified in this order by analyzing chromosome-level genome assemblies or by FISH screening the chromosomes of target species. Here, we analyzed chromosome-level genome assemblies of 16 species from three hemipteran suborders, including Sternorrhyncha (Coccoidea: Planococcus citri, Acanthococcus lagerstroemiae, and Trionymus diminutus; Aphidoidea: Tuberolachnus salignus, Metopolophium dirhodum, Rhopalosiphum padi, and Schizaphis graminum), Auhenorrhyncha (Cicadomorpha: Allygus modestus, Arthaldeus pascuellus, Aphrophora alni, Cicadella viridis, Empoasca decipiens, and Ribautiana ulmi), and Heteroptera (Gerromorpha: Gerris lacustris; Pentatomomorpha: Aradus depressus and A. truncatus). In addition, scaffold-level genome assemblies of three more species of Heteroptera (Gerromorpha: Gerris buenoi, Microvelia longipes, and Hermatobates lingyangjiaoensis) were examined. The presumably ancestral insect motif TTAGG was found at the ends of chromosomes of all species studied using chromosome-level genome assembly analysis, with four exceptions. In Aphrophora alni, we detected sequences of 4 bp repeats of TGAC, which were tentatively identified as a telomeric motif. In Gerris lacustris, from the basal true bug infraorder Gerromorpha, we found a 10 bp motif TTAGAGGTGG, previously unknown not only in Heteroptera or Hemiptera but also in Arthropoda in general. Blast screening of the scaffold-level assemblies showed that TTAGAGGTGG is also likely to be a telomeric motif in G. buenoi and Microvelia. longipes, while the results obtained for H. lingyangjiaoensis were inconclusive. In A. depressus and A. truncatus from the basal for Pentatomomorpha family Aradidae, we found a 10 bp motif TTAGGGATGG. While the available data allowed us to present two alternative hypotheses about the evolution of telomeric motifs in Heteroptera, further data are needed to verify them, especially for the yet unstudied basal infraorders Enicocephalomorpha, Dipsocoromorpha, and Leptopodomorpha. Full article