Search Results (26,877)

Current aftercare after early breast cancer overlooks recent evidence on circulating free tumor DNA (ctDNA). In this case report, we present a patient with low-risk hormone-receptor-positive breast cancer. ctDNA was first detected using a tumor-informed approach 12 months after the initial diagnosis and remained positive throughout adjuvant therapy with letrozole, while routine staging examinations showed no signs of relapse. Clinical relapse was ultimately identified nearly six years after the initial diagnosis, resulting in a lead time of four years and nine months. Current studies on ctDNA in the adjuvant setting have been conducted in high-risk cohorts and have shown a median molecular lead time of 8.9–12.4 months. Our study supports the need for large randomized clinical trials involving low-risk breast cancer patients to drive changes in clinical practice. Full article

Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality worldwide, with a high proportion of cases diagnosed at advanced stages. Accurate mediastinal staging is essential to guide optimal therapeutic decisions. This study aimed to evaluate the diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and to develop a composite clinical–molecular score (EXPoSURE) for risk stratification. Methods: A retrospective study was performed that included 131 patients diagnosed with lung cancer between December 2023 and December 2024 at a regional oncology center in Oltenia, Romania. All patients underwent bronchoscopy and EBUS-TBNA using a standardized protocol. Clinical, pathological, and molecular data were collected to assess diagnostic yield, staging performance, and the association with molecular markers. The EXPoSURE score integrated PD-L1, p63, EGFR status, comorbidities, histological type, and TNM stage. Results: EBUS-TBNA provided a conclusive diagnosis in 91.6% of cases, with a low rebiopsy rate of 8.4% and no requirement for mediastinoscopy. Most patients (68%) were diagnosed at stage IV. PD-L1, p63, and EGFR expression showed no significant correlation with TNM stage, while the EXPoSURE score demonstrated promising stratification capability. Occupational exposure appeared to influence disease severity in some subgroups, although further validation is needed. Conclusions: EBUS-TBNA is a valuable, safe, and effective approach for minimally invasive diagnosis and mediastinal staging of lung cancer. The proposed EXPoSURE composite score may contribute to a multidimensional risk assessment, supporting more tailored management strategies and warranting prospective validation. Full article

Gerronema lapidescens (Lei Wan), a valued medicinal basidiomycete traditionally employed for antiparasitic and digestive ailments, faces severe conservation threats due to unsustainable wild harvesting and the absence of reliable cultivation protocols. To address this crisis and unlock its pharmacotherapeutic potential, we present the first chromosome-scale genome assembly and comprehensive methylome profile for the wild strain G. lapidescens QL01, domesticated from the Qinling Mountains. A multi-platform sequencing strategy (Illumina and PacBio HiFi) yielded a high-quality 82.23 Mb assembly anchored to 11 chromosomes, exhibiting high completeness (98.4% BUSCO) and 46.03% GC content. Annotation predicted 15,847 protein-coding genes, with 81.12% functionally assigned. Genome-wide analysis identified 8.46 million high-confidence single-nucleotide polymorphisms (SNPs). Notably, methylation profiling revealed 3.25 million methylation events, with elevated densities on chromosomes 4, 9, and 10, suggesting roles in gene silencing and environmental adaptation. Phylogenomic analyses clarified the evolutionary status of G. lapidescens, whilst gene family evolution indicated moderate dynamics reflecting niche adaptation. Carbohydrate-Active enzymes (CAZymes) analysis identified 521 enzymes, including 211 Glycoside Hydrolases (GHs), consistent with organic matter degradation. Additionally, 3279 SSRs were catalogued as molecular markers. This foundational resource elucidates G. lapidescens’s genetic architecture, epigenetic regulation, evolutionary history, and enzymatic toolkit, underpinning future research into medicinal compound biosynthesis, environmental adaptation, germplasm conservation, and sustainable cultivation. Full article

Molecular imaging and precision therapies are transforming ophthalmology, enabling earlier and more accurate diagnosis and targeted treatment of sight-threatening diseases. This review focuses on age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis, examining high-resolution imaging techniques such as optical coherence tomography (OCT), OCT angiography, MALDI-MSI, and spatial transcriptomics. Artificial intelligence supports these methods by improving image interpretation and enabling personalized analysis. The review also discusses therapeutic advances, including gene therapies (e.g., AAV-mediated RPE65 delivery), stem cell-based regenerative approaches, and biologics targeting inflammatory and neovascular processes. Targeted molecular therapies targeting specific signaling pathways, such as MAPK, are also explored. The combination of single-cell transcriptomics, proteomics, and machine learning facilitates the development of personalized treatment strategies. Although these technologies hold enormous potential, their implementation in routine clinical care requires further validation, regulatory approval, and long-term safety assessment. This review highlights the potential and challenges of integrating molecular imaging and advanced therapies in the future of precision ophthalmic medicine. Full article

Hemoparasites are blood-borne parasites transmitted by vectors and are commonly found in wild birds worldwide. The most frequently reported genera include Plasmodium, Haemoproteus, Leucocytozoon, and Trypanosoma, while filarial worms and other hemoparasites are less frequently reported. Despite their importance, knowledge of their effects on the health of wild birds remains limited. This systematic review summarizes all scientific findings on hemoparasites in wild birds, emphasizing their implications for host health. The literature reveals a high number of articles in this area in recent decades, reflecting a growing concern about hemoparasites in wildlife and their ecological impact. However, studies remain unevenly distributed across regions and bird taxa. Diagnostic limitations, particularly in fieldwork and wildlife rehabilitation, continue to present challenges for the accurate detection and monitoring of these parasites. Nevertheless, molecular tools have advanced our understanding of parasite diversity and host–parasite dynamics. Our work highlights key knowledge gaps and stresses the need for further research to improve the understanding of the role of hemoparasites in avian ecology, particularly concerning environmental change and emerging infectious diseases. Full article

Rice (Oryza sativa), a crucial global staple, grapples with environmental stress and resource constraints, necessitating sustainable farming. This review explores the transformative role of transcription factors (TFs) in revolutionizing rice agriculture and their potential impact on global food security. It underscores TFs’ pivotal role in gene expression, particularly in responding to environmental stimuli, presenting a promising avenue for enhancing rice resilience. Delving into key TF families in rice, it highlights their multifaceted roles in abiotic stress responses, defense mechanisms, yield improvement, nutrient uptake, seed development, photosynthesis, and flowering regulation. Specific TFs, including DREB (Dehydration-Responsive Element-Binding), WRKY, NAC, MYB (Myeloblastosis), AP2/ERF (APETALA2/Ethylene Responsive Factor), and bHLH (basic Helix–Loop–Helix), are examined for their contributions to stress resilience, defense mechanisms, and yield enhancement. Concrete examples from cutting-edge research illustrate the tangible benefits of harnessing these molecular regulators. However, manipulating TFs presents challenges, necessitating innovative approaches such as predictive models, collaborative field testing, and transparent communication to navigate intricate regulatory networks and regulatory hurdles. Ultimately, a promising future emerges where manipulating rice TFs leads to the development of resilient, high-yielding, and nutritious varieties. Embracing research advancements and addressing existing challenges is imperative to unlock the full potential of these concealed regulators, ensuring sustainable food security for a growing global population. Full article

The BBX gene family functions as a key transcription factor implicated in plant growth, development, and stress responses. However, research on this gene family in melon remains absent. In the present study, we identified 19 BBX family genes within the melon genome, distributed across chromosomes 1, 2, 3, 4, 5, 7, 8, 10, 11, and 12. Phylogenetic analysis categorized these genes into five distinct subfamilies, with notable similarities observed in gene structure and conserved motifs among members of the same subfamily. Synteny analysis revealed seven syntenic relationships among melon BBX genes, 17 between melon and Arabidopsis, and one between melon and rice. Reanalysis of transcriptome data indicated that certain BBX genes exhibit high expression levels across various tissues and developmental stages of fruits, while others display tissue specificity. Under both abiotic and biotic stress conditions, genes such as CmBBX3, CmBBX5, CmBBX2, CmBBX18, CmBBX15, and CmBBX11 demonstrated significant differential expression, highlighting their critical roles in melon growth and development. Additionally, RT-qPCR analysis was conducted to examine the expression levels of melon BBX genes at different time points under salt stress, further validating the transcriptome data. This study provides a theoretical foundation for future molecular breeding efforts in melon. Full article

Monilinia fructigena, a causal agent of brown rot in apple and other fruit crops, poses a significant threat to fruit production and postharvest quality in temperate regions. This study reports on the molecular and morphological identification of M. fructigena isolates obtained from symptomatic apple fruits in the Almaty region of Kazakhstan. Nine isolates were characterized through a combination of morphological assessment, real-time PCR, target locus (ITS and TEF1-α gene) sequencing, and whole genome sequencing using nanopore sequencings. Morphological analysis revealed typical features of M. fructigena, including blastoconidia and microconidia. Pathogenicity tests on ‘Idared’ and ‘Golden Delicious’ apples confirmed the high aggressiveness of the isolates, with lesion development observed within 24–48 h post-inoculation. Molecular identification via real-time PCR and target sequencing confirmed all isolates as M. fructigena with high mapping quality and sequence identity. The whole genome sequencing of a representative isolate further validated the species identity based on comparative alignment with Monilinia reference genomes. Thus, the combination of the used traditional and molecular methods allowed us to unambiguously identify the isolated fungus as M. fructigena. This integrative approach enhances the understanding of Monilinia species in Central Asia and supports the implementation of modern molecular tools for phytopathogen surveillance and agricultural biosecurity. Full article

The livestock sector, a crucial source of revenue and global food security, is facing serious challenges due to climate change driven by global warming. This leads to serious effects on animal health and productivity, making it difficult for the livestock industry to meet the global demand and sustain the livelihoods of farmers. The main factor affecting livestock’s productivity is heat stress. However, animals develop various adaptive mechanisms to cope with the effects of heat stress. Cellular and molecular responses act as key defense mechanisms, enabling animals adapt to environmental changes. The recent advancements in molecular biology have opened up opportunities for extensive research on epigenetics, which has a key role in regulating gene expression in animals in response to environmental stimuli. Such studies have gained considerable attention regarding heat acclimation in animals due to the fact that epigenetic mechanisms have been recognized as key players in long-term adaptation to high temperatures in farm animals. This review summarizes the different mechanisms and methodologies used to assess heat stress-associated epigenetic changes, including DNA methylation, which is an extensively studied epigenetic regulatory mechanism in relation to gene expression. The review also highlights the mechanisms and regulation of adaptation to heat stress in animals and collates information related to various epigenetic markers to assess the heat stress response, thereby aiding in improving thermal resilience in animals. Full article

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by lung scarring, impaired function, and high mortality. Effective therapies to reverse fibrosis are lacking. This study aims to uncover the molecular mechanisms of IPF, explore diagnostic biomarkers, and identify therapeutic targets. Methods: Multi-omics data were integrated to identify biomarkers with causal associations to IPF using Mendelian randomization and transcriptomic analysis. Machine learning was employed to construct a diagnostic model, and single-cell transcriptomic analysis determined gene expression patterns in fibrotic lung tissue. Results: Seven core genes (GREM1, UGT1A6, CDH2, TDO2, HS3ST1, ADGRF5, and MPO) were identified, showing strong diagnostic potential (AUC = 0.987, 95% CI: 0.972–0.987). These genes exhibited distinct distribution patterns in fibroblasts, endothelial cells, epithelial cells, macrophages, and dendritic cells. Conclusions: This study highlights key genes driving IPF, involved in pathways related to metabolism, immunity, and inflammation. However, their utility as fluid-based biomarkers remains unproven and requires protein-level validation in prospective cohorts. By integrating genomic, immunological, and cellular insights, it provides a framework for targeted therapies and advances mechanism-based precision medicine for IPF. Full article

Vegetative propagation through stem cuttings represents the primary mode of reproduction in Rosa species. While numerous studies have reported physiological factors affecting cutting rooting, the genes regulating the formation of adventitious roots in roses have not yet been fully explored and studied. In this study, we demonstrate that Rosa rugosa ‘Feng Hua’ exhibits an indirect rooting pattern, requiring callus formation prior to root primordium differentiation. Phytohormone profiling revealed exceptionally high concentrations of auxin precursors, particularly tryptophan (Trp), in both callus and root tissues. Therefore, we identified and analyzed the members of the YUCCA family, which are the key rate-limiting enzymes in the tryptophan-dependent IAA biosynthesis pathway. A total of 11 RrYUCs family genes were identified, with RT-qPCR analysis showing that RrYUC10 was highly expressed in callus and root tissues. Functional studies confirmed its critical role in adventitious root formation: virus-induced gene silencing (VIGS) of RrYUC10 significantly inhibited AR development, whereas its overexpression enhanced rooting. Our findings have provided a molecular theoretical basis for the rooting of cuttings in roses. Full article

Background: Gastrointestinal neuroectodermal tumour (GNET), also known as clear cell sarcoma (CCS) of the gastrointestinal tract, is a rare neural crest-derived malignancy characterized by EWSR1-ATF1 or EWSR1-CREB1 fusions. Due to its rarity, there is limited evidence and no established guidelines for standard management. GNET is aggressive, with high rates of local recurrence, metastasis, and mortality. Case Presentation: We report the case of a 46-year-old woman with a family history of gastrointestinal cancers who was diagnosed in 2020 with an intestinal GNET. She underwent a segmental enterectomy as the first step of multimodal therapy. After three years of follow-up, she developed hepatic and peritoneal metastases. In November 2023, she began combined therapy with the anti-VEGF tyrosine kinase inhibitor cabozantinib and the immune checkpoint inhibitor nivolumab. The patient has maintained stable disease for 18 months with good tolerance and no adverse events. Molecular analysis of the tumour, which showed an EWSR1-CREB1 fusion, supported the selection of targeted therapy and immunotherapy as the preferred treatment approach. Conclusions: Immunotherapy and targeted therapy show promise for GNET/CCS treatment, but clinical standards are lacking, and evidence comes primarily from case reports. Additional data are needed to determine the best sequence and combination of therapies for this very rare disease. Full article

Nanopore-based DNA sequencing has emerged as a transformative biosensing technology, enabling real-time molecular diagnostics in compact and mobile form factors. However, the computational complexity of the basecalling process—the step that translates raw nanopore signals into nucleotide sequences—poses a critical energy challenge for mobile deployment. While deep learning (DL) models currently dominate this task due to their high accuracy, they demand substantial power budgets and computing resources, making them unsuitable for portable or field-scale biosensor platforms. In this work, we propose an embedded hardware–software framework for DNA sequence detection that leverages a Viterbi-based Hidden Markov Model (HMM) implemented on a custom 64-bit RISC-V core. The proposed HMM detector is realized on an off-the-shelf Virtex-7 FPGA and evaluated against state-of-the-art DL-based basecallers in terms of energy efficiency and inference accuracy. From one side, the experimental results show that our system achieves an energy efficiency improvement of 6.5×, 5.5×, and 4.6×, respectively, compared to similar HMM-based detectors implemented on a commodity x86 processor, Cortex-A9 ARM embedded system, and a previously published Rocket-based system. From another side, the proposed detector demonstrates 15× and 2.4× energy efficiency superiority over state-of-the-art DL-based detectors, with competitive accuracy and sufficient throughput for field-based genomic surveillance applications and point-of-care diagnostics. This study highlights the practical advantages of classical probabilistic algorithms when tightly integrated with lightweight embedded processors for biosensing applications constrained by energy, size, and latency. Full article

Pepper is a major horticultural crop cultivated extensively worldwide. Among its various agronomic characteristics, fruit length is a key trait influencing both yield and visual quality. Despite its importance, the genetic mechanisms regulating fruit length in Capsicum remain insufficiently characterized, hindering the development of high-yielding and aesthetically desirable cultivars. In this study, fruits at three developmental stages (0, 15, and 30 days after flowering) were sampled from the long-fruit mutant fe1 and its wild-type progenitor LY0. Phenotypic characterization and transcriptomic sequencing were conducted to identify candidate genes associated with fruit length regulation. Morphological analysis revealed that the most pronounced difference in fruit length occurred at 30 days after flowering. RNA-seq analysis identified 41,194 genes, including 13,512 differentially expressed genes (DEGs). Enrichment analysis highlighted key pathways, such as plant–pathogen interaction, plant hormone signal transduction, and the MAPK signaling pathway. DEG classification suggested that several downregulated genes related to early auxin responses may contribute to the regulation of fruit elongation. Notably, the gibberellin signaling gene SCL13 (Caz12g26660), transcription factors MYB48 (Caz11g07190) and ERF3-like (Caz10g00810), and the cell-wall-modifying gene XTH15-like (Caz07g19100) showed significantly elevated expression in 30-day-old fruits of fe1. Weighted gene co-expression network analysis (WGCNA) further revealed a strong positive correlation among these genes. Quantitative RT-PCR analysis of eight selected DEGs confirmed the RNA-seq results. This study provides a foundational framework for dissecting the molecular regulatory network of fruit length in Capsicum, offering valuable insights for breeding programs. Full article

Background and Clinical Significance: Rhabdomyosarcoma (RMS) is a rare and aggressive malignant soft-tissue sarcoma (STS) arising from skeletal connective tissues and is most commonly seen in the pediatric population. The pleomorphic subtype is mostly seen in adults in the sixth and seventh decades of life, representing 1% of all histological types of RMS and having a very poor prognosis. Case Presentation: This report presents the case of a 63-year-old male with a medical history of papillary thyroid cancer, who presented with an ulcer-hemorrhagic malignant tumor, namely, a poorly differentiated desmin-positive pleomorphic rhabdomyosarcoma (PRMS), with impressive dimensions located on the posterior thoracic wall. This tumor was surgically removed via a wide resection, followed by palliative chemotherapy and radiotherapy. However, the patient relapsed locally, with pulmonary, bone, and lymph node metastases. The peculiarity of this case is represented by the rapid growth, aggressive nature, and high metastatic potential of the adult RMS, as well as its poor response to treatment. Conclusions: The presented case underscores the need for early diagnosis, multidisciplinary management, and exploration of molecular profiling for therapeutic planning. Full article