Search Results (3,462)

Pyruvate kinase (PK) is a key enzyme in glycolysis that regulates sugar metabolism and energy production, thereby influencing fruit quality. The ‘Feizixiao’ litchi, widely cultivated in Hainan Province, faces sugar reduction during fruit ripening. This study evaluated the effects of the foliar application of calcium and magnesium (Ca+Mg) during the fruit expansion stage to alleviate this problem. Ca+Mg foliar application significantly enhanced soluble sugar content, promoted peel coloration, and reduced respiration and PK activity. Genome-wide analysis identified 19 PK genes (LcPKs) exhibiting diverse exon-intron structures and conserved motifs. Phylogenetic analysis revealed both conserved and species-specific features, while subcellular localization predicted that most LcPK proteins are likely to be localized in the cytoplasm. Synteny analysis showed closer evolutionary relationships with species in the same genus than with Arabidopsis. Cis-regulatory element analysis implicated LcPKs in light response, hormone signaling, growth, and stress adaptation. Hormonal assays at 63 and 70 DAA after treatment revealed increased abscisic acid (ABA) and ethylene levels under Ca+Mg application. These hormonal changes correlated with the downregulation of LcPK3, LcPK4, LcPK5, LcPK8, and LcPK15, as confirmed by qRT-PCR, indicating negative regulation by ABA and ethylene. This regulatory mechanism likely contributes to overcoming sugar receding in litchi pulp. These findings offer insights into the regulation of sugar metabolism and strategies for enhancing fruit quality through the management of genes and nutrients. Full article

Background/Objectives: Astrocytoma, IDH-mutant, CNS WHO grade 3, is a diffuse glioma with poor prognosis, molecularly defined by IDH mutations and frequently co-occurring TP53 and ATRX alterations. This study aimed to delineate the genomic landscape and identify clinically relevant molecular features of astrocytoma, IDH-mutant, CNS WHO grade 3 using this resource. Methods: Patients in the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (AACR Project GENIE) database were selected based on histological diagnosis of “anaplastic astrocytoma”, confirmed IDH1/2 mutation, and exclusion of CDKN2A/B homozygous deletions. We analyzed frequencies of somatic mutations, copy number alterations (CNAs), structural variants (SVs), assessed co-occurrence/exclusivity patterns, and explored associations with available demographic and limited survival data. Results: The most common somatic mutations were in IDH1 (98.0%), TP53 (94.8%), and ATRX (55.2%). The observed ATRX mutation frequency was lower than some historical reports (e.g., ~86%). Other recurrent alterations included phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (6.9%), Notch receptor 1 (NOTCH1) (6.9%), and platelet-derived growth factor receptor alpha (PDGFRA) (mutations 4.3%; CNAs also observed). Conclusions: This study provides a comprehensive genomic characterization of astrocytoma, IDH-mutant, CNS WHO grade 3 using the AACR GENIE database, confirming core mutational signatures while also highlighting potential variations in alteration frequencies, such as for ATRX. The findings establish a valuable real-world genomic benchmark for this tumor type, while promoting the need for continued data integration with robust clinical outcomes to identify actionable prognostic and therapeutic targets. Full article

Histiocytic sarcoma (HS) is an ultra-rare hematopoietic neoplasm that frequently occurs in extranodal sites of adults. Clinically, HS demonstrates aggressive behavior and can arise de novo or in association with other hematological neoplasms. The median overall survival from the time of diagnosis is approximately six months. Histologically, HS is composed of sheets of large, round to oval cells with abundant eosinophilic cytoplasm and can be confused with a variety of benign and malignant conditions. Immunohistochemistry plays a crucial role in the diagnosis of HS, showing expression of CD163, CD68, lysozyme, and PU.1 and negative staining with follicular dendritic cell markers and myeloid cell markers. Recent studies have demonstrated a high rate of PD-L1 expression, suggesting a potential therapeutic target. Several genomic alterations have been identified in HS, including mutations involving the RAS/MAPK and PI3K/AKT/mTOR signaling pathways, CDKN2A mutations/deletions, and TP53 mutations. There is no standard protocol for the management of HS. Surgical resection with or without radiotherapy is the most common first-line treatment for unifocal/localized disease. The systemic treatment options for multifocal/disseminated disease are very limited. This review provides an overview of the current knowledge on the clinicoradiological features, histopathology, pathogenesis, and management of HS. Full article

Social interaction between the domesticated animal and the domesticator is one of the key features of the “domestication syndrome”. Recent research has identified genes in the WBSCR (Williams–Beuren syndrome control region) locus as significant contributors to social behavior in dogs. Large chromosomal deletions and duplications in the human WBSCR locus lead to the development of WBS (Williams–Beuren syndrome) and WBSCR duplication syndrome, respectively. Hypersociability is one of the key symptoms of WBS, while the duplication syndrome is manifested as an autism spectrum disorder (ASD). The data from both humans and dogs highlight the WBSCR locus as one of the key genetic determinants of social behavior in mammals. Several genes in the WBSCR are candidates for the regulation of social behavior in mammals including GTF2I, GTF2IRD, AUTS2 and GALNT17. Here, we discuss the role of WBSCR locus in the regulation of social behavior in mammals including the recent data that highlight the importance of 3D genome alterations in this genomic region for both domestication of animals and development of neurobehavioral disorders in humans. In addition, we bring attention to the role of the poorly characterized GALNT17 gene as a putative player in the development of ASD symptoms and in the regulation of social behavior in animals. We provide a brief summary of its known functions and propose the future research directions aimed at the elucidation of Galnt17 involvement in the regulation of central nervous system (CNS) functions. 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

Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, with cure rates exceeding 80% due to advancements in treatment protocols and supportive care. However, in children with Down syndrome (DS), ALL (DS-ALL) presents distinct genomic and clinical challenges. These include mutations in Janus kinase 2 (JAK2), neuroblastoma RAS viral oncogene homolog (NRAS), and E1A-binding protein p300 (EP300), as well as cytokine receptor-like factor 2 (CRLF2) rearrangements—such as P2RY8-CRLF2 fusion—and intrachromosomal amplification of chromosome 21 (iAMP21). These aberrations are associated with poor prognosis and increased risk of relapse. The objective of this study was to present a unique DS-ALL case with five concurrent high-risk genomic lesions and to contextualize its management in light of existing literature, emphasizing minimal residual disease (MRD)-guided therapy and supportive care. Case Report and Results: We present the case of a three-year-old boy with DS and B-cell ALL (B-ALL), in whom multiple high-risk genomic features co-occurred. Despite these adverse prognostic markers, the patient achieved complete remission following an intensive high-dose induction protocol. We also discuss therapeutic strategies that aim at balancing individualized treatment approaches with optimized supportive care to reduce toxicity and minimize relapse risk. Conclusions: This case underlines the importance of comprehensive molecular diagnostics, serial MRD monitoring, and personalized multidisciplinary care in DS-ALL. Full article

Background: The chloroplast genome provides rich genetic information for plant evolutionary studies. This study aimed to assemble, annotate, and analyze the complete chloroplast genome of flax cultivar ‘Longya 15’ (Linum usitatissimum L.) and clarify its phylogenetic relationships with other Linaceae species. Methods: We assembled and annotated the chloroplast genome of ‘Longya 15’ and retrieved chloroplast genomes of related species (e.g., Linum grandiflorum NC_058845.1, Linum lewisii NC_058799.1) from the NCBI database for phylogenetic analysis. Results: The chloroplast genome of ‘Longya 15’ was a 157,074-bp quadripartite structure with 37.42% GC content, encoding 128 genes (83 mRNAs, 37 tRNAs, 8 rRNAs) without pseudogenes. It showed codon bias for leucine (28 codons with RSCU > 1, ending in A/U), 260 dispersed repeats, and 240 SSRs. Ka/Ks analysis revealed purifying selection for most genes, while rps18 and ycf2 had positive selection. ycf1 was identified as the hypervariable region (pi = 0.25024). Phylogenetically, it clustered closest with Linum grandiflorum, followed by L. lewisii and L. perenne, and was related to Hypericum species. Conclusions: This is the first fine assembly and annotation of ‘Longya 15’ chloroplast genome, confirming no pseudogenes in flax chloroplast. It elucidates flax chloroplast genome conservation and evolutionary dynamics, enriches the database, and provides a foundation for Linaceae phylogenetics, germplasm development, and stress-resistant breeding. Full article

Background: Traditional morphology-based classification of the Oriental Plover (Anarhynchus veredus) is inconsistent with molecular evidence, underscoring the necessity of incorporating molecular data to elucidate its evolutionary relationships within Charadriidae. Methods: Here, we present the first complete mitochondrial genome of A. veredus by Illumina NovaSeq Sequencing and explore its evolutionary implications within Charadriidae. Results: The mitogenome spans 16,886 bp and exhibits conserved structural features typical of Charadriidae, including gene order, overlapping coding regions, and intergenic spacers. Nucleotide composition analysis revealed a GC content of 44.3%, aligning with other Charadriidae species (44.5–45.8%), and hierarchical GC distribution across rRNA, tRNA, and protein-coding genes (PCGs) reflects structural and functional optimization. Evolutionary rate heterogeneity was observed among PCGs, with ATP8 and ND6 showing accelerated substitution rates (Ka/Ks = 0.1748 and 0.1352) and COX2 under strong purifying selection (Ka/Ks = 0.0678). Notably, a conserved translational frameshift in ND3 (position 174) was identified. Phylogenetic analyses (ML/NJ) of 88 Charadriiformes species recovered robust topologies, confirming that the division of Charadriidae into four monophyletic clades (Pluvialis, Vanellus, Charadrius, and Anarhynchus) and supporting the reclassification of A. veredus under Anarhynchus. Conclusions: This study resolves the systematic position of A. veredus and highlights the interplay between conserved mitochondrial architecture and lineage-specific adaptations in shaping shorebird evolution. Full article

Background: While enteroviruses (EVs) are recognized causes of diverse illnesses, little is known about the epidemiology and molecular characteristics of uncommon enterovirus C (EV-C) types, including EV-C104, EV-C105, and EV-C109. Methods: We conducted genomic surveillance of EVs at the Johns Hopkins Health System between 2018 and 2024 (a total of 3715 samples), identifying EV-C104, EV-C105, and EV-C109 in respiratory samples. VP4-VP2 and whole-genome sequencing were used to assess genetic diversity and intra-host evolution. Results: Five EV-C105 infections were identified primarily in pediatric patients, presenting with a range of clinical features including fever, gastrointestinal symptoms, and cerebellitis. Prolonged EV-C104 and EV-C109 infections were identified in two immunocompromised adults. EV-C104 persisted for over five months and showed evidence of viral genomic changes (intra-host evolution). EV-C109 was detected over a four-month period. Phylogenetic analysis revealed a novel EV-C105 clade (C3) closely related to recent USA strains. EV-C104 genomes aligned with genotype B sequences from the USA and Europe, while EV-C109 sequences were similar to 2014–2015 strains from the Netherlands. Conclusions: These findings highlight the emergence, persistence, and genetic evolution of uncommon EV-C types in Maryland, especially among immunocompromised hosts, emphasizing the importance of continued genomic surveillance and clinical correlations. Full article

Background: Chemokines play a pivotal role in the progression of osteoarthritis (OA), but their exact mechanisms remain unclear. This study aimed to identify potential chemokine-associated biomarkers and investigate their causal relationships with OA. Methods: Transcriptome and genome-wide association study (GWAS) data were obtained from public databases, while chemokine-related genes (CRGs) were sourced from the literature. Initially, CRGs were expanded, followed by Mendelian randomization (MR) analysis, differential expression analysis, machine learning, and receiver operating characteristic (ROC) curve plotting to identify potential biomarkers. The causal relationships between these biomarkers and OA, as well as their biological functions, were further explored. Results: Fourteen candidate genes were identified for machine learning analysis, with DDIT3, CEBPB, CX3CR1, and ARHGAP25 emerging as feature genes. CEBPB and CX3CR1, which exhibited AUCs > 0.7 in the GSE55235 and GSE55457 datasets, were selected as potential biomarkers. Notably, CEBPB expression was lower, while CX3CR1 expression was elevated in the case group. Furthermore, both genes were co-enriched in spliceosome, lysosome, and cell adhesion molecule pathways. MR analysis confirmed that CEBPB and CX3CR1 were causally linked to OA and acted as protective factors (IVW model for CEBPB: OR = 0.9051, p = 0.0001; IVW model for CX3CR1: OR = 0.8141, p = 0.0282). Conclusions: CEBPB and CX3CR1 were identified as potential chemokine-related biomarkers, offering insights into OA and suggesting new avenues for further investigation. Full article

Background/Objectives: Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder frequently associated with other neuropsychiatric conditions, characterized by high clinical heterogeneity and a complex genetic background. Recent studies suggest that copy number variations (CNVs) may contribute to ADHD susceptibility, particularly when involving genes related to brain development, attention regulation, and impulse control. This study investigated the association between CNVs and ADHD phenotype by identifying patients with and without potential pathogenic CNVs. Methods: We evaluated 152 well-characterized ADHD pediatric patients through comprehensive clinical assessments, including dysmorphic features, brain MRI, EEG patterns, and cognitive testing. CNVs were identified using array Comparative Genomic Hybridization (array-CGH). Participants were classified as carrying potentially causative CNVs (PC-CNVs), non-causative CNVs (NC-CNVs), or without CNVs (W-CNVs) and statistically compared across clinical and neurodevelopmental measures. Results: CNVs were identified in 81 participants (53%), comprising 13 with PC-CNVs (8.5%) and 68 with NC-CNVs (44.7%). ADHD symptoms were pronounced across all groups, but PC-CNVs showed a higher burden of comorbidities, suggesting a stronger genetic contribution to ADHD complexity. Significant differences were observed in oppositional behavior, inattentive symptoms, brain MRI findings, and developmental language anomalies. Several CNVs involved genes previously implicated in neurodevelopmental disorders, supporting a potential genetic contribution to the clinical complexity of ADHD. Conclusions: This exploratory study supports the role of CNVs in ADHD susceptibility and highlights the value of genetic screening for understanding clinical variability. Larger studies are needed to clarify genotype–phenotype correlations in ADHD and to guide personalized clinical management. Full article

A strictly aerobic, straight-rod, motile Gram-negative bacterium, SDUM041083^T, was isolated from marine sediment in Xiaoshidao, Weihai, China, in the formation of yellowish-brown colonies. Its growing conditions are as follows: 20–40 °C, pH 5.5–9.5, and 0.5–11% (w/v) NaCl. Phylogenetic analysis of the 16S rRNA gene sequence showed that SDUM041083^T was related to members of the genus Microbulbifer. Strain SDUM041083^T showed the highest 16S rRNA gene sequence similarity (98.23%) with Microbulbifer okinawensis JCM 16147^T. The primary cellular fatty acids of SDUM041083^T were iso-C11:0 3-OH, iso-C11:0, and iso-C15:0. The respiratory quinone of SDUM041083^T was Q-8, and the polar lipids were phosphatidylglycerol, phosphatidylethanolamine, and one aminolipid. The genomic DNA G+C content of SDUM041083^T was 57.5 mol%. The phenotypic and genotypic characteristics of SDUM041083^T indicate that the strain should be classified as a new species representing the genus Microbulbifer, with the name Microbulbifer weihaiensis sp. nov. being proposed. The type strain was SDUM041083^T (=KCTC 8896^T = MCCC 1H01537^T). Comparative genomic analysis showed that the 32 Microbulbifer species shared 1446 core genes and differed mainly in terms of lipid metabolism, signal transduction and xenobiotic biodegradation and metabolism. Preliminary research showed that SDUM041083^T has the potential to degrade chitin. Biogeographic distribution analysis showed that the marine environments constitute the main habitat of the genus Microbulbifer. Full article

Background: Breast cancer remains a critical public health problem worldwide and is a leading cause of cancer-related mortality. Optimizing clinical outcomes is contingent upon the early and precise detection of malignancies. Advances in medical imaging and artificial intelligence (AI), particularly in the fields of radiomics and deep learning (DL), have contributed to improvements in early detection methodologies. Nonetheless, persistent challenges, including limited data availability, model overfitting, and restricted generalization, continue to hinder performance. Methods: This study aims to overcome existing challenges by improving model accuracy and robustness through enhanced data augmentation and the integration of radiomics and deep learning features from the CBIS-DDSM dataset. To mitigate overfitting and improve model generalization, data augmentation techniques were applied. The PyRadiomics library was used to extract radiomics features, while transfer learning models were employed to derive deep learning features from the augmented training dataset. For radiomics feature selection, we compared multiple supervised feature selection methods, including RFE with random forest and logistic regression, ANOVA F-test, LASSO, and mutual information. Embedded methods with XGBoost, LightGBM, and CatBoost for GPUs were also explored. Finally, we integrated radiomics and deep features to build a unified multimodal feature space for improved classification performance. Based on this integrated set of radiomics and deep learning features, 13 pre-trained transfer learning models were trained and evaluated, including various versions of ResNet (50, 50V2, 101, 101V2, 152, 152V2), DenseNet (121, 169, 201), InceptionV3, MobileNet, and VGG (16, 19). Results: Among the evaluated models, ResNet152 achieved the highest classification accuracy of 97%, demonstrating the potential of this approach to enhance diagnostic precision. Other models, including VGG19, ResNet101V2, and ResNet101, achieved 96% accuracy, emphasizing the importance of the selected feature set in achieving robust detection. Conclusions: Future research could build on this work by incorporating Vision Transformer (ViT) architectures and leveraging multimodal data (e.g., clinical data, genomic information, and patient history). This could improve predictive performance and make the model more robust and adaptable to diverse data types. Ultimately, this approach has the potential to transform breast cancer detection, making it more accurate and interpretable. Full article

The rustrela virus (RusV), a recently discovered member of the Matonaviridae family and a close relative of the rubella virus, has emerged as the etiological agent of “staggering disease”—a progressive neurological disorder primarily affecting domestic cats and other mammals. Characterized by nonsuppurative meningoencephalomyelitis, RusV infection manifests with clinical signs such as ataxia, seizures, and behavioral abnormalities. First identified in 2020, RusV has since been detected in various mammalian species across Europe and, more recently, in North America. This review provides a comprehensive summary of the current knowledge of RusV, including its taxonomy, genomic structure, host range, transmission hypotheses, clinical and histopathological features, and diagnostic challenges. Although the potential for zoonotic spillover has not yet been confirmed, it highlights the need for increased surveillance and further research. As an emerging neurotropic virus with potential for cross-species transmission, RusV may represent a significant concern for veterinary medicine and public health. Full article

Hepatocellular carcinoma (HCC) is a malignancy that is notorious for its dismal prognosis. Dysregulation of the tumor microenvironment (TME) in HCC has emerged as a key hallmark in determining disease progression and the response to immunotherapy. The aim of this study was to identify novel TME regulators that contribute to therapeutic resistance, thus providing mechanistic insights for targeted interventions. The expression of SMIM25 was evaluated in the the Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC) and Guangxi HCC cohorts, and its clinicopathological significance was assessed. RNA sequencing and bioinformatics analyses were performed to elucidate the potential impact of elevated SMIM25 levels. Immunohistochemistry (IHC) and single-cell mass cytometry (CyTOF) were employed to examine the cellular composition of the tumor microenvironment. The biological effects of SMIM25 on cell proliferation and migration were studied in vitro using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide(MTT) and wound healing assays, while its impact on tumor growth was evaluated in vivo in a nude mouse model. Transcriptomic and single-cell proteomic analyses were integrated to explore the mechanism by which SMIM25 affects the progression of HCC. The expression of SMIM25 was significantly up-regulated in both HCC tissues and cell lines (p < 0.05). RNA sequencing analyses revealed a significant positive correlation between SMIM25 expression and immunosuppression, and between SMIM25 expression and extracellular matrix(ECM)-related molecular features. Single-cell mass cytometry revealed two immunosuppressive cell clusters that were enriched in HCC patients with high SMIM25 expression. Moreover, SMIM25 was associated with immune exclusion and ECM remodeling signals in the TME of HCC. SMIM25 overexpression was associated with the expression of the tumor inflammatory marker cyclooxygenase-2(COX-2), and a COX-2 inhibitor could partially reverse the biological phenotype associated with SMIM25 expression in HCC cells (p < 0.05). Further transcriptome analysis in immunotherapy cohorts suggested the SMIM25-COX-2 axis might have predictive value for the response to immunotherapy. Our results suggest that SMIM25 may serve as a biomarker for the prognosis of HCC patients and may also be a predictive biomarker for the response to immunotherapy, enabling more precise and personalized HCC treatment. Full article