Search Results (5,505)

The TCP gene family plays essential roles in plant growth, development, and stress responses, yet their evolutionary dynamics and functional characteristics remain poorly understood in Juglandaceae species. Here, we aimed to systematically identify, classify, and characterize TCP genes across three nut-producing Juglandaceae species—Carya illinoinensis, Annamocarya sinensis, and Juglans regia—to elucidate their evolutionary relationships and potential functions in fruit development. We identified 44, 35, and 36 TCP genes in C. illinoinensis, A. sinensis, and J. regia, respectively, and classified them into three subfamilies (PCF, CIN, and CYC/TB1). Physicochemical property analysis revealed that most proteins were hydrophilic but relatively unstable. Conserved motif and gene structure analyses showed strong similarity among closely related members, while promoter regions were enriched with cis-acting elements associated with development, hormone signaling, and stress responses. Chromosomal mapping demonstrated an uneven distribution of TCP genes, with frequent clustering, and synteny analysis indicated strong conservation and gene duplication within and across species. Transcriptome profiling revealed that approximately half of the TCP genes were expressed in fruit tissues, with CIN subfamily members showing preferential expression. qRT-PCR validation further highlighted AsTCP23, CiTCP14, and JrTCP09 as highly expressed during fruit development, suggesting potential regulatory roles in fruit maturation. These findings provide new insights into the evolutionary patterns and functional divergence of TCP genes in Juglandaceae and establish a valuable foundation for future studies on fruit development and genetic improvement. Collectively, these findings advance our understanding of TCP gene evolution and provide potential molecular targets for improving fruit development and nut quality in Juglandaceae crops. Full article

Rheumatoid arthritis (RA) is a heterogeneous autoimmune disease characterized by variable clinical manifestations and a complex, often unpredictable disease trajectory, which hinders early diagnosis and personalized treatment. This review highlights recent breakthroughs in biomarker discovery, emphasizing the transformative impact of multi-omics technologies and deep profiling of the synovial microenvironment. Advances in genomics and transcriptomics have identified key genetic variants and expression signatures associated with disease susceptibility, progression, and therapeutic response. Complementary insights from proteomics and metabolomics have elucidated dynamic molecular patterns linked to inflammation and joint destruction. Concurrently, microbiome research has positioned gut microbiota as a compelling source of non-invasive biomarkers with both diagnostic and immunomodulatory relevance. The integration of these diverse data modalities through advanced bioinformatics platforms enables the construction of comprehensive biomarker panels, offering a multidimensional molecular portrait of RA. When coupled with synovial tissue profiling, these approaches facilitate the identification of spatially resolved biomarkers essential for localized disease assessment and precision therapeutics. These innovations are transforming RA care by enabling earlier detection, improved disease monitoring, and personalized treatment strategies that aim to optimize patient outcomes. Full article

Russian dandelion (Taraxacum kok-saghyz Rodin, TKS) is a natural rubber (NR)-producing species whose roots contain 3% to 27% NR, underscoring its considerable research and economic significance. The myeloblastosis (MYB) transcription factor family, one of the largest in plants, plays pivotal roles in metabolic regulation, stress responses, and various growth and developmental processes. To identify key MYB transcription factors involved in hormone-induced rubber biosynthesis, we conducted homology-based and bioinformatic analyses to characterize 268 MYB family proteins in the TKS genome. Utilizing transcriptome data from jasmonic acid (JA) and ethylene (ET) treatments, we screened and shortlisted 10 candidate TkMYB transcription factors. Through tissue-specific expression profiling, TkMYB7 was selected as the primary candidate. We confirmed that promoter analysis combined with yeast one-hybrid assays confirmed that TkMYB7 directly binds to and regulates the expression of acetyl-CoA acetyltransferase (TkACAT5), a key enzyme in the mevalonate (MVA) pathway. Furthermore, heterologous overexpression of TkMYB7 in Arabidopsis thaliana significantly enhanced seed germination and root development. These findings identify TkMYB7 as a novel transcriptional regulator linking JA and ET signaling pathways to rubber biosynthesis in TKS, representing a promising target for the genetic improvement of rubber yield. Full article

Introduction: Gene therapy using siRNA is a current area of research in oncology. Although siRNA formulations have not yet been approved for cancer therapy, numerous studies have demonstrated their therapeutic potential for tumor remission. Objective: To provide an overview of the formulations designed and developed to date based on synthetic siRNA for systemic administration to silence cancer genes. Methodology: A thorough search was conducted using the keywords “siRNA”, “therapy”, and “cancer”, with further classification of the resulting works into the various topics addressed in this review. Results: This review encompasses a wide range of aspects, from the design of siRNA using bioinformatics tools to the primary cellular signals and mechanisms targeted for inhibition in cancer therapy. It describes the primary chemical modifications made to siRNA chains to enhance stability, improve bioavailability, and ensure their binding to nanocarrier systems. siRNA formulations ranging from simple conjugates with biomolecules and small molecules to organic, inorganic, and hybrid nanoparticles, which are examined focusing on their advantages and disadvantages. The significance of nanosystems in dual therapy, including siRNA, for developing personalized treatments that achieve better outcomes is emphasized. Conclusions: Personalized cancer therapy appears to be the preferred approach for oncological treatments. To progress, strategies need to be tailored to the patient’s genetic profile. siRNA therapies provide a flexible platform for targeting and inhibiting critical oncogenes, enhancing the prospects of genomics-guided, patient-specific therapies. Full article

Background/Objectives: Anthocyanins, water-soluble flavonoid pigments with critical roles in plant stress resistance, are not naturally accumulated in cultivated tomato (Solanum lycopersicum) due to an incomplete flavonoid metabolism pathway. In contrast, ‘Black Pearl’ tomato exhibits distinct peel color transitions (from indigo rose to deep purple–red) during ripening, making it an ideal model for investigating the regulatory mechanisms of anthocyanin synthesis. A comprehensive strategy was employed to elucidate these mechanisms, involving transcriptomic (Illumina HiSeq), metabolomic (UPLC-MS/MS), and functional analyses of the ‘Black Pearl’ tomato peel across four developmental stages: mature green (S1), coloring (S2), purple immature (S3), and fully ripened (S4). Results: Transcriptome profiling identified 597 core differentially expressed genes (DEGs) associated with anthocyanin accumulation. Temporal analysis indicated that structural genes and activators peaked at S3, whereas repressive MYBs, including SlMYB76 which peaked at S2, exhibited staged expression. In parallel, metabolomic analysis identified 36 metabolites, with cyanidin and pelargonidin derivatives being characterized as the principal pigments. Functionally, SlMYB76 was confirmed to be a negative regulator, as its transient overexpression reduced anthocyanin content and downregulated SlANS. Mechanistically, direct binding and repression of the SlANS promoter by SlMYB76 were confirmed through yeast one-hybrid and dual-luciferase assays. Furthermore, its physical interaction with the bHLH factor SlJAF13 in the nucleus was demonstrated by Y2H, BiFC, LCI, and Co-IP, supporting the formation of a repressive complex that co-regulates SlANS. Conclusions: A novel SlMYB76-SlJAF13-SlANS regulatory module controlling anthocyanin accumulation in the peel of ‘Black Pearl’ tomato was identified. This discovery enhances the current understanding of the tomato flavonoid regulatory network and provides strategic targets for the genetic improvement of fruit color and anthocyanin content through molecular breeding. Full article

Sports-associated traumatic brain injury is emerging as an under-recognized driver of acute and chronic cardiovascular diseases. Larger population-based studies show that individuals with moderate-to-severe traumatic brain injury experience up to a two-fold excess risk of incident hypertension, coronary artery disease, myocardial infarction, and stroke that persists for at least a decade. Among former professional American-style football players, a higher lifetime concussion burden is uniquely related to a more atherogenic cardiometabolic profile and greater long-term stroke risk. Mechanistically, an acute “sympathetic storm” triggered by cerebral injury provokes catecholamine surges, endothelial dysfunction, and myocardial stunning, manifesting as neurogenic stunned myocardium or Takotsubo-like cardiomyopathy and malignant arrhythmias. Sub-acute to chronic phases are characterized by persistent autonomic imbalance, reflected by reduced heart-rate variability and impaired baroreflex sensitivity weeks to months after concussion, coupled with neuroinflammation, hypothalamic–pituitary–adrenal axis dysregulation, and lifestyle changes that accelerate atherosclerosis. The interplay of these pathways accounts for the elevated burden of cardiovascular disease observed long after neurological function has been restored. Despite robust evidence linking TBI to adverse cardiac outcomes, contemporary sports–cardiology risk stratification prioritizes hemodynamic load, genetics, and performance-enhancing substances, largely overlooking brain injury history. This review integrates epidemiological, clinical, and mechanistic data to (i) delineate acute neurocardiac complications secondary of sports-related traumatic brain injury, (ii) synthesize evidence for chronic cardiovascular risk, (iii) highlight emerging autonomic and inflammatory biomarkers, and (iv) propose surveillance and therapeutic strategies, ranging from heart-rate-variability-guided return-to-play decisions to aggressive cardiometabolic risk modification aiming to mitigate long-term morbidity in this athletic population. By framing sports-related traumatic brain injury as a modifiable cardiovascular risk factor, we aim to foster interdisciplinary collaboration among neurologists, cardiologists, and sports medicine practitioners, ultimately improving both neurological and cardiovascular outcomes across the athlete’s lifespan. Full article

Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous spectrum of disorders that lead to progressive and irreversible vision loss. Gene therapy is the most promising emerging treatment for IRDs. While gene augmentation strategies have demonstrated clinical benefit and results within the first approved ocular gene therapy, their application is restricted by adeno-associated virus (AAV) packaging capacity and limited efficacy for dominant mutations. Recent breakthroughs in precision genome editing, particularly base editing (BE) and prime editing (PE), have provided alternatives capable of directly correcting pathogenic variants. BE enables targeted single-nucleotide conversions, whereas PE further allows for precise insertions and deletions, both circumventing the double-strand DNA cleavage or repair processes typically induced by conventional CRISPR–Cas editing systems, thereby offering advantages in post-mitotic retinal cells. Preclinical investigations across murine and non-human primate models have demonstrated the feasibility, molecular accuracy, and preliminary safety profiles of these platforms in targeting IRD-associated mutations. However, critical challenges remain before clinical application can be realized, including limited editing efficiency in photoreceptors, interspecies variability in therapeutic response, potential risks of off-target effects, and barriers in large-scale vector manufacturing. Moreover, the delivery of genome editors to the outer retina remains suboptimal, prompting intensive efforts in capsid engineering and the development of non-viral delivery systems. This review synthesizes the current progress in BE and PE optimization, highlights innovations in delivery platforms that encompass viral and emerging non-viral systems and summarizes the major barriers to clinical translation. We further discuss AI-driven strategies for the rational design of BE/PE systems, thereby outlining their future potential and perspectives in the treatment of IRDs. Full article

Background: Pediatric acute myeloid leukemia (pAML) is the second most common type of childhood leukemia, behind acute lymphoblastic leukemia. High-throughput technologies have enabled the identification of increasing molecular alterations linked to AML prognosis, revealing genomic heterogeneity among individual patients and providing clinically valuable diagnostic and prognostic information. This study systematically analyzed the correlation between high-frequency mutated genes and prognosis in pAML by performing whole-transcriptome sequencing (WTS) of bone marrow samples from newly diagnosed AML children in Southwest China and mapping their genetic profiles. Methods: pAML patients treated at the Department of Hematology and Oncology, Children’s Hospital of Chongqing Medical University, from January 2015 to October 2024, were enrolled, and WTS was performed. The study described the frequency, pathogenicity classification, and risk stratification of mutation genes and fusion genes, and constructed a genetic landscape. For high-frequency pAML mutations, the impact on early induction remission rate (CR) and long-term event-free survival (EFS) was evaluated. Results: A total of 134 pediatric AML patients from Southwest China were included, with a male-to-female ratio of 74:60 and a median diagnosis age of 5.96 years. Based on pathogenicity classification using WTS, fusion genes were categorized into level 1, level 2, and level 3 genes, as well as mutation genes. The study identified five fusion genes of level 1, the most frequent being RUNX1::RUNX1T1 (32/134, 23.88%), KMT2A rearrangements (29/134, 21.64%), and CBFB::MYH11 (13/134, 9.7%). Sixteen mutation genes of level 1 were detected, seven of which recurred in over 5% of patients, including NRAS (31/134, 23.13%), FLT3 (25/134, 18.66%), KIT (24/134, 17.91%), CEBPA (14/134, 10.45%), WT1 (13/134, 9.7%), KRAS (11/134, 8.2%), and PTPN11 (7/134, 5.22%). Sex-based analysis revealed that PTPN11 mutations were significantly more frequent in males (9.45% vs. 0%, p = 0.023), as were KIT mutations (24.32% vs. 10.00%, p = 0.044). Risk-stratified analysis showed that WT1 mutations (14.13% vs. 0%, p = 0.031) and FLT3-ITD mutations (13.19% vs. 0%, p = 0.042) were enriched in intermediate- and high-risk groups, whereas CEBPA (25.64% vs. 5.43%, p = 0.012), KIT (35.90% vs. 10.87%, p = 0.003), and KIT-E8 (20.51% vs. 1.10%, p < 0.001) mutations were more prevalent in low-risk groups. Prognostic analysis indicated that PTPN11 and KIT mutations did not affect CR or EFS across sexes, nor did WT1, CEBPA, or KIT mutations influence outcomes by risk stratification. However, FLT3-ITD-positive patients had significantly lower CRs (χ² value = 11.965, p = 0.007), although EFS differences were nonsignificant. In contrast, WT1 mutations were associated with inferior EFS compared to wild-type (p = 0.036). Furthermore, the univariate and multivariate Cox regression revealed consistent results with the above findings, indicating that WT1 mutation was an independent adverse prognostic factor for EFS (HR = 2.400, 95% CI: 1.101–5.233, p = 0.028). The results of univariate and multivariate logistic regression analyses also confirmed that FLT3-ITD mutation was an independent predictor of initial treatment response in our cohort (OR = 10.699, 95% CI: 2.108–54.302, p = 0.004). Conclusions: This study delineated the genetic landscape of pAML in Southwest China and explored the prognostic value of gene fusions and mutations in early and long-term outcomes. These findings provide a foundation for understanding the genetic heterogeneity of pAML and offer evidence for the development of precision medicine approaches. Full article

The HN pig, indigenous to Henan Province, is distinguished by its reduced lean meat yield and slower growth rates relative to commercial foreign breeds. To address these limitations, three hybrid combinations were generated through the crossbreeding of Huainan sows with Yorkshire, Landrace, and Berkshire sires. In this study, extensive transcriptomic and metabolomic analyses of the LD muscle were carried out for the first time, and carcass and meat quality characteristics were compared between hybrid and HN pigs. Slaughter and muscle quality assessments revealed that the lean meat percentage of LH and YH was significantly lower than that of HN, with YH exhibiting the lowest intramuscular fat level, indicating that this breed possesses enhanced lean meat production efficiency. Transcriptomic profiling revealed markedly increased expression of SLIT2, CH25H, NR4A2, NR4A1, FOSB, CRABP2, GDF10, and MRAP2 in all three hybrid groups compared to HN. Gene Ontology enrichment analysis identified that the skeletal muscle cell differentiation (GO:0035914) and transforming growth factor beta receptor signaling pathway (GO:0007179) were exclusively enriched in the YH vs. HN comparison. Non-targeted metabolomic analysis identified 31, 36, and 12 DAMs in BH vs. HN, LH vs. HN, and YH vs. HN comparisons, with pyruvate metabolism being the sole pathway common to all groups. An integrated multi-omics analysis revealed significant correlations between phytosphingosine levels and DEGs across all three comparisons. In summary, these results indicate that crossbreeding substantially improves lean meat yield in HN pigs while providing novel molecular insights into the underlying genetic and metabolic mechanisms. Full article

Background: Dirigent genes play crucial roles in regulating plant architecture development and responses to environmental stress. However, the pan-genomic attributes of these genes remain poorly characterized. Method: The dirigent pan-gene family was reconstructed using the public genome assemblies from the 26 maize Nested Association Mapping project founder lines. Orthogroup classification based on multiple sequence alignment revealed both core and variable family members. Evolutionary pressures were assessed through Ka/Ks ratio analysis, and promoter regions were examined for cis-acting regulatory elements. Haplotype, transcriptomic and genome-wide association study (GWAS) analyses were integrated to explore genetic diversity and functional relevance. Results: Most dirigent members were under purifying selection, whereas a subset may have undergone positive selection. Promoter analysis demonstrated enrichment of stress- and phytohormone-responsive cis-acting regulatory elements, suggesting that regulatory divergence was associated with environmental adaptation. Haplotype analysis revealed allelic diversity among heterotic clusters, potentially contributing to heterosis. Integration with public genome-wide association study datasets identified candidate genes significantly associated with plant architecture and kernel-quality-related traits. Transcriptome profiles indicated that several dirigent genes were preferentially expressed in the roots, suggesting their involvement in root development and nutrient uptake. In addition, public gene expression data showed that certain dirigent genes are induced in response to salt stress, supporting their putative roles in abiotic stress tolerance. Conclusions: These findings provide insights into the molecular mechanisms underlying dirigent gene functions and reveal candidate genes with potential utility for improving maize performance and stress resilience through molecular breeding. Full article

Heterozygous familial hypercholesterolemia (HeFH) is a common autosomal dominant genetic disease (1:250) characterized by elevated LDL-C. Patients with HeFH are at increased risk of premature atherosclerosis and have at least a 10-fold greater chance of cardiovascular disease (CVD). The present study examines the effect of PCSK9 inhibitor treatment (iPCSK9: arilocumab or evolocumab) on DNA damage in HeFH patients. Fifty-six patients were studied, with a normolipidemic group (control; n = 20) and patients with HeFH (study group; n = 36). DNA damage was determined by alkaline comet assay and PCSK9 protein level by ELISA. PCSK9i treatment was found to be associated with lower DNA damage, Lp(a), PCSK9, and lipid profile compared to before treatment. However, 16 of 36 patients still had Lp(a) values above 125 nmol/L, and reduced Lp(a) did not correlate with reduced DNA damage. Reduced PCSK9 demonstrated a moderately positive correlation (r = 0.48) with reduced DNA damage. PCSK9i therapy reduces the level of DNA damage in HeFH patients, regardless of the type of inhibitor. While our findings confirm that PCSK9 treatment can reduce DNA damage, the mechanism remains unclear. Full article

We report a unique pediatric acute myeloid leukemia (AML) case characterized by a CBFB::MYH11 fusion located on a supernumerary ring chromosome 16. Following diagnosis through comprehensive blood and bone marrow assays, the patient was enrolled in the Children’s Oncology Group (COG) study AAML1831 and randomized to the experimental treatment arm (Arm B). She received induction chemotherapy with CPX-351 (liposomal daunorubicin and cytarabine), gemtuzumab and ozogamicin (GO), and the cardioprotectant dexrazoxane and achieved complete remission (CR). The patient completed the treatment with sustained CR for 18 months. This case represents a rare cytogenetic phenomenon that is not well-documented in the current literature. Through a review of relevant publications, we contextualize this case within the spectrum of core binding factor AML (CBF-AML), highlighting diagnostic approaches, treatment strategies, and prognostic implications, particularly in cases involving atypical CBFB::MYH11 fusions. The durable remission observed in this patient, despite the unusual cytogenetic presentation, provides valuable insights into therapeutic management. This report underscores the cytogenetic and molecular heterogeneity of CBFB::MYH11 AML and emphasizes the importance of comprehensive genetic profiling using advanced techniques such as chromosomal microarray and next-generation sequencing. Full article

Salmonella Enteritidis (SE) remains a leading cause of human illness worldwide, and its persistence in poultry environments might be partially attributed to their ability to form biofilm. This study compared the biofilm capacity of 15 SE and 24 Salmonella Kentucky (SK) isolates from poultry products and processing facilities to uncover genetic factors driving biofilm heterogeneity. Biofilm formation and curli/cellulose production were evaluated at 20–22 °C. Genomic analyses included phylogenetic reconstruction, comparative system profiling, SNP variation, and BLASTp v2.17.0 comparisons. Phenotypic assays showed that most SE isolates (73%) were strong biofilm formers, while the majority of SK isolates (62%) failed to form biofilms, despite many carrying the complete curli–cellulose gene set and other biofilm-associated genes. Genomic analysis identified 124 biofilm-related genes, 108 of which were conserved across all isolates, and revealed 24 variants with potential functional impact. Mutations in cellulose biosynthesis (bcs) genes were linked to weaker biofilms, whereas nonsynonymous variants in tol family genes may impair flagellar biosynthesis and matrix stability. These findings demonstrate that genetic variation, not just gene presence, shapes biofilm phenotypes and highlight key molecular targets that may explain why SE persists in poultry production while SK is less successful. Full article

Coat color is a crucial production trait for fur-bearing animals and significantly influences their economic value. The remarkable diversity of coat colors in rex rabbits not only provides a wide range of market options but also serves as an essential resource for investigating the genetic mechanisms underlying coat color formation. In this study, we conducted integrated transcriptomic and proteomic profiling of skin tissues from black and white Rex Rabbits, revealing the presence of 52 co-expressed genes/proteins. Proteomic analysis revealed a significant upregulation of PMEL (p = 0.030, FC = 2.194), while transcriptomic data indicated an even more pronounced upregulation (p = 0.028, FC = 35.279). Therefore, PMEL (Premelanosome Protein) may serve as a pivotal regulator of melanogenesis in Rex Rabbits. Our findings indicate that PMEL overexpression in melanocytes increases melanin content, promotes melanocyte proliferation, and enhances the expression of melanin-related genes (MITF, TYR, TYRP1, and GPNMB) while inhibiting melanocyte apoptosis. Conversely, PMEL knockdown significantly reduces melanin content, melanocyte proliferation, and the expression of melanin-related genes while promoting melanocyte apoptosis. These findings suggest that PMEL contributes to melanogenesis in Rex Rabbits. Full article

Stenotrophomonas maltophilia (S. maltophilia) is a multidrug-resistant opportunistic pathogen. There are an increasing number of case reports on S. maltophilia infections in recent years, and the species is becoming a public health concern. Many studies have focused on profiling and pangenome of the species, particularly on their antibiotic resistance and virulence genes. However, there is a lack of studies on mobile genetic elements (MGEs), a subset of pangenome that significantly contributes to the diversity, stability, and plasticity of a population. In this study, 20 genomes of S. maltophilia were downloaded from the NCBI Genome database. The genomes were subjected to profiling of MGEs, their impact on the population structures, and the evaluation of evolutionary trends of the core genomes. The cataloguing of MGEs indicated active horizontal gene transfer events in the S. maltophilia’s population. Multiple virulence and drug resistance genes were predicted within and outside of the MGEs. We observed multiple chromosomal rearrangements in the genomes, most likely caused by MGEs, affecting up to approximately 50% of a single genome sequence. A high number of linkage disequilibrium sites were also predicted in the core genomes. This study provides insights into stability in the core and plasticity in the accessory regions in the S. maltophilia population. Full article