Search Results (10,991)

Genomic studies have provided key insights into the molecular pathogenesis of differentiated thyroid carcinoma (DTC), including the role of genes involved in the homologous recombination (HR) related to DNA repair and genomic stability. This research aimed to investigate the genetic landscape of HR genes in thyroid pathology, associated with recurrence risk and clinical prognosis. The study involved six individuals with thyroid conditions, including two patients diagnosed with papillary thyroid carcinoma (PTC) and four individuals with benign thyroid disease. The research material consisted of tumor samples collected during surgical procedures. Protein interactions were analyzed using the STRING database (string-db.org). Homologous recombination genes were sequenced using the HRR Panel vr1.0 on the MiSeq™ Sequencing System. Bioinformatics analysis revealed a relationship between BRAF mutations and HR gene defects in PTC. Mutations in BRCA1, BRCA2, and FANCA genes, typically associated with thyroid tumors, were identified in the tissue of papillary thyroid cancer (PTC). A statistically significant correlation was found between the FANCA gene mutation (rs7195066) and the recurrent course of the PTC. The preliminary findings suggest a potential role for non-pathogenic BARD1 mutations in follicular adenoma. No significant association was found between genes involved in homologous recombination repair and the incidence of papillary thyroid carcinoma, suggesting that these genes may not play a major role in the development of this type of thyroid cancer. Full article

Background: Colorectal cancer (CRC) is significantly associated with multiple metabolic diseases, with plasma metabolites potentially mediating this relationship. This large-scale metabolomics study aims to (1) quantify the genetic correlations and causal effects between 10 metabolic disease-related phenotypes and CRC risk; (2) identify the plasma metabolites mediating these effects; and (3) explore downstream regulatory genes and druggable targets. Methods: Using linkage disequilibrium score regression and two-sample Mendelian randomization, we assessed the causal relationships between each metabolic trait and CRC. A total of 1091 plasma metabolites and 309 metabolite ratios were identified and analyzed for mediating effects by a two-step MR approach. Colocalization analyses evaluated shared genetic loci. The findings were validated in the UK Biobank for metabolite-trait associations. The expression of candidate genes was explored using data from TCGA, GTEx, and GEO. A FADS1-centered protein–protein interaction (PPI) network was constructed via STRING. Results: BMI, waist circumference, basal metabolic rate, insulin resistance and metabolic syndrome exhibited both genetic correlation and causal effects on CRC. Five plasma metabolites—mannonate, the glucose/mannose ratio, plasma free asparagine, 1-linolenoyl-2-linolenoyl-GPC (18:2/18:3), and the mannose/trans-4-hydroxyproline ratio—were identified as shared central mediators. A colocalization analysis showed rs174546 linked CRC and 1-linolenoyl-2-linoleoyl-GPC. Validation in the UK Biobank confirmed the associations between phosphatidylcholine (the lipid class of this metabolite), adiposity measures, and CRC risk. An integrative analysis of TCGA, GTEx, and GEO revealed consistent upregulation of FADS1/2/3 and FEN1 in CRC, with high FADS1 expression predicting a poorer prognosis and showing the distinct cell-type expression in adipose and colon tissue. The PPI network mapping uncovered nine FADS1 interacting proteins targeted by supplements such as α-linolenic acid and eicosapentaenoic acid. Conclusions: This study systematically reveals, for the first time, the shared intermediary plasma metabolites and their regulatory genes in the causal pathway from metabolic diseases to CRC. These findings provide candidate targets for subsequent functional validation and biomarker development. Full article

The fall armyworm (Spodoptera frugiperda) is an invasive pest of global concern, posing a significant threat to food security. It can be divided into two biotypes: the rice strain (RS) and the corn strain (CS). These two biotypes are nearly indistinguishable morphologically but differ significantly in host adaptability. The two biotypes can hybridize, but the efficiency of their hybridization has not been conclusively determined. Our research has found that the two biotypes of fall armyworm exhibit significant differences in weight gain when feeding on different host plants and artificial diets. The rice strain has a broader diet range, showing notably stronger adaptability to rice and ryegrass compared to the corn strain, suggesting that the rice strain may possess more robust detoxification metabolism. Under laboratory conditions, the two biotypes can hybridize effectively, and their offspring exhibit certain hybrid advantages. The host adaptability traits of the rice strain are dominantly inherited. Our findings provide an important foundation for understanding the biological basis of host adaptability in the rice strain of fall armyworm. Full article

(1) Background: Invasive micropapillary carcinoma (IMPC) is a rare, aggressive breast cancer subtype marked by high lymph node metastasis rates. While Oncotype DX recurrence score (RS) offers prognostic information for patients with hormone-receptor-positive (HR+) breast cancer, its utility in IMPC—a histology with distinct biologic behavior—remains unvalidated. This study evaluates whether Oncotype DX offers prognostic information with respect to overall survival (OS) in non-metastatic, early-stage patients with IMPC of the breast. (2) Methods: The National Cancer Database (2004–2020) was queried to select for women with ER+/HER2−, T1-T2N0-N1 IMPC who underwent Oncotype DX testing and received no neoadjuvant therapy. Patients were stratified by RS: low (≤11), intermediate (12–25), and high (>25). Kaplan–Meier survival curves and log-rank tests compared 5-year OS between groups. Multivariable Cox proportional hazards models assessed RS as an independent predictor, adjusting for age, race, comorbidities, grade, radiation, and insurance status. (3) Results: A total of 1325 women met the selection criteria. The cohort demonstrated significant survival disparities by RS (log-rank p = 0.017). Five-year OS rates were 97.5%, 97.5%, and 93.7% for low, intermediate, and high-risk patients, respectively. Adjusted multivariate analysis confirmed RS as an independent prognosticator: low (HR = 0.31, 95% CI: 0.15–0.75) and intermediate (HR = 0.32, 95% CI: 0.15–0.75) scores correlated with reduced mortality versus high RS. Omission of radiation therapy (HR = 2.68, 95% CI: 1.05–6.86) and higher comorbidity burden (0 comorbidities vs. ≥2: HR = 0.25, 95% CI: 0.10–0.61) were significantly associated with worse survival. (4) Conclusions: Oncotype DX is predictive for OS in IMPC, with high RS (>25) portending poorer outcomes. The survival detriment associated with RT omission aligns with prior studies demonstrating RT benefit in higher-risk cohorts. These findings validate RS as a prognostic tool in IMPC and underscore its potential to refine adjuvant therapy, particularly RT utilization. Future studies should explore RS-driven treatment personalization in IMPC, including comorbidity management and adjuvant radiation to improve outcomes in this distinct patient population. Full article

Accurate assessment of a crop’s water requirement is essential for optimising irrigation scheduling and increasing the sustainability of water use. The crop coefficient (K_c) is a dimensionless factor that converts reference evapotranspiration (ET₀) into actual crop evapotranspiration (ET_c) and is widely used for irrigation scheduling. The K_c reflects canopy cover, phenology, and crop type/variety, but is difficult to measure directly in heterogeneous perennial systems, such as vineyards. Remote sensing (RS) products, especially open-source satellite imagery, offer a cost-effective solution at moderate spatial and temporal scales, although their application in vineyards has been relatively limited due to the large pixel size (~100 m²) relative to vine canopy size (~2 m²). This study aimed to improve grapevine K_c predictions using vegetation indices derived from harmonised Sentinel-2 imagery in combination with spectral unmixing, with ground data obtained from canopy light interception measurements in three winegrape cultivars (Shiraz, Cabernet Sauvignon, and Chardonnay) in the Barossa and Eden Valleys, South Australia. A linear spectral mixture analysis approach was taken, which required estimation of vine canopy cover through beta regression models to improve the accuracy of vegetation indices that were used to build the K_c prediction models. Unmixing improved the prediction of seasonal K_c values in Shiraz (R² of 0.625, RMSE = 0.078, MAE = 0.063), Cabernet Sauvignon (R² = 0.686, RMSE = 0.072, MAE = 0.055) and Chardonnay (R² = 0.814, RMSE = 0.075, MAE = 0.059) compared to unmixed pixels. Furthermore, unmixing improved predictions during the early and late canopy growth stages when pixel variability was greater. Our findings demonstrate that integrating open-source satellite data with machine learning models and spectral unmixing can accurately reproduce the temporal dynamics of K_c values in vineyards. This approach was also shown to be transferable across cultivars and regions, providing a practical tool for crop monitoring and irrigation management in support of sustainable viticulture. Full article

In this paper, we apply an information-theoretic method proposed by Ryabko and Savina (therefore called the RS-method), based on the use of data compression, to recognize the individual author’s style of a writer across four languages from different language groups and families. In this paper, the presented method was used to study fiction texts in Russian (East Slavic group of languages of the Indo-European language family), Amharic (South Ethiosemitic group of the Semitic language family), Chinese (Sinitic group of the Sino-Tibetan language family) and English (West Germanic language group of the Indo-European language family). It was found that the amount of data necessary for recognizing an author’s style is almost the same for all four languages, i.e., the amount of data is invariant across different language groups. The results obtained are of interest to computer science, literary studies, linguistics and, in particular, computational linguistics. Full article

Heart failure (HF) remains a major cause of mortality despite the advances in pharmacological treatment. Anticoagulation therapies, including Clopidogrel, Aspirin, Warfarin, and novel oral anticoagulants (NOACs) such as Apixaban, Rivaroxaban, Edoxaban, and Dabigatran, are frequently administered to HF patients to prevent thromboembolism and adverse, life-threatening outcomes (e.g., stroke and myocardial infarction). In these settings, drug resistance and variability in responsivity to therapeutic approaches are challenging issues. Recent studies suggest that non-coding RNAs, particularly microRNAs (miRs) may play a modulatory role in HF therapy context, affecting drug efficacy. Specific miRs have been associated with resistance to Clopidogrel (e.g., miR-223 and miR-26a), Aspirin (e.g., miR-19b-1-5p and miR-92a) and Warfarin (e.g., miR-133 and miR-137). Moreover, Digoxin, a cardiac glycoside acting also over bleeding risk, upregulates miR-132, which is involved in HF-associated cardiac alteration and hypertrophy. Evidence linking miR expression to NOAC pharmacodynamics, cardiac remodeling and regulation of the coagulation is growing. These findings highlight the need of deeply harnessing the potential of miRs as predictive biomarkers or therapeutic targets in HF. Improving the knowledge on the relationship between miR and anticoagulant drugs in HF patients will contribute to personalization of the anticoagulant therapies, aimed at enhancing patient responsivity and minimizing adverse effects, ultimately improving patient life quality. Full article

Autosomal-dominant sleep-related hypermotor epilepsy (ADSHE) was the first distinct genetic epilepsy proven to be caused by mutation of the CHRNA4 gene, originally reported in 1994. In the past three decades, pathomechanisms of ADSHE associated with mutant nicotinic acetylcholine receptors (nAChRs) have been explored via various studies, including in vitro experiments and genetic rodent models. However, findings emphasize that functional abnormalities of ADSHE-mutant nAChRs alone cannot generate ictogenesis; rather, development of abnormalities in various other transmission systems induced by ADSHE-mutant nAChRs during the neurodevelopmental process before the ADSHE onset is involved in development of epileptogenesis/ictogenesis. Intra-thalamic GABAergic disinhibition induced by loss-of-function of S284L-mutant nAChRs (S286L-mutant nAChRs in rat ADSHE models) contributes to enhancing propagation of physiological ripple-burst high-frequency oscillation (HFO) and Erk signaling during sleep, leading to enhancement of the trafficking of pannexin1, connexin43, and P2X7 purinergic receptor to the astroglial plasma membrane. The combination of activation of physiological ripple-HFO and upregulation of astroglial hemichannels under the GABAergic disinhibition plays an important role in generation of epileptogenic fast-ripple-HFO during sleep. Therefore, loss-of-function of the S284L-mutation alone cannot drive ictogenesis but contributes to the development of epileptogenesis as an initial abnormality. Based on these recent findings using genetic rat ADSHE models, harboring the rat S286L-mutant Chrna4 corresponding to the human S284L-mutant CHRNA4, this report proposes hypothetical pathomechanisms of ADSHE. Full article

The skin color of radish taproots is an important commodity character that directly affects the choice behavior of consumers. Here, we identified a skin color gene carried by a red-skinned inbred line, SXAU-R2. Genetic population was constructed by the crossing of SXAU-R2 and a white-skinned inbred line, SXAU-W2, and the taproots of F₁ plants exhibited intermediate color. In the F₂ population, the separation ratio of taproot skin color indicated that the phenotype was controlled by one major locus, named RST1 (Red-Skinned Taproot 1). Combined with bulked segregant analysis and RNA sequencing (BSA-seq), 2640 single nucleotide polymorphisms (SNPs) were detected between the annotated genes of the red skin bulk and white skin bulk. Molecular markers were developed in the SNP-enriched 27~32 Mbp region of chromosome 7, and then RST1 was mapped in the genetic interval between flanking markers SSR-14 and SSR-22. Using F_2:3 lines derived from a key F₂ heterozygote, RST1 was narrowed down into a 530 Kbp interval. There were 46 expressed annotated genes in the fine-mapping region, and a gene encoding MYB was selected as the candidate of RST1. Finally, based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and RT-qPCR, we identified the potential interacting genes RsbHLH and RsWD, as well as the latent target genes RsDFR and RsANS of RST1 in the anthocyanin synthesis pathway. These results provide an understanding of the genetic mechanisms regulating anthocyanin synthesis and offer an efficient molecular marker for the radish breeding of skin color. Full article

Introduction: Dry Eye Syndrome (DES) is a multifactorial disorder of the ocular surface, characterized by complex interactions between environmental factors, immune dysregulation, and potential genetic predispositions. Vitamin D deficiency, known for its immunomodulatory properties, has increasingly been implicated in the pathogenesis of DES; however, the underlying mechanisms remain insufficiently elucidated. Of particular interest is the vitamin D receptor (VDR) gene, whose polymorphisms may influence the bioavailability and biological activity of vitamin D. Objective: The aim of this study was to investigate the association between serum 25-hydroxyvitamin D [25(OH)D₃] levels and selected polymorphisms in the VDR gene (Taq, Fok, Apa, and Bsm) in patients with DES and to analyze their potential clinical and genetic interactions. Methods: This prospective observational study included 60 patients with a confirmed diagnosis of DES. Serum 25(OH)D₃ levels were measured, and genotyping of four VDR single-nucleotide polymorphisms (SNPs) was performed using PCR followed by restriction fragment length polymorphism analysis. Genotype distributions were assessed in relation to vitamin D status using appropriate statistical tests and Hardy–Weinberg equilibrium analysis. Results: Over 85% of patients exhibited insufficient or deficient vitamin D levels. Among the analyzed SNPs, only the ApaI polymorphism (rs7975232) showed a statistically significant association with vitamin D status (p = 0.0384), with the homozygous AA genotype being more prevalent among patients with hypovitaminosis. The remaining polymorphisms (TaqI, FokI, BsmI) did not reach statistical significance; however, potential trends were observed that may warrant further investigation in larger cohorts. Conclusion: The findings suggest a potential role for VDR gene variability in the regulation of systemic vitamin D levels in patients with DES. Identification of specific genotypes may contribute to the development of personalized diagnostic and therapeutic strategies, particularly for patients with treatment-resistant forms of the disease. These results support the integration of genetic biomarkers and nutritional parameters into modern ophthalmologic practice. Full article

Acne vulgaris is a multifactorial disease with high heritability, but the genetic determinants of severity remain incompletely defined. This study evaluated 650 individuals genotyped with a 60-single-nucleotide polymorphism (SNP) panel covering immune, lipid, endocrine, and barrier pathways. Acne severity was graded as 1 (n = 193), 2–3 (n = 383), or 4 (n = 74). Single-SNP analysis highlighted associations in loci such as LHCGR (rs13405728), TGF-β2 (rs1159268), FST (rs38055), WNT10A (rs74333950), PIK3R1 (rs10515088), and THADA (rs13429458) and barrier-related variants (FLG, FLG-AS1). Epistasis analysis of 44 quality-controlled SNPs revealed 190 significant interactions (false discovery rate, FDR ≤ 0.10), with TLR4 as the main hub (degree = 22), bridging immune (IL10, TNF), lipid (PNPLA3, APOE), and barrier (FLG-AS1, OVOL1) genes. Polygenic risk scoring (PRS) showed a monotonic increase across severity grades, with Grade 4 displaying higher median scores (0.319) compared to Grade 1 (−0.129) and Grades 2–3 (0.034). Discrimination was modest but consistent (AUC: 0.661 for Grade 4 vs. 1; 0.662 vs. 2–3; 0.679 vs. all others). These results support a framework where microbial sensing, lipid metabolism, and barrier function converge to drive severe acne, underscoring the potential of genetic profiling for risk stratification and precision therapy. Full article

Cardiovascular diseases (CVDs) cover various pathologies including heart failure (HF). Furthermore, vitamin D is involved in the regulation of the cardiovascular system. This study aimed to assess the association between the vitamin D receptor (VDR) genotypes and the occurrence of cardiovascular disorders in the Algerian population. VDR gene polymorphisms were identified using the PCR-RFLP method. Moreover, plasma concentrations of 25-hydroxyvitamin-D were assessed by a chemiluminescent immunoassay method and plasma NT-proBNP levels were determined in vitro by immunoenzymatic analysis. Interestingly, our results indicate that the genotypic frequencies of ApaI polymorphism of the VDR gene were significantly higher in CVD patients compared to the control group. Moreover, higher numbers of AA genotypes and A alleles were found in the CVD group. Our data indicate that the group of CVD patients with HF compared to those without HF showed the same genotype and allele distribution. Furthermore, low vitamin D rates and high N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels according to the VDR rs7975232 genotype were noted in CVD patients compared to healthy controls. Our results indicate that ApaI polymorphism of the VDR gene and lower vitamin D level may be associated with increased cardiovascular risk. These findings indicate that the ApaI AA genotype could be considered as a new HF risk marker in the Algerian population. Full article

Background: The biosynthesis of Lewis (Le) antigens depends on the FUT3 gene, encoding an α(1,3/4)-fucosyltransferase. Individuals lacking functional FUT3 exhibit a Le(a–b–) phenotype, regardless of secretor status. Methods: This study determined the prevalence of FUT3 single nucleotide variants (SNVs) in Thai blood donors and characterised genotype and allele distributions. We also examined the association between FUT3 variants and the presence of Le antibodies to better understand variability in immune responses. A total of 112 blood donors were recruited, comprising 52 non-responders and 60 responders for Le antibody detection. The FUT3 coding sequence was amplified by polymerase chain reaction and directly sequenced to identify single nucleotide variants (SNVs) and haplotypes. Results: Associations between FUT3 SNVs, haplotypes, and Le antibody responsiveness were subsequently analysed. Thirteen FUT3 SNVs were identified, with c.59T>G (rs28362459) present in all Le(a–b–) cases. The FUT3*01N.17.03 (le^59,1067) haplotype was most common (0.634) and showed the strongest association with Le antibody responsiveness (adjusted OR = 3.052, 95% CI: 1.683–5.534, p < 0.0001). Differences in antibody types, isotypes, and the FUT3*01N.17.03 genotype between groups were not statistically significant. Conclusions: This first study characterises FUT3 variations in Le(a–b–) Thai blood donors and identifies FUT3*01N.17.03 as associated with Le antibody responsiveness, highlighting its relevance for population-specific genetic diagnostics in transfusion medicine. Full article

Background: Physical conditioning is essential to meet the operational demands of military environments. However, high-intensity exercise provokes muscle microinjuries resulting in exercise-induced muscle damage. This condition is typically monitored using serum biomarkers such as creatine kinase (CK), myoglobin (MYO), and lactate dehydrogenase (LDH). Nevertheless, individual variability and genetic factors complicate the interpretation. In this context, the rs1815739 variant (ACTN3), the most common variant related to exercise phenotypes, hypothetically could interfere with the muscle physiological response. This study aimed to evaluate the kinetics of serum biomarkers during a high-intensity activity and their potential association with rs1815739 polymorphism. Materials and Methods: 32 male cadets were selected during the Army Paratrooper Course. Serum was obtained at six distinct moments while they performed regular course tests and recovery time. Borg scale was assessed in 2 moments (~11 and ~17). Results: Serum levels of CK, CK-MB, MYO, and LDH significantly increase after exercise, proportionally to Borg’s level, following the applicability of longitudinal studies to understand biomarker levels in response to exercise. R allele carriers (ACTN3) were only slightly associated with greater levels of MYO and CK, mainly in relative kinetic levels, and especially at moments of greater physical demand/recovery. Although the ACTN3 was slightly related to different biomarker levels in our investigation, the success or healthiness in military activities is multifactorial and does not depend only on interindividual variability or physical capacity. Conclusions: Monitoring biomarkers and multiple genomic regions can generate more efficient exercise-related phenotype interventions. Full article

Cytisine, a naturally occurring alkaloid and partial agonist of nicotinic acetylcholine receptors (nAChRs), has long been used as a smoking cessation aid and serves as the pharmacophore for varenicline. Recent research has expanded its therapeutic scope to neurodegenerative and neurological disorders, motivating the development of new cytisine derivatives. Among these, N-propargylcytisine combines the biological activity of the parent compound with the synthetic versatility of the terminal alkyne group. Herein, we report the synthesis and characterization of N-propargylcytisine, and its symmetrical dimer linked through 1,3-diyne moiety obtained via a copper-mediated Glaser–Hay oxidative coupling. The products were analyzed by NMR, FT-IR, and mass spectrometry, confirming the introduction of the propargyl moiety and the formation of the diyne bridge. Solvatochromic study of both compounds were performed using UV-VIS absorption spectroscopy in solvents of varying polarity, including protic solvents capable of hydrogen bonding. The 1,3-diyne motif, commonly found in bioactive natural products, endows the resulting dimer with potential for further derivatization and biological evaluation. This study demonstrates the utility of the Glaser–Hay reaction in the functionalization of alkaloid scaffolds and highlights the prospects of N-propargylcytisine derivatives in drug discovery targeting the central nervous system. Full article