Search Results (2,476)

In Africa, hares (Lepus spp.) show a high variability in external phenotypes. Species identification, delimitation, and distinction are difficult, due to the generally shallow evolutionary divergence of species, high intraspecific phenotypic variability, potentially complex reticulate evolutionary scenarios, and absence of relevant data across large areas. Our microsatellite and mitochondrial (mt) CR1 sequence data of hares from Tunisia with four different coat color morphs revealed high levels of gene flow both in nuclear and mt gene pools but no relevant partitioning of genetic variability parallel to the four coat color types. Nuclear and mt gene pool correspondence was at a very low level, and no phylogenetic gaps were observed in the mtDNA. Our results indicate only one hare species with different coat colors in Tunisia that shows no signals of reticulate evolution or incipient speciation. Because of potential reticulate evolutionary signals, especially in the mtDNA and the probably high adaptive significance of coat colors and patterns, external phenotypes combined with mtDNA alone may not serve as good proxies for species delimitation in hares from wide ranges in Africa. Combined nuclear and mtDNA population genetic and phylogenetic data allow more complex inferences on current and ancestral evolutionary processes for species identification and delimitation. Full article

Understanding the genetic diversity and population structure of Cucurbita species is essential for effective germplasm conservation and the development of improved cultivars. This study aimed to evaluate the genetic diversity, population structure, and genetic relationships among accessions of C. pepo, C. moschata and C. maxima and their interspecific hybrids (Tetsukabuto hybrid C. maxima × C. moschata). A total of 92 accessions were analyzed using 22 polymorphic simple sequence repeat (SSR) markers selected from previous studies due to their high polymorphic information content (PIC). Genetic diversity parameters were estimated, and population structure was inferred using Bayesian clustering, complemented by dendrogram and principal component analysis (PCA). All markers were successfully amplified in C. pepo, C. moschata, C. maxima, and the hybrids, with polymorphic information content (PIC) values ranging from 0.191 (CMTm232) to 0.448 (CMTm48) and average of 0.274. The AMOVA analysis showed that 50% of the total variation was attributed to differences both within and among groups. PCA revealed clear genetic differentiation among the analyzed species, with C. maxima and hybrid accessions clustering closely and exhibiting lower genetic dissimilarity. In contrast, C. pepo displayed greater genetic divergence, supporting its distinct evolutionary trajectory. According STRUCTURE analysis the accessions can be divided into four subpopulations, which are closely related to the species. PCA and dendrogram showed similar results for genetic structure of Cucurbita germplasm; C. maxima and hybrid accessions clustering closely and C. pepo as a distinct group. These findings provide valuable insights for breeding programs, germplasm management, and conservation strategies aimed at preserving genetic diversity and exploiting interspecific variation. Full article

Tilia cordata Mill. is a long-lived, ecologically important broadleaved tree species that maintains high genetic diversity despite habitat fragmentation and historical range shifts. In this study, we assessed genetic diversity, clonal structure, and population differentiation in six genetic conservation units (GCUs) in Lithuania using nuclear microsatellite markers. A total of 1109 individuals were successfully genotyped, revealing 979 unique multi-locus genotypes, with 17% of individuals assigned to clonal lineages. Clonal groups were generally small and spatially restricted, indicating localized vegetative regeneration. Genetic diversity was high across all populations, with similar levels of observed and expected heterozygosity, consistent with predominantly outcrossing reproduction. Juvenile cohorts exhibited slightly higher allelic richness and latent genetic potential compared to mature trees, suggesting effective regeneration and maintenance of genetic variation. Genetic differentiation among populations was low but significant (F_ST = 0.013; G″_ST = 0.051), with evidence of clustering corresponding to provenance regions. High gene flow (Nm ≈ 10) likely contributes to weak population structure, although regional differentiation persists. The results demonstrate that Lithuanian T. cordata populations retain a robust genetic framework, combining high within-population diversity with moderate structuring. These findings highlight the importance of conserving multiple GCUs and implementing genetic monitoring to ensure long-term population viability under changing environmental conditions. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy. Next-generation sequencing (NGS) enables molecular characterization and may identify clinically actionable alterations; however, real-world multicenter data linking genomic subgroups to survival outcomes remain limited. We aimed to characterize the molecular landscape of NGS-tested PDAC in a Turkish multicenter cohort and evaluate the association of key molecular alterations, including KRAS status and KRAS variant subgroups, with survival outcomes. Methods: We conducted a multicenter retrospective cohort study including patients with pathologically diagnosed PDAC between 2017 and 2025 who underwent tumor-based NGS in routine clinical practice. Overall survival (OS) was calculated from the date of metastasis, defined as the date of diagnosis for de novo metastatic disease and the date of first documented distant recurrence for recurrent cases. Progression-free survival (PFS) was calculated from the initiation of first-line systemic therapy for metastatic disease to progression or death. Survival was estimated using the Kaplan–Meier method and compared using the log-rank test. Multivariable Cox proportional hazards models were constructed for OS and PFS using clinically relevant covariates selected a priori. Results: A total of 98 patients underwent molecular profiling, and survival analyses were performed in 92 patients with available OS/PFS data. KRAS mutations were detected in 83.7% (82/98) of patients, with predominant variants G12D (47.6%), G12V (30.5%), and G12R (12.2%). TP53 mutations were present in 59.2% (58/98) of tumors, and all tumors were microsatellite stable. Tumor mutational burden data were available for 72 patients; the median TMB was 3.83 mutations/Mb, and 15.3% of evaluable tumors had a TMB ≥ 10 mutations/Mb. Excluding KRAS, clinically actionable alterations were identified in 4.1% of patients, whereas an additional 32.7% harbored potentially actionable or investigational alterations. Median OS was 14.0 months (95% CI, 11.7–16.3), and median PFS was 6.0 months (95% CI, 4.3–7.7). In unadjusted analyses, OS and PFS did not differ significantly according to KRAS mutation status (OS, p = 0.967; PFS, p = 0.652), TP53 mutation status (OS, p = 0.404; PFS, p = 0.510), or KRAS variant subgroup (OS, p = 0.332; PFS, p = 0.194). In multivariable Cox analyses, KRAS mutation status was not independently associated with OS (aHR 1.13, 95% CI 0.56–2.28; p = 0.727) or PFS (aHR 1.09, 95% CI 0.59–2.01; p = 0.780), whereas ECOG performance status remained the strongest adverse clinical factor. Conclusions: In this multicenter real-world PDAC cohort, the molecular landscape was dominated by KRAS and TP53 alterations, whereas clinically actionable non-KRAS alterations were identified in only a minority of patients. After adjustment for major clinical covariates, KRAS mutation status was not independently associated with OS or PFS. Molecular profiling may still be useful for identifying uncommon potentially targetable alterations; however, larger clinically annotated multicenter studies are needed to better define its prognostic and treatment-directing value in routine practice. Full article

Endometrial cancer (EC) is the sixth most common cancer in women. Its overall incidence has increased by 132% over the past 30 years, reflecting an increase in the prevalence of risk factors. The mortality rate decreased by 15% in the last 30 years, despite the high number of endometrial cancer-related deaths occurring world-wide. An inverse relationship has been observed between the incidence of EC, mortality and socio-economic status: more patients living in low-income countries die from EC because they do not have access to timely and effective treatment. About 80% of EC cases are diagnosed in an early stage and have a good prognosis. However, about 20% of cases present in advanced stages and are characterized by a poor prognosis. The molecular classification proposed by The Cancer Genome Atlas (TGCA) and its surrogate for clinical use allowed the adoption of personalized treatments. The assessment of the status of the MMR has revolutionized the treatment of advanced ECs, leading to significant results both in terms of PFS and OS. In this review we will focus on MMR deficiency (dMMR)/microsatellite instability-hypermutated (MSI-H) tumors, which globally account for 20–30% of ECs. The dMMR group encompasses multiple etiologies, including sporadic defects in MMR genes, germline mutations, and hypermethylation of the MLH1 promoter. Currently, the combination of immunotherapy (I-O) with standard chemotherapy has become the new standard first-line treatment for dMMR advanced or recurrent ECs. Although the main clinical trials involving patients with MMRd/MSI-H ECs treated with I-O and chemotherapy have demonstrated efficacy and long-term control of the disease, a significant number of patients do not respond to treatment (intrinsic or primary resistance) and others develop progression during treatment (acquired or secondary resistance). In this narrative approach the biological and molecular bases of these tumors have been integrated with recent advances involving diagnostic techniques, therapeutic opportunities and the genomic and phenotypical alterations underpinning the mechanisms of resistance. Special attention was given to the need for robust, clinically affordable biomarkers to promptly identify responders and non-responders to the current treatment regimens. Full article

The new-generation global navigation satellite system (GNSS) demands enhanced satellite autonomy, where high-precision orbit prediction plays a pivotal role. Traditional dynamic models depend heavily on long-term on-orbit observations, making hybrid deep-learning-based orbit prediction models an efficient alternative. Although existing studies have validated that temporal networks can effectively capture orbit error variations, improving prediction accuracy under short input sequences remains a critical challenge. To address this issue, this paper proposes an improved short-sequence-adaptive Bidirectional Long Short-Term Memory (BiLSTM) network to enhance orbit prediction performance of BeiDou Medium Earth Orbit satellites. Specifically, we design a scale-aware hybrid convolution module and an attention-driven feature fusion module to generate feature representations with high information density, which outperform the standalone BiLSTM under short input sequences. Experiments on the BeiDou system (BDS) C19 satellite demonstrate that our method reduces the mean residual rates from 54.03%, 41.18%, 80.10% to 4.36%, 6.12%, 5.39% in the X, Y, and Z axes, respectively, surpassing BiLSTM alone by over 85% across all metrics. Notably, the proposed method exhibits robust generalization capabilities across similar satellites with similar orbital configurations and dynamic environments. Full article

Colorectal cancer is a heterogeneous malignancy characterized by alterations in oncogenic signaling pathways and epigenetic mechanisms involved in gene regulation. Aberrant activation of the Wnt/β-catenin pathway represents a central molecular event in colorectal tumorigenesis, while histone-associated epigenetic modifications may contribute to tumor progression and variability. This study aimed to investigate the relationship between Wnt pathway activation and histone H3 lysine 27 trimethylation in colorectal cancer and to examine their associations with clinicopathological and molecular characteristics. A retrospective observational study was performed on 83 colorectal adenocarcinoma cases using immunohistochemical evaluation of nuclear β-catenin and H3K27me3 expression in formalin-fixed, paraffin-embedded tumor samples, together with molecular analysis of KRAS, NRAS, and BRAF mutations and microsatellite instability status. Nuclear β-catenin expression was observed in 39.8% of cases, while H3K27me3 exhibited negative, mosaic, or diffuse nuclear staining patterns. Nuclear β-catenin expression was significantly associated with patient sex and age, whereas H3K27me3 expression patterns were significantly associated with tumor location, histological grade, disease stage, and metastatic status. These results indicate that Wnt pathway activation and H3K27me3-associated epigenetic alterations frequently coexist in colorectal cancer and support the value of integrated molecular and epigenetic assessment. Full article

Erythema gyratum repens (EGR) is a rare figurate erythema strongly associated with internal malignancy and recognized as one of the most specific cutaneous paraneoplastic syndromes. Its recognition is clinically important, as it frequently precedes the diagnosis of an underlying neoplasm. We report the case of an 80-year-old woman who presented to the emergency department with a rapidly progressive, intensely pruritic eruption displaying a characteristic concentric “wood-grain” pattern. Laboratory evaluation revealed iron-deficiency anemia. Contrast-enhanced computed tomography identified a right-sided colonic mass, and colonoscopy with biopsy confirmed adenocarcinoma of the cecum. The patient underwent elective laparoscopic right hemicolectomy with complete tumor resection (pT3N0, microsatellite stable). Following surgery, the cutaneous lesions resolved completely and did not recur during follow-up. This case highlights erythema gyratum repens as a clinically relevant early marker of colorectal cancer and emphasizes the importance of prompt recognition of this distinctive dermatosis to trigger urgent and comprehensive malignancy screening, enabling timely diagnosis and definitive treatment. Full article

Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality globally. Approximately 45% of these tumors harbor oncogenic mutations that drive carcinogenesis and are amenable to targeted therapies. Other predictive biomarkers—e.g., PD-L1, TMB, and MSI—play a crucial role in patients’ management. This study aims to investigate the existence of mutation clusters (co-mutations) and evaluate the correlation of these clusters with various clinical and laboratory parameters. Methods: A retrospective study was conducted utilizing pathological samples from lung cancer patients harboring mutations in EGFR, KRAS, ALK, BRAF, MET, HER2, ROS1, NTRK, and NRG1. Data were collected from the Institute of Pathology at Carmel Medical Center between the years 2022 and 2024. Patients were stratified using a Two-Step Cluster Analysis algorithm based on actionable mutations and co-mutations. Heatmaps and dendrograms were generated to assess the correlation between these genomic clusters, clinical metrics, and predictive biomarkers. Results: The study cohort included 129 patients with actionable mutations. Five distinct clusters were identified: Clusters 1, 2, and 3 exhibited a high expression of STK11 and TP53 co-mutations alongside KRAS drivers (n = 38, n = 12, and n = 23, respectively). Clusters 4 and 5 demonstrated high expression of ALK alterations and tumor suppressor gene mutations (n = 31 and n = 25, respectively). Cluster comparisons demonstrated statistically significant differences between clusters regarding age, gender, PD-L1 expression, and tumor mutational burden. No significant associations were found regarding ethnicity or microsatellite instability status. Conclusions: By constructing clusters based on the aggregate of genomic alterations in patients with actionable mutations, it is possible to predict associations with distinct demographic and clinical characteristics. Future research should apply this analytical approach to larger cohorts to further characterize these subgroups and investigate potential correlations with therapeutic efficacy. Full article

Early-onset colorectal cancer (EOCRC), defined as diagnosis before the age of 50 years, is increasing globally and is frequently characterized by aggressive biology and a disproportionate burden of liver metastases. This review synthesizes emerging evidence on the distinct molecular, immunologic and clinical features that differentiate EOCRC liver metastases from those arising in older adults. Genomic studies revealed increased chromosomal instability, increased copy number variation burden and unique amplification patterns involving MYC, RAD21, GNAS and MAPK1, alongside altered frequencies of classical driver mutations and increased germline predisposition. EOCRC liver metastases also exhibit a progenitor-like transcriptional state and an immune-cold microenvironment marked by reduced myeloid infiltration, impaired antigen presentation and profound resistance to immunotherapy, particularly in microsatellite-stable disease. Mechanistic insights into ferroptosis highlight therapeutic vulnerabilities, especially in PIK3CA-mutant tumors, where aspirin and ferroptosis inducers show synergistic potential. Clinically, high-risk EOCRC patients often present with left-sided primary tumors, synchronous metastases, adverse histology, elevated CEA levels and a hereditary predisposition, with prognostic models incorporating these variables outperforming traditional staging. Collectively, accumulating evidence suggests that EOCRC liver metastases may represent a biologically and clinically distinct entity, although ongoing debates regarding the extent of this distinction underscore the need for age-specific molecular profiling and prospectively validated therapeutic strategies. Full article

Microsatellite instability (MSI) testing is frequently used to screen patients for the early detection of Lynch syndrome, the most common hereditary colorectal cancer syndrome. MSI testing compares microsatellite repeat lengths in tumor DNA with those in matched normal tissue from the same patient. Therefore, precise sample identification is critical for obtaining reliable test results. The Penta-C and Penta-D pentanucleotide markers are widely used for sample identification in MSI testing. We investigated instability, defined as allelic mismatches or shifts, discordant fragment sizes, or the appearance of alleles in tumor DNA that were absent in the corresponding normal DNA, in the Penta-C and Penta-D loci across 2609 paired colorectal tumor and matched normal tissue or blood DNA samples. The allele sizes of both markers did not match in 0.3% of microsatellite-stable (MSS) and 12.3% of microsatellite instability-high (MSI-H) patients (p < 0.001, difference in proportions, 12.0% (95% CI, 8.9–15.1%)). Non-matching allele sizes in 12.3% of the MSI-H tumors suggest that other repeat markers may also be unstable and not suitable for sample identification in these tumors. Full article

Despite the endangered status of the Oriental Stork (Ciconia boyciana) on the IUCN Red List, a critical lack of contemporary mitochondrial genomic data from its core distribution areas in mainland China has hindered our understanding of the species’ long-term evolutionary stability and spatiotemporal variation. This study addresses this gap by sequencing and assembling the complete mitogenome (17,608 bp) of a contemporary individual from Hongze Lake, Jiangsu (PX682155), and conducting a rigorous comparative analysis against a historical reference sequence published 25 years ago in Japan (NC_002196). Our results demonstrate striking structural and functional conservation across a quarter-century span; the 13 protein-coding genes exhibit highly synchronized gene arrangements, base composition biases, and Relative Synonymous Codon Usage (RSCU) patterns, indicative of stringent purifying selection maintaining oxidative phosphorylation efficiency. While phylogenetic analysis reinforces its sister-group relationship with the White Stork (C. ciconia), significant length polymorphisms were identified within the D-loop control region, primarily driven by microsatellite repeat variations. These findings provide a vital genomic benchmark for mainland populations, offering high-resolution molecular markers essential for future large-scale assessments of geographic isolation and the refinement of targeted conservation strategies for this flagship wetland species. Full article

Background: Heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL) is an RNA-binding protein involved in alternative splicing and immune regulation; however, its role in liver hepatocellular carcinoma (LIHC) remains unclear. Methods: We performed integrative multi-omics analyses using data from TCGA, GEO, and the Human Protein Atlas to evaluate the expression patterns, prognostic value, and potential biological functions of HNRNPLL. Functional enrichment and immune-related analyses were conducted to explore associated pathways. Experimental validation was performed in LIHC cell lines using Western blotting, RT-qPCR, CCK-8, colony formation, and Transwell assays, along with a xenograft mouse model. Results: HNRNPLL was significantly upregulated in LIHC at both transcriptomic and proteomic levels and was associated with advanced clinicopathological features and poor overall survival. Multivariate Cox regression analysis identified HNRNPLL as an independent prognostic factor. Enrichment analyses suggested that HNRNPLL-related genes are mainly involved in cell cycle regulation, mitotic progression, epithelial–mesenchymal transition, and immune-related pathways. In addition, HNRNPLL expression was correlated with immune cell infiltration, tumor mutational burden, microsatellite instability, ferroptosis-related genes, and m6A methylation regulators. Functional experiments demonstrated that HNRNPLL knockdown suppressed proliferation, migration, and invasion of liver cancer cells and inhibited tumor growth in vivo. Conclusions: These findings suggest that HNRNPLL may act as a potential regulator of LIHC progression and is associated with tumor-related biological processes and immune features. HNRNPLL may serve as a candidate biomarker for prognosis and a potential therapeutic target in LIHC, although further mechanistic studies are required. Full article

The conservation of genetic diversity in historically structured horse breeds requires fi-ne-scale population genetic evaluation beyond conventional pedigree-based approaches. The present study assessed genetic diversity, population structure, and mare family differentiation in a Lipizzan horse population using 16 ISAG/FAO-recommended microsatellite markers. A total of 172 mares representing 29 mare families were genotyped. All loci were polymorphic, with a mean number of alleles per locus of 6.69 and a mean effective number of alleles of 3.56. The average polymorphism information content (PIC = 0.66) indicated high marker informativeness. Mean observed heterozygosity was slightly lower than expected heterozygosity, although the overall negative inbreeding coefficient suggested general heterozygote excess and low population-level inbreeding, whilst the genetic differentiation among mare families was moderate. The principal components and the STRUCTURE analysis indicated admixture among mare families. Seven private alleles were detected across six loci, highlighting the presence of rare lineage-specific variants. These findings emphasize the importance of mare family-based analyses for identifying hidden genetic structures that may not be captured by population-level averages. The integration of microsatellite-based diversity evaluation provides a robust framework for de-signing sustainable breeding and conservation strategies aimed at preserving both overall variability and rare lineage-specific genetic components. Full article

A simple, fast, and cost-effective organic solvent-based protocol was developed for DNA extraction from deer antlers and prepared trophy skulls, eliminating the need for commercial kits or cryogenic grinding. The method combines bead-based mechanical homogenization with a 4 h enzymatic digestion in EDTA buffer containing N-lauryl sarcosine and Proteinase K, followed by phenol–chloroform–isoamyl alcohol purification and centrifugal filtration. DNA quality and quantity were evaluated using agarose gel electrophoresis, Qubit fluorometry, and Nanodrop spectrophotometry. The protocol was tested on 60 samples, comprising 30 antlers and 30 pedicle parts from prepared trophy skulls of roe deer (Capreolus capreolus), fallow deer (Dama dama), and red deer (Cervus elaphus). To assess suitability for downstream applications, species-specific microsatellite markers were amplified using multiplex PCR, successfully generating complete genotypes from all 60 samples. These results, along with a demonstrated case study, confirm that the developed protocol provides high-quality DNA suitable for molecular genetic investigations, enabling reliable genotyping from small amounts of both antler and processed trophy materials in forensic and conservation contexts. Full article