Search Results (4,189)

Varicocele is a common, potentially correctable condition associated with impaired male fertility. Despite being frequently encountered in clinical andrology, its pathophysiological mechanisms, diagnostic criteria, and therapeutic approaches remain areas of active investigation and debate. The authors conducted a comprehensive literature search, using the PubMed database, covering clinical studies, systematic reviews, meta-analyses, and current international guidelines from the past ten years. Emphasis was placed on studies investigating novel diagnostic modalities, therapeutic innovations, and prognostic markers. Emerging evidence supports the multifactorial pathophysiology of varicocele, involving oxidative stress, hypoxia, inflammatory pathways, and potential genetic predisposition. Biomarkers, including microRNAs, antisperm antibodies, and sperm DNA fragmentation, offer diagnostic and prognostic utility, though their routine clinical implementation requires further validation. Advances in imaging, such as shear wave elastography, may improve diagnostic accuracy. While microsurgical subinguinal varicocelectomy remains the gold standard, technological refinements and non-surgical alternatives are being explored. Indications for treatment have expanded to include selected cases of non-obstructive azoospermia, hypogonadism, and optimization for assisted reproduction, though high-level evidence is limited. Full article

Plant genetics and chemotaxonomic analysis are considered key parameters in understanding evolution, plant diversity and adaptation. Korean Peninsula has a unique biogeographical landscape that supports various aromatic plant species, each with considerable ecological, ethnobotanical, and pharmacological significance. This review aims to provide a comprehensive overview of the chemotaxonomic traits, biological activities, phylogenetic relationships and potential applications of Korean aromatic plants, highlighting their significance in more accurate identification. Chemotaxonomic investigations employing techniques such as gas chromatography mass spectrometry, high-performance liquid chromatography, and nuclear magnetic resonance spectroscopy have enabled the identification of essential oils and specialized metabolites that serve as valuable taxonomic and diagnostic markers. These chemical traits play essential roles in species delimitation and in clarifying interspecific variation. The biological activities of selected taxa are reviewed, with emphasis on antimicrobial, antioxidant, anti-inflammatory, and cytotoxic effects, supported by bioassay-guided fractionation and compound isolation. In parallel, recent advances in phylogenetic reconstruction employing DNA barcoding, internal transcribed spacer regions, and chloroplast genes such as rbcL and matK are examined for their role in clarifying taxonomic uncertainties and inferring evolutionary lineages. Overall, the search period was from year 2001 to 2025 and total of 268 records were included in the study. By integrating phytochemical profiling, pharmacological evidence, and molecular systematics, this review highlights the multifaceted significance of Korean endemic aromatic plants. The conclusion highlights the importance of multidisciplinary approaches including metabolomics and phylogenomics in advancing our understanding of species diversity, evolutionary adaptation, and potential applications. Future research directions are proposed to support conservation efforts. Full article

Background: Colorectal liver metastasis (CRLM) represents a major clinical challenge in oncology, affecting 25–50% of colorectal cancer patients and significantly impacting survival. While multimodal therapies—including surgical resection, systemic chemotherapy, and local ablative techniques—have improved outcomes, prognosis remains heterogeneous due to variations in tumor biology, patient factors, and institutional practices. Methods: This review synthesizes current evidence on prognostic factors influencing CRLM management, encompassing clinical (e.g., tumor burden, anatomic distribution, timing of metastases), biological (e.g., CEA levels, inflammatory markers), and molecular (e.g., RAS/BRAF mutations, MSI status, HER2 alterations) determinants. Results: Key findings highlight the critical role of molecular profiling in guiding therapeutic decisions, with RAS/BRAF mutations predicting resistance to anti-EGFR therapies and MSI-H status indicating potential responsiveness to immunotherapy. Emerging tools like circulating tumor DNA (ctDNA) and radiomics offer promise for dynamic risk stratification and early recurrence detection, while the gut microbiome is increasingly recognized as a modulator of treatment response. Conclusions: Despite advancements, challenges persist in standardizing resectability criteria and integrating multidisciplinary approaches. Current guidelines (NCCN, ESMO, ASCO) emphasize personalized strategies but lack granularity in terms of incorporating novel biomarkers. This exhaustive review underscores the imperative for the development of a unified, biomarker-integrated framework to refine CRLM management and improve long-term outcomes. Full article

Genetic transformation is an essential tool for investigating gene function and editing genomes. Kiwifruit, recognized as a significant global fresh fruit crop, holds considerable economic and nutritional importance. However, current genetic transformation techniques for kiwifruit are impeded by low efficiency, lengthy culture durations (a minimum of six months), and substantial labor requirements. In this research, we established an efficient system for shoot regeneration and the stable genetic transformation of the ‘Hayward’ cultivar, utilizing leaf explants in conjunction with two strains of Agrobacterium that harbor the expression vector pBI121-35S::GFP, which contains the green fluorescent protein (GFP) gene as a visible marker within the T-DNA region. Our results show that 93.3% of leaf explants responded positively to the regeneration medium, producing multiple independent adventitious shoots around the explants within a six-week period. Furthermore, over 71% of kanamycin-resistant plantlets exhibited robust GFP expression, and the entire transformation process was completed within four months of culture. Southern blot analysis confirmed the stable integration of GFP into the genome, while RT-PCR and fluorescence microscopy validated the sustained expression of GFP in mature plants. This efficient protocol for regeneration and transformation provides a solid foundation for micropropagation and the enhancement of desirable traits in kiwifruit through overexpression and gene silencing techniques. Full article

Prognostic markers such as overall survival (OS) and tertiary lymphoid structure (TLS) ratios, alongside diagnostic signatures like primary cancer-type classification, provide critical information for treatment selection, risk stratification, and longitudinal care planning across the oncology continuum. However, extracting these signals solely from sparse, high-dimensional multi-omics data remains a major challenge due to heterogeneity and frequent missingness in patient profiles. To address this challenge, we present SeNMo, a self-normalizing deep neural network trained on five heterogeneous omics layers—gene expression, DNA methylation, miRNA abundance, somatic mutations, and protein expression—along with the clinical variables, that learns a unified representation robust to missing modalities. Trained on more than 10,000 patient profiles across 32 tumor types from The Cancer Genome Atlas (TCGA), SeNMo provides a baseline that can be readily fine-tuned for diverse downstream tasks. On a held-out TCGA test set, the model achieved a concordance index of 0.758 for OS prediction, while external evaluation yielded 0.73 on the CPTAC lung squamous cell carcinoma cohort and 0.66 on an independent 108-patient Moffitt Cancer Center cohort. Furthermore, on Moffitt’s cohort, baseline SeNMo fine-tuned for TLS ratio prediction aligned with expert annotations (p < 0.05) and sharply separated high- versus low-TLS groups, reflecting distinct survival outcomes. Without altering the backbone, a single linear head classified primary cancer type with 99.8% accuracy across the 33 classes. By unifying diagnostic and prognostic predictions in a modality-robust architecture, SeNMo demonstrated strong performance across multiple clinically relevant tasks, including survival estimation, cancer classification, and TLS ratio prediction, highlighting its translational potential for multi-omics oncology applications. Full article

Genomic instability markers are important hallmarks of aging, as previously evidenced within the European study of biomarkers of human aging, MARK-AGE; however, establishing the specific metabolic determinants of vascular aging is challenging. The objective of the present study was to evaluate the impact of the susceptibility to oxidation of serum LDL particles (LDLox) and the plasma metabolization products of nitric oxide (NOx) on relevant genomic instability markers. The analysis was performed on a MARK-AGE cohort of 1326 subjects (635 men and 691 women, 35–75 years old) randomly recruited from the general population. The Inverse Probability of Treatment Weighting causal inference algorithm was implemented in order to assess the potential causal relationship between the LDLox and NOx octile-based thresholds and three genomic instability markers measured in mononuclear leukocytes: the percentage of telomeres shorter than 3 kb, the initial DNA integrity, and the DNA damage after irradiation with 3.8 Gy. The results showed statistically significant telomere shortening for LDLox, while NOx yielded a significant impact on DNA integrity. Overall, the effect on the genomic instability markers was higher than for the confirmed vascular aging determinants, such as low HDL cholesterol levels, indicating a meaningful impact even for small changes in LDLox and NOx values. Full article

Rye regeneration in anther cultures is problematic and affected by albino plants. DNA methylation changes linked to Cu²⁺ ions in the induction medium affect reprogramming microspores from gametophytic to sporophytic path. Alternations in S-adenosyl-L-methionine (SAM), glutathione (GSH), or β-glucans and changes in DNA methylation in regenerants obtained under different in vitro culture conditions suggest a crucial role of biochemical pathways. Thus, understanding epigenetic and biochemical changes arising from the action of Cu²⁺ and Zn²⁺ that participate in enzymatic complexes may stimulate progress in rye doubled haploid plant regeneration. The Methylation-Sensitive Amplified Fragment Length Polymorphism approach was implemented to identify markers related to DNA methylation and sequence changes following the quantification of variation types, including symmetric and asymmetric sequence contexts. Reverse-Phase High-Pressure Liquid Chromatography (RP-HPLC) connected with mass spectrometry was utilized to determine SAM, GSH, and glutathione disulfide, as well as phytohormones, and RP-HPLC with a fluorescence detector to study polyamines changes originating in rye regenerants due to Cu²⁺ or Zn²⁺ presence in the induction medium. Multivariate and regression analysis revealed that regenerants derived from two lines treated with Cu²⁺ and those treated with Zn²⁺ formed distinct groups based on DNA sequence and methylation markers. Zn²⁺ treated and control samples formed separate groups. Also, Cu²⁺ discriminated between controls and treated samples, but the separation was less apparent. Principal coordinate analysis explained 85% of the total variance based on sequence variation and 69% of the variance based on DNA methylation changes. Significant differences in DNA methylation characteristics were confirmed, with demethylation in the CG context explaining up to 89% of the variance across genotypes. Biochemical profiles also demonstrated differences between controls and treated samples. The changes had different effects on green and albino plant regeneration efficiency, with cadaverine (Cad) and SAM affecting regeneration parameters the most. Analyses of the enzymes depend on the Cu²⁺ or Zn²⁺ ions and are implemented in the synthesis of Cad, or SAM, which showed that some of them could be candidates for genome editing. Alternatively, manipulating SAM, GSH, and Cad may improve green plant regeneration efficiency in rye. Full article

Due to their nutritional value and sustainability, edible insect-based foods are gaining popularity in Europe. Their use is regulated by EU legislation, which defines authorised species and sets labelling requirements. Molecular tools are being developed to authenticate such products. In this study, yellow mealworm (Tenebrio molitor) larvae authorised for human consumption were fed wheat flour-based diets containing varying proportions of house cricket (Acheta domesticus) flour for 21 days. This was followed by a 48 h starvation period to assess the persistence of insect DNA in the digestive tract. Two novel, species-specific, single-copy markers were designed: ampd gene for the Acheta domesticus and MyD88 gene for the Tenebrio molitor. These were applied using qPCR and ddPCR. Both methods successfully detected cricket DNA in the guts of starved larvae. Linear regression analysis revealed a strong, statistically significant correlation between the proportion of Acheta domesticus flour in the diet and the normalised relative quantity of DNA. ddPCR proved to be more sensitive than qPCR, particularly in the detection of low DNA levels. These results suggest that the presence of DNA from undeclared insect species in edible insects may be indicative of their diet rather than contamination or adulteration. This highlights the importance of contextual interpretation in food authenticity testing. Full article

Background/Objectives: The gene pool of the Apennine wolf is affected by admixture with domestic variants due to anthropogenic hybridisation with dogs. Genetic monitoring at the population level involves assessing the extent of admixture in single individuals, ranging from pure wolves to recent hybrids or wolf backcrosses, through the analysis of nuclear and mitochondrial DNA (mtDNA) markers. Although individually non-diagnostic, mtDNA is nevertheless essential for completing the final diagnosis of genetic admixture. Typically, the identification of wolf mtDNA haplotypes is carried out via sequencing of coding genes and non-coding DNA stretches. Our objective was to develop a fast real-time PCR assay to detect the mtDNA haplotypes that occur exclusively in the Apennine wolf population, as a valuable alternative to the demanding sequence-based typing. Methods: We validated a qualitative duplex real-time PCR that exploits the combined presence of diagnostic point mutations in two mtDNA segments, the NDH-4 gene and the control region, and is performed in a single-tube step through TaqMan-MGB chemistry. The aim was to detect mtDNA multi-fragment haplotypes that are exclusive to the Apennine wolf, bypassing sequencing. Results: Basic validation of 149 field samples, consisting of pure Apennine wolves, dogs, wolf × dog hybrids, and Dinaric wolves, showed that the assay is highly specific and sensitive, with genomic DNA amounts as low as 10⁻⁵ ng still producing positive results. It also proved high repeatability and reproducibility, thereby enabling reliable high-throughput testing. Conclusions: The results indicate that the assay presented here provides a valuable alternative method to the time- and cost-consuming sequencing procedure to reliably diagnose the maternal lineage of the still-threatened Apennine wolf, and it covers a wide range of applications, from scientific research to conservation, diagnostics, and forensics. Full article

The ongoing genetic erosion of natural Prunus armeniaca populations in their native habitats underscores the urgent need for targeted conservation and restoration strategies. This study provides the first comprehensive characterization of P. armeniaca populations in the Almaty region of Kazakhstan, integrating morphological descriptors (46 parameters), molecular markers, geobotanical, and remote sensing analyses. Geobotanical and remote sensing analyses enhanced understanding of accession distribution, geological features, and ecosystem health across sites, while also revealing their vulnerability to various biotic and abiotic threats. Of 111 morphologically classified accessions, 54 were analyzed with 13 simple sequence repeat (SSR) markers and four DNA barcoding regions. Our findings demonstrate the necessity of integrated morphological and molecular analyses to differentiate closely related accessions. Genetic analysis identified 11 distinct populations with high heterozygosity and substantial genetic variability. Eight populations exhibited 100% polymorphism, indicating their potential as sources of adaptive genetic diversity. Cluster analysis grouped populations into three geographic clusters, suggesting limited gene flow across Gorges (features of a mountainous landscape) and greater connectivity within them. These findings underscore the need for site-specific conservation strategies, especially for genetically distinct, isolated populations with unique allelic profiles. This study provides a valuable foundation for prioritizing conservation targets, confirming genetic redundancies, and preserving genetic uniqueness to enhance the efficiency and effectiveness of the future conservation and use of P. armeniaca genetic resources in the region. Full article

Background: Second-generation androgen receptor signaling inhibitors are one of the main treatment options in metastatic castration-resistant prostate cancer (mCRPC). Nonetheless, a considerable proportion show limited response to treatment, which indicates the need for convenient, easily accessible predictor biomarkers, a role suited for liquid biopsy. Methods: We conducted a PRISMA-compliant systematic review of four databases (Embase, Medline, Scopus, Web of Science) to identify all studies (observational studies and clinical trials) investigating cell-free DNA, circulating tumor cells, exosomes, and circulating RNAs as prognostic markers in metastatic castration-resistant patients starting androgen receptor signaling inhibitors. We excluded studies that evaluated combination therapies, rare histological subtypes or included nonmetastatic or castrate-sensitive disease. We also evaluated whether published papers followed reporting guidelines (REMARK, STROBE, or CONSORT for abstracts). Results: We identified a total of 123 reports, from which we identified only a few well-studied and consistent biomarkers: androgen receptor overexpression/copy number gain and splice variant 7, as well as disease burden markers (circulating tumor DNA fraction and circulating tumor cell concentration). Alterations or copy number loss in tumor suppressors PTEN, RB1, and TP53 were second in terms of quantity and consistency of evidence. However, a large majority of identified biomarkers were relatively understudied or inconsistent. We identified two potential vulnerabilities: inconsistent adherence to reporting guidelines and the under-inclusion of patients of non-Western European ancestry. Conclusions: A large number of biomarkers were linked to worse outcomes in prostate cancer; nonetheless, in most cases, the evidence is limited or inconsistent, or even contradictory. The main exceptions pertain to androgen receptor signaling and disease burden, and, to a smaller extent, to certain tumor suppressor genes. Further studies are needed to confirm their clinical utility, using clear and consistent methodologies and including patients from currently understudied populations. Full article

With ketamine gaining attention as a therapeutic drug, oral administration offers an effective alternative to traditional parenteral routes. However, a significant gap remains in understanding its use via voluntary ingestion. This preliminary study aimed to explore the feasibility of oral ketamine self-administration in mice (Mus musculus), while investigating the effects of low concentrations on the brain, liver, and kidney. Adult mice were divided into three groups and received ketamine in their drinking water for 16 days at 0 (control), 5 (K5), or 10 mg/L (K10). A transient decrease in water consumption was observed in both sexes in the K10 group; however, only females in this group showed differences in ketamine intake between groups on some days. Oxidative stress markers measured in the brain, liver, and kidney only revealed higher catalase activity in the brains of females. No significant alterations were observed in liver and kidney function in either sex, nor in inflammation, apoptosis, or DNA damage in kidney tissues. Overall, these findings support the viability of voluntary oral ketamine administration and accentuate the need to refine the proposed model, not only to prevent water consumption inhibition but also to extend the exposure period, explore potential sex-related differences in ketamine intake, and further confirm the safety of oral ketamine administration. Full article

The ecological drivers of wildlife crop-foraging behavior—whether as a compensatory response to natural resource scarcity or as opportunistic exploitation of anthropogenic food sources—remain poorly understood in human–wildlife conflict research. Traditional methodologies, which primarily rely on direct observation and morphological identification, have limitations in comprehensively quantifying wildlife dietary composition, particularly in accurately distinguishing between morphologically similar plant species and conducting precise quantitative analyses. This study utilized DNA metabarcoding technology (rbcL gene markers) to identify and quantify plant dietary components through fecal sample analysis, systematically investigating the dietary composition and patterns of agricultural resource utilization of wild rhesus macaques (Macaca mulatta) in human–wildlife interface zones of southwestern China. A total of 29 rhesus macaque fecal samples were analyzed (15 from spring and 14 from winter), identifying 142 plant genera, comprising 124 wild plant genera, and 18 crop genera. The results revealed distinct seasonal foraging patterns: crops accounted for 32.11% of the diet in winter compared to 7.66% in spring. Notably, rhesus macaques continued to consume crops even during spring when wild resources were relatively abundant, challenging the traditional hypothesis driven by resource scarcity and suggesting that crop-foraging behavior may reflect an opportunistic, facultative resource selection strategy. This study demonstrates the significant value of DNA metabarcoding technology in wildlife foraging behavior research, providing scientific evidence for understanding human–primate conflict ecology and developing effective management strategies. Full article

This study investigates the genetic diversity and population structure of Castanopsis tribuloides, a vital tree species in Asian forest ecosystems. Understanding the genetic patterns of keystone forest species provides critical insights into forest resilience and ecosystem function and informs conservation strategies. We analyzed population samples collected from three distinct locations within Doi Suthep Mountain in northern Thailand using Short Tandem Repeat (STR) markers to assess both intra- and inter-population genetic relationships. DNA was extracted from leaf samples and analyzed using a panel of polymorphic microsatellite loci specifically optimized for Castanopsis species. Statistical analyses included the assessment of forensic parameters (number of alleles, observed and expected heterozygosity, gene diversity, polymorphic information content), population differentiation metrics (G_ST), inbreeding coefficients (F_IS), and gene flow estimates (N_m). We further examined population history through bottleneck analysis using three models (IAM, SMM, and TPM) and visualized genetic relationships through principal coordinate analysis and cluster analysis. Our results revealed significant patterns of genetic structuring across the sampled populations, with genetic distance metrics showing statistically significant differentiation between certain population pairs. The PCA and cluster analyses confirmed distinct population groupings that correspond to geographic distribution patterns. These findings provide the first comprehensive assessment of C. tribuloides population genetics in this region, establishing baseline data for monitoring genetic diversity and informing conservation strategies. This research contributes to our understanding of how landscape features and ecological factors shape genetic diversity patterns in essential forest tree species, with implications for managing forest genetic resources in the face of environmental change. Full article

Due to their clinical heterogeneity, nonspecific symptoms, and the limitations of existing biomarkers and imaging modalities, metabolic brain diseases (MBDs), such as mitochondrial encephalopathies, lysosomal storage disorders, and glucose metabolism syndromes, pose significant diagnostic challenges. This review examines the growing potential of cell-free DNA (cfDNA) derived from cerebrospinal fluid (CSF) epigenetic profiling as a dynamic, cell-type-specific, minimally invasive biomarker approach for MBD diagnosis and monitoring. We review important technological platforms and their use in identifying CNS-specific DNA methylation patterns indicative of neuronal injury, neuroinflammation, and metabolic reprogramming, including cfMeDIP-seq, enzymatic methyl sequencing (EM-seq), and targeted bisulfite sequencing. By synthesizing current findings across disorders such as MELAS, Niemann–Pick disease, Gaucher disease, GLUT1 deficiency syndrome, and diabetes-associated cognitive decline, we highlight the superior diagnostic and prognostic resolution offered by CSF cfDNA methylation signatures relative to conventional CSF markers or neuroimaging. We also address technical limitations, interpretive challenges, and translational barriers to clinical implementation. Ultimately, this review explores CSF cfDNA epigenetic analysis as a liquid biopsy modality. The central objective is to assess whether epigenetic profiling of CSF-derived cfDNA can serve as a reliable and clinically actionable biomarker for improving the diagnosis and longitudinal monitoring of metabolic brain diseases. Full article