Search Results (426)

Despite significant advances in prostate cancer treatment over the past two decades, metastatic castration-resistant prostate cancer (mCRPC) remains incurable. We present the case of a patient with aggressive prostate cancer diagnosed 20 years ago, underscoring the value of longitudinal genomic profiling and advanced imaging to guide clinical decisions. After multiple treatment failures, genomic analyses of tissue and liquid biopsies revealed dynamic changes in tumor biology and the emergence of resistance mechanisms, particularly AR amplification, identified with a liquid biopsy test and validated by [¹⁸F]-FDHT PET scan. This finding guided treatment with bipolar androgen therapy (BAT), which achieved a dramatic clinical response, reduced AR expression, improved symptoms, and restored sensitivity to enzalutamide. This case exemplifies the utility of serial liquid biopsies in uncovering mechanisms of tumor evolution and resistance, and the crucial role of cutting-edge diagnostics in personalized cancer treatment. Full article

Given the environmental significance of the textile industry, especially the accumulation of nondegradable materials, there is extensive development of greener approaches to fabric waste management. Here, we investigated the biodegradation potential of three Streptomyces strains in model compost on polyamide (PA) and polyamide-elastane (PA-EA) as synthetic, and on cotton (CO) as natural textile materials. Weight change of the materials was followed, while Fourier-Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) were used to analyze surface changes of the materials upon biodegradation. The bioluminescence-based toxicity test employing Aliivibrio fischeri confirmed the ecological safety of the tested textiles. After 12 months, the increase of 10 and 16% weight loss, of PA-EA and PA, respectively, was observed in compost augmented with Streptomyces sp. BPS43. Additionally, a 14% increase in cotton degradation was recorded after 2 months in compost augmented with Streptomyces sp. NP10. Genome exploration of the strains was carried out for potential plastic-degrading enzymes. It highlighted BPS43 as the most versatile strain with specific amidases that show sequence identity to UMG-SP-1, UMG-SP-2, and UMG-SP-3 (polyurethane degrading enzymes identified from compost metagenome). Our results showcase the behavior of Streptomyces sp. BPS43 in the degradation of PA and PA-EA textiles in composting conditions, with enzymatic potential that could be further characterized and optimized for increased synthetic textile degradation. Full article

Lonicera japonica Thunb. is a traditional Chinese medicinal herb whose floral buds are the primary source of pharmacological compounds that require manual harvesting. As a result, its floral bud duration, determined by the opening time, is a key determinant of both quality and economic value. However, the genetic mechanisms controlling floral bud duration remain poorly understood. In this study, we employed population structure analysis and molecular experiments to identify candidate genes associated with this trait. The improved cultivar Beihua No. 1 (BH1) opens its floral buds significantly later than the landrace Damaohua (DMH). Exogenous application of methyl jasmonate (MeJA) to BH1 indicated that jasmonate acts as a negative regulator of floral bud duration by accelerating floral bud opening. A genome-wide selection scan across 35 germplasms with varying floral bud durations identified the transcription factor LjWRKY50 as the causative gene influencing this trait. The dual-luciferase reporter assay and qRT-PCR experiments showed that LjWRKY50 activates the expression of the jasmonate biosynthesis gene, LjAOS. A functional variant within LjWRKY50 (Chr7:24636061) was further developed into a derived cleaved amplified polymorphic sequence (dCAPS) marker. These findings provide valuable insights into the jasmonate-mediated regulation of floral bud duration, offering genetic and marker resources for molecular breeding in L. japonica. Full article

Reducing the application of chemical fertilizers and remediating heavy metal pollution in soil are important directions in current agricultural research. Utilizing the plant-growth-promoting and remediation capabilities of bacteria can provide more environmentally friendly assistance to agricultural production. In this study, the Burkholderia alba YIM B08401 strain was isolated and identified from rhizospheric soil, subjected to whole-genome sequencing and analysis, and its Cd²⁺ adsorption efficiency and characteristics were confirmed using multiple experimental methods, including atomic absorption spectrometry (AAS), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS). The results showed that the genome of strain YIM B08401 has a total length of 7,322,157 bp, a GC content of 66.39%, and predicts 6504 protein-coding sequences. It contains abundant functional genes related to nutrient conversion (phosphate solubilization, sulfur metabolism, zinc solubilization, siderophore production), plant hormone regulation (indole-3-acetic acid secretion, ACC deaminase production), phenolic acid degradation, root colonization, heavy metal tolerance, pathogen antagonism, and the production of antagonistic secondary metabolites. Additionally, strain YIM B08401 can specifically bind to Cd²⁺ through various functional groups on the cell surface, such as C-O-C, P=O, and O-H, enabling biosorption. In conclusion, strain YIM B08401 is an excellent strain with plant-growth-promoting, disease-resistant, and bioremediation capabilities, warranting further development as a biofertilizer for agricultural applications to promote green and sustainable agricultural development. Full article

The rapid advancement of genomic technologies has significantly transformed biomedical research and clinical applications, particularly in oncology. Identifying patient-specific genetic mutations has become a crucial tool for early cancer detection and personalized treatment strategies. Detecting tumors at the earliest possible stage provides critical insights beyond traditional tissue analysis. This paper presents a novel cyber-physical system that combines high-resolution tissue scanning, laser microdissection, next-generation sequencing, and genomic analysis to offer a comprehensive solution for early cancer detection. We describe the methodologies for scanning tissue samples, image processing of the morphology of single cells, quantifying morphometric parameters, and generating and analyzing real-time genomic metadata. Additionally, the intelligent system integrates data from open-access genomic databases for gene-specific molecular pathways and drug targets. The developed platform also includes powerful visualization tools, such as colon-specific gene filtering and heatmap generation, to provide detailed insights into genomic heterogeneity and tumor foci. The integration and visualization of multimodal single-cell genomic metadata alongside tissue morphology and morphometry offer a promising approach to precision oncology. Full article

The zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) has emerged as a critical regulator of diverse cellular processes, including autophagy, cell cycle progression, and tumorigenesis. Structurally, ZKSCAN3 is characterized by its conserved DNA-binding zinc finger motifs, a SCAN domain mediating protein–protein interaction, and a KRAB repression domain implicated in transcriptional regulation. Post-translational modifications, such as phosphorylation and ubiquitination, dynamically modulate its subcellular localization and activity, enabling context-dependent functional plasticity. Functionally, ZKSCAN3 acts as a master switch in autophagy by repressing the transcription of autophagy-related genes under nutrient-replete conditions, while its nuclear-cytoplasmic shuttling under stress conditions links metabolic reprogramming to cellular survival. Emerging evidence also underscores its paradoxical roles in cancer: it suppresses tumor initiation by maintaining genomic stability yet promotes metastasis through epithelial–mesenchymal transition induction. Furthermore, epigenetic mechanisms, including promoter methylation and non-coding RNA regulation, fine-tune ZKSCAN3 expression, contributing to tissue-specific outcomes. Despite these insights, gaps remain in understanding the structural determinants governing its interaction with chromatin-remodeling complexes and the therapeutic potential of targeting ZKSCAN3 in diseases. Future investigations should prioritize integrating multi-omics approaches to unravel context-specific regulatory networks and explore small-molecule modulators for translational applications. This comprehensive analysis provides a framework for advancing our mechanistic understanding of ZKSCAN3 and its implications in human health and disease. This review synthesizes recent advances in elucidating the regulatory networks and functional complexity of ZKSCAN3, highlighting its dual roles in physiological and pathological contexts. Full article

The rising prevalence of antibiotic-resistant bacteria demands exploration of alternative antimicrobials. Antimicrobial peptides (AMPs) are a promising group of compounds naturally produced by microorganisms and could serve as potent agents against resistant pathogens. In this study, we evaluated the antimicrobial potential of the cell-free supernatant obtained from Pedobacter silvilitoris—a bacterium originally isolated from decomposing wood—and performed comprehensive genomic screening to uncover novel AMP-encoding genes. The supernatant showed strong inhibitory effects against a diverse selection of pathogens. Scanning electron microscopy (SEM) revealed extensive membrane damage, including pore formation in target bacterial cells, suggesting AMP-mediated activity. A genomic analysis identified 11 candidate AMP genes, named PS_AMP1 to PS_AMP11, based on the significant sequence similarity with known AMPs. Transcriptomic profiling further indicated that several candidates are expressed differentially between the logarithmic and stationary growth phases. Functional assays via gene cloning and peptide synthesis confirmed antimicrobial activity against both Gram-stain-negative and Gram-stain-positive bacteria, with PS_AMP11 emerging as the most effective candidate. Our findings demonstrate that AMPs derived from P. silvilitoris hold substantial promise as alternative antimicrobial agents. Nonetheless, additional structural optimizations may be necessary to fine-tune specificity and to reduce potential host toxicity before clinical deployment. Full article

Background/Objectives: Karyomapping, a genome-wide SNP analysis, has drastically changed the approach to preimplantation genetic testing for monogenic disorders (PGT-M). However, there are cases in which karyomapping cannot be applied due to an insufficient number of informative SNPs. In this study, we aimed to analyze for the first time whether an insufficient number of informative SNPs is related to the family member used as a reference. Methods: For the karyomapping pre-clinical test, in addition to the couple, one of the DNA samples from an additional family member (children, parent, sibling) is used as a reference for phasing the SNP allele. We analyzed 263 couples who underwent karyomapping for PGT-M at the CHA Fertility Center from May 2020 to December 2022. karyomapping data was scanned on an Illumina NextSeq and analyzed through the BlueFuse Multi software version 4.5. Results: Preclinical karyomapping tests were performed in 263 couples with 58 monogenic diseases. Karyomapping was applicable to PGT-M for 241 (91.6%) couples and not applicable for 22 (8.4%) couples. The percentages of “not applicable” cases according to the reference family member were 1.3% (1/80) in the children group, 5.4% (8/148) in the parent group, and 37.1% (13/35) in the sibling group. Among the genetic diseases studied, couples with neurofibromatosis type 1 (6/27, 22.2%) and Kennedy disease (5/5, 100%) had the highest rate of non-applicable cases. Conclusions: Our results suggest that a child or parent may be better than the sibling for karyomapping in PGT-M. These data provide useful information for selecting a reference among the family members for preclinical karyomapping tests. Full article

Bloodstream infections (BSIs) are a major cause of morbidity and mortality in acute myeloid leukemia (AML) patients undergoing induction chemotherapy. Staphylococcus epidermidis, typically a skin commensal, is increasingly recognized as a pathogen in these vulnerable individuals. This study investigated whether genomic differences exist between infectious and gastrointestinal colonizing S. epidermidis isolates from AML patients and how these compare to colonizing and infectious isolates from other patient groups and biogeographic sites. We analyzed 114 isolates—44 from AML patients (23 infections, 21 GI colonizers) and 70 from public datasets (34 infections, 36 colonizers). Stool samples underwent 16S rRNA sequencing and culture to identify colonization, while bloodstream isolates were sequenced and compared. Genomic profiling using Roary, Scoary, Phyre2, and InterProScan revealed that infectious and GI-colonizing AML isolates were phylogenetically close but genomically distinct. Infectious isolates from AML patients were significantly enriched for resistance genes (e.g., mecA, mecR1, mecI, ANT(4′)-Ib) and the biofilm-associated gene icaA. AML infectious isolates harbored more resistance genes and mobile elements than non-AML strains but lacked widespread classical virulence factors. These results suggest that S. epidermidis pathogenicity in immunocompromised hosts is driven by genomic adaptability and antibiotic tolerance rather than traditional virulence mechanisms. Full article

Enterococcus faecalis (E. faecalis) is a major pathogen responsible for refractory apical periodontitis (RAP). It can penetrate deep into dentinal tubules, form persistent biofilms, and exhibit antibiotic resistance, thereby limiting the efficacy of conventional antimicrobial treatments. Bacteriophages (phages), due to their strong lytic activity and host specificity, have emerged as promising alternatives. In this study, a novel strictly lytic phage, ZXL-01, was isolated from lake water in Jilin, China. ZXL-01 demonstrated remarkable stability under extreme conditions, including thermal tolerance at 60 °C for 1 h and a wide pH range (4–11). Whole-genome sequencing (GenBank accession number: ON113334) revealed a genome of 40,804 bp with no virulence or tRNA genes, confirming its identity as an E. faecalis phage. Importantly, ZXL-01 exhibited potent antibiofilm activity, reducing biofilm biomass by approximately 69.4% in the inhibition group and 68.4% in the lysis group (both p < 0.001). In an in vitro root canal infection model induced by E. faecalis, scanning electron microscope (SEM) observations confirmed that ZXL-01 effectively inhibited biofilm formation and disrupted mature biofilms. These findings highlight the potential of ZXL-01 as a novel antimicrobial agent for the treatment of E. faecalis-associated apical periodontitis. Full article

The medicinal plant Siraitia grosvenorii produces sweet-tasting cucurbitane-type mogrosides from the atypical triterpenoid precursor 2,3,22,23-dioxidosqualene (SDO), rather than the conventional 2,3-oxidosqualene (SQO). However, SDO formation in mogroside biosynthesis remains unclear. Here, we systematically characterized two squalene epoxidases (SgSQE1/2) through phylogenetic analysis, heterologous expression, subcellular localization, qRT-PCR, and alanine scanning studies. Both SgSQE1 and SgSQE2 exhibited squalene epoxidase activity, with SgSQE2 catalyzing SDO formation in yeast. We identified two critical catalytic residues governing epoxidation efficiency through mutagenesis. Both SgSQEs were localized in the ER, while expression profiling revealed a similar trend between SgSQE2 expression and mogroside accumulation in fruits. In our study, we developed a genomically engineered strategy for heterologous SQE characterization. These results lay the foundation for the SQE catalytic reaction involved in mogroside biosynthesis, and provide gene resources and a feasible approach for triterpene metabolic engineering. Full article

Background: The 2C protein of foot-and-mouth disease virus (FMDV), a member of helicase superfamily 3 (SF3), drives viral genome replication and serves as a critical target for antiviral drug development. Methods: A fluorescence resonance energy transfer (FRET)-based high-throughput screening (HTS) platform was developed to identify 2C helicase inhibitors. Primary screening evaluated 4424 compounds for helicase inhibition. Molecular docking analyzed inhibitor interactions with the N207 residue within the catalytic core and helicase inhibition assays classified the inhibitor type (mixed, competitive, noncompetitive). Differential scanning fluorimetry (nanoDSF) quantified 2C thermal destabilization. Antiviral activity was assessed via indirect immunofluorescence, RT-qPCR, and plaque reduction assays. Results: Six compounds inhibited 2C helicase activity at >620 μM. Molecular docking revealed hydrogen bonding, hydrophobic interactions, and π-cation stabilization at the catalytic core. 2-MPO and MPPI were classified as mixed-type inhibitors, 5-TzS⁻ and 2-PyOH as competitive, and DCMQ/Spiro-BD-CHD-dione as noncompetitive. NanoDSF showed a ΔT_m ≥ 1.5 °C (2.5 mM compounds), with reduced destabilization in N207A mutants. Antiviral assays identified 2-MPO and MPPI as optimal inhibitors. MPPI achieved effective FMDV suppression at 160 μM, exhibiting two orders of magnitude higher potency than 2-MPO (400 μM). Conclusions: The established FRET-based HTS platform targeting 2C helicase facilitates anti-FMDV lead discovery, while 2C inhibitors may serve as an effective therapeutic strategy against other picornaviruses. Full article

Brucella intermedia, a gram-negative, non-lactose-fermenting, aerobic, rod-shaped bacterium, is found in environmental sources (e.g., soil and water). In 2020, Ochrobactrum was reclassified as Brucella. We conducted a genomic analysis of B. intermedia from hospital wastewater samples in western Ghana. A hybrid genome assembly was constructed integrating short-read data from DNA Nanoball sequencing with long-read sequences generated by Oxford Nanopore MinION technology. Identification and antimicrobial susceptibility profiles were determined using MicroScan autoSCAN-4 based on Clinical and Laboratory Standard Institute documents. ResFinder and CARD Resistance Gene Identifier (RGI) were used to identify antimicrobial resistance (AMR) genes, and BLAST and VFDB datasets were used to identify virulence factor genes. The complete genome had two chromosomes, no plasmid, and a high average nucleotide identity value (98.05%) with B. intermedia. Resistance to trimethoprim-sulfamethoxazole was revealed, the first report in this species. CARD RGI revealed the presence of AMR genes, including ANT(9)-Ic and adeF. Local BLAST analysis revealed Cgs, a B. melitensis virulence factor. B. intermedia is an opportunistic human pathogen clinically isolated several times, suggesting the importance of accurately identifying multidrug resistance. B. intermedia may possess virulence factors similar to those of B. melitensis. Further study is needed to fully elucidate its pathogenesis. Full article

Tilapia (Oreochromis spp.) is a globally important farmed fish. Analyses of genetic variation across different types of tilapia are essential for the development of superior breeding populations. We investigated the genetic structures of breeding populations of blue tilapia (Oreochromis aureus) (OA), Nile tilapia (Oreochromis niloticus) (ON), and red tilapia (Oreochromis spp.) (OS) by whole-genome resequencing. The results showed that the OS population had maintained high genetic diversity but significant genetic differentiation from the OA population. Principal component analysis, phylogenetic analysis, and genetic clustering analysis revealed a clear pattern of genetic differentiation among the three populations. The genetic structure of the ON population differed from that of the OA population but was similar to that of the OS population. Population kinship analysis revealed a close relationship between the ON and OS populations. Selective scanning analyses of three comparison groups (OA vs. ON, OA vs. OS, and ON vs. OS) revealed population-selected regions related to metabolism, endocrine, and immune systems, harboring key genes (qrsl1, pde4d, hras, ikbkb, prkag1, prkaa2, prkacb, irs2, and eif4e2). These key genes were related to growth, reproduction, and disease resistance, indicating that breeding programs have selected for these traits. Due to the lack of stable morphological characteristics of juvenile fish and the changes in external environmental conditions that lead to changes in individual morphological characteristics, SNP fingerprints were successfully constructed for the identification of the three populations based on the differences in SNPs. Based on the five core SNP markers, two combinations of SNP markers were developed to accurately identify the three populations of tilapia at the genomic level. These results provide new information about tilapia genetic resources and reference data for identification and breeding purposes. Full article

The roles of endophytes in Cannabis sativa (cannabis, hemp) remain poorly explored. While in vitro studies suggest that there can be several benefits, such as plant growth promotion and protection against pathogens, more in planta studies are needed. This review summarizes the bacterial and fungal endophytes previously reported in tissues of C. sativa and discusses the factors influencing their presence, as well as their potential beneficial and detrimental effects. Using genome sequencing and culture-based approaches, we describe the microbial diversity in hydroponically cultivated cannabis plants at several developmental stages. These include mother plants, cuttings, vegetative and flowering plants, and tissue-cultured plantlets. Microbes that were present include fungal, yeast, and bacterial endophytes found in roots, stems, leaves, inflorescences, and seeds. These may have originated from the growing substrate or be transmitted through vegetative propagation. Notable endophytes included Rhizophagus irregularis (a mycorrhizal fungus), Penicillium chrysogenum (an antibiotic producer), and various endophytic yeast species not previously described in C. sativa. Endophytes representing potential plant pathogens, such as Fusarium oxysporum, are also present within cannabis tissues, which can negatively impact plant health. Using scanning electron microscopy, we observed that fungal propagules are present within pith parenchyma cells and xylem vessel elements in stem tissues, illustrating for the first time the in situ localization and distribution of endophytes in cannabis vascular tissues. The mechanism of spread through xylem vessels likely contributes to the spread of endophytes within cannabis and hemp plants. Further research is required to validate the roles of endophytes in cannabis and hemp plants grown under commercial production conditions. Full article