Search Results (414)

Background: In plants, members of the MADS-box gene family encode transcription factors that regulate a wide range of developmental processes, including cell differentiation, organ identity, floral induction, and responses to environmental stimuli. Moreover, MADS-box genes play central roles in the well-known ABCDE model of floral development. Teak (Tectona grandis), a woody species belonging to the Lamiaceae family, is recognized for its medicinal and agricultural significance. The recent availability of a chromosome-level genome assembly for T. grandis has enabled the genome-wide identification of 87 MADS-box genes, which are distributed across 18 pseudo-chromosomes. Methods: The amino acid sequences of these genes were compared with orthologous proteins from Arabidopsis thaliana, Sesamum indicum, and Amborella trichopoda to infer the phylogenetic relationships. The structures of key floral quartets in the MADS-box proteins were predicted, and the stability of these predicted tetramers were analyzed via molecular dynamics simulations. Results: The phylogenetic analysis classified the genes into 33 Type I and 54 Type II MADS-box members, forming four major clades (MIKC^C, MIKC*, Mα, and Mγ), while the Mβ-type clade was absent. A conserved motif analysis revealed that the Type II genes exhibited greater motif diversity than the Type I, suggesting that T. grandis Type II MADS-box genes possess more complex structures and potentially broader functions. The transcriptomic data from different tissues showed that the MIKC-type genes were particularly active during flower development. Although stable over the simulation time, the T. grandis AP3 ortholog had shorter I and K domains and had an odd mode of protein–protein interaction. Conclusion: Overall, the presented genome-wide analysis provides a comprehensive base for understanding the evolutionary diversification of the MADS-box gene family in T. grandis and identifies candidate genes for future structural and functional characterization. Full article

Drug- and alcohol-induced liver injury involves impaired bile acids or bilirubin secretion, but it is not known how senescence influences the secretion of hepatocytes exposed to drugs and alcohol. In this study, the toxic effects of ritonavir, lopinavir, and alcohol on hepatocyte transporters and the secretion of bile acids and bilirubin were investigated in hydrogen peroxide-induced senescent HepG2 and doxorubicin-induced senescent primary human hepatocytes. In HepG2, intracellular conjugated bilirubin increased upon senescence and extracellular conjugated bilirubin in culture medium was decreased by ritonavir and lopinavir treatment. In the primary hepatocytes, intracellular bile acids or medium bilirubin were not significantly changed upon senescence. However, intracellular bile acids were increased, and medium conjugated bilirubin were decreased in senescent primary hepatocytes treated with alcohol and the two drugs. Transcriptional expressions of adenosine triphosphate (ATP)-binding cassette (ABC) transporters (ABCB4, ABCC6, ABCB11, and ABCD3) were decreased whereas UDP-glucuronosyltransferase (UGT1A1) was increased by ritonavir and lopinavir in senescent HepG2. In senescent primary hepatocytes, expressions of ABCB11, ABCC1, ABCC2, ABCC3, ABCC4, and ABCC6 were apparently reduced whereas UGT1A1 and the cytochrome P450 enzyme CYP7A1 were markedly increased by alcohol combined with ritonavir and lopinavir. Selective ABCC6 knockdown in the primary hepatocytes altered expressions of two senescence markers, Lamin A/C and cyclin-dependent kinase inhibitor CKI (p21), increased expressions of CYP7A1 and hydroxy methyl glutaryl-CoA reductase (HMGCR), and increased intracellular bile acids. Further, anti-cholestasis agents, ursodeoxycholic acid and glycyrrhizin, significantly ameliorated the impaired secretions of bile acids and bilirubin as well as reducing intracellular lipid accumulation and cell death caused by ritonavir, lopinavir, and alcohol in the primary hepatocytes with ABCC6 knockdown. These results indicate that senescence moderately impairs the ABC transporters of hepatocytes and secretion of bile acids or bilirubin, which become worse in the presence of the drugs and alcohol but could be improved by anti-cholestasis agents. Full article

Methicillin-resistant coagulase-negative staphylococci (MRCoNS) are a major cause of infectious diseases, owing to their ability to form biofilms and colonize community and hospital environments. MRCoNS strains were identified using biochemical tests, an MALDI-TOF MS analyzer, and PCR-based 16S rRNA gene confirmation. This study was designed to assess antibiotic resistance and biofilm-forming capacity and to determine the presence of the mecA, mecC, agrA, srtA, icaABCD, bap, fnbAB, and clfAB genes in MRCoNS isolates. From patients undergoing random screening during hospitalization in the Orthopedics Clinic in Slovakia, 28 strains of MRCoNS were identified: S. epidermidis (n = 10), S. hominis (n = 8), S. haemolyticus (n = 4), S. lugdunensis (n = 3), while S. simulans, S. pasteuri, and S. warneri were detected only once. The highest rates of resistance were observed for ampicillin, oxacillin, rifampicin, trimethoprim (100%), and erythromycin (62%). The mecA gene was detected in 12 analyzed isolates. In 12 isolates, MDR, strong efflux pump activity, and strong or moderate biofilm formation were simultaneously detected. Our findings highlight the problems posed by biofilm-forming, resistant CoNS in hospitalized patients and the importance of diagnostics, separation, rapid treatment, and proper hospital hygiene. Full article

Background: Nutritional status assessment is the cornerstone of the Nutrition Care Process, guiding diagnosis, intervention, and monitoring. The classical ABCD model (Anthropometry, Biochemical, Clinical, Dietary) has been widely applied; however, it presents limitations in addressing current nutritional and epidemiological challenges. Objective: This narrative review aims to synthesize and update the scientific evidence on the expanded nutritional assessment model, known as ABCDEFG, which incorporates the Ecological–microbiota (E), Functional (F), and Genomic–nutrigenomic (G) approaches. Methods: A narrative review of the literature was conducted through PubMed, Scopus, and Web of Science, covering publications from 2013 to 2025. Articles were selected based on relevance to at least one of the seven assessment domains. Findings were synthesized descriptively and critically, highlighting applications, strengths, and limitations. Results: The ABCDEFG framework offers a multidimensional perspective of nutritional assessment. While anthropometric, biochemical, clinical, and dietary methods remain essential, the inclusion of ecological dimensions (gut microbiota, environmental influences), functional measures (e.g., muscle strength, physical performance), and genomics enables a more sensitive and personalized evaluation. This integrative approach supports better clinical decision-making and research innovation in nutrition and health sciences. Conclusions: The seven-method model broadens the scope of nutritional assessment, bridging traditional and emerging tools. Its application enhances the capacity to identify nutritional risks, design targeted interventions, and advance precision nutrition. Full article

Adiposity-Based Chronic Disease (ABCD) is known to increase the risk of aggressive prostate cancer (PCa), recurrent disease after treatment for localized PCa, and PCa mortality. A key mechanistic link contributing to this enhanced risk is chronic inflammation originating from excess white visceral adipose tissue (WAT; VAT) and periprostatic adipose tissue (ppWAT). Contributing to systemic inflammation is gut dysbiosis, which itself may be caused by ABCD as well as background local inflammation (prostatitis), which is common in aging men and may be exacerbated by the urinary microbiome. Investigating the molecular biology driving inflammation and its association with increased PCa risk, a recent paper applied a network and gene set enrichment to adipokine drivers in the ABCD-PCa network. It found prominent roles for MCP-1, IL-1β, and CXCL-1 in addition to confirming the importance of exposure to lipopolysaccharides and bacterial components, corroborating the role of gut dysbiosis. To further unravel the mechanistic links between ABCD and PCa risk, this critical review will discuss the current literature on prominent inflammatory signaling pathways activated in ABCD; the influence of gut dysbiosis, the urinary microbiome, and chronic prostatitis; and current hypotheses on how these domains may result in the development of aggressive PCa over a man’s life. Moreover, we performed a novel pathway enrichment analysis to further evaluate the associations between ABCD, PCa risk, gut dysbiosis, and the prostate microbiome, the results of which were partitioned into extracellular and intracellular signaling pathways. In the extracellular space, novel mechanistic links between gut dysbiosis and MCP-1, IL-1β, CXCL1, and leptin via bacterial pathogen signaling and the intestinal immune network (for IgA production), crucial for gut immune homeostasis, were found. Within the intracellular space, there were downstream signals activating chemokine and type 2 interferon pathways, focal adhesion PI3K/Akt/mTOR pathways, as well as the JAK/STAT, NF-κB, and PI3K/Akt pathways. Overall, these findings point to an emerging molecular pathway for PCa oncogenesis influenced by ABCD, gut dysbiosis, and inflammation, and further research, possibly with lifestyle program-based clinical trials, may discover novel biomarker panels and molecular targeted therapies for the prevention and treatment of PCa. Full article

Cancer remains a leading cause of mortality worldwide, and new chemical leads are essential for developing potent anticancer therapies. Evidence suggests that Pseudomonas aeruginosa (Pa) may suppress tumorigenesis, although the underlying mechanisms remain largely unclear. This study characterized a novel small molecule quinolone, JH62 (E-2-(tridec-4-en-1-yl)-quinolin-4(1H)-one, C₂₂H₃₁NO), from Pa. JH62 exhibited broad-spectrum anticancer activity, inhibiting the proliferation of A549 lung cancer cells in a time- and dose-dependent manner with an IC₅₀ of 15 μM, while showed low cytotoxicity toward normal cells. In xenograft mice model, treatment with JH62 (10 mg/kg) reduced tumor weight and volume by 73% and 79%, respectively. Mechanistically, treatment with JH62 induced structural and functional disruption of mitochondria in cancer cells, triggered autophagic cell death, and did not cause DNA damage. Genetic analysis confirmed that JH62 biosynthesis depends on the pqsABCDE gene cluster and that JH62 positively regulates its own production. ADMET profiling further indicated promising drug-like properties for future development. These findings establish JH62 as a promising anticancer lead compound derived from microbial metabolism. Full article

Background: Mismatch repair (MMR) and microsatellite instability (MSI) testing have become essential biomarkers in the molecular classification of endometrial cancer (EC), guiding adjuvant treatment decisions and eligibility for immune checkpoint inhibition. Although international guidelines recommend universal testing, real-world implementation remains heterogeneous. This study aimed to evaluate trends in MMR and MSI testing and associated molecular diagnostics in Germany between 2018 and 2022. Methods: A retrospective multicenter analysis was conducted across German tertiary care centers. Data from patients with histologically confirmed EC between 2018 and 2022 were extracted from standardized electronic pathology records. Annual testing rates for MSI, MMR, POLE, TP53, and L1CAM were analyzed using descriptive statistics and trend analysis (Chi-square test for trend, p < 0.05). Therapeutic data were collected to assess the use of immune checkpoint inhibitors. Results: There was a significant increase in the annual rates of molecular testing for MSI, POLE, TP53, and L1CAM over the five-year observation period (all p < 0.05). TP53 testing showed the highest increase (13.1% → 78.6%), while MSI testing rose from 82.9% to 97.4%. Both POLE and L1CAM testing were virtually absent in 2018 (0% and 1.6%) but reached 15.7% by 2022. Conclusions: This study demonstrates a rapid and substantial implementation of MMR and MSI testing in German clinical practice, reflecting successful translation of trial results into routine care. However, implementation of testing in guidelines appeared time-shifted. For bridging this gap, annual guideline updates seem to be necessary. Full article

Staphylococcus aureus (S. aureus) is a major Gram-positive pathogen, and treatment of S. aureus infections is often challenging due to widespread antibiotic resistance. In Gram-positive bacteria such as S. aureus, D-alanylation of teichoic acids (TA) reduces the net negative charge of the cell envelope and contributes to resistance to diverse antibiotics, particularly cationic antimicrobial peptides. D-alanylation is mediated by the dltABCD operon, which encodes four proteins (DltA, DltB, DltC, and DltD), all of which is essential for the multistep transfer of D-alanine to teichoic acids. Here, we present the first crystal structure of the S. aureus D-alanyl carrier protein DltC and analyze its interaction with DltA using AlphaFold3 and all-atom molecular dynamics simulations. We further show that single substitutions of SaDltA-SaDltC interface residues abolish SaDltC mediated enhancement of SaDltA catalysis. Together, these findings define a catalytically critical S. aureus DltA-DltC interface and provide a structural insight for targeting the D-alanylation pathway as a potential anti-Staphylococcus strategy. Full article

A cone calix[4]arene having one tert-butyl group and three amino groups at the wide rim was bis-N-protected stepwise using sulfonylation with 4-nitrobenzylsulfonyl chloride, followed by acylation with di-tert-butyl dicarbonate. The selective sulfonylation was shown to prefer the amino group located in the proximal calixarene aromatic unit relative to the tert-butylated moiety, resulting in the formation of an inherently chiral calix[4]arene with a wide-rim substitution pattern of AABC type. Further acylation of one of the two remaining amino groups also proceeded selectively. It involved the calixarene aromatic unit adjacent to the sulfonylated moiety, as clearly demonstrated by 2D NMR data for the ABCD-substituted reaction product, which was obtained as a mixture of enantiomers. The mixture was acylated with (R)-mandelic acid succinimide ester, and the resulting diastereomers were separated by conventional column chromatography, thus demonstrating the applicability of the stepwise protection strategy for the further preparation of enantiopure calix[4]arene cores possessing inherent chirality due to four different substituents at their wide rims. Full article

The ATP-binding cassette (ABC) transporter family is one of the oldest conserved protein families and is widely present in animal and plant cells. However, few studies have investigated the role of ABC in the forest musk deer (FMD; Moschus berezovskii). In this study, we employed bioinformatics methods to identify and analyze the ABC transporter genes in M. berezovskii to elucidate the potential function of ABC genes in musk secretion. A total of 51 members of the MbABC gene family were identified. The analysis encompassed various aspects including physical and chemical properties, phylogenetic tree, structure prediction, conserved motifs, gene structures, chromosome localization, collinearity analysis, and KEGG and GO enrichment. Collinearity analysis revealed that the ABC transporter gene family is conserved in FMD, Cervidae, and five Bovinae species. MbABCB6, MbABCD4, MbABCF3, and MbABCG5 are key genes in protein–protein interaction networks, which are primarily involved in the transport of vitamins, lipids, and proteins. Tissue expression analysis showed that MbABCs were expressed at different stages. The RT-qPCR analysis revealed that 12 MbABC genes were up-regulated in musk gland cells during the non-secretion phase and stimulation phase, particularly MbABCC4d and MbABCC3. This study provides comprehensive information on the ABC gene family in FMD which can be further used for their functional validation. Full article

Pigs play a vital role in global food security as a major source of animal protein. Enhancing growth and reproductive traits is of great economic importance to the swine industry. To systematically identify genetic determinants underlying key economic traits, we performed an integrative multi-omics analysis in a population of 1624 Duroc pigs, focusing on backfat thickness (BF), loin muscle area (LMA), and total teat number (TTN). Our genome-wide association study (GWAS) identified twenty-one significant single nucleotide polymorphisms (SNPs)—fourteen for BF, three for LMA, and seven for TTN. Candidate genes located within 1 Mb of these SNPs, such as ZC3HAV1L and FAM3A for BF, PTGR2 for LMA, and VRTN and ABCD4 for TTN, were further investigated. Functional genomic annotations revealed that genetic variants near the significant SNPs were enriched in tissue-specific enhancer elements, implying regulatory potential. Transcriptome-wide association study (TWAS) further supported the candidate genes such as ABCD4 and YLPM1 for TTN and predicted several putative functional mutations that may affect transcription factor binding sites. This study demonstrates the power of integrative genomics to prioritize candidate genes and causal variants for animal complex traits, offering valuable resources for future precision breeding in pigs. Full article

Background/Objectives: Melanoma is a highly malignant skin tumor with poor response to conventional chemotherapeutic regimens. Melanoma cells induce cytotoxic T cell-mediated immune responses, and immunotherapy has significantly improved survival rates for patients with advanced disease. Methods: Here, we investigate NK cell-mediated melanoma cell killing and its regulation by PD-L1/PD-1 blockade and IFNβ. Four melanoma cell lines were used in this study. To evaluate NK cell cytotoxicity, cells were exposed to NK cells with or without IFNβ. The calcein release assay was used to measure cell death, while specific inhibitors and siRNA silencing were applied to determine the contribution of individual effector pathways. Results: NK cells were able to kill melanoma cells with sensitivity to killing varying between different cell lines. Cytotoxic effects were mainly mediated through activation of the TRAIL signaling cascade. In cell lines with low sensitivity to NK cell killing, expression of PD-L1 was noted and killing by NK cells could be significantly increased by inhibition of the PD-L1/PD-1 checkpoint. Killing of melanoma cells could be further increased by incubation of NK cells with IFNβ. Conclusions: Our results point to a role of NK cells in the killing of melanoma cells and a potential clinical benefit of a combination therapy of IFNβ and anti-PD-1 antibody. Full article

Natural heritage digitization has evolved beyond simple 3D representation. Contemporary approaches require transparent documentation integrating biological, heritage, and digitization standards, yet existing frameworks operate in isolated domains without semantic interoperability. Current digitization frameworks fail to integrate biological standards (Darwin Core, ABCD), heritage standards (CIDOC-CRM), and digitization standards (CRMdig, PROV-O) into a unified semantic architecture, limiting transparent documentation of natural heritage data across its entire lifecycle—from physical observation through digital reconstruction to knowledge reasoning. This study proposes an integrated semantic framework comprising three components: (1) the E-DNH ontology, which adopts a triple-layer architecture (data–metadata–paradata) and a triple-module structure (nature–heritage–digital), bridging Darwin Core, CIDOC-CRM, CRMdig, and PROV-O; (2) the HR3D workflow, which establishes a standardized high-precision 3D data acquisition protocol that systematically documents paradata; and (3) the C-EDNH platform, which implements a Neo4j-based knowledge graph with semantic search capabilities, AI-driven quality assessment, and persistent identifiers (NSId/DOI). The framework was validated through digitization of 197 natural heritage specimens (68.5% avian, 24.9% insects, 5.1% mammals, 1.5% reptiles), demonstrating high geometric accuracy (RMS 0.18 ± 0.09 mm), visual fidelity (SSIM 0.92 ± 0.03), and color accuracy (ΔE₀₀ 2.1 ± 0.7). The resulting knowledge graph comprises 15,000+ nodes and 45,000+ semantic relationships, enabling cross-domain federated queries and reasoning. Unlike conventional approaches that treat digitization as mere data preservation, this framework positions digitization as an interpretive reconstruction process. By systematically documenting paradata, it establishes a foundation for knowledge discovery, reproducibility, and critical reassessment of digital natural heritage. Full article

X-linked adrenoleukodystrophy (X-ALD) is a monogenic progressive neurodegenerative disorder, being simultaneously a systemic metabolic disease and demonstrating severe neurological manifestations with effects to the brain and spinal cord. The objective of the current review is to provide a detailed approach to adeno-associated virus (AAV)-based gene therapy for neurological manifestations of X-ALD. The development of a successful AAV-mediated gene therapy hinges on its ability to deliver ABCD1 cDNA effectively to the relevant organs and cell types, induce therapeutic levels of protein expression, and ultimately, restore normal very-long chain fatty acids (VLCFA) metabolic function. Thus, several key considerations should be addressed when designing AAV-based gene therapy for X-ALD, including the genetic background of the disease and requisite transgene expression levels, the biochemical function of the adrenoleukodystrophy protein (ALDP), the identification of target cells and their role in pathogenesis, the regulation of expression within the genetic construct, the route of administration, the selection of an AAV serotype with high tropism for the central and peripheral nervous systems, and the development of robust in vitro and in vivo models. Full article

Background/Objectives: This study analyzed the impact of operator experience on the detection of PC and csPC using a standardized MRI/TRUS-fusion biopsy protocol in an experienced high-volume center. Methods: Men with mpMRI and subsequent combined TB and SB (2019–2024) using transrectal, software-assisted MRI/TRUS-fusion were retrospectively included. Operators were stratified by experience subgroups (<100 vs. ≥100 procedures). Clinical, MRI, and biopsy data have been assessed. The primary objective was the analysis of the effect of biopsy experience on patient-level PC detection. The secondary objective was the PC detection of PI-RADS and DRE. Results: A total of 683 consecutive patients were included (median age 63 years, median PSA 6.5 ng/mL, and median prostate volume 41 mL). Overall, PC and csPC detection were 67% and 51%, with no significant difference in the operator experience subgroups (p = 0.63; p = 0.23). There were no significant differences for additional csPC detection by SB (7% vs. 5%; p = 0.31) or TB (9% vs. 10%; p = 0.93) in both subgroups. DRE showed limited diagnostic value (SEN 32%, SPE 88%, PPV 74%, NPV 55%) with no significant variation regarding the experience (p = 0.12–1.0). Limitations include a single-center, retrospective design and a lack of a radical prostatectomy specimen. Conclusions: In a standardized MRI-targeted biopsy setting, operator experience seems to have a lower influence on PC or csPC detection. High csPC detection in PI-RADS 4–5 supports a TB-only approach, while low rates in PI-RADS 3 suggest follow-up MRI over immediate biopsy. Limited DRE accuracy highlights its declining role in PC assessment. Full article