Search Results (10,193)

De-S-acylation enzymes mediate the reversible S-acylation cycle and play critical roles in plant development and stress responses. However, the precise origin and evolutionary dynamics of this gene family in plants remain poorly understood. In this study, a total of 718 ABAPT genes were identified across 73 plant genomes, including 622 ABHD17 and 96 ABHD13 homologs, which share only a 20–30% conserved sequence identity between them. We further performed comprehensive analyses of gene duplication and structure, protein properties, synteny networks, and expression profiles to establish a systematic framework by classifying ABAPT genes in land plants. Our results revealed that ABHD13 genes have been retained as a single copy in most angiosperm genomes, whereas ABHD17 genes have undergone extensive expansion. ABAPT genes formed three major evolutionary clades: Clade 1 contained ABHD13 homologs, while Clades 2 and 3 harbored ABHD17 homologs. The three clades showed distinct disparities in intron–exon structural patterns and IDR properties. Phylogenomic synteny network analyses revealed the deeply conserved genomic syntenies within each of the six ABAPT subclades among the three clades, while Cluster4-Monocot was more dynamic and showed distinct lineage-specific duplication patterns restricted to Poaceae. ABHD13s exhibited constitutive expression patterns, while the tissue-specific expression genes were predominantly found within the ABHD17s subfamily. Notably, the ABAPT8/9 subgroups were specifically expressed in reproductive organs, and the weighted gene co-expression network identified specific groups to find ABAPT-specific regulatory features, implying the presence of potential modules for the protein S-acylation cycle during pollen development. Additionally, our results suggested that C-terminal Cys-rich region was required for ABAPT10 localization. Altogether, this study sheds light on the evolutionary divergence of the ABAPT subclades across major green plant lineages and emphasizes the need for future functional characterizations. Full article

Background/Objectives: The Korean Global Antimicrobial Resistance Surveillance System monitors bloodstream Staphylococcus aureus infections by combining antimicrobial susceptibility testing (AST) with conventional polymerase chain reaction (PCR). Considering the clinical significance of methicillin-resistant S. aureus (MRSA), we performed an in-depth analysis of isolates showing genotypic–phenotypic discrepancies. Methods: Isolates were collected from designated collection centers in the Republic of Korea between 2017 and 2024. The 30 μg cefoxitin disk diffusion method was used to define the phenotypes. PCR targeting mecA and the staphylococcal cassette chromosome mec (SCCmec) was used to identify genotypes through gel electrophoresis. Long-read whole-genome sequencing (WGS) was performed using the Revio system (Pacific Biosciences) for isolates exhibiting discrepancies between phenotypes and genotypes. Results: In total, 5808 isolates were screened, and seven cases of genotypic–phenotypic discrepancies were identified, including one infant and six elderly patients with chromosomal SCCmec type IV. Although WGS confirmed intact PCR primer-binding sites, structural alterations were observed: three isolates had normal-length mecA and mecR1, two had partial deletions in mecA, and two featured either mecA or mecR1 split into two proteins. Notably, although the six isolates with intact mecR1 genes matched the nucleotide length of SCCmec type IV, their sequences exhibited high homology with SCCmec type II. Conclusions: Despite the presence of mecA, the non-standard configuration of regulatory genes within the SCCmec elements suppressed actual resistance expression. Because conventional PCR focusing on partial gene segments could overlook such phenotypic traits, the meticulous observation and implementation of WGS are crucial for the accurate characterization of genotypic–phenotypic discrepancies. Full article

The protozoan parasite Leishmania mexicana serves as a widely used model for studying trypanosomatid biology, yet the demand for stable, high-intensity fluorescent tools for precise subcellular protein localization remains unmet. In this study, we developed a versatile molecular toolbox by re-engineering the pLEXSY-hyg2.1 vector to express mNeonGreen (mNG), a next-generation fluorophore with superior brightness and photostability. Using a modular cloning strategy, we introduced a customized multiple cloning site (MCS) upstream of the mNG sequence to facilitate seamless N-terminal tagging of target proteins. The construct was integrated into the 18S rRNA locus via homologous recombination to ensure stable, constitutive expression. As a proof-of-concept, we fused a flagellar marker to the mNG reporter, resulting in a transgenic line exhibiting robust and specific subcellular fluorescence without compromising cellular fitness. Our results demonstrate that this integration-based system provides a highly efficient and stable platform for visualizing protein distribution within Leishmania. This tool significantly simplifies the generation of reporter strains and will facilitate high-resolution imaging studies of parasite organelle dynamics and functional genomics. Full article

Cholangiocarcinoma (CCA) is an aggressive malignancy with a poor prognosis that is strongly associated with chronic Clonorchis sinensis (C. sinensis, Cs) infection; however, its underlying molecular mechanisms remain elusive. Recent studies suggest that C. sinensis-derived extracellular vesicles (CsEVs) play a crucial role in host–parasite interactions and in shaping the tumor microenvironment during infection. Acting as key delivery vehicles, these CsEVs can transfer specific functional molecules, such as microRNAs (miRNAs), to host cholangiocytes, thereby modulating cellular behaviors—a process that may represent a significant pathway in parasite-induced carcinogenesis. Despite this, the specific miRNAs shuttled by CsEVs and their concrete functions and mechanisms in driving CCA proliferation and metastasis remain largely unexplored. To this end, we investigated Csi-miR-125a, a miRNA abundantly expressed in CsEVs, aiming to systematically elucidate its dual regulatory functions in CCA progression. Our findings offer novel mechanistic insights into host–parasite crosstalk, further the understanding of CCA pathogenesis, and point to potential therapeutic avenues. Using gain-and loss-of-function approaches in RBE and HuCCT1 cell lines, we demonstrated that Csi-miR-125a promotes cell proliferation by accelerating cell-cycle progression and suppressing apoptosis through direct targeting of BAK1. Concurrently, Csi-miR-125a enhances the migratory and invasive capacities of CCA cells via activation of the ERK signaling pathway. In a BALB/c nude mouse lung metastasis model, CsEVs depleted of Csi-miR-125a significantly inhibited pulmonary metastasis. Collectively, This study found that Csi-miR-125a derived from C. sinensis can regulate apoptosis and cell cycle progression by targeting BAK1, thereby promoting the proliferation of cholangiocarcinoma cells; meanwhile, it enhances cell migration and invasion by activating the ERK signaling pathway. These results suggest that Csi-miR-125a participates in and promotes the malignant progression of CCA. However, given its high homology with human endogenous miR-125a, its function may partially overlap with host endogenous miRNAs, rather than representing a completely independent carcinogenic effect. These findings provide mechanistic insights into host–parasite interactions during C. sinensis infection and lay a theoretical foundation for subsequent targeted intervention studies. Full article

Deoxynivalenol (DON), a Group III carcinogenic mycotoxin frequently detected in cereals and animal-derived food products, poses serious health risks to animals and humans. In this study, we developed a genetically engineered Saccharomyces cerevisiae strain as a proof-of-concept platform for DON detoxification. The yeast was engineered to co-express two detoxification genes, YTDepA and YTDepB (homologs of DepA and DepB from Devosia mutans 17-2-E-8) originally identified in Youhaiella tibetensis. Concurrently, the pyrroloquinoline quinone (PQQ) biosynthesis gene cluster from Klebsiella pneumoniae was integrated to supply the essential cofactor. Gene expression was verified by qRT-PCR and Western blot. The recombinant strain demonstrated a significant 13.98% detoxification of DON after 72 h of fermentation (p < 0.05), as confirmed by HPLC–MS, while the strain expressing only the PQQ cluster showed no detoxification activity. This study establishes an integrated yeast cell factory for DON detoxification and highlights key limitations to guide future optimization efforts. Full article

Background/Objectives: The clinical challenges of PARP inhibitors in ovarian cancer include the lack of effective maintenance regimens for homologous recombination proficiency (HRP) patients and the emergence of acquired resistance in initially responsive homologous recombination deficiency (HRD) patients. This study aims to explore the synergistic effect and molecular mechanism of the bispecific tyrosine phosphorylation-regulated kinase 1B (DYRK1B) inhibitor AZ191 combined with the PARP inhibitor Niraparib on high-grade serous ovarian cancer (HGSOC). Methods: This study first explored the expression and prognostic significance of DYRK1B in ovarian cancer through bioinformatics analysis. Subsequently, the therapeutic effect of the DYRK1B inhibitor AZ191 combined with Niraparib on HGSOC cells and organoids was evaluated by MTT examination. Flow cytometry and Western blot were used to investigate the synergistic mechanism between the two agents. Results: Bioinformatics analysis shows that the high expression of DYRK1B in serous ovarian cancer is associated with poor prognosis of the patients. The experiments in vitro have shown that the DYRK1B inhibitor AZ191 can enhance the therapeutic effect of Niraparib on HGSOC cells and organoids, whether HRD-positive or not. Mechanistic studies have shown that the combination of AZ191 and Niraparib can synergistically increase the accumulation of DNA damage, thereby intensifying the apoptosis of HGSOC cells. In addition, the combination therapy induces ferroptosis by inhibiting the Nrf2/SLC7A11/GPX4 axis, thereby exerting cytotoxic effects. Conclusions: Our results uncover a novel mechanism by which inhibiting DYRK1B enhances the anti-HGSOC efficacy of Niraparib and may offer a promising treatment strategy to improve the maintenance therapy in both HRD and HRP ovarian cancer patients. Full article

Background: Topological Data Analysis (TDA) captures multi-scale geometric features of data as persistence diagrams, yet no principled information-theoretic framework quantifies how much information those features carry, how efficiently they compress, or when they are informationally irreducible. Methods: We construct a measure-theoretic probability space over persistence diagram space using a Poisson-process reference measure, and define topological entropy (H-T), topological mutual information (I-T), and a topological rate–distortion function as the core objects of a new theory. Results: Four theorems with full proofs establish finite stability, axiomatic uniqueness, a Topological Data Processing Inequality, and a Rate–Distortion Theorem with explicit Poisson-model closed-form formula. A Renyi generalization of topological entropy is also established. Computational and practical implementation aspects—including finite-sample estimation, multi-parameter extension, and algorithmic realization—are addressed inline throughout the paper. Conclusions: This framework provides a rigorous measure-theoretic information-theoretic foundation for persistent homology, demonstrated on simulated brain connectivity and point cloud data, with applications to threshold selection, genomic classification bounds, and compressed sensing. Full article

Background: INDETERMINATE DOMAIN proteins (IDDs) are a plant-specific transcription factor family, and members of this family play crucial roles in regulating growth and development as well as environmental adaptation. However, a comprehensive analysis of the IDD family in soybean [Glycine max (L.) Merrill] is limited. Methods and Results: A total of 27 GmIDD genes were identified in the soybean genome, unevenly distributed across 14 chromosomes, and their encoded proteins all harbor a conserved INDETERMINATE (ID) domain with two Cys2His2 (C2H2) and two Cys2HisCys (C2HC) zinc finger motifs. Phylogenetic analysis classified these GmIDD genes into three subgroups. Soybean GmIDD genes exhibit high homology with their Arabidopsis thaliana IDD counterparts. Cis-acting element analysis indicated that the promoters of GmIDD genes are enriched in light-responsive elements (such as Box4), hormone-responsive elements (such as ABRE and AuxRR-core), and abiotic stress-responsive elements (such as MBS and LTR). The qRT-PCR results showed that GmIDD3/5/14/22/26 were upregulated under salt stress, while GmIDD8/9/10/12/16/17/19/20/23/24/25/27 were obviously downregulated during treatment. Under drought stress, the expression levels of GmIDD4/6/7/10/14/16/19/22/24/25/26/27 were upregulated during the treatment. The expression levels of GmIDD1/2/3/4/12/14/15/16/17/18/22/23/25/26 were induced by short-day conditions, whereas GmIDD9/13/19/21 were induced by long-day conditions in soybean leaves. Conclusions: This study provides a theoretical basis for further understanding the functions of the soybean IDD gene family in abiotic stress tolerance and photoperiod adaptability. Full article

Short-horizon equity forecasting remains challenging because daily prices are noisy, heavy-tailed, and subject to structural breaks and regime shifts. We develop a fully automated, reproducible, and leakage-controlled multi-model pipeline for daily forecasting with horizon-specific configuration selection. The task is formulated as predicting cumulative H-day log-returns from OHLCV-derived information and converting them to implied price forecasts. All model families share a homologated design: causal feature construction, a strictly chronological split with an explicit purging rule to prevent label-window overlap for multi-day targets, training-only robustification (winsorization and adaptive clipping), and a unified metric suite computed consistently in return and price spaces. The framework benchmarks transparent baselines (zero- and mean-return), gradient-boosted trees (XGBoost), and deep temporal models (LSTM and CNN/TCN). Lookback length $L\in \{60,180,500\}$ is selected via an internal walk-forward procedure on the pre-evaluation block, and final performance is reported on an external hold-out segment (last 15% of instances). Experiments on daily data for MT, DELL, and the S&P 500 index (through 3 February 2026) show that all families achieve similarly strong price-level fit at $H=1$, largely driven by persistence in the price process, while separation across families becomes more visible at $H=5$. However, predictive performance in return space remains weak, with $R^2$ close to zero or negative, and Diebold–Mariano tests do not provide consistent evidence of statistical superiority over naive benchmarks. Under an operational rule that minimizes hold-out RMSE on the price scale, selected models are asset- and horizon-dependent, supporting horizon-wise selection rather than a single global architecture. Overall, the primary contribution lies in the proposed leakage-controlled evaluation and benchmarking framework rather than in demonstrating consistent predictive gains in financial time series forecasting. Full article

Vibrio alginolyticus is a common pathogenic bacterium and can cause diseases in aquaculture animals. Lysine lactylation (Kla) is a novel post-translational modification (PTM) that has been confirmed to play critical roles in key biological processes. However, the modification landscape and functions of Kla in V. alginolyticus remain unclear. In this study, lactylation modification profiles of the bacterial pathogen V. alginolyticus were first systematically characterized; a total of 9308 lactylation sites on 2155 proteins were successfully identified. The lactylation of cAMP receptor protein (CRP) and triosephosphate isomerase (TPI) was verified by Co-immunoprecipitation (Co-IP) and Western blot to validate the lactylome data. Bioinformatic analysis of the Kla sites revealed 32 conserved sequence motifs surrounding the modified residues. Kla proteins were mainly involved in central metabolic pathways, including glycolysis/gluconeogenesis and ribosome biogen regulators were found to contain Kla modification sites. To investigate crosstalk among lysine acylations in V. alginolyticus, we integrated Kla, lysine acetylation (Kac), and lysine succinylation (Ksuc) profiles and identified 337 co-modified proteins and 5 co-modified sites. Additionally, phylogenetic analysis of Vibrio alginolyticus CobQ based on protein sequence alignment revealed no homology to the known delactylase CobB. Combined in vitro and in vivo functional validation identified VaCobQ as a candidate delactylase with potential NAD⁺-independent activity. This study establishes a lysine lactylation landscape in V. alginolyticus, providing a resource for exploring Kla functions in bacterial metabolism and its possible connections to virulence. Full article

Tumor-associated Tie2-expressing monocytes/macrophages (TEMs) have been implicated in promoting angiogenesis and metastasis in colorectal cancer (CRC), yet the molecular mechanisms linking TEMs infiltration to tumor metastasis and progression remain incompletely defined. This study investigated the distribution of TEMs in CRC and their association with gene expression profiles, microvessel density (MVD), and clinical outcomes. Immunohistochemistry on 30 formalin-fixed paraffin-embedded (FFPE) primary CRC samples revealed that TEMs, which characteristically express tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (Tie2) receptor and CD14, preferentially localize to perivascular regions and are associated with higher histological grade, tumor size, lymph node metastasis, and increased MVD. However, Tie2⁻/CD14⁺ macrophages and CD68⁺ tumor-associated macrophages (TAMs) showed uniform stromal distribution. Gene set enrichment analysis (GSEA) of in silico transcriptomic datasets of metastatic CRC (mCRC) identified enrichment of pathways related to cell–cell recognition, calcium signaling, transcription regulation, and metalloexopeptidase activity in Tie2⁺/CD14⁺ tumors. Subsequent qRT-PCR validation on FFPE primary CRC samples confirmed significant upregulation of C-C chemokine receptor 7 (CCR7), platelet-derived growth factor A (PDGFRA), CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2), and carboxypeptidase E (CPE) in TEMs⁺ regions. Notably, angiopoietin1 (Ang1), but not angiopoietin2 (Ang2), was significantly elevated in TEMs⁺ primary tumors. Kaplan–Meier analysis on 1336 CRC patients indicated that high expression of CITED2, CPE, and Ang2 is associated with reduced overall survival. Collectively, these findings suggest that TEM infiltration is linked to transcriptional regulation, biological processes, and enzymatic programs in CRC, potentially contributing to tumor progression and poor prognosis, and highlight CCR7, PDGFRA, CITED2, CPE, and Ang1 as candidate biomarkers for further mechanistic exploration. Full article

A homologous classification for vespid venoms is missing. This study compared Polistes dominula and Vespula spp. venoms to evaluate their homology level. P. dominula and Vespula spp. extracts, including V. germanica, V. maculifrons, V. pensylvanica, V. alascensis, and V. squamosa in equal proportions, were generated from venom sacs and were subjected to sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot using Vespula-positive sera. Bands described as allergenic were excised and sequenced through Liquid Chromatography–Mass Spectrometry tandem analysis (LC-MS/MS) to confirm their identity. Phospholipase (group 1) and hyaluronidase (group 2) enzymatic activities were measured. Group 1 and 5 3-D structures and sequence identity were analyzed in silico. The results showed that the P. dominula and Vespula spp. venom extracts exhibit similar protein profiles and comparable allergen composition, with phospholipase and hyaluronidase activities. The structures of Pol d 1 and Ves v 1 and Pol d 5 and Ves v 5 were highly similar, and the identity levels were high across and within the Polistes and Vespula genera (≥50%). These results suggest the inclusion of venoms from Polistes and Vespula genera as candidates to create a new homologous group for wasp venoms and indicate that the currently described homologous groups require revision. Full article

Bacterial β-barrel pore-forming toxins, including Staphylococcus aureus α-toxin (Hla) and Bacillus cereus toxins hemolysin II (HlyII) and cytolytic toxin K2 (CytK-2), are secreted by bacterial cells as water-soluble monomers. These monomers assemble within lipid bilayers to form cylindrical pores, leading to lysis of target eukaryotic cells. We created mutant forms of these toxins that, based on the results of X-ray structural analysis of Hla and the prediction of the 3D structure of HlyII and CytK2, can form intramolecular disulfide bonds in monomers. The substitutions were made in the region responsible for toxin insertion into the target membrane. The mutant forms reversibly altered their hemolytic activity depending on the presence of reducing reagents and were non-toxic when injected into experimental animals. The immune response to injection of the mutant forms of Hla and CytK-2 toxins resulted in higher antibody titers against the wild-type toxins and a higher level of immunological memory than with injection of the HlyII mutant. The mutant form of CytK-2 demonstrates the properties of a prototype vaccine, as immunization with this protein protects animals against the effects of the wild-type toxin. Full article

Population aging increases the demand for different assistive devices enabling independent mobility and safe vehicle boarding. This paper presents the design and development of a universal lifting platform intended to support the legs of people with reduced mobility during vehicle entry. The device was designed to be independent of a specific vehicle and to be powered by vehicle standard 12 Volt current. A CAD model of the proposed device was modeled in SolidWorks 2017 and validated through analytical calculations and finite element simulations. Based on the calculation results, a functional prototype was manufactured and tested under real operating conditions, confirming the feasibility and usability of the proposed solution. The presented platform provides a low-cost, lightweight and vehicle-independent assistive device, supporting controlled and safe leg transfer without the need for vehicle modification or homologation. Full article

DNA damage requires repair via the endonuclease IV-mediated base excision repair (BER) pathway, which corrects apurinic/apyrimidinic (AP) sites. Chlamydophila pneumoniae AP endonuclease IV (CpEndoIV), the sole AP endonuclease in this pathogen, is crucial for genomic integrity. As humans lack a homologous protein, it represents a potential therapeutic target. In this study, we report the first crystal structure of CpEndoIV at 1.97 Å resolution. The structure reveals two Zn²⁺, one Mg²⁺, and a malonate molecule bound in the active site, marking the first observation of Mg²⁺ coordination in the EndoIV family. Compared to the three-Zn²⁺ model with a narrow, deep pocket for precise AP-site cleavage, the Zn²⁺/Mg²⁺-bound state has a wider, shallower pocket that might promote diverse catalytic activities. Combined with enzymatic assays, we suggest that the mixed Zn²⁺/Mg²⁺ model is better adapted for CpEndoIV to operate under host oxidative stress. Malonate binds to the metal ions, occupying the positions normally coordinated by water molecules. This binding mode may mimic the coordination of the substrate to the metal ions, and the protein conformation resembles that of the enzyme upon substrate binding at the active site. This study provides a structural basis for the functional characterization of CpEndoIV and offers a reference for the development of targeted inhibitors against diseases caused by Chlamydophila pneumoniae. Full article