Search Results (5,371)

Staphylococcus aureus is an ESKAPE pathogen, defined by its ability to evade antibacterial treatment, and together with S. epidermidis is a leading Gram-positive cause of wound infection. The emergence of methicillin- and vancomycin-resistant strains further limits conventional antibiotic treatment. The staphylococcal endolysin LysSte134_1 was produced recombinantly, its proper folding confirmed by zymography, and its lytic activity demonstrated against planktonic cultures of both S. aureus and S. epidermidis. The combination of LysSte134_1 with 10% 1,3-propanediol and Zn²⁺ increased CFU reduction in both species relative to LysSte134_1 with Zn²⁺ alone. In a murine wound model, topical application of LysSte134_1 significantly reduced the bacterial burden in wound tissue, achieving a 2–3-log reduction in MRSA and below the detection limit for S. epidermidis. Treatment was accompanied by normalization of peripheral leukocyte counts and a shift in the serum cytokine profile from a sustained pro-inflammatory state with elevated IL-6, IL-17 and IL-10 toward levels comparable to non-infected controls. These results suggest the potential utility of LysSte134_1 as a component of topical antibacterial formulations and support further investigation in models of staphylococcal wound infection. Full article

Samples of stingless honey from six species of stingless bees collected at nine stations in different Brazilian states were analyzed by chemometric methods for moisture, impurities and solid residues, ash, pH, electrical conductivity, proteins, proline, identification of adulteration, presence of substances such as phytochemical analysis, color and levels of HMF. The color (C) varied between water white and dark amber. Proteins (mL) varied from 0.00 (S5) to 2.00 (S4). Lund test from 0.00% (S5) to 3.10% (S6), total phenols (TP%) from 0.04 to 13.45 mg/100 g GAE, total flavonoids from (TF%) 0.03 to 0.11 mg/100 g QE, and HMF from 0.00 to 14.28 mg/kg. There was an increased amount of PRO in S7 and S8. S1, S4, S7 and S8 had the best antioxidant activity (EC₅₀). A heat map showed that S2 was the sample with the highest %Brix, %insoluble solids, %humidity and pH, but the lowest TP%. S7 had the highest C, proline (PRO), TF%, EC₅₀ and EC. S4 had high %A and intermediate results between groups 9, 5, 6 and groups 1, 3, 8. The sample honey S6 showed a high content of TP (13.45 ± 0.98 mg/100 g of GAE). In contrast, stingless honey samples exhibited better DPPH scavenging activity (EC₅₀: 21.45 ± 0.54 to 53.71 ± 0.24 mg/mL). The chemometric classification of stingless bee honey revealed that the physicochemical properties contributed significantly to the classification of stingless bee honey from different bee species. With all the information presented here, the results obtained and correlations from multivariate statistical analysis, we propose the creation of a standard for the technical regulation of Brazilian native bee honey, based on the literature and quality parameters described here. Full article

Graph theory has become a fundamental mathematical framework with broad applications across various scientific fields, such as biology, network security, computer science, and chemistry. A specialized branch known as chemical graph theory employs graph-based mathematical principles to model and analyze molecular architectures. Typically, molecular graphs are generated from 2D representations of chemical structures, where physicochemical properties play a decisive role in interpreting a molecule’s physical and chemical behavior. Structural symmetry within these molecular graphs significantly aids in deriving fundamental graph parameters. Recently, a novel theoretical method has been introduced to perform a comparative analysis of seven significant domination parameters alongside the p-electronic energy of benzenoid hydrocarbons. In the field of graph theory, the independence, covering, and domination numbers stand as fundamental parameters. Inspired by this methodology and related research, this study presents an exploratory investigation into the physicochemical properties of 10 selected drug and bioactive molecules from diverse therapeutic classes to evaluate bulk size-dependent properties using these fundamental graph parameters. Various regression models were evaluated alongside leave one out cross validation (LOOCV) diagnostics for six specific properties of these compounds: boiling point (BP), enthalpy of vaporization (EV), flash point (FP), molar refractivity (MR), polarizability (P), and molar volume (MV). The results highlight the potential of these fundamental graph parameters in QSPR modeling, establishing an exploratory proof of concept that warrants future support from more comprehensive independent datasets. Full article

The global proliferation of multidrug-resistant Pseudomonas aeruginosa stimulates the search for alternatives to conventional therapy. This study developed human serum albumin (HSA)-based hydrogels for the delivery of bacteriophage PA57. Matrices were fabricated via combined thermal- and ethanol-induced gelation. The release kinetic was dependent on protein concentration: 20% (w/v) HSA provided sustained release over 48 h, whereas 10–15% (w/v) HSA exhibited burst release effects. Combined systems effectively suppressed P. aeruginosa growth in vitro during the early and middle stages of incubation, maintaining low culture optical density for up to 28 h. Although late-stage bacterial regrowth was observed, the final bacterial load remained significantly lower than in the control. Furthermore, cytocompatibility assays with HaCaT keratinocytes and MRC-5 fibroblasts demonstrated high cell viability, confirming the safety of the hydrogel matrix for wound healing applications. These results demonstrate the promise of HSA-based hydrogels as a platform for localized phage therapy of infected wounds. Full article

Plant growth-promoting bacteria (PGPB) are increasingly deployed as biofertilizers, yet the link between an inoculant’s genomic potential and its realized effect on the plant is rarely assessed within an integrative framework that jointly captures the rhizosphere microbiome, plant phenotype, and strain genome. Two Bacillus strains—B. halotolerans 1453 and B. pumilus 630—were applied to wheat and soybean in a factorial pot experiment (2 strains × 2 application methods × 3 frequencies + control, 3–4 replicates). Rhizosphere samples (n = 67 after filtering) were profiled by 16S rRNA sequencing with PICRUSt2 functional prediction and compositional validation (Aitchison PERMANOVA, ALDEx2, ANCOM-BC2). The PGPB gene repertoire was characterized by genome mining (481 marker genes, 14 categories). Wheat phenotype (six traits) and soybean height were analyzed with models appropriate for count data (Negative Binomial and binomial GLMs) for treatment-vs.-control comparisons, and with factorial ANOVA for decomposition into main effects and interactions. Crop identity was the dominant factor shaping both microbiome structure and function (PERMANOVA R² = 14.7% taxonomically and R² = 7.8% functionally, both p < 0.001), with biologically meaningful taxonomic differences between wheat and soybean; strain, application count and method had no significant effect on community composition (R² < 4% each), and co-occurrence networks showed no reliable differences between crops once read depth and sample size were controlled for. Despite this neutrality at the microbiome level, inoculation significantly increased wheat spike count (NB-GLM, all 12 treatments vs. control, padj 0.0002–0.031), ear weight, and stem count, with application count the strongest source of variability and a pronounced strain × application count. Strain 1453 outperformed 630 in spike count (+23.1%, p = 0.012) and ear weight (+20.4%, p = 0.023); we hypothesize that this may be related to its more complete DNRA pathway (narGHI + nirB-nirD) and biocontrol genes (bacE, srfAA). Strain 630 produced a less pronounced effect than strain 1453 but was subject to smaller fluctuations across replicates (CV ≈ 16–21% vs. ≈24–26% for 1453), which may reflect better resilience to environmental fluctuations, possibly due to its confirmed rsbV/rsbW stress-tolerance regulon. Rhizosphere microbiome composition differed clearly by crop (wheat vs. soybean) but showed no detectable response to strain, application method, or application count. Despite this lack of a microbiome signal, inoculation significantly increased wheat spike count and ear weight, with the magnitude and stability of this effect differing by strain. We hypothesize that this strain-dependent difference relates to underlying genomic differences—particularly in nitrogen metabolism (DNRA pathway) and stress-tolerance genes—though this link has not been tested directly and remains a hypothesis for future work. Full article

Pseudomonas aeruginosa is a nosocomial pathogenic bacterium that causes a wide range of human infectious diseases. The type III secretion system (T3SS) serves as a key virulence determinant underlying the pathogenesis of this bacterium in acute infections. As the master transcriptional activator of T3SS, ExsA binds to target promoter regions and modulates the expression of all currently identified T3SS genes. In this study, we identified tyrosine phosphoprotein A (TypA) as a repressor that restricts expression of the T3SS in P. aeruginosa. TypA interacts with ExsA to block its binding to target promoters, thereby inhibiting T3SS expression. We show that the typA expression is induced in response to low calcium, low temperature, a biofilm lifestyle, and direct contact with host cells. Additionally, the absence of TypA caused a growth defect in P. aeruginosa at low temperatures. Collectively, these data confirm the significant role of TypA and reveal a novel molecular mechanism by which P. aeruginosa regulates T3SS. Full article

Thirty-two Chinese Anastatus species (Hymenoptera: Chalcidoidea: Eupelmidae) are studied, comprising 20 previously described species and 11 new species. Ten of the new species belong to the subgenus A. (Anastatus): A. (Anastatus) nozdormusp. nov., A. (Anastatus) kryptos sp. nov., A. (Anastatus) napoleonissp. nov., A. (Anastatus) yalini sp. nov., A. (Anastatus) battutai sp. nov., A. (Anastatus) beagleisp. nov., A. (Anastatus) neltharionsp. nov., A. (Anastatus) tigrinussp. nov., A. (Anastatus) huijuanaesp. nov., A. (Anastatus) ashrafisp. nov. One belongs to the subgenus A. (Cladanastatus): A. (Cladanastatus) alexstraszasp. nov. One additional species is newly recorded from China: A. (Anastatus) mantoidae Motschulsky rec. nov. A new synonymy is also proposed: A. (Anastatus) flavaeratus Peng & Tang, 2020 syn. nov. under A. (Anastatus) gastropachae Ashmead, 1904. Morphologically similar species were assigned to three informal species groups (formosanus, fulloi, and japonicus groups) based on morphology. Of the already-described species of the Chinese Anastatus, 15 were newly recorded from different provinces of China; this was true for all species except A. colemani, A. bifasciatus, A. polikiarkoudus, A. taibaiensis, and A. zdenekbouceki. Molecular analyses based on the mitochondrial cytochrome c oxidase subunit I (COI) gene were conducted on a total of 34 species (26 species derived from the specimens collected from China and eight species’ sequences downloaded from the BOLD and NCBI). Multivariate morphometric analyses (PCA, LDA, MANOVA) were employed to distinguish morphologically similar species. A comprehensive diagnostic key to all Chinese Anastatus species is also provided, accompanied by photographs of diagnostic characters. Full article

Nanofillers are widely used to enhance the performance of polymer composites; however, their effectiveness strongly depends on their physicochemical properties and dispersion behavior. In this study, five commercially available nanofillers, namely multi-walled carbon nanotubes (CNTs), nanoclay, halloysite, Cloisite^® 30B, and zinc oxide (ZnO), were comprehensively characterized as potential modifiers of unsaturated polyester resin. The results confirm the characteristic chemical composition and crystalline structure of all investigated nanomaterials. CNTs exhibited the highest specific surface area (213.7 m² g⁻¹) and pore volume, whereas ZnO showed the lowest median equivalent particle diameter determined by laser diffraction (D₅₀ = 2.09 μm). The clay-based fillers displayed comparable particle size distributions, with D₅₀ values ranging from 8.29 to 9.00 μm. SEM observations revealed substantial differences in morphology and agglomeration state, with CNTs forming compact entangled agglomerates, while ZnO exhibited the most homogeneous microstructure. Suspension stability analysis demonstrated that particle size alone could not explain the observed sedimentation behavior. ZnO exhibited the highest dispersion stability, whereas halloysite and Cloisite showed progressive sedimentation. Nanoclay displayed delayed destabilization associated with agglomeration processes, while CNT suspensions were governed by structural rearrangements rather than classical sedimentation. The obtained results indicate that the dispersion behavior of nanofillers in unsaturated polyester resin is associated with differences in particle size, morphology, and agglomeration tendency. The presented comparative characterization provides a basis for the rational selection of nanofillers for polyester resin-based nanocomposites. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease associated with insulin resistance and hepatic lipid accumulation. Polyphenols have attracted considerable attention for their hepatoprotective and lipid-lowering activities. Our previous studies characterized a bound polyphenol extracted from the inner shell of foxtail millet (BPIS) and identified its major active components. In the present study, we investigated the molecular mechanisms underlying its biological activity using HepG2 cells and Caenorhabditis elegans. BPIS activated AMPK signaling, normalized intracellular glutathione (GSH) levels, and upregulated SLC7A11 and GPX4, suggesting modulation of ferroptosis-related pathways and improved cellular redox homeostasis. BPIS also alleviated endoplasmic reticulum stress by increasing GRP78 expression, inhibiting DRAK2, and regulating the ERK pathway, thereby improving the regulation of key lipid-metabolism-related signaling pathways, including SREBP1c, SCD1, CD36, FASN, and CPT1A. Consistent with these findings, BPIS reduced glucose- and free fatty acid-induced lipid accumulation and improved lipid-related phenotypes in C. elegans. Overall, BPIS attenuated hepatic steatosis through modulation of ferroptosis-related markers, endoplasmic reticulum stress, and lipid metabolism. These findings provide new mechanistic insights into the biological activities of BPIS and support its potential application as a nutraceutical ingredient for the prevention and management of MASLD. Full article

Forests are an indispensable resource for human existence in the different regions of the world. Forests are often concentrated in a few parts and vary in size. The most important and extensive green reserve on Earth is the Amazon rainforest. Unfortunately, the forests are continually suffering massive losses due to abiotic stresses and deforestation to obtain other arable lands and microbial diseases, particularly those caused by pathogenic fungi. Pathogenic fungi play an important role in inducing oak decline, which is one of the most relevant forest diseases globally. The pathogens also affect disease development and its global distribution. In this review, the phytotoxins produced by fungal pathogens of different oak species in various world regions are described in depth. In particular, the isolation, the chemistry and biology of phytotoxins synthesized by oak pathogenic fungi are reported, and their role in pathogenesis is also discussed. For some phytotoxins, the enantioselective synthesis, the structure–biological activity relationships, and their utilization in agro-industry and medical applications are also discussed. In addition, for the Diplodia species, the comparison between their secondary metabolite profile and taxonomy with those of fungal pathogens of other close forest plants is discussed. Thus, fungal diseases of numerous oak trees and the serious damages they cause to the forest heritage are described, as well as the chemical and biological properties and results of some of the structure–activity relationship (SAR) studies of the phytotoxins involved. In addition, for the Diplodia species both phylogenetically closely related and unrelated, comparison between their secondary metabolite profile with those of pathogens of other close forest plants, in combination with traditional taxonomic characteristics, has helped to better understand the pathogenic process relationships within the same fungal f the pathogenic process within the same fungal family. Full article

Background/Objectives: Tryporyza intacta is a stem-boring pest that readily causes dead hearts in sugarcane seedlings and dead tops in mature plants, leading to large-scale yield reduction. Reverse chemical ecology studies of this pest contribute to its field biological control. During olfactory recognition, odor molecules are integrated by the olfactory nervous system after interacting with odorant-binding proteins (OBPs) and chemosensory proteins (CSPs), thereby regulating insect behavior. Methods: Two novel full-length general odorant-binding protein (GOBP) genes were cloned from antennal tissues using reverse transcription PCR. Protein sequence analysis was conducted to determine sequence similarity and conserved structural features. The recombinant GOBP1-2 protein was expressed in Escherichia coli and purified via Ni-ion affinity chromatography. Fluorescence binding assays were performed to evaluate the binding affinities of GOBP1-2 with various volatile odorant molecules. Results: Protein sequence analysis revealed that the two identified GOBPs shared high sequence similarity with other insect GOBPs and contained the characteristic six-cysteine motif. Fluorescence binding assays demonstrated that GOBP1-2 proteins exhibited differential binding affinities to distinct volatile odorant molecules, indicating selective ligand recognition. Conclusions: These findings suggest that GOBPs and effective volatile odorants likely play a functional role in the olfactory behavioral responses of this moth. This research provides valuable insights for developing field attractants targeting this sugar borer. Full article

Sea cucumbers exhibit rapid recovery of all organs and the body following various injuries, making them highly promising models for investigating the mechanisms of self-regeneration. This study provides the first comprehensive comparative analysis of DNase activities in both homogenates and highly stable multiprotein complexes isolated from five distinct organs—gut, respiratory trees, body wall, gonads, and coelomic fluid—of the sea cucumber Paracaudina chilensis. Using in situ zymography following SDS-PAGE with copolymerized polymeric DNA, we systematically profiled the molecular weights, optimal pH values, and metal ion dependencies of DNases across these tissues and their corresponding stable complexes (1.2–1.8 MDa). Our results reveal that each organ possesses a unique DNase repertoire, with at least 25 distinct enzymatic species identified on the basis of molecular masses (~19, 23, 30, 35, 50, 100, 130, and 150 kDa) and pH optima ranging from 4.5 to 9.5. Notably, the gut homogenate contained the greatest diversity of DNases, whereas the respiratory tree and coelomic fluid complexes harbored highly active enzymes that were undetectable in the corresponding homogenates, indicating selective enrichment during complex assembly. Most DNases were Mg²⁺-dependent, with optimal MgCl₂ concentrations between 5 and 10 mM; however, two metal-independent DNases (~50 and ~100 kDa) were identified exclusively in respiratory tree complexes, and their activity was strongly enhanced by EDTA, suggesting suppression by endogenous metal ions. Additionally, Ca²⁺-activated DNases (~19 and ~23 kDa) were found in complexes from body wall, gonads, and coelomic fluid. Several DNases with high relative activity in the complexes were not reliably detected in the corresponding tissue homogenates, whereas some abundant homogenate enzymes were absent from the complexes. This implies that the formation of these supramolecular assemblies is not random but rather involves the specific recruitment of low-abundance enzymes, potentially concentrating them to achieve high local activity for organ-specific functions. The gut, which undergoes complete regeneration after evisceration, contained the most varied set of DNases, hinting at a possible role in DNA metabolism during tissue renewal. Thus, we have shown for the first time that the multiprotein complexes from different organs of the sea cucumber differ not only in molecular weight and protein/peptide composition but also in the number and types of DNases they contain. We propose that in each organ of the sea cucumber, a specific multiprotein complex is formed, which may be necessary to perform additional extended functions of this complex beyond those of canonical individual proteins, peptides, and enzymes. Full article

Interleukin-12 (IL-12) potently promotes the recruitment and activation of immune cells within the tumor microenvironment (TME), highlighting its immense potential for cancer therapy. However, its dose-limiting systemic toxicity and short half-life severely hinder its clinical translation. Here, we design a tumor-conditionally activated IL-12 prodrug termed αHSA-proIL-12. This engineered molecule integrates a cleavable albumin-binding nanobody (αHSA) domain to extend the half-life and enhance tumor targeting alongside a masking domain that occludes the IL-12 receptor-binding site to prevent nonspecific activation. This construct undergoes selective cleavage by matrix metalloproteinases (MMPs) that are highly expressed in the TME to release highly penetrant, free, low-molecular-weight IL-12 locally. This tumor-restricted activation process directly facilitates the selective recruitment and activation of tumor-infiltrating lymphocytes (TILs). The intravenous administration of an extremely low dose of 108 pmol per dose of αHSA-proIL-12 completely cleared MC38 tumors without inducing systemic toxicity. The maximum tolerated dose of this molecule exceeded 2 nmol, yielding a remarkably wide therapeutic index >18.5. Mechanistically, αHSA-proIL-12 effectively reprogrammed the immunosuppressive TME by expanding the numbers of effector CD8⁺ T cells and natural killer cells while upregulating IFN-γ expression and significantly reducing the proportion of regulatory T cells. This immunological remodeling has the potential to convert “cold” tumors into “hot” tumors. Notably, this treatment achieved complete regression and durable immunity in a subset of mice with multiple refractory immune-cold tumors, including Panc02 pancreatic cancer, 4T1 triple-negative breast cancer, and B16F10 melanoma, when administered as a monotherapy or in combination with PD-L1 blockade. Furthermore, when combined with surgery, αHSA-proIL-12 effectively prevented the postoperative recurrence and distant metastasis of advanced 4T1 tumors. This modular platform provides a clinically promising strategy to overcome the toxicity bottleneck of cytokines and substantially advances the development of combination cancer immunotherapies. Full article

Dual inhibition of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT) has emerged as a promising therapeutic strategy due to its ability to simultaneously target oncogenic signaling and cellular metabolism in cancer. While existing inhibitors such as KPT9274 and PF-3758309 have demonstrated preclinical activity, their clinical translation has been limited by poor selectivity, suboptimal efficacy, and dose-limiting toxicities. Reliance on a small number of available compounds is therefore insufficient, highlighting the need for systematic optimization to identify candidates with improved therapeutic profiles. Although several dual PAK4 and NAMPT inhibitors such as GNE2861, LCH7749944, and PF3758309 have been identified in our previous study, the number of compounds available is limited. Identification of new candidate compounds would allow researchers to identify those that are the most efficient, those that are the most potent and selective, and those that have optimal pharmacokinetics. In this study, we performed additional large-scale drug screening to identify new candidate dual PAK4 and NAMPT inhibitors and expand the diversity of this inhibitor class. Computational molecular docking was used to evaluate binding affinities toward both targets, followed by drug–protein interaction analyses to assess binding stability and interaction patterns at the molecular level. Several new candidate compounds demonstrated favorable predicted binding to both PAK4 and NAMPT, with distinct interaction profiles compared to previously reported inhibitors. Biochemical assays further demonstrated inhibitory activity against both PAK4 and NAMPT among several selected compounds, supporting their potential as dual-target inhibitors. These findings provide mechanistic insight into dual-target engagement and highlight structural features associated with improved binding behavior. Expanding the pool of dual inhibitors enhances opportunities for preclinical development, supports optimization of pharmacokinetic and safety profiles, and strengthens datasets for drug discovery. Collectively, this work broadens the landscape of dual PAK4 and NAMPT inhibitors and supports their potential application across multiple cancer types beyond triple-negative breast cancer. Full article

Molecular property prediction is a fundamental task in drug discovery and chemical biology, where effective molecular representations are essential for accurate prediction. Learning transferable motif-level representations remains challenging because explicit motif annotations are scarce and existing representations may be altered during downstream supervised optimization. In this study, we propose MSGRL, a motif-driven self-supervised graph representation learning framework for interpretable molecular property prediction. MSGRL represents each molecule through a hierarchical graph structure, consisting of a motif-based graph for inter-motif organization and motif-specific atom-based graphs for intra-motif atomic structure. Its central design is to decouple label-agnostic intra-motif structural learning from label-dependent inter-motif property learning. An MPNN-GRU encoder is pretrained on motif-specific atom-based graphs using a variational motif graph autoencoder (VMGAE), which reconstructs the internal bond topology of motifs in a self-supervised manner. After pretraining, the intra-motif encoder is kept frozen, while the downstream module pools atom-level feature matrices into motif vectors, propagates information over the motif-based graph, and applies attention-based pooling for molecular property prediction. This design keeps the pretrained intra-motif representations fixed while allowing the inter-motif network and prediction head to adapt to individual downstream tasks. Experiments on eight MoleculeNet benchmark datasets show that MSGRL achieves the highest ROC-AUC scores on all five classification datasets and the lowest RMSE on Lipophilicity, while its performance on ESOL and FreeSolv is more mixed. Ablation studies further support the contributions of encoder freezing, motif-based graph construction, and attention-based pooling. Motif-level attribution analyses provide qualitative and dataset-level evidence regarding the substructures emphasized by the model. These results demonstrate the effectiveness of the proposed hierarchical representation strategy, particularly for the evaluated molecular classification tasks. Full article