Search Results (1,098)

With the increasing emergence of multidrug-resistant (MDR) bacteria, there is an urgent need to discover new antibiotics. In this study, genome mining coupled with anti-bacterial assay guided the targeted isolation of two new heptapeptides nobilamide Q3 (1) and R3 (2). These compounds were identified as new stereoisomers of the known scaffold A-3302-B (3). The structures of these compounds were elucidated through a combination of MS, NMR spectroscopy and Marfey’s analysis. Anti-MDR bacterial assays showed that compounds 2 and 3 exhibited effective growth inhibition against the Gram-positive MDR bacterial strain Staphylococcus aureus CCARM 3090 with MIC values of 3.25–6.5 μg/mL. Notably, our study reveals stereochemistry-dependent differences in their antibacterial activities, providing new insights into the structure–activity relationship of this class of peptides. Finally, an analysis of the biosynthetic gene cluster responsible for their production was conducted. This study underscores the significance of exploring cold-seep environments as a reservoir for discovering new antibiotics and provides a structural starting point for the future optimization of antimicrobial peptides. Full article

Artisanal colonial cheese (ACC) produced from raw milk is a rich reservoir of autochthonous lactic acid bacteria (LAB), but strain-level evidence supporting safe downstream application and technological stability remains limited. In this study, 10 LAB isolates from ACC were screened for phenotypic safety, antimicrobial susceptibility, and probiotic-related traits, and their viability was further assessed after inulin-based spray-drying microencapsulation under different storage temperatures. All isolates showed no hemolytic or mucinolytic activity and did not produce gelatinase, supporting an initial safety profile, and all strains were sensitive to at least two antimicrobial classes. Strain prioritization identified Lacticaseibacillus casei LAB06, LAB09, and LAB10 and Lactiplantibacillus plantarum LAB03 as the most robust candidates for downstream development because they maintained stable cell counts throughout simulated gastrointestinal digestion. Inulin spray-drying yielded structurally stable microcapsules and supported refrigerated storage, with substantially lower viability losses at 4 °C than at 25 °C; notably, L. plantarum LAB01 and LAB02 showed the best refrigerated shelf-life, remaining above 6.0 log CFU/g after 45 days. Together, these results position ACC as a source of promising LAB candidates and highlight cold-chain-compatible microencapsulation as a strategy to support safe functional food development with potential public health benefits. Full article

Land desertification poses a major ecological challenge and threatens agricultural productivity. This study investigated the seed endophytic microbiomes of desert plants as a potential resource for mitigating salt stress in crops. Using high-throughput sequencing, we characterized the bacterial and fungal communities within seeds of 12 desert plant species. Dominant taxa included Firmicutes (particularly Bacillus), Bacteroidota, Proteobacteria, Ascomycota, and Basidiomycota. Culturable bacteria were subsequently isolated from Haloxylon ammodendron (C.A.Mey.) Bunge (HB) and Hedysarum scoparium Fisch. & C.A.Mey. (HSA) seeds. These isolates were screened for plant growth-promoting (PGP) traits and tolerance to salt (NaCl) and alkali (NaHCO₃). Selected strains, including the high indole-3-acetic acid (IAA)-producing Bacillus sp. HB-4, were used to inoculate wheat (Triticum aestivum L.) under 150 mM NaCl or 150 mM NaHCO₃ stress. Inoculation with strain HB-4 significantly improved wheat growth under stress. This improvement was associated with increased chlorophyll and proline content, enhanced activities of the antioxidant enzymes catalase and peroxidase, and reduced levels of malondialdehyde, a marker of oxidative damage. Our results demonstrate that desert plant seeds harbor taxonomically distinct and functionally resilient endophytes. The successful application of a desert-adapted Bacillus strain to alleviate salt stress in wheat highlights the potential of such microbiomes as a novel source of inoculants for sustainable agriculture in saline-affected regions. Full article

Background/Objectives: The high prevalence of fluoroquinolone-resistant E. coli in healthy children represents a significant public-health risk, facilitating the spread of antimicrobial resistance and increasing the potential for difficult-to-treat extraintestinal infections with severe clinical outcomes. This study aimed to investigate the prevalence of fluoroquinolone resistance in multidrug-resistant E. coli isolated from presumptively healthy children in St. Petersburg, Russia, with a particular focus on fluoroquinolone resistance determinants. Methods: Phenotypic AST was performed on 307 E. coli isolates from fecal pediatric samples, comprising 230 isolates from 2012 to 2013 and 77 isolates from 2021 to 2022. A subset (n = 47) of MDR isolates underwent whole-genome sequencing. Results: The frequency of MDR E. coli strains rose significantly from 15.7% to 32.5% over the study period. The most significant increases in resistance among E. coli strains were to third-generation cephalosporins (CTX, CTZ) and fluoroquinolones (CIP), rising fourfold over a decade. Based on phenotypic resistance profiles of MDR E. coli to quinolones, the highest resistance rates were observed for MFX (80.9%) followed by NAL (74.5%), LVX (44.7%) and CIP (40.4%). Genotypic analysis revealed distinct pathways: low-level NAL resistance required only an S83 mutation in gyrA, whereas low-level MFX resistance was predominantly conferred by a plasmid-borne qnr gene. In contrast, resistance to CIP and LVX involved at least three QRDR mutations: S83L and D87N/Y in gyrA, and S80I in parC. Notably, our study showed the predominance of the ST131 and ST38 clones in E. coli isolated from pediatric samples. Conclusions: Our findings suggest that the efficacy of moxifloxacin for empirical treatment of infections caused by MDR E. coli might be severely compromised. Overall, the current study highlights that the pediatric gut microbiota serves as a reservoir for resistant E. coli with the expansion of multidrug-resistant clones independently of direct antibiotic selection pressure. Full article

The thermophilic bacterium Thermus thermophilus represents a crucial genetic reservoir for exploring thermostable enzymes as valuable biocatalysts for industrial and biotechnology applications. Here, we identify, clone, and characterize Ces1-ET, Est1-ET, and Plp1-ET, three lipolytic enzymes obtained from T. thermophilus strain ET-1 isolated from El Tatio Geothermal Field in Northern Chile. To enable recombinant expression, we constructed the pTGT-1 expression system, a versatile bifunctional shuttle vector compatible with both Escherichia coli and T. thermophilus. The three thermoenzymes Ces1-ET, Est1-ET, and Plp1-ET, were successfully cloned, expressed, and purified using the pTGT-1 system, with a molecular mass of 25 kDa, 36 kDa, and 28 kDa, respectively. The recombinant purified enzymes displayed optimal temperatures at 60 °C, 80 °C, and 70 °C and optimal pH of 7.5, 9.0, and 8.0 for Ces1-ET, Est1-ET, and Plp1-ET, respectively. Functional biochemical assays revealed a broad tolerance to surfactants, detergents, divalent cations, and high salinity, relevant properties for their application in an industrial setting. These thermostable esterases expand the repertoire of thermozymes from Thermus spp., introducing pTGT-1 as an innovative tool for thermophilic protein expression and highlighting T. thermophilus strain ET-1 from El Tatio Geothermal Field as a valuable source of thermostable enzymes for industrial and biotechnology applications. Full article

Staphylococcus are common bacteria that can be a component of the natural microbiota of the body of human and animal hosts or cause serious infections. The aim of this study was to analyze the presence of S. aureus in samples from two sheep breeds (Świniarka and Uhruska), assess the antimicrobial susceptibility and virulence profile of these microorganisms, and perform molecular comparative analysis of these bacteria. One hundred and three isolates of S. aureus strains were obtained (including five MRSA strains) and the highest phenotypic resistance to tetracycline (46.6%), clindamycin (45.6%), erythromycin (39.8%), and penicillin (31.1%) was confirmed. The tetL gene (27.2%) and the seB gene (44.7%) were the most frequently detected in strains. Three new sequence types in the MRSA isolates (ST 9313, ST 9314, ST 9315) were identified. In conclusion, our results confirm that sheep are significant reservoirs of S. aureus, especially MRSA strains, varying in terms of both resistance and virulence and with the potential to spread between individuals in the same herd, which may pose a potential health problem. Full article

Protists represent a vast yet underexplored reservoir of enzymatic diversity across the eukaryotic tree of life. In this study, we established axenic strains of diverse protists from four major eukaryotic supergroups using single-cell isolation and generated de novo transcriptomes for each strain, as reference genomes or transcriptomes are not available for these strains. As a test case for industrial enzyme discovery, we targeted nine enzyme classes used in pulp processing and evaluated whether protist-derived sequences occupy underrepresented sequence space relative to major public databases. Functional annotation combined with Sequence Similarity Network analysis revealed multiple clusters composed exclusively of protist-origin sequences, indicating candidate enzymes with high sequence-level novelty. These results suggest that protists may provide a practical resource for expanding the repertoire of industrially relevant enzymes and prioritizing targets for further characterization. However, additional in silico analyses and experimental validation will be required to determine whether these sequence-divergent candidates exhibit properties that meet industrial requirements. Full article

The mechanical response of geomembranes in hydraulic structures is strongly influenced by temperature variations, which alter both material stiffness and interface shear strength behavior. This study develops a non-linear, temperature-dependent tensile behavior constitutive model for a polyvinyl chloride (PVC) geomembrane and evaluates its implications for the stability of geomembrane-lined reservoir slopes. The empirical relationship was calibrated using tensile tests reported in literature for temperatures between 10 °C and 60 °C, reproducing the observed non-linear softening and modulus reduction with increasing temperature. A classical thermal dilation formulation was incorporated to simulate cyclic thermal expansion and contraction. The constitutive and thermal formulations were implemented in FLAC2D and applied to a 2H:1V covered geomembrane slope representative of dam lining systems. The results show that temperature-induced softening significantly increases tensile strain within the geomembrane. The model also shows that the lower surface interface friction angle of the geomembrane plays a significant role in the slope stability. Thermal cycle analysis demonstrates the accumulation of efforts resulting from the fatigue of the geomembrane. The proposed model provides a practical framework for incorporating thermo-mechanical coupling in design analyses and highlights the necessity of accounting for realistic thermal conditions in assessing the long-term stability of geomembrane-lined reservoirs. Full article

Lignin is a complex aromatic polymer that constitutes a major fraction of plant biomass and represents a valuable renewable carbon resource. Naturally decaying wood serves as an environmental reservoir of microorganisms capable of degrading lignin. In this study, we isolated and characterized sixteen bacterial strains from decaying Tilia cordata wood using an enrichment culture technique with lignin as the sole carbon source. Taxonomic identification via 16S rRNA gene sequencing revealed microbial diversity spanning the genera Bacillus, Pseudomonas, Stenotrophomonas, and several members of the Enterobacteriaceae family, including Raoultella terrigena isolates. Metagenomic sequencing of the wood substrate revealed an exceptionally rich and balanced bacterial community (Shannon index H′ = 5.07), dominated by Streptomyces, Bradyrhizobium, Bacillus, and Pseudomonas, likely reflecting a specialized consortium adapted to lignin rich late-stage decay. Functional phenotyping demonstrated that all isolates possess ligninolytic potential, evidenced by peroxidase/laccase-type activity through methylene blue decolorization. Dynamic Light Scattering (DLS) and HPLC analyses showed that some isolates, such as Raoultella terrigena MGMM806, effectively depolymerized lignosulfonate into low molecular weight fragments (1.23 nm), while others accumulated intermediate metabolites or completely mineralized the substrate. Growth profiling on monolignol substrates revealed a broad spectrum of catabolic specialization in lignin monomer degradation. The results demonstrate a complex system of metabolic partitioning within a natural bacterial consortium. This collection represents a foundational genetic resource for developing engineered biocatalysts and synthetic microbial communities aimed at the efficient conversion of lignin into valuable aromatic compounds. Full article

Background: Gestational diabetes mellitus (GDM) is associated with metabolic disturbance and subclinical cardiovascular changes during pregnancy and after birth. Optimal glycaemic control remains challenging for many patients despite existing management strategies. Ursodeoxycholic acid (UDCA) has shown potential metabolic effects, including enhanced insulin sensitivity and anti-inflammatory effects. Previously, we demonstrated that UDCA improves glycaemic control in women achieving higher circulating UDCA concentrations; however, its effect on maternal cardiac function remains unknown. The objective was to evaluate whether treatment with UDCA compared with placebo is associated with differences in maternal cardiac function in pregnancies complicated by GDM. Methods: In this randomized, placebo-controlled trial, 113 women with GDM were recruited, with 56 allocated to UDCA and 57 to placebo (IMIB-GU-2019-02, registration date: 17 June 2020; first participant enrolled: 3 March 2021). After measurement of maternal blood UDCA levels, 43 participants in the treatment group with levels ≥ 0.5 μmol/L were included in a per-protocol analysis. Participants had cardiac assessments at baseline, in the late third trimester (36 weeks) and postpartum. Detailed left ventricular systolic and diastolic functional indices were assessed using conventional pulse and tissue Doppler indices as well as strain imaging. Right ventricular systolic function was also assessed. Results: Baseline maternal characteristics and cardiac functional indices were comparable between the UDCA and placebo groups. In the third trimester, women treated with UDCA showed more negative left atrial strain during atrial contraction (LASct_AC) compared with placebo (p = 0.016), while no significant between-group differences were observed in conventional left ventricular systolic or diastolic parameters. In the postpartum period, UDCA treatment was associated with higher left atrial reservoir function, reflected by increased LASr_ED (p = 0.041) and LASr_AC (p = 0.036), as well as more negative left atrial conduit strain at end-diastole (LAScd_ED; p = 0.043). No consistent differences were observed in left ventricular systolic function, haemodynamic indices, or right ventricular functional parameters between the two groups. Conclusions: These findings are associated with small and time-dependent differences in reducing atrial dysfunction and improving cardiac efficiency during late pregnancy and postpartum. However, given the lack of long-term follow-up, further research is needed to determine the long-term cardiovascular relevance of UDCA in this population. Full article

Microbial biological control agents are a sustainable alternative to synthetic pesticides, yet their widespread application is limited by a lack of environmental resilience of commercial products. To address this, we exploited honey—a stringent ecological niche—as a reservoir for stress-tolerant bacteria. In this study, the bioprospection utilizing five types of commercially available honeys yielded a collection of 53 bacteria and 10 fungi. All bacterial isolates were evaluated for antimicrobial activity against a laboratory-standard bacterium and yeast, and six economically relevant phytopathogenic microorganisms. Initial screening with standard laboratory organisms proved to be an efficient method to detect strains with antimicrobial potential, correlating significantly with further phytopathogen inhibition (Spearman’s r = 0.4512, p = 0.0005). Two promising strains, M2.7 and M3.18, were selected for quantitative dual-culture assays along with molecular identification using 16S rDNA and gyrA gene sequencing, classifying them as Bacillus velezensis. These strains exhibited high inhibitory effects against the pathogens (p > 0.001), often with equivalent efficacy to the commercial biocontrol strain, and also induced significant phytopathogen hyphal deformities, such as increased septation and swelling. These findings support honey as a viable source of robust biocontrol agents, offering a sustainable strategy to substitute or complement current agrochemicals. Full article

Accurately assessing collapse risks of high-elevation, concealed rock mass blocks within the steep cliffs of Bijiashan, Three Gorges Reservoir Area, is challenging. This study employed a multidimensional approach—integrating airborne Light Detection and Ranging (LiDAR), the transient electromagnetic method (TEM), close-range photogrammetry, horizontal drilling, and borehole optical imaging—to characterize the rock mass structure of the WD1 cliff belt and delineate 52 individual blocks. Stability analysis incorporated stereographic projection for macro-scale assessment and employed mechanical models specific to three primary failure modes (toppling, sliding, falling). Finite element strength reduction quantified the stress–strain response of a representative block under natural and rainstorm conditions. Particle Flow Code (PFC) simulated dynamic instability of the exceptionally large block W1-37. Results indicate the WD1 rock mass is highly fractured, with base sections prone to weakness. Toppling failure dominates (90.4%). Under rainstorm conditions, the average Factor of Safety (FOS) decreased by 14.7%, and 73.1% of the blocks that were stable under natural conditions were destabilized—specifically transitioning to marginally stable or substable states—often triggering chain-reaction instability characterized by “crack propagation—base buckling”. W1-37 exhibited staged failure under rainstorm: “strain localization at fissure tips—penetration of basal cracks—overturning of the upper rock mass”. Its frontal rock reached a peak sliding velocity of 15.17 m/s, indicative of base-breaking toppling. The integrated “multi-technology survey—multi-method evaluation—multi-scale simulation” framework provides a quantitative basis for risk assessment of rock mass disasters in the Three Gorges Reservoir Area and offers a technical paradigm for similar high-steep canyon regions. Full article

Background: Immune checkpoint inhibitors (ICIs) improve cancer outcomes but may cause cardiovascular toxicity, including early subclinical myocardial injury. Conventional echocardiography has limited sensitivity, whereas speckle-tracking echocardiography (STE) allows for early detection of myocardial deformation. Data on short-term ICI-related effects on biventricular mechanics are limited, and atrial function remains poorly characterized. This study evaluated the early impact of ICI therapy on biventricular and biatrial mechanics using STE in patients with advanced cancer. Methods: In this prospective, single-center study, 28 consecutive patients with advanced cancer undergoing ICI therapy were followed for 3 months. Clinical, laboratory, electrocardiographic, and echocardiographic assessments were performed at baseline, 1 month, and 3 months. STE was used to assess left ventricular global longitudinal strain (LV-GLS) and circumferential strain; right ventricular GLS (RV-GLS); and left and right atrial reservoir, conduit, and contractile strain parameters. Subclinical LV dysfunction was defined as a relative LV-GLS reduction >15%. Logistic and Cox regression analyses identified predictors of strain impairment and adverse clinical events. Results: Conventional echocardiographic parameters, including left ventricular ejection fraction, remained stable. In contrast, LV-GLS declined progressively from 20.7 ± 2.1% to 17.6 ± 2.7% at 3 months (p = 0.002), with subclinical LV dysfunction observed in 85.7% of patients. RV-GLS also deteriorated despite preserved TAPSE. Both left and right atrial strain and strain-rate parameters showed an early and marked decline, accompanied by increased left atrial stiffness despite unchanged atrial volumes. Older age and higher neutrophil-to-lymphocyte ratio (NLR) were associated with LV-GLS impairment. Over a mean follow-up of 5.4 ± 3 months, baseline LV-GLS independently predicted adverse clinical events and mortality. Optimal cut-off values were 67 years for age, 4 for NLR, and 19.5% for LV-GLS. Conclusions: Short-term ICI therapy is associated with early, diffuse subclinical myocardial dysfunction involving both ventricles and atria, detectable only by STE. Comprehensive biventricular and biatrial strain assessment may enhance early cardio-oncology surveillance and risk stratification in ICI-treated patients. Full article

Shiga toxin-producing Escherichia coli (STEC) is a zoonotic pathogen of public health concern, requiring a One Health approach to clarify its transmission and distribution. However, its prevalence and genomic characteristics in livestock and companion animals remain underexplored in low-income countries. We investigated prevalence and genomic features of STEC in animals in western Ghana, representing the first genomic report of STEC in Ghana. Fecal samples (97) were collected from goats (n = 33), sheep (n = 33), dogs (n = 30), and a cat (n = 1), with STEC detected in 12.1% of goats and sheep samples. Whole-genome sequencing identified serotypes O38:H26, O43:H2, and O157:H7. stx1c and stx2b genes were detected in O38:H26 and O43:H2, whereas stx2c and key virulence genes (chuA, eae, esp, nle, tir, and toxB) were exclusively found in O157:H7. Phylogenetic analysis revealed that O38:H26 isolates form a cluster closely related to clinical strains from the UK. O43:H2 isolates exhibited diverse stx profiles, linking animal, environmental, and clinical strains from North America and the UK. O157:H7 isolates were genetically similar to European clinical and food-derived strains, suggesting that goats and sheep are important STEC reservoirs in Ghana, offering data for public health risk assessment and effective One Health-based control strategies. Full article

Background: Cardiac amyloidosis is characterized by progressive myocardial and atrial infiltration, leading to atrial mechanical dysfunction, atrial fibrillation, and thromboembolic complications. Left atrial (LA) strain is an established marker of atrial function; however, data on triplane LA strain in cardiac amyloidosis are limited. Methods: We evaluated transthoracic echocardiographic examinations of 24 patients with cardiac amyloidosis and 24 age-, sex-, rhythm-, and ejection fraction-matched control subjects (9 with atrial fibrillation in each group). Among amyloidosis patients, 21 had transthyretin and 3 had light-chain cardiac amyloidosis. All examinations were performed during 2025. Triplane and biplane LA reservoir strain were assessed using speckle-tracking echocardiography. Two-way analysis of variance tested the effects of disease (amyloidosis vs. control) and rhythm (sinus rhythm vs. atrial fibrillation). Agreement between triplane and biplane measurements was evaluated using Pearson correlation and Bland–Altman analyses. Results: Triplane LA reservoir strain was significantly lower in patients with cardiac amyloidosis compared with controls (6.7 ± 2.7% vs. 16.2 ± 8.3%, p < 0.001). Even in sinus rhythm, amyloidosis patients demonstrated markedly impaired LA strain, with mean values similar to those observed in control subjects with atrial fibrillation. Two-way ANOVA revealed significant main effects of disease (F = 68.9, p < 0.0001) and rhythm (F = 45.0, p < 0.0001), as well as a significant disease–rhythm interaction (F = 26.5, p < 0.0001). Triplane and biplane LA strain showed strong correlation (r = 0.90, p < 0.0001) with good agreement. Reproducibility was excellent (intra-observer ICC = 0.97; inter-observer ICC = 0.94). Conclusions: Triplane LA reservoir strain is markedly reduced in cardiac amyloidosis and enables comprehensive visualization of atrial mechanical dysfunction. The technique demonstrates high reproducibility and strong agreement with biplane analysis, supporting its use as a complementary tool for characterizing amyloid atriopathy. Full article