Pseudomonas aeruginosa remains a major cause of healthcare-associated infections worldwide, with clinical management increasingly compromised by the emergence and dissemination of multidrug-resistant (MDR) and extensively drug-resistant (XDR) lineages. In this study, we evaluated the antibacterial and antibiofilm activity of purified S-type pyocins (AP41, SX1, SX2, G, S5, and M1) against a panel of 29 MDR or XDR clinical P. aeruginosa isolates collected from across Thailand in 2021–2022, integrating phenotypic data with comparative genomic analyses. Susceptibility screening using overlay spot assays identified AP41, SX1, and SX2 as the pyocins with the broadest activity. These pyocins exhibited potent killing activity across MDR and XDR isolates, including strains resistant to last-resort antibiotics such as carbapenems and colistin. Minimum inhibitory concentration assays demonstrated high antibacterial potency, with AP41 and SX1 achieving inhibitory activity at low concentrations within the microgram range. In biofilm eradication experiments, AP41, SX1, and SX2 produced dose-dependent reductions in the metabolic activity of established biofilms, indicating efficacy against both planktonic and biofilm-associated cells. Whole-genome analysis of a combined dataset comprising Thai clinical P. aeruginosa genomes retrieved from the National Center for Biotechnology Information (NCBI) Pathogen Detection database, together with genomes from isolates included in this study ( n = 105), revealed that pyocin transporter genes were widely conserved, whereas repertoires of genes encoding pyocins and determinants of cognate immunity to them displayed marked heterogeneity and strong lineage association. Notably, the transporter gene associated with SX1 and SX2 uptake ( crtA ) was conserved across the genome dataset, while no genes conferring cognate immunity against SX1 or SX2 were identified. This suggested that SX1 and SX2 retain activity across a broad range of isolates. Collectively, these findings demonstrate that pyocins exhibit potent antibacterial and antibiofilm activity against MDR and XDR P. aeruginosa , underscoring their potential as candidates for the development of alternative antimicrobial therapies.
Background This study aimed to investigate the associations of senescence-associated secretory phenotype (SASP)-related genes with the tumor immune microenvironment (TIME) and clinical outcomes in lung adenocarcinoma (LUAD) and to develop and evaluate a prognostic signature for risk stratification and exploratory treatment-response prediction. Methods Non-negative matrix factorization (NMF) was conducted to identify distinct molecular subtypes. Least absolute shrinkage and selection operator (LASSO), Random Forest, and extreme gradient boosting (XGBoost) were utilized to identify core prognostic SASP genes. The expression patterns of selected SASP-related genes were explored using multi-omics datasets, LUAD cell lines, and clinical specimens. Results Cluster 1 was associated with significantly shorter overall survival (OS), enhanced senescence pathway activity, and computationally inferred immunosuppressive and immune-exclusion features. Five intracellular SASP regulators— ANGPTL4 , CDKN2A , H2AX , MMP1 , and CCL20 —were selected through machine learning to construct the SASP Protein Regulator Score (SASP-PRS). A high SASP-PRS was associated with the activation of senescence/SASP and cell-cycle pathways, suppression of antitumor immune signatures, and distinct immune-checkpoint and chemokine expression profiles. A higher SASP-PRS was also associated with advanced disease stage, poorer OS, predicted lower responsiveness to immunotherapy, lower predicted sensitivity to erlotinib, and higher predicted sensitivity to selected chemotherapeutic agents. The nomogram incorporating the SASP-PRS demonstrated discriminatory ability and calibration for predicting 1-, 3-, and 5-year OS in the analyzed LUAD cohorts. Conclusion These findings suggest that SASP-related gene-expression patterns are associated with LUAD molecular subtypes, senescence signaling, computationally inferred immune features, and treatment-related outcomes. The SASP-PRS may serve as a potential biomarker for prognostic stratification in LUAD. However, its utility for treatment-response assessment remains exploratory. Prospective external validation and functional studies are required to establish its clinical applicability and clarify the mechanisms linking SASP-related networks to the LUAD immune microenvironment.
A new naturally occurring polyketide, pseurotin A 3 -10,11-acetonide (1), along with two known analogs, pseurotin A (2) and pseurotin A 3 (3), was isolated from the culture broth of Streptomyces sp. CSDX076. The structures of these compounds were determined by extensive 1D and 2D nuclear magnetic resonance (NMR), ultraviolet (UV), and high-resolution electrospray ionization mass spectrometry (HRESIMS) spectroscopic analyses. All isolated compounds (1-3) were evaluated for antimicrobial activity against a panel of seven pathogenic strains using disc diffusion and broth microdilution methods. Notably, compound 1 exhibited moderate activity against Brucella melitensis with a minimum inhibitory concentration (MIC) of 8.0 μg/mL, while compound 2 showed weak activity against Staphylococcus epidermidis (MIC = 128.0 μg/mL); compound 3 was inactive against all tested strains. This study reports, for the first time, the antibacterial effects of these compounds against the respective pathogens.
Background/objectives While the association between food quantity and obesity is well studied, the impact of diet components on specific body compartments is less well understood. Furthermore, there seem to be sex differences in the metabolism of different foods and the response towards physical activity (PA). Methods We investigated the association between diet components using a food frequency questionnaire, and body composition using bioimpedance analysis. We assessed data from 2021 of a cohort study of the Swiss general population, including 435 persons of both sexes (age range of 19–84 years). We used multivariable linear regression models separated by sex to assess the association between body composition (body mass index (BMI), skeletal muscle mass index (SMI), fat mass index (FMI), and visceral fat (VAT)), and diet quality and PA. Age, education, and place of residence were included as potential confounders. Results For both sexes, age showed the strongest positive association with FMI and VAT, while PA was negatively associated, especially in men. In men PA was also associated with BMI (not in women). Diet quality showed associations with body composition measures in women (not in men). In women, meat consumption was positively associated with SMI and FMI (not in men). In men fruits and wholegrain foods were negatively associated with FMI. VAT was negatively associated with fruits in women, and with fruits and wholegrain foods in men. Conclusion Our results are in line with evolutionary hypotheses on sex specific energy allocation and might contribute to more precise diet recommendations.
The foot is a multi-segment structure whose segments function together. Due to its ongoing connection with the support surface, the foot must be capable of managing loads that vary with gait speed. Previous studies have provided considerable insight into the relationship between foot joint kinematics and gait speed. However, their primary reliance on discrete measures, such as peak joint angles, has limited understanding of how these relationships evolve throughout the stance phase. The aim of this study was to investigate the effects of gait speed on full time-series trajectories of multiplanar foot joint kinematics using statistical parametric mapping. According to our findings, faster walking primarily increased ankle eversion and midfoot dorsiflexion during weight acceptance (∼17–29% of the stance phase). In contrast, during propulsion, faster walking increased ankle plantar flexion (∼80–100% of the stance phase) and inversion (∼82–90%), as well as midfoot plantar flexion (∼82–100%) and adduction (∼90–98%), together with greater dorsiflexion of the first metatarsophalangeal joint after heel-off (∼43–98% of the stance phase). These multiplanar joint kinematic alterations across the ankle–foot joints throughout the stance phase reflect greater foot-arch collapse in early stance and foot-arch recoil in late stance, which may facilitate appropriate energy absorption and generation in response to increasing gait speed. Importantly, these adaptive foot motions were not captured by previous discrete analyses, which may obscure phase-dependent changes during gait. The present continuous time-series approach revealed detailed temporal adaptations in foot kinematics across the stance phase, providing a more comprehensive characterization of gait mechanics.
