Long-term exposure to fine particulate matter (PM2.5) is associated with respiratory and cardiovascular diseases. PM2.5 consists of a complex mixture of organic and inorganic species, with toxicity varying based on its chemical composition, sources, and physicochemical properties. This study investigates the oxidative potential (OP), cellular oxidative stress, and inflammatory response induced by five distinct chemical fractions of urban PM2.5: water-soluble total, water-soluble metals, water-soluble non-metal, lipid-soluble, and total PM2.5 extract. We also analyzed the synergistic and antagonistic interactions among these fractions contributing to overall PM2.5 toxicity. Comprehensive chemical characterization and OP analysis of PM2.5 extracts revealed that metals primarily drive dithiothreitol (DTT) consumption, while organics predominantly contribute to hydroxyl radical (∙OH) generation. Notably, high PM2.5 samples exhibited significant antagonistic interactions between water-soluble metals and organic fractions in the generation of ∙OH. The water-soluble total fraction induced the highest levels of TNF-α secretion and upregulated the expression of genes associated with inflammation and oxidative stress, including Cxcl2, Hmox-1, and Cyp1a1, emphasizing its dominant role in PM2.5-induced cytotoxicity. Synergistic upregulation of Hmox-1 expression was observed between water-soluble metals and non-metal fractions, whereas Cxcl2 expression was antagonistically modulated. Conversely, the lipid-soluble fraction exhibited an antagonistic effect on TNF-α secretion and oxidative stress gene expression relative to the water-soluble total fraction. These findings highlight the pivotal role of water-soluble components in PM2.5 toxicity and provide a comprehensive framework for understanding the individual and combined effects of chemical fractions on PM2.5-induced toxicity, which is vital for accurately assessing its impact on human health.

Critical windows and joint effects of prenatal heat and relative humidity exposure on stillbirth: A prospective longitudinal cohort study.

The lateral migration of bubbles in wall-bounded shear flows arises from the interaction between wall-induced and shear-induced forces, yet the combined effect has remained insufficiently investigated. In this study, we conduct dedicated bubble column experiments with a controlled shear field and wall proximity to investigate the dynamics of single bubbles rising near a vertical wall over a wide range of Eötvös numbers ( E o ). In the first stage, we isolate the wall-induced effect under stagnant water conditions: bubble rise velocity is reduced in the vertical direction but enhanced laterally. A wall force coefficient ( C W 3 ) is established that increases linearly with E o for low-viscosity systems. In the second stage, we examine the combined effect under wall-shear conditions. Two scenarios are considered and evaluated, where the bubbles show distinct behaviors: (i) cooperative cases, where both lateral forces act in concert to enhance migration away from the wall; and (ii) antagonistic cases, where they oppose each other, suppressing lateral motion. This work bridges a long-standing gap in bubbly flow hydrodynamics by providing a closure model that integrates wall and shear contributions in both bounded and unbounded conditions. • Measurements quantify combined wall-shear effects on deformable bubbles. • Distinct cooperative and antagonistic interaction mechanisms are identified in wall-bounded shear flows. • Near-wall lift amplification follows an exponential decay with respect to the dimensionless wall distance. • A closure model for the lift coefficient covering both bounded and unbounded conditions is proposed.

Straw-Degrading microbiota Exhibit a pivotal ecological function in pathogen elimination for composting with corn straw addition.

Metabolite profiling of the effect of prenatal stimuli across postnatal treatments in the liver.

Windows of susceptibility and the modifying role of residential greenness in the association between prenatal exposure to non-optimal temperatures and infant BMIZ trajectories.

Smallholder subsistence farmers dominate banana ( Musa spp.) production across East and Central Africa, yet their yields are constrained by a suite of co-occurring biotic threats. Three major diseases, Xanthomonas wilt (XW), Fusarium wilt (FW), and banana bunchy top disease (BBTD) threaten productivity. These are compounded by two established pests (black weevil, plant-parasitic nematodes) and an emerging pest (banana thrips). Integrated pest and disease management (IPDM) protocols aim to mitigate these challenges by coupling disease-specific interventions with broader agronomic practices. While individual IPDM packages share core components, including biosecurity, accurate diagnosis, roguing, clean planting material, resistant cultivars, vector avoidance, and judicious chemical control, their efficacy can be compromised when multiple threats coexist. Synergistic or antagonistic interactions may arise under these conditions. Part 1 of this review synthesizes current literature on the core components of IPDM strategies for these six biotic stresses, highlighting commonalities and divergences among the recommended packages. In Part 2, it further evaluates the role of standard cultural and agronomic practices in disease-pest management outcomes. These include crop diversification, weed management, planting density, sucker and leaf removal, tillage, mineral and organic fertilization, biocontrol, mulching, pest suppression, and irrigation. By identifying compatibilities and incompatibilities in management when biotic constraints co-occur, and by addressing knowledge gaps across the various protocols, the review provides actionable insights for designing holistic extension programs that harmonize prevention and control measures. As such, IPDM programs should be better equipped to avoid unintended trade-offs and enhancing resilience in banana systems where these threats co-occur.

Molecular and hormonal regulation of plant responses to waterlogging stress: From fundamental mechanisms to potential strategies of crop tolerance engineering.

Warming fluctuating temperature shifts the BPA-damage threshold of a freshwater microplankton community.

Cardiovascular disease (CVD) remains a leading cause of mortality in China. The triglyceride-glucose (TyG) index and body roundness index (BRI)-have separately shown associations with CVD risk, but their interaction, as well as their combined effects and interplay with inflammatory markers remain unclear. We conducted a prospective cohort study using data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2020. A total of 7,853 participants without pre-existing CVD were included. We examined mediation, cross-lagged path, interaction and joint association analysis to explore the interrelationships between TyG and BRI on CVD. Cox proportional hazards models and restricted cubic spline analysis, receiver operating characteristic (ROC), and weighted quantile sum (WQS) were performed to further investigate the associations between TyG, BRI, and CVD. During a median follow-up of 9.0years, 1,922 participants (24.48%) developed CVD. In fully adjusted models, baseline BRI mediated 40.14% of the association between baseline TyG and CVD risk, with an indirect effect HR of 1.053 (95% CI: 1.035-1.073). Follow-up BRI mediated 51.46% of the association between baseline TyG and CVD risk, with an indirect effect HR of 1.046 (95% CI: 1.028-1.068). Per standard deviation increase in baseline BRI led to an average increase of 0.12 standard deviation in follow-up TyG levels. A significant antagonistic interaction was observed, aligned with the finding that the combination of low TyG and high BRI presents the highest CVD risk. Additionally, WQS analysis highlights waist circumference (WC) as the most substantial contributor (weight = 0.523). Joint elevation of composite indexes (TyG-BRI and TyG + BRI) with hs-CRP further stratified CVD risk, with participants having elevated levels of all markers showing the highest risk. Composite indexes, particularly TyG + BRI, showed the highest CVD risk (HR: 1.773, 95% CI: 1.499-2.097), along with the limited discriminatory ability on CVD (AUC < 0.65). In conclusion, our study highlights the critical role of BRI as a mediator in the relationship between TyG and CVD risk. The findings indicate that both baseline and follow-up BRI significantly contribute to the pathway linking TyG to CVD, suggesting that individuals with higher BRI are at an increased risk. The antagonistic interaction underscores the complexity of metabolic risk factors in CVD development and emphasizes the need for a multifaceted approach in risk assessment and management. Future research should focus on elucidating the biological mechanisms underlying this interaction and exploring potential interventions that target body composition and metabolic health to mitigate CVD risk in high-risk populations.

The increasing demand for sustainable agricultural production has intensified the search for environmentally friendly strategies capable of mitigating soil degradation, climate-related stresses, heavy metal contamination, and the rising resistance of phytopathogens to conventional chemical control methods. In this context, the integration of soil amendments and biological control agents has emerged as a promising approach for enhancing plant health and maintaining soil functionality. This review critically evaluates the potential of biochar and microbial biological control agents as complementary tools for improving soil quality and suppressing plant diseases in agricultural systems. Biochar, a carbon-rich material produced through the pyrolysis of biomass under limited oxygen conditions, has gained considerable attention due to its ability to improve soil physicochemical properties, including soil structure, nutrient retention, pH regulation, and water-holding capacity. These improvements contribute to the development of a favorable rhizosphere environment that promotes beneficial microbial activity and enhances soil microbial diversity. In addition to its direct effects on soil properties, biochar plays a crucial role in the suppression of diverse plant pathogens, including fungi, bacteria, nematodes, oomycetes, and viruses, through both direct antagonistic interactions and indirect mechanisms such as the stimulation of plant defense pathways, including systemic acquired resistance (SAR) and induced systemic resistance (ISR). Recent studies further indicate that the combined application of biochar with microbial biological control agents, particularly members of the genera Trichoderma, Bacillus, and Pseudomonas, can significantly enhance microbial colonization, persistence, and antagonistic activity within the rhizosphere. This synergistic interaction leads to more consistent and effective disease suppression compared with single applications. Furthermore, the integration of biochar and beneficial microorganisms contributes to improved plant tolerance against abiotic stresses such as drought, salinity, and heavy metal toxicity while simultaneously supporting soil fertility and crop productivity. Despite these promising outcomes, variations in biochar characteristics and the limited number of long-term field studies highlight the need for standardized application strategies and further mechanistic research to optimize the biochar–microbial interaction for sustainable agricultural systems

Coal ash disposal poses a significant environmental risk due to the potential leaching of toxic elements into surrounding ecosystems. Here, we analysed the phytotoxic effect of two coal ash disposal sites after 50 years of weathering to evaluate whether coal ash remains toxic after long-term disposal and whether vegetated areas are less toxic than bare ones. To analyse that, a combination of multielement analysis of coal ash and eluates and two bioassays-seed germination and Allium test-was used. Multielement analysis revealed that some samples exceed the World Health Organization's drinking water thresholds; however, biological responses did not consistently align with the total element concentrations. Seed germination was inhibited in 7 out of 12 samples, most strongly in soil and bare ash eluates from both sites. The Allium-based cytogenetic assay showed high mitotic inhibition and genotoxicity in most eluates. Correlation analyses linked Al, As, and V with increased chromosomal aberrations. However, the potential for synergistic or antagonistic interactions among elements complicates the straightforward predictions of toxicity based on concentration alone. Overall, these results advocate for the integration of biological endpoints with chemical data and highlight the persistent toxicity of coal ash even after 50 years of weathering.

Cadmium (Cd) contamination in paddy soils threatens rice production and food safety. This study investigated the effects of manganese (Mn)-enriched biochar on soil Cd immobilization and Cd accumulation in rice using a pot experiment with Cd-contaminated soil. Unenriched biochar and Mn-enriched biochar prepared from rice straw were applied at two rates (0.5% and 1.0%). Both biochar types significantly increased soil pH and organic matter and promoted the transformation of Cd from labile fractions to more stable residual forms, thereby reducing Cd bioavailability. As a result, Cd accumulation in rice tissues, including straw and brown rice, was significantly reduced. Correlation analysis further indicated that increased soil pH was associated with reduced Cd mobility and plant uptake. Mn-enriched biochar markedly increased Mn accumulation and uptake efficiency in rice while decreasing Cd uptake efficiency, indicating a strong antagonistic interaction between Mn and Cd in the soil-plant system. Notably, a low application rate of Mn-enriched biochar (0.5%) achieved Cd reduction effects comparable to those of a higher dose of unenriched biochar (1.0%). These results suggest that Mn-enriched biochar is an effective and potentially cost-efficient strategy for reducing Cd bioavailability in paddy soils and mitigating Cd accumulation in rice.

Certain bacteria are known for their remarkable genetic and phenotypic diversity, as well as rapid morphological diversification during evolution experiments. An example is Bacillus subtilis, which can switch motility, biofilm, or antagonistic interaction patterns. Here, we investigated how different forms of disruption at the spsM locus, including SPβ integration, insertional mutagenesis (spsM::kan), and markerless spsM deletion, influence colony morphology, motility, and the emergence of spontaneous variants in B. subtilis natural isolates. We reassessed a previously reported biofilm defect of an spsM::kan mutant and found that the phenotype stemmed from an undetected secondary mutation rather than from loss of spsM. We observed that spsM::kan mutants frequently developed spontaneous mutations in key regulators of swarming motility and biofilm development. Consistently, we show that spsM::kan significantly elevates mutation rates, explaining why unnoticed mutations can arise rapidly during strain construction and phenotyping. In contrast, a markerless ΔspsM strain did not show a detectable increase in mutation rate relative to wild type, indicating that the elevated mutation rate is not attributable to loss of SpsM function. The SPβ lysogen produced far fewer visible variant morphotypes, indicating that reversible prophage integration does not lead to the same degree of diversification observed in the spsM::kan background. Our findings show that different modes of disrupting the spsM locus can alter the likelihood of selecting recurrent regulatory mutations, highlighting how local genomic context shapes phenotypic diversification. This work highlights the interplay between prophage integration, local genome architecture, and the selective pressures that influence diversification of bacterial multicellular behaviors.IMPORTANCEProphages, defined as viruses integrated into bacterial genomes, can reshape bacterial physiology and evolution. Previous studies suggested that disruption of an integration site (spsM) by the SPβ prophage impairs biofilm formation in Bacillus subtilis. Here, we show that insertion of a kanamycin resistance cassette at the native spsM locus (spsM::kan) promotes the rapid emergence of spontaneous mutations in key regulatory genes. In contrast, a markerless ΔspsM strain does not show a detectable increase in mutation rate, indicating that elevated mutation supply is not a general consequence of spsM loss. Our results indicate that different modes of spsM disruption have distinct consequences for phenotypic diversification. These findings help clarify earlier observations and show that phenotypic diversification depends strongly on the mode of spsM disruption and the genetic background. This has broader implications for how we understand the genetic basis of microbial adaptation, the genetic manipulation, and the evolutionary roles of prophages.

Francisella tularensis is a highly virulent intracellular pathogen for which treatment options remain limited and vulnerable to resistance development. Tolfenpyrad, a pesticide with selective antibacterial activity against Francisella species, has emerged as a promising compound, yet its mechanism of action remains poorly defined. Here, we investigated how tolfenpyrad modulates the activity of established antibiotics and probed its effects on bacterial energy metabolism in Francisella. In this study, we used combinatorial drug experiments to identify both synergistic and antagonistic drug-drug interactions. Tolfenpyrad synergized with polymyxin B and azithromycin to inhibit Francisella novicida in vitro, and this synergistic activity was also observed with azithromycin in an intramacrophage infection model, resulting in enhanced bacterial clearance. In contrast, tolfenpyrad antagonized aminoglycoside and tetracycline-class antibiotics, restoring bacterial survival under otherwise inhibitory conditions. Consistent with this antagonism, tolfenpyrad attenuated uptake of tetracycline and doxycycline, suggesting that it may disrupt proton motive force-dependent transport. Supporting this model, tolfenpyrad synergized with multiple electron transport chain inhibitors in F. novicida and in F. tularensis, and reduced ATP levels in F. novicida. Collectively, these data indicate that tolfenpyrad disrupts bacterial energy metabolism in Francisella, likely impairing oxidative phosphorylation and proton motive force generation. These findings define a mechanistic framework for tolfenpyrad's antibacterial activity and highlight its potential as an inhibitor of Francisella bioenergetics and a potential partner in combinatorial antibiotic therapies.

Propolis and plant-derived oils are currently being investigated as alternative sources against increasing antibiotic resistance. For this purpose, in this study, the antifungal activity of propolis ethanol extract and lemon oil, orange oil (obtained from 2 different producers), garlic oil, black grape seed oil, grape seed oil, pomegranate seed oil, black cumin oil, rosemary and thyme oils was evaluated against Candida albicans and Pichia manshurica and Candida albicans ATCC 10231 yeasts isolated from the human oral cavity. Antifungal activity was determined by the agar well diffusion method, and the results were statistically evaluated. Among the oils tested, rosemary and oregano oil exhibited the highest antifungal activity, forming inhibition zones ranging from 15.53 ± 3.28 to 39.25 ± 2.02 mm against the tested yeasts. No activity was detected in the other oils tested. Propolis was found to be as effective as amphotericin B antifungal (with inhibition zones between 16.31 ± 0.16 and 25.44 ± 1.34 mm), with inhibition zones ranging from 20.85 ± 0.95 to 25.95 ± 1.22 mm. In 1:1 mixtures of oils with propolis, antifungal activity increased compared to the oils used individually but decreased compared to propolis alone. Indeed, in mixtures of rosemary and oregano oils with propolis, inhibition zones ranged from 16.88 ± 2.75 to 34.06 ± 1.57 mm, with inhibition zones reduced compared to those observed with the oils used individually. Therefore, a potential antagonistic interaction was determined between the tested oils and propolis (P&amp;lt;0.001). In conclusion, while it might be assumed that combinations of natural substances strategically increase activity, this is not always the case. Therefore, it is necessary to investigate the effects of combining natural substances on biological activity.

Cholangiocarcinoma (CCA) is a highly aggressive malignancy with limited treatment options and frequent chemoresistance. Peanut hairy root culture crude extract (PCE) has previously demonstrated selective cytotoxicity toward CCA cells. Here, we investigated the combinatorial effects of PCE with standard chemotherapeutic agents on CCA cell lines. In KKU-213A cells, PCE exhibited antagonistic and additive interactions with gemcitabine (Gem) and 5-fluorouracil (5-FU), respectively. In contrast, both combinations showed synergistic effects in KKU-100 cells, with the strongest synergy observed for PCE and Gem. Further investigation in KKU-100 cells revealed that the PCE-Gem combination significantly induced apoptosis, as evidenced by increased levels of cleaved caspase-8, caspase-3, and PARP, without affecting cell cycle progression. Notably, no cytotoxic effect was observed in normal human fibroblasts (HSF-hTERT). In a nude mouse xenograft model, co-treatment with PCE and Gem significantly inhibited tumor growth and reduced Ki-67 expression compared to monotherapies. These findings suggest that PCE enhances the anticancer efficacy of Gem in CCA and may serve as a supportive combinatorial strategy.

Lithium-sulfur (Li-S) batteries are a promising next-generation energy storage solution, as they can reduce reliance on critical transition metals while offering high energy densities. However, their deployment is hindered by low sulfur utilization and the formation/diffusion of lithium polysulfides (LiPSs). While transition-metal catalysts and polymeric binders have been independently developed to enhance redox kinetics and LiPS adsorption, their mutual compatibility has remained largely unexplored. We show here that binder-catalyst interactions can significantly impact catalytic performance. Employing TiO2 as a generic catalyst, the electrochemical performance is shown to depend strongly on the binder environment. TiO2 paired with lithiated polyacrylic acid (LiPAA) shows benign interactions, resulting in enhanced cycle life. In contrast, pairing TiO2 with protonated PAA produces antagonistic interactions that hinder Li2S growth. A mechanistic analysis unveils that the carboxylic H atom in PAA promotes COO- coordination to Ti sites, occupying catalytic centers and suppressing LiPS adsorption, increasing charge transfer and diffusion resistances. This phenomenon is observed across multiple catalysts, indicating that COOH-functionalized binders may broadly hinder catalytic activity. Overall, this study underscores the need for holistic cathode design and identifies binder-catalyst compatibility as an important parameter for high-performance Li-S batteries.

DNA methylation is a widespread but incompletely characterized regulatory feature of bacterial genomes. While restriction-modification systems represent well-studied sources of DNA methylation, the full complement of methyltransferases shaping bacterial epigenomes and their physiological consequences remain poorly understood. Here, we used Oxford Nanopore sequencing to comprehensively map DNA methylation in the model oral pathogen Streptococcus mutans UA159. Genome-wide analysis identified extensive N6-methyladenosine (6mA) modification and revealed three predominant methylation motifs. Using targeted deletion mutants, we demonstrate that methylation at GATC sites is mediated by the conserved DpnII restriction-modification system, while a novel bipartite CGANNNNNNNTCY/RGANNNNNNNTCA motif is methylated by the HsdM component of the type I Hsd restriction-modification system. The remaining 6mA sites corresponded to a CTGNAG/CTNCAG motif, defining the activity of a third methyltransferase. Genetic and epigenomic analyses identified SMU.43 as the enzyme responsible for this modification, which we designate DnmA, a novel orphan adenine methyltransferase with homology to regulatory methyltransferases rather than defense-associated systems. Functional characterization of single and double mutants revealed that distinct methylation systems differentially influence biofilm formation and antagonistic interactions with the commensal, Streptococcus sanguinis . Notably, loss of dnmA reversed biofilm and aggregation defects associated with deletion of dpnII , indicating epistatic interactions between methylation pathways. Together, this study resolves the major sources of DNA methylation in S. mutans UA159, identifies a novel regulatory methyltransferase, and highlights the utility of nanopore sequencing for bacterial epigenome discovery. These findings expand our understanding of bacterial DNA methylation and suggest that epigenomic enzymes may represent targets for modulation of microbial physiology and virulence.

Ochratoxin A (OTA) and citrinin (CIT) are mycotoxins that frequently co-contaminate food, posing a significant risk of co-exposure. This study aimed to explore the renal injury effects of the co-exposure of these two mycotoxins, including the types of co-effects of OTA and CIT and their impact on endoplasmic reticulum stress (ERS) by utilizing a constructed 3D renal microsphere model (HK-2: EA.hy926: HEK293T = 4:1:1). In the renal microsphere model, co-exposure to OTA and CIT exhibited an antagonistic interaction at all tested concentrations (CI = 1.12-1.24). Mechanistically, co-exposure induced mitochondrial dysfunction and reactive oxygen species imbalance and activated the ERS pathway. ERS further amplified the inflammatory response, leading to increased secretion of pro-inflammatory cytokines. Transcriptome analysis indicates that the Hippo signaling pathway also contributes to the promotion of cellular damage. Our findings reveal a complex toxicological interaction between OTA and CIT and highlight the critical role of physiologically relevant models in ensuring accurate risk assessment.