Significant Antagonistic Effect Research Articles

Multifaceted toxicity assessment of Au, Ag, and TiO2 nanoparticles synthesized by quorum quenching bacterium Salmonella bongori: Impact on bacterial pathogens, cancer cells, mosquitoes, zebrafish, and brine shrimp

The present study pertained to evaluate biological properties of the nanoparticles synthesised using quorum quenching-QQ Salmonella bongori-SB. The QQ potential of SB was confirmed through streaking (halos) and diffusing cell-free-supernatant (decolored) against Chromobacterium violaceum-CV and significant antagonistic effect on Pseudomonas aeruginosa-PA and P. fluorescens-PF. HPLC peaks confirmed the degradation of 3-oxo-C12-HSL (3.185) by QQ-SB at 2.579 and 2.924. The morphological characteristics-(crystallite size; shape with size range), and significant antibacterial-ABA, antibiofilm-ABFA and anti-proliferative-APA (with IC50 values on HeLa and A549 cells) activities of different-NPs were recorded as follows: SB-AuNPs (31.61 nm; aggregated spherical (13.66–18.38 nm)) resulted in good ABA (on PF and Serratia marcescens), ABFA (on PF) and APA (IC50: 33.79 and 33.74 µgmL−1). Similarly, SB-AgNPs (19.83 nm; clustered spherical; 4.81–8.58 nm) showed the most-significant ABA (CV and PF), ABFA (PA, CV and PF) and APA (IC50: 24.57, and 22.7 µgmL−1). Whereas, SB-TiO2NPs (47.33 nm; spherical with 75.13 nm) did not produced significant activities. Overall, the first report on the QQ potential of SB and its NPs emerged to be good candidate that might combat the pragmatic difficulties against MDR strains and drug failures in cancer treatments. Therefore, standardizing its applications in quorum sensing inhibitory mechanisms and anti-proliferative effects is warranted.

The dominant influencing factors of desertification and ecological risk changes in Qinghai Area of Qilian Mountains National Park: Climate change or human activity?

Transitional features of desert environments partially determine the risks associated with ecosystems. Influenced by climate change and human activities, the variability and uncertainty of desertification levels and ecological risks in the Qinghai Area of Qilian Mountain National Park (QMNPQA) has become increasingly prominent. As a critical ecological barrier in northwest China, monitoring desertification dynamics and ecological risks is crucial for maintaining ecosystem stability. This study identifies the optimal monitoring model from four constructed desertification monitoring models and analyzes spatiotemporal changes in desertification. The spatial and temporal changes in ecological risks and their primary driving factors were analyzed using methods such as raster overlay calculation, geographic detector, cloud model, and trend analysis. The main conclusions are as follows: The desertification feature spatial model based on GNDVI-Albedo demonstrates better applicability in the study area, with an inversion accuracy of 81.24%. The levels of desertification and ecological risks in QMNPQA exhibit significant spatial heterogeneity, with a gradual decrease observed from northwest to southeast. From 2000 to 2020, there is an overall decreasing trend in desertification levels and ecological risks, with the decreasing trend area accounting for 89.82% and 85.71% respectively, mainly concentrated in the southeastern and northwestern parts of the study area. The proportion of areas with increasing trends is 4.49% and 7.05% respectively, scattered in patches in the central and southern edge areas. Surface temperature (ST), Digital Elevation Map (DEM), and Green normalized difference vegetation index (GNDVI) are the most influential factors determining the spatial distribution of ecological risks in QMNPQA. The effects of management and climatic factors on ecological risks demonstrate a significant antagonistic effect, highlighting the positive contributions of human activities in mitigating the driving effects of climate change on ecological risks. The research results can provide reference for desertification prevention and ecological quality improvement in QMNPQA.

Multifactorial inhibition of Candida albicans by combinations of lactobacilli and probiotic Saccharomyces cerevisiae CNCM I-3856

Strategies against the opportunistic fungal pathogen Candida albicans based on probiotic microorganisms represent a promising alternative to traditional antifungals. Here, we investigated the effects of Lactobacillaceae isolates from fermented foods or the human vagina, alone or in combination with the probiotic yeast Saccharomyces cerevisiae CNCM I-3856, against C. albicans in vitro. Nine out of nineteen tested strains of Lactobacillaceae inhibited growth of C. albicans with inhibition zones of 1–3 mm in spot assays. Five out of nineteen lactobacilli tested as such or in combination with S. cerevisiae CNCM I-3856 also significantly inhibited C. albicans hyphae formation, including Limosilactobacillus fermentum LS4 and L. fermentum LS5 resulting in respectively 62% and 78% hyphae inhibition compared to the control. Thirteen of the tested nineteen lactobacilli aggregated with the yeast form of C. albicans, with Lactiplantibacillus carotarum AMBF275 showing the strongest aggregation. The aggregation was enhanced when lactobacilli were combined with S. cerevisiae CNCM I-3856. No significant antagonistic effects were observed between the tested lactobacilli and S. cerevisiae CNCM I-3856. The multifactorial activity of Lactobacillaceae strains alone or combined with the probiotic S. cerevisiae CNCM I-3856 against C. albicans without antagonistic effects between the beneficial strains, paves the way for developing consortium probiotics for in vivo applications.

Antagonistic effects of a COX1/2 inhibitor drug in human HepG2 cells exposed to an environmental carcinogen

Understanding interactions between legacy and emerging environmental contaminants has important implications for risk assessment, especially when mutagens and carcinogens are involved, whose critical effects are chronic and therefore difficult to predict. The current work aimed to investigate potential interactions between benzo[a]pyrene (B[a]P), a carcinogenic polycyclic aromatic hydrocarbon and legacy pollutant, and diclofenac (DFC), a non-steroidal anti-inflammatory drug and pollutant of emerging concern, and how DFC affects B[a]P toxicity. Exposure to binary mixtures of these chemicals resulted in substantially reduced cytotoxicity in human HepG2 cells compared to single-chemical exposures. Significant antagonistic effects were observed in response to high concentrations of B[a]P in combination with DFC at IC50 and ⅕ IC50. While additive effects were found for levels of intracellular reactive oxygen species, antagonistic mixture effects were observed for genotoxicity. B[a]P induced DNA strand breaks, γH2AX activation, and micronuclei formation at ½ IC50 concentrations or lower, whereas DFC induced only low levels of DNA strand breaks. Their mixture caused significantly lower levels of genotoxicity by all three endpoints compared to those expected based on concentration additivity. In addition, antagonistic mixture effects on CYP1 enzyme activity suggested that the observed reduced genotoxicity of B[a]P was due to its reduced metabolic activation as a result of enzymatic inhibition by DFC. Overall, the findings further support the growing concern that co-exposure to environmental toxicants and their non-additive interactions may be a confounding factor that should not be neglected in environmental and human health risk assessment.

A Novel Strain of Bacillus cereus with a Strong Antagonistic Effect Specific to Sclerotinia and Its Genomic and Transcriptomic Analysis.

Sclerotinia, which is caused by Sclerotinia sclerotiorum, is a severe disease of oilseed rape, which is an important oil crop worldwide. In this study, we isolated a novel strain of Bacillus cereus, named B. cereus HF10, from the rhizosphere soil of the reed on the seaside of Yagzhou Bay, Sanya city, Hainan Province, China. HF10 exhibited a significant antagonistic effect on Sclerotinia sclerotiorum, with an inhibition rate of 79%, and to other species in Sclerotinia, but no antagonistic effect was found on various other fungi or bacteria. HF10 had an 82.3% inhibitory effect on the S. sclerotiorum infection of oilseed rape leaves and a 71.7% control effect on Sclerotinia infection in oilseed rape based on in vitro and in vivo experiments, respectively. The genomics and transcriptomics of HF10 and its loss of the antifungal function mutant Y11 were analyzed, and the results provided insight into potential antifungal substances. Our work provides a novel strain, HF10, for developing a promising biological control agent against Sclerotinia, which infects oilseed rape and other plants.

Bacillus velezensis BE2 controls wheat and barley diseases by direct antagonism and induced systemic resistance.

Wheat and barley rank among the main crops cultivated on a global scale, providing the essential nutritional foundation for both humans and animals. Nevertheless, these crops are vulnerable to several fungal diseases, such as Septoria tritici blotch and net blotch, which significantly reduce yields by adversely affecting leaves and grain quality. To mitigate the effect of these diseases, chemical fungicides have proven to be genuinely effective; however, they impose a serious environmental burden. Currently, biocontrol agents have attracted attention as a sustainable alternative to fungicides, offering an eco-friendly option. The study aimed to assess the efficacy of Bacillus velezensis BE2 in reducing disease symptoms caused by Zymoseptoria tritici and Pyrenophora teres. This bacterium exhibited significant antagonistic effects in vitro by suppressing fungal development when pathogens and the beneficial strain were in direct confrontation. These findings were subsequently confirmed through microscopic analysis, which illustrated the strain's capacity to inhibit spore germination and mycelial growth in both pathogens. Additionally, the study analysed the cell-free supernatant of the bacterium using UPLC-MS (ultra-performance liquid chromatography-mass spectrometry). The results revealed that strain BE2 produces, among other metabolites, different families of cyclic lipopeptides that may be involved in biocontrol. Furthermore, the beneficial effects of strain BE2 in planta were assessed by quantifying the fungal DNA content directly at the leaf level after bacterization, using two different application methods (foliar and drenching). The results indicated that applying the beneficial bacterium at the root level significantly reduced pathogens pressure. Finally, gene expression analysis of different markers showed that BE2 application induced a priming effect within the first hours after infection. KEY POINTS: • BE2 managed Z. tritici and P. teres by direct antagonism and induced systemic resistance. • Strain BE2 produced seven metabolite families, including three cyclic lipopeptides. • Application of strain BE2 at the root level triggered plant defense mechanisms.

Characterization of the Endophytic Bacillus subtilis KRS015 Strain for Its Biocontrol Efficacy Against Verticillium dahliae.

Endophytes play important roles in promoting plant growth and controlling plant diseases. Verticillium wilt is a vascular wilt disease caused by Verticillium dahliae, a widely distributed soilborne pathogen that causes significant economic losses on cotton each year. In this study, an endophyte KRS015, isolated from the seed of the Verticillium wilt-resistant Gossypium hirsutum 'Zhongzhimian No. 2', was identified as Bacillus subtilis by morphological, phylogenetic, physiological, and biochemical analyses. The volatile organic compounds (VOCs) produced by KRS015 or its cell-free fermentation extract had significant antagonistic effects on various pathogenic fungi, including V. dahliae. KRS015 reduced Verticillium wilt index and colonization of V. dahliae in treated cotton seedlings significantly; the disease reduction rate was ∼62%. KRS015 also promoted plant growth, potentially mediated by the growth-related cotton genes GhACL5 and GhCPD-3. The cell-free fermentation extract of KRS015 triggered a hypersensitivity response, including reactive oxygen species (ROS) and expression of resistance-related plant genes. VOCs from KRS015 also inhibited germination of conidia and the mycelial growth of V. dahliae, and were mediated by growth and development-related genes such as VdHapX, VdMcm1, Vdpf, and Vel1. These results suggest that KRS015 is a potential agent for controlling Verticillium wilt and promoting growth of cotton.

Optimization and Validation of Sensitive UPLC-PDA Method for Simultaneous Determination of Thymoquinone and Glibenclamide in SNEDDs Formulations Using Response Surface Methodology

The development of analytical procedures capable of simultaneous determination of two or more drugs is in crucial demand due to the availability of different formulations that are composed of different APIs. The presented study aimed to optimize and validate a simple, accurate, and sensitive UPLC analytical method for the simultaneous determination of thymoquinone (TQ) and Glibenclamide (GB) using response surface methodology, and apply this method in pharmaceutical formulations. A 32 full design of experiment was utilized to study the impacts of the independent parameters (acetonitrile ACN concentration, A; and column temperature, B) on the drugs’ analytical attributes (viz, retention time, peak area, and peak asymmetry, in addition to the resolution between TQ and GB peaks). The results revealed that the independent parameters exhibited highly significant (p < 0.05) antagonistic effects on retention times for TQ and GB peaks, in addition to the agnostic effect on GB peak symmetry (p-value = 0.001). Moreover, antagonistic impacts (p < 0.05) on the resolution between TQ and GB peaks were found for both independent factors (A and B). The statistical software suggested 46.86% of ACN (A) and 38.80 °C for column temperature (B) for optimum analytical responses. The optimized green method was discovered to be acceptable in terms of selectivity, precision, accuracy, robustness, sensitivity, and specificity. Moreover, the optimized simultaneous method was successfully able to determine the contents of TQ and GB in self-nanoemulsifying drug delivery (SNEDD) formulation, in which the results showed that GB and TQ content within the prepared formulations were 1.54 ± 0.023 and 3.62 ± 0.031 mg/gm, respectively. In conclusion, the developed assay was efficient and valid in analyzing TQ and GB simultaneously in bulk and self-nanoemulsifying drug delivery system (SNEDDs) formulations.

OpiCa1-PEG-PLGA nanomicelles antagonize acute heart failure induced by the cocktail of epinephrine and caffeine

BackgroundReducing Ca2+ content in the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs) by calcin is a potential intervention strategy for the SR Ca2+ overload triggered by β-adrenergic stress in acute heart diseases. MethodsOpiCal-PEG-PLGA nanomicelles were prepared by thin film dispersion, of which the antagonistic effects were observed using an acute heart failure model induced by epinephrine and caffeine in mice. In addition, cardiac targeting, self-stability as well as biotoxicity were determined. ResultsThe synthesized OpiCa1-PEG-PLGA nanomicelles were elliptical with a particle size of 72.26 nm, a PDI value of 0.3, and a molecular weight of 10.39 kDa. The nanomicelles showed a significant antagonistic effect with 100 % survival rate to the death induced by epinephrine and caffeine, which was supported by echocardiography with significantly recovered heart rate, ejection fraction and left ventricular fractional shortening rate. The FITC labeled nanomicelles had a strong membrance penetrating capacity within 2 h and cardiac targeting within 12 h that was further confirmed by immunohistochemistry with a self-prepared OpiCa1 polyclonal antibody. Meanwhile, the nanomicelles can keep better stability and dispersibility in vitro at 4 °C rather than 20 °C or 37 °C, while maintain a low but stable plasma OpiCa1 concentration in vivo within 72 h. Finally, no obvious biotoxicities were observed by CCK-8, flow cytometry, H&E staining and blood biochemical examinations. ConclusionOur study also provide a novel nanodelivery pathway for targeting RyRs and antagonizing the SR Ca2+ disordered heart diseases by actively releasing SR Ca2+ through RyRs with calcin.

Effectiveness of a Novel Endophyte Bacillus velezensis Strain B1 in the Biocontrol of Pear Postharvest Ring Rot

Pear ring rot caused by Botryosphaeria dothidea severely affects the quality and storage life of pear fruit. Plant endophytes are potential new sources of biocontrol agents due to their abilities to produce novel bioactive products. In this work, we focused on an endophytic strain B1, which was isolated from roots of Dendrobium huoshanense. Notably, strain B1 exhibited strongly inhibitory effects against the growth of Botryosphaeria dothidea with an inhibition rate of 73.2% after 1 week of co-cultivation. Furthermore, it displayed a broad-spectrum inhibitory activity. Strain B1 also effectively delayed the onset of ring rot caused by B. dothidea in pear fruit and reduced the lesion diameter by 73.4%. Strain B1 was identified as Bacillus velezensis based on core-genome phylogeny. Genome mining with antiSMASH revealed 13 potential gene clusters involved in antimicrobial metabolites. Three main groups of lipopeptides (surfactin, iturin and fengycin) were identified with MALDI-TOF-MS, and the lipopeptides in the inhibition zone were greatly upregulated by B. dothidea; especially, fengycin isoforms were detected with higher abundance. These results proved that lipopeptides produced by strain B1 had significant antagonistic effect on B. dothidea. In conclusion, our results suggest that strain B1 has potential applications in the biocontrol of B. dothidea in postharvest fruit.

Genome Sequence, assembly and characterization of Bacillus velezensis VR-34 used as biocontrol agent of Peyronellaea arachidicola (peanut web blotch, Pathogen)

Peyronellaea arachidicola, a fungus that specifically targets the foliage of peanut plants, causes web blotch disease, which has an impact on the crop's yield and quality. In the present study, Whole-genome sequencing identified and characterized Bacillus velezensis VR-34, as a biocontrol antagonistic strain. In vitro assay showed that VR-34 had a significant antagonistic effect on P. arachidicola with an inhibition zone of 90.39 mm, which was higher than the inhibition zone of 80.45 mm for Ck. In greenhouse assay, in the pre-inoculated treatment, it was observed that the VR-34 strain exhibited a biocontrol efficacy of 93.52% against peanut web blotch disease, whereas the control group showed a biocontrol efficacy of 95.64%.. However, in the post-inoculated treatment, it was observed that the VR-34 strain exhibited a biocontrol efficacy of 89.89% against peanut web blotch disease, whereas the control group showed a biocontrol efficacy of 88.71%. The SEM analysis revealed that VR-34 caused damaged the hyphal surfaces and broken of spores of P. arachidicola. Whole-genome sequencing revealed twenty functional groups from 2833 annotations in the COG database, most of which were involved in transcription, secondary metabolite biosynthesis, amino acid transport and metabolism, and carbohydrate metabolism. 1694 KEGG annotations link 33 metabolic pathways. Glycoside hydrolases, glycosyl transferases, carbohydrate esterases, auxiliary activities, carbohydrate-binding modules, and polysaccharide lyases were among the 172 annotations in the CAZy database. antiSMASH analysis predicted that strain VR-34 can produce the secondary metabolites difficidin, aurantinin, elansolid, basiliskamide macrobrevin, kalimantacin, sowinholide A, bacillaene, and calyculin. In vitro, and greenhouse studies revealed that VR-34 controlled peanut web blotch disease. The whole genome study showed the VR-34 strain is B. velezensis and could synthesize antifungal secondary metabolites.

The antagonistic effect of urban growth pattern and shrinking cities on air quality: Based on the empirical analysis of 174 cities in China

Air pollution is an important issue facing the sustainable development of cities. In the context of rapid urbanization in China, a considerable number of cities show the coexistence of external morphological expansion and internal functional shrinkage, as well as obvious spatial heterogeneity in a large-scale region. The systematic construction of their interaction mechanisms is of great significance for air pollution remediation. Therefore, this study attempts to apply geographically weighted regression (GWR) to analyze the effect of urban growth patterns and urban shrinkage on air quality based on 10-year PM2.5 concentration change data from 174 prefecture-level cities in China. The results of the study indicate that: (1) The relationship between urban growth pattern and air quality has spatial heterogeneity. (2) The impact of shrinking cities on air quality is greater in colder regions and highly industrialized areas. (3) Urban growth pattern and shrinking cities show significant antagonistic effects on air quality, and the infilling growth of shrinking cities can cause serious deterioration of air quality. Considering the different urban evolutionary paths in developed and developing countries, this study provides different suggestions for city managers to promote sustainable urban development.

Bacteriophage-mediated biosynthesis of MnO2NPs and MgONPs and their role in the protection of plants from bacterial pathogens.

Xanthomonas oryzae pv. oryzae (Xoo) is the plant pathogen of Bacterial Leaf Blight (BLB), which causes yield loss in rice. In this study, the lysate of Xoo bacteriophage X3 was used to mediate the bio-synthesis of MgO and MnO2. The physiochemical features of MgONPs and MnO2NPs were observed via Ultraviolet - Visible spectroscopy (UV-Vis), X-ray diffraction (XRD), Transmission/Scanning electron microscopy (TEM/SEM), Energy dispersive spectrum (EDS), and Fourier-transform infrared spectrum (FTIR). The impact of nanoparticles on plant growth and bacterial leaf blight disease were evaluated. Chlorophyll fluorescence was used to determine whether the nanoparticles application were toxic to the plants. An absorption peak of 215 and 230 nm for MgO and MnO2, respectively, confirmed nanoparticle formation via UV-Vis. The crystalline nature of the nanoparticles was detected by the analysis of XRD. Bacteriological tests indicated that MgONPs and MnO2NPs sized 12.5 and 9.8 nm, respectively, had strong in vitro antibacterial effects on rice bacterial blight pathogen, Xoo. MnO2NPs were found to have the most significant antagonist effect on nutrient agar plates, while MgONPs had the most significant impact on bacterial growth in nutrient broth and on cellular efflux. Furthermore, no toxicity to plants was observed for MgONPs and MnO2NPs, indeed, MgONPs at 200 μg/mL significantly increased the quantum efficiency of PSII photochemistry on the model plant, Arabidopsis, in light (ΦPSII) compared to other interactions. Additionally, significant suppression of BLB was noted in rice seedlings amended with the synthesized MgONPs and MnO2NPs. MnO2NPs showed promotion of plant growth in the presence of Xoo compared to MgONPs. An effective alternative for the biological production of MgONPs and MnO2NPs was reported, which serves as an effective substitute to control plant bacterial disease with no phytotoxic effect.

Steroidal saponin SSPH I induces ferroptosis in HepG2 cells via regulating iron metabolism.

Hepatocellular carcinoma (HCC) is a common type of solid liver carcinoma. Regulating ferroptosis is important for the treatment of HCC. SSPH I is an anti-HCC steroidal saponin isolated from Schizocapsa plantaginea Hance. In this study, we found that SSPH I exerted significant anti-proliferation and anti-migration effects on HepG2 cell, ferroptosis inhibitor ferrostatin-1 or iron chelator ciclopirox partly attenuated the effect of SSPH I. SSPH I also induced apoptosis and G2/M phase cell cycle arrest. ROS accumulation, glutathione depletion and malondialdehyde accumulation were detected after SSPH I treatment, which leads to lipid peroxidation. Ferrostatin-1 or ciclopirox showed a significant antagonist effect towards SSPH I induced lipid peroxidation. Furthermore, typical morphologic changes of ferroptosis, such as increasing density of mitochondrial membrane and reduction of mitochondrial cristae were observed in HepG2 cells after SSPH I treatment. SSPH I does not regulate the xCT protein. Interestingly, SSPH I elevated the expression levels of SLC7A5, which is the negative regulator of ferroptosis. In contrast, SSPH I upregulated the expression of TFR and Fpn proteins, leading to the accumulation of Fe2+. Ferrostatin-1 and ciclopirox presented a similar antagonist effect on SSPH I. In conclusion, our research first reveals that SSPH I induced ferroptosis in HepG2 cells. In addition, our results suggest that SSPH I induces ferroptosis by causing iron overload in HepG2 cells.

Quantitative analysis of dose interval effect of Pb-Cd interaction on Oryza sativa L. root

Combined pollution of cadmium (Cd) and lead (Pb) occurs frequently in agriculture lands, which has received increasing research attention. However, little is known about the interaction behaviors of Cd and Pb at various concentrations in the mixture. This study evaluated the single and combined effects of Cd and Pb on rice (Oryza sativa L.) root elongation through acute exposure test. The combined pollution was analyzed with the concentration addition (CA) model, independent action (IA) model and mathematical statistical methods. The dose-response results revealed that the interaction could weaken the toxicity of both Pb and Cd, and Cd had a more significant inhibitory effect on Pb toxicity. The predicted values of CA and IA models were consistently lower than the observed values in the relative root elongation range of 0–60%. Further, combining the CA or IA model with mathematical statistical methods, the interaction of Pb and Cd at similar concentrations showed a significant antagonistic effect on rice root elongation. At low Pb concentrations (Cd > 0.0195, Pb < 0.015 mg/L), there was a synergistic effect of the mixture on rice root; at high Pb concentrations (Cd < 0.225, Pb ≥ 1.25 mg/L), Pb dominated the toxicity on rice root. This is the first report of a systematic method for assessing heavy metal interaction at different concentration levels, which may facilitate the formulation of control standards of heavy metal combined pollution in agricultural land.

Optimization of apigenin nanoparticles prepared by planetary ball milling: In vitro and in vivo studies

Abstract This study intended to optimize apigenin (APG) nanoparticle formulation prepared by planetary ball milling to enhance its dissolution rate and bioavailability using a design of experiment (DoE). In this study, polyvinyl pyrrolidone (PVP K30) was used as a nanoparticle stabilizer. The independent parameters of milling speed, milling ball size, and drug to solvent ratio were evaluated for their impacts on APG nanoparticles concerning the nanoparticle size (Y1), zeta potential (Y2), and drug dissolution efficiency after 60 min, notated as % DE60 (Y3). The milling ball size showed a significant antagonistic effect (P = 0.0210) on the size of APG nanoparticles, while milling speed had an agonistic effect on the zeta potential values of drug nanoparticles, ranging from low to medium speed levels. In addition, ANOVA analysis indicated that the effect of the drug-to-solvent ratio on the % DE60 of APG from the nanoparticle formulations was antagonistically significant (P = 0.015), and the quadratic effect of milling speed (AA) also had a significant antagonistic effect (P = 0.025) on the % DE60. Risk assessment analytical tools revealed that milling ball size and milling speed significantly affect the nanoparticle size. The drug/solvent ratio exerted a strong impact on % DE60. Furthermore, the maximum plasma concentration (C max) of the optimized APG nanoparticle formula increased by four folds. In addition, AUC0–t (ng·mL−1·h−1) for APG nanoparticle (353.7 ± 185.3 ng·mL−1·h−1) was higher than that noticed in the case of the untreated drug (149 ± 137.5 ng·mL−1·h−1) by more than two folds.

Management of take-all disease caused by Gaeumannomyces graminis var. tritici in wheat through Bacillus subtilis strains.

Wheat (Triticum aestivum) is the second largest grain crop worldwide, and one of the three major grain crops produced in China. Take-all disease, caused by Gaeumannomyces graminis var. tritici (Ggt) infection, is a widespread and devastating soil-borne disease that harms wheat production. At present, the prevention and control of wheat take-all depend largely on the application of chemical pesticides. Chemical pesticides, however, not only lead to increased drug resistance of pathogens but also leave significant residues in the soil, causing serious environmental pollution. In this study, we investigated the application of Bacillus subtilis to achieve take-all disease control in wheat while reducing pesticide application. Antagonistic bacteria were screened by plate test, species identification of strains was performed by Gram staining and sequencing of 16s rDNA, secondary metabolite activity of strains was detected by clear circle method, strain compatibility and effect of compounding on Ggt were detected by plate, and the application prospects of specific strains were analyzed by greenhouse and field experiments. We found that five B. subtilis strains, JY122, JY214, ZY133, NW03, Z-14, had significant antagonistic effects against Ggt, and could secrete antimicrobial proteins including amylase, protease, and cellulase. Furthermore, Z-14 and JY214 cultures have also been shown to change the morphology of Ggt mycelium. These results also showed that Z-14, JY214, and their combination can control take-all disease in wheat at a reduced level of pesticide use. In summary, we screened two Bacillus spp. strains, Z-14 and JY214, that could act as antagonists that contribute to the biological control of wheat take-all disease. These findings provide resources and ideas for controlling crop diseases in an environmentally friendly manner.

Identification of a novel P2X7 antagonist using structure-based virtual screening.

P2X4 and P2X7 receptors are ATP-gated ion channels, which play important roles in neuropathic and inflammatory pain, and as such they are important drug targets in diseases of inflammatory origin. While several compounds targeting P2X4 and P2X7 receptors have been developed using traditional high-throughput screening approaches, relatively few compounds have been developed using structure-based design. We initially set out to develop compounds targeting human P2X4, by performing virtual screening on the orthosteric (ATP-binding) pocket of a molecular model of human P2X4 based on the crystal structure of the Danio rerio receptor. The screening of a library of approximately 300,000 commercially available drug-like compounds led to the initial selection of 17 compounds; however, none of these compounds displayed a significant antagonist effect at P2X4 in a Fluo-4 ATP-induced calcium influx assay. When the same set of compounds was tested against human P2X7 in an ATP-stimulated Yo-Pro1 dye uptake assay, one compound (an indeno(1,2-b)pyridine derivative; GP-25) reduced the response by greater than 50% when applied at a concentration of 30µM. GP-25 displayed an IC50 value of 8.7μM at human P2X7 and 24.4μM at rat P2X7, and was confirmed to be active using whole-cell patch clamp electrophysiology and not cytotoxic. Schild analysis suggested that mode of action of GP-25 was orthosteric. Screening of a further 16 commercially available analogues of GP-25 led to the discovery of five additional compounds with antagonist activity at human P2X7, enabling us to investigate the structure-activity relationship. Finally, docking of the R- and S-enantiomers of GP-25 into the orthosteric pocket of molecular models of human P2X4 and human P2X7 revealed that, while both enantiomers were able to make multiple interactions between their carboxyl moieties and conserved positively charged amino-acids in human P2X7, only the S-enantiomer of GP-25 was able to do this in human P2X4, potentially explaining the lack of activity of GP-25 at this receptor.

Variability in bat morphology is influenced by temperature and forest cover and their interactions.

Multiple climatic and landscape drivers have been linked to variations in bat body size and wing functional traits. Most previous studies used proxies rather than actual climate and land-use data, and their interactions are rarely explored. We investigate whether higher summer average temperatures are driving decreasing bat body size as predicted by Bergmann's rule or increasing appendage size as per Allen's rule. We also explore whether temperature or resource availability (namely forest cover) is responsible for changes in wing functional traits. Using land-use data from historical maps and national statistics combined with climatic data, we assessed the effect of temperature and resource availability on bat morphology. We used 464 museum specimens of three bat species (Eptesicus nilssonii, Pipistrellus pygmaeus, and Plecotus auritus), spanning 180 years, across a 1200 km latitudinal gradient. We found no evidence of higher summer average temperatures driving decreases in body size in bats. Jaw sizes of P. auritus and P. pygmaeus changed over time but in different directions. The geographical variation of forest cover was also related to differences in wing functional traits in two species. Crucially, there was a significant antagonistic interactive effect of forest and temperature on tip index in P. pygmaeus whereby above 14.5°C the relationship between forest and tip index actually reversed. This could indicate that higher temperatures promote more pointed wings, which may provide energetic benefits. Our results show the importance of including both climatic and land-use variables when assessing trends in bat morphology and exploring interactions. Encouragingly, all three species have shown an ability to adapt their body size and functional traits to different conditions, and it could demonstrate their potential to overcome future negative impacts of climate and land-use change.

In-vitro screening of antagonistic potential of native endophyte strains of banana (Musa spp.) against Fusarium oxysporum f. sp. cubense TR4 causing Fusarium wilt of banana

The experiment was done in the Department of Plant Pathology, RPCAU, Pusa, Bihar during 2021-22 to identify the antagonistic potential of native endophytes of bananas against FocTR4. An in-vitro investigation revealed that only four bacterial endophytes, GNBE4, GNBE9, GNBE12, and GNBE14, showed significant antagonistic effects against FocTR4out of 18 screened endophytes (13 bacterial and 5 fungal) of banana. The GNBE4 (Alcaligens sp.) showed maximum mycelial inhibition (75.18%), followed by GNBE9 (Stenotrophomonas maltophilia) (71.90%) and GNBE12 (Staphylococcus warneri) (70.69%), while lowest in GNBE14 (Bacillus subtilis) (61.07%). Among the fungal endophytes, the maximum mycelial growth inhibition was shown in RzFE and LfFE (42.78%) followed by PsdFE (36.11%), while lowest in PtFE1 (26.67%). Apart from that already identified antagonistic PGPR like Pseudomonas fluorescens was obtained from the Department of Microbiology were tested which significantly suppressed the mycelial growth of fungus having a mycelial inhibition of 70.01 %.