Synergistic Interaction Research Articles

Mining and multifaceted applications of phage lysin for combatting Vibrio parahaemolyticus

Vibrio parahaemolyticus, a prevalent foodborne pathogen found in both water and seafood, poses substantial risks to public health. The conventional countermeasure, antibiotics, has exacerbated the issue of antibiotic resistance, increasing the difficulty of controlling this bacterium. Phage lysins, as naturally occurring active proteins, offer a safe and reliable strategy to mitigate the impact of V. parahaemolyticus on public health. However, there is currently a research gap concerning bacteriophage lysins specific to Vibrio species. To address this, our study innovatively and systematically evaluates 37 phage lysins sourced from the NCBI database, revealing a diverse array of conserved domains and notable variations in similarity among Vibrio phage lysins. Three lysins, including Lyz_V_pgrp, Lyz_V_prgp60, and Lyz_V_zlis, were successfully expressed and purified. Optimal enzymatic activity was observed at 45℃, 800 mM NaCl, and pH 8–10, with significant enhancements noted in the presence of 1 mM membrane permeabilizers such as EDTA or organic acids. These lysins demonstrated effective inhibition against 63 V. parahaemolyticus isolates from clinical, food, and environmental sources, including the reversal of partial resistance, synergistic interactions with antibiotics, and disruption of biofilms. Flow cytometry analyses revealed that the combination of Lyz_V_pgp60 and gentamicin markedly increased bacterial killing rates. Notably, Lyz_V_pgrp, Lyz_V_pgp60, and Lyz_V_zlis exhibited highly efficient biofilm hydrolysis, clearing over 90 % of preformed V. parahaemolyticus biofilms within 48 h. Moreover, these lysins significantly reduced bacterial loads in various food samples and environmental sources, with reductions averaging between 1.06 and 1.29 Log CFU/cm2 on surfaces such as stainless-steel and bamboo cutting boards and approximately 0.87 CFU/mL in lake water and sediment samples. These findings underscore the exceptional efficacy and versatile application potential of phage lysins, offering a promising avenue for controlling V. parahaemolyticus contamination in both food and environmental contexts.

Antimicrobial resistance induction potential of grapefruit seed extract on multi-species biofilm of E. coli in food industry

Biofilm formation in natural environments involving complex multi-structural arrangements hinders challenges in antimicrobial resistance. This study investigated the antimicrobial resistance potential of grapefruit seed extract (GSE) by examining the formation of mono-, dual-, and multi-species biofilms. We also explored the counterintuitive effect in response to GSE at various concentrations, including minimum inhibitory concentration (MIC) and sub-MIC (1/2 and 1/4 MIC). The results of the swimming and swarming motility tests revealed increased motility at the sub-MIC of GSE. The crystal violet assay demonstrated increased biofilm formation in multi-species biofilms, highlighting the synergistic effect of Escherichia coli, Salmonella Typhimurium, and Listeria monocytogenes. At the MIC concentration of GSE, field emission scanning electron microscopy (FE-SEM) revealed cell morphology damage, while sub-MIC increased biofilm formation and architectural complexity. Multi-species biofilms demonstrated greater biofilm-forming ability and antimicrobial resistance than mono-species biofilms, indicating synergistic interactions and enhanced resilience. These findings highlight the importance of understanding biofilm dynamics and antimicrobial resistance to ensure environmental safety.

Novel insights from agricultural waste to acetic acid through regulated high-solids anaerobic digestion: Focus on the key microbial communities

Acetic acid (HAc) is an essential intermediate for improving the efficiency of biogas production in anaerobic digestion (AD) or for the production of liquid chemicals. The relationships between the mechanisms and microbial contributions of targeted regulation of HAc production in high-solids AD remains unclear. This study represents a breakthrough in revealing the mechanism of pH directed regulation of HAc production and microbial interactions. The regulation of the initial spray pH effectively improved the substrate hydrolysis rate and increased the concentration of HAc, with an average HAc percentage of total organic acids was 66.20 %. Microecological analysis revealed that rare species played a vital role in acidification, with all key acetogenic microbes identified as rare species. Additionally, the construction of a bacterial–environmental factor co-occurrence network revealed that lowering the initial spray pH enhanced the synergistic interactions among bacterial communities, and proportion of positive interactions among bacteria was 82.23 %. The gene abundance of key enzymes in the acetate-type metabolic pathway dominated in the acidogenesis phase. Furthermore, a regression model was established between the HAc indicator microbe (Acinetobacter) and HAc yields. Overall, the results of this study indicate that pH regulation plays an important role in strengthening the production of HAc and rare species significantly contributed to HAc production.

Fe2N5P dual-atom catalysts: A pathway to efficient hydrogen evolution in renewable energy applications

Dual-atom catalysts (DACs) are expected to improve the catalytic activity compared to single-atom catalysts (SACs). This improvement is attributed to the synergistic interaction between adjacent bimetallic atoms in DACs. Recently, the highly active Fe2N5P sites embedded in covalent organic framework-derived carbon have been demonstrated to catalyze oxygen reduction reaction (doi:10.1021/acscatal.3c02186). Motivated by this fascinating finding of Fe2N5P-based DACs, their potential for catalyzing hydrogen evolution reaction (HER) has been investigated. Thus, electrocatalytic activities of the Fe2N6 and Fe2N5P-based DACs embedded in graphene layer were systematically investigated toward the HER. Our results show that the Fe2N6 site embedded in graphene shows high catalytic activity and selectivity toward the HER. However, our results reveal that the P atom in the Fe2N5P dual-site facilitates the × H formation and thus improves its catalytic activity toward HER due to a greater degree of synergistic effect. The computed Gibbs free energies confirm the higher feasibility of HER on the Fe center of Fe2N5P compared to the Fe2N6 DAC.

Synergistic Interactions between Selected β-Lactam Antibiotics and Cinnamic Acid and Its Chosen Derivatives.

Staphylococcus epidermidis, a component of human microbiota, may also cause life-threatening opportunistic infections. These are becoming increasingly common infections associated with the implantation of various implants. Due to the exhaustion of antibiotic resources, new substances with antimicrobial activity are being sought. The present study examined the antibacterial effect of cinnamic acid and its derivatives and their combinations with β-lactam antibiotics on the growth of Staphylococcus epidermidis strains isolated from vascular infections. The data obtained during the research indicated that cinnamic acid and its derivatives, sinapic acid, ferulic acid, and p-coumaric acid, have weak antibacterial activity (MIC values at the level of 2048 and 4096 mg/L). The combination of cinnamic acid and its derivatives with β-lactam antibiotics increases the effectiveness of their action and may demonstrate various pharmacological effects depending on the established cutoff.

Tuning Morphologies of Metal-Organic Framework-Derived Ni3P/Ni Carbon Nanocomposites for Water Oxidation.

The oxygen evolution reaction (OER) frequently acts as a kinetic bottleneck in various energy storage and conversion systems. Effective electrocatalysts for the OER play a crucial role in reducing the reaction barrier and expediting the reaction. Multicomponent transition metal phosphides (TMPs) have garnered an extensive amount of attention as a result of their exceptional performance in the OER. Here, we present a direct method for preparing two intrinsic morphologies of metal-organic frameworks (MOFs), barrel-like BMM-10 and pancake-like BMM-10(Ac), achieved by establishing a protonation/deprotonation equilibrium with varying NO3-/Ac- ratios. The BMM-10(Ac)-C catalyst was synthesized via heat treatment of the BMM-10(Ac) precursor, exhibiting superior OER performance. It realized an overpotential of 286 mV at a current density of 10 mA cm-2, with a Tafel slope of 111.17 mV decade-1 and a current retention of 98.03%. This improvement arises from the synergistic interaction between Ni3P/Ni nanoparticles and the partially graphitic carbon layer, augmenting the exposure of active sites. Furthermore, alterations in the morphological features of MOF-derived Ni3P/Ni carbon nanocomposites adjusted the active electrochemical surface area, thereby modulating the overall OER performance of the corresponding TMP carbon nanocomposites. This methodology can be extended to control the morphology of other MOFs and their derivatives, providing innovative avenues for the design and synthesis of new MOF-based TMP nanomaterials.

Dietary patterns associated with obesity and its comorbidities

Obesity is a major public health challenge, in Spain the prevalence of excess of weight and obesity and is 56 % and 19 %, respectively, and it is linked to numerous preventable chronic diseases. Nutritional epidemiology focused on nutrients has evolved towards the study of dietary patterns that consider synergistic interactions between foods and nutrients. This study aims to investigate the relationship between obesity and its treatment by healthy dietary patterns. The Mediterranean diet and Dietary Approaches to Stop Hypertension (DASH), based on plant products, whole grains and low levels of salt, sugars and red meat, have been shown to promote weight loss and reduce comorbidities associated with obesity. Although vegetarian and vegan diets are adequate options for disease management and prevention, they require planning to avoid nutritional deficiencies. In conclusion, healthy dietary patterns such as the Mediterranean diet, DASH and vegetarian options are effective in both the prevention and treatment of obesity, highlighting the importance of considering the synergy between foods and nutrients in the management of this health condition.

Differential Patterns of Gut and Oral Microbiomes in Hispanic Individuals with Cognitive Impairment.

Alzheimer's disease and related dementias (ADRD) have been associated with alterations in both oral and gut microbiomes. While extensive research has focused on the role of gut dysbiosis in ADRD, the contribution of the oral microbiome remains relatively understudied. Furthermore, the potential synergistic interactions between oral and gut microbiomes in ADRD pathology are largely unexplored. This study aims to evaluate distinct patterns and potential synergistic effects of oral and gut microbiomes in a cohort of predominantly Hispanic individuals with cognitive impairment (CI) and without cognitive impairment (NC). We conducted 16S rRNA gene sequencing on stool and saliva samples from 32 participants (17 CI, 15 NC; 62.5% female, mean age = 70.4 ± 6.2 years) recruited in San Antonio, Texas, USA. Correlation analysis through MaAslin2 assessed the relationship between participants' clinical measurements (e.g., fasting glucose and blood cholesterol) and their gut and saliva microbial contents. Differential abundance analysis evaluated taxa with significant differences between CI and NC groups, and alpha and beta diversity metrics assessed within-sample and group compositional differences. Our analyses revealed no significant differences between NC and CI groups in fasting glucose or blood cholesterol levels. However, a clear association was observed between gut microbiome composition and levels of fasting glucose and blood cholesterol. While alpha and beta diversity metrics showed no significant differences between CI and NC groups, differential abundance analysis revealed an increased presence of oral genera such as Dialister , Fretibacterium , and Mycoplasma in CI participants. Conversely, CI individuals exhibited a decreased abundance of gut genera, including Shuttleworthia , Holdemania , and Subdoligranulum , which are known for their anti-inflammatory properties. No evidence was found for synergistic contributions between oral and gut microbiomes in the context of ADRD. Our findings suggest that similar to the gut microbiome, the oral microbiome undergoes significant modifications as individuals transition from NC to CI. Notably, the identified oral microbes have been previously associated with periodontal diseases and gingivitis. These results underscore the necessity for further investigations with larger sample sizes to validate our findings and elucidate the complex interplay between oral and gut microbiomes in ADRD pathogenesis.

Microbial Biostimulants and Seaweed Extract Synergistically Influence Seedling Growth and Morphology of Three Onion Cultivars

Onion (Allium cepa L.), a globally cultivated vegetable crop, possesses a shallow root system, making it vulnerable to abiotic stresses. The increasing frequency of extreme weather events in recent years necessitates sustainable solutions to enhance onion growth. Biostimulants offer a promising and accessible approach to promote onion growth and quality in an environmentally friendly and sustainable manner. This study investigated the effects of nine commercial microbial biostimulants (LALRISE Mycorrhizae, LALRISE Bacillus, Mighty Mycorrhizae, MycoApply, Spectrum DS, Spectrum Myco, Spectrum, Tribus Original, and Tribus Continuum) and one non-microbial commercial biostimulant (Kelpak—seaweed extract) on the seedling growth of three onion cultivars: Carta Blanca (white), Don Victoro (yellow), and Sofire (red). The results indicated that biostimulants did not significantly affect onion seed germination, but germination rates did vary among the onion cultivars. These cultivars also exhibited significant morphological and biomass differences, with principal component analysis revealing a more obvious effect on root growth compared to shoot growth. Kelpak seaweed extract increased the plant height, leaf area, and shoot fresh weight and dry weight of onion seedlings but decreased the root-to-shoot dry-weight ratio. The effects of microbial biostimulants on onion seedling growth depended on both the onion cultivar and Kelpak seaweed extract. In general, LALRISE Mycorrhizae, Mighty Mycorrhizae, Spectrum Myco, Spectrum DS, and Tribus Continuum exhibited positive effects on seedling growth in certain onion cultivars. Furthermore, the benefits of microbial biostimulants were amplified when combined with Kelpak seaweed extract application. These findings suggest a synergistic interaction between microbial and non-microbial biostimulants, leading to enhanced onion seedling growth. Further research is required to evaluate the long-term effects of these biostimulants on onion plant growth after transplanting to fields.

Bioaugmentation protocols involving Methanobrevibacter thaueri and Pecoramyces ruminantium for investigating lignocellulose degradation and methane production from alfalfa stalks

Two protocols involving batch cultures were used to investigate the bioaugmentation of methane production by Pecoramyces ruminantium, and Methanobrevibacter thaueri. Protocol I examined the effect of altering the proportion of the microbial constituents in inoculum on alfalfa stalk fermentations and showed a 25 % improvement in dry matter loss in cultures where the inoculum contained just 30 % of co-culture and 70 % of fungal monoculture. Protocol II involved consecutive cultures and alternating inoculations. This protocol resulted in 17–22 mL/g DM methane production with co-cultures a 30 % increase in methane relative to the fungal monoculture. Both protocols indicate that the co-culture rapidly dominated and was more resilient than the monoculture. Synergistic interaction between fungus and methanogen, promoted more efficient lignocellulose degradation and higher methane yield. This study highlighted the potential of microbial co-cultures for enhancing methane production from lignocellulosic biomass, offering a promising bioaugmentation strategy for improving biogas yields and waste valorization.

A Synergistic Indole-3-Acetic Acid-Producing Synthetic Bacterial Consortium Benefits Walnut Seedling Growth

Synthetic microbial communities (SynComs) have been shown to be an ecofriendly alternative for promoting plant growth. However, the mechanisms by which SynCom inoculants drive plant growth promotion in rhizosphere soil are still not fully explored. Herein, we designed a three-strain consortium based on the biocompatibility among strains and indole-3-acetic acid (IAA) production. The consortium containing Bacillus safensis 5-49, Bacillus stratosphericus 5-54, and Bacillus halotolerans 6-30 possessed a synergistic effect on IAA production and biofilm formation. Genetic analysis suggested that IAA was synthesized through tryptophan-dependent pathways in the strains. The consortium outperformed the plant growth-promoting effect observed with single strains, showing an increase in walnut (Juglans regia) seedling dry weight by 92.3% over the non-inoculated plants after 60 days of cultivation. This effect was underpinned by the synergistic interactions of the consortium, which was evidenced by the significantly increased relative abundance of Bacillus and tryptophan metabolism-associated genes in the rhizosphere of consortium-inoculated plants. Meanwhile, the consortium increased the relative abundance of indigenous Pseudomonas in rhizosphere soil, providing a synergistic effect on improving soil enzyme activities and thus available nutrients. The available N, P, and K contents in the consortium-inoculated plant rhizosphere were 3.77–28.4% higher than those in non-inoculated samples. This work provided an efficient bacterial consortium and proposed the mode of action by which this consortium improved plant growth and soil fertility.

Recent Advances in Biomacromolecule‐Reinforced 2D Material (2DM) Hydrogels: From Interactions, Synthesis, and Functionalization to Biomedical Applications

AbstractRegenerative biomedicine has emerged as a forefront area in medical research, heralding a new era of therapeutic strategies. This review delineates the integration of 2D materials (2DMs) within the area of biomedical engineering, leveraging their superior physicochemical attributes for enhance biomedical outcomes. The synergistic interaction between biomacromolecules and 2DMs is explored, demonstrating their potential to mitigate the limitations inherent to each while simultaneously augmenting their beneficial properties. In particular, incorporating 2DMs into hydrogels highlights their capability to enhance the mechanical strength of hydrogels, providing a biomimetic scaffold for tissue engineering regeneration and cancer diagnosis and therapy. An overview of the synthetic methodologies are provided for 2DMs, elucidating their interaction dynamics with biomacromolecules. The review primarily concentrates on the applications of biomacromolecule‐reinforced 2DM hydrogels across various biomedical fields, including bone tissue engineering, wound healing, neural tissue engineering, cardiac tissue engineering, as well as in the delivery of drugs and genes, cancer therapy, and biosensing technologies. Finally, the review discusses the existing challenges and future outlook for developing and using biomacromolecule‐reinforced 2DM hydrogels, underlining their transformative potential in regenerative medicine.

Diversity and potential functional role of phyllosphere-associated actinomycetota isolated from cupuassu (Theobroma grandiflorum) leaves: implications for ecosystem dynamics and plant defense strategies.

Exploring the intricate relationships between plants and their resident microorganisms is crucial not only for developing new methods to improve disease resistance and crop yields but also for understanding their co-evolutionary dynamics. Our research delves into the role of the phyllosphere-associated microbiome, especially Actinomycetota species, in enhancing pathogen resistance in Theobroma grandiflorum, or cupuassu, an agriculturally valuable Amazonian fruit tree vulnerable to witches' broom disease caused by Moniliophthora perniciosa. While breeding resistant cupuassu genotypes is a possible solution, the capacity of the Actinomycetota phylum to produce beneficial metabolites offers an alternative approach yet to be explored in this context. Utilizing advanced long-read sequencing and metagenomic analysis, we examined Actinomycetota from the phyllosphere of a disease-resistant cupuassu genotype, identifying 11 Metagenome-Assembled Genomes across eight genera. Our comparative genomic analysis uncovered 54 Biosynthetic Gene Clusters related to antitumor, antimicrobial, and plant growth-promoting activities, alongside cutinases and type VII secretion system-associated genes. These results indicate the potential of phyllosphere-associated Actinomycetota in cupuassu for inducing resistance or antagonism against pathogens. By integrating our genomic discoveries with the existing knowledge of cupuassu's defense mechanisms, we developed a model hypothesizing the synergistic or antagonistic interactions between plant and identified Actinomycetota during plant-pathogen interactions. This model offers a framework for understanding the intricate dynamics of microbial influence on plant health. In conclusion, this study underscores the significance of the phyllosphere microbiome, particularly Actinomycetota, in the broader context of harnessing microbial interactions for plant health. These findings offer valuable insights for enhancing agricultural productivity and sustainability.

Ibuprofen as an adjuvant to conventional antimicrobials and essential oil compounds against skin pathogens.

Antimicrobial resistance continues to be a growing concern, resulting in increased use of drug combinations. Antibiotic adjuvants are an emerging strategy that may potentiate an antibiotics efficacy. Ibuprofen's polypharmacological properties have been investigated for their antimicrobial and host-modulating potential. This study aimed to investigate the potential of a novel multidrug combination involving ibuprofen, essential oil compounds (EOCs), and conventional antimicrobials against skin pathogens. The minimum inhibitory concentrations of ibuprofen, conventional antimicrobials, and EOCs were determined and then combined and tested against 14 (reference and clinical) skin pathogens. The cytotoxicity was analysed using the MTT assay, whilst the anti-inflammatory effects were evaluated using lipopolysaccharide activated RAW264.7 murine macrophages. Four pairwise (Ibuprofen and antibiotic) (ΣFIC 0.33-0.50) and three triple (Ibuprofen and antibiotic with EOC) (ΣFIC 0.44-0.47) synergistic antimicrobial interactions were identified. These combinations demonstrated cell viability of 77.59%-100%. No combination significantly reduced nitric oxide production. The results from this study provide insight into the potential of a multidrug combination involving ibuprofen with conventional antimicrobials and EOCs against common skin pathogens.

Synergistic interaction between pay-it-forward incentives and recreational drug use on hepatitis B virus and hepatitis C virus testing among men who have sex with men in China

ObjectivesPay-it-forward incentives effectively promote hepatitis B virus (HBV) and hepatitis C virus (HCV) testing among men who have sex with men (MSM) by offering free testing and donation opportunities. This...

Interactions between phenanthrene exposure and historical chemical stress: Implications for fitness and ecological resilience of the sentinel species Daphnia magna

Polycyclic aromatic hydrocarbons (PAHs) arise from incomplete combustion of oil, coal, and gasoline, with lipophilic properties facilitating their widespread distribution and persistence. Due to their biochemical attributes, PAHs can accumulate in animal tissues, potentially causing mutagenic and carcinogenic effects. Since the industrial revolution, PAH concentrations in the environment have risen, with lakes showing levels from 0.159 to 33,090 μg/kg sediment. Despite acute toxicity studies showing adverse effects on freshwater organisms, the long-term impacts and synergistic interactions with other pollutants remain largely unexplored.This study investigates the impact of phenanthrene (PHE), a prominent PAH found in aquatic environments, on Daphnia magna, a species of significant ecological importance in freshwater ecosystems globally, being both a sentinel species for chemical pollution and a keystone organism in freshwater aquatic ecosystems. Leveraging the dormancy of D. magna, which spans decades or even centuries, we exposed strains with diverse histories of chemical contaminant exposure to environmentally relevant concentrations of PHE. Initially, acute exposure experiments were conducted in accordance with OECD guidelines across 16 Daphnia strains, revealing substantial variation in acute toxic responses, with strains naïve to chemical pollutants showing the lowest toxicity. Utilizing the median effect concentration EC10 derived from acute exposures, we assessed the impacts of chronic PHE exposure on life history traits and ecological endpoints of the 16 strains. To elucidate how historical exposure to other environmental stressors may modulate the toxicity of PHE, temporal populations of D. magna resurrected from a lake with a well-documented century-spanning history of environmental impact were utilized. Our findings demonstrate that PHE exposure induces developmental failure, delays sexual maturation, and reduces adult size in Daphnia. Populations of Daphnia historically exposed to chemical stress exhibited significantly greater fitness impacts compared to naïve populations. This study provides crucial insights into the augmented effects of PAHs interacting with other environmental stressors.

Graphene oxide/Cu–MOF-based electrochemical immunosensor for the simultaneous detection of Mycoplasma pneumoniae and Legionella pneumophila antigens in water

The combination of copper–metal organic framework (Cu–MOF) with graphene oxide (GO) has received growing interest in electrocatalysis, energy storage and sensing applications. However, its potential as an electrochemical biosensing platform remains largely unexplored. In this study, we introduce the synthesis of GO/Cu–MOF nanocomposite and its application in the simultaneous detection of two biomarkers associated with lower respiratory infections, marking the first instance of its use in this capacity. The physicochemical properties and structural elucidation of this composite were studied with the support of XRD, FTIR, SEM and electrochemical techniques. The immunosensor was fabricated by drop casting the nanocomposite on dual screen-printed electrodes followed by functionalization with pyrene linker. The covalent immobilization of the monoclonal antibodies of the bacterial antigens of Mycoplasma pneumoniae (M. pneumoniae; M. p.) and Legionella pneumophila (L. pneumophila; L. p.) was achieved using EDC-NHS chemistry. The differential pulse voltammetry (DPV) signals of the developed immunosensor platform demonstrated a robust correlation across a broad concentration range from 1 pg/mL to 100 ng/mL. The immunosensor platform has shown high degree of selectivity against antigens for various respiratory pathogens. Moreover, the dual immunosensor was successfully applied for the detection of M. pneumoniae and L. pneumophila antigens in spiked water samples showing excellent recovery percentages. We attribute the high sensitivity of the immunosensor to the enhanced electrocatalytic characteristics, stability and conductivity of the GO–MOF composite as well as the synergistic interactions between the GO and MOF. This immunosensor offers a swift analytical response, simplicity in fabrication and instrumentation, rendering it an appealing platform for the on-field monitoring of pathogens in environmental samples.

Synergy of CoN3 and CuN3O2 sites in single atom-decorated biochar for peroxymonosulfate activation: Accelerating the production of SO4•− and •OH

The coordination environment of metal affects the catalytic activity significantly, and synergistic interactions between metal sites might play an important role in the peroxymonosulfate (PMS) activation process. Bimetallic doped biochar exhibited greater PMS activation capability than single metal doped biochar. Quenching experiments revealed that cobalt (Co) and copper (Cu) doping could promote the generation of SO4•− and •OH, but was detrimental to the production of 1O2. Density functional theory (DFT) simulations demonstrated that biochar loaded with both CoN3 and CuN3O2 sites had the largest absolute value of Eads, the longest O-O bond length and the maximal electrons transfer, thus facilitating the production of SO4•− and •OH. The CuN3O2 site was excellent for generating 1O2 due to its low reaction energy barrier. In addition, NBC-Cu-Co was an environmentally friendly catalyst in activating PMS to produce low-toxicity intermediates as well as reduce leaching of metal ions.

Antidepressant effects of selective adenosine receptor antagonists targeting the A1 and A2A receptors administered jointly with NMDA receptor ligands: behavioral, biochemical and molecular investigations in mice

BackgroundThe objective of the study was to ascertain the antidepressant potential of the co-administration of NMDA receptor ligands and selective adenosine A1 and A2A receptor antagonists.MethodsThe forced swim test (FST) and spontaneous locomotor activity test were carried out in adult male naïve mice. Before the behavioral testing, animals received DPCPX (a selective adenosine A1 receptor antagonist, 1 mg/kg) or istradefylline (a selective adenosine A2A receptor antagonist, 0.5 mg/kg) in combination with L–701,324 (a potent NMDA receptor antagonist, 1 mg/kg), D–cycloserine (a partial agonist at the glycine recognition site of NMDA receptor, 2.5 mg/kg), CGP 37849 (a competitive NMDA receptor antagonist, 0.3 mg/kg) or MK–801 (a non-competitive NMDA receptor antagonist, 0.05 mg/kg). Additionally, serum BDNF level and the mRNA level of the Adora1, Comt, and Slc6a15 genes in the murine prefrontal cortex were determined.ResultsThe obtained results showed that DPCPX and istradefylline administered jointly with NMDA receptor ligands (except for DPCPX + D–cycloserine combination) produced an antidepressant effect in the FST in mice without enhancement in spontaneous motility of animals. An elevation in BDNF concentration was noted in the D–cycloserine-treated group. Adora1 expression increased with L–701,324, DPCPX + D–cycloserine, and DPCPX + CGP 37849, while D–cycloserine, CGP 37849, and MK–801 led to a decrease. Comt mRNA levels dropped with DPCPX + L–701,324, istradefylline + L–701,324/CGP 37849 but increased with D–cycloserine, MK–801, CGP 37849 and DPCPX + MK–801/ CGP 37849. Slc6a15 levels were reduced by D–cycloserine, DPCPX + L–701,324 but rose with DPCPX + CGP 37849/MK–801 and istradefylline + D–cycloserine/MK–801/CGP 37849.ConclusionOur study suggests that selective antagonists of adenosine receptors may enhance the antidepressant efficacy of NMDA receptor ligands highlighting a potential synergistic interaction between the adenosinergic and glutamatergic systems. Wherein, A2A receptor antagonists are seen as more promising candidates in this context. Given the intricate nature of changes in BDNF levels and the expression of Adora1, Comt, and Slc6a15 seen after drug combinations exerting antidepressant properties, further research and integrative approaches are crucial understand better the mechanisms underlying their antidepressant action.

The enhanced nonlinear absorption, nonlinear refraction and optical limiting properties of Bi2WO6/ZnO composites

The Bi2WO6/ZnO (BWO/ZnO) composites were synthesized by using a hydrothermal method. Then, the BWO/ZnO composites were poured into methyl methacrylate through polymerization to make the BWO/ZnO/PMMA organic glasses (OGs) with different amounts. The X-ray diffraction (XRD) and transmission electron microscopy (TEM) were used to investigate the crystal structures and morphology size of BWO/ZnO composites. The nonlinear absorption (NLA), nonlinear refraction (NLR) and optical limiting (OL) properties were systematically investigated by using the Z-scan technique at 532 nm. The BWO/PMMA and BWO/ZnO/PMMA OGs may transform from saturable absorption (SA) to reverse saturable absorption (RSA) by varying the input energy. The NLA, NLR and OL performances of the BWO/ZnO/PMMA OGs are superior to those of the BWO/PMMA OGs and other bismuth-based metal oxides. The synergistic interaction of BWO and ZnO plays a crucial role in the BWO/ZnO/PMMA OGs. The NLA mechanisms were analyzed using an energy-level model.