Antagonistic Effects Research Articles

Robust Evidence in Integrative Medicine: Innovations, Challenges, and Future Directions

Integrative Medicine (IM), which includes therapies such as acupuncture, herbal medicine, yoga, and meditation, is gaining attention for managing chronic pain conditions. However, concerns about the quality of evidence supporting the use of these interventions persist. The 5th Annual Jaseng Academic conference 2024, in Seoul, South Korea, themed "Robust Evidence in Integrative Medicine: Innovations, Challenges, and Future Directions," addressed these concerns by focusing on advancements in study design, evidence synthesis, and open science practices. This conference proceeding summarizes key insights from the conference, emphasizing the role of pragmatic randomized controlled trials (pRCTs) in evaluating real-world effectiveness, and addressing the complexities involved in IM research such as sham controls. The integration of IM therapies into comprehensive pain management strategies (particularly in Korea), supported by government-backed research and policy initiatives was also discussed. Advancements in methodologies were addressed, such as bibliometric analysis, evidence mapping, and the development of clinical practice guidelines (CPGs) for integrative therapies. These methodologies offer valuable insights but face challenges due to the heterogeneity of IM interventions, and potential synergistic or antagonistic effects when combined with conventional medicine. Finally, the potential of open science to enhance transparency, reporting, and reproducibility in IM was explored, emphasizing the increased role of adherence to reporting guidelines (CONSORT and PRISMA). The future of IM research is built upon the continued efforts of refined study designs, rigorous evidence synthesis, and the integration of open science principles, for a robust and more credible evidence base.

Developing Stapled Aptamers with a Constrained Conformation for Osteogenesis Imperfect Therapeutics.

Despite the extensive development of aptamers in basic research, only a limited number have successfully progressed to clinical trials. This limitation is primarily attributed to the inherent instability of aptamers' conformation, resulting in low affinity, poor serum stability, and inconsistent potency, posing a significant challenge to their stabilization. Herein, we established a feasible strategy to develop staple aptamers using the predicted binding conformations and titration cross-linking (TTC) method. Through this strategy, we successfully synthesized various stapled sclerostin aptamers with over 70% yield. Importantly, we demonstrated that stapled aptamers significantly enhanced their affinity (approximately 20-fold) and serum stability (negligible degradation within 32 h). Moreover, in an osteogenesis imperfecta mouse model (Col1a2+/G610C mice), the stapled aptamer (named c-0127OA) exhibited a potent antagonistic effect on sclerostin, leading to enhanced anabolic bone anabolic potential. Collectively, our established stapling strategy is effective in stabilizing aptamers' conformation, with c-0127OA emerging as a promising therapeutic candidate for osteogenesis imperfecta.

Effects of mineralocorticoid receptor antagonists on new-onset or recurrent atrial fibrillation: a Bayesian and frequentist network meta-analysis of randomized trials

Abstract Aims Clinical and translational research suggests that mineralocorticoid receptor antagonists (MRAs) may prevent atrial fibrosis and electrical remodeling associated with atrial fibrillation (AF). This study aimed to consolidate existing evidence from randomized controlled trials (RCTs) evaluating the effect of MRAs on incident or recurrent AF. Methods Medline, Cochrane Library and Scopus were searched until February 12, 2024. Triple-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using both pairwise and Bayesian and frequentist network meta-analyses. Results Twenty-three RCTs (13,358 participants) were identified. Based on the pairwise random effects meta-analysis, MRAs were associated with a significant reduction in AF events compared to placebo or usual care (risk ratio {RR}= 0.75; 95% confidence interval {CI}= [0.66, 0.87]; P< 0.001; I2= 3%). This protective effect was robust both for new-onset and recurrent AF episodes (subgroup p-value= 0.69), while the baseline HF status was not a significant effect modifier (subgroup p-value= 0.58). MRAs demonstrated a significantly higher reduction in AF events for patients with chronic renal disease compared to placebo (RR= 0.78; 95% CI= [0.62, 0.98]; P= 0.03; I2= 0%). The network meta-analyses revealed that only spironolactone was associated with a significant reduction in AF events (Bayesian RR= 0.76; 95% CI= [0.65, 0.89]; P< 0.001; level of evidence moderate; SUCRA 0.731), while eplerenone and finerenone showed a neutral effect. Conclusion MRAs confer a significant benefit in terms of reducing incident or recurrent AF episodes, irrespective of HF status. In this context, spironolactone may be preferable compared to eplerenone or finerenone.

Aconitine in Synergistic, Additive and Antagonistic Approaches

Aconitine is a highly poisonous C19-diterpenoid alkaloid identified and isolated from the species of the genus Aconitum. Aconitine is indicated in the treatment of cardiovascular diseases (CVDs) and, due to its neurotoxic effects, is a very effective drug in pain release. A total of 101 relevant scientific papers were manually searched on the Web of Science, Scopus, Science Direct, Google Scholar, PubMed and Dovepress databases and in the books available in the library of the Department of Natural Sciences, the National University of Science and Technology POLITEHNICA Bucharest, Pitesti University Centre, Romania. In combination treatments, aconitine shows antiarrhythmic and anti-inflammatory activity, a synergistic antiproliferative effect and decreased reactive oxygen species (ROS) generation, an improved biodistribution and bioavailability. Additionally, the entrapment of aconitine in engineered nanoparticles represents a promising method for reducing the toxicity of this alkaloid. This review provides, for the first time, a comprehensive picture of the knowledge and research on the synergistic, additive and antagonistic effects of aconitine in combination treatments applied in vivo or in vitro. The summarized studies represent important clues in addressing the multitude of knowledge, which can find their utility in practical and clinical applications.

Isolation, Potential Beneficial Properties, and Assessment of Storage Stability of Direct-Fed Microbial Consortia from Wild-Type Chicken Intestine.

Direct-fed microorganisms (DFM) are recognized as an alternative to antibiotic-based growth promoters in poultry production due to their health benefits. DFM, however, should undergo rigorous safety testing to ensure they meet the criteria to be "Generally Recognized as Safe." This study assessed eight bacterial consortia (BC) isolated from the ileal and cecal intestinal regions of wild-type chickens, subjecting them to probiotic tests. Subsequently, they were spray- and freeze-dried to evaluate their storage stability for 30days. BC5-I and BC7-I, isolated from the ileum, emerged as promising DFM, displaying a high content of Lactobacillales using a selective medium and higher susceptibility to Gram-positive and Gram-negative antibiotics. These BC showed a high tolerance to temperature (> 90%), pH > 4 (88-98%), and antagonist effects against Escherichia coli and Salmonella. BC5-I exhibited superior survival in the simulated gastric conditions and satisfactory intestine mucus adhesion. Freeze-drying was the best method to obtain BC5-I and BC7-I powders, with a survival efficiency of 80.3% and 73.2%, respectively, compared to the beginning of storage. BC5-I presented the lowest cell death rate and prolonged half-life through survival storage kinetics. BC5-I only contained Lactobacillus, and Limosilactobacillus reuteri was the predominant species in liquid (78.3%) and freeze-dried (59.8%) forms. BC5-I stands out as a promising Lactobacillus-based DFM that could improve chicken intestinal health and enhance meat and egg production.

Evaluating the effects of adrenalectomy and mineralocorticoid receptor antagonist on cardiac remodeling and diastolic function in patients with aldosterone-producing adenoma.

Cardiac remodeling and diastolic dysfunction in patients with aldosterone-producing adenomas (APA) can be improved after adrenalectomy. However, the effect of mineralocorticoid receptor antagonist (MRA) treatment remains unclear. The aim of this study is to evaluate the effect of MRA on cardiac remodeling and diastolic dysfunction in patients with PA. We prospectively enrolled patients with APA from 1993 to 2023, who either received medical treatment with MRAs or underwent adrenalectomy. Biochemical characteristics and echocardiographic findings were collected at baseline and one year after treatment. Propensity score matching was conducted based on baseline biochemical characteristics, left ventricular mass index (LVMI), and diastolic function. A total of 467 APA patients were enrolled in the study. After propensity score matching, 159 patients who underwent adrenalectomy were matched with 159 patients who received MRAs. After therapy, patients who received MRAs showed significant improvement in diastolic function after one year of treatment but not LVMI. Compared to the MRA group, the adrenalectomy group had greater improvement in systolic blood pressure, plasma aldosterone concentration, plasma renin activity, aldosterone-to-renin ratio, and LVMI. In multivariable regression analysis, pretreatment echocardiographic values were significantly associated with changes in both LVMI and E/e', while the treatment strategy showed a significant association with changes in LVMI. Thus, one year after therapy, both adrenalectomy and MRA are effective in improving diastolic function in patients with APA. However, adrenalectomy is more effective than MRA treatment in reversing cardiac remodeling in patients with APA.

Effects of combined application of phosphorus and zinc on growth and physiological characteristics of apple rootstock M9-T337 seedlings (Malus domestica Borkh.)

BackgroundBalancing nutrient application is crucial for plant growth. However, excessive fertilizer use, especially imbalanced applications of macronutrients such as phosphate (P), can hinder plant uptake of micronutrients. Balanced P and zinc (Zn) are vital for apple yield and quality, and apple trees are highly sensitive to deficiencies in these nutrients. Therefore, this study was conducted in May 2022, employed a sand culture experiment to investigate the effects of varying P and Zn levels on the growth phenotype, photosynthetic capacity, antioxidant enzyme activity, sugar composition, endogenous hormone levels, and nutrient absorption and utilization of M9-T337 seedlings. Three levels of P (low, medium, high) and three levels of Zn (low, medium, high) were combined to create a total of nine distinct treatment.ResultsThe results indicate that combined P and Zn fertilization at various levels exerts either synergistic or antagonistic effects on the growth, nutrient absorption, and utilization of M9-T337 seedlings. Compared to low and medium levels of P, a combination of high P (4 mmol·L−1) and an adequate amount of Zn significantly enhanced plant growth, root system development, and the microstructure of leaves. Notably, seedlings treated with high P and low Zn (HPLZn) reached a height 1.54 times that of the medium P and medium Zn (MPMZn, control). Physiological indicators under HP conditions revealed significant increases in antioxidant enzyme activity, leaf water retention, photosynthetic pigment concentration, osmotic adjustment substances, and the contents of glucose, sucrose, fructose, endogenous hormones, as well as P and Zn accumulation in the leaves, compared to the control. However, an increase in Zn application led to a declining trend in these parameters. Specifically, the HPLZn treatment exhibited substantial increases in Net photosynthetic rate (Pn), Total chlorophyll (Chl a + b), glucose, fructose, sucrose, and Auxin(IAA), with increments of 7.12%, 27.32%, 11.40%, 23.20%, 16.67%, and 55.11%, respectively, compared to the control.ConclusionBased on the comprehensive ranking from principal component analysis, the combination of HP ( 4 mmol·L−1) and LZn (0.5 µmol·L−1) was found to be the most effective in enhancing the antioxidant capacity, sugar accumulation, osmotic regulation ability, photosynthetic capacity, endogenous hormone levels, as well as P and Zn nutrient absorption and utilization in M9-T337 seedlings.

Pleiotropic regulatory function of the RNA chaperone Hfq in the Pseudomonas protegens FD6

The rhizosphere bacterium Pseudomonas protegens FD6, which is associated with the production of antibiotics such as pyoluteorin (PLT) and 2,4-diacetylphloroglucinol (2,4-DAPG), has strong antagonistic effects on phytopathogens. Hfq is a conserved RNA chaperone involved in the regulation of stress tolerance, antibiotic production, and bacterial virulence. Here, we determined the regulatory effects of Hfq on biocontrol traits in P. protegens FD6. Mutation of hfq in FD6 reduced the growth rate, swimming and swarming ability, and production of proteases, siderophores, and hydrogen cyanide (HCN). Transmission electron microscopy revealed that disruption of hfq led to the loss of flagella. Furthermore, Hfq exerted a suppressive effect on biofilm formation and PLT production while not affecting antagonistic activity and control effect against tomato bacterial wilt. However, Hfq positively regulated the production of 2,4-DAPG and activated the phlD expression. Additionally, mutation of hfq abolished the function of the type VI secretion system (T6SS) due to a decrease in the expression of T6SS-related genes. Overall, these results suggest that Hfq plays a pleiotropic role in modulating the expression of biocontrol trait-related genes in P. protegens FD6.

Mechanistic investigation of ferric ion and ferriferous oxide on M. barkeri-mediated copper corrosion

Methanosarcina barkeri (M. barkeri) can cause microbiologically influenced corrosion (MIC) of copper in heat exchangers, where ferric ion (Fe3+) and ferriferous oxide (Fe3O4) also exist due to the corrosion of iron pipes with flowing water. It is worth noting that M. barkeri can reduce Fe3+ to Fe2+ or Fe, which may exhibit an unknown effect on copper corrosion. In this study, the molecular mechanism of copper corrosion by M. barkeri with Fe3+ and Fe3O4 was explored. In the presence of Fe3+, the corrosion was enhanced by 82.5 %, and M. barkeri and Fe3+ exhibited a synergistic effect on copper corrosion. It is attributed to that Fe3+ oxidized the copper and promoted the growth of M. barkeri and biofilm formation, thus promoting corrosion. Moreover, the corrosion by M. barkeri with Fe3O4 increased by only 27.7 %, and M. barkeri and Fe3O4 exhibited an antagonistic effect on the corrosion. Fe3O4 covered the coupon surface, which reduced the contact between the cells and the coupon, and thus inhibited electrochemical corrosion. This study provides new insights for methanogens-induced MIC, and also has far-reaching implication for the mitigation of MIC in heat exchangers.

Endophytic bacteria in Camellia reticulata pedicels: isolation, screening and analysis of antagonistic activity against nectar yeasts

Camellia reticulata, an ancient plant species endemic to Yunnan Province, China, remains underexplored in terms of its endophytic bacterial communities. The plant tissue pedicel serves as the connection between the flower and the stem, not only delivers nutrients but also transmits metabolic substances from endophytic bacteria to the nectar during long-term microbial colonization and probably improves the antagonistic activity of nectar against yeast. Hence, 138 isolates of endophytic bacteria have been isolated in this study from the pedicels of 12- and 60-year-old C. reticulata. Comparative analysis revealed significantly higher density of endophytic bacteria in older trees. Among these isolates, 29 exhibited inhibitory effects against nectar yeasts. Most of the isolates displayed positive results for Gram staining, catalase reaction, gelatin liquefaction, and motility. Additionally, the isolates demonstrated the ability to utilize diverse substrates, such as glucose, nitrate, and starch. Based on 16S rRNA molecular biology analysis, these isolates were identified to be 11 different species of 6 genera, with the majority belonging to Bacillus genus. Notably, C1 isolate, identified as Bacillus spizizenii, exhibited strongest antagonistic effect against three yeasts, i.e., Metschnikowia reukaufii, Cryptococcus laurentii, and Rhodotorula glutinis, with minimum inhibitory concentration values below 250 μg/mL. Major metabolites of B. spizizenii were aminoglycosides, beta-lactams, and quinolones, which possess antimicrobial activities. Furthermore, KEGG enrichment pathways primarily included the synthesis of plant secondary metabolites, phenylpropanoids, amino acids, alkaloids, flavonoids, neomycin, kanamycin, and gentamicin. Therefore, antagonistic activity of B. spizizenii against yeasts could be attributed to these antibiotics. The findings highlight the diverse endophytic bacteria associated with C. reticulata, indicating their potential as a valuable resource of bioactive metabolites. Additionally, this study provides new insights into the role of endophytic bacteria of pedicels in enhancing nectar resistance against yeasts.

Phytochemical Constituent and Cumulative or Antagonistic Effects of Crops Plant Organ Combination on Free Radical Scavenging Capacity and Antioxidant Compound Content

Aims: In Burkina Faso, the majority of plant-based recipes are a combination of plant organs from the same or different species. For these recipes’ producers, the aim is to improve efficiency. However, our ethnobotanical surveys have revealed that for some species, efficacy is better when the species is not combined, or when it is combined in small proportions with other species. The aim of this study is to assess the effect of plant organ combination on free radical scavenging activity, phenolic compound content and flavonoid content. Study Design: The work combined harvesting and processing of plant material from September to November 2023, and laboratories analysis from January to March 2024 at Natural Substances Departement of Institut de Recherche en Sciences Appliquées et Technologie, Ouagadougou. Methodology: We prepared two batches of recipes, first combining two species from the same genus, then two species from different genera. The powder of each plant without combination was also used to compare data. Phytochemical screening was first carried out with TLC and LC-MS analysis on each plant extract. We then assessed the phenolic compound content (PCC) using Folin-Ciocalteu method, flavonoid content (FCC) using aluminum chloride test, antioxidant content using TEAC method and free radical scavenging activity using DPPH method, for different batches. Results: Phytochemical constituent in the three species are phenolic compounds, terpenoids and nitrogen derivatives. The results of biological property evaluation suggest that for best efficacy and to obtain a high phenolic compound content, Lippia multiflora leaves should be used separately, or combined in 70% proportions with Lippia alba, then in 50% proportions if the combination is made with Ocimum basilicum. Conclusion: This research has provided relevant results to guide players in the field of traditional medicine and users of herbal remedies.

Chilling and Forcing Requirements of Wintersweet (Chimonanthus praecox L.) Flowering in China

Numerous studies have reported phenological changes and their driving mechanisms in spring flowering plants. However, there is little research on the shifts of winter flowering phenology and its response to forcing and chilling requirements. Based on the China Phenological Observation Network (CPON) ground observation data from nine sites over the past 20 years, we explored the spatial and temporal variation patterns of flowering plants and their response to chilling and forcing in wintersweet (Chimonanthus praecox L.), a common winter flowering plant species in temperate and subtropical zones of China. We used three chilling models (chilling hour, Utah, and dynamic models) and the growing degree hours (GDHs) model to calculate each site’s daily chilling and forcing. Using the partial least squares (PLSs) regression approach, we established the relationship between the first flowering date (FFD) and pre-season chilling and forcing in wintersweet, based on which we identified chilling and forcing periods and calculated chilling and forcing requirements. This study found that the FFD of wintersweet in China showed an overall advancement trend during the last 20 years. Still, there were temporal and spatial differences in the FFD of wintersweet among different sites. The PLS results showed that wintersweet also had periods of chilling and forcing, both of which co-regulated wintersweet flowering. We found the forcing and chilling requirements of wintersweet varied significantly from site to site. The higher the latitude is, the more chilling requirements are needed. The chilling requirements for wintersweet were about 6.9–34.9 Chill Portions (CPs) and 1.4–21.6 CP in the temperate and subtropical zones, respectively, with corresponding forcing requirements of 3.2–1922.9 GDH and 965.3–8482.6 GDH, respectively. In addition, we found that the temperature requirements of wintersweet were correlated by a negative exponential relationship, suggesting that chilling and forcing requirements have an antagonistic effect on initiating flowering phenology. Our results could help us understand how flowering dates of winter flowering plants respond to climate change.

Effects of indigenous microorganisms on the CO2 adsorption capacity of coal

The adsorption capacity of coal is a crucial criterion for CO2 sequestration in deep unminable coal seams. Previous studies have documented how indigenous microorganisms interact with supercritical carbon dioxide (ScCO2) in coal. But how these interactions affect the adsorption capacity were rarely investigated. In this study, we treated bituminous coal samples with ScCO2-H2O and ScCO2-H2O-microorganism interactions in high-pressure reactors for 120 days at 35 °C and 10 MPa, respectively. After the treatments, we characterized both coal pore types and structures. The comparisons between two different post-treatments indicate that no significant change in coal pore types but notable alterations in pore structures are observed. Specifically, the treated coal with microorganisms exhibits a significant increase in micropore specific surface area (SSA) and surface roughness than the one without them. However, changes in meso/macropore structures and overall pore complexity of the coal sample treated with microorganisms were less pronounced than in coal sample treated with ScCO2-H2O alone. FTIR spectra analysis indicated that the absorption peak intensity of oxygen-containing groups and aliphatic functional groups in the sample treated with microorganisms decreased much more significantly than the sample treated without microorganisms. The CO2 adsorption capacity slightly increased in all treated samples at equilibrium pressures below 2.5 MPa. Above this pressure, the coal sample treated with microorganisms maintained a higher CO2 adsorption capacity, while the sample treated without microorganisms exhibited lower CO2 adsorption capacity compared to untreated coal sample. The increased SSA and the reduced oxygen-containing functional groups of coal after the treatment exerted antagonistic effects on CO2 adsorption. These findings suggest that indigenous microorganisms in coal seams affect CO2 adsorption through antagonistic effects, necessitating site-specific microbial assessments.

In vitro and in vivo study of the antagonistic effects of a Trichoderma strain against four isolates of Fusarium that are pathogenic to chickpea.

This study investigated the antagonistic activity of Trichoderma asperellum against chickpea Fusarium wilt through in vitro and in vivo experiments. The dual culture test showed that Trichoderma had a significant inhibitory effect on the growth of the tested Fusarium isolates, with an inhibition rate ranging from 71.33% to 80.66%. The volatile and non-volatile metabolites produced by Trichoderma also showed antagonistic effects, with a growth inhibition rate ranging from 47.33% to 51.33% and a colonization rate ranging from 60% to 67%. In vivo experiments demonstrated that treating chickpea seeds with Trichoderma asperellum 48 h after inoculation with Fusarium significantly enhanced chickpea growth compared to seeds inoculated with Fusarium alone. Arial part length enhancement ranged between 69.3% and 92,19% while root length increased by 61,9% and 127%, this implied a significant improvement in biomass. These findings highlight Trichoderma's potential in controlling chickpea Fusarium wilt and enhancing plant growth, making it an environmentally friendly method in sustainable agriculture and crop protection.

Molecular Dynamics (MD) Simulations Provide Insights into the Activation Mechanisms of 5-HT2A Receptors

Recent breakthroughs in the determination of atomic resolution 3-D cryo-electron microscopy structures of membrane proteins present an unprecedented opportunity for drug discovery. Structure-based drug discovery utilizing in silico methods enables the study of dynamic connectivity of stable conformations induced by the drug in achieving its effect. With the ever-expanding computational power, simulations of this type reveal protein dynamics in the nano-, micro-, and even millisecond time scales. In the present study, aiming to characterize the protein dynamics of the 5HT2A receptor stimulated by ligands (agonist/antagonist), we performed 1 µs MD simulations on 5HT2A/DOI (agonist), 5HT2A/GSK215083 (antagonist), and 5HT2A (APO, no ligand) systems. The crystal structure of 5HT2A/zotepine (antagonist) (PDB: 6A94) was used to set up the simulation systems in a lipid bilayer environment. We found the monitoring of the ionic lock residue pair (R3.50-E6.30) of 5HT2A in MD simulations to be a good approximation of the effects of agonists (ionic lock breakage) or antagonists (ionic lock formation) on receptor activation. We further performed analyses of the MD trajectories, including Principal Component Analysis (PCA), hydrogen bond, salt bridge, and hydrophobic interaction network analyses, and correlation between residues to identify key elements of receptor activation. Our results suggest that in order to trigger receptor activation, DOI must interact with 5HT2A through residues V5.39, G5.42, S5.43, and S5.46 on TM5, inducing significant conformational changes in the backbone angles of G5.42 and S5.43. DOI also interacted with residues W6.48 (toggle switch) and F6.51 on TM6, causing major conformational shifts in the backbone angles of F6.44 and V6.45. These structural changes were transmitted to the intracellular ends of TM5, TM6, and ICL3, resulting in the breaking of the ionic lock and subsequent G protein activation. The studies could be helpful in future design of selective agonists/antagonists for various serotonin receptors (5HT1A, 5HT2A, 5HT2B, 5HT2C, and 5HT7) involved in detrimental disorders, such as addiction and schizophrenia.

Growth hormone-releasing hormone and cancer.

The hypothalamic hormone growth hormone-releasing hormone (GHRH), in addition to promoting the synthesis and release of growth hormone (GH), stimulates the proliferation of human normal and malignant cells by binding to GHRH-receptor (GHRH-R) and its main splice variant, SV1. Both GHRH and GHRH-Rs are expressed in various cancers, forming a stimulatory pathway for cancer cell growth; additionally, SV1 possesses ligand independent proliferative effects. Therefore, targeting GHRH-Rs pharmacologically has been proposed for the treatment of cancer. Various classes of synthetic GHRH antagonists have been developed, endowed with strong anticancer activity in vitro and in vivo, in addition to displaying anti-inflammatory, antioxidant and immune-modulatory functions. GHRH antagonists exert indirect effects by blocking the pituitary GH/hepatic insulin-like growth factor I (IGF-I) axis, or directly inhibiting the binding of GHRH on tumor GHRH-Rs. Additionally, GHRH antagonists block the mitogenic functions of SV1 in tumor cells. This review illustrates the main findings on the antitumor effects of GHRH antagonists in experimental human cancers, along with their underlying mechanisms. The development of GHRH antagonists, with reduced toxicity and high stability, could lead to novel therapeutic agents for the treatment of cancer and inflammatory diseases.

Investigating the impact of nanoplastics in altering the efficacy of clarithromycin antibiotics through In vitro studies

Plastics have significant global implications due to their environmental contamination from extensive use and improper disposal. Among plastic particles, nanoplastics (<1 μm) pose notable risks to organisms and ecosystems due to their high surface area, reactivity, and potential to carry environmental pollutants. This study explores the interaction between polystyrene nanoplastics (PSNPs) and clarithromycin (CLA), a broad-spectrum antibiotic, focusing on their combined impact on insulin (INS) and antibiotic-resistant (AMR) bacteria. PSNPs can adsorb CLA, leading to structural changes in insulin and affecting its physiological functions, potentially causing insulin resistance. Additionally, PSNPs reduce CLA's inhibitory effects on pathogenic bacteria, facilitating antibiotic resistance. Our research utilized UV–Vis Spectroscopy, FTIR, Fluorescence spectroscopy, and Circular dichroism (CD) spectroscopy to assess INS structural changes, alongside the Kirby-Bauer disk diffusion method for microbiological examination. The findings highlight the synergistic and antagonistic effects of PSNPs and CLA, underscoring the enhanced toxicity of CLA when adsorbed onto PSNPs and the complex interactions affecting both human health and bacterial resistance. Further studies are essential to fully understand these mechanisms and their broader implications.

Trans regulation of an odorant binding protein by a proto-Y chromosome affects male courtship in house fly.

The male-limited inheritance of Y chromosomes favors alleles that increase male fitness, often at the expense of female fitness. Determining the mechanisms underlying these sexually antagonistic effects is challenging because it can require studying Y-linked alleles while they still segregate as polymorphisms. We used a Y chromosome polymorphism in the house fly, Musca domestica, to address this challenge. Two male determining Y chromosomes (YM and IIIM) segregate as stable polymorphisms in natural populations, and they differentially affect multiple traits, including male courtship performance. We identified differentially expressed genes encoding odorant binding proteins (in the Obp56h family) as candidate agents for the courtship differences. Through network analysis and allele-specific expression measurements, we identified multiple genes on the house fly IIIM chromosome that could serve as trans regulators of Obp56h gene expression. One of those genes is homologous to Drosophila melanogaster CG2120, which encodes a transcription factor that binds near Obp56h. Upregulation of CG2120 in D. melanogaster nervous tissues reduces copulation latency, consistent with this transcription factor acting as a negative regulator of Obp56h expression. The transcription factor gene, which we name speed date, demonstrates a molecular mechanism by which a Y-linked gene can evolve male-beneficial effects.

Kinetics and Mechanism of PPh3/Ni-Catalyzed, Zn-Mediated, Aryl Chloride Homocoupling: Antagonistic Effects of ZnCl2/Cl.

The Ni/PPh3-catalyzed homocoupling of aryl chlorides in DMF using Zn as the stochiometric reducing agent is one of a general class of Ni-catalyzed processes, where the mechanism has been a matter of long-standing debate. This study re-evaluates prior conclusions and insights. NMR spectroscopy is used to identify [(PPh3)2NiII(Ar)Cl] as a key intermediate and to explore the indirect roles of using Zn as the reductant. The [ZnCl2] coproduct is responsible for several features, including a sequential transmetalation pathway involving [ArZnCl]. [ZnCl2] also abstracts halide from [(PPh3)2NiCl2] to generate [NiIICl(DMF)5]+[ZnCl3(DMF)]-, and in doing so, affects the NiII + Ni0 ↔ 2 NiI speciation. [ZnCl2] thus acts as an accelerator and inhibitor, resulting in mildly sigmoidal reaction profiles. When the [ZnCl2] concentration becomes too high or the phosphine ligand concentration too low, catalysis stalls. Turnover is restored by the addition of further phosphine ligand, or chloride ion. In the presence of an exogenous chloride ion, turnover is rapid, again proceeding via [(PPh3)2NiII(Ar)Cl] but via dinuclear metathesis. The generation of [ZnCl3(DMF)]- results in mutually antagonistic effects between [ZnCl2] and [Cl]- such that turnover proceeds via one mechanism or the other, depending on which species is in excess. The intermediacy of [ArZnCl] suggests a solution to the long-standing anomaly that many other reductants were found to be much less effective than Zn in inducing turnover of Ni/PPh3 catalyzed aryl chloride homocoupling in DMF. The use of DMAc as a solvent in place of DMF inhibits stalling through the steric inhibition of mixed metalate generation.

Non-linear dynamics and control of COVID-19 in india revisited : evidence of synergistic, antagonistic and threshold effects

Various researchers have investigated the COVID-19 pandemic dynamics since 2020 focusing on various aspects of the epidemics. However, the non-linear dynamics of this epidemic is still not well understood. India having the largest population in the world with wide cultural, genomics, and immunity diversity is being considered a suitable case for present investigation to generate the crucial information of non-linear phenomena during the first two waves of the epidemics. An SIRD model is suggested, integrating varying transmission, recovery, and mortality rates over time to explore the nonlinear behavior of the epidemic in India. The time-dependent transmission, recovery, and mortality are calculated using the finite difference method with the aid of actual data released by the Indian government, for the periods before and during the lockdown phases. The novel results generated from the model show evidence of synergistic, antagonistic, and threshold effects and the role of various measures in controlling these epidemic trends.