Synergistic and Antagonistic Activity of Selected Dietary Phytochemicals against Oxidative Stress-Induced Injury in Cardiac H9c2 Cells via the Nrf2 Signaling Pathway.

The antioxidant activities of lycopene (LY), lutein (LU), chlorogenic acid (CA), and delphinidin (DP) were tested in vitro on H9c2 cell-based models. Some indicators, such as the generation of reactive oxygen (ROS), the quantification of cell antioxidant activity (CAA), and the expressions of SOD, GSH-Px, and CAT, were calculated to examine their antioxidant interactions. From our results, the phytochemical mixtures (M1: CA-LU: F3/10, M2: DP-CA: F7/10, M3: DP-LY: F5/10) displayed strong synergistic effects based on the generation of ROS and the quantification of CAA. However, great antagonistic bioactivities were seen in the combinations of LY-LU: F5/10 (M4), CA-LU: F9/10 (M5), and DP-LY: F7/10 (M6). Western blotting analysis indicated that the possible mechanism underlying the synergistic antioxidant interactions among phytochemical combinations was to enhance the accumulation of Nrf2 in the nucleus and the expression of its downstream antioxidant enzymes, HO-1 and GCLC. The combinations (M1-M3 groups) showed significant protection against the loss of mitochondrial membrane potential than individual groups to avoid excessive ROS production. The M4-M6 groups exerted antagonistic protective effects compared with the individual groups. In addition, lutein and lycopene absorption was improved more because of the presence of chlorogenic acid and delphinidin in the M1 and M3 groups, respectively. However, delphinidin significantly reduced the cellular uptake of lycopene in the M6 group. It appeared that antioxidant interactions of phytochemical combinations may contribute to the restoration of cellular redox homeostasis and lead to an improvement in diet quality and collocation.

Single and combined effect of polyethylene microplastics (virgin and naturally aged) and cadmium on pakchoi (Brassica rapa subsp. chinensis) under different growth stages.

To protect agro-systems and food security, study on the effect of microplastics and heavy metals on edible plants is of great significance. Existing studies mostly used virgin microplastics to evaluate their effects on plants, effects of naturally aged microplastics and their combined effects with heavy metals are rarely explored. In this study, single and combined effect of polyethylene microplastics (PE, both virgin and naturally aged) and cadmium (Cd) on pakchoi under seedling and mature stages were analyzed from perspectives of growth inhibition, oxidative damage, nutrition content and soil enzyme activities. Results showed that inhibiting effects of naturally aged PE (PEa) on the growth of pakchoi were stronger than virgin PE (PEv), whereas co-contamination of PEa and Cd was less toxic than that of PEv and Cd. The co-contamination of PE and Cd could inhibit pakchoi dry biomass by over 85 %. Both single and combined contamination of PE and Cd promoted soil fluorescein diacetate hydrolase (FDA) activities, which were 1.11 to 2.04 times of that in control group. Soluble sugar contents under co-contamination of PEa and Cd were 14 % to 22 % higher than those in control group. PEa and PEv showed different effects on oxidative damage of pakchoi. Compared with PEv, catalase (CAT) activities were more sensitive with PEa, whereas PEa had lower effect on superoxide dismutase (SOD) activities. The response of pakchoi to PE and Cd changed with growth stage. Chlorophyll contents in pakchoi under seedling stage were generally higher than those under mature stage. For Cd contaminated soils, PE benefited pakchoi growth under seedling stage, i.e. antagonistic effect between Cd and PE but hindered their growth under mature stage, i.e. synergistic effect. The results unraveled here emphasized PE, especially PEa, could trigger negative effects on agro-systems, whereas PE could be beneficial for heavy metal contaminated agro-systems under specific situations.

Antagonistic Mechanism Analysis of Bacillus velezensis JLU-1, a Biocontrol Agent of Rice Pathogen Magnaporthe oryzae.

Magnaporthe oryzae, the causal agent of rice blast, is a fungal disease pathogen. Bacillus spp. have emerged as the most promising biological control agent alternative to chemical fungicides. In this study, the bacterial strain JLU-1 with significant antagonistic activity isolated from the rhizosphere soil of rice was identified as Bacillus velezensis through whole-genome sequencing, average nucleotide identity analysis, and 16S rRNA gene sequencing. Twelve gene clusters for secondary metabolite synthesis were identified in JLU-1. Furthermore, 3 secondary metabolites were identified in JLU-1, and the antagonistic effect of secondary metabolites against fungal pathogens was confirmed. Exposure to JLU-1 reduced the virulence of M. oryzae, and JLU-1 has the ability to induce the reactive oxygen species production of rice and improve the salt tolerance of rice. All of these results indicated that JLU-1 and its secondary metabolites have the promising potential to be developed into a biocontrol agent to control fungal diseases.

Improving Resistance of Mango to Colletotrichum gloeosporioides by Activating Reactive Oxygen Species and Phenylpropane Metabolism of Bacillus amyloliquefaciens GSBa-1.

This study aimed to explore the effects of Bacillus amyloliquefaciens GSBa-1 treatment on anthracnose disease resistance and the metabolism of reactive oxygen species (ROS) and phenylpropanoids in mangoes during storage. Mangoes were soaked in a solution containing 1 × 108 CFU/mL of B. amyloliquefaciens GSBa-1. The anthracnose disease incidence, disease index, respiration intensity, ethylene release, reactive oxygen species content, and the activities of related metabolic enzymes, phenylpropanoid-related metabolic enzymes, and phenolic acids in the skin and pulp of mangoes were investigated under normal temperature storage conditions. The results showed that the antagonistic bacterial treatment (ABT) did not significantly inhibit the growth of Colletotrichum gloeosporioides in vitro. However, it significantly reduced the incidence of mango anthracnose disease when applied to the mango peel. ABT enhanced the latent resistance of mango to anthracnose disease by activating its reactive oxygen and phenylpropanoid metabolism. It maintained higher levels of ROS production and elimination in the peel. Moreover, it rapidly activated manganese superoxide dismutase, induced the accumulation of H2O2, and enhanced the activity of manganese superoxide dismutase, catalase, ascorbate peroxidase, and peroxidase in the mango peel. Furthermore, ABT activated phenylalanine ammonia-lyase, cinnamic acid-4-hydroxylase, 4-coumaroyl-CoA ligase, and cinnamyl alcohol dehydrogenase in the mango peel and pulp, promoting the accumulation of antifungal phenolic acids such as gallic acid, catechins, and ellagic acid. Bacillus amyloliquefaciens GSBa-1 may be a potent inhibitor of mango anthracnose, primarily enhancing the resistance of mangoes to anthracnose by synergistically activating ROS in the peel and phenylpropanoid metabolism in the pulp, thereby reducing the incidence of anthracnose effectively.

Isolation of Antagonistic Endophytic Fungi from Postharvest Chestnuts and Their Biocontrol on Host Fungal Pathogens.

In this study, antagonistic endophytic fungi were isolated from postharvest chestnut fruits; endophytic antagonistic fungi and their combination of inhibitory effects on the fungal pathogen Neofusicoccum parvum were evaluated. A total of 612 endophytic fungi were isolated from 300 healthy chestnut kernels, and 6 strains out of them including NS-3, NS-11, NS-38, NS-43, NS-56, and NS-58 were confirmed as antagonistic endophytic fungi against Neofusicoccum parvum; these were separately identified as Penicillium chermesinum, Penicillium italicum, Penicillium decaturense, Penicillium oxalicum, Talarmyces siamensis, and Penicillium guanacastense. Some mixed antagonistic endophytic fungi, such as NS-3-38, NS-11-38, NS-43-56, and NS-56-58-38, exhibited a much stronger antifungal activity against N. parvum than that applied individually. Among them, the mixture of NS-3-38 showed the highest antifungal activity, and the inhibition rate was up to 86.67%. The fermentation broth of NS-3, NS-38, and their combinations exhibited an obvious antifungal activity against N. parvum, and the ethyl acetate phase extract of NS-3-38 had the strongest antifungal activity, for which the inhibitory rate was up to 90.19%. The NS-3-38 fermentation broth combined with a chitosan coating significantly reduced N. parvum incidence in chestnuts from 100% to 19%. Furthermore, the fruit decay and weight loss of chestnuts during storage were significantly decreased by the NS-3-38 fermentation broth mixture along with a chitosan coating. Therefore, a mixture of P. chermesinum and P. decaturense could be used as a potential complex biocontrol agent to control postharvest fruit decay in chestnuts.

The interaction between biochar and earthworms: Revealing the potential ecological risks of biochar application and the feasibility of their co-application.

Biochar's interaction with soil-dwelling organisms, particularly earthworms, is crucial in ensuring the effective and secure utilization of biochar in the soil. This review introduces the application of biochar in soil, summarizes how earthworms respond to biochar-amended soil and the underlying factors that can influence their response, discusses the synergistic and antagonistic impacts of earthworm activity on the efficacy of biochar, and considers the feasibility of applying them together. A review of existing research has identified uncertainty in the effect of biochar exposure on earthworms, with biochar derived from animal wastes, produced at higher pyrolysis temperatures, and used at higher doses of biochar having more negative effects on earthworms. Habitat modification, toxicity release, particle effects, and contaminant immobilization are underlying factors in how biochar affects earthworm indicators. While biochar in contaminated soils may alleviate the stress of pollutants on earthworms by decreasing their bioaccumulation, this remedial effect is not always effective. Additionally, earthworm bioturbation can enhance the migration, fragmentation, and oxidation of biochar, while also stimulating extracellular enzymes that convert biochar into 'vermichar'. Earthworms and biochar can synergize well to improve soil fertility and remediate soil organic pollution, yet exhibit contrasting roles in soil C sequestration and immobilizing heavy metals in soil. These findings highlight both the advantages and risks of their co-application. Therefore, when considering the use of biochar alone or with earthworms, it is crucial to thoroughly assess its potential ecotoxicity on earthworms and other soil organisms, as well as the influence of bioturbation, such as that caused by earthworms, on the effectiveness of biochar.

More evidence for widespread antagonistic pleiotropy in polymorphic disease alleles.

Introduction: Many loci segregate alleles classified as "genetic diseases" due to their deleterious effects on health. However, some disease alleles have been reported to show beneficial effects under certain conditions or in certain populations. The beneficial effects of these antagonistically pleiotropic alleles may explain their continued prevalence, but the degree to which antagonistic pleiotropy is common or rare is unresolved. We surveyed the medical literature to identify examples of antagonistic pleiotropy to help determine whether antagonistic pleiotropy appears to be rare or common. Results: We identified ten examples of loci with polymorphisms for which the presence of antagonistic pleiotropy is well supported by detailed genetic or epidemiological information in humans. One additional locus was identified for which the supporting evidence comes from animal studies. These examples complement over 20 others reported in other reviews. Discussion: The existence of more than 30 identified antagonistically pleiotropic human disease alleles suggests that this phenomenon may be widespread. This poses important implications for both our understanding of human evolutionary genetics and our approaches to clinical treatment and disease prevention, especially therapies based on genetic modification.

Antagonistic interaction between caffeine and ketamine in zebrafish: Implications for aquatic toxicity.

The coexistence of caffeine (CF) and ketamine (KET) in surface waters across Asia has been widely reported. Previous studies have implied that CF and KET may share a mechanism of action. However, the combined toxicity of these two chemicals on aquatic organisms remains unclear at environmental levels, and the underlying mechanisms are not well understood. Here we demonstrate that KET antagonizes the adverse effects of CF on zebrafish larvae by modulating the gamma-aminobutyric acid (GABA)ergic synapse pathway. Specifically, KET (10-250 ng L-1) ameliorates the locomotor hyperactivity and impaired circadian rhythms in zebrafish larvae induced by 2 mg L-1 of CF, showing a dose-dependent relationship. Additionally, the developmental abnormalities in zebrafish larvae exposed to CF are mitigated by KET, with an incidence rate reduced from 26.7% to 6.7%. The competition between CF and KET for binding sites on the GABA-A receptor (in situ and in silico) elucidates the antagonistic interactions between the two chemicals. Following a seven-day recovery period, the adverse outcomes of CF exposure persist in the fish, whereas the changes observed in the CF + KET groups are significantly alleviated, especially with KET at 10 ng L-1. Based on these results, it is imperative to further assess the environmental risks associated with CF and KET co-pollution. This pilot study underscores the utility of systems toxicology approaches in estimating the combined toxicity of environmental chemicals on aquatic organisms. Moreover, the nighttime behavioral functions of fish could serve as a sensitive biomarker for evaluating the toxicity of psychoactive substances.

[Male reproductive damage caused by phthalate esters: Progress in research].

Phthalate esters are plasticizers that people are often exposed to in daily life. They are closely related to our lives and generally exist in the air, soil and water. Studies show that the exposure to phthalates is associated with male reproductive damage. When the concentration of phthalates reaches a certain level in the body, it can reduce the count and motility of sperm, induce abnormalities in the reproductive system and organs, and affect male fertility. This review summarizes the advances in the studies of the metabolic pathway of phthalate esters in the human body, the mechanism underlying their damage to the male reproductive system and their antagonistic effect.

The Influence of Lactobacillus spp. Secondary Metabolites Isolated from Immature Egyptian Honey on Human Pathogens, Transcription of Virulence Genes and Lung Cancer.

This work aimed to isolate, and identify Lactic Acid Bacteria LAB from Egyptian immature citrus honey, and characterize their secondary metabolites, as well as determine the antibacterial activities and transcription of virulence genes (stx1, stx2, and eae) influenced by these bacterial secondary metabolites. From twenty hives, twenty immature citrus bee honey samples were taken. Traditional cultural and biochemical testing were used, followed by molecular confirmation. Further, LAB isolates' antibacterial and cytotoxic properties were investigated. 16S rRNA gene sequencing were assessed and, two lactic acid bacterial isolates were identified as Lactobacillus acidophilus Ch2 and Levilactobacillus brevis Ch1. Both isolates have good antagonistic action against clinical pathogens, with Levilactobacillus brevis Ch1 exhibiting the best antibacterial activity against all indicator pathogens examined. When compared to untreated cancer cells, the isolates demonstrated significant cytotoxic activity. Ch1 and Ch2 cell viability percentages were 39.5% and 18.76%, respectively. Furthermore, when exposed to Levilactobacillus brevis Ch1 metabolites, Shiga-producing Escherichia coli (STEC) virulence gene expression was suppressed. To identify bacterial secondary metabolites, a high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOF) approach was developed. Twenty-seven metabolites from diverse chemical classes were discovered in the crude extracts with antibacterial and anticancer characteristics. This is the first thorough investigation on the metabolic profile of LAB isolated from immature Egyptian honey and the findings suggested that isolates or their secondary metabolites could be used in the food sector as medicinal alternatives or as a biocontrol agent.

Prey size reflected in tooth wear: a comparison of two wolf populations from Sweden and Alaska.

Ingesta leaves distinct patterns on mammalian teeth during mastication. However, an unresolved challenge is how to include intraspecific variability into dietary reconstruction and the biomechanical aspects of chewing. Two extant populations of the grey wolf (Canis lupus), one from Alaska and one from Sweden, were analysed with consideration to intraspecific dietary variability related to prey size depending on geographical origin, sex and individual age as well as tooth function. Occlusal enamel facets of the upper fourth premolars, first molars and the second lower molar were analysed via three-dimensional surface texture analysis. The Swedish wolves displayed facets characterized by higher peaks and deeper, more voluminous dales, featuring an overall rougher surface than the wolves from Alaska. Compared to females, the Swedish male wolves had a slightly larger dale area and hill volume on their facets. Upper fourth premolars are smoother and had higher values in texture direction compared to upper first molars. The upper first molars were rougher than the occluding lower second molars and were characterized by larger and deeper dales. We find evidence supporting intraspecific dietary segregation, and antagonistic asymmetry in occlusal wear signatures. The data offer new insights into the roles of apex predators like the grey wolf.

Employing antagonistic C-X-C motif chemokine receptor 4 antagonistic peptide functionalized NaGdF4 nanodots for magnetic resonance imaging-guided biotherapy of breast cancer.

C-X-C motif chemokine receptor 4 (CXCR4) is a promising therapeutic target of breast cancer because it is overexpressed on cell surface of all molecular subtypes of breast cancer including triplenegative breast cancer (TNBC). Herein, CXCR4 antagonistic peptide-NaGdF4 nanodot conjugates (termed as anti-CXCR4-NaGdF4 NDs) have been constructed for magnetic resonance imaging (MRI)-guided biotherapy of TNBC through conjugation of the C-X-C Motif Chemokine 12 (CXCL12)-derived cyclic peptide with tryptone coated NaGdF4 nanodots (5 ± 0.5 nm in diameter, termed as Try-NaGdF4 NDs). The as-prepared anti-CXCR4-NaGdF4 NDs exhibits high longitudinal relaxivity (r1) value (21.87 mM-1S-1), reasonable biocompatibility and good tumor accumulation ability. The features of anti-CXCR4-NaGdF4 NDs improve the tumor-MRI sensitivity and facilitate tumor biotherapy after injection in mouse-bearing MDA-MB-231 tumor model in vivo. MRI-guided biotherapy using anti-CXCR4-NaGdF4 NDs enables to suppress 46% tumor growth. In addition, about 47% injection dose of anti-CXCR4-NaGdF4 NDs is found in the mouse urine at 24 h post-injection. These findings demonstrate that anti-CXCR4-NaGdF4 NDs enable to be used as renal clearable nanomedicine for biotherapy and MRI of breast cancer.

Uncovering the Antifungal Potential of Plant-Associated Cultivable Bacteria from the Aral Sea Region against Phytopathogenic Fungi.

Two freshwater rivers, the Amu Darya and Syr Darya, flow into the Aral Sea, but they began to diminish in the early 1960s, and by the 1980s, the lake had nearly ceased to exist due to excessive water consumption for agriculture and the unsustainable management of water resources from rivers, which transformed the Aral Sea into a hypersaline lake. Despite this, the flora and fauna of the region began to evolve in the high-salinity seabed soil, which has received little attention in studies. In this study, we isolated approximately 1400 bacterial strains from the rhizosphere and phyllosphere of plant species of distinct families. Bacterial isolates were examined for antifungal activities against a range of pathogenic fungi such as Rhizoctonia gossypii, Trichothecium ovalisporum, Fusarium annulatum, F. oxysporum, F. culmorum, F. brachygibbosum, F. tricinctum, F. verticillioides, Alternaria alternata, A. terreus, Aspergillus niger, and As. flavus. Eighty-eight bacterial isolates exhibited varying antagonistic ability against pathogenic fungi. Furthermore, DNA barcoding of isolates using the 16S rRNA gene indicated that most antagonistic bacteria belonged to the Bacillus and Pseudomonas genera. The study also explored the activity of hydrolytic and cell-wall-degrading enzymes produced by antagonistic bacteria. The findings revealed that antagonistic bacteria can be utilized to widely protect seabed plants and plants growing in saline areas against pathogenic fungi, as well as agricultural crops.

Screening (ant)agonistic activities of xenobiotics on the retinoic acid receptor alpha (RARα) using in vitro and in silico analysis.

Retinoic acid receptors (RARs) are known as crucial endocrine receptors that could mediate a broad diversity of biological processes. However, the data on endocrine disrupting effects of emerging chemicals by targeting RAR (ant)agonism are far from sufficient. Herein, we investigated the RARα agonistic or antagonistic activities for 75 emerging chemicals of concern, and explored their interactions with this receptor. A recombinant two-hybrid yeast assay was used to examine the RARα activities of the test chemicals, wherein 7 showed effects of RARα agonism and 54 exerted potentials of RARα antagonism. The representative chemicals with RARα agonistic activities, i.e. 4-hydroxylphenol (4-HP) and bisphenol AF (BPAF), significantly increased the mRNA levels of CRABP2 and CYP26A1, while 4 select chemicals with RARα antagonistic potentials, including bisphenol A (BPA), tetrabromobisphenol A (TBBPA), 4-tert-octylphenol (4-t-OP), and 4-n-nonylphenol (4-n-NP), conversely decreased the transcriptional levels of the test genes. The in silico molecular docking analysis using 3 different approaches further confirmed the substantial binding between the chemicals with RARα activities and this nuclear receptor protein. This work highlights the promising strategy for screening endocrine-disrupting effects of emerging chemicals of concern by targeting RARα (ant)agonism.

A Heterogeneous Acid-Base Organocatalyst For Cascade Deacetalisation-Knoevenagel Condensations.

Multifunctional heterogeneous catalysts are an effective strategy to drive chemical cascades, with attendant time, resource and cost efficiencies by eliminating unit operations arising in normal multistep processes. Despite advances in the design of such catalysts, the fabrication of proximate, chemically antagonistic active sites remains a challenge for inorganic materials science. Hydrogen-bonded organocatalysts offer new opportunities for the molecular level design of multifunctional structures capable of stabilising antagonistic active sites. We report the catalytic application of a charge-assisted, hydrogen-bonded crystalline material, bis(melaminium)adipate (BMA), synthesised from melamine and adipic acid, which possesses proximate acid-base sites. BMA exhibits high activity for the cascade deacetalisation-Knoevenagel condensation of dimethyl acetals to form benzylidenemalononitriles under mild conditions in water; BMA is amenable to large-scale manufacture and recycling with minimal deactivation. Computational modelling of the melaminium cation in protonated BMA explains the observed catalytic reactivity, and identifies the first demethoxylation step as rate-limiting, in good agreement with time-dependent 1H NMR and kinetic experiments. A broad substrate scope for the cascade transformation of aromatic dimethyl acetals is demonstrated.

Probiotic evaluation, adherence capability and safety assessment of Lactococcus lactis strain isolated from an important herb "Murraya koenigii".

Lactic acid bacteria (LAB) isolated from medicinal herb Murraya koenigii, commonly known as curry leaf, which promotes the growth and maintenance of gut microbiota, were studied for their probiotic potential. The key objective of this research was to isolate and evaluate probiotic characteristics, test adherence capabilities, and confirm their safety. Lactococcus lactis (MKL8), isolated from Murraya koenigii, was subjected to in vitro analysis to assess its resistance to the gastric environment, ability to adhere Caco-2 cells, anti-microbial activity, hydrophobicity, auto-aggregation, and safety profiling through MTT assay and hemolytic. MKL8 exhibited growth at 0.5% phenol concentrations (> 80%) and was able to survive in conditions with high bile concentrations (> 79%) and a relatively low pH (72%-91%). It shows high tolerance to high osmotic conditions (> 73%) and simulated gastric juice (> 72%). Additionally, MKL8 demonstrated strong hydrophobicity (85%), auto-aggregation (87.3%-91.7%), and adherence to Caco-2 cells. Moreover, it had an inhibitory effect against pathogens too. By performing the hemolytic and MTT assays, the non-toxicity of MKL8 isolate was examined, and it exhibited no harmful characteristics. Considering MKL8's resistance to gastrointestinal tract conditions, high surface hydrophobicity, non-toxicity, and ability to inhibit the tested pathogens, it can be concluded that MKL8 demonstrated promising probiotic properties and has potential for use in the food industry.

Effects of Multiple Stressors, Pristine or Sulfidized Silver Nanomaterials, and a Pathogen on a Model Soil Nematode Caenorhabditis elegans.

Previous research using the model soil nematode Caenorhabditis elegans has revealed that silver nanoparticles (AgNP) and their transformed counterpart, sulfidized AgNP (sAgNP), reduce their reproduction and survival. To expand our understanding of the environmental consequences of released NP, we examined the synergistic/antagonistic effects of AgNP and sAgNP along with AgNO3 (ionic control) on C. elegans infected with the pathogen Klebsiella pneumoniae. Individual exposures to each stressor significantly decreased nematode reproduction compared to controls. Combined exposures to equitoxic EC30 concentrations of two stressors, Ag in nanoparticulate (AgNP or sAgNP) or ionic form and the pathogen K. pneumoniae, showed a decline in the reproduction that was not significantly different compared to individual exposures of each of the stressors. The lack of enhanced toxicity after simultaneous combined exposure is partially due to Ag decreasing K. pneumoniae pathogenicity by inhibiting biofilm production outside the nematode and significantly reducing viable pathogens inside the host. Taken together, our results indicate that by hindering the ability of K. pneumoniae to colonize the nematode's intestine, Ag reduces K. pneumoniae pathogenicity regardless of Ag form. These results differ from our previous research where simultaneous exposure to zinc oxide (ZnO) NP and K. pneumoniae led to a reproduction level that was not significantly different from the controls.

The structure and function of antagonistic ties in village social networks.

Negative or antagonistic relationships are common in human social networks, but they are less often studied than positive or friendly relationships. The existence of a capacity to have and to track antagonistic ties raises the possibility that they may serve a useful function in human groups. Here, we analyze empirical data gathered from 24,770 and 22,513 individuals in 176 rural villages in Honduras in two survey waves 2.5 y apart in order to evaluate the possible relevance of antagonistic relationships for broader network phenomena. We find that the small-world effect is more significant in a positive world with negative ties compared to an otherwise similar hypothetical positive world without them. Additionally, we observe that nodes with more negative ties tend to be located near network bridges, with lower clustering coefficients, higher betweenness centralities, and shorter average distances to other nodes in the network. Positive connections tend to have a more localized distribution, while negative connections are more globally dispersed within the networks. Analysis of the possible impact of such negative ties on dynamic processes reveals that, remarkably, negative connections can facilitate the dissemination of information (including novel information experimentally introduced into these villages) to the same degree as positive connections, and that they can also play a role in mitigating idea polarization within village networks. Antagonistic ties hold considerable importance in shaping the structure and function of social networks.

The Role of Selection and Migration in the Evolution of (Auto)Immunity Genes.

The genetic architecture of multiple sclerosis is complicated. Additionally, the disease incidence varies per population or per geographical region. A recent study gives convincing explanations about the north-south incidence gradient of multiple sclerosis in Europe, by analyzing ancient and modern human genomes. Interestingly, the evidence shows that multiple sclerosis associated immunogenetic variants underwent positive selection in Asian and European populations. Lifestyle and pathogen infections probably shaped the overall multiple sclerosis risk. These results complete the findings of previous studies that showed that a high percentage of the autoimmunity associated genetic variants are under selection pressure.

Rethinking Aspergillosis in the Era of Microbiota and Mycobiota.

Aspergillosis encompasses a wide range of clinical conditions based on the interaction between Aspergillus and the host. It ranges from colonization to invasive aspergillosis. The human lung provides an entry door for Aspergillus. Aspergillus has virulence characteristics such as conidia, rapid growth at body temperature, and the production of specific proteins, carbohydrates, and secondary metabolites that allow A. fumigatus to infiltrate the lung's alveoli and cause invasive aspergillosis. Alveolar epithelial cells play an important role in both fungus clearance and immune cell recruitment via cytokine release. Although the innate immune system quickly clears conidia in immunocompetent hosts, A. fumigatus has evolved multiple virulence factors in order to escape immune response such as ROS detoxifying enzymes, the rodlet layer, DHN-melanin and toxins. Bacterial co-infections or interactions can alter the immune response, impact Aspergillus growth and virulence, enhance biofilm formation, confound diagnosis, and reduce treatment efficacy. The gut microbiome's makeup influences pulmonary immune responses generated by A. fumigatus infection and vice versa. The real-time PCR for Aspergillus DNA detection might be a particularly useful tool to diagnose pulmonary aspergillosis. Metagenomics analyses allow quick and easy detection and identification of a great variety of fungi in different clinical samples, although optimization is still required particularly for the use of NGS techniques. This review will analyze the current state of aspergillosis in light of recent discoveries in the microbiota and mycobiota.