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The complexity of the interaction between the necrotrophic pathogen Botrytis cinerea and grape berries ( Vitis vinifera spp.) can result in the formation of either the preferred noble rot (NR) or the loss-making grey rot (GR), depending on the prevailing climatic conditions. In this study, we focus on the functional gene set of V. vinifera by performing multidimensional scaling followed by differential expression and enrichment analyses. The aim of this study is to identify the differences in gene expression between grape berries in the phases of grey rot, noble rot, and developing rot (DR, in its early stages) phases. The grapevine transcriptome at the NR phase was found to exhibit significant differences from that at the DR and GR stages, which displayed strong similarities. Similarly, several plant defence-related pathways, including plant-pathogen interactions as hypersensitive plant responses were found to be enriched. The results of the analyses identified a potential plant stress response pathway (SGT1 activated hypersensitive response) that was found to be upregulated in the GR berry but downregulated in the NR berry. The study revealed a decrease in defence-related in V. vinifera genes during the NR stages, with a high degree of variability in functions, particularly in enriched pathways. This indicates that the plant is not actively defending itself against Botrytis cinerea , which is otherwise present on its surface with high biomass. This discrepancy underscores the notion that during the NR phase, the grapevine and the pathogenic fungi interact in a state of equilibrium. Conversely the initial stages of botrytis infection manifest as a virulent fungus-plant interaction, irrespective of whether the outcome is grey or noble rot., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Váczy, Otto, Gomba-Tóth, Geiger, Golen, Hegyi-Kaló, Cels, Geml, Zsófi and Hegyi.)

A comprehensive understanding of carbon cycling pathways in the soil-plant system is needed to develop models that accurately predict global carbon reservoir responses to anthropogenic perturbations. Honey is a carbon-rich natural food produced by wild and managed pollinating insects all over the world; the composition of a single sample is a function of millions of pollinator-plant interactions. We studied the 13 C/ 12 C and Δ 14 C of 121 honey samples sourced from the United States, and found a significant older carbon contribution. The effect is observed from 25 to 45° latitude, not correlated with 13 C/ 12 C, and consistent with a previously published study on European honeys. In specific cases, the measured values were up to 20 ‰ (Δ 14 C) higher than the expected atmospheric 14 CO 2 value for the given year, which shows a significant older carbon contribution. We hypothesize that the older carbon is from plant liquids derived in part from soil carbon or stored nonstructural carbohydrates from plants, which shifts the calibrated age of the sample by 5 years or more. Our work is the first to describe the widespread occurrence of older carbon in honey and shows that radiocarbon measurements can be a powerful tool to trace carbon allocations in terrestrial food webs and detect the atmosphere-soil-plant carbon cycle contributions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zsuzsa Lisztes-Szabó reports financial support was provided by Ministry for Culture and Innovation, Hungary. Edina Baranyai reports financial support was provided by Ministry for Culture and Innovation, Hungary. Ágota Ragyak reports financial support was provided by Ministry for Culture and Innovation, Hungary. Zsófi Sajtos reports financial support was provided by Ministry for Culture and Innovation, Hungary. Mihály Molnár reports financial support was provided by National Research, Development and Innovation Fund of Hungary. Szilárd Szabó reports financial support was provided by Széchenyi Plan Plus program. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: A false positive (FP) referral after screening mammography may influence a woman's likelihood to re-attend the screening program. The impact of having a FP result in the first or subsequent screening round on re-attendance after a FP result was investigated. In addition, we aimed to study differences in re-attendance rates between women who underwent non-invasive and invasive additional examinations as part of the diagnostic work-up following a FP referral., Methods: A consecutive series of 13,597 women with a FP referral following biennial screening mammography in the south of the Netherlands between 2009 and 2019 was included., Results: The screening re-attendance rate was 81.2% after a FP referral, and 91.3% when also including women who had clinical mammographic follow-up. Women who received a FP referral in the first screening round were less likely to re-attend the screening programme in the following three years, compared to those with a FP test in any subsequent round (odds ratio (OR): 0.59, 95%-confidence interval (CI): 0.51-0.69). Women with a FP referral who underwent invasive examinations after referral were less likely to re-attend the screening programme than those who only received additional imaging (OR, 0.48; 95% CI 0.36-0.64)., Conclusion: Women with a FP referral are less likely to re-attend the screening programme if this referral occurs at their first screening round or when they undergo invasive diagnostic workup. Hospitals and screening organizations should prioritize informing women about the importance of re-attending the programme following a FP referral., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The immune-modulating protein CD52 attenuates lymphocyte function and is associated with autoimmune disorders, for example, multiple sclerosis (MS). CD52 represents a therapeutic target in MS and chronic lymphocytic leukemia (CLL). Its expression has prognostic and predictive value in CLL and is prognostic in breast cancer. Its significance in melanoma is unclear. We analyzed CD52 mRNA expression data from tumor bulk tissues of N = 445 untreated melanoma patients from The Cancer Genome Atlas (TCGA) Research Network and of N = 121 melanoma patients undergoing anti-PD-1 immune checkpoint blockade (ICB) with regard to outcome (overall survival [OS], disease control [DC], and progression-free survival [PFS]), single-cell RNA-Seq data of N = 4645 cells from N = 19 melanoma tissues, and N = 15,457 cells from normal skin provided by N = 5 donors. Higher CD52 mRNA expression was associated with favorable OS (hazard ratio (HR) = 0.820, [95% CI 0.734-0.916], p < .001) in non-ICB-treated melanoma and with PFS (HR = 0.875, [95% CI 0.775-0.989], p = .033) and DC (p = .005) in ICB-treated melanoma. CD52 expression correlated significantly with distinct immune cell subsets and correlated negatively with immune checkpoint expression in T cells. Moreover, our results suggest CD52 expression by a certain type of tissue-resident macrophages. CD52 mRNA was expressed in a small subgroup (8%) of immune checkpoint coexpressing melanoma cells. CD52 expression is associated with features of ICB response in melanoma. Concomitant ICB and anti-CD52 treatment requires critical review., (© 2023 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

Soil contamination caused by the presence of Cd and the excess amount of Zn is a widespread concern in agricultural areas, posing significant risks to the growth and development of crops. In this paper, the early-stage development and metal (Cd and Zn) accumulation potential of rapeseed (Brassica napus L.) grown under different metal application schemes were assessed by determining radicle and hypocotyl length and the micro- and macro elemental composition of plantlets after 24, 72, and 120 h. The results indicated that the single and co-application of Cd and Zn significantly reduced the radicle and hypocotyl lengths. Accumulation intensity for Cd and Zn was affected by Cd and the combination of Cd and Zn in the solution, respectively. In addition, both metals significantly influenced the tissue Mn and had a minor effect on Cu and Fe concentrations. Both Cd and Zn significantly affected macro element concentrations by decreasing tissue Ca and influencing K and Mg concentrations in a dose- and exposure time-dependent manner. These findings specify the short-term and support the long-term use of rapeseed in remediation processes. However, interactions of metals are crucial in determining the concentration patterns in tissues, which deserves more attention in future investigations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The composition, diversity and dynamics of microbial communities associated with grapevines may be influenced by various environmental factors, including terroir , vintage, and season. Among these factors, terroir stands out as a unique possible determinant of the pathobiome, the community of plant-associated pathogens. This study employed high-throughput molecular techniques, including metabarcoding and network analysis, to investigate the compositional dynamics of grapevine fungal pathobiome across three microhabitats (soil, woody tissue, and bark) using the Furmint cultivar. Samples were collected during late winter and late summer in 2020 and 2021, across three distinct terroirs in Hungary's Tokaj wine region. Of the 123 plant pathogenic genera found, Diplodia, Phaeomoniella , and Fusarium displayed the highest richness in bark, wood, and soil, respectively. Both richness and abundance exhibited significant disparities across microhabitats, with plant pathogenic fungi known to cause grapevine trunk diseases (GTDs) demonstrating highest richness and abundance in wood and bark samples, and non-GTD pathogens prevailed soil. Abundance and richness, however, followed distinct patterns Terroir accounted for a substantial portion of the variance in fungal community composition, ranging from 14.46 to 24.67%. Season and vintage also contributed to the variation, explaining 1.84 to 2.98% and 3.67 to 6.39% of the variance, respectively. Notably, significant compositional differences in fungi between healthy and diseased grapevines were only identified in wood and bark samples. Cooccurrence networks analysis, using both unweighted and weighted metrics, revealed intricate relationships among pathogenic fungal genera. This involved mostly positive associations, potentially suggesting synergism, and a few negative relationships, potentially suggesting antagonistic interactions. In essence, the observed differences among terroirs may stem from environmental filtering due to varied edaphic and mesoclimatic conditions. Temporal weather and vine management practices could explain seasonal and vintage fungal dynamics. This study provides insights into the compositional dynamics of grapevine fungal pathobiome across different microhabitats, terroirs , seasons, and health statuses. The findings emphasize the importance of considering network-based approaches in studying microbial communities and have implications for developing improved viticultural plant health strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Leal, Geiger, Molnár, Váczy, Kgobe, Zsófi and Geml.)

Background: The majority of patients with recurrent or metastasized head and neck squamous cell carcinoma (HNSCC) do not benefit from immune checkpoint blockade (ICB) while several patients experience severe and persistent immune-mediated side effects. Therefore, predictive biomarkers are urgently needed to allow for a personalized treatment. In this study, we investigated DNA methylation of the immune checkpoint gene CTLA4 with regard to its predictive value., Methods: We analyzed CTLA4 promoter methylation in tumors of HNSCC patients (N = 29) treated with ICB at the University Medical Center Bonn with regard to response to ICB and progression-free survival. We further analyzed a second cohort (N = 138) of patients that did not receive ICB with regard to CTLA4 promoter methylation, CTLA-4 protein expression, and immune cell infiltrates. Finally, we tested inducibility of CTLA-4 protein expression in HNSCC cells using the DNA methyltransferase inhibitor decitabine., Results: Lower CTLA4 promoter methylation correlated with response to ICB and prolonged progression-free survival. We could show that not only tumor infiltrating immune cells, but also HNSCC cells harbor cytoplasmic and nuclear CTLA-4 expression. CTLA4 promoter methylation inversely correlated with infiltrates of CD3 + , CD4 + , CD8 + , and CD45 + immune cells. CTLA4 methylation did not correlate with protein expression in tumors, however, decitabine treatment led to decreased CTLA4 methylation and an induction of CTLA4 mRNA and CTLA-4 protein expression in HNSCC cell lines., Conclusions: Our results indicate that CTLA4 DNA hypomethylation is a predictive biomarker for response to ICB in HNSCC. Our study warrants further analyses of the predictive value of CTLA4 DNA methylation in clinical trials of anti-PD-1 and/or anti-CTLA-4 immunotherapy in HNSCC., (© 2023. The Author(s).)

Background: Inducible T cell costimulator ICOS is an emerging target in immuno-oncology. The aim of this study was to investigate the epigenetic regulation of ICOS in melanoma by DNA methylation., Methods: We comprehensively investigate ICOS DNA methylation of specific CpG sites and expression pattern within the melanoma microenvironment with regard to immune correlates, differentiation, clinical outcomes, and immune checkpoint blockade (ICB) response., Results: Our study revealed a sequence-contextual CpG methylation pattern consistent with an epigenetically regulated gene. We found a cell type-specific methylation pattern and locus-specific correlations and associations of CpG methylation with ICOS mRNA expression, immune infiltration, melanoma differentiation, prognosis, and response to ICB. High ICOS mRNA expression was identified as a surrogate for enriched immune cell infiltration and was associated with favorable overall survival (OS) in non-ICB-treated patients and predicted response and a prolonged progression-free survival (PFS) following ICB therapy initiation. ICOS hypomethylation, however, significantly correlated with poor OS in non-ICB patients but predicted higher response and prolonged PFS and OS in ICB-treated patients. Moreover, we observed cytoplasmic and sporadically nuclear tumor cell-intrinsic ICOS protein expression. Tumor cell-intrinsic ICOS protein and mRNA expression was inducible by pharmacological demethylation with decitabine., Conclusion: Our study identified ICOS DNA methylation and mRNA expression as promising prognostic and predictive biomarkers for immunotherapy in melanoma and points towards a hitherto undescribed role of ICOS in tumor cells., (© 2023. The Author(s).)

Electrospinning has recently been recognized as a potential method for use in biomedical applications such as nanofiber-based drug delivery or tissue engineering scaffolds. The present study aimed to demonstrate the electrospinning preparation and suitability of β-tricalcium phosphate-modified aerogel containing polyvinyl alcohol/chitosan fibrous meshes (BTCP-AE-FMs) for bone regeneration under in vitro and in vivo conditions. The mesh physicochemical properties included a 147 ± 50 nm fibrous structure, in aqueous media the contact angles were 64.1 ± 1.7°, and it released Ca, P, and Si. The viability of dental pulp stem cells on the BTCP-AE-FM was proven by an alamarBlue assay and with a scanning electron microscope. Critical-size calvarial defects in rats were performed as in vivo experiments to investigate the influence of meshes on bone regeneration. PET imaging using 18 F-sodium fluoride standardized uptake values (SUVs) detected 7.40 ± 1.03 using polyvinyl alcohol/chitosan fibrous meshes (FMs) while 10.72 ± 1.11 with BTCP-AE-FMs after 6 months. New bone formations were confirmed by histological analysis. Despite a slight change in the morphology of the mesh because of cross-linking, the BTCP-AE-FM basically retained its fibrous, porous structure and hydrophilic and biocompatible character. Our experiments proved that hybrid nanospun scaffold composite mesh could be a new experimental bone substitute bioactive material in future medical practice.

Unrecorded alcohol has been linked to illness above and beyond that caused by ethanol alone because of the presence of toxic contaminants. While it can be found in all countries, consumption is high in Albania, where it is frequently consumed as a fruit brandy known as rakia. Among the contaminants identified previously in such products, metals including lead have been detected at levels posing a risk to health but there is little information on their presence in rakia. To fill this gap, we measured the level of ethanol and 24 elements among them toxic metals in 30 Albanian rakia samples. We found that 63.3% of rakia samples had ethanol concentration above 40% v/v. We also showed that there was a significant difference between the measured [mean: 46.7% v/v, interquartile range (IQR): 43.4-52.1% v/v] and reported (mean: 18.9% v/v, IQR: 17.0-20.0% v/v) concentrations of ethanol in rakia. Among the metals detected, aluminium, copper, iron, manganese, lead, and zinc were present in rakia samples at concentrations ranging between 0.013 and 0.866 mg/l of pure alcohol (pa), 0.025-31.629 mg/l of pa, 0.004-1.173 mg/l of pa, 0.185-45.244 mg/l of pa, 0.044-1.337 mg/l of pa, and 0.004-10.156 mg/l of pa, respectively. Copper and lead were found to be the greatest concern posing a potential public health risk. Although the estimated daily intake of these heavy metals from unrecorded rakia was below their toxicological threshold, the concentrations of lead and copper exceeded their limit value of 0.2 and 2.0 mg/l of pa specified for spirits in 33% and 90% of samples, respectively. Therefore, the possibility of adverse health effects cannot be excluded completely. Our findings highlight the need for action by policymakers against the risks posed by these products in Albania., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

In this study, growth and ionomic responses of three duckweed species were analyzed, namely Lemna minor , Landoltia punctata , and Spirodela polyrhiza , were exposed for short-term periods to hexavalent chromium or nickel under laboratory conditions. It was found that different duckweed species had distinct ionomic patterns that can change considerably due to metal treatments. The results also show that, because of the stress-induced increase in leaf mass-to-area ratio, the studied species showed different order of metal uptake efficiency if plant area was used as unit of reference instead of the traditional dry weight-based approach. Furthermore, this study revealed that μXRF is applicable in mapping elemental distributions in duckweed fronds. By using this method, we found that within-frond and within-colony compartmentation of metallic ions were strongly metal- and in part species-specific. Analysis of duckweed ionomics is a valuable approach in exploring factors that affect bioaccumulation of trace pollutants by these plants. Apart from remediating industrial effluents, this aspect will gain relevance in food and feed safety when duckweed biomass is produced for nutritional purposes.

Background: The elderly use antibiotics frequently due to their increasing infection susceptibility. Given the high and increasing proportion of elderly in the population, their antibiotic use is substantial. Objective: This study aimed to compare antibiotic use in the elderly in the ambulatory care sector between Hungary and Sweden. Methods: This retrospective, descriptive, cross-national, comparative study included antibacterial use data from the Hungarian National Health Insurance Fund and the Swedish eHealth Agency. Antibiotic use (anatomical therapeutical chemical: J01) was expressed as the number of prescriptions/1000 inhabitants/year or month and was further stratified by age and sex. Results: Antibiotic exposure was higher in the Hungarian elderly population (649.8 prescriptions/1000 inhabitants/year) compared to its Swedish counterparts (545.0 prescriptions/1000 inhabitants/year). Hungary had a similar scale of antibacterial exposure across all elderly age subgroups, with different trends in males and females, while Sweden had a stepwise increase in antibiotic exposure by age in both sexes. The seasonal fluctuation was high in Hungary and reached a peak of 80.7 prescriptions/1000 inhabitants/month in January 2017, while even antibiotic use was detected throughout the year in Sweden. The pattern of antibiotic use in the elderly considerably differed between the two countries. Penicillin and beta-lactamase combinations, such as co-amoxiclav, were more frequently used in Hungary than in Sweden (19.08% vs 1.83% of corresponding total ambulatory antibiotic use). Likewise, quinolones were more commonly used in Hungary than in Sweden (34.53% vs. 9.98). The elderly in Sweden were mostly prescribed narrow spectra penicillins (26.71% vs. 0.29% in Hungary). Conclusion: This cross-national comparison revealed important differences in all aspects of antibiotic use in the elderly between the two countries. The identical scale and pattern of antibiotic use cannot be anticipated due to the poorer health status of the Hungarian elderly population. However, the substantial differences indicate some room for improvement in the antibiotic prescription for the Hungarian elderly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kusuma, Matuz, Bordás, Juhasz Haverinen, Bahar, Hajdu, Visnyovszki, Ruzsa, Doró, Engi, Csupor and Benko.)

Given the risk of Candida albicans overgrowth in the gut, novel complementary therapies should be developed to reduce fungal dominancy. This study highlights the antifungal characteristics of a Bacillus subtilis-derived secondary metabolite, surfactin with high potential against C. albicans. Surfactin inhibited the growth of C. albicans following a 1-hour exposure, in addition to reduced adhesion and morphogenesis. Specifically, surfactin did not affect the level of reactive oxygen species but increased the level of reduced glutathione. Surprisingly, ethanol production was increased following 2 h of surfactin exposure. Surfactin treatment caused a significant reduction in intracellular iron, manganese and zinc content compared to control cells, whereas the level of copper was not affected. Alongside these physiological properties, surfactin also enhanced fluconazole efficacy. To gain detailed insights into the surfactin-related effects on C. albicans, genome-wide gene transcription analysis was performed. Surfactin treatment resulted in 1390 differentially expressed genes according to total transcriptome sequencing (RNA-Seq). Of these, 773 and 617 genes with at least a 1.5-fold increase or decrease in transcription, respectively, were selected for detailed investigation. Several genes involved in morphogenesis or related to metabolism (e.g., glycolysis, ethanol and fatty acid biosynthesis) were down-regulated. Moreover, surfactin decreased the expression of ERG1, ERG3, ERG9, ERG10 and ERG11 involved in ergosterol synthesis, whereas genes associated with ribosome biogenesis and iron metabolism and drug transport-related genes were up-regulated. Our data demonstrate that surfactin significantly influences the physiology and gene transcription of C. albicans, and could contribute to the development of a novel innovative complementary therapy., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Improving our knowledge on biotic and abiotic factors that influence the composition of the grapevine mycobiome is of great agricultural significance, due to potential effects on plant health, productivity, and wine characteristics. Here, we assessed the influence of scion cultivar on the diversity and composition of fungal communities in the berries and leaves of three different cultivars. We generated DNA metabarcoding data, and statistically compared the richness, relative abundance, and composition of several functional groups of fungi among cultivars, which are partly explained by measured differences in chemical composition of leaves and berries and physiological traits of leaves. Fungal communities in leaves and berries show contrasting patterns among cultivars. The richness and relative abundance of fungal functional groups statistically differ among berry and leaf samples, but less so among cultivars. Community composition of the dominant functional groups of fungi, i.e., plant pathogens in leaves and saprotrophs in berries, differs significantly among cultivars. We also detect cultivar-level differences in the macro- and microelement content of the leaves, and in acidity and sugar concentration of berries. Our findings suggest that there appears to be a relatively diverse set of fungi that make up the grapevine mycobiome at the sampled terroir that spans several cultivars, and that both berry and leaf mycobiomes are likely influenced by the chemical characteristics of berries and leaves, e.g., pH and the availability of nutrients and simple carbohydrates. Finally, the correlation between fungal community composition and physiological variables in leaves is noteworthy, and merits further research to explore causality. Our findings offer novel insights into the microbial dynamics of grapevine considering plant chemistry and physiology, with implications for viticulture.

β-Tricalcium phosphate was combined with silica aerogel in composites prepared using the sol-gel technique and supercritical drying. The materials were used in this study to check their biological activity and bone regeneration potential with MG63 cell experiments. The composites were sintered in 100 °C steps in the range of 500-1000 °C. Their mechanical properties, porosities, and solubility were determined as a function of sintering temperature. Dissolution studies revealed that the released Ca-/P molar ratios appeared to be in the optimal range to support bone tissue induction. Cell viability, ALP activity, and type I collagen gene expression results all suggested that the sintering of the compound at approximately 700-800 °C as a scaffold could be more powerful in vivo to facilitate bone formation within a bone defect, compared to that documented previously by our research team. We did not observe any detrimental effect on cell viability. Both the alkaline phosphatase enzyme activity and the type I collagen gene expression were significantly higher compared with the control and the other aerogels heat-treated at different temperatures. The mesoporous silica-based aerogel composites containing β-tricalcium phosphate particles treated at temperatures lower than 1000 °C produced a positive effect on the osteoblastic activity of MG63 cells. An in vivo 6 month-long follow-up study of the mechanically strongest 1000 °C sample in rat calvaria experiments provided proof of a complete remodeling of the bone.

In this paper, we present the time-dependent elemental composition and AMS radiocarbon dating results of 36 rape, sunflower and forest honey samples, collected between 1985 and 2018 in geographically close locations. Based on the elemental information, we conclude that bee products regardless the type provide useful environmental information of the previous decades, such as the decreasing trend of airborne Pb emission can be traced. However, radiocarbon results agree less with the atmospheric bomb peak. Random offsets were observed in the specific radiocarbon activity of the honey samples indicating that rape, sunflower and forest honey samples are not as reliable materials for radiocarbon dating as acacia honeys. The radiocarbon results show that the rape, sunflower and forest honey samples can contain non-photosynthetic carbon, presumably derived from the soil. Thus, the complex application of honey samples for environmental reconstruction requires the species-separated investigation of bee products to reveal their adaptability for assessment approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The antifungal resistance threat posed by Candida auris necessitates bold and innovative therapeutic options. Farnesol is a quorum-sensing molecule with a potential antifungal and/or adjuvant effect; it may be a promising candidate in alternative treatment regimens. To gain further insights into the farnesol-related effect on C. auris, genome-wide gene transcription analysis was performed using transcriptome sequencing (RNA-Seq). Farnesol exposure resulted in 1,766 differentially expressed genes. Of these genes, 447 and 304 genes with at least 1.5-fold increase or decrease in transcription, respectively, were selected for further investigation. Genes involved in morphogenesis, biofilm events (maturation and dispersion), gluconeogenesis, iron metabolism, and regulation of RNA biosynthesis showed downregulation, whereas those related to antioxidative defense, transmembrane transport, glyoxylate cycle, fatty acid β-oxidation, and peroxisome processes were upregulated. In addition, farnesol treatment increased the transcription of certain efflux pump genes, including MDR1 , CDR1 , and CDR2 . Growth, measured by the change in the number of CFU, was significantly inhibited within 2 h of the addition of farnesol (5.8 × 10 7 ± 1.1 × 10 7 and 1.1 × 10 7 ± 0.3 × 10 7 CFU/ml for untreated control and farnesol-exposed cells, respectively) ( P < 0.001). In addition, farnesol treatment caused a significant reduction in intracellular iron (152.2 ± 21.1 versus 116.0 ± 10.0 mg/kg), manganese (67.9 ± 5.1 versus 18.6 ± 1.8 mg/kg), and zinc (787.8 ± 22.2 versus 245.8 ± 34.4 mg/kg) ( P < 0.05 to 0.001) compared to untreated control cells, whereas the level of cooper was significantly increased (274.6 ± 15.7 versus 828.8 ± 106.4 mg/kg) ( P < 0.001). Our data demonstrate that farnesol significantly influences the growth, intracellular metal ion contents, and gene transcription related to fatty acid metabolism, which could open new directions in developing alternative therapies against C. auris. IMPORTANCE Candida auris is a dangerous fungal pathogen that causes outbreaks in health care facilities, with infections associated with a high mortality rate. As conventional antifungal drugs have limited effects against the majority of clinical isolates, new and innovative therapies are urgently needed. Farnesol is a key regulator molecule of fungal morphogenesis, inducing phenotypic adaptations and influencing biofilm formation as well as virulence. Alongside these physiological modulations, it has a potent antifungal effect alone or in combination with traditional antifungals, especially at supraphysiological concentrations. However, our knowledge about the mechanisms underlying this antifungal effect against C. auris is limited. This study has demonstrated that farnesol enhances the oxidative stress and reduces the fungal survival strategies. Furthermore, it inhibits manganese, zinc transport, and iron metabolism as well as increases fungal intracellular copper content. In addition, metabolism was modulated toward β-oxidation. These results provide definitive explanations for the observed antifungal effects.

Background: Mineral oils have been widely used in the pest control of several crops. However, their mode of action is poorly understood, especially in the case of their antifungal properties. The possible direct fungicidal activity and the stress-inducing capability of paraffin oil on grapevine were examined using Vitis vinifera L. cv 'Kékfrankos' cuttings and the fungus Erysiphe necator, the causal agent of powdery mildew., Results: Our experiments demonstrated that paraffin oil does not have fungicide activity on E. necator, but induces significant stress-related changes in grapevine physiology. Elevated H 2 O 2 production and the accumulation of the phytohormone salicylic acid were measured. Secondary thickening of the cell wall by lignin deposition and the accumulation of phenolic compounds were also observed. Some enzyme activities related to the detoxification of reactive oxygen species, disease response, and the synthesis of lignin were changed in accordance with the determined changes in cell wall composition and H 2 O 2 levels., Conclusion: The results suggest that paraffin oil induces stress responses on grapevine leaves through oxidative burst, and this response is systemized by salicylic acid. The accumulation of lignin and water-soluble phenolics may be directly responsible for the paraffin oil-induced resistance of grapevine against powdery mildew. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

The glucocorticoid betamethasone (BM) has potent anti-inflammatory and immunosuppressive effects; however, it increases the susceptibility of patients to superficial Candida infections. Previously we found that this disadvantageous side effect can be counteracted by menadione sodium bisulfite (MSB) induced oxidative stress treatment. The fungus specific protein phosphatase Z1 (CaPpz1) has a pivotal role in oxidative stress response of Candida albicans and was proposed as a potential antifungal drug target. The aim of this study was to investigate the combined effects of CaPPZ1 gene deletion and MSB treatment in BM pre-treated C. albicans cultures. We found that the combined treatment increased redox imbalance, enhanced the specific activities of antioxidant enzymes, and reduced the growth in cappz1 mutant (KO) strain. RNASeq data demonstrated that the presence of BM markedly elevated the number of differentially expressed genes in the MSB treated KO cultures. Accumulation of reactive oxygen species, increased iron content and fatty acid oxidation, as well as the inhibiting ergosterol biosynthesis and RNA metabolic processes explain, at least in part, the fungistatic effect caused by the combined stress exposure. We suggest that the synergism between MSB treatment and CaPpz1 inhibition could be considered in developing of a novel combinatorial antifungal strategy accompanying steroid therapy.

The biggest threat to beekeeping is varroosis caused by the mite Varroa destructor . Chemicals available to treat this fatal disease may present problems of resistance or inconsistent efficacy. Recently, lithium chloride has appeared as a potential alternative. To date, the amount of residue lithium treatments may leave in honeybee products is poorly understood. Honeybees were fed with 25 mM lithiated sugar syrup, which was used in earlier studies. The accumulation and elimination of the lithium were monitored in bees and their products for 22 days. Lithium concentration increased in the entire body of the bees to day 4 post-treatment and then recovered rapidly to the control level. Lithium exposure was found to affect uncapped honey in the short term (<16 days), but ripe (capped) honey measured at the end of the trial remained affected. On the other hand, lithium treatment left beeswax lithium-free. Based on these data, we propose that comprehensive research on harvested honey is needed to decide on the veterinary use of lithium.

In present study the effect of iron (Fe) and manganese (Mn) contamination was assessed by modeling a freshwater food web of water, zooplankton (Daphnia pulex), and zebrafish (Danio rerio) under laboratory conditions. Metals were added to the rearing media of D. pulex, and enriched zooplankton was fed to zebrafish in a feeding trial. The elemental analysis of rearing water, zooplankton, and fish revealed significant difference in the treatments compared to the control. In D. pulex the Mn level increased almost in parallel with the dose of supplementation, as well as the Fe level differed statistically. A negative influence of the supplementation on the fish growth was observed: specific growth rate (SGR%) and weight gain (WG) decreased in Fe and Mn containing treatments. The redundancy analysis (RDA) of concentration data showed strong correlation between the rearing water and D. pulex, as well as the prey organism of Fe- and Mn-enriched D. pulex and the predator organism of D. rerio. The bioconcentration factors (BCF) calculated for water to zooplankton further proved the relationship between the Fe and Mn dosage applied in the treatments and measured in D. pulex. Trophic transfer factor (TTF) results also indicate that significant retention of the metals occurred in D. rerio individuals, however, in a much lower extent than in the water to zooplankton stage. Our study suggests that Fe and Mn significantly accumulate in the lower part of the trophic chain and retention is effective through the digestive track of zebrafish, yet no biomagnification occurs. Graphical abstract.

Botrytis cinerea is a well-known pathogen of grapevine. However, under certain microclimatic conditions, Botrytis infection results in noble rot, an essential process in the production of the world-known Tokaji aszú wines in Hungary. We investigated the physico-chemical characteristics and culturable microorganisms associated with grape berries through several noble rot phases in the two main cultivars grown in Tokaj: Vitis vinifera cv. " Furmint " and " Hárslevelű ". We measured physical and analytical parameters routinely tested in viticulture and analyzed the ITS rDNA sequence data of fungi isolated from the sampled berries. We observed significant differences in the physico-chemical parameters among the noble rot phases as well as sampling dates. The greatest variation in berry texture and microbial structure was observed in the initial phases, with variables converging as the noble rot progressed. By finding a bijection between the examined chemical properties and the factorial parameters (e.g., noble rot phase, collection time, cultivar), an appropriate sweet winemaking material can be designed. Fungal community differed significantly among cultivars, with higher number of species observed in Hárslevelű . Our results reveal that there is more to noble rot than only Botrytis cinerea and other microorganisms may play important roles in the aszú process.

Several studies show that the elemental content of honey entirely depends on the botanical and geographical origin, but the information is incomplete regarding its time-dependent composition changes. Twenty-six acacia and three honey samples with unknown botanical origin were collected between 1958 and 2018 and analysed for elemental composition by Microwave Plasma Atomic Emission Spectrometry (MP-AES). The elemental analysis was coupled with independent dating method by Accelerator Mass Spectrometry (AMS) to confirm the calendar age of the honey samples and test the possibility of radiocarbon based dating of bee products, which has not been applied before. According to the analytical measurements and statistical analysis, we can conclude that the elemental composition shows change with time in the acacia honey during the last five decades. We have proven that honey preserves carbon isotopic and elemental information of its production time and thus can be applied as an environmental indicator (e.g. trace urban pollutants, precipitation, local industrial or agricultural emission) in reconstruction studies by analysing the non-degradable mineral content. Our results further show that acacia honey is a suitable material for radiocarbon dating, proved by the results compared to the atmospheric radiocarbon bomb-peak. The new approach presented for investigation of honey by radiocarbon-based age determination coupled with elemental analysis can be used in biological, dietary, archaeological or other multidisciplinary studies as well. Some samples show slightly depleted radiocarbon content. This could be an indication of local fossil CO 2 emission. Based on these depleted 14 C results, honey could be used for atmospheric monitoring of fossil CO 2 urban or industrial hot-spots., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Taste is not a veridical perception: it is modifiable by cognitive and affective processes, as well as by expectations. Even though molecular composition determines the savor, various other factors such as external characteristics and basic assumptions have a sway over perceived pleasantness of food and drink. The rituals associated with wine tastings especially underscore the importance of these subjective ramifications. While auditory stimuli are known to influence drinking experience, the impact of melody on the product itself and on corollary consumer preference is unknown. As routine judgments are also influenced by informational cues, here we evaluated whether description of a unique technological innovation (i.e., serenaded grapes and barrels) as cogent suggestion of quality improves willingness to buy. This project unveils that the belief about music-fed wines, which might be construed as a motivational bias, can alter purchasing decisions; however, further neuro-marketing studies are warranted with this respect., (Copyright © 2019 Soós, Csernák, Lakatos, Zsófi and Palotás.)

Unlabelled: Previous studies have suggested an increasing use of complementary and alternative medicine (CAM) in patients with inflammatory bowel disease (IBD). Furthermore, a significant number of IBD patients fail to comply with treatment. The aim of our study was to evaluate the prevalence of non-adherence the use of CAM in Hungarian patients with IBD., Methods: A total of 655 consecutive IBD patients (Crohn's disease [CD]: 344, age: 38.2 + or - 12.9 years; ulcerative colitis [UC]: 311, age: 44.9 + or - 15.3 years) were interviewed during the visit at specialists by self-administered questionnaire including demographic and disease-related data, as well as items analyzing the extent of non-adherence and CAM use. Patients taking more then 80% of each prescribed medicine were classified as adherent., Results: The overall rate of self reported non-adherence (CD: 20.9%, UC: 20.6%) and CAM (CD: 31.7%, UC: 30.9%) use was not different between CD and UC. The most common causes of non-adherence were: forgetfulness (47.8%), too many/unnecessary pills (39.7%), being afraid of side effects (27.9%) and too frequent dosing. Most common forms of CAM were herbal tee (47.3%), homeopathy (14.6%), special diet (12.2%), and acupuncture (5.8%). In CD, disease duration, date of last follow-up visit, educational level and previous surgeries were predicting factors for non-adherence. Alternative medicine use was associated in both diseases with younger age, higher educational level and immunosuppressant use. In addition, CAM use in UC was more common in females and in patients with supportive psychiatric/psychological therapy., Conclusions: Non-adherence and CAM use is common in patients with IBD. Special attention should be paid to explore the identified predictive factors during follow-up visits to improve adherence to therapy and improving patient-doctor relationship.

Heat sensitivity of grapevine (Vitis vinifera L. cv. Kékfrankos) photosynthesis was studied in two vineyards (Eger-Kőlyuktető, flat; and Eger-Nagyeged hill, steep slope) with different mesoclimates and water supply conditions in two climatically different years. 2007 was drier and warmer, with higher vapour pressure deficit (VPD) than 2005. Pre-dawn water potential measurements indicated mild water deficit at the steep-sloped vineyard. In July 2005 mild water deficit enhanced the thermostability of grapevine photosynthesis, as reflected in the temperature dependence of optimal quantum yield (F v /F m ) and in the critical temperature of initial fluorescence (F 0 T c ). Decreased F v /F m and actual quantum yield (ΔF/F m ') was recorded at most temperatures in September at the water-stressed (steep slope) site. This time, F 0 T c s were also lower due to early leaf senescence. In September 2007, heat sensitivity of F v /F m was similar to 2005, and ΔF/F m ' indicated higher thermostability at both sites, but keeping the consistent difference between the two vineyards. The critical points of steady-state fluorescence (F s T c ) were higher by 3-6°C at both vineyards in 2007 than in 2005. Although, in September thermolabile F 0 signals were measured at the water-stressed vineyard, the heat sensitivity was not decreased in light adapted state, assumingly as a result of enhanced xanthophyll cycle pigment pool size. The higher xanthophyll pigments pool size (V + A + Z) in 2007 (compared to 2005) at the unstressed (flat) vineyard suggests that high temperature and VPD play a role in changing (V + A + Z)/(chl a + b), and, thus, results in higher thermostability under high light conditions.

The hybrid Richter-110 (Vitis berlandieri x Vitis rupestris) (R-110) has the reputation of being a genotype strongly adapted to drought. A study was performed with plants of R-110 subjected to water withholding followed by re-watering. The goal was to analyze how stomatal conductance (g(s)) is regulated with respect to different physiological variables under water stress and recovery, as well as how water stress affects adjustments of water use efficiency (WUE) at the leaf level. Water stress induced a substantial stomatal closure and an increase in WUE, which persisted many days after re-watering. The g(s) during water stress was mainly related to the content of ABA in the xylem and partly related to plant hydraulic conductivity but not to leaf water potential. By contrast, low g(s) during re-watering did not correlate with ABA contents and was only related to a sustained decreased hydraulic conductivity. In addition to a complex physiological regulation of stomatal closure, g(s) and rate of transpiration (E) were strongly affected by leaf-to-air vapor pressure deficit (VPD) in a way dependent of the treatment. Interestingly, E increased with increasing VPD in control plants, but decreased with increasing VPD in severely stressed plants. All together, the fine stomatal regulation in R-110 resulted in very high WUE at the leaf level. This genotype is revealed to be very interesting for further studies on the physiological mechanisms leading to regulation of stomatal responsiveness and WUE in response to drought.