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The combined use of non-invasive on-site portable techniques, Raman microscopy, and X-ray fluorescence spectroscopy on seven imperial bowls and two decorated dishes, attributed to the reigns of the Kangxi, Yongzheng, Qianlong, and Daoguang emperors (Qing Dynasty), allows the identification of the coloring agents/opacifiers and composition types of the glazes and painted enamels. Particular attention is paid to the analysis of the elements used in the (blue) marks and those found in the blue, yellow, red, and honey/gilded backgrounds on which, or in reserve, a floral motif is principally drawn. The honey-colored background is made with gold nanoparticles associated with a lead- and arsenic-based flux. One of the red backgrounds is also based on gold nanoparticles, the second containing copper nanoparticles, both in lead-based silicate enamels like the blue and yellow backgrounds. Tin and arsenic are observed, but cassiterite (SnO2) is clearly observed in one of the painted decors (dish) and in A676 yellow, whereas lead (calcium/potassium) arsenate is identified in most of the enamels. Yellow color is achieved with Pb-Sn-Sb pyrochlore (Naples yellow) with various Sb contents, although green color is mainly based on lead-tin oxide mixed with blue enamel. The technical solutions appear very different from one object to another, which leads one to think that each bowl is really a unique object and not an item produced in small series. The visual examination of some marks shows that they were made in overglaze (A608, A616, A630, A672). It is obvious that different types of cobalt sources were used for the imprinting of the marks: cobalt rich in manganese for bowl A615 (Yongzheng reign), cobalt rich in arsenic for bowl A613 (but not the blue mark), cobalt with copper (A616), and cobalt rich in arsenic and copper (A672). Thus, we have a variety of cobalt sources/mixtures. The high purity of cobalt used for A677 bowl indicates a production after similar to 1830-1850., NA

The in vitro effects on mycelial growth of the antagonistic fungi Trichoderma asperellum (ICC 012) and Trichoderma gamsii (ICC 080) were studied based on the active ingredients of 12 commonly used herbicides: amidosulfuron, dicamba, fluazifop-P-butyl, fluorochloridone, foramsulfuron, isoxaflutole, metribuzin, pendimethalin, prosulfocarb, pyridate, S-metolachlor and tembotrione. The fungal growth rates were evaluated at 20 °C and 25 °C using PDA plates that included 100%, 75%, 50%, 25%, 12.5%, 6.25% and 0% of the recommended herbicide application rates. These herbicides were classified into four categories based on inhibition of mycelial growth in the toxicity testing. Growth inhibition of Trichoderma spp. was seen for all of these herbicides at almost all doses and at both temperatures, although some major differences were seen. Lower herbicide concentrations in the agar also reduced the inhibitory effects, but generally not linearly. Temperature had no significant effects on the levels of inhibition of mycelial growth. Amidosulfuron, dicamba and isoxaflutole showed the least inhibition of mycelial growth of both Trichoderma spp., and the lowest doses with amidosulforone (6.25%, 12.5%) even significantly stimulated mycelial growth of both Trichoderma spp. Fluazifop-P-butyl, pyridate and tembotrione showed moderately harmful to harmful effects on mycelial growth, with 70% to 80% inhibition at the recommended herbicide application rates. Fluorochloridone, S-metolachlor, prosulfocarb, metribuzin and pendimethalin inhibited mycelial growth the most, in descending order of inhibition. At 50% to 100%, fluorochloridone, prosulfocarb and S-metolachlor had fungicidal effects. Fluorochloridone and prosulfocarb had significant inhibitory effects (> 75%) even at the lowest concentration of 6.25%. Of these herbicides tested, the least adverse effects were seen for amidosulfuron, dicamba and isoxaflutole, which are thus likely to be compatible with Trichoderma spp. in the field.

Gram-negative bacteria release Outer Membrane Vesicles (OMVs) into the extracellular environment. Recent studies recognized these vesicles as vectors to horizontal gene transfer, however, the parameters that mediate OMVs transfer within bacterial communities remain unclear. The present study highlights for the first time the transfer of plasmids containing resistance genes via OMVs derived from Klebsiella pneumoniae (K. pneumoniae). This mechanism confers DNA protection, it is plasmid copy number dependent with a ratio of 3.6 times among high copy number plasmid (pGR) versus low copy number plasmid (PRM), and the transformation efficiency was 3.6 times greater. Therefore, the DNA amount in the vesicular lumen and the efficacy of horizontal gene transfer was strictly dependent on the identity of the plasmid. Moreover, the role of K. pneumoniae-OMVs in interspecies transfer was described. The transfer ability was not related to the phylogenetic characteristics between the donor and the recipient species. K. pneumoniae-OMVs transferred plasmid to Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa and Burkholderia cepacia. These findings address the pivotal role of K. pneumoniae-OMVs as vectors for antimicrobial resistance genes spread, contributing to the development of antibiotic resistance in the microbial communities.

Viral infections represent a serious threat to the world population and are becoming more frequent. The search and identification of broad-spectrum antiviral molecules is necessary to ensure new therapeutic options, since there is a limited availability of effective antiviral drugs able to eradicate viral infections, and consequently due to the increase of strains that are resistant to the most used drugs. Recently, several studies on antimicrobial peptides identified them as promising antiviral agents. In detail, amphibian skin secretions serve as a rich source of natural antimicrobial peptides. Their antibacterial and antifungal activities have been widely reported, but their exploitation as potential antiviral agents have yet to be fully investigated. In the present study, the antiviral activity of the peptide derived from the secretion of Rana tagoi, named AR-23, was evaluated against both DNA and RNA viruses, with or without envelope. Different assays were performed to identify in which step of the infectious cycle the peptide could act. AR-23 exhibited a greater inhibitory activity in the early stages of infection against both DNA (HSV-1) and RNA (MeV, HPIV-2, HCoV-229E, and SARS-CoV-2) enveloped viruses and, on the contrary, it was inactive against naked viruses (PV-1). Altogether, the results indicated AR-23 as a peptide with potential therapeutic effects against a wide variety of human viruses.

In recent years, the sanitization of environments, devices, and objects has become mandatory to improve human and environmental safety, in addition to individual protection and prevention measures. International studies considered ozone one of the most useful and easy sanitization methods for indoor environments, especially hospital environments that require adequate levels of disinfection. The purpose of this work was to evaluate the microclimate influence on sanitizing procedure for indoor settings with ozone, to prevent infections and ensure the safe use of the environments. The concentration of ozone was measured during sanitization treatment and estimation of microorganisms’ survival on the air and different contaminated plates after the sanitization operations were performed. The results demonstrated a significant reduction in the microbial count that always fell below the threshold value in different conditions of distance, temperature, and relative humidity.

Introduction: The transition to menopause is characterized by mood, behavioral and metabolic changes. However, little is known about the changes in adrenal response to stress. Aims: The aim of the study was to evaluate, in an animal model of perimenopause induced by 4-vinylcyclohexene diepoxide (VCD), (1) the endocrine and neuronal stress system activity in response to acute restraint stress and (2) the effect of hormonal therapy in this response. Methods: Prepubertal female Wistar rats received daily injections (s.c) of oil or VCD (160 mg/kg) for 15 days. On 56th–66th days after treatment onset, the groups to be stressed received s.c implants containing placebo (PL), 17β-estradiol (E2), progesterone (P4), or E2P4. At 80 ± 5 days after VCD/oil injections, stress was applied for 30 min. Blood samples were collected immediately after and 60 min after the end of stress session from the tail tip followed by transcardial perfusion with PFA 4% for the assessment of c-Fos expression in the medial and posterior parvocellular (PaMP and PaPo) subdivisions of the paraventricular nucleus (PVN) and c-Fos/tyrosine hydroxylase in the locus coeruleus (LC) using immunohistochemistry. Control groups were not stressed nor received hormone therapy. Results: While basal corticosterone levels were similar between VCD-periestropausal and control rats, the secretion in response to stress in the VCD group was lower. This effect was prevented by P4 therapy. Inversely, basal levels of P4 were lower in VCD-periestropausal rats than in the controls, and no differences were found in response to stress between the groups. As expected, 30-min restraint stress increased c-Fos immunoreactivity in all brain areas studied in both control and VCD-periestropausal rats. However, the c-Fos increase in the PaMP region was attenuated. In all areas examined, there were no significant differences in the number of c-Fos-positive neurons across hormonal therapies. Discussion/Conclusion: This is the first study to demonstrate in a perimenopausal rat model that reproductive aging is accompanied by inadequate secretion of corticosterone in response to acute stress in association with the hypoactivation of the PaMP region of the PVN, while adrenal P4 response is preserved. Moreover, P4 therapy was shown to attenuate the effects of progressive ovarian failure on adrenal functioning during stress.

The increase in multidrug-resistant bacteria represents a true challenge in the pharmaceutical and biomedical fields. For this reason, research on the development of new potential antibacterial strategies is essential. Here, we describe the development of a green system for the synthesis of silver nanoparticles (AgNPs) bioconjugated with chitosan. We optimized a Prunus cerasus leaf extract as a source of silver and its conversion to chitosan–silver bioconjugates (CH-AgNPs). The AgNPs and CH-AgNPs were characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV–Vis), and zeta potential measurement (Z-potential). The cytotoxic activity of AgNPs and CH-AgNPs was assessed on Vero cells using the 3-[4.5-dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide (MTT) cell proliferation assay. The antibacterial activity of AgNPs and CH-AgNPs synthesized using the green system was determined using the broth microdilution method. We evaluated the antimicrobial activity against standard ATCC and clinically isolated multisensitive (MS) and multidrug-resistant bacteria (MDR) Escherichia coli (E. coli), Enterococcus faecalis (E. faecalis), Klebsiella pneumonia (K. pneumoniae), and Staphylococcus aureus (S. aureus), using minimum inhibitory concentration (MIC) assays and the broth dilution method. The results of the antibacterial studies demonstrate that the silver chitosan bioconjugates were able to inhibit the growth of MDR strains more effectively than silver nanoparticles alone, with reduced cellular toxicity. These nanoparticles were stable in solution and had wide-spectrum antibacterial activity. The synthesis of silver and silver chitosan bioconjugates from Prunus cerasus leaf extracts may therefore serve as a simple, ecofriendly, noncytotoxic, economical, reliable, and safe method to produce antimicrobial compounds with low cytotoxicity.

The increasing spread of multidrug-resistant pathogenic bacteria is one of the major threats to public health worldwide. Bacteria can acquire antibiotic resistance and virulence genes through horizontal gene transfer (HGT). A novel horizontal gene transfer mechanism mediated by outer membrane vesicles (OMVs) has been recently identified. OMVs are rounded nanostructures released during their growth by Gram-negative bacteria. Biologically active toxins and virulence factors are often entrapped within these vesicles that behave as molecular carriers. Recently, OMVs have been reported to contain DNA molecules, but little is known about the vesicle packaging, release, and transfer mechanisms. The present review highlights the role of OMVs in HGT processes in Gram-negative bacteria.

Here we present results of digital modelling of a specific setting of hypogenic carbonic acid speleogenesis (CAS). We study an unconfined aquifer where meteoric water seeps through the vadose zone and becomes saturated with respect to calcite when it arrives at the water table. From below, deep-seated water with high p CO 2 and saturated with respect to calcite invades the limestone formation by forced flow. Two flow domains arise that host exclusively water from the meteoric or deep-seated source. They are separated by a water divide. There by dispersion of flow, a fringe of mixing arises and widening of the fractures is caused by mixing corrosion (MC). The evolution of the cave system is determined by its early state. At sites with high rates of fracture widening, regions of higher hydraulic conductivity are created. They attract flow and support one-by-one mixing with maximal dissolution rates. Therefore, the early evolution is determined by karstification originating close to the input of the upwelling water and at the output at a seepage face. In between these regions, a wide fringe of moderate dissolution is present. In the later stage of evolution, this region is divided by constrictions that originate from statistical variations of fracture aperture widths that favour high dissolution rates and focus flow into this region. This MC-fringe instability is an intrinsic property of cave evolution and is present in all scenarios studied. We have investigated the influence of defined regions with higher fracture aperture widths. These determine the cave patterns and suppress MC-fringe instabilities. We have discussed the influence of the ratio of upwelling water flux rates on the rates of meteoric water. This ratio specifies the position of the mixing fringe and consequently that of the cave system. In a further step, we have explored the influence of time-dependent meteoric recharge. Furthermore, we have modelled scenarios where waters are undersaturated with respect to calcite. These findings give important insight into mechanisms of CAS in a special setting of unconfined aquifers. They also have implications for the understanding of corresponding sulfuric acid speleogenesis (SAS).

In this study, crude glycerol from the biodiesel industry was tested as a co-substrate in biogas production. To investigate the influence of crude glycerol and the underlying trace element (TE) content on the efficiency of biomethane production, a batch experiment using Automatic Methane Potential Test System (AMPTS II) was carried out. The single addition of crude glycerol significantly contributed only to the total content of K (14.4%), Si (17.3%), and P (11.6%), whereas the contributions of other metals were within the range of other substrates. The addition of crude glycerol increased biomethane production, however, its utilization beyond 1% of total volume resulted in prolonged lag phase and final cessation of biomethane production. The negative effects of inorganic salts present in crude glycerol were reflected in progressively diminishing parts of glycerol and methanol being utilized in its anaerobic digestion, posing serious problems for daily routine use. A nonlinear least square regression analysis was performed to fit the Gompertz, Logistic, Transfer, and Richards models to biomethane production. The most suitable model was the Richards model, exhibiting the best fit to the experimental curves for complex substrates. Glycerol fractions remaining after biodiesel production have to be pre-tested for their negative effects on the content of TEs and inorganic salts, lag phase in biogas production, before they are used as co-substrates in biogas production phase.

Background At present, although cholecalciferol represents the form of vitamin D of choice for the treatment of vitamin D deficiency, there is a growing interest in calcifediol. Aims This study aimed to evaluate the efficacy and the safety of two different daily doses of calcifediol. Methods Fifty osteopenic/osteoporotic women with serum levels of 25-hydroxyvitamin D (25OHD) between 10 and 20 ng/ml were randomized to a 6-month treatment with oral calcifediol 20 µg/day (n = 25) or oral calcifediol 30 µg/day (n = 25). In all, we measured the time course of the levels of 25OHD and other biochemical parameters. Moreover, we evaluated handgrip strength and serum levels of myostatin. Results The peak increase in 25OHD levels was reached after 90 days of treatment in group 1 (59.3 ng/ml) and after only 60 days in group 2 (72.3 ng/ml); thereafter in both groups, the levels of 25OHD showed a tendency towards stabilization. After 30 days, all the patients treated with 30 µg/day had values of 25OHD > 30 ng/ml. Handgrip strength showed a modest but progressive increase which reached the statistical significance in the 30 µg/day group. This latter group also presented a modest and non-significant decrease in serum levels of myostatin. Conclusions Calcifediol is able to rapidly normalize the vitamin D deficiency, and the 30 µg daily dosage could be suggested in those patients who need to rapidly reach optimal 25OHD levels. Moreover, the 6-month treatment with calcifediol at a dose of 30 µg results in a modest but significant increase in upper limb strength.

Purpose The purpose of this study is the design, fabrication and evaluation of a miniature ozone generator using the principle of electric discharge are presented. Design/methodology/approach The device was fabricated using a low-temperature co-fired ceramics (LTCC) technology, by which a multilayered ceramic structure with integrated electrodes, buried channels and cavities in micro and millimeter scales was realized. Findings The developed ozone generator with the dimensions of 63.6 × 41.8 × 1.3 mm produces approximately 1 vol. % of ozone in oxygen flow of 15 ml/min, at an applied voltage of 7 kV. Originality/value A miniature ozone generator, manufactured in LTCC technology, produces high amount of ozone and more than it is described in the available references or in datasheets of commercial devices of similar size.

Graphical abstract, Highlights • High-resolution solution NMR structure of rhNGF has been determined. • Quinary interactions characterize ATP binding to rhNGF. • SPR, ITC and STD-NMR reveal ATP binding to rhNGF with mM affinity. • NMR and MD analysis pinpoint to the presence of two binding sites of ATP on rhNGF. • Stoichiometry of ATP-Mg2+ or Zn2+-rhNGF mixtures affects KD affinity to TrkA/p75NTR., The Nerve Growth Factor (NGF) neurotrophin acts in the maintenance and growth of neuronal populations. Despite the detailed knowledge of NGF’s role in neuron physiology, the structural and mechanistic determinants of NGF bioactivity modulated by essential endogenous ligands are still lacking. We present the results of an integrated structural and advanced computational approach to characterize the extracellular ATP-NGF interaction. We mapped by NMR the interacting surface and ATP orientation on NGF and revealed the functional role of this interaction in the binding to TrkA and p75NTR receptors by SPR. The role of divalent ions was explored in conjunction with ATP. Our results pinpoint ATP as a likely transient molecular modulator of NGF signaling, in health and disease states.

Background Metallic nanoparticles (NPs) are highly exploited in manufacturing and medical processes in a broad spectrum of industrial applications and in the academic sectors. Several studies have suggested that many metallic nanomaterials including those derived by silver (Ag) are entering the ecosystem to cause significant toxic consequences in cell culture and animal models. However, ecotoxicity studies are still receiving limited attention when designing functionalized and non.-functionalized AgNPs. Objective This study aimed to investigate different ecotoxicological profiles of AgNPs, which were analyzed in two different states: in pristine form uncoated AgNPs and coated AgNPs with the antimicrobial peptide indolicidin. These two types of AgNPs are exploited for a set of different tests using Daphnia magna and Raphidocelis subcapitata, which are representatives of two different levels of the aquatic trophic chain, and seeds of Lepidium sativum, Cucumis sativus and Lactuca sativa. Results Ecotoxicological studies showed that the most sensitive organism to AgNPs was crustacean D. magna, followed by R. subcapitata and plant seeds, while AgNPs coated with indolicidin (IndAgNPs) showed a dose-dependent decreased toxicity for all three. Conclusion The obtained results demonstrate that high ecotoxicity induced by AgNPs is strongly dependent on the surface chemistry, thus the presence of the antimicrobial peptide. This finding opens new avenues to design and fabricate the next generation of metallic nanoparticles to ensure the biosafety and risk of using engineered nanoparticles in consumer products.

Introduction Lipoprotein (a) [Lp(a)] is a risk factor for coronary artery disease (CAD). To the best of our knowledge, this is the first study addressing the relationship between Lp(a) and platelet reactivity in primary and secondary prevention. Methods Lp(a) was evaluated in 396 individuals with (82.3%) and without (17.7%) obstructive CAD. The population was divided into two groups according to Lp(a) concentrations with a cutoff value of 50 mg/dL. The primary objective was to evaluate the association between Lp(a) and adenosine diphosphate (ADP)-induced platelet reactivity using the VerifyNow™ P2Y12 assay. Platelet reactivity was also induced by arachidonic acid and collagen–epinephrine (C-EPI) and assessed by Multiplate™, platelet function analyzer™ 100 (PFA-100), and light transmission aggregometry (LTA) assays. Secondary objectives included the assessment of the primary endpoint in individuals with or without CAD. Results Overall, 294 (74.2%) individuals had Lp(a) 0.05). Finally, multivariable analysis did not show a significant association between ADP-induced platelet reactivity and Lp(a) ≥ 50 mg/dL [adjusted OR = 1.00 [(95% CI 0.99–1.01), P = 0.590]. Conclusion In individuals with or without CAD, Lp(a) ≥ 50 mg/dL was not associated with higher platelet reactivity. Electronic supplementary material The online version of this article (10.1007/s12325-020-01483-y) contains supplementary material, which is available to authorized users.

Drying fruit is one of the simplest ways to extend the shelf-life of fruit, especially berries. Both higher temperature and time of heating significantly change the contents of some primary and secondary metabolites in honeysuckle fruit. Differences in their contents arising from different heat treatments were determined with the aid of high-performance liquid chromatography (HPLC) coupled with mass spectrophotometry (MS). The content of sugars showed a small change with drying, while organic acid contents decreased with a longer drying time. Ascorbic acid was totally degraded, regardless of the time or heating temperature. Different phenolic groups responded differently to heat intensity and time of drying. Flavanols were more sensitive to higher temperature than to duration of heating and they decreased by more than 70% at 75 °C. In contrast, the content of hydroxycinnamic acids, increased with drying by more than 75%, regardless of the time and temperature.

A produção de microalgas nas Estações de Tratamento de Esgoto (ETE) está deixando de ser vista como um problema e passando a ser vislumbrada como matéria-prima para a obtenção de biocombustível. A biomassa algal apresenta poder calorífico superior (PCS) similar ao da madeira e pode ser usado em processos termoquímicos para a geração de energia. Contudo, essa análise requer mais atenção, uma vez que a literatura normalmente apresenta o PCS para espécies puras de microalgas e sem a presença de coagulantes. Este trabalho analisou a influência de diferentes coagulantes comerciais no PCS da biomassa algal, obtida em lagoas de alta taxa com efluente de reator UASB. Além dos coagulantes inorgânicos tradicionais, polímeros catiônicos também foram avaliados. O coagulante polímero catiônico polydadmac teve o melhor custo-benefício e o PCS deste lodo foi de 21,19MJ/Kg.

Simple Summary RAB7A (RAs-related in Brain 7A) is a master regulator of intracellular traffic controlling transport to late endosomes and lysosomes, two organelles of the endocytic pathway important for degradation. Thanks to this function, RAB7A is also involved in cellular processes linked to cancer, such as apoptosis, cytoskeletal reorganization, and cell migration. Therefore, the interest in the role of RAB7A in cancer progression is increasing. Previously, we demonstrated that RAB7A regulates phosphorylation and assembly of vimentin, a cytoskeletal intermediate filament protein, which is also an important mesenchymal marker of cancer cells. The aim of the present study is the identification of the kinases responsible for vimentin phosphorylation whose activity is affected by the modulation of RAB7A expression. We found that RAB7A is able to regulate AKT (also called protein kinase B or PKB) and PAK1 (P21-Activated Kinase 1) and several of their downstream effectors, which control proliferation, apoptosis, survival, migration, and invasion. These data suggest that RAB7A could have a key role in cancer development. Abstract RAB7A is a small GTPase that controls the late endocytic pathway but also cell migration through RAC1 (Ras-related C3 botulinum toxin substrate 1) and vimentin. In fact, RAB7A regulates vimentin phosphorylation at different sites and vimentin assembly, and, in this study, we identified vimentin domains interacting with RAB7A. As several kinases could be responsible for vimentin phosphorylation, we investigated whether modulation of RAB7A expression affects the activity of these kinases. We discovered that RAB7A regulates AKT and PAK1, and we demonstrated that increased vimentin phosphorylation at Ser38 (Serine 38), observed upon RAB7A overexpression, is due to AKT activity. As AKT and PAK1 are key regulators of several cellular events, we investigated if RAB7A could have a role in these processes by modulating AKT and PAK1 activity. We found that RAB7A protein levels affected beta-catenin and caspase 9 expression. We also observed the downregulation of cofilin-1 and decreased matrix metalloproteinase 2 (MMP2) activity upon RAB7A silencing. Altogether these results demonstrate that RAB7A regulates AKT and PAK1 kinases, affecting their downstream effectors and the processes they regulate, suggesting that RAB7A could have a role in a number of cancer hallmarks.

Honeysuckle berries are becoming an attractive organically grown fruit with many aspects as a new functional food. They have the benefit of containing health-promoting compounds, such as saponins, ascorbic acid, iridoids, flavonoids, and anthocyanins. Fruit berries can be processed into many products with various contents of selected bioactive compounds. The contents of individual compounds were identified with the aid of high-performance liquid chromatography coupled with mass spectrophotometry. Their concentrations significantly differed among the various food products. Ascorbic acid had the highest values in blue honeysuckle spread (302.02 mg/100 g of dry weight), while infusion (119.17 mg/100 g) and juice (118.17 mg/100 g) had the lowest values. All the food products had low sugar contents. Of the health beneficial phenolic compounds honeysuckle spread had the highest content (1753.54 mg/100 g) and honeysuckle infusion (196.61 mg/100 g) had the lowest content. Honeysuckle liqueur and smoothie also had high total analyzed phenolic contents (1138.75 mg/100 g and 1108.25 mg/100 g, respectively).

The purpose of the current study was to determine the phenolic composition, antioxidant, and antimicrobial activities in grape cane extracts from typical cultivars of Southern Italy. Aqueous extracts at different pHs (1–13) were prepared from “Aglianico”, “Fiano”, and “Greco” grape canes. The results demonstrated that an alkaline pH (13.00) produced the best polyphenol-rich extracts, as the total phenolic content was more than double when compared to the respective extracts prepared at pH 1.00. “Greco” grape canes gave the highest quantity of phenolic compounds at each pH, ranging from 42.7 ± 0.4 to 104.3 ± 3.0 mg Gallic Acid Equivalents (GAE)/g Dry Extract (DE) from pH 1.00 to 13.00. The Radical Scavenging Activity (RSA) and the Ferric Reducing Antioxidant Power (FRAP) were measured. The highest antioxidant activity was showed by “Greco” extract at pH 7.00. Seventy-five compounds were identified in the extracts by HPLC-MS with six of them described for the first time in grape canes. Procyanidins were highly abundant in extracts at pH 7.00, whereas stilbenoids were the most represented compounds at pH 13.00. Very strong antiviral activity against herpes simplex viruses was recorded for the extracts at pH 7.00 and 13.00 that were active in the early stages of infection by acting directly against the viral particles. The overall results suggest that grape canes, currently underutilized, can be usefully valorised by providing active extracts to use as antioxidant and antiviral agents.

Aerobic vaginitis (AV) is a vaginal infectious condition, characterized by a high inflammatory response and/or signs of epithelial atrophy, a decrease in the amount of Lactobacillus spp. and an increase in enteric origin bacteria. AV, often misdiagnosed, is difficult to treat due to the emerging spread of multi-drug resistant bacterial strains. The present study aimed to define the prevalence of AV, to detect causative bacteria and their antimicrobial resistance pattern. Women 10–95 years old, admitted to San Giovanni di Dio e Ruggi d’Aragona Hospital, Salerno, Italy (in the years 2015–2019) are included in the study. Bacterial identification and antibiotic susceptibility tests were carried out by VITEK® 2. Among 2069 patients, 1176 tested positive for microbial growth. A higher incidence of infection was found in the 55–64 age group. Among the pathogenic strains, 50.4% were Gram-negative, and 49.6% were Gram-positive. Escherichia coli (E. coli) (32.5%) was the most representative strain, followed by Enterococcus faecalis (E. faecalis) (29.4%), Klebsiella pneumoniae (K. pneumoniae) (7.8%) and Enterococcus faecium (E. faecium) (7.7%). E. coli showed high sensitivity to carbapenems and amikacin. K. pneumoniae carbapenems resistance was fluctuating over time. Alarming resistance to vancomycin was not recorded for Enterococci. Both strains were sensitive to teicoplanin, linezolid and tigecycline. Proper diagnosis and an effective therapeutic approach are needed to improve AV management.

Lamb's lettuce is a popular winter salad, often grown in private vegetable plots, small local farms or in intensive vegetable production. It is usually marketed as a ready-to-eat produce in supermarkets. The aim of the study was to evaluate the changes in biochemical composition and degradation of bioactive compounds during consumer-relevant time of home-grown and store-bought Valerianella locusta “Vit” salad. Primary metabolites, assimilatory pigments as well as secondary metabolites were monitored during 1 week of refrigerated storage. Home-grown lamb's lettuce exhibited highest levels of total sugars, total organic acids, vitamin C, and total phenolic content as well as enhanced levels of most individual phenolic compounds and chloroplast pigments. Locally produced samples of lamb's lettuce also contained high levels of analyzed bioactive components. All samples retained most bioactive components during the entire period of refrigerated storage. The results underline the instability of vitamin C during refrigerated storage of lamb's lettuce and pinpoint this parameter as being the most affected by storage.

Triclosan (TCS) is a phenolic compound with broad-spectrum antimicrobial action that has been incorporated into a variety of personal care products and other industry segments such as toys, textiles, and plastics. Due to its widespread use, TCS and its derivatives have been detected in several environmental compartments, with potential bioaccumulation and persistence. Indeed, some studies have demonstrated that TCS may act as a potential endocrine disruptor for the reproductive system. In the current study, we are reporting on the results obtained for male rats after a two-generation reproduction toxicity study conducted with TCS. Female and male Wistar rats were treated daily by gavage with TCS at doses of 0.8, 2.4, and 8.0 mg/kg/day or corn oil (control group) over 10 weeks (F0) and over 14 weeks (F1) before mating and then throughout mating, until weaning F2 generations, respectively. TCS exposure decreased sperm viability and motility of F1 rats at the dose of 2.4 mg/kg. The effects of TCS on sperm quality may be related to the exposure window, which includes the programming of reproductive cells that occurs during fetal/neonatal development.

Speleothems have proven to be one of the most reliable terrestrial archives for palaeoclimate research. However, due to the complexity of karst systems, long-term monitoring and high-resolution analyses of the cave atmosphere and water geochemistry have become essential to better constrain the factors that control calcite growth and how geochemical palaeoclimate proxies are encoded into speleothems. While calcite precipitation incorporates the palaeoclimate signals into the speleothem fabric, certain conditions in caves can favour dissolution, which may form hiatuses or even destroy these signals. In extreme cases, in-cave dissolution by dripwater can form cup-shaped features (i.e., corrosion cups), which were the main focus of this study. The study site in Postojna Cave, Slovenia, was investigated through cave climate monitoring and drip and cup water sampling, which took place during 2017–2021. We found that the cups are fed by low calcium drips as the consequence of the thin vadose zone above the cave. Due to the specific configuration of airflow pathways, the study site accumulates high levels of CO2 (>10,000 ppm), which shifts low calcium dripwater into undersaturation. This causes dissolution on rock surfaces and speleothems on the cave floor. The results of this study have broader significance in addressing the suitability of cave environments and speleothems used in paleoclimate research.

Interactions of novel bi-dimensional nanomaterials and live matter such as bacteria and viruses represent an extremely hot topic due to the unique properties of the innovative nanomaterials, capable in some cases to exhibit bactericide and antiviral actions. The interactions between bacteria and viruses and two dimensional nanosheets are here investigated. We extensively studied the interaction between a gram-negative bacterium, Escherichia coli, and a gram-positive bacterium, Staphylococcus aureus, with two different types of 2D nanoflakes such as MoS2, belonging to the Transition Metal Dichalcogenides family, and Graphene Oxide. The same two types of nanomaterials were employed to study their antiviral action toward the Herpes simplex virus type-1, (HSV-1). The experimental results showed different bactericide impacts as well as different antiviral power between the two nanomaterials. The experimental findings were interpreted in bacteria on the base of the Derjaguin–Landau–Verwey–Overbeek theory. A simple kinetic model of bacterial growth in the presence of the interacting nanosheets is also elaborated, to explain the observed results. The experimental results in viruses are really novel and somewhat surprising, evidencing a stronger antiviral action of Graphene Oxide as compared to MoS2. Results in viruses are complicated to quantitatively interpret due to the complexity of the system under study, constituted by virus/host cell and nanoflake, and due to the lack of a well assessed theoretical context to refer to. Thus, these results are interpreted in terms of qualitative arguments based on the chemical properties of the interactors in the given solvent medium.

It has been estimated that the 90% of the world population is affected by HSV-1 or HSV-2 infections. Clinical manifestations associated with these infectious agents range from cold sores and genital lesions to keratitis, encephalitis and meningoencephalitis. Nowadays these viruses represent a global health and economic burden. Despite a century of scientific research a vaccine for HSV-1 and HSV-2 viruses is still not available. However, in the last years HSV glycoproteins have strongly emerged as putative candidates for vaccine development. In this chapter we provide insights into HSV glycoproteins structure, function and the current state of art in the development of a vaccine for these pathogens.

Conformational changes of viral glycoproteins govern the fusion of viral and cellular membranes in the entry of enveloped viruses. Peptides mimicking domains of viral glycoproteins are apt to interfere with the fusion event, likely hampering the conformational rearrangements from the pre- to the post-fusion structures. We previously developed a peptide sequence with a high potential to inhibit the entry of herpes simplex type 1, which was able to trap glycoprotein B at an intermediate stage, arresting fusion. We propose that similarly to other viruses, membrane targeting through cholesterol conjugation may potently block fusion. The peptide conjugated to polyethylenglycol and cholesterol interacts with viral and cell membranes thanks to the presence of cholesterol and blocks the conformational rearrangements of the glycoprotein B. Here, we also probed the effect of the linker (polyethylenglycol) length on the activity. By targeting the peptide gBh1m to the membranes where fusion occurs and by engineering sequences with increased binding affinity for gB we have enhanced the antiviral potency of our prototype inhibitors. Our results provide proof of concept for the application of cholesterol tagging to develop inhibitors of HSV-1.

(1) Background: In dentistry, silver nanoparticles (AgNPs) have progressively earned great interest as antimicrobial drugs and are widely used in several biomedical fields. Recent progress in the analysis of complex bacterial communities has demonstrated the richness of the oral microbiota and the presence of numerous previously unexplained strains. Several efforts have been dedicated to the investigation of antimicrobial peptides (AMPs). Those peptides are a widespread group of small peptides against invading microbes. We report the production of a hybrid molecule composed of AgNPs and indolicidin, a well-known antibacterial peptide. (2) Methods: Spectroscopy and microscopy were used to analyze the optical features and to determine the size of the generated AgNPs. The AgNP antibacterial activity was evaluated versus oral Gram-positive and Gram-negative bacteria. (3) Results: The coated nanoparticles&rsquo, antibacterial activity strongly inhibited the growth of microorganisms, with very low minimum inhibitory concentration (MIC) values in the range of 5&ndash, 12.5 &mu, g/mL. We hypothesize that this effect depended on the specific characteristics of the metal surface coated with indolicidin. The second result was that the coated nanoparticles observed cellular toxicity, was lower with respect to the toxicity of peptide and the naked AgNPs when used individually. (4) New investigations regarding antimicrobial effect of AgNPs coated with AMPs in oral infections are an urgent task.

The aim of this study is to estimate the uncertainty of a portable X-ray fluorescence (p-XRF) instrument for the (semi-quantitative) analyses of tiles with underglaze decoration. Before starting the campaign of on-site measurements, the optimum acquisition time and the most accurate calibration mode were selected. For this purpose, the elemental composition of two glass standards of NIST (SRM610 and SRM612) and a Corning A standard were measured with varied times (5-360 s) and in different calibration modes (Mining, Mining Light Elements, Soil, and Rare Earth Elements). Afterwards, a set of blue-and-white tiles that was unearthed at Iznik Tile Kilns Excavation between the dig seasons of 2015 and 2019 was examined with p-XRF by selecting ten points of measure from each layer (body, transparent glaze, and blue coloured areas). The elemental composition of different layers was evaluated by means of the intragroup and intergroup data. They were also compared to the previous studies and found that the corrosion-free, homogeneous, and non-porous surfaces decrease the relative standard deviation (RSD) by increasing the consistency of the compositional data. The major elements found in the matrix of each layer (Al and Si for the body, Pb and Sn for the glaze) have the lowest value of RSD, as expected. However, the comparison of the data with the analysis of the reference materials showed that the content of Mg and also Si, which belong to the low-Z elements group, is shifted relatively towards the higher compositional values. The impossibility of measuring the elemental composition of sodium does not hinder the classification of the samples. Although the transition metals have very low concentrations, p-XRF measurements appear rather consistent and the intrinsic scattering of the data observed for a single artefact is largely smaller than those observed for the tiles of different historical buildings. Thus, it allows the classification to be made related to the different techniques used., İstanbul University Scientific Research Projects Coordination Unit

The KV10.1 voltage-gated potassium channel is highly expressed in 70% of tumors, and thus represents a promising target for anticancer drug discovery. However, only a few ligands are known to inhibit KV10.1, and almost all also inhibit the very similar cardiac hERG channel, which can lead to undesirable side-effects. In the absence of the structure of the KV10.1–inhibitor complex, there remains the need for new strategies to identify selective KV10.1 inhibitors and to understand the binding modes of the known KV10.1 inhibitors. To investigate these binding modes in the central cavity of KV10.1, a unique approach was used that allows derivation and analysis of ligand–protein interactions from molecular dynamics trajectories through pharmacophore modeling. The final molecular dynamics-derived structure-based pharmacophore model for the simulated KV10.1–ligand complexes describes the necessary pharmacophore features for KV10.1 inhibition and is highly similar to the previously reported ligand-based hERG pharmacophore model used to explain the nonselectivity of KV10.1 pore blockers. Moreover, analysis of the molecular dynamics trajectories revealed disruption of the π–π network of aromatic residues F359, Y464, and F468 of KV10.1, which has been reported to be important for binding of various ligands for both KV10.1 and hERG channels. These data indicate that targeting the KV10.1 channel pore is also likely to result in undesired hERG inhibition, and other potential binding sites should be explored to develop true KV10.1-selective inhibitors as new anticancer agents.

Nitrogen is an integral element of foliar sprays during apple fruit formation. However, in red cultivars, the application may have adverse effects on color in the second stage of fruit development. The effect of a low-dose foliar application of urea was monitored on ‘Topaz’ apple pomometric (fruit mass, firmness, total solids, starch content, skin color) and biochemical traits (primary metabolites, phenolic compounds, and assimilatory pigments). Three applications (17 July, 27 July, and 18 August) of two different urea doses (N1 = 1.4 kg N ha−1, N4 = 4 kg N ha−1) and control (N0, only sprayed with water) were used. Low doses of urea did not affect flesh firmness, total soluble, solid, and starch content, but individual fruit mass was significantly higher in N1 treatment compared to the other two treatments. Significantly lower a* parameters and a lower content of anthocyanins were measured on apples subject to N4 treatment. Many secondary metabolites (phenolic acids, flavan-3-ols, flavonols, and chalcones) were also negatively affected by low-dose urea application. Conversely, urea treatments significantly increased total assimilatory pigments in apple skin. Even minor levels of nitrogen, applied directly on the leaf at later stages of red apple fruit development, negatively altered color traits and the composition of metabolites.

Introduction The interaction between anticoagulants and platelet function is complex. Previous publications showed mixed results regarding the role of heparins in platelet aggregation. On the other hand, the direct thrombin inhibitor (DTI) dabigatran might enhance the risk of myocardial infarction in patients with atrial fibrillation, which could be related to increased platelet aggregability. Methods This was a prospective, interventional study of patients with chronic coronary artery disease (CAD) taking low-dose aspirin. The objective of the current study was to compare the effects of dabigatran versus enoxaparin on platelet aggregability. Subjects initially were on orally administered dabigatran for 5 days followed by subcutaneously administered enoxaparin after a 30-day washout period. Platelet function was assessed at baseline and after each intervention by multiple electrode aggregometry (MEA-ASPI) (primary endpoint), serum thromboxane B2 (TXB2), VerifyNow Aspirin™, and coagulation tests (secondary endpoints). Results Compared to baseline MEA-ASPI values, dabigatran increased platelet aggregation while enoxaparin decreased platelet aggregation (+ 5 U ± 24.1 vs − 6 U ± 22.2, respectively, p = 0.012). The TXB2 assay showed the same pattern (+ 2 pg/ml for dabigatran vs − 13 pg/ml for enoxaparin, p = 0.011). None of the additional tests showed significant differences between the groups. Individually, compared to baseline TXB2 results, enoxaparin significantly decreased platelet activation [33 (16.5–95) pg/mL vs 20 (10–52) pg/mL, respectively, p = 0.026], but no significant differences were observed with dabigatran. Conclusions DTI and anti-Xa drugs exert opposite effects on platelet function. A significant decrease in platelet activation through COX1 (also known as prostaglandin G/H synthase 1) was observed with enoxaparin, but no significant differences in platelet function were observed with dabigatran. Trial Registration ClinicalTrials.gov identifier, NCT02389582.

Background Patients with coronary artery disease (CAD) and previous ischemic cerebrovascular events (ICVE, ischemic stroke, or transitory ischemic attack) constitute a high‐risk subgroup for cardiovascular outcomes. High‐density lipoprotein cholesterol (HDL‐C) levels are correlated with cardiovascular events. Lipid transfer to HDL affects structure size and HDL subclass profile. Impairment of this transfer could influence ischemic risk seen in patients with CAD + ICVE. The objective was to evaluate the HDL ability to receive the lipids in patients with CAD with or without ICVE. Methods Patients with CAD + ICVE (n = 60) and patients with CAD only (n = 60) were matched by age, sex, acute coronary syndromes (ACS) event type, and time elapsed between the ACS event and inclusion in the study. Lipid transfer to HDL was evaluated by incubating donor lipid nanoparticles labeled with radioactive unesterified cholesterol (UC) and esterified cholesterol (EC), phospholipid (PL), and triglyceride (TG) with whole plasma. After the chemical precipitation of non‐HDL fractions and nanoparticles, the supernatant was counted for HDL radioactivity. Results CAD + ICVE group presented with impaired lipid transfer to HDL for PL (CAD + ICVE: 21.14 ± 2.7% vs CAD: 21.67 ± 3.1%, P = .03), TG (CAD + ICVE: 4.88 ± 0.97% vs CAD: 5.63 ± 0.92%, P = .002), and UC (CAD + ICVE: 5.55 ± 1.19% vs CAD: 6.16 ± 1.14%, P = .009). Lipid transfer to HDL was similar in both groups for EC. Adjusted models showed similar results. Conclusion Patients with CAD and ICVE have reduced lipid transfer to HDL compared to those with CAD only. Dysfunctional HDL may account for the higher incidence of ischemic outcomes observed in this population.

Despite fruit seeds being considered fruit waste, they have good potential in human diet. The present research investigated the levels of bioactive compounds (phenolics and cyanogenic glycosides) in apple seeds of the cultivar ‘Golden Delicious’ grown in four different orchards in the world and their change over the course of 8 months of storage. Both phenolics and cyanogenic glycosides certainly respond to some environmental conditions, mainly temperature, precipitation and altitude. Apple seeds from Azerbaijan, with the highest temperature and the lowest annual precipitation, contained the highest cyanogenic glycosides contents (2.2 mg/g) and apple seeds from Russia, with the highest altitude and the lowest temperatures, had the highest levels of phenolics (6.2 mg/g). Additionally, their initial contents further altered over the course of 8 months of storage in a controlled atmosphere.

An exceptionally high mortality rate is observed in sepsis and septic shock. Systemic administration of lipopolysaccharide (LPS) has been used as an experimental model for sepsis resulting in an exacerbated immune response, brain neurochemistry adjustments, hypotension, and hypothermia followed by fever. Central serotonergic pathways not only modulate systemic inflammation (SI) but also are affected by SI, including in the anteroventral region of the hypothalamus (AVPO), which is the hierarchically most important region for body temperature (Tb) control. In this study, we sought to determine if central serotonin (5-HT) plays a role in SI induced by intravenous administration of LPS (1.5 mg/kg) in male Wistar rats (280–350 g) by assessing 5-HT levels in the AVPO, mean arterial pressure, heart rate, and Tb up to 300 min after LPS administration, as well as assessing plasma and spleen cytokine levels, nitric oxide (NO) plasma levels, and prostaglandin (PG) E2 levels in the AVPO at 75 min and 300 min after LPS administration. We observed reduced AVPO 5-HT levels, hypotension, tachycardia, hypothermia followed by fever, as well as observing increased plasma NO, plasma and spleen cytokines and AVPO PGE2 levels in SI. Intracerebroventricular (icv) administration of 5-HT 30 min before LPS administration prevented hypotension and hypothermia, which were accompanied by reduced plasma NO, as well as plasma TNF-α, IL-1β, IL-6, and IL-10 and spleen TNF-α and IL-10 levels. We suggest that SI reduced 5-HT levels in the AVPO favor an increased pro-inflammatory status both centrally and peripherally that converge to hypotension and hypothermia. Moreover, our results are consistent with the notion that exogenous 5-HT given icv prevents hypotension and hypothermia probably activating the splenic anti-inflammatory pathway.