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Dose–response relationships are important in assessing the efficacy and potency of compounds, which can usually be characterized by a 4-parameter logistic (4-PL) model estimating EC50, slope factor, lower asymptote, and upper asymptote. EC50, the concentration of a compound that induces a response halfway between the baseline and maximum, is a key quantity to evaluate compound potency. For multi-donor dose–response data, it is often of interest to estimate the overall EC50 (i.e. the average EC50 of the population of donors) and its 95% confidence interval (CI). A few multi-donor EC50 estimation methods have been proposed in the literature. Jiang and Kopp-Schneider (2014) systematically compared the meta-analysis approach and the nonlinear mixed-effects approach and concluded that the meta-analysis approach is simple and robust to summarize EC50 estimates from multiple experiments, especially suited in the case of a small number of experiments, while the nonlinear mixed-effects approach has the issue of convergence failures probably due to overparameterization. In this article, we propose a modification of the nonlinear mixed-effects approach by using the stochastic approximation expectation-maximization (SAEM) algorithm to estimate model parameters and using multiple starting points to search for globally optimal values, which can substantially alleviate the issue of convergence failures even for small number of donors (e.g. n = 3), and achieve a smaller absolute median bias and better coverage probability of 95% confidence interval than the meta-analysis approach when the number of donors is not too small (e.g. n ≥ 7). [ABSTRACT FROM AUTHOR]

The objective of this study is to investigate the effects of various doses of esketamine on the median effective concentration (EC50) of propofol required for inhibiting body movement during hysteroscopy. Additionally, this research aims to explore the pharmacodynamic interactions between esketamine and propofol. Prospective, double-blind, up-down sequential allocation study. Operating room, post-anesthesia care unit (PACU), and general ward. A total of 90 patients were allocated into three groups in a randomized, double-blinded manner as follows: 0.1 mg/kg esketamine combined with propofol intravenous injection (EP0.1) group, 0.2 mg/kg esketamine combined with propofol intravenous injection (EP0.2) group, 0.3 mg/kg esketamine combined with propofol of intravenous injection (EP0.3) group. For the initial patient in each group, the starting effector target concentration of propofol was set at 4 µg/ml. Each patient received an initial intravenous injection of 0.04 mg/kg midazolam, followed by the administration of the appropriate dose of esketamine. Ten seconds after the esketamine injection, propofol was administered intravenously to achieve the target concentration. In accordance with the sequential method principle, the concentration of propofol for the subsequent patient was adjusted based on the response of the previous patient. Effective inhibition of body movement was defined as the absence of any involuntary body movements throughout the entire surgical process. If the previous patient exhibited body movements, the propofol concentration for the next patient was increased by 0.5 µg/ml; conversely, if no movements were observed, it was decreased by 0.5 µg/ml. The up-down sequential allocation method and probit regression were used to calculate the EC50 of propofol. Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and Depression (HADS-D) score, adverse events, hemodynamic changes, demographic data and clinical characteristics. The EC50 of propofol was 3.849 μg/ml (95% CI: 3.419–4.281) in the EP0.1 group, 3.641 μg/ml (95% CI: 2.807−4.200) in the EP0.2 group, and 3.417 μg/ml (95% CI: 2.845–3.852) in the EP0.3 group. These findings suggest that esketamine can dose-dependently reduce the EC50 of propofol. Esketamine can dose-dependently reduce the EC50 of propofol in hysteroscopy, while concurrently lowering patients' HADS-A and HADS-D scores 24 h post-operation. It is concluded that the optimal dose of esketamine, when combined with propofol for hysteroscopy, is 0.3 mg/kg. [ABSTRACT FROM AUTHOR]

Bioassays are regulated, analytical methods used to ensure proper activity (potency) of biological products at release and during long-term storage. Potency is commonly reported on a relative basis by comparing and calibrating a concentration–response curve from the test material to that of a reference standard material. The relative potency approach depends on an assumption that the two concentration–response curves exhibit similar (equivalent) shapes, except for a potency shift. In certain circumstances, however, biological factors preclude the similarity assumption, and the traditional approach becomes unworkable. The antibody-mediated cytotoxicity assay is one example where the similarity assumption does not always hold. Other examples also arise in the fields of toxicology and pharmacology. In this work, we present a non-constant mean relative potency approach which averages the relative potency across a common range of the concentration-response curves. The proposed method captures the changing nature of the relative potency into a summary statistic that can be reported for batch calibration and quality control purposes. We provide inferential methods for this statistic and summarize the results of a simulation comparing these methods across a number of non-constant relative potency scenarios and assay conditions. [ABSTRACT FROM AUTHOR]

AbstractThe unmanaged waste disposal, coupled with the increased industrialization and urbanization, has aggravated the problem of heavy metal contamination in the environment, especially in the agricultural soils. In view of this, the present study was planned to evaluate the effectiveness of zinc (Zn) in the amelioration of cadmium (Cd) toxicity in plants, thereby sustaining the crop productivity in near future. The experiment was performed in two parts. The first part focused on calculating the EC50 (half-effective concentration) of Cd, for which the potted experimental plants (Amaranthus cruentus L.) were treated with different doses of Cd (10, 20, 30, 40, and 50 mgL−1). In the second part, the EC50 Cd dose was combined with different Zn doses (100, 200, 300, 400, and 500 mgL−1) and the effect of Zn supplementation on Cd exposed plants was studied by evaluating the response of different biochemical, physiological and yield parameters. The EC50 Cd dose was calculated to be 26.5 mgL−1. Plant yield increased significantly with reduced Zn dosages. Biochemical parameters improved more than physiological parameters after Zn treatment in Cd-stressed plants. At higher Zn doses, its toxic effects exacerbate Cd toxicity. The study indicates that Zn partially decreases Cd toxicity in Amaranthus plants. The results suggest that 300 mgL−1 Zn dose was sufficient to bring about maximum recorded mitigation of Cd toxicity. However, since the synergistic effects of high doses of Zn with Cd cannot be ruled out, the selection of the applied Zn dose should be carefully selected. [ABSTRACT FROM AUTHOR]

The characterization of bioactive components in the methanolic and isopropyl alcoholic plant extracts of Spermadictyon suaveolens Roxb. (Rubiaceae) was undertaken with the help of GC-MS technique, followed by the study of free-radical scavenging capabilities of the plant hydroalcoholic extracts using DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) test technique with ascorbic acid as the standard. There's a constant formation of free radicals in the human body tissues originating due to the oxidation of specific chemical components, whereas the antioxidant molecules prevent or inhibit this free radical formation that may lead to lifelong or terminal diseases. The comparison of the antioxidant capacity of the plant extracts with that of the standard revealed that the leaf extracts showed maximum inhibition of DPPH, or radical scavenging activity. The EC50 values of ascorbic acid, leaves, stem, and root were found to be 18.62 μg/mL, 44.668 μg/mL, 89.125 μg/mL, and 97.723 μg/mL, respectively. The different peaks in the GC-MS analysis spectrum determined 24, 19, and 26 phytochemicals in leaves, stems, and roots, respectively. Out of all the phytoconstituents found, the major ones were n-Hexadecanoic acid or palmitic acid, squalene, 1.4-tert-Butylcalix[4]arene, and 1.3,5-Dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one in leaves. 11-Bromoundecanoic acid, Ethylhexanol, Tetratetracontane, 2-Decanol, Propanoate in Stem, and n-Hexadecanoic acid 9,12-Octadecadienoic acid (Z,Z), 4,6-Bis(4-fluoro-3-(trifluoromethyl) phenoxy)-2-pyrimidinol, squalene in roots. Thus, the different bioactive constituents found to be present in the plant under study prove that the plant has the capacity to exhibit good antioxidant and other pharmacological properties. [ABSTRACT FROM AUTHOR]

Microalgae are unicellular, photosynthetic organisms in aquatic environments and are sensitive to water quality and contaminants. While green algae and diatoms are widely used for toxicity assessments, there is a relatively limited amount of toxicity data available for freshwater dinoflagellates. Here, we evaluated the sub‐lethal effects of the metals Cu, Cr, Ni, and Zn and the herbicides atrazine and S‐metolachlor on the freshwater dinoflagellate Palatinus apiculatus. Based on the 72‐h median effective concentration (EC50), P. apiculatus showed sensitive responses to metals in the order of Cu (0.052 mg L−1), Cr (0.085 mg L−1), Zn (0.098 mg L−1), and Ni (0.13 mg L−1). Among the tested herbicides, P. apiculatus was more sensitive to atrazine (0.0048 mg L−1) than S‐metolachlor (0.062 mg L−1). In addition, we observed morphological alterations and significant increases in reactive oxygen species (ROS) production in cells exposed to 0.05 mg L−1 of Cu and 0.005 mg L−1 of atrazine. These indicated that metals and pesticides induced oxidative stress in cellular metabolic processes and consequently caused severe physiological damage to the cells. Our results provide baseline data on the toxic effects of typical environmental contaminants on freshwater dinoflagellate, suggesting that P. apiculatus could be used as a bioindicator in freshwater toxicity assessments. Practitioner Points: The sub‐lethal effects of metals and pesticides on the freshwater dinoflagellate Palatinus apiculatus were evaluated.Palatinus sensitively responded to metals and pesticides; of test chemicals, atrazine (0.0048 mg L−1 of EC50) was the most sensitive.Metals and pesticides induced oxidative stress and consequently caused severe physiological damage to the Palatinus cells.The freshwater dinoflagellate Palatinus can be used as a bioindicator in freshwater toxicity assessments. [ABSTRACT FROM AUTHOR]

A novel synthetic route has been designed to introduce fluorine functionality into a series of compounds containing thiazolidin-4-one rings. These compounds were synthesised from various aniline derivatives using a two-step approach: an addition reaction of ethyl isothiocyanate with different aromatic fluorinated anilines, followed by cyclisation to yield the final products. A total of 15 novel fluorinated thiazolidinone compounds were synthesised and characterised using 1H NMR, 19F NMR, Fourier transform–infrared, elemental analysis and liquid chromatography–mass spectrometry. Stereochemistry around the imine bond in the synthesised derivatives was determined using nuclear Overhauser effect spectroscopy. The in vitro anticancer potential of the compounds was tested against two human cancer cell lines, liver (HepG2) and colon (HCT116). The study revealed that the derivatives having fluorine functionality at both the m- positions in the aromatic ring showed promising anticancer potential, as compared to those at o- and p- positions. A series of thiourea intermediates were prepared by addition reaction between various aniline derivatives and ethyl isothiocyanate. These intermediates were further cyclised with the help of ethyl bromofluoroacetate to yield fluorinated thiazolidin-4-one derivatives. The anticancer activities of these novel fluorinated moieties against human liver and colon cancer cell lines have been investigated. (Image credit: Shreyash Kadam.) [ABSTRACT FROM AUTHOR]

There is still much to learn with respect to the potential for microplastics (MPs) to interact with environmental toxins and biota. In the present study, we investigated the effect of MPs on the toxicity of copper (Cu) to rice seeds (Oryza sativa L.). The 7‐day median effective concentration (EC50) value of MPs on rice seed germination was 864 mg/L (95% confidence interval [CI] 839 to 897 mg/L). We found that MPs slightly reduced Cu toxicity to rice seeds. The 7‐day EC50 of Cu on rice seed germination increased from 7.29 mg/L (95% CI 7.10–7.52 mg/L) to 7.93 mg/L (95% CI 7.58–8.08 mg/L) in the presence of 20 mg/L MPs. We examined this toxicity reduction phenomenon by investigating the role of MPs in the process of Cu transport, Cu accumulation, and metabolic responses. Further investigation found that the MPs used in the present study hardly adsorbed Cu, but these MPs accumulated on the coats of rice seeds and significantly reduced Cu accumulation in rice seedlings. When Cu concentration was 10 mg/L, the presence of MPs reduced the accumulation of Cu in rice seedlings by 34%. We also found that, compared with only Cu present, the addition of MPs resulted in lower reactive oxygen species accumulation and higher catalase activity and glutathione levels in rice seedlings, which also contributed to Cu toxicity reduction. Collectively, the present study shows that polystyrene MPs have the potential to form associations with plant structures which can ultimately impact heavy metal bioaccessibility and therefore toxicity. Environ Toxicol Chem 2024;43:1870–1879. © 2024 SETAC [ABSTRACT FROM AUTHOR]

Fluoroquinolones (FQs) have achieved significant success in both human and veterinary medicine. However, regulatory authorities have recommended limiting their use, firstly because they can have disabling side effects; secondly, because of the need to limit the spread of antibiotic resistance. This review addresses another concerning consequence of the excessive use of FQs: the freshwater environments contamination and the impact on non-target organisms. Here, an overview of the highest concentrations found in Europe, Asia, and the USA is provided, the sensitivity of various taxa is presented through a comparison of the lowest EC50s from about a hundred acute toxicity tests, and primary mechanisms of FQ toxicity are described. A risk assessment is conducted based on the estimation of the Predicted No Effect Concentration (PNEC). This is calculated traditionally and, in a more contemporary manner, by constructing a normalized Species Sensitivity Distribution curve. The lowest individual HC5 (6.52 µg L−1) was obtained for levofloxacin, followed by ciprofloxacin (7.51 µg L−1), sarafloxacin and clinafloxacin (12.23 µg L−1), and ofloxacin (17.12 µg L−1). By comparing the calculated PNEC with detected concentrations, it is evident that the risk cannot be denied: the potential impact of FQs on freshwater ecosystems is a further reason to minimize their use. [ABSTRACT FROM AUTHOR]

Background: Pregnant women in Chongwe, Zambia traditionally use the root of Azanza garckeana (F.Hffm.) Exell & Hillc (Malvalceae) to induce or accelerate labour. A previous study on the plant showed the methanol crude root extracts to possesses the highest uterotonic potential. Aim: To evaluate the phytopharmacological activity of the Methanol root extract of Azanza garckeana. Methods: This was a laboratory-based study designed using the uterus isolated from estrogenised adult non-gravid female virgin Wistar rats. The methanol crude extract was obtained by continuous maceration. The crude was partitioned using hexane, chloroform, ethyl acetate and n-butanol in the increasing order of polarity. The most active fraction was fractionated using silica gel column chromatography. Fourier Transform Infrared Spectroscopy and High-Performance Liquid Chromatography were used to identify the major uterotonic compound. One-way ANOVA, Bonferroni post hoc tests were used to analyze data using STATA version 13. Bar charts and dose-response curves were done using Graphpad Prism version 5.00 for Windows (San Diego California USA). Results: The final aqueous suspension demonstrated - the highest uterotonic potency (EC50 = 2.49 x 10-3 mg/ml; 95% CI 1.19 x 10-3 to 5.23 x 10-3 mg/ml, p=0.0001), while sub-fraction pool number 2 (sub-fractions number 41 to 61) demonstrated the highest terotonic potency (EC50 at 2.05 x 10-3 mg/ml; 95% CI 2.09 x 10-3 to 3.85 x 10-3 mg/ml, p=0.0001). Sub-fraction pool number 2 demonstrated highest uterotonic activity, and the compound was suggested to be related to the family of glycosides. Conclusions: The study suggests the presence of a major uterotonic phytochemical constituent in the methanol root crude extract of Azanza garckeana, which was indicated to be related to the family of glycosides. Further pharmacological and toxicological studies need to be undertaken on the plant. [ABSTRACT FROM AUTHOR]

Simple Summary: Castration is commonly performed in young dairy calves and results in pain and discomfort. This study aimed to assess the effective tissue concentrations of the current standard of care for pain mitigation in calves during castration (injectable lidocaine) and to assess the ability of lidocaine-loaded bands (LLBs) to deliver effective concentrations into the scrotal tissue over time. The injectable lidocaine provided effective anesthesia for up to 60 min, highlighting the importance of finding additional strategies to manage long-term pain. A ligation band impregnated with lidocaine could provide a suitable alternative, as it appears to deliver effective lidocaine concentrations starting as early as 2 h following application and lasting at least 28 days after application. Further studies are warranted to compare the use of LLBs to injectable local anesthetics. This study aimed to assess the effective tissue concentrations of the current standard of care for pain mitigation in calves during castration (injectable lidocaine) and to assess the ability of a lidocaine-loaded elastration band (LLB) to deliver effective concentrations into the scrotal tissue over time. This study comprised two different trials: (1) effective concentrations of injectable lidocaine in the scrotal tissue; and (2) the in vivo delivery of effective concentrations of lidocaine from LLBs placed on the calf scrotums. Sensation in the scrotal tissue was assessed by electrocutaneous stimulation. Injectable lidocaine allowed for short-term anesthesia for up to 60 min, highlighting the importance of finding additional strategies to mitigate long-term pain. An elastomeric ligation band impregnated with lidocaine could provide a suitable alternative, as it yielded tissue levels of lidocaine that approached EC50 and exceeded EC95 at 2 and 72 h following application, respectively, and remained above those levels for at least 28 days after application. Further studies are warranted to compare the use of LLBs to injectable local anesthetics. [ABSTRACT FROM AUTHOR]

Nowadays, pesticides are widely used in agricultural activities, and their intensive and indiscriminate use causes pesticides to threaten public health and the ecosystem. As with many environmental pollutants, the cytotoxic and genotoxic effects of pesticides have been a concern for many years. In this study, the cytotoxic and genotoxic effects of a synthetic pyrethroid tau-fluvalinate-containing insecticide (Mavrik® 2F) on Allium cepa root tip meristems were investigated. As a result of the root growth inhibition test, the effective concentration (EC50) for tau-fluvalinate was found to be 330 mg/L. Afterwards, onion roots were exposed to three different tau-fluvalinate concentrations (165, 330 and 660 mg/L) for 24 hours and mitotic index (MI), phase index (PI) values and chromosome aberration (CA) frequencies were calculated by microscopic examinations. After the statistical analyzes, as well as the conclusion that the tau-fluvalinate-containing model insecticide showed the root elongation-inhibiting effect, it was concluded that it had cytotoxicity because it decreased MI value and changed the PI values in A. cepa and that it had genotoxicity because it increased the formation of CA. In addition, in the case of the use of the model insecticide, it was assessed that 330 mg/L tau-fluvalinate concentration could cause sublethal effects and that 660 mg/L tau-fluvalinate concentration could cause lethal effects on A. cepa. In the light of the results of this study, it is recommended to be very careful during the use of pesticides containing tau-fluvalinate in agricultural activities and to apply concentrations much lower than 165 mg/L in order to reduce their toxic effects. [ABSTRACT FROM AUTHOR]

The use of biological nitrification inhibitors (BNIs) holds a great potential to effectively reduce nitrogen losses from agroecosystems and conforms with the current move toward ecological-intensified agriculture. Knowledge of the activity of BNIs to soil nitrifiers is limited and is generally based on a single Nitrosomonas europaea bioassay. We determined the in vitro activity of multiple plant-derived compounds as BNIs such as (i) root-derived compounds [sakuranetin, methyl 3-(4-hydroxyphenyl)-propionate (MHPP), and zeanone]; (ii) other phytochemicals (caffeic, quinic, chlorogenic, and shikimic acids); and (iii) analogs of statins (simvastatin), triazoles (1-butyl-4-propyltriazole, 1,4-dibutyltriazole), and zeanone (2-methoxy-1,4-naphthoquinone) on distinct soil-derived ammonia-oxidizing bacteria (AOB) (Nitrosospira multiformis and Nitrosomonas europaea), ammonia-oxidizing archaea (AOA) (Candidatus Nitrosotalea sinensis and Candidatus Nitrosocosmicus franklandianus), and a nitrite-oxidizing bacterium (NOB) (Nitrobacter sp.). Our results indicate that AOA were more sensitive than AOB to BNIs. Sensitivity within the AOA group was BNI dependent, unlike AOB, for which N. multiformis was consistently more sensitive than N. europaea. Several compounds were inhibitory to Nitrobacter sp. with MHPP and caffeic acid being more potent against NOB compared to the ammonia-oxidizing strains, an observation with potential implications for soil quality and productivity. Overall, zeanone was the most potent NI against ammonia oxidizers, while caffeic acid was the most potent BNI against Nitrobacter sp. We provide pioneering evidence for the activity range of multiple BNIs on soil nitrifiers, stress the need for revisiting the biological screening systems currently used for BNI determination, and advocate for a more thorough monitoring of the impact of BNI candidates on a range of target and non-target microorganisms. IMPORTANCE Synthetic nitrification inhibitors are routinely used with nitrogen fertilizers to reduce nitrogen losses from agroecosystems, despite having drawbacks like poor efficiency, cost, and entry into the food chain. Plant-derived BNIs constitute a more environmentally conducive alternative. Knowledge on the activity of BNIs to soil nitri fiers is largely based on bioassays with a single Nitrosomonas europaea strain which does not constitute a dominant member of the community of ammonia-oxidizing microorganisms (AOM) in soil. We determined the activity of several plant-derived molecules reported as having activity, including the recently discovered maize-isolated BNI, zeanone, and its natural analog, 2-methoxy-1,4-naphthoquinone, on a range of ecologically relevant AOM and one nitrite-oxidizing bacterial culture, expanding our knowledge on the intrinsic inhibition potential of BNIs toward AOM and highlighting the necessity for a deeper understanding of the effect of BNIs on the overall soil microbiome integrity before their further use in agricultural settings. [ABSTRACT FROM AUTHOR]

Cyanobacteria produce a wealth of secondary metabolites. Since these organisms attach fatty acids into molecules in unprecedented ways, cyanobacteria can serve as a novel source for bioactive compounds acting as ligands for Peroxisome Proliferator-Activated Receptors (PPAR). PPARs (PPARα, PPARβ/δ and PPARγ) are ligand-activated nuclear receptors, involved in the regulation of various metabolic and cellular processes, thus serving as potential drug targets for a variety of pathologies. Yet, given that PPARs' agonists can have pan-, dual- or isoform-specific action, some controversy has been raised over currently approved drugs and their side effects, highlighting the need for novel molecules. Here, we expand and validate a cell-based PPAR transactivation activity biosensor, and test it in a screening campaign to guide drug discovery. Biosensor upgrades included the use of different reporter genes to increase signal intensity and stability, a different promoter to modulate reporter gene expression, and multiplexing to improve efficiency. Sensor's limit of detection (LOD) ranged from 0.36–0.89 nM in uniplex and 0.89–1.35 nM in multiplex mode. In triplex mode, the sensor's feature screening, a total of 848 fractions of 96 cyanobacteria extracts were screened. Hits were confirmed in multiplex mode and in uniplex mode, yielding one strain detected to have action on PPARα and three strains to have dual action on PPARα and -β. [ABSTRACT FROM AUTHOR]

Comparative assessment of stress responses of two microalgal species differing in their cell structure and habitats, Prorocentrum cordatum and Dunaliella salina, to the presence of copper oxide nanoparticles (NP) in the medium was carried out. The nanoparticles were found to have a similar effect on both species. Their toxic effect resulted in progressing production of reactive oxygen species in the algal cells, while their specific growth rates decreased, probably due to Cu2+ release from the oxide or to penetration of some nanoparticles into the cells. NP mechanical impact resulted in their aggregation at the cell surface and deformation of the cell envelopes. The presence in the toxicant in the medium caused a reliable increase in cell volume, plasmalemma perforation, and predominance of deformed cells of irregular shape in the cultures. Two species exhibited different resistance to CuO NP. The sublethal and lethal concentrations for P. cordatum were 400 and 520 µg/L, respectively, compared to 3000 and 3750 µg/L for D. salina. The possible causes for resistance of D. salina to CuO NP are discussed. D. salina is able to produce ligands (phytochelatins and metallothionenis) in high concentrations, which may be released into the medium and bind the Cu2+ ions. Moreover, the habitats of D. salina are extreme, which may promote its stress tolerance, probably a genetically determined feature and a part of their overall resistance to other contaminants. High resistance of D. salina to CuO NP may also be due to its ability to secrete extracellular polymers under stress conditions; they may form a protective layer preventing the interaction between the microalgae and NP. Application of P. cordatum for biomonitoring of NP-contaminated seawater environments is proposed. D. salina may be promising for water bioremediation. [ABSTRACT FROM AUTHOR]

Phytopythium vexans isolated from potatoes rhizospheres in Ngablak, Magelang, Central Java was reported to potentially cause potato tuber rot in in vitro test. Fungicides had been intensively applied in this area to control potato late blight, including mancozeb, dimethomorph, mixture of mancozeb and mefenoxam, and mixture of oxathiapiprolin and famoxadone. Experiment was conducted to observe the pathogen sensitivity against those fungicide and growing isolates in sublethal concentration to observe the resistance response. Based on Probit Analysis results, P. vexans were insensitive against dimethomorph at 50,000 ppm, but it was sensitive against mancozeb at 4,000 ppm, mixture of mancozeb and mefenoxam at 10 ppm, as well as mixture of oxathiapiprolin and famoxadone at 0.1 ppm. Mycelia were inhibited 100% after mancozeb treatment at recommended concentration. However, at sublethal concentration mycelial collony grew abnormally, which then were used for following experiment of resistance response. The effect of the sublethal application of mancozeb to P. vexans caused resistance to mancozeb itself and cross resistance against dimethomorph and mixture of oxathiapiprolin and famoxadone based on higher predicted EC50 and EC95 on the second experiment compared to first ones. Furthermore, the resistant P. vexans isolate was able to produce sporangium and chlamydospore. [ABSTRACT FROM AUTHOR]

Background: Berberis commutata Eichler is a berry that grows in the Peruvian Andes and has been consumed in the Andes of South America since ancient times. The edible fruits have an intense purple color and are rich in anthocyanins and phenolic compounds that are available from February until May each year. The color of the fruits is a soft purple dye for natural fibers, and many birds use them as food. Objective: This study quantified the total phenolic, monomeric anthocyanin content and antioxidant activity of Berberis commutata Eichler berries. Methods: The total phenolic content was determined by the Folin-Ciocalteu colorimetric assay. Monomeric anthocyanin content was determined by the method is pH differential, and the antioxidant activity was measured using the Brand-Williams method. Results: The total phenolic content was 7,490 ± 0.85 mg GAE/100g, and the monomeric anthocyanin content was 70 ± 0.03 mg/100g. The antioxidant activity of the berries showed a tendency to increase with B. commutata extract concentration; an EC50 of 0.91 mg/mL was calculated, indicating a high antioxidant power. Conclusion: Our results showed that B. commutata E. has both high total phenolic content and monomeric anthocyanins comparable to other superfruits and high antioxidant activity, which means that it is possible to use this berberis species as a functional food. [ABSTRACT FROM AUTHOR]

Allelopathy is a physiological process with an ecological concept and application. Allelopathy is the result of the production of biologically active molecules by growing plants or their remains, which may have a direct effect on the growth and development of individuals of the same species or other species after changing their shape and entering the environment. As regards, the use of natural compounds in the control of weeds and pests is a priority. In this research, the allelopathic activity of 123 specimens of medicinal and aromatic plants were investigated individually by the dish-pack method using lettuce seeds as a model. Then, the strongest inhibitory ones were selected and their allelopathic interaction effects were investigated for the first time by interacting them together. Two methods were used to evaluate allelopathic interaction effects: calculating Fractional Inhibitory Concentration (FIC) and drawing Isobologram diagrams. Lettuce hypocotyl length, root length, germination percentage, and germination rate were investigated. Pelargonium graveolens (leaf) had the greatest inhibitory effect on lettuce radicle growth (EC50 = 5.31 mg/well) and Echinophora platyloba (stem) had the greatest effect on hypocotyl growth inhibition (EC50 = 7.91 mg/well). Also, the lowest lettuce germination percentages were observed in the treatments Lavandula officinalis (flower) and Nepeta binaloudensis (leaf), respectively (23.61, 22.85%). The highest inhibitory effect by considering lettuce germination rate was detected in Salvia ceratophylla (leaf), (12.86 seed/day) and the lowest belonged to Nepeta binaloudensis (leaf) and Lavandula officinalis (flower), respectively (3.60, 3.32 seed/day). According to FIC calculations and isobolograms, two types of interaction, including synergist (Nepeta binaloudensis (leaf) with Trachyspermum ammi (fruit) and Nepeta binaloudensis (leaf) with Lavandula officinalis (flower) and antagonist (Pelargonium graveolens (leaf) with Lavandula officinalis (flower)), were observed significantly among the plants tested in this research. These interactions can be used to prepare more effective natural herbicides and decrease the use of herbicides. [ABSTRACT FROM AUTHOR]

A lack of chronic rare earth element (REE) toxicity data for marine organisms has impeded the establishment of numerical REE water quality benchmarks (e.g., guidelines) to protect marine life and assess ecological risk. This study determined the chronic no (significant) effect concentrations (N(S)ECs) and median-effect concentrations (EC50s) of eight key REEs (yttrium (Y), lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), gadolinium (Gd), dysprosium (Dy) and lutetium (Lu)) for 30 coastal marine organisms (encompassing 22 phyla and five trophic levels from temperate and tropical habitats). Organisms with calcifying life stages were most vulnerable to REEs, which competitively inhibit calcium uptake. The most sensitive organism was a sea urchin, with N(S)ECs ranging from 0.64 μg/L for Y to 1.9 μg/L for La and Pr, and EC50s ranging from 4.3 μg/L for Y to 14.4 μg/L for Pr. Conversely, the least sensitive organism was a cyanobacterium, with N(S)ECs ranging from 121 μg/L for Y to 469 μg/L for Pr, and EC50s ranging from 889 μg/L for Y to 3000 μg/L for Pr. Median sensitivity varied 215-fold across all organisms. The two-fold difference in median toxicity (μmol/L EC50) among REEs (Y ∼ Gd > Lu ∼ Nd ∼ Dy ∼ Ce > La ∼ Pr) was attributed to offset differences in binding affinity (log K) to cell surface receptors and the percentage of free metal ion (REE3+) in the test waters. The toxicity (EC50) of the remaining REEs (samarium, europium, terbium, holmium, thulium and ytterbium) was predicted using a combination of physicochemical data and measured EC50s for the eight tested REEs, with good agreement between predicted and measured EC50s for selected organisms. Numerical REE water quality guidelines to protect marine life were established using species sensitivity distributions (e.g., for 95 % species protection, values ranged from 1.1 μg/L for Y to 3.0 μg/L for La, Pr or Lu). [Display omitted] • New rare earth element (REE) chronic toxicity data for 30 marine organisms. • Calcifying organisms (e.g., sea urchin) were typically the most sensitive to REEs. • Two-fold difference in toxicity among REEs (Y ∼ Gd most toxic and Lã Pr least toxic). • Toxicity differences among REEs explained by % REE3+ and cell binding affinity. • Numerical REE water quality guidelines were established to protect marine life. [ABSTRACT FROM AUTHOR]

The present study had the objective of evaluating the in vitro sensitivity of Fusarium sacchari to five fungicides of different chemical groups. An isolate of F. sacchari obtained from sugarcane plants (Saccharum officinarum) with wilt symptoms and identified morphologically and molecularly by the characteristics of the genus Fusarium and amplification of the ITS and TEF regions, respectively, was used to evaluate the fungicides azoxystrobin, difenoconazole, hymexazole, cyprodinil and thiabendazole, at concentrations of 1, 10, 100 and 1000 μg mL-1, using the poison plate technique. The effect of the fungicides and EC50 was determined by the percentage inhibition of F. sacchari growth with respect to the growth on the plates without fungicide. The fungicides difenoconazole at 1000 μg mL-1 and thiabendazole at 100, 1000 and 10 μg mL-1 were statistically equal and presented the highest mycelial growth inhibition percentages (93.5 and 92.1, 91.4 and 89.8 %, respectively). The lowest EC50 values were presented by difenoconazole (9.2 μg mL-1), thiabendazole (9.9 μg mL-1) and cyprodinil (10.6 μg mL-1). In conclusion, F. sacchari presented higher in vitro sensitivity to the fungicides difenoconazole (1000 μg mL-1) and thiabendazole (100, 1000 and 10 μg mL-1). [ABSTRACT FROM AUTHOR]

Dimethyl sulfoxide (DMSO) is widely used as a vehicle solvent in ecotoxicity bioassays.Despite its frequent use, it could be toxic for organisms at some concentrations. Hence, this study aims to investigate the effects of DMSO on the model organisms: microalgae Raphidocelis subcapitata, microcrustacean Daphnia magna, and rotifer Brachionus calyciflorus. DMSO was applied to the organisms in concentrations ranging from 0.031% to 4%. For R. subcapitata the lowest observed effect concentration (LOEC) after 72 h of exposure was 0.125% DMSO. The 50% effective concentration (EC50) was 2.138 ± 0.372%. In D. magna, significant differences in the mobility after 24 h or 48 h of exposure were observed for 1% DMSO being 1.712 ± 0.207% and 1.167 ± 0.220% DMSO the EC50 observed for 24 h and 48 h exposure, respectively. For B. calyciflorus, it was not possible to validate the tests performed, as there were insufficient animals alive in the control conditions at the end of the exposure period. Therefore, we recommended avoiding DMSO as a vehicle in assays using B. calyciflorus, and to use final DMSO concentrations in an experimental solution not exceeding 0.125% for R. subcapitata and 0.5% for D. magna. Finally, using a maximum of 0.01% DMSO is safe for the organisms tested. The effects of the vehicle solvent dimethyl sulfoxide (DMSO) were investigated in three aquatic model organisms, the microalgae Raphidocelis subcapitata, the microcrustacean Daphnia magna and the rotifer Brachionus calyciflorus. As a result, negative effects on growth rate for the algae population, immobilisation of daphnids and inhibition of rotifer reproduction was observed obtaining EC50 close to 1% of DMSO for all these cases. [ABSTRACT FROM AUTHOR]

Sodium alginate (ALG) and sodium carboxymethyl cellulose (CMC) are two polysaccharides that have a wide range of applications, which could lead to accidental pollution of the environment, making the assessment of their potential ecotoxicity imperative. The present study assesses the effects of ALG and CMC on the growth response of common duckweed (Lemna minor L.). The results emphasize that both polysaccharides can be classified as practically nontoxic based on their EC50 values, with ALG having a relatively higher toxicity compared to CMC. It was also observed that high doses of 1, 5 and 10 mg mL-1 of the two polysaccharides produced growth inhibitory effects against common duckweed. The toxicity of biopolymers against common duckweed, measured as EC50 values, seems to be correlated to the hydrophobicity of the monomers building the polymer. The EC50 values increase linearly with increasing water solubility (log S) values and decrease linearly with the lipophilicity (log P) values. [ABSTRACT FROM AUTHOR]

Aims: Propofol may result in hypotension, bradycardia and loss of protective reflexes, especially in elderly patients, while esketamine, a N‐methyl‐D‐aspartate receptor antagonist, has analgesic, anaesthetic and sympathomimetic properties and is known to cause less cardiorespiratory depression. We hypothesized that esketamine may reduce the median effective concentration (EC50) of propofol and coadministration is less likely to produce hypotension during gastrointestinal endoscopy in elderly patients. Methods: Ninety elderly patients, aged 65–89 years, undergoing gastrointestinal endoscopy were randomly assigned into 3 groups: SK0 (control) group (0 mg/kg esketamine); SK0.25 group (0.25 mg/kg esketamine); and SK0.5 group (0.5 mg/kg esketamine). Anaesthesia was achieved by plasma target‐controlled infusion of propofol with different bolus doses of esketamine. The EC50 of propofol for gastrointestinal endoscopy was determined by using the up‐and‐down method of Dixon. The initial plasma target concentration is 2.5 μg/mL and the adjacent concentration gradient is 0.5 μg/mL. Cardiovascular variables were also measured. Results: Propofol EC50s and its 95% confidence interval for gastrointestinal endoscopy in elderly patients were 3.69 (2.59–4.78), 2.45 (1.85–3.05) and 1.71 (1.15–2.27) μg/mL in the SK0, SK0.25 and SK0.5 groups, respectively (P <.05). The average percent change from baseline mean arterial pressure was −19.7 (7.55), −15.2 (7.14) and −10.1 (6.73), in the SK0, SK0.25 and SK0.5 groups, respectively (P <.001). Conclusion: Combination medication of propofol with esketamine reduced the propofol EC50 during gastrointestinal endoscopy in elderly patients compared with administration of propofol without esketamine. Increasing doses of SK with propofol are less likely to produce hypotension with shorter recovery time. [ABSTRACT FROM AUTHOR]

Rigidoporus microporus is the main causal of white root disease (WRD) in rubber trees (Hevea brasiliensis). The present study investigates the use of rhamnolipid, a biosurfactant produced by Pseudomonas aeruginosa USM-AR2 against R. microporus. In vitro doseresponses towards rhamnolipid were determined on different isolates of R. microporus using the poisoned food technique (PFT). Inhibition of mycelial growth was found to be dose-dependent, with the highest inhibition of 76.74% at 200 ppm (pH 6.29) on SEG isolate. On the contrary, the lowest concentration of rhamnolipid applied at 10 ppm (pH 5.97) had effectively inhibited the growth of RL 19 to 34.36%. AM isolate was assumed to be the most aggressive pathogen due to the lowest inhibition recorded on all rhamnolipid concentrations tested. At the same time, RL 19 was the least aggressive pathogen compared to the other R. microporus isolates. The rhamnolipid concentrations (ppm), which reduced mycelial growth at 50% (EC50), were recorded at 17.82 ppm for AM isolate, 12.52 ppm for RL 26, and 11.80 ppm for RL 19 isolate. This result indicated that rhamnolipid concentrations to inhibit 50% of mycelial growth might vary based on the aggressiveness and the virulence levels of different R. microporus isolates. It was found that pH changes after incorporating rhamnolipid into the PDA were not the main factor affecting the inhibition of R. microporus isolates. It is obvious that rhamnolipid had an inhibitory effect on fungal growth in vitro. It is the first report on rhamnolipid that has been shown to control R. microporus potentially. [ABSTRACT FROM AUTHOR]

In this research, benzene, a toxic compound encountered in industrial wastewater, was extracted using a mixture of saponin and sodium dodecyl sulfate (SDS) as anionic surfactants. Also, a biosensor system for assessment of toxicity and detection of extracted benzene was designed using the Luc strains of luminescent Escherichia coli. Results showed saponin and SDS were synergistic for the extraction of benzene. An optimal hydrophilic–lipophilic balance value for extraction was determined to be about 24.1, representing a mixture of 40 wt% SDS and 60% saponin. Under optimal conditions, the concentration of extracted benzene in extraction phase reached 27 ppm. When extracted benzene solution was injected into the biosensor system, the luminescence level of biosensor decreased dramatically, reflecting toxicity. The concentration of benzene in the extracted solution correlated well with toxicity levels measured by the biosensor system. Using the luminescence biosensor system, the half‐maximal effective concentration (EC50) value of benzene was about 26.2 ppm. Our results demonstrate that the designed biosensor system has good sensitivity for toxicity assessment of extracted benzene, and therefore can be proposed as an approach to detect of benzene and other toxic compounds in wastewater. [ABSTRACT FROM AUTHOR]

Spot blotch of barley, caused by Bipolaris sorokiniana, has increased its intensity during the last growing seasons in Argentina. The in vitro inhibitory effect of different fungicide premixes on the mycelial radial growth of 10 B. sorokiniana isolates from different locations was assessed. Effective fungicide concentration that caused 50% inhibition of mycelial growth (EC50) was determined using a linear log analysis. The EC50 values varied from 0.05 to 0.37 µg mL−1 among fungicides. The lower EC50 values were obtained with premixes containing carboxamides. An additional in vivo experiment was performed to test the SB control when fluxapyroxad + pyraclostrobin + epoxiconazole was applied preventively or curatively. The fungicide significantly reduced the SB intensity (incidence, severity, number and size of lesions) when applied preventively. To our knowledge, this is the first report of sensitivity of B. sorokiniana and EC50 estimation to fungicides worldwide. [ABSTRACT FROM AUTHOR]

The in vitro antitumor activity (e.g. IC50) of anticancer drugs is important for selecting candidate compounds for in vivo drug efficacy study in the early stage of drug discovery. In this study, we investigated the relationship between in vitro IC50 and in vivo EC50 using six heat shock protein 90 (HSP90) inhibitors. IC50 of each compound was calculated from in vitro cell proliferation assays using the NCI-N87 cancer cell line. Each compound was administered to NCI-N87 xenograft mice, and EC50 and the maximum tumour-killing rate constant were calculated from pharmacokinetics/pharmacodynamics analyses using plasma concentrations and tumour volumes. IC50 obtained in vitro was poorly correlated with EC50 obtained in vivo, while a good correlation (r = 0.856) was observed between them when corrected with the unbound fraction ratio. The results of this study using of HSP90 inhibitors as model compounds suggest importance of the consideration of an unbound fraction to evaluate the relationship between IC50 and EC50. These results will contribute to improvement in the prediction accuracy of in vivo drug efficacy from in vitro activity and the efficiency of drug discovery research. [ABSTRACT FROM AUTHOR]

Anti-PD-1 therapies can activate tumor-specific T cells to destroy tumors. However, whether and how T cells with different antigen specificity and affinity are differentially regulated by PD-1 remain vaguely understood. Upon antigen stimulation, a variety of genes is induced in T cells. Recently, we found that T cell receptor (TCR) signal strength required for the induction of genes varies across different genes and PD-1 preferentially inhibits the induction of genes that require stronger TCR signal. As each T cell has its own response characteristics, inducibility of genes likely differs across different T cells. Accordingly, the inhibitory effects of PD-1 are also expected to differ across different T cells. In the current study, we investigated whether and how factors that modulate T cell responsiveness to antigenic stimuli influence PD-1 function. By analyzing TCRs with different affinities to peptide-MHC complexes (pMHC) and pMHCs with different affinities to TCR, we demonstrated that PD-1 inhibits the expression of TCR-inducible genes efficiently when TCR:pMHC affinity is low. In contrast, affinities of peptides to MHC and MHC expression levels did not affect PD-1 sensitivity of TCR-inducible genes although they markedly altered the dose responsiveness of T cells by changing the efficiency of pMHC formation, suggesting that the strength of individual TCR signal is the key determinant of PD-1 sensitivity. Accordingly, we observed a preferential expansion of T cells with low-affinity to tumor-antigen in PD-1-deficient mice upon inoculation of tumor cells. These results demonstrate that PD-1 imposes qualitative control of T cell responses by preferentially suppressing low-affinity T cells. [ABSTRACT FROM AUTHOR]

Essential oils have been used in aquaculture due to their wide range of biological activities. However, even though they have a potentially low risk for fish, it is necessary to assess the risks to nontarget organisms to guarantee their safe use in the environment. Here, we assessed the acute toxicity on the model organism Daphniamagna of seven essential oils of interest in aquaculture (Lippiaalba, Lippiagracilis, Lippiasidoides, Menthaarvensis, Menthapiperita, Ocimumgratissimum and Pipercallosum). Furthermore, we also studied the chemical composition of essential oils using gas chromatography‐mass spectrometry (GC‐MS) to relate toxicity to the chemical composition. The half maximal effective concentration values during 48 hours of exposure (EC50‐48 h) of the essential oils for D. magna showed toxicity ranging from moderately (EC50‐48 h 3.59 mg/L for L. gracilis, followed by L. sidoides, L. alba and O. gratissimum) to slightly toxic (EC50‐48 h 43.74 mg/L for M. piperita as the least toxic, M. arvensis and P. callosum). Thus, for the purpose of establishing ecologically safe therapeutic protocols, the correct use of these substances in aquaculture should be considered, as the toxicity of the essential oils observed indicates potential interference with the nontarget organism D. magna. [ABSTRACT FROM AUTHOR]

HIV-associated lipodystrophy has been reported in people taking anti-retroviral therapy (ART). Lipodystrophy can cause cardiovascular diseases, affecting the quality of life of HIV-infected individuals. In this study, we propose a pharmacological lipid index to estimate the risk of hyperlipidemia caused by anti-retroviral drugs. Lipid droplets were stained in cells treated with anti-retroviral drugs and cyclosporin A. Signal intensities of lipid droplets were plotted against the drug concentrations to obtain an isodose of 10 μM of cyclosporin A, which we call the Pharmacological Lipid Index (PLI). The PLI was then normalized by EC 50. PLI/EC 50 values were low in early proteinase inhibitors and the nucleoside reverse transcriptase inhibitor, d4T, indicating high risk of hyperlipidemia, which is consistent with previous findings of hyperlipidemia. In contrast, there are few reports of hyperlipidemia for drugs with high PLI/EC 50 scores. Data suggests that PLI/EC 50 is a useful index for estimating the risk of hyperlipidemia. • We generated a lipid index, PLI/EC50 score, for estimating the risk of hyperlipidemia caused by anti-retroviral drugs. • The index was determined by calculating the pharmacological lipid index (PLI) of drugs and dividing it by its EC50 values. • Lower PLI/EC50 were seen in drugs with high frequently reported risk of hyperlipidemia in clinical settings. • PLI is a suitable for drug development that can be performed in 48 h with culture cells using small amount of drug. • The PLI/EC50 score should serve as a valuable indicator for evaluating the lipotoxicity of antiviral drugs. [ABSTRACT FROM AUTHOR]

Background: Nebulized lidocaine reduced stress response for endotracheal intubation. However, the impact of novel lidocaine aerosol inhalation for intubation by ultrasonic atomizer was unclear. Hence, we designed aerosol inhalation of lidocaine by ultrasonic atomizer, to seek whether the dosage of sufentanil for intubation could be less or not. Methods: Intravenous injection of sufentanil started at 0.5 μg/kg, and sufentanil dosage was increased/decreased (step-size 0.05 μg/kg for sufentanil) using Dixon's up and down method. The observation was terminated after 8 reflexes. Results: The EC50 and EC95 of sufentanil with lidocaine by ultrasonic atomizer for intubation were found to be 0.232 μg/kg (95% CI: 0.187–0.270 μg/kg) and 0.447 μg/kg (95% CI: 0.364–0.703 μg/kg). 55.88% out of 34 patients showed hemodynamic index change < 20% of baseline during intubation. Conclusion: Aerosol inhalation of lidocaine by ultrasonic atomizer reduced the dosage of sufentanil for endotracheal intubation. Lidocaine inhalation by ultrasonic atomizer for airway anesthesia with minimal dosage of sufentanil could be recommended, particularly in patients who need more stable hemodynamic changes or spontaneous respiration. Trial registration: Chinese Registry of Central Trial, ChiCTR-IOR-17014198. Registered 28 December 2017. [ABSTRACT FROM AUTHOR]

[Objective] The paper was to screen the effective agents for effectively controlling the occurrence and prevalence of taro soft rot. [Method] The fungicidal effects of 11 fungicides on taro soft rot were determined by inhibition zone method. [Result] 0.3% Tetramycin, 25% bromothalonil, 3% Zhongshengmycin and 30% zinc thiazole had better antifungal effect on Pectobacterium aroidearum at recommended concentration. The indoor toxicity of four fungicides showed that the EC50 of 0.3% tetramycin AS was the smallest of 0.6 µg/mL, indicating that tetramycin had the largest toxicity and the best inhibitory effect against P. aroidearum-, followed by 25% bromothalonil EC and 3% Zhongshengmycin WP, with the EC50 of 2.57 and 97.72 µg/mL, respectively, the inhibitory effect of 30% zinc thiazole SC against P. aroidearum was the poorest. [Conclusion] The study provides a reference for screening out new and efficient chemical agents against taro soft rot. [ABSTRACT FROM AUTHOR]

Silver nanoparticles were synthesized by chemical reduction of silver nitrate using arabinogalactan polysaccharide as a reducing agent and a stabilizer. The average size of nanoparticles, obtained by analyzing TEM-images, was 10.8 nm; zeta potential -20 mV. A study of the sol by electron diffraction showed that silver in the sample is in metallic form. The resulting preparation of silver nanoparticles showed both antibacterial and antifungal activity. A pronounced antibacterial activity of silver nanoparticles was demonstrated both in relation to conditionally pathogenic gram-positive (Bacillus subtilis and B. coagulans) and gram-negative (Escherichia coli) bacteria. Silver nanoparticles also possess antifungal activity against macromycete Fomitopsis sp., as well as two strains of micromycetes Trichoderma citrinoviride and Fusarium sporotrichioides. Using the methods of light and fluorescence microscopy, MTT-analysis and Real-time cell analysis, the cytotoxic activity of silver nanoparticles was investigated on HepG2 human hepatocellular carcinoma cells. It was demonstrated that nanoparticles cause a suppression of cell metabolic and proliferative activity, as well as dose-dependent induction of cell death (average relative EC50 value was 9 ± 2:7 μg/ml). The preparation of silver nanoparticles stabilized by arabinogalactan can be used in medicine, as a potential antimicrobial and antitumor agent. [ABSTRACT FROM AUTHOR]

A stable preparation of agaricinic acid nanoparticles was obtained. The mean hydrodynamic size of nanoparticles according to photon correlation spectroscopy was 200 nm and zeta potential was -57 mV. Cytotoxic activity of agaricinic acid nanoparticles against human HepG2 hepatoma cells was evaluated. Nanoparticles with a low concentration of agaricinic acid stimulated and with high concentration — suppressed metabolic activity and viability of hepatoma cells. The EC50 for the stimulating effect was 32.8 μg/ml, and the IC50=602.1 mg/ml. The preparation of agaricinic acid nanoparticles can be used in medicine as a potential antitumor agent. [ABSTRACT FROM AUTHOR]

Objective: Naja ashei is a snake of medical importance in Kenya, Ethiopia, Somalia, Uganda, and Tanzania. Little is known about the enzymatic (snake venom phospholipases A2; svPLA2's) and toxic (lethal) activities of N. ashei venom and crucially, the safety and capacity of available antivenom to neutralize these effects. This study aimed to determine the enzymatic and toxic activities of N. ashei venom and the capacity of Indian and Mexican manufactured antivenoms to neutralize these effects. The protein content of the venom and the test antivenoms were also evaluated. A 12-point log concentration–response curve (0.5–22.5 µg/mL) was generated on an agarose-egg yolk model to predict the svPLA2 activity of the venom. The toxicity profiles of the venom and antivenoms were evaluated in the brine shrimp lethality assay. Lowry's method was used for protein estimation. Results: Low and intermediate concentrations of the venom exhibited similar svPLA2 activities. The same was true for concentrations > 15 µg/mL. Intermediate and high doses of the venom exhibited similar mortalities in brine shrimp and test antivenoms were generally non-toxic but poorly neutralized svPLA2 activity. Mexican manufactured antivenom had lower protein content but neutralized venom-induced brine shrimp lethality much more effectively than Indian manufactured antivenom. [ABSTRACT FROM AUTHOR]

The most recent outbreaks of boxwood blight caused by Calonectria pseudonaviculata, in Hyrcanian forests of Iran, have sparked the need for research to identify eco‐friendly fungicides for management purposes. Our study was conducted to test the efficacy of humic substances against C. pseudonaviculata under both in vitro and in vivo conditions. For this purpose, humic acids (HA) and fulvic acids (FA) extracted from tea waste compost (HAT & FAT), sawdust compost (HAW & FAW) and manure compost (HAM & FAM) were tested against hyphal growth and conidial germination of C. pseudonaviculata. In addition, EC50 and MIC50 were determined for all humic substances tested. While none of the substances caused complete inhibition of the fungus, they showed a range of antifungal activities. Based on the high inhibitory efficacy and low related EC50 and MIC50, HAT and FAT provided the highest efficacy against the pathogen. In the greenhouse, curative and protective effects of the humic treatments at 2,000 mg/L were also investigated against disease severity. Of the substances tested, FAW and FAM showed the weakest antifungal effects and HAT had the greatest curative and protective effects. These results indicate that HAT application can be used as an eco‐friendly control method for boxwood blight epidemics in the disease hotspots of Hyrcanian forests. [ABSTRACT FROM AUTHOR]

Biocides are multi-component products used to control undesired and harmful organisms able to affect human or animal health or to damage natural and manufactured products. Because of their widespread use, aquatic and terrestrial ecosystems could be contaminated by biocides. The environmental impact of biocides is evaluated through eco-toxicological studies with model organisms of terrestrial and aquatic ecosystems. We focused on the development of in silico models for the evaluation of the acute toxicity (EC50) of a set of biocides collected from different sources on the freshwater crustacean Daphnia magna, one of the most widely used model organisms in aquatic toxicology. Toxicological data specific for biocides are limited, so we developed three models for daphnid toxicity using different strategies (linear regression, random forest, Monte Carlo (CORAL)) to overcome this limitation. All models gave satisfactory results in our datasets: the random forest model showed the best results with a determination coefficient r2 = 0.97 and 0.89, respectively, for the training (TS) and the validation sets (VS) while linear regression model and the CORAL model had similar but lower performance (r2 = 0.83 and 0.75, respectively, for TS and VS in the linear regression model and r2 = 0.74 and 0.75 for the CORAL model). [ABSTRACT FROM AUTHOR]

Worldwide, there are only few studies focusing on labor analgesia on the MLAC (minimum local analgesic concentration) or EC50 (median effective concentration) of sufentanil and ropivacaine. Therefore, we determine the MLAC or EC50 of sufentanil and ropivacaine for epidural analgesia by using an up–down sequential allocation and survey its adverse effect in a prospective blinded randomized trial. Sixty nulliparous full-term parturients who required labor analgesia were recruited and randomly divided into the sufentanil and ropivacaine groups. The formulation was 25 μg sufentanil combined with 0.1% ropivacaine (added 0.9% normal saline to 75 ml). According to the response of a previous parturient, the dosage of sufentanil was increased or decreased by 5 μg in the sufetanil group; meanwhile, we also administrated an initial concentration of 0.1% ropivacaine combined with 22.5 μg sufentanil (added 0.9% normal saline to 75 ml) in the ropivacaine group. The concentration of ropivacaine was increased or decreased by 0.01% following the response of the previous parturient. The Brownlee up–down sequential allocation was used to estimate the MLAC of epidural ropivacaine and its 95% confidence intervals in labor analgesia. There were no significant changes for the two groups, including for age, height weight, active stage, second stage of labor, and gestational weeks (P = 0.769, 0.900, 0.603, 0.441, 0.577, and 0.695, respectively). The VAS scores of the parturient decreased to varying degrees (P < 0.0001) after labor analgesia compared with VAS before labor analgesia, and the most effective analgesia was reached in 60 min. The EC50 dose of epidural ropivacaine combined with 0.3 μg/mL sufentanil was 0.09687%, and the 95% CI was 0.08944%~0.1043%. Five parturients had PONV, and the incidence rate was 16.7%; one parturient had pruritus, so the incidence rate was 3.3%. The EC50 dose of epidural sulfetanil combined with 0.1% ropivacaine was 18.76 μg with a 95% confidence interval of 13.5–24.48 μg. There were no significant differences in the active stage, second stage of labor, and maternal and fetal hemodynamic data between the two groups. Notably, the Apgar scores for 1 min and 5 min were 10 scores for almost all of these patients. There were no significant differences between the two groups for maternal and fetal side effects, which had very low incidence rates. The MLAC of epidural sufentanil or ropivacaine could provide satisfactory and safe analgesia for parturients while having a low incidence rate of side effects. [ABSTRACT FROM AUTHOR]

Rapeseed isolates of Sclerotinia sclerotiorum (Lib.) de Bary 1884 from the Nitra Region of Slovakia were investigated for their in vitro sensitivity to azoxystrobin and picoxystrobin; and for determining their EC50 value. The growth of S. sclerotiorum was evaluated on a PDA medium amended with the selected fungicide´s active ingredient at 4 different concentrations – 0.08, 0.83, 8.33, and 83.30 ppm. The overall mean EC50 values for azoxystrobin and picoxystrobin were 2.73 ppm and 3.12 ppm, respectively. The majority of the isolates had resistance factors up to 20, which suggests a shift in the S. sclerotiorum population sensitivity towards the resistance. [ABSTRACT FROM AUTHOR]

Background: Tenofovir disoproxil fumarate (TDF) imposes a high genetic barrier to drug resistance and potently inhibits replication of multidrug‐resistant hepatitis B virus. Few clinical cases with confirmed TDF‐resistance have been reported to date. Methods and Results: Here, we report viral rebound in a patient with chronic hepatitis B who underwent TDF monotherapy and harboured a quadruple mutant consisting of classic entecavir (ETV)‐resistance mutations (rtL180M/T184L/M204V) together with an rtA200V mutation in the reverse transcriptase gene. Sequencing analysis revealed that this quadruple mutant emerged as a major viral population. In vitro phenotyping demonstrated that the rtL180M/T184L/A200V/M204V mutant had moderate resistance to TDF treatment, with a 4.52‐fold higher half maximal effective concentration than that of wild‐type virus. Importantly, this patient with TDF resistance achieved virological suppression after TDF/ETV combination rescue therapy. Conclusion: An rtL180M/T184L/A200V/M204V mutant with moderate resistance to TDF monotherapy was selected during sequential nucleoside analogue (NA) treatment in a stepwise manner. ETV/TDF combination therapy effectively suppressed replication of this TDF‐resistant mutant. Our studies provide novel insights into the treatment of NA‐naïve patients as well as patients with TDF resistance. [ABSTRACT FROM AUTHOR]

Application of pesticides creates hazards to the aquatic organisms. This study aimed to determined influence of bromacil, thiabendazole, malathion and mixtures of it on Tilapia nilotica (fish) and D magna. Effects included determination of mortality rate, losing sensation and behavior change (jump attempts) of fish and mortality rate for D. magna using concentration range from 0-6 mg/l. Normal growth of fish and D. Magana was observed under suitable laboratory conditions. The most toxic compound to D. magna was malathion, has an EC50 (Effective concentration that affect 50% of experimental animal) value of 0.43 (mg/l) compared to that of bromacil 0.59 (mg/l). Mixture of bromacil and malathion was less toxic than separately and have larger EC50 value 0.64 in toxic unit (TU) indicating potential antagonistic effect. Moreover, thiabendazole was more effective to fish than malathion. Relative toxicity (RT) indicates that thiabendazole has a lower value (0.276) than malathion indicating higher toxicity of thiabendazole. Furthermore, fish and D. magna were sensitive to low concentrations. These data indicate potent threats to aquatic organisms. [ABSTRACT FROM AUTHOR]

The elevated interest in silver ions (Ag+) as a broad spectrum antimicrobial for use on medical devices has increased the number and importance of in vitro biocompatibility testing, however little consideration is given to the culture environment in which the assessments are performed. The current investigation assessed the viability of mouse fibroblasts (L929) exposed to different concentrations of Ag+ in both Dulbecco's modified Eagle's medium (DMEM) and minimal essential medium Eagle, alpha modification (αMEM). We identified a significant increase in the EC 50 of L929 cells exposed to Ag+ in αMEM compared to DMEM, which was matched by a corresponding decrease in Ag+ availability in αMEM at concentrations ≤400 μM, as detected by inductively coupled plasma mass spectrometry (ICP-MS). The reduced availability was not observed for Ag+ > 400 μM, the concentration above which caused in vitro cytotoxicity in L929 cells in αMEM; while linear quantification of Ag+ was observed in DMEM. Equilibration of the chloride and glucose components between media did not affect cytotoxicity on primary test cells; mesenchymal stromal cells (MSCs). Overall, our results present evidence of the importance of culture conditions on the in vitro evaluation of silver, with DMEM providing a reliable basal media in which to conduct assessments. • Antimicrobial concentrations of silver ions (Ag+) may cause cytotoxicity. • Ag+ cytotoxicity is significantly modified by culture media (αMEM versus DMEM). • Bioavailability of Ag+ is reduced in αMEM at concentrations ≤400 μM. • Ag+ quantification in DMEM is linear, providing a predictive media for testing. [ABSTRACT FROM AUTHOR]

As population growth places greater pressures on potable water supplies, nonpotable recycled irrigation water is becoming widely used on turfgrass areas including golf courses, sports fields, parks, and lawns. Nonpotable recycled waters often have elevated salinity levels, and therefore turfgrasses must, increasingly, have good salinity tolerance to persist in these environments. This greenhouse study evaluated 10 commonly used cultivars representing warm-season turfgrass species of bermudagrass (Cynodon spp.), zoysiagrass (Zoysia spp.), st. augustinegrass [Stenotaphrum secundatum (Walt.) Kuntze], and seashore paspalum (Paspalum vaginatum Swartz) for their comparative salinity tolerance at electrical conductivity (EC) levels of 2.5 (control), 15, 30, and 45 dS·m-1. Salinity treatments were imposed on the grasses for 10 weeks via subirrigation, followed by a 4-week freshwater recovery period. Attributes, including turf quality, the normalized difference vegetation index (NDVI), canopy firing, and shoot biomass reductions were evaluated before and after salinity stress, as well as after the 4-week freshwater recovery period. Results showed considerable differences in salinity tolerance among the cultivars and species used, with the greatest tolerance to elevated salinity noted within seashore paspalum cultivars and Celebration® bermudagrass. In comparison with growth in 2.5-dS·m-1 control conditions, increased shoot growth and turf quality were noted for many bermudagrass and seashore paspalum cultivars at 15 dS·m-1. However, st. augustinegrass and some zoysiagrass cultivars responded to elevated salinity with decreased growth and turf quality. No cultivars that had been exposed to 30- or 45-dS·m-1 salinity recovered to acceptable levels, although bermudagrass and seashore paspalum recovered to acceptable levels after exposure to 15-dS·m-1 salinity. More severe salinity stress was noted during year 2, which coincided with greater greenhouse temperatures relative to year 1. [ABSTRACT FROM AUTHOR]

This study investigated the in vitro efficacy of essential oils (OEs) of four species of plants of the family Piperaceae, these being; Piper hispidinervum, Piper hispidum, Piper marginatum and Piper callosum, in the control of Neoechinorhynchus buttnerae acanthocephalus that affect tambaqui. The tested concentrations of OE were: 0.19; 0.39; 0.78; 1.56; 3.125; 6.25; 12.5; 25 and 50 mg.mL-1, in triplicate, into petri dishes containing 10 parasites per plate. In this in vitro assay, all OEs studied showed significant activity against the acanthocephal N. buttnerae. There was higher mortality of the parasites at the highest concentrations and times of exposure to the OEs tested. Effective concentrations of 50% (EC50) were obtained through probit analysis and evaluated according to the exposure time in 2, 6 and 24 hours. The OE of P. hispidinervum showed lower values of EC50 (0,56; 0,54 e 0,51 mg.mL-1) compared to the values obtained for Piper hispidum (EC50 de 5,44; 3,85 e 1,75 mg.mL-1), Piper marginatum (EC50 de 2,98; 1,3 e 1,27 mg.mL-1) and Piper callosum (EC50 de 2,66; 2,16 e 2,16 mg.mL-1). [ABSTRACT FROM AUTHOR]

The toxicity of extracts of lavender (Lavandula officinalis) leaves and flowers was evaluated. Aqueous ethanolic and acetone extracts had higher tannin content than that in the aqueous solution. Polyphenol and flavonoid contents were measured in aqueous extracts of leaves and flowers. Polyphenol concentration in aqueous leaf and flower extracts was 61.31 and 84.43 mg tannic acid/g, respectively, whereas flavonoid concentration was 194.1 and 109.9 mg quercetin/g, respectively. Saponin content was 7.85% and 6.22% in leaves and flowers extract, respectively, and alkaloids content was 0.2651% and 0.2132% for leaves and flowers extract, respectively. The EC50 (36 h) of hatching success of Artemia salina cysts was 0.301 and 0.915 mg/mL for aqueous extracts of leaves and flowers, respectively, whereas that for aqueous ethanolic extracts of leaves and flowers, it was 0.111 and 0.586 mg/mL, respectively. The EC50 (36 h) was 0.011 mg/mL for tannic acid. Additionally, the LC50 (24 h) for aqueous extracts of leaves and flowers was 0.467 and 0.724 mg/mL, respectively, whereas that of the aqueous ethanolic extracts of leaves and flowers was 0.074 and 0.126 mg/mL, respectively. The LC50 was 0.015 mg/mL for tannic acid. Although aromatherapy using lavender oils or extracts is beneficial to human health, particularly owing to its anxiolytic, analgesic, and antihyperlipidemic effects, we demonstrated that these extracts might exhibit toxicity. Hence, lavender should be used carefully by health practitioners, and lavender therapies should be closely monitored by medical staff to avoid its toxic effects. [ABSTRACT FROM AUTHOR]

Abstract With the increasing applications in various industrial areas, toxicity of ionic liquids (ILs) has gained much attention in recent years. In this work, 1-octyl-3-methylimidazolium nitrate ([C 8 mim]NO 3), 1-octyl-3-methylimidazolium chloride ([C 8 mim]Cl), N-octyl-3-metylpyridinium chloride ([C 8 mpy]Cl) and N-octyl-3-metylpyridinium bromide ([C 8 mpy]Br) were used to investigate the impacts of different types of cations and anions on their toxicity to a marine diatom Phaeodactylum tricornutum. Results showed that the four ILs had poor degradability under the culture conditions used in this study, and significantly inhibited the growth of this diatom with 96-h EC 50 values of 24.0, 33.6, 16.1 and 14.4 mg L−1 for [C 8 mim]NO 3 , [C 8 mim]Cl, [C 8 mpy]Cl and [C 8 mpy]Br, respectively. The data indicated that types of cations and anions would affect the toxicity of ILs to this diatom. Additionally, photosynthesis of this diatom was inhibited because significant decrease of chlorophyll a content and damage of PSII reaction centers were observed when it was exposed to the four ILs. Remarkable physiological and biochemical responses occurred in the cells of this diatom to alleviate the damaging effects of the four ILs. For example, content of soluble protein and activities of superoxide dismutase (SOD) and catalase (CAT) in the cells of this diatom increased significantly to form a protective mechanism against the toxicity of ILs, although they decreased in the cultures with high concentrations of ILs (≥20 mg L−1). Thus, these results would not only provide strong evidences for evaluating the ecological risks and toxicity of ILs to marine ecosystem, but also help for understanding their toxic mechanisms to marine diatoms. Graphical abstract Unlabelled Image Highlights • Four ILs ([C 8 mim]NO 3 , [C 8 mim]Cl, [C 8 mpy]Cl and [C 8 mpy]Br) were not easily degraded. • Types of cations and anions would affect the toxicity of ILs to P. tricornutum. • The photosynthesis of P. tricornutum was inhibited by the four ILs. • Contents of protein and MDA changed remarkably when the diatom was exposed to ILs. • Significant changes in SOD and CAT activities occurred under the exposure of ILs. [ABSTRACT FROM AUTHOR]

Abstract Zinc (Zn) and copper (Cu) are essential elements for living organisms, but they are also among the most frequent soils pollutants. Toxicity of these elements is difficult to assess and often shows contradictory results among authors due to the great complexity of the interactions with soil properties and constituents. The study of the individual metal behaviour will help provide a complete overview of the metal patterns in field pollution processes. Here, the influence of different soil properties on the mobility of Zn and Cu is studied in laboratory spiked soil samples by assessing metal toxicity from three different toxicity tests: root elongation, heterotrophic soil respiration and Microtox® toxicity tests. The results indicate that toxicity is significantly correlated with soil properties, calcium carbonate and organic carbon being the variables with highest influence in the reduction of Zn and Cu toxicity. However, large differences among soil samples in the toxicity results are observed. Thus, endpoints measured differ strongly in each soil sample because of the different sensibility of the organisms used in the toxicity tests and the high variability in soil properties. In addition, the results indicate differences between the soil toxicity depending on whether total or bioavailable metal concentrations are taken into account. Therefore, the current threshold concentrations usually selected for determining soil toxicity are not realistic, and a new approach is necessary taking into account the soil properties and the metal availability as well as using different toxicity tests to assess the toxic risk of metal-polluted soils. Highlights • Copper showed lower water-solubility than Zn in soils. • Carbonates content in soils is a good buffer for Zn and Cu retention. • Toxicity thresholds strongly difference among toxicity test. • Soil properties and constituents are key factors for assessing metal pollution. [ABSTRACT FROM AUTHOR]

Abstract Readily biodegradable and "practically non-toxic" dual functionalized imidazolium ionic liquids (ILs) carrying nitrile and varying number of ether group were developed to improve the extractive desulfurization performance and ecotoxicity of ILs. Dicyanamide (N(CN) 2), trifluoroacetate (CF 3 COO) and bis(trifluoromethylsulfonyl)imide (NTf 2) were selected as anions. Evaluation of thermophysical properties of the synthesized ILs revealed that bis(trifluoromethylsulfonyl)imide anion based ILs have lowest viscosity, which contributed to excellent mass transfer and enhanced desulfurization performance. The effect of temperature, time and mass ratio (ILs: model oil) were investigated for extractive desulfurization and the performance of ILs were in the anion order; dicyanamide < trifluoroacetate < bis(trifluoromethylsulfonyl)imide. Dibenzothiophene was more selectively extracted over 4,6- dimethyldibenzothiophene. Increasing alkoxy group on the cation side chain improved the desulfurization efficiency. More than 70% of dibenzothiophene was extracted in 15 min (single stage extraction) with a mass ratio of 1.5:1 at 25 °C by bis(trifluoromethylsulfonyl)imide anion based ILs with three ether groups on the imidazolium cation. Conductor like Screening Model for Real Solvents tool (COSMO-RS) and FTIR spectroscopy study revealed that interaction between dibenzothiophene and ILs were mainly dominated by π-π interaction and hydrogen bonding. The microbial toxicity and biodegradability assessment indicated that ILs were "practically harmless" and "readily biodegradable" through the incorporation of alkoxy groups on the cationic core of bis(trifluoromethylsulfonyl)imide anion based ILs. The ILs can be reused more than 8 cycles for the desulfurization process without regeneration. Graphical abstract Image 1 Highlights • Imidazolium ionic liquids (ILs) carrying nitrile and ether group were developed. • Desulfurization efficiency increased with the anion size having fixed cation. • COSMO-RS and FTIR used to study the interaction between ILs and dibenzothiophene. • More than 70 % of dibenzothiophene extracted by ILs with highest ether group. • Microbial toxicity studies depicted that the ILs to be as "practically harmless". [ABSTRACT FROM AUTHOR]

Abstract Major sugar constituents in young coconut husk were found to be glucans (0.30 g/g husk), while xylans were 0.10 g/g husk. Pre-treatments were carried out using phosphoric acid with dried coconut husk powder under steam heating. The effect of phosphoric acid on coconut husk hydrolysis was observed using acid concentrations of 0%, 1%, 5% and 10% (v/v). Soluble sugar concentration in hydrolysate was increasing proportional to acid concentration, as the total recovered solid decreases. FTIR and XRD analysis showed that acid hydrolysis led to the disruption of internal chemical bonds, causing coconut husk structural sugars to be released into the hydrolysate. Highest soluble sugar concentration, 29.9 g/L with a total suspended solid of 75.1 g/L, was obtained when the coconut husk was pre-treated with 10% phosphoric acid, and can be utilised for biohydrogen fermentation. Biotoxicity testing of the hydrolysates shows that half-maximal inhibition concentration of phosphoric acid was around 4.41% for a 24-h incubation and 3.80% for a 96-h incubation. Graphical abstract Image 1 Highlights • Coconut husk sugar yield increases 18.3 g/L for 0% H 3 PO 4 to 29.9 g/L for 10% H 3 PO 4. • Biohydrogen yield of 0.68 mol H 2 /mol sugar is obtained with 1% H 3 PO 4 hydrolysate. • The half-maximal inhibition concentration of H 3 PO 4 is 4.41% for 24-h incubation. • The decrease order of biotoxicity is 10% H 3 PO 4 > 5% H 3 PO 4 > 1% H 3 PO 4 > 0% H 3 PO 4. [ABSTRACT FROM AUTHOR]

Abstract Background Double-stranded (ds) DNA virus infections often occur concomitantly in immunocompromised patients. We performed a systematic search of published in vitro activity for nine approved and investigational antivirals to understand the spectrum of in vitro activity against dsDNA viruses. Methods A literature search was performed (PubMed and the WoS Core Collection) using keywords related to: 1) targeted approved/developmental antivirals (acyclovir, artesunate, brincidofovir, cidofovir, cyclopropavir (filociclovir), foscarnet, ganciclovir, letermovir, and maribavir); 2) pathogenic dsDNA viruses; 3) in vitro activity. We summarized data from 210 publications. Results Activity against ≤3 viruses was documented for maribavir (cytomegalovirus, Epstein-Barr virus), and letermovir, while activity against > 3 viruses was shown for ganciclovir, cidofovir, acyclovir, foscarnet, cyclopropavir, artesunate, and brincidofovir. The EC 50 values of brincidofovir were the lowest, ranging from 0.001 to 0.27 μM, for all viruses except papillomaviruses. The next most potent agents included cidofovir, ganciclovir, foscarnet, and acyclovir with EC 50 values between 0.1 μM and >10 μM for cytomegalovirus, herpes simplex virus, and adenovirus. Conclusion Most of the identified antivirals had in vitro activity against more than one dsDNA virus. Brincidofovir and cidofovir have broad-spectrum activity, and brincidofovir has the lowest EC 50 values. These findings could assist clinical practice and developmental research. Highlights • This is the first full summary of in vitro antiviral activity for 9 antivirals against human pathogenic dsDNA viruses. • Published in vitro activity often extended beyond the virus(es) covered by the labelled indication. • Most agents have good in vitro activity against individual or small subsets of dsDNA viruses that infect humans. • Based on an EC 50 cut off of 10 μM, the spectrum of antiviral activity ranged from broadest to narrowest as follows: o brincidofovir > cidofovir > ganciclovir > artesunate > acyclovir > cyclopropavir (filociclovir) > maribavir > letermovir > foscarnet. [ABSTRACT FROM AUTHOR]