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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]

Ecuador’s wetlands and aquatic ecosystems are chronically exposed to ash contamination due to the frequent volcanoes’ eruptions in the country. Still, the short and long-term effects of ash contamination on the aquatic biota are not well understood. We used ashes released by the Cotopaxi volcano in 2016 to investigate their acute and chronic effects in Daphna magna. We calculated the half maximal effective concentration (EC50) after 2 and 21 days of exposure, the non-observed effect concentration (NOEC), and the lowest observed effect concentration (LOEC) on offspring production. We also analyzed the metal concentration present in the ashes. The EC50 values at 2 and 21 days were found at 80% and 5% ash leachate concentrations, respectively. After 21 days of exposure, high mortality and low neonatal production were observed in all leachate concentrations (NOEC was at 15%, and LOEC was at 20% leachate concentration). Our results suggest that the ashes from the Cotopaxi volcano can cause acute and chronic toxicity to aquatic life and should be classified as hazardous waste, depending on the dose. There is an urgent need for further studies that assess toxicity caused by the intense volcanic activity in Ecuador. [ABSTRACT FROM AUTHOR]

Abstract 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.

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.

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]

Strawberry red core root rot disease affects the growth and yield of strawberry (Fragaria ananassa Duch), which leads to economic losses in China. The study employed a tissue separation method to isolate and identify the causal agent responsible for strawberry red core root rot. This was achieved by the observation of its morphological characteristics, sequencing analyses, and pathogenicity tests. The sensitivity of five chemical fungicides against the two species of Fusarium was determined using the mycelial growth rate method, and the biological characteristics of the two species were examined. The pathogens were identified as Fusarium solani and Fusarium oxysporum. The optimal conditions for the mycelial growth of F. solani and F. oxysporum were determined to be potato sucrose agar at 25 °C and pH 6, and potato dextrose agar at 30 °C and pH 8, respectively, with a 24:24 light cycle. The most suitable carbon and nitrogen sources for the mycelial growth of F. solani were sucrose and sodium nitrate (NaNO3), while for F. oxysporum, they were glucose and peptone. A fungicide sensitivity test indicated that Prochloraz had a good inhibitory effect on the growth of F. solani and F. oxysporum with EC50 values of 0.088 mg L−1 and 0.162 mg. The growth inhibition effect of Azoxystrobin to F. solani and Carbendazim to F. oxysporum was not obvious. This study provides a theoretical basis for further research on strawberry red core root disease and its prevention. [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]

Aquatic ecosystems can suffer inadvertent contamination from widely used herbicides. This study delves into the relative toxicity of 36 herbicides on green algae, exploring 11 distinct modes of action and 25 chemical structure classes. Through a 72-h algal growth inhibition test, it was found that herbicides targeting acetolactate synthase (ALS), photosystem II (PSII inhibitors), microtubule assembly, very-long-chain fatty acid (VLCFA) synthesis, and lipid synthesis exhibited high toxicity, with 72-h EC50 (half-maximal effective concentration) values ranging from 0.003 mg/L to 24.6 mg/L. Other pesticide types showed moderate to low toxicity, with EC50 values ranging from 0.59 mg/L to 143 mg/L. Interestingly, herbicides sharing the same mode of action but differing in chemical composition displayed significantly varied toxicity. For instance, penoxsulam and pyribenzoxim, both ALS inhibitors, demonstrated distinct toxicity levels. Similarly, terbuthylazine and bentazone, both PSII inhibitors, also exhibited differing toxicities. Notably, herbicides approved for rice cultivation showed lower toxicity to green algae compared to those intended for terrestrial plants. These data offer valuable insights for assessing the potential risks posed by these chemicals to aquatic organisms. Additionally, to prevent or minimize herbicide residual effects, modern management practices were reviewed to offer practical guidance. [ABSTRACT FROM AUTHOR]

Aquatic ecosystems can suffer inadvertent contamination from widely used herbicides. This study delves into the relative toxicity of 36 herbicides on green algae, exploring 11 distinct modes of action and 25 chemical structure classes. Through a 72-h algal growth inhibition test, it was found that herbicides targeting acetolactate synthase (ALS), photosystem II (PSII inhibitors), microtubule assembly, very-long-chain fatty acid (VLCFA) synthesis, and lipid synthesis exhibited high toxicity, with 72-h EC50 (half-maximal effective concentration) values ranging from 0.003 mg/L to 24.6 mg/L. Other pesticide types showed moderate to low toxicity, with EC50 values ranging from 0.59 mg/L to 143 mg/L. Interestingly, herbicides sharing the same mode of action but differing in chemical composition displayed significantly varied toxicity. For instance, penoxsulam and pyribenzoxim, both ALS inhibitors, demonstrated distinct toxicity levels. Similarly, terbuthylazine and bentazone, both PSII inhibitors, also exhibited differing toxicities. Notably, herbicides approved for rice cultivation showed lower toxicity to green algae compared to those intended for terrestrial plants. These data offer valuable insights for assessing the potential risks posed by these chemicals to aquatic organisms. Additionally, to prevent or minimize herbicide residual effects, modern management practices were reviewed to offer practical guidance.

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]

Pesticides are commonly found in the environment and pose a risk to target and non-target species; therefore, employing a set of bioassays to rapidly assess the toxicity of these chemicals to diverse species is crucial. The toxicity of nine individual pesticides from organophosphate, organochlorine, phenylurea, dinitroaniline, carbamate, and viologen chemical classes and a mixture of all the compounds were tested in three bioassays (Hydra vulgaris, Lemna minor, and Caenorhabditis elegans) that represent plant, aquatic, and soil-dwelling species, respectively. Multiple endpoints related to growth and survival were measured for each model, and EC10 and EC50 values were derived for each endpoint to identify sensitivity patterns according to chemical classes and target organisms. L. minor had the lowest EC10 and EC50 values for seven and five of the individual pesticides, respectively. L. minor was also one to two orders of magnitude more sensitive to the mixture compared to H. vulgaris and C. elegans, where EC50 values were calculated to be 0.00042, 0.0014, and 0.038 mM, respectively. H. vulgaris was the most sensitive species to the remaining individual pesticides, and C. elegans consistently ranked the least sensitive to all tested compounds. When comparing the EC50 values across all pesticides, the endpoints of L. minor were correlated with each other while the endpoints measured in H. vulgaris and C. elegans were clustered together. While there was no apparent relationship between the chemical class of pesticide and toxicity, the compounds were more closely clustered based on target organisms (herbicide vs insecticide). The results of this study demonstrate that the combination of these plant, soil, and aquatic specie can serve as representative indicators of pesticide pollution in environmental samples. [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]

Background. Scab plays the leading role in terms of significance and harmfulness among apple-spotted spots. The use of fungicides with a highly specific mechanism of action against the pathogen can lead to the development of resistance in the pathogen. Purpose. To assess the sensitivity of monospore isolates of Venturia inaequalis from a population with different histories of interaction with fungicides to the active substances of the SDHI chemical class boscalid and fluxapiroxad in vitro. Materials and methods. The in vitro sensitivity of isolates was assessed by mycelial growth at various concentrations of boscalid and fluxapiroxad and expressed as an effective 50% concentration (EC50). Results. Boscalid EC50 values for all populations ranged from 0.04 to

Fusarium species are common plant pathogens that cause serious crop losses worldwide. Fusarium spp. colonize not only the main host plants, crops, but also alternative hosts. The effectiveness of fungicide use in disease management ranges from very successful to possibly promoting the growth of the pathogen. Triazole fungicides are widely used to control these pathogens due to their broad-spectrum activity and systemic nature. This paper reviews the sensitivity of 40 Fusarium strains isolated from weeds, non-gramineous plants, and spring wheat to metconazole, prothioconazole, and tebuconazole. The effect of fungicides was determined by the percentage inhibition of F. graminearum, F. culmorum, F. sporotrichioides, and F. avenaceum fungal mycelial growth. The 50% effective concentration (EC50) values of all isolates on metconazole were lower than 2.9 mg L−1, prothioconazole EC50 ranged from 0.12 to 23.6 mg L−1, and tebuconazole ranged from 0.09 to 15.6 mg L−1. At 0.00025–0.025 mg L−1, the fungicides were ineffective, except for the growth of the F. avenaceum species. It was observed that isolates from weeds were more sensitive to low concentrations of fungicide than isolates from crop plants. In general, information is scarce regarding the comparison of fungicide resistance in Fusarium isolates from weed and crop plants, making this study an additional contribution to the existing knowledge base. [ABSTRACT FROM AUTHOR]

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Biosensors based on an oxygen electrode, a mediator electrode, and a mediator microbial biofuel cell (MFC) using the bacteria Gluconobacter oxydans B-1280 were formed and tested to determine the integral toxicity. G. oxydans bacteria exhibited high sensitivity to the toxic effects of phenol, 2,4-dinitrophenol, salicylic and trichloroacetic acid, and a number of heavy metal ions. The system "G. oxydans bacteria–ferrocene–graphite-paste electrode" was superior in sensitivity to biosensors formed using an oxygen electrode and MFC, in particular regarding heavy metal ions (EC50 of Cr3+, Mn2+, and Cd2+ was 0.8 mg/dm3, 0.3 mg/dm3 and 1.6 mg/dm3, respectively). It was determined that the period of stable functioning of electrochemical systems during measurements was reduced by half (from 30 to 15 days) due to changes in the enzyme system of microbial cells when exposed to toxicants. Samples of the products made from polymeric materials were analyzed using developed biosensor systems and standard biotesting methods based on inhibiting the growth of duckweed Lemna minor, reducing the motility of bull sperm, and quenching the luminescence of the commercial test system "Ecolum". The developed bioelectrocatalytic systems were comparable in sensitivity to commercial biosensors, which made it possible to correlate the results and identify, by all methods, a highly toxic sample containing diphenylmethane-4,4′-diisocyanate according to GC-MS data. [ABSTRACT FROM AUTHOR]

Strawberry red core root rot disease affects the growth and yield of strawberry (Fragaria ananassa Duch), which leads to economic losses in China. The study employed a tissue separation method to isolate and identify the causal agent responsible for strawberry red core root rot. This was achieved by the observation of its morphological characteristics, sequencing analyses, and pathogenicity tests. The sensitivity of five chemical fungicides against the two species of Fusarium was determined using the mycelial growth rate method, and the biological characteristics of the two species were examined. The pathogens were identified as Fusarium solani and Fusarium oxysporum. The optimal conditions for the mycelial growth of F. solani and F. oxysporum were determined to be potato sucrose agar at 25 °C and pH 6, and potato dextrose agar at 30 °C and pH 8, respectively, with a 24:24 light cycle. The most suitable carbon and nitrogen sources for the mycelial growth of F. solani were sucrose and sodium nitrate (NaNO3), while for F. oxysporum, they were glucose and peptone. A fungicide sensitivity test indicated that Prochloraz had a good inhibitory effect on the growth of F. solani and F. oxysporum with EC50 values of 0.088 mg L−1 and 0.162 mg. The growth inhibition effect of Azoxystrobin to F. solani and Carbendazim to F. oxysporum was not obvious. This study provides a theoretical basis for further research on strawberry red core root disease and its prevention.

Phytopythium vexans isolated from potatoes rhizospher in Ngablak, Magelang, Central Java was reported having a potency to cause potato tuber rot in in vitro test. Some fungicides had been intensively applied in this area to control potato late blight even using sublethal dose. This study investigated resistance response of the pathogen against several fungicides which were Mancozeb, Dimethomorph, mixture of Mancozeb and Mefenoxam, and mixture of Oxathiapiprolin and Famoxadone. The experiment was conducted to observe the sensitivity response of pathogen against those fungicide and the experiment repeated with one of the isolates which growth in sublethal concentration to observe the resistance response. Both experiment data was analyzed by Probit Analysis. On sentivity test, data showed that P. vexans were insensitive against Dimethomorph, but it was sensitive against Mancozeb, mixture of Mancozeb and Mefenoxam, as well as mixture of Oxathiapiprolin and Famoxadone. On Mancozeb treatment, mycelia were inhibited 100% at the sugested concentration. However, at the sublethal concentration the mycelial collony grew abnormally. Pathogen isolate from the sublethal concentration were used as material for the resistance response study. The effect of the sublethal application of Mancozeb to P. vexans caused resistance to Mancozeb itself and cross resistance against Dimetomorph and mixture of Oxathiapiprolin and Famoxadone. It was proven by higher value of predicted EC50 and EC95 on the second experiment compared to the predicted EC50 and EC95 from the first one. The resistant P. vexans isolate was able to produce sporangium and chlamydospore.

Scab is one of the most harmful diseases of the world's main fruit crop, the apple tree. Purpose. To evaluate the fungicide influence on the population structure of Venturia inaequalis, by its sensitivity to difenoconazole and morphotypic composition. Materials and methods. The study was conducted on 88 monospore isolates isolated from two populations of V. inaequalis. The baseline population, which was not treated with fungicides, was selected from natural populations of Malus orientalis. A population of commercial apple orchards was treated with difenoconazole. The sensitivity of isolates was evaluated under laboratory conditions by mycelial growth at different fungicide concentrations and expressed as effective 50% concentration (EC50). Morphotypes were distinguished by comparing photo-images of isolates with morphotype images in a database. Results. The populations differed in their sensitivity to difenoconazole at a high level of significance (p≤0.003), with median EC50 values of 0.5 and 2.5 mg a.i./l. The resistance factor of the orchard population had a value of 22. Morphological analysis of the isolates also showed an uneven distribution of morphotypes in the populations. Of the 15 morphotypes isolated, 73 % were unique to a particular population. A medium positive correlation between the traits "morphotype" and "fungicide sensitivity" was found. Conclusion. For the first time, a change in the population structure of Venturia inaequalis under the influence of a fungicide was shown not only for a trait under selection pressure (sensitivity), but also for an evolutionarily neutral trait, morphotypic composition.

The recent COVID-19 pandemic again highlighted the urgent need for broad-spectrum antivirals, both for therapeutic use in acute viral infection and for pandemic preparedness in general. The targeting of host cell factors hijacked by viruses during their replication cycle presents one possible strategy for development of broad-spectrum antivirals. By inhibiting the Raf/MEK/ERK signaling pathway, a central kinase cascade of eukaryotic cells, which is being exploited by numerous viruses of different virus phyla, the small-molecule MEK inhibitor zapnometinib has the potential to address this need. We here performed a side-by-side comparison of the antiviral efficacy of zapnometinib against IAV and SARS-CoV-2 to determine the concentration leading to 50% of its effect on the virus (EC50) and the concentration leading to 50% reduction of ERK phosphorylation (IC50) in a comparable manner, using the same experimental conditions. Our results show that the EC50 value and IC50 value of zapnometinib are indeed lower for IAV compared to SARS-CoV-2 using one representative strain for each. The results suggest that IAV's replication has a stronger dependency on an active Raf/MEK/ERK pathway and, thus, that IAV is more susceptible to treatment with zapnometinib than SARS-CoV-2. With zapnometinib's favorable outcome in a recent phase II clinical trial in hospitalized COVID-19 patients, the present results are even more promising for an upcoming phase II clinical trial in severe influenza virus infection. [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]

The acute aquatic toxicity of anionic surfactants, including fatty acid salts, changes depending on water hardness. Generally, the acute aquatic toxicity of Daphnia magna is caused by the adsorption of surfactants and other substances. Despite the low environmental risk, the effect of water hardness on the acute aquatic toxicity of soap should be discussed to improve the assessment accuracy. Previously, we evaluated the effects of water hardness and the presence of an adsorbent on the acute aquatic toxicity of soap by performing an immobility test using D. magna in accordance with Japanese Industrial Standards (JIS) K 0229. Immobility was low at 50 ppm and a higher water hardness was indicated owing to the loss of interfacial activities caused by the formation of insoluble fatty acid calcium or magnesium complexes (soap scum). In the current study, we evaluate the effects of water hardness on the acute aquatic toxicity of C10, C12, C14, C16, and C18 saturated and C18:1 unsaturated fatty acid sodium salts. The EC50 is measured via an immobility test in accordance with JIS K 0229 using D. magna, and the surface tension is measured as an indicator of surface activity. Results show that the EC50 and surface tension curves change with water hardness in single and mixed solutions. C18:1 indicates the least change and the highest surface activity. Moreover, immobility change is not observed when C18:1 is filtered, whereas the immobility of other solutions decreased significantly. This implies the effect of soap scum on immobility, such as the clogging of gills by soap scum. Based on quantitative analysis, the percentage of C18:1 that transformed soap scum to its initial concentration exceeds 80%. This implies that calcium deficiency under 5 and 25 ppm water hardness affects the immobility of larval D. magna. The effects of soap scum clogging and calcium deficiency on D. magna should be considered before assessing the soap. [ABSTRACT FROM AUTHOR]

Copyright of Forest Research is the property of Forest Research Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Objectives: We have recently reported that Fluvastatin, Atorvastatin, Simvastatin and Rosuvastatin have calcium channel antagonistic activities using rabbits' intestinal preparations. The current study is focused on the effects of Pitavastatin and Lovastatin for possible inhibition of vascular L-Type calcium channels, which may have vasorelaxant effect(s). Combined effects of Pitavastatin and Lovastatin in the presence of Amlodipine were also tested for vasorelaxation. Materials and Methods: Possible relaxing effects of Pitavastatin and Lovastatin on 80 mM Potassium chloride (KCL)-induced contractions and on 1 µM norepinephrine (N.E)-induced contractions were studied in isolated rabbit's aortic strips preparations. Relaxing effects on 80 mM KCL-induced vascular contractions were further verified by constructing Calcium Concentration Response Curves (CCRCs), in the absence and presence of three different concentrations of Pitavastatin and Lovastatin using CCRCs as negative control. Verapamil was used as a standard drug that has L-Type calcium channel binding activity. In other series of experiments, we studied drug interaction(s) among Pitavastatin, Lovastatin, and amlodipine. Results: The results of this study imply that Lovastatin is more potent than Pitavastatin for having comparatively lower EC50 (7.44 × 10−5 ± 0.16 M) in intact and (4.55 × 10−5 ± 0.10 M) in denuded aortae for KCL-induced contractions. Lovastatin amplitudes in intact and denuded aortae for KCL-induced contractions were, respectively, 24% and 35.5%; whereas amplitudes for Pitavastatin in intact and denuded aortae for KCL-induced contractions were 34% and 40%, respectively. A left shift in the EC50 values for the statins was seen when we added amlodipine in EC50 (Log Ca++ M). Right shift for CCRCs state that Pitavastatin and Lovastatin have calcium channel antagonistic effects. Lovastatin in test concentration (6.74 × 10−7 M) produced a right shift in relatively lower EC50 (−2.5 ± 0.10) Log Ca++ M as compared to Pitavastatin, which further confirms that lovastatin is relatively more potent. The right shift in EC50 resembles the right shift of Verapamil. Additive effect of Pitavastatin and Lovastatin was noted in presence of amlodipine (p < 0.05). Conclusions: KCL (80 mM)-induced vascular contractions were relaxed by Pitavastatin and Lovastatin via inhibitory effects on L-Type voltage-gated calcium channels. Lovastatin and Pitavastatin also relaxed Norepinephrine (1 µM)-induced contractions giving an insight for involvement of dual mode of action of Pitavastatin and Lovastatin. [ABSTRACT FROM AUTHOR]

Context: Trimethoprim (TMP) is a common antibacterial medication used in human and veterinary medicine, including in aquaculture. Antibiotic misuse and abuse results in the antibiotic pollution of water and has attracted increasing attention. Antibiotics are frequently detected in water bodies and pose a certain environmental risk to the aquatic system. Aims: Two marine diatoms, i.e. Phaeodactylum tricornutum and Skeletonema costatum , were tested for toxicity to better understand the ecological implications of TMP in the marine system. Methods: The routine static toxicity test method for microalgae was selected to be used. Key results: The 96-h median effective concentration (EC50) values based on average specific growth rate (96-h ErC50) were >1.000 and >5.000 mg L−1 for P. tricornutum and S. costatum respectively. Conclusions: P. tricornutum was more sensitive than S. costatum in its exposure to TMP, with a no observation-effect concentration (NOEC) value of 0.063 mg L−1. On the basis of the risk data, TMP poses a great risk to the aquatic system in certain countries. Implications: The results of this study provide a better understanding of the potential ecological risks of TMP in the marine environment. Few researches were on the toxicity of marine ecosystems of trimethoprim (TMP) in the previous study. In this paper, two species of marine diatoms, Phaeodactylum tricornutum and Skeletonema costatum , were selected to study the toxic effects of TMP. The results will be benefit to give a better understanding of the potential ecological risks of TMP in marine environment. [ABSTRACT FROM AUTHOR]

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.

BackgroundCombined epidural-general anesthesia (GA + EA) has been recommended as a preferred technique for both thoracic and abdominal surgery. The epidural anesthesia on the general anesthetic (GA) requirements has not been well investigated. Therefore, we conducted the present study to explore the predicted effect-site concentration of propofol (Ceprop) required for achieving the loss of consciousness (LOC) in 50% of patients (EC50) with or without epidural anesthesia.MethodsSixty patients scheduled for gastrectomy were randomized into the GA + EA group or GA alone group to receive general anesthesia alone. Ropivacaine 0.375% was used for epidural anesthesia to achieve a sensory level of T4 or above prior to the induction of general anesthesia. The EC50 of predicted Ceprop for LOC was determined by the up–down sequential method. The consumption of anesthetics, emergence time from anesthesia, and postoperative outcomes were also recorded and compared.ResultsThe EC50 of predicted Ceprop for LOC was lower in the GA + EA group than in the GA alone group [2.97 (95% CI: 2.63–3.31) vs. 3.36 (95% CI: 3.19–3.53) μg mL−1, (p = 0.036)]. The consumption of anesthetics was lower in the GA + EA group than in the GA alone group (propofol: 0.11 ± 0.02 vs. 0.13 ± 0.02 mg kg−1 min−1, p = 0.014; remifentanil: 0.08 ± 0.03 vs. 0.14 ± 0.04 μg kg−1 min−1, p

The recent COVID-19 pandemic again highlighted the urgent need for broad-spectrum antivirals, both for therapeutic use in acute viral infection and for pandemic preparedness in general. The targeting of host cell factors hijacked by viruses during their replication cycle presents one possible strategy for development of broad-spectrum antivirals. By inhibiting the Raf/MEK/ERK signaling pathway, a central kinase cascade of eukaryotic cells, which is being exploited by numerous viruses of different virus phyla, the small-molecule MEK inhibitor zapnometinib has the potential to address this need. We here performed a side-by-side comparison of the antiviral efficacy of zapnometinib against IAV and SARS-CoV-2 to determine the concentration leading to 50% of its effect on the virus (EC50) and the concentration leading to 50% reduction of ERK phosphorylation (IC50) in a comparable manner, using the same experimental conditions. Our results show that the EC50 value and IC50 value of zapnometinib are indeed lower for IAV compared to SARS-CoV-2 using one representative strain for each. The results suggest that IAV’s replication has a stronger dependency on an active Raf/MEK/ERK pathway and, thus, that IAV is more susceptible to treatment with zapnometinib than SARS-CoV-2. With zapnometinib’s favorable outcome in a recent phase II clinical trial in hospitalized COVID-19 patients, the present results are even more promising for an upcoming phase II clinical trial in severe influenza virus infection.

Background: Aloe vera L. Burman (AV) is a semi-tropical plant with many medicinal applications including wound healing, antioxidant, anti-inflammatory, and anticancer properties. It is used in Chinese medicine to treat diabetes, hypertension, infection, and dermatitis. The flowers of Aloe vera contain volatile compounds and ascorbic acid, the leaves are a good source of organic acids, phenols, enzymes, and minerals while the rind contains pectin, lignin, and polysaccharides. This study evaluated the total phenol, flavonoid, and tannin contents of aqueous and methanol extracts of Aloe vera as well as the reducing power and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities. Methods: The aqueous and methanol extracts of Aloe vera were extracted using the maceration technique. The total phenol, tannin, and total flavonoid contents of both were estimated using standard methods. The In-vitro antioxidant activities (reducing power activity and DPPH free radical scavenging activity) were also evaluated using standard methods. The EC50 and IC50 were evaluated using Non-Linear Regression. Results: Both aqueous and methanol extracts of AV revealed the presence of phenols, tannins, and flavonoids. The methanol extract produced a better-reducing power activity (EC50 = 249316 µg/ml) compared to the aqueous extract (EC50 = 463045 µg/ml) while the aqueous extract produced a better DPPH free radical scavenging activity (IC50 = 54.0 µg/ml) compared to the methanol extract (IC50 = 103.4 µg/ml). Conclusion: The reducing power and DPPH free radical scavenging activities of the two extracts are attributed to the presence of phenols, tannins, and flavonoids. It also suggests that the presence of different compounds in plants is ascribed to the solvent polarity.

Sodium silicate (Na2SiO3) and ethylenediaminetetraacetic acid disodium salt (EDTA-Na2) are inorganic salts classified as 'Generally Recognized as Safe' (GRAS) compounds with great advantages in controlling various pathogens of postharvest fruits and vegetables. Here, we determined the median effective concentration (EC50) of Na2SiO3 (0.06%, 0.05%, 0.07% and 0.08%) and EDTA-Na2 (0.11%, 0.08%, 0.5%, and 0.07%) against common pathogens affecting postharvest citrus fruit, including Penicillium digitatum, Penicillium italicum, Geotrichum citri-aurantii, and Colletotrichum gloeosporioides. Na2SiO3 and EDTA-Na2 treatments at the EC50 decreased the spore germination rate, visibly disrupted the spore cell membrane integrity, and significantly increased the lipid droplets (LDs) of the four postharvest pathogens. Moreover, both treatments at EC50 significantly reduced the disease incidence of P. italicum (by 60% and 93.335, respectively) and G. citri-aurantii (by 50% and 76.67%, respectively) relative to the control. Furthermore, Na2SiO3 and EDTA-Na2 treatment resulted in dramatically lower disease severity of the four pathogens, while also demonstrating no significant change in citrus fruit quality compared with the control. Therefore, Na2SiO3 and EDTA-Na2 present a promising approach to control the postharvest diseases of citrus fruit. [ABSTRACT FROM AUTHOR]

Metal presence in the aquatic ecosystem has increased and diversified over the last decades due to anthropogenic sources. These contaminants cause abiotic stress on living organisms that lead to the production of oxidizing molecules. Phenolic compounds are part of the defense mechanisms countering metal toxicity. In this study, the production of phenolic compounds by Euglena gracilis under three different metal stressors (i.e. cadmium, copper, or cobalt) at sublethal concentration was assessed using an untargeted metabolomic approach by mass spectrometry combined with neuronal network analysis (i.e. Cytoscape). The metal stress had a greater impact on molecular diversity than on the number of phenolic compounds. The prevalence of sulfur- and nitrogen-rich phenolic compounds were found in Cd- and Cu-amended cultures. Together these results confirm the impact of metallic stress on phenolic compounds production, which could be utilized to assess the metal contamination in natural waters. [ABSTRACT FROM AUTHOR]

Toxic substances used as chemical weapons present a number of particularities that affect the surrounding environment, having a wide range of action by disrupting the ecological balance: they may infect soil or air, or form aerosols through smoke or toxic fog. Such substances can have a long duration of action, from minutes to weeks, which is why they are used in military attacks. This study evaluated the toxicological character of o-chlorobenzyliden malonitrile (CBM) in order to study the toxicity limit of this substance using microbiological cultures of Saccharomyces sp., Chlorella sp., Lactobacillus sp. and Paramecium sp., which were used to determine their rate of growth in the presence of different concentrations of o-chlorobenzyliden malonitrile and their ability to respond to this toxic stimulus. [ABSTRACT FROM AUTHOR]

Biosensors based on an oxygen electrode, a mediator electrode, and a mediator microbial biofuel cell (MFC) using the bacteria Gluconobacter oxydans B-1280 were formed and tested to determine the integral toxicity. G. oxydans bacteria exhibited high sensitivity to the toxic effects of phenol, 2,4-dinitrophenol, salicylic and trichloroacetic acid, and a number of heavy metal ions. The system “G. oxydans bacteria–ferrocene–graphite-paste electrode” was superior in sensitivity to biosensors formed using an oxygen electrode and MFC, in particular regarding heavy metal ions (EC50 of Cr3+, Mn2+, and Cd2+ was 0.8 mg/dm3, 0.3 mg/dm3 and 1.6 mg/dm3, respectively). It was determined that the period of stable functioning of electrochemical systems during measurements was reduced by half (from 30 to 15 days) due to changes in the enzyme system of microbial cells when exposed to toxicants. Samples of the products made from polymeric materials were analyzed using developed biosensor systems and standard biotesting methods based on inhibiting the growth of duckweed Lemna minor, reducing the motility of bull sperm, and quenching the luminescence of the commercial test system “Ecolum”. The developed bioelectrocatalytic systems were comparable in sensitivity to commercial biosensors, which made it possible to correlate the results and identify, by all methods, a highly toxic sample containing diphenylmethane-4,4′-diisocyanate according to GC-MS data.

Yan-Lei Tai,1 Li Peng,1 Ying Wang,2 Zi-Jun Zhao,3 Ya-Nan Li,1 Chun-Ping Yin,1 Zhi-Yong Hou,4 De-Cheng Shao,5 Ya-Hui Zhang,1 Qiu-Jun Wang1 1Department of Anesthesiology, Third Hospital Affiliated to Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Anesthesiology, Tangshan Gongren Hospital, Tangshan, Hebei, People’s Republic of China; 3Department of Anesthesiology, Hebei Chest Hospital, Shijiazhuang, Hebei, People’s Republic of China; 4Center of Emergency and Trauma, Third Hospital Affiliated to Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 5Department of Sport Medicine, Third Hospital Affiliated to Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Qiu-Jun Wang, Department of Anesthesiology, Third Hospital Affiliated to Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China, Tel +8618533112929, Email wangqiujunsy@163.comBackground: Femoral nerve block combined with general anesthesia is commonly used for patients undergoing knee arthroscopy in ambulatory care centers. An ideal analgesic agent would selectively (differentially) block sensory fibers, with little or no effect on motor nerves. Ropivacaine is considered to cause less motor block than others. This study investigated the median effective concentration (EC50) of ropivacaine for differential femoral nerve block in adults either younger or older than 60 years.Methods: Patients with American Society of Anesthesiologists physical status I–III and scheduled for knee arthroscopy were categorized as 18- to 60-years-old (Group 1), or older than 60 years (Group 2). Surgeries were performed under general anesthesia combined with femoral nerve block via 22 mL ropivacaine. The EC50 of ropivacaine for differential femoral nerve block was determined using the up-and-down method and probit regression. The primary outcome was the EC50 (95% confidence interval [CI]) of the 2 groups. Data on the sensory block, analgesic effect, complications, and hemodynamics during surgery were also recorded.Results: The EC50 of 22 mL ropivacaine for differential femoral nerve block of Group 1 (0.124%, 95% CI 0.097– 0.143%) was significantly higher than that of Group 2 (0.088%, 95% CI 0.076– 0.103%). The sensory block and hemodynamic data of the 2 groups were comparable. None of the patients experienced neurological complications.Conclusion: The EC50 of ropivacaine administered for differential femoral nerve block during knee arthroscopy was lower in patients older than 60 years, relative to younger adults.Keywords: femoral nerve block, ropivacaine, motor block, age groups, EC50

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]

The sugar beet crop is essential for the production of refined sugar in Morocco. It is cultivated in four large areas (Gharb, Tadla, Doukalla, and Moulouya). A reported reduction in efficacy for fungicide treatments led to an in vitro sensitivity study of isolates collected in 2017 and 2018 from sugar beet areas. After authentication of the pathogen by specific primers amplifying 959 pb of the actin gene of Cercospora beticola Sacc, the inhibition tests on a modified medium by different fungicide molecules belonging to three groups (benzimidazole, demethylation inhibitors, and quinone outside inhibitors) were carried out. Measurement of inhibition allowed the calculation of EC50, which showed that resistance is present in isolates collected for the three fungicide groups with different levels by group and year. All isolates were resistant to thiophanate methyl (EC50 > 5 ppm) in 2017 and 2018. At least 70% of the isolates (in 2018) were resistant to azoxystrobin (EC50 > 10 ppm) and at least 68% of the isolates (in 2018) were resistant to difenoconazole (EC50 > 0.01 ppm). In parallel, in vivo tests on three sites in the Gharb area were conducted during 2017 and 2018 to monitor the severity of Cercospora beticola on the host under different fungicide treatments (thiophanate methyl, chlorothalonil, tetraconazole, epoxiconazole, difenoconazole, penthiopyrad, azoxystrobin, trifloxystrobin, and Pythium oligandrum) by measuring the area under the disease progress curve. The fungicide molecules all had better efficacy in preventive treatment, with the best results for trifloxystrobin, difenoconazole, and epoxiconazole. In curative treatment, three molecules stood out: trifloxystrobin, difenoconazole, and penthiopyrad. [ABSTRACT FROM AUTHOR]

Avocado is a healthy fruit and the consumption is continuously growing worldwide. The fruit contains polyphenolic compounds with antioxidant effects. Globally, research has been devoted to exploring the fruit quality, especially compounds with antioxidant effects, from different avocado-growing sites. However, the fruit quality of the Tanzanian avocado has so far not been investigated. In this study, the contents of polyphenols in peel, pulp and seed of avocados sampled in south-western Tanzania are described. The levels of total polyphenolic and flavonoid contents were measured, and antioxidant activity was evaluated using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The total polyphenolic content was highest in the seed and lowest in the peel (424 and 200 mg GAE/100 g DW, respectively). As for the total flavonoid content, the pulp had the highest value of 36.98 mg RE/100 g DW, while the seed had the lowest value of 32.54 mg RE/100 g DW. The overall average half maximal effective concentration (EC50) values in decreasing order, corresponding to an increasing antiradical activity, were 4.90 (peel), 3.63 (seed) and 3.24 µg/mL (pulp). The seed and peel possessed high levels of total polyphenolic and flavonoid content, thus demonstrating substantial antioxidant capacity. Seed and peel can potentially be processed and included in the diet to provide inexpensive antioxidant ingredients of natural origin. Consumption of the seed will not only improve human health but also reduce the environmental pollution, as many thousand tonnes of avocado seeds are produced in Tanzania per year; a huge amount currently remains as waste. [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]