Predicting oxidative stress induced by organic chemicals by using quantitative Structure-Activity relationship methods.

Cellular exposure to xenobiotic human-made products will lead to oxidative stress that gives rise to DNA damage, as well as chemical or mechanical damage. Distinguishing the chemicals that will induce oxidative stress and predicting their toxicity is necessary. In the present study, 4270 compounds in the ARE-bla assay were investigated to predict active and inactive compounds by using simple algorithms, namely, recursive partitioning (RP) and binomial logistic regression, and to develop the quantitative structure-activity relationship (QSAR) models of chemicals that activate the ARE pathway to induce oxidative stress and exert toxic effects on cells. A decision tree based on scaffold-based fragments obtained through RP analysis showed the best identification accuracy. However, the overall identification accuracy of this model for active compounds was unsatisfactory due to limited fragments. Furthermore, a binomial logistic regression model was developed from 638 active compounds and 3632 inactive chemicals. The model with a cutoff of 0.15 could predict chemicals that were active or inactive with the prediction accuracy of 69.1%. Its area under the receiver operating characteristic (ROC) curve metric (AUROC) was 0.762, which indicated the acceptable predictive ability of this model. The parameters nBM (number of multiple bonds) and H% (percentage of H atom) played dominant roles in the prediction of the activity (inactive or active) of chemicals. A global QSAR model was developed to predict the toxicity of active chemicals. However, the model displayed an unsatisfactory result with R2 = 0.316 and R2ext = 0.090. Active chemicals were then classified on the basis of structure. A total of 79 compounds with carbon chains could be predicted with acceptable performance by using a QSAR model with six descriptors (R2 = 0.722, R2ext = 0.798, Q2Loo = 0.654, Q2Boot = 0.755, Q2ext = 0.721). The simple models established here contribute to efforts on identification compounds inducing oxidative stress and provide the scientific basis for risk assessment to organisms in the environment.

Novel application of a Z-scheme photocatalyst of Ag3PO4@g-C3N4 for photocatalytic fuel cells.

A composite of Ag3PO4@g-C3N4 with the Z-scheme structure was synthesized, and used as the photoanode in a photocatalytic fuel cell (PFC). With the help of the Z-scheme design, both the degradation of tetracycline and the output of maximum power density (Pmax) were greatly enhanced in this PFC system. The degradation rate of tetracycline in the Ag3PO4@g-C3N4 PFC was 2.53 times and 3.65 times that in the PFC systems with the Ag3PO4 photoanode and the g-C3N4 photoanode, respectively. The Pmax of the Ag3PO4@g-C3N4 PFC was 6.06 µW cm-2, which was 1.46 times and 90.4 times that of the Ag3PO4 PFC (4.16 µW cm-2) and the g-C3N4 PFC (0.067 µW cm-2), respectively. The possible mechanism was proposed. The Z-scheme photoanode could not only contribute to the separation of photogenerated carriers to achieve a high photocatalytic activity, but also reserve a good redox capacity. Additionally, aeration played an important role on the PFC performance. It was demonstrated that N2 purging facilitated the electricity generation, while O2 purging promoted the pollutant degradation.

Aqueous OH Radical Reaction Rate Constants for Organophosphorus Flame Retardants and Plasticizers: Experimental and Modeling Studies.

Aqueous ·OH reaction rate constants ( kOH) for organophosphate esters (OPEs) are essential for assessing their environmental fate and removal potential in advanced oxidation processes (AOPs). Herein experimental and in silico approaches were adopted to obtain kOH values for a variety of OPEs. The determined kOH for 18 OPEs varies from 4.0 × 108 M-1 s-1 to 1.6 × 1010 M-1 s-1. Based on the experimental kOH values, a quantitative structure-activity relationship model that involves molecular structural information on the number of heavy atoms, content index, and the most negative charge of C atoms was developed for predicting kOH of other OPEs. Furthermore, appropriate density functional theory (DFT) and solvation models were selected, which together with transition state theory were employed to predict kOH of three representative OPEs. The deviation between the DFT calculated and the experimental kOH values ( kcal/ kexp) is within 2. Half-lives of the OPEs were estimated to be 0.5-22791.3 days in natural waters and 0.044-19.7 s in AOPs, indicating the OPEs are potentially persistent in natural waters and can be quickly eliminated by AOPs. The determined kOH values and the in silico methods offer a scientific base for assessing OPEs fate in aquatic environments.

[Study on the polarized reflectance hyperspectral characteristics and models of typical saline soil in the west of Jilin Province, China].

In recent years, the area of saline soil in the west of Jilin Province expands increasingly, and soil quality is becoming more and more worsening, which not only caused great damage to the land resources, but also posed a huge threat to agricultural production and ecological environment. We combined with polarized and hyperspectral information to establish the general model and scientifically validated it. The results show that there is a strong relationship between the saline soil hyperspectral polarized information and its physicochemical property parameters, and with regularity. This paper has important theoretical significance for the mechanism of saline soil surface reflection, recognition and classification of saline soil and background, the utilization of soil polarization sensor and the development of quantitative remote sensing.

A case report to increase awareness of the accuracy of different methods for the identification of Listeriamonocytogenes.

Listeria monocytogenes, is a Gram-positive facultative intracellular bacterium without spores. It can cause invasive diseases such as septicemia, meningitis, and encephalitis, and has a high mortality rate. This is a report on a recent case of neurolisteriosis isolated from cerebrospinal fluid sample of a patient with diabetes and chronic heart failure in our hospital. The patient initially received the combined treatment of cephalosporin and meropenem (both 1.0 g every 8 hours). We identified the pathogenic organism as L. monocytogenes using three identification methods: mass spectrometry, biochemical assays, and molecular techniques. After determining the pathogenic bacteria, we quickly informed the clinician and suggesting a change in antibiotic treatment and immediately discontinued cephalosporin and meropenem. The patient's symptoms were significantly improved after 9 days of penicillin G treatment, and the patient chose to be discharged for personal reasons. In conclusion, certain strains of wild-type Listeria monocytogenes can lead to identification errors that occur across platforms and methods.

Photochemical behavior and photo-induced toxicity of chiral pesticides and their chiral monomers in aqueous environment.

The photochemical behaviors of chiral pollutants in aqueous solutions are rarely studied using chiral monomers, which may hamper their precise risk assessment and lead to suspicious conclusions. In this study, we systematically investigated the phototransformation behavior and toxicity evolution of two widely used chiral pesticides (triadimefon (TF) and triadimenol (TN)) at enantiomer and diastereomer levels, and proposed a calculation method of total photolysis rate constants of chiral mixture. Results show that TF and TN could be photodegraded faster in pure water than in natural waters, and the observed photolysis rate constants (kobs) of TN with two chiral centers exhibit enantioselectivity, i.e., kobs(TN-RS) = kobs(TN-SR) > kobs(TN-RR) = kobs(TN-SS). The photolysis of TF and TN mainly occurs through their excited singlet and triplet states, respectively. Their photodegradation pathways mainly include dechlorination and elimination of triazole ring. TF could also undergo ether bond cleavage. It is also found that, both TF and TN exhibit photo-induced toxicity to V. fischeri, due to the generation of more toxic products than parent compounds. Furthermore, TN exhibits enantioselective photo-induced toxicity after 240-min irradiation, which could be ascribed to the formation of chiral products. These results could benefit the understanding of enantioselective environmental behavior of chiral pollutants.

A case report of sepsis and death caused by Parvimonas micra, a rare anaerobe.

Parvimonas micra is a type of Gram-positive anaerobic cocci widely distributed in the oral cavity, gastrointestinal tract, respiratory tract, and female reproductive system mucosa. It is a conditional pathogen that can cause infections in the human oral cavity, wounds, and other areas as well as sepsis. In this case report, the patient's immune system was compromised by various underlying diseases and a pulmonary infection, which led to the entry of P. micra infection into the bloodstream. P. micra is a slow-growing organism (When a bloodstream infection occurs, flagging an anaerobic bottle of blood culture as positive will usually take >48 h), which makes it hard to secure timely blood culture results. Our patient's poor physical condition eventually led to sepsis, and she died after 5 days in the hospital.

Tuberculosis with cavities? Rapid diagnosis of Rhodococcus equi pulmonary infection with cavities by acid-fast staining: A case report.

Rhodococcus equi is a conditionally pathogenic bacterium widely distributed in soil, water, and marine environments, which can cause respiratory infections, pleurisy, blood and even bone marrow infections in immunocompromised people, and particularly in patients with acquired immunodeficiency syndrome (AIDS). This case report describes a patient with initially suspicion of tuberculosis (TB) as an outpatient in a TB clinic. However, laboratory findings identified R. equi in his sputum sample based on a positive acid-fast stain, which was highly suggestive of a pulmonary infection caused by R. equi. The patient was subsequently admitted to the respiratory unit for treatment. Once the source of infection was identified, the patient was treated with a combination of antibiotics for 2 weeks and was discharged with a significant improvement in symptoms.

Programmable molecular circuit discriminates multidrug-resistant bacteria.

Recognizing multidrug-resistant (MDR) bacteria with high accuracy and precision from clinical samples has long been a difficulty. For reliable detection of MDR bacteria, we investigated a programmable molecular circuit called the Background-free isothermal circuital kit (BRICK). The BRICK method provides a near-zero background signal by integrating four inherent modules equivalent to the conversion, amplification, separation, and reading modules. Interference elimination is largely owing to a molybdenum disulfide nanosheets-based fluorescence nanoswitch and non-specific suppression mediated by molecular inhibitors. In less than 70 â€‹min, an accurate distinction of various MDR bacteria was achieved without bacterial lysis. The BRICK technique detected 6.73 â€‹CFU/mL of methicillin-resistant Staphylococcus aureus in clinical samples in a proof-of-concept trial. By simply reprogramming the sequence panel, such a high signal-to-noise characteristic has been proven in the four other superbugs. The proposed BRICK method can provide a universal platform for infection surveillance and environmental management thanks to its superior programmability.

Discrimination of active and inactive substances in cytotoxicity based on Tox21 10K compound library: Structure alert and mode of action.

In vitro cytotoxicity assay is an ideal alternative method for the in vivo toxicity in the risk assessment of pollutants in environment. However, modes of action (MOAs) of cytotoxicity have not been investigated for a wide range of compounds. In this paper, binomial and recursive partitioning analysis were carried out between the cytotoxicity and molecular descriptors for 8981 compounds. The results showed that cytotoxicity is strongly related to the chemical hydrophobicity and excess molar refraction, indicating the bio-uptake and chemical-receptor interaction through π and n electron pair play important roles in the cytotoxicity. The decision tree derived from recursive partitioning analysis revealed that the studied compounds could be divided into 25 groups and their structural characteristics could be used as structure alert to identify active and inactive compounds in cytotoxicity. The descriptors used in the decision tree revealed that chemical ionization and bioavailability could affect the cytotoxicity for ionizable and highly hydrophobic compounds. Comparison of MOAs based on Verhaar's classification scheme showed that many inert or less inert compounds were inactive substance, and many reactive or specifically-acting compounds were active substances in the cytotoxicity. In vitro toxicity assay instead of in vivo toxicity assay can be used in the environmental hazard and risk assessment of organic pollutants. The descriptors used in the binomial equation and decision tree reveal that chemical hydrophobicity, ionization and solubility play very important roles for identification of active and inactive compounds. The results obtained in this paper are valuable for understanding the modes of action in cytotoxicity and in vivo-in vitro toxicity relationship.

MOA-based linear and nonlinear QSAR models for predicting the toxicity of organic chemicals to Vibrio fischeri.

Risk assessment of pollutants to humans and ecosystems requires much toxicological data. However, experimental testing of compounds expends a large number of animals and is criticized for ethical reasons. The in silico method is playing an important role in filling the data gap. In this paper, the acute toxicity data of 1221 chemicals to Vibrio fischeri were collected. The global models obtained showed that there was a poor relationship between the toxicity data and the descriptors calculated based on linear and nonlinear regression analysis. This is due to the fact that the studied compounds contain not only non-reactive compounds but also reactive and specifically acting compounds with different modes of action (MOAs). MOAs are fundamental for the development of mechanistically based QSAR models and toxicity prediction. To investigate MOAs and develop MOA-based prediction models, the compounds were classified into baseline, less inert, reactive, and specifically acting compounds based on the modified Verhaar's classification scheme. Satisfactory models were established by multivariate linear regression (MLR) and support vector machine (SVM) analysis not only for baseline and less inert chemicals, but also for reactive and specifically acting compounds. Compared with linear models obtained by the MLR method, the nonlinear models obtained by the SVM method had better performance. The cross validation proved that all of the models were robust except for those for reactive chemicals with nN (number of nitrogen atoms) = 0 and n(C=O) (number of carbonyl groups) > 0 (Q2ext < 0.5). The application domains and outliers are discussed for those MOA-based models. The models developed in this paper are significantly helpful not only because the application domains for baseline and less inert compounds have been expended, but also the toxicity of reactive and specifically acting compounds can be successfully predicted. This work will promote understanding of toxic mechanisms and toxicity prediction for the chemicals with structural diversity, especially for reactive and specifically acting compounds.

Combined Toxicity of Nitro-Substituted Benzenes and Zinc to Photobacterium Phosphoreum: Evaluation and QSAR Analysis.

The single toxicity (IC50) of zinc (Zn) and 11 nitro-substituted benzenes to Photobacterium phosphoreum were determined, respectively. On basis of single toxicity, the joint toxicity of binary mixtures of Zn and 11 nitro-substituted benzenes at different Zn concentrations of 0.2 IC50, 0.5 IC50, and 0.8 IC50 were measured. The joint toxicity was evaluated by toxic unit (TU) and additive index (AI) methods. The results indicated that the joint toxicity was not only depending on the Zn concentrations but also on the substituted groups of nitro-substituted benzenes. The quantitative structure-activity relation (QSAR) equations were developed and the results showed that the toxicity of nitro-substituted benzenes has different joint effect at the different Zn concentrations. At the Zn concentration of 0.2 IC50, the binary joint effects were mainly antagonism and the joint toxicity was negatively related to descriptors called VE2_B(p) and TIC3. At the Zn concentration of 0.5 IC50 and 0.8 IC50, the binary joint effects were mainly antagonism and simple addition, and the joint toxicity was related to the same descriptor Eig06_ AEA(dm). It indicated that the joint toxic actions were similar when combined at the medium and high concentrations of Zn.

Trace amounts of fenofibrate acid sensitize the photodegradation of bezafibrate in effluents: Mechanisms, degradation pathways, and toxicity evaluation.

Effluent organic matter (EfOM), which is composed of background natural organic matter (NOM), soluble microbial degradation products, and trace amounts of organic pollutants, can play an important role in the photodegradation of emerging pollutants in the effluent. In this study, the impact of organic pollutants, using fenofibrate acid (FNFA) as a representative, on the photodegradation of emerging contaminants, using bezafibrate (BZF) as a representative, in effluents was investigated. It is found that BZF undergo fast degradation in the presence of FNFA although BZF is recalcitrant to degradation under simulated sunlight irradiation. The promotional effect of FNFA is due to the generation of singlet oxygen (1O2) and hydrated electrons (e-aq). Based on the structures of the identified intermediates, 1O2 initiated oxidation and e-aq initiated reduction reactions were the main photodegradation pathways of BZF in the effluents. The toxicity of the main photodegradation intermediates for BZF and FNFA was higher than that of the parent compounds, and the acute toxicity increased during simulated sunlight irradiation. The results demonstrated that trace amounts of organic compounds in EfOM can play an important role in sensitizing the photodegradation of some emerging pollutants in the effluent.

Combined effects of dissolved organic matter, pH, ionic strength and halides on photodegradation of oxytetracycline in simulated estuarine waters.

Estuarine waters of variable compositions are sinks for many micropollutants. The varying water properties can impact the photodegradation of organic pollutants. In this study, the combined effects of dissolved organic matter (DOM), pH, ionic strength, and halides on the photodegradation of the model organic pollutant oxytetracycline (OTC) were investigated. Suwannee River natural organic matter (SRNOM) was used as a representative DOM. The results showed that the observed photolysis rate constant (kobs) of OTC increased rapidly upon increase of pH. SRNOM induced a 11.0-17.9% decrease of the kobs for OTC. In the presence of SRNOM, the ionic strength and specific halide effects promote OTC photodegradation with a 39.2-84.2% and 7.1-28.8% increase of the kobs, respectively. The effects of SRNOM, ionic strength and halides on OTC photodegradation are pH-dependent. Direct photolysis half-lives (t1/2) of OTC were estimated in view of the more important role of direct photolysis compared to indirect photolysis. The estimated t1/2 values decreased from 187.4-206.6 d to 34.4-36.6 d as the pH increases in the Yellow River estuarine region. The results of this research demonstrate that the photodegradation rate of OTC increases rapidly in the gradient from river water to marine water in estuarine regions.

Diaqua-bis(9-oxo-4,5-diaza-fluoren-3-olato-κN,O)cadmium(II).

The title compound, [Cd(C(11)H(5)N(2)O(2))(2)(H(2)O)(2)], is a mononuclear complex consisting of a Cd(II) atom, two 3-hydr-oxy-4,5-diaza-fluoren-9-one ligands and two coordinated water mol-ecules. The Cd(II) atom, lying on a twofold axis, displays a distorted octa-hedral coordintion. Adjacent mol-ecules are linked by O-H⋯O hydrogen bonds and π-π inter-actions [centroid-centroid distance = 3.84 (1) Å], leading to a one-dimensional chain. Weak C-H⋯O hydrogen bonds connect the chains into a two-dimensional supra-molecular structure.

Linear and nonlinear relationships between biodegradation potential and molecular descriptors/fragments for organic pollutants and a theoretical interpretation.

Prediction of the biodegradability of organic pollutants is an ecologically desirable and economically feasible tool for estimating the environmental fate of chemicals. In this paper, linear and nonlinear relationships between biological oxygen demand (BOD) and molecular descriptors/fragments have been investigated for 1130 organic chemicals. Significant relationships have been observed between the simple molecular descriptors and %BOD for some homologous compounds, but not for the whole set of compounds. Electronic parameters, such as E(HOMO) and E(LUMO), are the dominant factors affecting the biodegradability for some homologous chemicals. However, other descriptors, such as molecular weight, acid dissociation constant and polarity still have a significant impact on the biodegradation. The best global model for %BOD prediction is that developed from a chain-based fragmentation scheme. At the same time, the theoretical relationship between %BOD and molecular descriptors/fragments has been investigated, based on a first-order kinetic process. The %BOD is nonlinearly, rather than linearly, related to the descriptors. The coefficients of determination can be significantly improved by using nonlinear models for the homologous compounds and the whole data set. After analysing 1130 ready and not ready biodegradable compounds using 23 simple descriptors and various fragmentation schemes, it was revealed that biodegradation could be well predicted from a chain-based fragmentation scheme, a decision tree and a %BOD model. The models were capable of separating NRB and RB with an overall accuracy of 87.2%, 83.0% and 82.5%, respectively. The best classification model developed was a chain-based model but it used 155 fragments. The simplest model was a decision tree which only used 10 structural fragments. The effect of structures on the biodegradation has been analysed and the biodegradation pathway and mechanisms have been discussed based on activating and inactivating fragments.

Discrimination of excess toxicity from narcotic effect: comparison of toxicity of class-based organic chemicals to Daphnia magna and Tetrahymena pyriformis.

The discrimination of excess toxicity from narcotic effect plays a crucial role in the study of modes of toxic action for organic compounds. In this paper, the toxicity data of 758 chemicals to Daphnia magna and 993 chemicals to Tetrahymena pyriformis were used to investigate the excess toxicity. The result showed that mode of toxic action of chemicals is species dependent. The toxic ratio (TR) calculated from baseline model over the experimentally determined values showed that some classes (e.g. alkanes, alcohols, ethers, aldehydes, esters and benzenes) shared same modes of toxic action to both D. magna and T. pyriformis. However, some classes may share different modes of toxic action to T. pyriformis and D. magna (e.g. anilines and their derivatives). For the interspecies comparison, same reference threshold need to be used between species toxicity. The excess toxicity indicates that toxicity enhancement is driven by reactive or specific toxicity. However, not all the reactive compounds exhibit excess toxicity. In theory, the TR threshold should not be related with the experimental uncertainty. The experimental uncertainty only brings the difficulty for discriminating the toxic category of chemicals. The real threshold of excess toxicity which is used to identify baseline from reactive chemicals should be based on the critical concentration difference inside body, rather than critical concentration outside body (i.e. EC50 or IGC50). The experimental bioconcentration factors can be greatly different from predicted bioconcentration factors, resulting in different toxic ratios and leading to mis-classification of toxic category and outliers.

Evaluation of joint toxicity of nitroaromatic compounds and copper to Photobacterium phosphoreum and QSAR analysis.

The individual toxicities of Cu and 11 nitroaromatic compounds to Photobacterium phosphoreum were determined. The toxicity was expressed as the concentrations causing a 50% inhibition of bioluminescence after 15 min exposure (IC(50)). To evaluate the joint effect between the metal ion and the 11 nitroaromatic compounds, the joint toxicity of Cu and 11 nitroaromatic compounds were measured at different Cu concentrations (0.2IC(50), 0.5IC(50) and 0.8IC(50)), respectively. The result shows that the binary joint effect between Cu and nitroaromatic compounds is mainly simple addition at the low Cu concentration (0.2IC(50)). However, an antagonism effect, 55% and 64%, was observed between Cu and 11 nitroaromatic compounds for Cu at medium and high concentrations (0.5IC(50) and 0.8IC(50)). Quantitative structure-activity relationship (QSAR) analysis was performed to study the joint toxicity for the 11 nitroaromatic compounds. The result shows that the toxicity of nitroaromatic compounds is related to descriptors of Connolly solvent-excluded volume (CSEV) and dipolarity/polarizability (S) at low Cu concentration. On the other hand, the toxicity is related to Connolly accessible area (CAA) at medium and high Cu concentrations. The result indicates that different QSAR models on complex mixtures need to be developed to assess the ecological risk in real environments. Using single toxic data to evaluate the toxic effect of mixtures may result in wrong conclusions.

A common polymorphism in CD40 Kozak sequence (-1C/T) is associated with acute coronary syndrome.

OBJECTIVE: Evidence suggests the CD40-CD40L pathway as a key process in the development, progression, and outcome of acute coronary syndrome (ACS). We hypothesized that the -1C/T polymorphism of the CD40 gene would be associated with ACS and influence the CD40 expression. METHODS: The genotype distribution and allele frequency of CD40-1C/T polymorphism in 248 ACS patients and 206 controls were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Monocytes from 90 healthy volunteers were incubated with IFN-gamma. CD40 expression was detected by flow cytometry. RESULT: Patients with ACS showed a significant increase of CD40 expression compared with controls (P<0.001). The frequency of the CC genotype in the ACS group was significantly higher than that of the controls (P<0.001). Frequency of the C allele was higher among ACS patients compared with controls (P<0.001). Case control association analysis of the CD40 -1C/T SNP showed an association between the C allele and ACS (OR=1.991, 95%CI: 1.526 approximately 2.596, P<0.001). -1C/C carriers presented significantly higher CD40 expression levels than -1C/T and -1T/T subjects, both in ACS group and controls (P<0.001). When stimulated by IFN-gamma, CD40 expression levels on monocytes in individuals with CC, CT and TT genotypes were increased by 9.16, 3.83 and 1.53 fold, respectively, compared with the levels absent with IFN-gamma. CONCLUSIONS: These results suggest that the -1C allele of the CD40 (-1C/T) gene polymorphism is a genetic factor that may determine an individual's susceptibility by ACS in Chinese. The CD40 -1C/T polymorphism is a novel regulator of CD40 expression.