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Biomedical subjects

Liansheng Wang

Publications and source records attributed to Liansheng Wang.

At least 19 recordsLinked to original sources

Causal conclusions are most sensitive to unobserved binary covariates.

There is a rich literature that considers whether an observed relation between treatment and response is due to an unobserved covariate. In order to quantify this unmeasured bias, an assumption is made about the distribution of this unobserved covariate; typically that it is either binary or at least confined to the unit interval. In this paper, this assumption is relaxed in the context of matched pairs with binary treatment and response. One might think that a long-tailed unobserved covariate could do more damage. Remarkably that is not the case: the most harm is done by a binary covariate, so the case commonly considered in the literature is most conservative. This has two practical consequences: (i) it is always safe to assume that an unobserved covariate is binary, if one is content to make a conservative statement; (ii) when another assumption seems more appropriate, say normal covariate, there will be less sensitivity than with a binary covariate. This assumption implies that it is possible that a relation between treatment and response that is sensitive to unmeasured bias (if the unobserved covariate is dichotomous), ceases to be sensitive if the unobserved covariate is normally distributed. These ideas are illustrated by three examples. It is important to note that the claim in this paper applies to our specific setting of matched pairs with binary treatment and response. Whether the same conclusion holds in other settings is an open question.

Bias↗

Safety evaluation of short-term exposure to chitooligomers from enzymic preparation.

Chitooligomers have significant application to the development of functional foods. This paper evaluated systematically the safety of chitooligomers, which were prepared by enzymatic depolymerization of chitosan. The oral maximum tolerated dose of this chitooligomes was more than 10 g/kg body weight in mice. It had no mutagenicity judged by negative experimental results of Ames test, mouse bone marrow cell micronucleus test and mouse sperm abnormality test. A 30-day feeding study shows that no abnormal symptoms and clinical signs or deaths were found in rats during the test. There were no significant difference in body weight, food consumption and food availability of rats in each test group. No significant differences were found in each hematology value, clinical chemistry value and organ/body weight ratio, either. No abnormality of any organ was found during histopathological examination. It is concluded that short-term ingestion of chitooligomers is of non-toxicity.

Animals↗

Associations of plasma 8-isoprostane levels with the presence and extent of coronary stenosis in patients with coronary artery disease.

Oxidative stress may play a role in the development of atherosclerosis. The purpose of the present study was to explore the relationship between 8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)) levels and the presence of coronary artery disease (CAD) and to also clarify whether 8-iso-PGF(2alpha) might add independently to measures of CAD extent. The study group consisted of 241 consecutive patients who were undergoing coronary angiography for suspected CAD. 8-iso-PGF(2alpha) levels were recorded for all participants. The analysis revealed a significant difference in 8-iso-PGF(2alpha) levels in patients with and without hypertension (P<0.001), in patients with diabetes relative to nondiabetic patients (P<0.05), and in males respect to females (P<0.001). A significant positive correlation was found between age and 8-iso-PGF(2alpha) levels (P<0.001). 8-iso-PGF(2alpha) levels correlated with the number of cardiovascular risk factors (P<0.001). 8-iso-PGF(2alpha) levels were higher in the CAD(+) respect to the CAD(-) groups (337.7+/-80.2 and 263.8+/-74.2 pg/ml and P<0.001). A stepwise elevation in the 8-iso-PGF(2alpha) levels was found depending on the number of affected vessels (P<0.001). The 8-iso-PGF(2alpha) levels showed a significant positive correlation with the numbers of >50 and >25% stenotic segments (P<0.001) and the extent score of coronary stenosis (P<0.001). The multivariate logistic regression analysis indicated 8-iso-PGF(2alpha) as an independent factor associated with CAD (odds ratio, 2.47 and P=0.001). The results suggested that 8-iso-PGF(2alpha) is associated with the presence of CAD in patients undergoing coronary angiography and is also related to the extent of coronary stenosis in Chinese population.

Aged↗

Mechanism of concentration addition toxicity: they are different for nonpolar narcotic chemicals, polar narcotic chemicals and reactive chemicals.

According to the toxicity mechanism of the individual chemicals, the concentration addition toxicity mechanism is revealed for nonpolar-narcotic-chemical mixtures, polar-narcotic-chemical mixtures and reactive-chemical mixtures, respectively. For nonpolar-narcotic-chemical mixtures, the partitioning of individual chemicals from water to biophase was determined, and the result shows that their concentration additive effect results from no competitive partitioning among individual chemicals. For polar-narcotic-chemical mixtures, their toxicity are contributed by two factors (the total baseline toxicity and the hydrogen bond donor activity of individual chemicals), and it is the concentration additive effect for either of these two factors that leads to their concentration addition toxicity. In addition, the interactions between the reactive chemicals and the biological macromolecules are discussed thoroughly. The results suggest that the net effect of these interactions is zero, and it is this zero net effect that leads to the concentration addition toxicity mechanism for reactive-chemical mixtures.

Drug-Related Side Effects and Adverse Reactions↗

Holographic QSAR of selected esters.

The HQSAR (Holographic QSAR) method, which has been recently developed, can offer the ability to rapidly and easily generate QSAR models of high statistical quality and predictive value. HQSAR analysis requires selecting values for parameters that specify the size of the hologram that is to be used, and the size and type of fragment substructures that are to be encoded. The color coding is provided by HQSAR to reflect which molecular fragments may be important contributors to the biological activity. In this work, we studied the quantitative structure activity relationship of selected esters using the HQSAR method. A robust HQSAR model with r(2) (non-cross-validated regression coefficient) of 0.981 and q(2) (cross-validated regression coefficient) of 0.912, was developed after optimizing the fragment size and the hologram length. The color coding analysis, which has rarely been reported before, was done here to explain the outlier successfully.

Animals↗

[Purification efficiency of several wetland macrophytes on COD and nitrogen removal from domestic sewage].

In order to investigate the role of wetland macrophytes in waster water purification and to select appropriate native filter plants in constructed wetland, three vertical-flow constructed wetlands were built with river sands as the substrates of Acorus gramineus, Juncus effusus and Iris japonica, and one without plant as the control. Investigation on the removal of COD and total nitrogen (TN) from domestic sewage showed that within lower concentrations of COD (<200 mg x L(-1)) and TN (<30 mg x L(-1)), more than 90% of COD and 80% of TN were removed from domestic sewage in all constructed wetlands. When the concentration of COD and TN increased, the purification efficiency of all constructed wetlands decreased to some extent. The constructed wetlands with macrophytes had a higher efficiency than control. Among the three constructed wetlands with macrophytes, the one with Acorus gramineus had an average purification efficiency of 80.46% for COD and 77.77% for TN, that with Juncus effusus was 75.53% for COD and 71.17% for TN, and the one with Iris japonica was 70.50% for COD and 66.38% for TN. The constructed wetland without vegetation had an average purification efficiency of 61.39% for COD and 55.81% for TN. Acorus gramineus was more capable of removing COD and TN than Juncus effusus and Iris japonica. Vegetation biomass was the main factor affecting the removal rate of COD and nitrogen, because it significantly correlated with the ability of absorbing organic substance and nitrogen, and with the nitrification and denitrification around roots.

Acorus↗

Use of partition coefficients to predict mixture toxicity.

By using the C(18)-Empore disks/water partition coefficient (K(MD)) to describe the toxicity of 50 mixed halogenated benzenes to Photobacterium phosphoreum, an approach is proposed in this study. Application of the approach to the 15 other related mixtures prove the predictive capability of this K(MD)-based approach, due to the consistency between the predicted toxicity and the observed ones with r(2)=0.929, SE=0.104, F=169.513 at P<0.001. Further analysis of this approach finds that, for the mixtures, although the toxicity is highly correlated with their hydrophobicity, this correlation is free from the range difference of the hydrophobicity, the ratio or the number of the individual chemicals. These analysis results suggest that this K(MD)-based approach is able to predict the toxicity of mixture pollutants in wastewater.

Benzene Derivatives↗

Acute toxicity and quantitative structure-activity relationships of alpha-branched phenylsulfonyl acetates to Daphnia magna.

The acute toxicity (48 h-EC50, microM) of 20 alpha-substituted phenylsulfonyl acetates was measured using Daphnia magna with a static method. On the basis of physicochemical parameters (octanol/water partition coefficient logK(ow) and aqueous solubility logS(w)), the theoretical linear solvation energy relationships (TLSER) and Charge model descriptors, QSARs were calculated for the immobilization of D. magna. For the models with the physicochemical parameters logK(ow) and logS(w), the low squared correlation coefficients indicate that hydrophobicity plays a dominant role on the toxicity and hydrophobicity is not the only factor that influences the activity of the compounds. For the TLSER model and the Charge model, the great squared correlation coefficients suggest that the models have good predictive capability. The higher activity of the compounds can be explained with the disruption of van der Waals interactions between lipid and/or protein compounds within the membrane and the possibility of the compounds to form hydrogen bonds with the receptor molecules. The models may more completely illustrate the toxicity mechanisms.

Animals↗

Molecular hologram derived quantitative structure-property relationships to predict physico-chemical properties of polychlorinated biphenyls.

Polychlorinated biphenyls (PCBs) congeners with various degrees of chlorination and substitution patterns are among the most widespread and persistent man-made organic pollutants. They are toxic, lipophilic and tend to be bioaccumulated. The knowledge of the physico-chemical properties is very useful to explain the environmental behavior of PCBs and to perform an exposure assessment. In this paper, we have used a new molecular representation, the molecular hologram, to generate quantitative structure-property relationship models to predict the physico-chemical properties of biphenyl and all of its chlorinated congeners. The investigated properties include 1-octanol/water partition coefficient (logK(ow)), aqueous solubility (-logS(w)), aqueous activity coefficient (-logY(w)), Total molecular surface area, Henry's law constant (logH). The results show that this new quantitative structure-activity relationship approach presents highly predictive models for important physico-chemical properties of PCBs.

Chemical Phenomena↗

Quantification of joint effect for hydrogen bond and development of QSARs for predicting mixture toxicity.

A QSAR model is successfully proposed to predict the toxicity effect on Photobacterium phosphoreum by nonpolar-narcotic-chemical mixtures and/or polar-narcotic-chemical mixtures. For nonpolar-narcotic-chemical mixtures and polar-narcotic-chemical mixtures, their corresponding hydrophobicity-based QSAR models are derived from regression analysis. Comparison of these two QSAR models make us believe that it is the joint effect of hydrogen bond in polar-narcotic-chemical mixture that leads to the difference between these two models. Such joint effect of hydrogen bond can be quantified as AMH and BMH by using the different partition coefficients of mixtures in various organic phase/water systems. And the regression analysis results convinced us that the introduction of AMH does improve the quality of the QSAR model with r2=0.948, S.E.=0.166 and F=745.201 at P=0.000 for total 84 mixtures.

Drug Synergism↗

Three-dimensional quantitative structure-activity relationship study for phenylsulfonyl carboxylates using CoMFA and CoMSIA.

From both the comparative molecular field analysis (CoMFA) and the comparative molecular similarity indices analysis (CoMSIA), the paper describes two three-dimensional quantitative structure-activity relationship (3D-QSAR) models for the acute toxicity logEC50 (15 min-EC50 in micromoll(-1)) of 56 phenylsulfonyl carboxylates on Photobacterium phosphoreum. Two models yield the leave-one-out cross-validated correlation coefficient q2 values of 0.823 and 0.713, and the conventional correlation coefficient r2 values of 0.958 and 0.933, respectively. The achievement of higher q2 and r2 values of CoMFA model indicates the significance of correlation of steric and electrostatic fields with biological activities. The key features in the CoMFA contour maps are critical to trace the important properties and gain insight into the toxic mechanism of tested compounds. The quality of CoMSIA model is slightly lower than that of CoMFA in terms of q2 and r2 values. Not requiring molecular superposition, CoMSIA is faster than CoMFA in data processing.

Models, Chemical↗

Acute toxicity of benzene derivatives to the tadpoles (Rana japonica) and QSAR analyses.

Acute lethal toxicity (the negative logarithm of molar concentrations of 12 h acute median lethal, expressed as 12 h-log1/LC50) of 46 benzene derivatives to Rana japonica tadpoles was determined. 1-octanol/water partition coefficient (logKow)-dependent models were developed to study the toxicity of different categories chemicals. In an effort to model all chemicals, response surface analyses and stepwise multiple regression analyses were performed and successful models were obtained. A general and robust QSAR model was achieved with the combined application of variables reflecting hydrophobicity, electric property, and molecular size respectively (12h-log1/LC50 = 0.393logKow - 0.428Elumo + 0.0110Vol. + 1.362 n = 51, r2 = 0.834) using stepwise multiple regression analyses. Because of strong dissociation of carboxyl group greatly decreasing their observed toxicity, using logDow in instead of logKow the quality of the models is greatly improved. The conventional r2 and cross-validation r2(CV) were 0.914 and 0.785, respectively, indicating that QSAR was both internally consistent and highly predictive.

Animals↗

Application of toxicity identification evaluation procedures to an effluent from a nitrogenous fertilizer plant in China.

The integrated method combining chemistry and toxicology, toxicity identification evaluation (TIE), was conducted to identify key toxicants in an effluent from a nitrogen fertilizer plant in China. Toxicity characterization, phase I of TIE, revealed that the suspected toxicant in the effluent was an anion that could be changed into a volatile acid. The results of toxicity identification and confirmation procedures indicated potassium cyanide to be the primary toxicant in the effluent.

Algorithms↗

Development of QSARs for predicting the joint effects between cyanogenic toxicants and aldehydes.

Quantitative structure-activity relationship (QSAR) approaches are proposed in this study to predict the joint effects of mixture toxicity. The initial investigation studies the joint effects between cyanogenic toxicants and aldehydes to Photobacterium phosphoreum. Joint effects are found to result from the formation of a carbanion intermediate produced through the chemical interactions between cyanogenic toxicants and aldehydes. Further research indicates that the formation of carbanion intermediate is highly correlated with not only the charge of the carbon atom in the -CHO of aldehydes but also the charge of the carbon atom (C) in the carbochain of cyanogenic toxicants. The charge of the carbon atom in the -CHO of aldehydes is quantified by using the Hammett constant (sigma(p)), and then, sigma(p)-based QSAR models are proposed to describe the relationships between the joint effects and the chemical structures of the aldehydes. By using the charge of carbon atom (C) in the carbochain of cyanogenic toxicants, another QSAR model is proposed to describe the relationship between the joint effects and the chemical structures of cyanogenic toxicants.

Aldehydes↗

Prediction and application in QSPR of aqueous solubility of sulfur-containing aromatic esters using GA-based MLR with quantum descriptors.

Quantitative structure-property relationships (QSPR) were developed using a genetic algorithm (GA)-based variable-selection approach with quantum chemical descriptors derived from AM1-based calculations (MOPAC7.0). With the QSPR models, the aqueous solubility of 71 aromatic sulfur-containing carboxylates, including phenylthio, and phenylsulfonyl carboxylates were efficiently estimated and predicted. Using GA-based multivariate linear regression (MLR) with cross-validation procedure, the most important descriptors were selected from a pool of 28 quantum chemical semi-empirical descriptors, including steric and electronic types, to build QSPR models. The molecular descriptors included molecular surface (SA), charges on carboxyl group (Q(oc)), the magnitude of the difference between E(HOMO) of the solute and ELUMO of water, divided by 100 (E(B)), which were main factors affecting the aqueous solubility of the compounds of interest. The resulted coefficients R and R2 of 0.9571 and 0.9161 and the prediction residual error sum of squares (PRESS) of 13.1768, revealed that it was accurate and reliable for the model to predict the aqueous solubility of the investigated organic compounds. If two outliers were omitted from the dataset, the resulted coefficients R = 0.9619, R2 = 0.9253, and PRESS = 10.3875 were significantly improved. Compared with stepwise regression analysis, the results obtained in this work were better and more reasonable. The best QSPR model were obtained by GA-based MLR. Reasonable mechanisms for aqueous solubility of the sulfur-containing carboxylates were investigated and interpreted.

Algorithms↗

Mechanism-based quantitative structure-activity relationships for the inhibition of substituted phenols on germination rate of Cucumis sativus.

Comparative inhibition activity (GC50) of 42 structurally diverse substituted phenols on seed germination rate of Cucumis sativus was investigated. Quantitative structure-activity relationships (QSARs) were developed by using hydrophobicity (1-octanol/water partition coefficient, logKow) and electrophilicity (the energy of the lowest unoccupied molecule orbital, Eluma) for the toxicity of phenols according to their modes of toxic action. Most phenols elicited their response via a polar narcotic mechanism and a highly significant log Kow-based model was obtained (GC50 = 0.92 log Kow + 1.99, r2 0.84, n = 29). The inclusion of E(lumo) greatly improved the predictive power of the polar narcotic QSAR (GC50 = 0.88 log Kow - 0.30E(lumo) + 1.99, r2 = 0.93, n = 29). pKa proved to be an insignificant influencing factor in this study. Poor correlation with hydrophobicity and strong correlation with electrophilicity were observed for the nine bio-reactive chemicals. Their elevated toxicity was considerably underestimated by the polar narcotic logKow-dependent QSAR. The nine chemicals consist of selected nitro-substituted phenols, hydroquinone, catechol and 2-aminophenol. Their excess toxic potency could be explained by their molecular structure involving in vivo reaction with bio-macromolecules. Strong dissociation of carboxyl group of the four benzoic acid derivatives greatly decreased their observed toxicity. In an effort to model all chemicals including polar narcotics and bio-reactive chemicals, a response-surface analysis with the toxicity, logKow and E(lumo) was performed. This resulted in a highly predictive two-parameter QSAR for most of the chemicals (GC50 = 0. 70 logKow - 0.66E(lumo) + 2.17, r2 = 0.89, n = 36). Catechol and 2,4-dinitrophenol proved to be outliers of this model and their much high toxicity was explained.

Cucumis↗

Prediction of mixture toxicity with its total hydrophobicity.

Based on the C18 Empore disk/water partition coefficient of a mixture, quantitative structure-activity relationships (QSARs) are presented, which are used to predict the toxicity of mixed halogenated benzenes to P. phosphoreum. The predicted toxicity of 10 other related mixtures based on the QSAR model, agree well with the observed data with r2 = 0.973, SE = 0.113 and F = 287.785 at a level of significance P < 0.0001. The joint effect of these chemicals is simple similar action and the toxicity of the mixtures can be predicted from total hydrophobicity and is independent of hydrophobicity of the components or the ratio of the individual chemicals.

Bacteria↗

Quantitative structure-activity relationships for the inhibition toxicity to root elongation of Cucumis sativus of selected phenols and interspecies correlation with Tetrahymena pyriformis.

The comparative toxicities of selected phenols to higher plants Cucumis sativus were measured and the negative logarithm molar concentration of the root elongation median inhibition (IRC50) were derived. Quantitative structure-activity relationships (QSARs) were developed to explore the toxicity influencing factors and for predictive purpose. The toxicity data, fell into two classes: polar narcosis and bio-reactive. For polar narcotic phenols, a highly significant two-parameter QSAR based on 1-octanol/water partition coefficient (logKow) and energy of the lowest unoccupied orbital (E(lumo)) was derived (IRC50 = 0.77 log Kow - 0.39E(lumo) + 2.36 n = 22 r2 = 0.89). The five bio-reactive chemicals proved to show elevated toxicity due to their typical substructure involved diverse reactive mechanisms. In an effort to model all chemicals, a robust multiple-variable QSAR combining logKow, E(lumo) and Qmax, the most negative net atomic charge, was developed (IRC50 = 0.65 logKow - 0.72E(lumo) + 0.23Qmax + 2.81 n = 27 r2 = 0.94), indicating that hydrophobicity, electrophilicity and hydrogen bond interaction contribute mainly to the phytotoxicity. The toxicological data was compared with Tetrahymena pyriformis 2-d population growth inhibition toxicity (IGC50) and excellent interspecies correlations were observed both for the polar narcotics and for five reactive chemicals (for polar narcotics: IRC50 = 0.95IGC50 + 1.07 n = 16 r2 = 0.89; for bio-reactive chemicals: IRC50 = 0.98IGC50 + 2.19 n = 5 r2 = 0.97; and for all: IRC50 = 0.93IGC50 + 1.63 n = 21 r2 = 0.87). This suggested that T pyriformis toxicity could serve as a surrogate of C. sativus toxicity for phenols and interspecies correlation also could be established for reactive chemicals.

Animals↗