In Silico Methods for Identification of Potential Active Sites of Therapeutic Targets.

Target identification is an important step in drug discovery, and computer-aided drug target identification methods are attracting more attention compared with traditional drug target identification methods, which are time-consuming and costly. Computer-aided drug target identification methods can greatly reduce the searching scope of experimental targets and associated costs by identifying the diseases-related targets and their binding sites and evaluating the druggability of the predicted active sites for clinical trials. In this review, we introduce the principles of computer-based active site identification methods, including the identification of binding sites and assessment of druggability. We provide some guidelines for selecting methods for the identification of binding sites and assessment of druggability. In addition, we list the databases and tools commonly used with these methods, present examples of individual and combined applications, and compare the methods and tools. Finally, we discuss the challenges and limitations of binding site identification and druggability assessment at the current stage and provide some recommendations and future perspectives.

Multiphase distribution and migration characteristics of heavy metals in typical sandy intertidal zones: insights from solid-liquid partitioning.

With the increase of development and utilization of coastal tidal flats, the desertification of intertidal zone is becoming more and more serious, which will inevitably lead to changes in the distribution and migration of heavy metals. This study reported the multiphase distribution and solid-liquid partitioning of Cr, Ni, Cu, Zn, Pb and Cd in typical sandy intertidal zones and predicted the migration of heavy metals with stepwise multiple linear regression. The distribution of heavy metals in surface water was comparable with that in pore water, while the content of heavy metals in suspended solids was obviously greater than that in sediments. Compared to non-sandy sediments, the bioavailability state of heavy metals extracted from sandy sediments by diethylene triamine penta-acetic acid was much smaller. The mean partitioning coefficient values (Kd) ranged from 21.56 to 166.18, which were 10-40 times lower than those of organic-rich sediments and 100-750 times lower than those of mineral soils. The dynamics in solid clay, SOC and ORP greatly affected the variations of Kd values. Clay had a significant positive correlation with bioavailability but did not have a significant correlation with logKd, indicating that the adsorption capacity of heavy metals in the intertidal zone is not the only factor controlling heavy metal migration. Stepwise multiple linear regression analysis confirmed that the prediction equations of heavy metals are composed of multiple physicochemical factors. All predicted and tested values were of the same order of magnitude, with R2 values ranging from 0.8223 to 0.9775. Although our data focus on a single species of sandy intertidal zone, characterizing the Kd value and its relationship with site-specific factors provides different tools for assessing the probability of heavy metal contamination and migration in sandy intertidal zones.

Multi-phase distribution and comprehensive ecological risk assessment of heavy metal pollutants in a river affected by acid mine drainage.

To date, there is a lack of a comprehensive research on heavy metals detection and ecological risk assessment in river water, sediments, pore water (PW) and suspended solids (SS). Here, the concentrations of heavy metals, including Cu, Zn, Mn, Cd, Pb and As, and their distribution between the four phases was studied. Samples for analysis were taken from twelve sites of the Hengshi River, Guangdong Province, China, during the rainy and dry seasons. A new comprehensive ecological risk index (CERI) based on considering metal contents, pollution indices, toxicity coefficients and water categories is offered for prediction of potential risk on aquatic organisms. The results of comprehensive analysis showed that the highest concentrations of Cu, Zn and Mn of 6.42, 87.17 and 98.74mg/L, respectively, in PW were comparable with those in water, while concentrations of Cd, Pb and As of 609.5, 2757 and 96.38µg/L, respectively, were 2-5 times higher. The sum of the exchangeable and carbonate fractions of target metals in sediments followed the order of Cd > Mn > Zn > Pb > Cu > As. The distribution of heavy metals in phases followed the order of sediment > SS > water > PW, having the sum content in water and PW lower than 2% of total. The elevated ecological risk for a single metal and the phase were 34,585 for Cd and 1160 for water, respectively, implied Cd as a priority pollutant in the considered area. According to the CERI, the maximum risk value of 769.3 was smaller than 1160 in water, but higher than those in other phases. Out of considering the water categories and contribution coefficients, the CERI was proved to be more reliable for assessing the pollution of rivers with heavy metals. These results imply that the CERI has a potential of adequate assessment of multi-phase composite metals pollution.

Distribution and migration of heavy metals in soil and crops affected by acid mine drainage: Public health implications in Guangdong Province, China.

Acid mine drainages (AMD) contain high concentrations of heavy metals, and their discharges into streams and rivers constitute serious environmental problems. This article examines the effects of AMD on soil, plant and human health at Dabaoshan mine in Guangdong Province, China. Although the large scale mining was stopped in 2011, the heavy metal pollution in soil continues to endanger crops and human health in that region. The objectives of this study were to elucidate distribution and migration of Cd, Cu, Zn, As and Pb and associated health implications to local inhabitants. We collected and analyzed 74 crop samples including 28 sugarcane, 30 vegetables, 16 paddy rice and the corresponding soil samples, used correlation and linear relationship for transformation process analysis, and applied carcinogenic and non-carcinogenic risk for hazard evaluation. Results showed that the local soils were heavily polluted with Cd, Cu and As (especially for Cd) and the mean Igeo value was as high as 3.77. Cadmium, Cu, and Zn in rice and vegetables were comparable with those found four years ago, while As and Pb in edible parts were 2 to 5 times lower than before. The root uptake of Cd and Zn contributed mainly to their high concentrations in crops due to high exchangeable fraction of soil, while leafy vegetables accumulated elevated As and Pb contents mainly due to the atmospheric deposition. Metal concentrations in sugarcane roots were higher than those in rice and vegetable roots. The risk assessment for crops consumption showed that the hazard quotients values were of 21 to 25 times higher than the threshold level for vegetables and rice, indicating a potential non-carcinogenic risk to the consumers. The estimated mean total cancer risk value of 0.0516 more than 100 times exceeded the USEPA accepted risk level of 1×10(-4), indicating unsuitability of the soil for cultivating the food crops. Therefore, the local agricultural and the land-use policies need to be reevaluated.

A methodology for evaluating the relative pollution level of metal pollution in surface sediments of rivers based on the statistical results of relevant literatures covering world-wide rivers.

Due to the intervention of human activities, the background values of riverbed sediment exhibit spatiotemporal variability, which can affect the accuracy of risk assessment results. Using risk assessment that do not rely on background values is an executable alternative to avoid such problems. In this study, a relative pollution level assessment (RPLA) method which was based on the statistical results of relevant literatures was proposed. This method includes a four-step data processing procedure to extract the evaluation indexes of relative pollution degree of pollutants in environment and a series of relative pollution status assessment methods to evaluate the overall relative pollution level and regional difference of world-wide rivers. To demonstrate how to use RPLA method, 310 relevant literatures covering world-wide rivers were selected. And the ambient background value (x̅), the world-wide threshold values (WWTV) and the relative pollution grades (LEVEL I ∼ IV) of 9 target metals (Cr, Ni, Cu, Zn, As, Cd, Pb, Sb and Tl) in riverbed surface sediments of world-wide rivers were extracted and used for evaluation. Moreover, the stability and applicability of RPLA method were evaluated. Results show that the evaluation results of RPLA method are robust and comparable with traditional evaluation method.

Synthesis and Characterization of a Temperature-Sensitive Microcapsule Gelling Agent for High-Temperature Acid Release.

Deep, high-temperature carbonate reservoirs, represented by the Chuanzhong-Gaomo Block and the Penglai Gas Field, have become important supports for increased storage and production in Sichuan Basin. However, acidization in high-temperature to ultrahigh-temperature reservoirs faces several technical challenges, such as fast acid-rock reaction rates, limited acid corrosion distances, and high risks of tubular corrosion. In this study, a novel high-temperature-resistant microencapsulated gelling agent GLE-3 was prepared using N-isopropylacrylamide (NIPAM) as the wall material, acrylamide (AM), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), and N-vinylcaprolactam (NVCL) as the core materials, and N,N'-methylenebis(acrylamide) (MBA) as the cross-linking agent through inverse emulsion polymerization. GLE-3 was structurally characterized using infrared spectroscopy, transmission electron microscopy, and particle size analysis, and its properties were evaluated. The results showed that GLE-3 exhibited uniform particle size distribution ranging from 10 to 100 µm. Under high-temperature conditions of 180 °C and a shear rate of 170 s-1, the viscosity of the gel acid solution remained above 27.8 mPa·s, with a viscosity retention rate of 63.76%. Compared to GLE-1 (uncapsulated), GLE-3 demonstrated improved thermal stability and shear stability after microencapsulation. After 60 min of shearing at 180 °C and shear rate of 170 s-1, the viscosity retention rate was 88.99%. Furthermore, under 180 °C conditions, GLE-3 exhibited good high-temperature slow-release performance compared to GLE-1, which unencapsulated with the same raw materials. By increasing the viscosity of the gel acid, delaying the acid-rock reaction rate, and providing high-temperature slow-release effects, the high-temperature resistance of the acid system was enhanced, ultimately achieving deep acidization in high-temperature reservoirs.

The stable operation of nitritation process with the continuous granular sludge-type reactor and microbial community analysis.

The nitritation step is the fundament for the biological nitrogen removal regardless of the traditional nitrification and denitrification process, the nitrite shunt process or the anammox process. Thus, exploring the effective nitritation performance is an important aspect of biological nitrogen removal. This study explored the upper limit of nitritation rate by increasing hydraulic residence time with the well-mixed and continuous granular sludge-type reactor characterized with low complexity and easy operation. The results showed that with the nitrogen loading rate of 1.0 kg/m3/d, the nitrite production rate could reach up to 0.65 kg/m3/d with the nitrite production efficiency of 63.49%, which is remarkable compared to that in the previously similar research. The microbial analysis indicated that ammonia-oxidizing bacteria was successfully enriched (13.27%) and genus Nitrosomonas was the dominant bacteria type. Besides, the activity of ammonium oxidizing bacteria in the continuous flow reactor was higher than that of other reactor types. The growth of vorticella on the sludge was also found in the reactor. The test of specific sludge activity and the microbe analysis both indicated that the nitrite-oxidizing bacteria was well inhibited during the whole experiment, which indicated the strategy of simply adjusting the dissolved oxygen is effective for running of nitritation process. The phosphorus removal performance was also achieved with a removal efficiency of 23.53%. The functional composition of the microbial community in the samples was predicted and finally transformation mechanism of nitrogen in sludge was drawn. In sum, this study indicated the superior performance of the granule sludge-type nitritation process and give a reference for the application of biological nitrogen removal technology.

[Multiphase Spatial Distribution Characteristics of Cd Morphology in Typical Intertidal Zones in the Guangdong-Hong Kong-Macao Greater Bay Area and Its Influencing Factors].

Simultaneous sampling and observation were conducted at 14 stations in typical intertidal zones of the Guangdong-Hong Kong-Macao greater bay area. The spatial distribution characteristics of Cd morphology in surface water, pore water, suspended matters, and sediments at each sampling site were analyzed, and the influencing factors of Cd morphology changes in each medium were discussed using statistical analyses based on environmental factors. The results showed that the total contents of Cd in surface water, pore water, suspended matters, and sediments in each intertidal zone ranged from 0.41-15.03 µg·L-1, 0.41-27.54 µg·L-1, 0.41-4.88 mg·kg-1, and 0.20-5.30 mg·kg-1, respectively. The contents of Cd in Shajiao Bay were significantly higher than those in other sampling sites, which should be related to the developed electronics and manufacturing industries in Dongguan. The concentration of Cd in surface water was slightly lower than that in pore water, whereas the content of Cd in suspended matter was comparable to that in sediment at the same sampling site. The results of morphological analysis showed that the ionic-state Cd was dominant in both surface water and pore water, accounting for 67.23%-97.56% and 33.33%-97.16%, respectively. In suspended matter and sediment, Cd was mainly in the residual state, accounting for 45.45%-96.36% and 45.80%-97.27%, respectively. Pearson correlation analysis showed that the complex-state Cd in the aqueous phase was negatively correlated with oxidation reduction potential (ORP) and pH and positively correlated with total organic carbon. The bioavailable Cd in solid sediment was significantly positively correlated with the proportion of clay, ORP, and solid organic carbon and significantly negatively correlated with pH. The single factor linear regression analysis showed that ORP had the greatest effect on the complex-state Cd in the aqueous phase, with regression coefficients of 0.864 and 0.824, respectively. The bioavailable Cd in solid sediment at different depths was significantly affected by the proportion of clay, and the regression coefficients were 0.968, 0.980, 0.977, and 0.877, respectively. The above results indicate that the distribution of total Cd content in the typical intertidal environment of the Greater Bay Area was affected by the characteristics of urban economic development, whereas the allocation of Cd morphology was closely related to environmental factors.

In silico Methods for Identification of Potential Therapeutic Targets.

At the initial stage of drug discovery, identifying novel targets with maximal efficacy and minimal side effects can improve the success rate and portfolio value of drug discovery projects while simultaneously reducing cycle time and cost. However, harnessing the full potential of big data to narrow the range of plausible targets through existing computational methods remains a key issue in this field. This paper reviews two categories of in silico methods-comparative genomics and network-based methods-for finding potential therapeutic targets among cellular functions based on understanding their related biological processes. In addition to describing the principles, databases, software, and applications, we discuss some recent studies and prospects of the methods. While comparative genomics is mostly applied to infectious diseases, network-based methods can be applied to infectious and non-infectious diseases. Nonetheless, the methods often complement each other in their advantages and disadvantages. The information reported here guides toward improving the application of big data-driven computational methods for therapeutic target discovery.

Nontarget analysis and comprehensive characterization of halogenated organic pollutants by GC-Q-Orbitrap-HRMS in association with chromatogram segmentation and Cl/Br-specific screening algorithms.

Nontarget analysis enables high-efficiency screening and identification of halogenated organic pollutants (HOPs) in complex matrices irrespective of lacking authentic standards, particularly for novel and emerging species, thereby realizing comprehensive component characterization of HOPs. Notwithstanding, nontarget analysis and comprehensive characterization of HOPs remain on the way to improvement. In this study, we implemented nontarget analysis of HOPs in fly ash, egg and sediment using gas chromatography quadrupole-orbitrap high-resolution mass spectrometry with the aid of chromatogram segmentation and Cl/Br-specific screening algorithms, and further performed comprehensive characterization of components and distribution of HOPs. In total, 122 HOP formulas were identified and tentatively assigned with structures, of which 28 were found in ≥ two matrices. Taking isomers into account, in total 1059 HOP congeners were found. Based on the identification and semiquantification results, the chemical components and concentration profiles of HOPs were preliminarily clarified, and accordingly the overall pollution signatures of HOPs were sketched. The total concentrations of HOPs in the fly ash, egg and sediment were 4.7, 41.2 and 750.8 µg g-1, respectively. Organochlorines were the most abundant among the categories classified by halogen types, and halogenated benzenes, halogenated dioxins, halogenated biphenyls/terphenyls and halogenated polycyclic aromatic hydrocarbons (H-PAHs) were the predominant of the structurally classified categories. Moreover, dozens of formulas of novel/little-known HOPs such as mix-chlorinated/brominated PAHs with ≥4 aromatic rings and polychlorinated terphenyls were identified. This study presents an accurate and high-performance nontarget analysis method for HOPs in complex matrices, and yields new cognitions on the pollution status of HOPs from an overall perspective.

Energy-efficient for advanced oxidation of bio-treated landfill leachate effluent by reactive electrochemical membranes (REMs): Laboratory and pilot scale studies.

This study for the first time investigated the advanced treatment of bio-treated landfill leachate effluent using a novel reactive electrochemical membrane (REM) technology at the laboratory and pilot scales. At the laboratory scale, RuO2-Ir-REM, Ti4O7-REM, and ß-PbO2-REM featured similar properties in pore size and water flux. Although RuO2-Ir-REM holds more reactive sites than the other two REMs, ß-PbO2-REM and Ti4O7-REM featured higher oxidation ability than RuO2-Ir-REM, causing their high yield of hydroxyl radical. Consequently, ß-PbO2-REM and Ti4O7-REM performed better than RuO2-Ir-REM, which removed total organic carbon and ammonia nitrogen by 70%-76% and 100%, respectively, after 45 minutes of treatment. Fluorescence spectroscopy analysis showed that humic acid-like substances were oxidized by the REM treatment. Using the ß-PbO2-REM in the lab-scale setup with the solutions circulated, we observed a greater removal of chemical oxygen demand (COD) at a higher applied current or a faster water flux. The pilot system with four large size of ß-PbO2-REMs modules in series was developed based on the lab-scale setup, which steadily treated landfill leachate in compliance with the disposal regulations of China, at an energy consumption of 3.6 kWh/m3. Also, a single-pass REM can effectively prevent the transformation of chloride to chlorate and perchlorate. Our study showed REM technology is a powerful and promising process for the advanced treatment of landfill leachate.

Coking wastewater treatment plant as a sources of polycyclic aromatic hydrocarbons (PAHs) in sediments and ecological risk assessment.

The spatial and temporal distribution of polycyclic aromatic hydrocarbons (PAHs) was investigated in sediments of Maba River, a major tributary of Beijiang River (South China). A total of 13 samples from Maba River and its tributary, Meihua River, were analyzed for 16 PAHs. The total concentration of 16 PAHs (ΣPAH) in high and low water period ranged between 47.61 to 25480.98 ng g-1, with a mean concentration of 4382.98 ng g-1, and 60.30 to 15956.62 ng g-1 with a mean concentration of 3664.32 ng g-1, respectively. Three-ring and four-ring PAHs were the dominant species. It was concluded that a pattern of pyrolytic input as a major source of PAHs in sediments through the molecular ratio method for the source identification, such as HMW/LMW PAHs, Flu/(Flu+Pyr), IcdP/(IcdP+BghiP) and BaA/(BaA+Chr). It is suggested that the pollution emission from the iron and steel plant might be the most important sources of PAHs into Maba River water system. The threat of PAHs contamination to biota of the river was assessed using effect range low (ERL) and effect range median (ERM) values, which suggested that PAHs in Maba River and its tributary had already caused ecological risks.

Quantification of the relationship between multiple metal(loid) distribution and integrated effect of internal-external factors in riverbed sediments across Xijiang River basin, South China.

Understanding the integrated effect of external factors (e.g., human activities) and internal factors (e.g., hydrodynamics, sediment properties) on metal(loid) distributions is necessary for relevant decision-makers to develop river basin management strategies. In attempts to understand the possible causes of the distribution of nine target metal(loid)s in riverbed sediments across Xijiang River basin in China, we grouped and portrayed the multiple metal(loid) distributions by calculating metal(loid)'s normalised-and-weighted average concentrations, and then canonical correlation analysis combined with a series of statistical operations, collectively called optimized CCA analysis, was applied to quantify the strength of relationship between multiple metal(loid) distribution and integrated effect of internal-external factors. Results showed that the target metal(loid)s can be divided into three groups according to their distribution patterns: Group A (including Zn, As, Cd, Sb and Pb), Group B (including Cr, Ni and Cu) and Group C (including Tl). Among them, metal(loid)s in Group A was significantly enriched in comparison with the reference values of Chinese sediments, and the wide-ranging accumulation of Cd and Sb in the whole study area needs paying great attention to. For those metals in natural states (e.g., metals in Group B), the affinity of sediment (e.g., Fe and Mn oxides) is responsible for their distributions. By contrast, when metal(loid)s (e.g., metal(loid)s in Group A and Group C) had obvious anthropogenic sources, the interferences of anthropogenic inputs (e.g., non-ferrous metal enterprises' waste-discharging activities) and the specific sedimentary characteristics (e.g. karst topography and low-energy hydrodynamic depositional conditions) in study area can weaken the correlation between the binding affinity of sediment and the contents of metal(loid)s. The optimized CCA analysis can be an alternative and advantageous statistical operation for determining the main types of causes of multiple metal(loid) distribution in the case of observations with relatively low case-per-variable ratios.