Adaptive pressure-driven multi-criteria spatial decision-making for a targeted placement of green and grey runoff control infrastructures.

Traditional runoff control measures ignore the spatial imbalance of regional pressures, thereby failing to achieve a site-specific placement for green and grey infrastructure simultaneously. A multi-criterion decision-making framework for runoff control infrastructure spatial planning was therefore developed in this study. The pressure-state-response framework was applied to creatively match the pressure induced adjustment demands with the infrastructure effectiveness. The pressures were quantified from the perspective of environment, economy, and ecology on a grid scale. States were considered as the relative priority of regional pressure adjustment demand in multiple perspectives. Responses were presented as state-targeted green and grey infrastructure placement. Multi-perspective effectiveness of different green and grey infrastructure was simultaneously evaluated at an effective scale of controlling 1 m3/s runoff for comparison. Methods such as data mining, hydrological model simulation, and remote sensing inversion were combined to quantify the regional pressures. The capital investment and ecological impact of infrastructures were quantified from a life cycle perspective. A case study was carried out in Wuhan, China. The study area was clustered by gridded pressure into three regions. In region Ⅰ, ecological and environmental pressure were of higher weight. In region Ⅱ, the environmental pressure was dominant. In region Ⅲ, the ecological pressure took precedence over the environmental and economic constraints. The area ratios of the region Ⅰ, Ⅱ, and Ⅲ were 43%, 36%, and 21% respectively. The result indicated a synergy and spatial heterogeneity of multi-perspective pressures, and further demonstrating that expert experience tends to fail to weigh the multi-function of green and grey infrastructures for coping with the pressures. Results also stated that green infrastructures were more acceptable in areas that aspire to achieve simultaneous runoff control and ecological improvement. The decision-making framework developed in this study can maximize the overall performance by providing targeted infrastructure placement solutions.

Design, synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152): a novel triple angiokinase inhibitor for cancer therapy.

Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure-activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRß simultaneously in vitro. Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.

Integrated 1D and 2D model for better assessing runoff quantity control of low impact development facilities on community scale.

This study proposes a modelling framework of integrated one-dimensional (1D) and two-dimensional (2D) hydrodynamic modelling to evaluate the effectiveness of sponge city construction at community scale. Through a case study in Zhuhai, we integrate Stormwater Management Model (SWMM) and Cellular Automata Dual-DraInagE Simulation (CADDIES) 2D model to analyze the rainfall-runoff process involving green infrastructures. SWMM is applied to analyze the change of surface runoff control effects before and after the implementation of sponge city low impact development (LID) facilities, and CADDIES is adopted to simulate the propagation of excess runoff on the surface. The results show that the LID facilities can effectively reduce the runoff volume of small and medium-sized rainfall events since the maximum runoff reduction rate is 94.4%. For long-term operation, the LID can capture 52.9% of annual rainfall volume and reduce annual runoff by 28.0%. However, the CADDIES 2D model simulations indicate that LID facilities have little effect on flood alleviation in specific regions under extreme rainfall conditions. In addition, we compared the modelling performance using four different terrain Digital Elevation Model (DEM) resolutions and found that 1 m terrain DEM resolution can produce comparable results to 0.25 m DEM with a fraction of computational time. We also find that the MIKE FLOOD model and the integrated model of SWMM and CADDIES 2D can obtain similar simulation results, the p-value = 0.09 which is >0.05, but SWMM-CADDIES integrated model is more suitable for small-scale simulation.

Comparative Transcriptome Analysis Reveals the Cause for Accumulation of Reactive Oxygen Species During Pollen Abortion in Cytoplasmic Male-Sterile Kenaf Line 722HA.

Cytoplasmic male sterility (CMS) is a maternally inherited trait used for hybrid production in plants, a novel kenaf CMS line 722HA was derived from the thermo-sensitive male-sterile mutant 'HMS' by recurrent backcrossing with 722HB. The line 722HA has great potential for hybrid breeding in kenaf. However, the underlying molecular mechanism that controls pollen abortion in 722HA remains unclear, thus limiting the full utilization of this line. To understand the possible mechanism governing pollen abortion in 722HA, cytological, transcriptomic, and biochemical analyses were carried out to compare the CMS line 722HA and its maintainer line 722HB. Cytological observations of the microspore development revealed premature degradation of the tapetum at the mononuclear stage, which resulted in pollen dysfunction. The k-means clustering analysis of differentially expressed genes (DEGs) revealed that these genes are related to processes associated with the accumulation of reactive oxygen species (ROS), including electron transport chain, F1F0-ATPase proton transport, positive regulation of superoxide dismutase (SOD), hydrogen peroxide catabolic, and oxidation-reduction. Biochemical analysis indicated that ROS-scavenging capability was lower in 722HA than in 722HB, resulting in an accumulation of excess ROS, which is consistent with the transcriptome results. Taken together, these results demonstrate that excessive ROS accumulation may affect the normal development of microspores. Our study provides new insight into the molecular mechanism of pollen abortion in 722HA and will promote further studies of kenaf hybrids.

Determination sources of nitrates into the Three Gorges Reservoir using nitrogen and oxygen isotopes.

Identification of nitrate sources and its transformations are important for the management of large lakes and reservoirs. The Three Gorges Reservoir (TGR) in China is one of the largest reservoirs around the world. In this study, stable isotopes of nitrogen (δ15N-NO3-) and oxygen (δ18O-NO3-) of nitrate in water were used to gain insights into nitrate sources and transformations in the tail area of the TGR. Bayesian mixing model has been conducted to estimate the proportional contribute of nitrate sources. The mixing modelling results indicated that NH4+ fertilizer (range 7-54%) and soil organic nitrogen (range 2-45%) were the dominant NO3--N sources in the tail area of the TGR during the three season study period. Nitrification contributed a part of NO3--N in the river water during the dry season. The nitrate from soil solution in the riparian zone with denitrified NO3- might be another major reason for the enrichment of δ15N-NO3- and δ18O-NO3- during the normal season. Reducing the use of chemical nitrogen fertilizers, especially NH4+ fertilizers, and protecting soil from erosion may be effective measures to improve water quality in the TGR.

Synthesis and Biological Evaluation of a Series of Bile Acid Derivatives as FXR Agonists for Treatment of NASH.

Farnesoid X receptor (FXR) has become a particularly attractive target for the discovery of drugs for the treatment of liver and metabolic diseases. Obeticholic acid (INT-747), a FXR agonist, has advanced into clinical phase III trials in patients with nonalcoholic steatohepatitis (NASH), but adverse effects (e.g., pruritus, LDL increase) were observed. Pruritus might be induced by Takeda G-protein-coupled receptor 5 (TGR5, GPBAR1), and there are chances to develop FXR agonists with higher selectivity over TGR5. In this letter, novel bile acids bearing different modifications on ring A and side chain of INT-747 are reported and discussed. Our results indicated that the side chain of INT-747 is amenable to a variety of chemical modifications with good FXR potency in vitro. Especially, compound 18 not only showed promising FXR potency and excellent pharmacokinetic properties, but also proved superior pharmacological efficacy in the HFD + CCl4 model.

Discovery and optimization of selective FGFR4 inhibitors via scaffold hopping.

Introduction of a Michael acceptor on a flexible scaffold derived from pan-FGFR inhibitors has successfully yielded a novel series of highly potent FGFR4 inhibitors with selectivity over FGFR1. Due to reduced lipophilicity and aromatic ring count, this series demonstrated improved solubility and permeability. However, plasma instability and fast metabolism limited its potential for in vivo studies. Efforts have been made to address these problems, which led to the discovery of compound (-)-11 with improved stability, CYP inhibition, and good activity/selectivity for further optimization.

[Pollution of Halogenated Polycyclic Aromatic Hydrocarbons in Atmospheric Particulate Matters of Shenzhen].

Concentrations of halogenated polycyclic aromatic hydrocarbons ( HPAHs) in atmospheric PM10 and PM2.5 samples collected from Shenzhen were determined using GC-MS. Total concentrations of nine HPAHs in atmospheric PM10 and PM2.5 samples ranged from 118 to 1,476 pg · m(-3) and 89 to 407 pg · m(-3), respectively. In PM10 and PM(2.5) samples, the concentration of 9-BrAnt was the highest, followed by 7-BrBaA and 9, 10-Br2Ant. Seasonal levels of total HPAHs in atmospheric PM10 and PM2.5 samples in Shenzhen decreased in the following order: winter > autumn > spring > summer, whereas concentrations of individual HPAHs showed different seasonal levels. Meteorological conditions, including temperature, precipitation, and relative humidity, might be important factors affecting the seasonal levels of HPAHs in atmospheric PM10 and PM2.5 In addition, there were significant correlations between concentrations of HPAHs and parent PAHs. Finally, the toxic equivalency quotients (TEQs) of HPAHs were estimated. The TEQs of HPAHs in atmospheric PM10 and PM2.5 samples ranged from 17.6 to 86.2 pg · m(-3) and 14.6 to 70.4 pg · m(-3), respectively. Among individual HPAHs, 7-BrBaA contributed greatly to the total TEQs of HPAHs. Our results indicated that the total TEQs of HPAHs were lower than parent PAHs in atmospheric PM10 and PM2.5 samples in Shenzhen.

Plant uptake, translocation, and return of polycyclic aromatic hydrocarbons via fine root branch orders in a subtropical forest ecosystem.

Fine roots of woody plants are a heterogeneous system differing markedly in structure and function. Nevertheless, knowledge about the plant uptake of organic pollutants via fine roots is scarce to date. In the present study, plant uptake, translocation, and return of polycyclic aromatic hydrocarbons (PAHs) via fine roots in a subtropical forest ecosystem were investigated. Levels of Σ15PAHs in different fine root branch orders of Michelia macclurei, Cryptocarya concinna, Cryptocarya chinensis, and Canthium dicoccums varied from 5072±1419 ng g(-1) to 6080±1656 ng g(-1), 4037±410 ng g(-1) to 6101±972 ng g(-1), 3308±1191 ng g(-1) to 4283±237 ng g(-1), and 3737±800 ng g(-1) to 4895±1216 ng g(-1), respectively. Overall, concentrations of low-molecular-weight PAHs with 2-3 aromatic rings were higher than high-molecular-weight PAHs with 4-6 aromatic rings in all fine root branch orders. There were obvious translocations of PAHs between adjacent branch orders and a net accumulation of PAHs may occur in the fourth- and fifth-order roots. The storage of PAHs in the fine root system showed an obvious increasing trend along the branch orders ascending for all tree species. The return flux of PAHs via fine roots mortality showed an obvious decreasing trend with the branch orders ascending across the four tree species. Lower order roots contributed greatly to the total PAHs return flux. Our results indicated that fine roots turnover is an effective pathway for perennial tree species to remove environmental toxicants absorbed into them.

Cumulative health risk assessment of halogenated and parent polycyclic aromatic hydrocarbons associated with particulate matters in urban air.

Halogenated polycyclic aromatic hydrocarbons (HPAHs) have been reported to occur widely in urban air. Nevertheless, knowledge about the human health risk associated with inhalation exposure to HPAHs is scarce so far. In the present study, nine HPAHs and 16 PAHs were determined in atmospheric particulate matter (PM) collected from Shenzhen, China to address this issue. Concentrations of Σ9HPAHs varied from 0.1 to 1.5 ng/m(3) and from 0.09 to 0.4 ng/m(3) in PM10 and PM2.5 samples, respectively. As for individuals, 9-bromoanthracene, 7-bromobenz(a)anthracene, and 9,10-dibromoanthracene were the dominant congeners. Levels of Σ16PAHs in PM10 and PM2.5 samples ranged from 3.2 to 81 ng/m(3) and from 2.8 to 85 ng/m(3), respectively. Among individual PAHs, chrysene, benzo[b]fluoranthene, and indeno[1,2,3-c,d]pyrene were the main congeners. According to the season, concentrations of HPAHs and PAHs in atmospheric PM10/PM2.5 samples show a similar decreasing trend with an order: winter>autumn>spring>summer. The daily intake (DI) of PM10/PM2.5-bound HPAHs and PAHs were estimated. Our results indicated that children have the highest DI levels via inhalation exposure. The incremental lifetime cancer risk (ILCR) induced by PM10/PM2.5-bound HPAHs and PAHs were calculated. The ILCR values showed a similar decreasing trend with an order: adults>children>seniors>adolescent. Overall, the ILCR values induced by HPAHs and PAHs were far below the priority risk level (10(-4)), indicating no obvious cancer risk. To our knowledge, this is the first study to investigate the human health risk associated with inhalation exposure to PM10/PM2.5-bound HPAHs.

Variation of the linkage of root function with root branch order.

Mounting evidence has shown strong linkage of root function with root branch order. However, it is not known whether this linkage is consistent in different species. Here, root anatomic traits of the first five branch order were examined in five species differing in plant phylogeny and growth form in tropical and subtropical forests of south China. In Paramichelia baillonii, one tree species in Magnoliaceae, the intact cortex as well as mycorrhizal colonization existed even in the fifth-order root suggesting the preservation of absorption function in the higher-order roots. In contrast, dramatic decreases of cortex thickness and mycorrhizal colonization were observed from lower- to higher-order roots in three other tree species, Cunninghamia lanceolata, Acacia auriculiformis and Gordonia axillaries, which indicate the loss of absorption function. In a fern, Dicranopteris dichotoma, there were several cortex layers with prominently thickened cell wall and no mycorrhizal colonization in the third- and fourth-order roots, also demonstrating the loss of absorptive function in higher-order roots. Cluster analysis using these anatomic traits showed a different classification of root branch order in P. baillonii from other four species. As for the conduit diameter-density relationship in higher-order roots, the mechanism underpinning this relationship in P. baillonii was different from that in other species. In lower-order roots, different patterns of coefficient of variance for conduit diameter and density provided further evidence for the two types of linkage of root function with root branch order. These linkages corresponding to two types of ephemeral root modules have important implication in the prediction of terrestrial carbon cycling, although we caution that this study was pseudo-replicated. Future studies by sampling more species can test the generality of these two types of linkage.

PBDEs as indicator chemicals of urbanization along an urban/rural gradient in South China.

Fourteen polybrominated diphenyl ethers (PBDEs) were measured in surface sediments collected from an urban watershed in a rapidly urbanizing region, Shenzhen, China. BDE209 was the predominant congener of PBDEs detected in surface sediments, which was consistent with the fact that technical deca-BDE mixtures are the dominant PBDE formulation used in China, especially the Pearl River Delta. A positive association between sediment PBDEs and catchment degree of urbanization suggested that the rapid urbanization process may be affecting the PBDEs levels in surface sediments. Similar to the "urban heat island effect", an "urban pollution island effect" was observed in the present study. These results indicated that PBDEs can be used as potential indicator chemicals of catchment's urbanization process in the present region.

Pore structures of ordered large cage-type mesoporous silica FDU-12s.

The pore variations of ordered cage-type mesoporous silica FDU-12s have been analyzed in detail by PXRD, SAXS, nitrogen sorption, and electron crystallography. FDU-12s with a cubic symmetry (space group, Fmm) were templated by amphiphilic triblock copolymer F127 with the addition of 1,3,5-trimethylbenzene and KCl under an acidic condition. Three typical samples with different unit cell sizes, pore cage diameters, and entrance sizes were obtained from different synthesis and hydrothermal treatment temperatures, as indicated by the differences in the PXRD and SAXS patterns. The pore structure changes in the three materials were observed by nitrogen adsorption/desorption and 3-D reconstruction of HRTEM images taken from different crystal orientations. The approximate pore structures of FDU-12s can be regarded as a face-centered cubic (fcc) close-packing of spherical cages, each connected to 12 nearest neighboring cages. However, the ideal spherical model is only valid for the FDU-12s prepared at a low temperature (L-FDU-12-100). The cage shape of the FDU-12s synthesized at a high temperature deviates from perfect spheres and is accompanied by an entrance enlargement. The temperature-dependent behavior of the PEO block is discussed with regard to its influence on the micelles and hence the cage configuration. The better understanding of the formation mechanism via the combined characterization techniques and modeling may lead to a more rational approach for tuning the pore cages and entrances of the mesoporous FDU-12 materials.

Fast simultaneous determination of niobium and tantalum by Kalman Filter analysis with flow injection chemiluminescence method.

A fast and highly efficient Kalman Filter analysis-flow injection chemiluminescence (FI-CL) method was developed to simultaneously determine trace amounts of niobium and tantalum in geological samples. The method, without the boring process of separation and dear instruments, is suitable for field scene analysis. The mixed chemiluminescence kinetic curve was analyzed by a Kalman Filter (KF) in this method to realize the simultaneous determination of niobium and tantalum. Possible interference elements in the determination were investigated. Under the selected conditions, the detection limits (3sigma, n = 11) of niobium(V) and tantalum(V) were 2.1 x 10(-3) microg g(-1) and 4.0 x 10(-3) microg g(-1), respectively, and the relative standard deviations were 4.9% and 3.3% (n = 9). The method was applied to the determination of niobium and tantalum in geological samples with satisfactory results.