Discovery of novel phenoxypyridine as promising protoporphyrinogen IX oxidase inhibitors.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is a significant target for the discovery of novel bleaching herbicides. Starting from the active fragments of several known commercial herbicides, a series of PPO inhibitors with diphenyl ether scaffolds were designed and synthesized by substructure splicing and bioisosterism methods. The greenhouse herbicidal activity and the PPO inhibitory activity in vitro were measured. The results showed that the novel synthesized compounds have good PPO inhibitory activity, and the IC50 value against corn PPO ranges from 0.032 ± 0.008 mg/L to 3.245 ± 0.247 mg/L. Among all target compounds, compound P2 showed the best herbicidal activity, with a half inhibitory concentration (IC50) of 0.032 ± 0.008 mg/L. In addition, the molecular docking results showed that the benzene ring part of compound P2 can form a π-π stacking with PHE-392, and the trifluoromethyl group and ARG-98 form two hydrogen bonds. Crop safety experiments and cumulative concentration analysis experiments indicated that compound P2 can be used for weed control in rice, wheat, soybean and corn. Therefore, compound P2 can be selected to develop potential lead compounds for novel PPO inhibitors.

Design, Synthesis, and Herbicidal Activity of Diphenyl Ether Derivatives Containing a Five-Membered Heterocycle.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is an important target for discovering novel herbicides, and it causes bleaching symptoms by inhibiting the synthesis of chlorophyll and heme. In this study, the active fragments of several commercial herbicides were joined by substructure splicing and bioisosterism, and a series of novel diphenyl ether derivatives containing five-membered heterocycles were synthesized. The greenhouse herbicidal activity and the PPO inhibitory activity in vitro were discussed in detail. The results showed that most compounds had good PPO inhibitory activity, and target compounds containing trifluoromethyl groups tended to have higher activity. Among them, compound G4 showed the best inhibitory activity, with a half-maximal inhibitory concentration (IC50) of 0.0468 µmol/L, which was approximately 3 times better than that of oxyfluorfen (IC50 = 0.150 µmol/L). In addition, molecular docking indicated that compound G4 formed obvious π-π stacking interactions and hydrogen bond interactions with PHE-392 and ARG-98, respectively. Remarkably, compound G4 had good safety for corn, wheat, rice, and soybean, and the cumulative concentration in crops was lower than that of oxyfluorfen. Therefore, compound G4 can be used to develop potential lead compounds for novel PPO inhibitors.

The clinical value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) semi-quantitative parameters in monitoring neoadjuvant chemotherapy response of osteosarcoma.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive technique which could monitor tumor morphology, blood vessel dynamics, and micro-environmental changes. PURPOSE: To evaluate the value of DCE-MRI semi-quantitative parameters in monitoring the neoadjuvant chemotherapy (NAC) response of osteosarcoma. MATERIAL AND METHODS: Twenty-five patients pathologically confirmed as osteosarcoma received four cycles of NAC followed by surgery. All patients underwent conventional and dynamic MRI twice, before starting chemotherapy and before surgical treatment. With a reference standard of histological response (tumor necrosis rate), semi-quantitative parameters were compared between good response group (TNR ≥ 90%) and non-response group (TNR < 90%). The differences between intra- and inter-group parameters before and after NAC were analyzed by Mann-Whitney U test. Receiver operating characteristic (ROC) analysis was generated to assess the parameters' efficacy in predicting the outcome of NAC. RESULTS: The changes were statistically significant on slope, maximum signal intensity (SImax), time to peak (TTP), signal enhanced extent (SEE), peak percent enhancement (PPE), washout rate (WOR), and enhancement rate (ER) in the good response group (P < 0.05), while only SImax and SEE were different in the non-response group after NAC. The changes in Slope, SImax, TTP, SEE, WOR, and ER were markedly different (P < 0.05) between the two groups after NAC. Also, at the threshold values of 3.2%/s, 175 s, and 5.4% (slope, TTP, and ER), the sensitivity and specificity for predicting good response to chemotherapy were 83.3% and 92.3%, 91.7% and 69.2%, 84.6% and 75.0%, respectively. CONCLUSION: Slope, TTP, and ER values could be used to evaluate and predict the response to NAC in osteosarcoma.

[Responses of tree-ring width of Pinus tabuliformis plantation to climatic factors in Songshan Mountains, central China]. / åµ©å±±åœ°åŒºæ²¹æ¾äººå·¥æž—æ ‘è½®å®½åº¦å¯¹æ°”å€™å› å­çš„å“åº”.

Taking Pinus tabuliformis plantations at different slopes in Songshan Mountains, Henan Province, China as subjects, we established different residual chronologies of P. tabuliformis in Paomaling (PML) and Junjifeng (JJF) and whole region (RC). The results showed that the chro-nological quality of PML was higher than that of JJF. Chronologies of PML and JJF had more climate information, which had significant positive relationship with mean temperature in current February, mean temperature and mean maximum temperature at the end of growing season (September-October), and significant negative relationship with mean maximum temperature in current May. The response of radial growth of P. tabuliformis to climate differed in PML and JJF. Radial growth of P. tabuliformis in PML was positively correlated with mean minimum temperature in March and precipitation in September, while that in JJF was positively correlated with precipitation in May and mean minimum temperature in September. Residual chronologies of P. tabuliformis in whole region contained more climate information. The multiple regression analysis method was used to simulate that the main limiting factors of tree-ring width growth of P. tabuliformis, which was a range of temperature indicators, especially current mean temperature in September. The result was consistent with that of correlation analysis. This study could provide basic services for forest protection and ecological construction in Songshan Mountains region.

[Responses of radial growth of two coniferous species to climate factors in western Sichuan Plateau, China]. / å·è¥¿é«˜åŽŸä¸¤ç§é’ˆå¶æ ‘å¾„å‘ç”Ÿé•¿å¯¹æ°”å€™å› å­çš„å“åº”.

Based on the method of tree-ring chronology, we established ring-width standard chrono-logies of Abies faxoniana and Sabina saltuaria in Liangtaigou, Lixian County, western Sichuan Province, and their regional composite chronology (RC) to study the responses of radial growth of those two coniferous species to climate change, which provided a basis for the protection and mana-gement of forest ecosystems in this region under the background of global warming. The results showed that the RC contained the common climatic information of two individual chronologies, which had higher signal-to-noise ratio and expressed population signal. The correlation analysis showed that three chronologies had a good consistency in the response to climate factors. All chronologies were significantly correlated with temperature, with S. saltuaria being more sensitive to temperature changes. Relative humidity had stronger limiting effect on both species than precipitation in May and October. After the abrupt warming in 1994, the correlation between ring-width chrono-logy of A. faxoniana and monthly mean temperature shifted obviously from negative to positive in some months, which indicated the radial growth of A. faxoniana showed unstable in response to temperature. However, the radial growth of both species showed different broadening trend and the sensitivity to temperature response was weakened.

Design, synthesis, and herbicidal activity of novel phenoxypyridine derivatives containing natural product coumarin.

BACKGROUND: In recent years, protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors have been widely studied as important agricultural herbicides. Our research focused on the design and synthesis of novel PPO inhibitor herbicides, through linking of a diphenylether pyridine bioisostere structure to substituted coumarins, which aims to enhance environmental and crop safety while retaining high efficacy. RESULTS: A total of 21 compounds were synthesized via acylation reactions and all compounds were characterized using infrared, 1 H NMR, 13 C NMR, and high-resolution mass spectra. The respective configurations of compounds IV-6 and IV-12 were also confirmed using single crystal X-ray diffraction. The bioassay results showed that the title compounds displayed notable herbicidal activity, particularly compound IV-6 which displayed better herbicidal activity in greenhouse and field experiments, crop selectivity and safety for cotton and soybean compared with the commercial herbicide oxyfluorfen. CONCLUSION: The work revealed that compound IV-6 deserves further attention as a candidate structure for a novel and safe herbicide. © 2021 Society of Chemical Industry.

[Analysis of the Temporal and Spatial Distribution of the Diversity of the Denitrifying Anaerobic Methane-Oxidizing Bacterial Community in the Sediments of the Hunhe River and Its Relationship with Environmental Factors].

16S rRNA and pmoA functional genes were used as biomarker genes to investigate the temporal and spatial distribution of community diversity of Candidatus Methylomirabilis oxyfera (M. oxyfera) in the sediments of the Hunhe River by clone library technology. The dependence relationship between the physicochemical property of water and sediment samples and the diversity characteristics of the M. oxyfera community were analyzed by multivariate direct gradient analysis. Among the examples collected in September 2014, the OTU number of the 16S rRNA gene of M. oxyfera was 2-5, the Shannon-Wiener diversity index was 0.21-1.4, and the distribution characteristics in the middle reaches > upstream > downstream were presented. The OTU number and Shannon-Wiener diversity index of the pmoA functional gene in upstream samples are significantly higher than those in the middle and lower reach samples, and the Shannon-Wiener diversity indices in the upstream samples are 3.5 times and 2.3 times higher than that of the middle and the downstream samples, respectively. The community diversity of M. oxyfera showed a distinct regional distribution. Samples were collected at 3 sampling points in March 2015. The OTU values of 16S rRNA and pmoA for M. oxyfera are 6 and 5 respectively, which were obviously higher than those in September 2014. The Shannon-Wiener index is also higher than that in September 2014 (1.4>0.68; 57>0.00). The community diversity of M. oxyfera showed obvious seasonal distribution characteristics. Multivariate direct gradient analysis results showed that the concentration of DOC in water, sediment conductivity, TOC concentration, and nitrite concentration in the sediment are the main environmental factors affecting the community diversity of M. oxyfera.

[δ¹5N-NO3⁻ and δ¹8O-NO3⁻ Tracing of Nitrate Sources in Beijing Urban Rivers].

In order to quantitatively identify sources of nitrate pollution in Beijing urban area and provide effective guidance for relevant departments to control the pollution of Beijing rivers, δ¹5N-NO3⁻ and δ¹8O-NO3⁻ isotope tracing method was used to analyze the composition of nitrogen and oxygen stable isotopes from nitrate in Beijing urban river. Besides, stable isotope mixing model was adopted to track nitrogen sources of nitrate in Beijing urban rivers and the contribution rates of respective pollution sources were evaluated. The results showed that: (1) NO3⁻-N pollution was the main inorganic nitrogen pollution in Beijing rivers and pollution of downstream was more serious than that of upstream. (2) δ¹5N-NO3⁻ in Beijing urban surface rivers was in range of 6.26 per thousand-24.94 per thousand, while δ¹8O-NO3⁻ ranged -0.41 per thousand-11.74 per thousand; δ¹5N-NO3⁻ increased from upstream to downstream along the flow of the surface water. (3) The nitrate pollution composition of Beijing rivers could be gained from the stable isotope mixing model. The average contribution rates of manure and sewage, soil nitrate and atmospheric deposition were 61.2%, 31.5% and 7.3%, respectively.

[Characterizing Structural Composition of Dissolved and Particulate Organic Matter from Sediment Pore Water in a Urban River Using Excitation-Emission Matrix Fluorescence with Self-Organizing Map].

Excitation-emission matrix (EEM) fluorescence with self-organizing map was applied to characterize structural composition and spatial distribution of dissolved (DOM) and particulate (POM) organic matter from sediment pore water in a typical urban river. Ten sediment pore water samples were collected from the mainstream of Baitabuhe River in Shenyang City of northeast China, along a human impact gradient, i. e. river source, rural and urban regions. DOM and POM were extracted from the pore water, and their EEM fluorescence spectra were measured. ƒ450/500 of DOM ranged from 1.82 to 1.91, indicating that DOM is mainly from microbial source; ƒ450/500 of POM ranged from 1.42 to 1.68, suggesting that POM derived from land. Four components were identified from DOM and POM fractions by self-organizing map, which included tyrosine-like, tryptophan-like, fulvic-like and humic-like matters. Tyrosine-like originated from fresh and less-degraded material with a high potential for oxida- tion, which was considered as representative components of DOM and POM. Tryptophan-like was associated with microbial byproduct-like material, and can indicate microbial activities. The abundance sum of all components in DOM is roughly 2 times more than that in POM. The mean relative abundance of tyrosine-like was more than 50%, while tryptophan-like was about 18.6%-23.1%. Abundance of fulvic-like was much more than that of humic-like, but they were only a small proportion of organic matter fractions. Based on principal component analysis, the characteristics of DOM and POM distinctly were distributed along river source, rural region and urban region, proving that the river was deeply influenced by human activity.

[Dendroclimatic potentials for the tree rings of Huangshan pine (Pinus taiwanensis ) at Xiaolinhai in the western Dabie Mountains, China].

By using the dendrochronology research methods, this paper developed the 1915-2011 tree ring-width standard chronology of the Huangshan pine (Pinus taiwanesis) at the north slope of western Dabie Mountains in the junction of Hubei, Henan and Anhui provinces. High mean sensitivity (MS) indicated that there was conspicuous high-frequency climate signals and high first-order autocorrelation (AC) showed there were significant lag-effects of tree previous growth. The higher signal-to-noise ratio (SNR) and expressed population signal (EPS) indicated that the trees had high levels of common climate signals. Correlations between the tree ring-width standard chronology and climatic factors (1959-2011) revealed the significant influences of temperature, precipitation and relative humidity on the tree width growth of Huangshan pine by the end of growing season (September and October). Significant positive correlations were found between the tree-ring indices and the Palmer drought severity index (PDSI) of current September and October. In conclusion, the combination of water and heat of September and October is the major effect factor for the growth of Huangshan pine in western Dabie Mountains.

[Modeling nitrogen transformation in a novel circular-flow corridor wetland].

Nitrogen transformation and removal in a novel circular-flow corridor (CFC) wetland was simulated. A computer model covering 6 nitrogen forms, 3 media and 10 transferring pathways, was developed. The results show that the TN removal is attributed to zeolite adsorption (53.3%), plants NH4(+) -N uptake (27.6%), denitrification (10.2%), plants NO3(-) -N uptake (2.9%) and short-cut denitrification (1.5%). The major removal pathway for NH4(+) -N varies from season to season. In January, the zeolite adsorption played the most important role in NH4(+) -N removal with a contribution of 84.5%. From April to June, the plants uptake accounted for 76.4%-85.3% NH4(+) -N removal. While in July, there were three removal pathways, namely zeolite absorption (36.1%), nirtosation (45.8%) and plants uptake (21.4%), playing an important role in nitrogen removals. Additionally, regular plants harvesting, periodical zeolite regenerating and aquatic plants growing can improve the TN removal rate by 1.7%-7.7%, 43.1%-72.2% and 19.8%-36.2%, respectively. In short, it is by the diverse removal pathways in CFC wetland that nitrogen can be continuously removed.

[Forming processes of micro-ecology in anaerobic sludge granulation].

By use of the fluorescence in situ hybridization (FISH) and the polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) methods, the diversity and similarity of microbial community during anaerobic sludge granulation were studied. The relative abundance and their succession of H2-producing acetogens (HPA), homoacetoges (HOMA) and methanogens were monitored. And the whole forming processes of micro-ecology were investigated correspondingly. The results showed that for an anaerobic reactor during normal startup, only through 33-days continuous operation, the healthy microecology of granular sludge could be formed, which is much less than the growth period of granular sludge ( > 180 d) and the time for achieving good COD removal (about 50 d). During the granulation processes of anaerobic sludge, the Shannon-Wiener diversity index of the microbial community increased firstly to 3.11 and then decreased to 2.88, and their similarity increased from 44% to 86% continuously. It is through these three stages, namely the adaptive stage, the growth stage and the stabilization stage in turn, the stable microecology could be formed gradually. In the initial granulation stage, the methanogens had a higher growth speed, resulting in methanogens, HPA and HOMA studied being produced in a ratio of approximately 42: 2: 1, respectively. However, with the healthy mocroecology been formed gradually, the ratio of methanogens to HPA and HOMA decreased to 2.8: 2.4: 1.0 finally.

Nutrients removal and recovery from anaerobically digested swine wastewater by struvite crystallization without chemical additions.

Anaerobically digested swine wastewater contains high concentrations of phosphorus (P) and nitrogen (N). A pilot-scale experiment was carried out for nutrients removal and recovery from anaerobically digested swine wastewater by struvite crystallization. In the pilot plant, a sequencing batch reactor (SBR) and a continuous-flow reactor with struvite accumulation devices were designed and employed. The wastewater pH value was increased by CO(2) stripping, and the struvite crystallization process was performed without alkali and Mg(2+) additions. Results of the long-term operation of the system showed that, both reactors provided up to 85% P removal and recovery over wide ranges of aeration times (1.0-4.0 h), hydraulic retention times (HRT) (6.0-15.0 h) and temperatures (0-29.5°C) for an extended period of 247 d, in which approximate 30% of P was recovered by the struvite accumulation devices. However, 40-90% of NH(4)(+)-N removed was through air stripping instead of being immobilized in the recovered solids. The recovered products were detected and analyzed by scanning electron microscope (SEM), X-ray diffraction (XRD) and chemical methods, which were proved to be struvite with purity of more than 90%. This work demonstrated the feasibility and effects of nutrients removal and recovery from anaerobically digested swine wastewater by struvite crystallization without chemical additions.

[Acidification and its effect on the population distributions of microorganisms in an anaerobic baffled reactor].

The changes of pH, COD, volatile fatty acids (VFA) and microbial morphology of the acidification process in an anaerobic baffled reactor (ABR) were investigated. And the population succession process of the anaerobic microorganisms was quantitatively analyzed by using the Fluorescent In situ hybridization technology (FISH). The results show that the ABR reactor is acidified gradually from the front to the back. After the reactor is entirely acidified, the COD removal efficiency is only 30.9%, and the pH values are lowered by 1.0-2.2, while the VFA in effluent increases by 5.1 times. Additionally, the microbial morphology is significantly affected by the acidification process, in which not only the bacteria are deformed or died, but also the internal and external mass transfer of granular sludge becomes difficult. The quantitative analyses with FISH shows that in the acidification process the Archaea growth is inhibited but the Eubacteria growth is promoted, thus resulting in the sharp decrease of the three crucial microorganisms of the anaerobic digestion. The abundance of the butyrate-oxidizing acetogenic bacteria Syntrophomonas spp. reduces by 30.9%, the propionate-oxidizing acetogenic bacteria Syntrophobacter wolinii reduces by 85.5%, the homoacetogenic bacteria Acetobacterium species E. limosum reduces by 60.0%, and methanomicrobium Methanomicrobiales reduces by 54.3%. All these result in the upsetting of the mass transfer balances of different anaerobic microorganism populations.

The remediation of heavy metals contaminated sediment.

Heavy metal contamination has become a worldwide problem through disturbing the normal functions of rivers and lakes. Sediment, as the largest storage and resources of heavy metal, plays a rather important role in metal transformations. This paper provides a review on the geochemical forms, affecting factors and remediation technologies of heavy metal in sediment. The in situ remediation of sediment aims at increasing the stabilization of some metals such as the mobile and the exchangeable fractions; whereas, the ex situ remediation mainly aims at removing those potentially mobile metals, such as the Mn-oxides and the organic matter (OM) fraction. The pH and OM can directly change metals distribution in sediment; however oxidation-reduction potential (ORP), mainly through changing the pH values, indirectly alters metals distribution. Mainly ascribed to their simple operation mode, low costs and fast remediation effects, in situ remediation technologies, especially being fit for slight pollution sediment, are applied widely. However, for avoiding metal secondary pollution from sediment release, ex situ remediation should be the hot point in future research.

[Study on nitrogen cycling and transformations in a duckweed pond by means of modeling analysis].

Based on the simulated results from N cycling and transformation model of duckweed pond, the influences of different major transfer pathways on various nitrogen removal performances are investigated. The effects of seasonal variations of water conditions on nitrogen transformations are determined. The simulated results show that nitrification and denitrification were the major removal pathways for nitrogen in duckweed pond, and the removal contributions of organic nitrogen sedimentation and ammonia volatilization for total nitrogen removal were less than 2.1%. Furthermore, in duckweed pond, nitrification and denitrification decided the removal efficiencies of ammonia and NOx., respectively; both algae decaying and organic nitrogen ammonification controlled primarily the organic nitrogen removal performances; both organic nitrogen sedimentation and mineralization of sedimentary nitrogen determined the variations of sedimentary nitrogen. Duckweed pond with duckweed growing largely can increase sharply algae mortality and keep the low content of algae in effluent. Besides, through accelerating the nitrification and denitrification rate, duckweed can evidently improve the removal efficiencies of total nitrogen.

Multi-stage ponds-wetlands ecosystem for effective wastewater treatment.

The performance of the Dongying multi-stage ponds-wetlands ecosystem was investigated in this work. Study of the removal of different pollutants (BOD(5), COD, SS, TP, TN, NH(3)-N, etc.) in different temperature seasons and different units in this system indicated that effluent BOD(5) and SS were constant to less than 11 mg/L and 14 mg/L throughout the experimental processes; but that the removal efficiencies of pollutants such as TP, TN, NH(3)-N, COD varied greatly with season. The higher the temperature was, the higher was the observed removal in this system. Additionally, each unit of the system functioned differently in removing pollutants. BOD(5) and SS were mainly removed in the first three units (hybrid facultative ponds, aeration ponds and aerated fish ponds), whereas nitrogen and phosphates were mainly removed in hydrophyte ponds and constructed reed wetlands. The multi-stage ponds-wetlands ecosystem exhibits good potential of removing different pollutants, and the effluent quality meet several standards for wastewater reuse.

Interleukin-1beta enhanced action of kinins on extracellular matrix of spontaneous hypertensive rat cardiac fibroblasts.

Interaction between an enhanced action of kinins and cytokines is accepted as important to the cardioprotective effect of angiotensin-converting-enzyme inhibitors. Kinins mediate their effects through B1 and B2 subtype receptors that may be modulated by cytokines including interleukin (IL)-1beta. We examined expression of kinin receptors and the effects of bradykinin (B2 agonist) and des-Arg10-kallidin (B1 agonist) on extracellular matrix components of adult rat cardiac fibroblasts with or without prior exposure to IL-1beta. We compared responses of cells cultured from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) hearts. mRNA levels of kinin receptors, procollagens, promatrix metalloproteinases (proMMP-2 and proMMP-9), and tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2) were all assessed by a semiquantitative RT-PCR. In the absence of IL-1beta, SHR cells expressed more B2 receptor, procollagen alpha1(I), procollagen alpha1(III), and proMMP-9 mRNA than WKY cells. IL-1beta exposure enhanced B1, B2, proMMP-2, and proMMP-9 mRNA in cells of both strains to equivalent levels. Zymographic studies confirmed the results of proMMPs. Following IL-1beta treatment, bradykinin attenuated procollagens alpha1(I) and alpha1(III) mRNA expression in SHR but not WKY cells. In contrast, des-Arg10-kallidin did not show any significant effects in either SHR or WKY cells. Our findings indicate greater extracellular matrix turnover in cultured SHR cardiac fibroblasts than WKY under basal conditions, an IL-1beta stimulation of turnover in cells from both strains, and a strain-differential effect of bradykinin following cytokine treatment. These results imply a genetically determined response of cardiac extracellular matrix and the potential of direct enhancement of the efficacy of kinins by the local release of IL-1beta in hearts genetically programmed to exhibit excessive remodeling to injury.