Discovery of Novel (5-Mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)methyl Phenyl Carbamate as a Potent Phytoene Desaturase Inhibitor through Scaffold Hopping and Linker Modification.

Phytoene desaturase (PDS) is a key rate-limiting enzyme in the carotenoid biosynthesis pathway. Although commercial PDS inhibitors have been developed for decades, it remains necessary to develop novel PDS inhibitors with higher bioactivity. In this work, we used the scaffold hopping and linker modification approaches to design and synthesize a series of compounds (7a-7o, 8a-8l, and 14a-14d). The postemergence application assay demonstrated that 8e and 7e separately showed the best herbicidal activity at 750 g a.i./ha and lower doses (187.5 g, 375g a.i./ha) without no significant toxicity to maize and wheat. The surface plasmon resonance revealed strong binding affinity between 7e and Synechococcus PDS (SynPDS). The HPLC analysis confirmed that 8e at 750 g a.i./ha caused significant phytoene accumulation in Arabidopsis seedlings. This work demonstrates the efficacy of structure-guided optimization through scaffold hopping and linker modification to design potent PDS inhibitors with enhanced bioactivity and crop safety.

Urban flood-bearing vulnerability evaluation based on the moment estimate weighting and improved gray target model.

Increasingly severe flooding seriously threatens urban safety. A scientific urban flood-bearing vulnerability assessment model is significant to improve urban risk management capacity. The gray target model (GTM) has advantages in urban flood-bearing vulnerability assessment. However, indicator correlation and single bull's-eye are commonly neglected, leading to defective evaluation results. By integrating the four base weights, an improved weighting method based on the moment estimate was proposed. Then, the marginal distance was used to quantify the indicator correlation, and the TOPSIS model was introduced to define the relative bull's-eye distance. Thus, an improved gray target evaluation method was established. Finally, an urban flood-bearing vulnerability evaluation model was presented based on the moment estimate weighting-improved GTM. In this study, Zhengzhou City, China, was taken as an example. The spatial and temporal changing characteristics of the flood-bearing vulnerability of Zhengzhou from 2006 to 2020 were investigated. The results show that: (1) On the temporal scale, the disaster-bearing vulnerability of Zhengzhou City showed an upward trend during the 15 years; (2) On the spatial scale, Guancheng District of Zhengzhou City had the relatively highest vulnerability to urban flooding. This study is expected to provide a scientific reference for urban flood risk management.

Discovery of (5-(Benzylthio)-4-(3-(trifluoromethyl)phenyl)-4H-1,2,4-triazol-3-yl) Methanols as Potent Phytoene Desaturase Inhibitors through Virtual Screening and Structure Optimization.

Phytoene desaturase (PDS) is not only an important enzyme in the biosynthesis of carotenoids but also a promising target for herbicide discovery. However, in recent years, no expected PDS inhibitors with new scaffolds have been reported. Hence, a solution for developing PDS inhibitors is to search for new compounds with novel chemotypes based on the PDS protein structure. In this work, we integrated structure-based virtual screening, structure-guided optimization, and biological evaluation to discover some PDS inhibitors with novel chemotypes. It is noteworthy that the highly potent compound 1b, 1-(4-chlorophenyl)-2-((5-(hydroxymethyl)-4-(3-(trifluoromethyl)phenyl)-4H-1,2,4-triazol-3-yl)thio)ethan-1-one, exhibited a broader spectrum of post-emergence herbicidal activity at 375-750 g/ha against six kinds of weeds than the commercial PDS inhibitor diflufenican. Surface plasmon resonance (SPR) assay showed that the affinity of our compound 1b (KD = 65.9 µM) to PDS is slightly weaker but at the same level as diflufenican (KD = 38.3 µM). Meanwhile, determination of the phytoene content and PDS mRNA quantification suggested that 1b could induce PDS mRNA reduction and phytoene accumulation. Moreover, 1b also caused the increase of reactive oxygen species (ROS) and the change of ROS-associated enzyme activity in albino leaves. Hence, all these results indicated the feasibility of PDS protein structure-based virtual screen and structure optimization to search for highly potent PDS inhibitors with novel chemotypes for weed control.

Association of UBE3C Variants with Reduced Kidney Function in Patients with Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of morbidity and mortality in patients with diabetes mellitus (DM) and the most common variant of end-stage renal disease (ESRD) globally. The economic burden of ESRD treatment with dialysis is substantial. The incidence and prevalence of ESRD in Taiwan remain the highest worldwide. Therefore, identifying genetic factors affecting kidney function would have valuable clinical implications. We performed microarray experiments and identified that ubiquitin protein ligase E3C (UBE3C) is differentially expressed in two DKD patient groups with extreme (low and high) urine protein-to-creatinine ratios. A follow-up genotyping study was performed in a larger group to investigate any specific variants of UBE3C associated with DKD. A total of 263 patients were included in the study, comprising 172 patients with DKD and 91 control subjects (patients with DM without chronic kidney disease (CKD)). Two UBE3C variants (rs3802129(AA) and rs7807(CC)) were determined to be associated with reduced kidney function. The haplotype analysis revealed that rs3802129/rs3815217 (block 1) with A/G haplotype and rs8101/rs7807 (block 2) with T/C haplotype were associated with higher risks of CKD phenotypes. These findings suggest a clinical role of UBE3C variants in DKD risk.

Gender Differences in Genetic Associations of RAB38 with Urinary Protein-to-Creatinine Ratio (UPCR) Levels in Diabetic Nephropathy Patients.

Renal dysfunction is common in patients with diabetes mellitus (DM). Previous findings from a meta-analysis of GWAS indicated that the variation of RAB38/CTSC is highly associated with the urinary albumin-to-creatinine ratio (UACR) in European populations. In addition, RAB38 knockout rats showed an increase in urinary albumins. Although the prevalence of chronic kidney disease is high in Taiwan, the role of genetic variants in diabetic renal function is still unclear. In the current study, 275 diabetic nephropathy (DN) patients were recruited to perform a genetic association study. Our results indicated that rs1027027, rs302647, and rs302646 in RAB38 were significantly associated with urinary protein-to-creatinine ratio (UPCR) levels in DN patients. Importantly, after analysis stratified by gender, a significant genetic influence on UPCR levels was observed in the male population. The findings confirmed the roles of gender and variants of RAB38 in the risk of UPCR in Diabetic Nephropathy patients.

Anthropogenic Effects on Hydrogen and Oxygen Isotopes of River Water in Cities.

Stable hydrogen and oxygen isotopes are important indicators for studying water cycles. The isotopes are not only affected by climate, but are also disturbed by human activities. Urban construction has changed the natural attributes and underlying surface characteristics of river basins, thus affecting the isotopic composition of river water. We collected urban river water isotope data from the Global Network for Isotopes in Rivers (GNIR) database and the literature, and collected river water samples from the Naqu basin and Huangshui River basin on the Tibetan Plateau to measure hydrogen and oxygen isotopes. Based on 13 pairs of urban area and non-urban area water samples from these data, the relationship between the isotopic values of river water and the artificial surface area of cities around rivers was analyzed. The results have shown that the hydrogen and oxygen isotope (δD and δ18O) values of river water in urban areas were significantly higher than those in non-urban areas. The isotopic variability of urban and non-urban water was positively correlated with the artificial surface area around the rivers. In addition, based on the analysis of isotope data from 21 rivers, we found that the cumulative effects of cities on hydrogen and oxygen isotopes have led to differences in surface water line equations for cities with different levels of development. The combined effects of climate and human factors were the important reasons for the variation of isotope characteristics in river water in cities. Stable isotopes can not only be used to study the effects of climate on water cycles, but also serve as an important indicator for studying the degree of river development and utilization.

Bioelectricity generation from air-cathode microbial fuel cell connected to constructed wetland.

The aim of this study was to investigate the different performance of bioelectricity generation and wastewater treatment between constructed wetland (CW) respectively coupled with air-cathode microbial fuel cell (ACMFC) and microbial fuel cell (MFC) under a fed-batch mode. During a 75-day-operation, the voltage of CW-ACMFC and CW-MFC ranged from 0.36 to 0.52 V and from -0.04 to 0.07 V, indicating that the bioenergy output of CW-ACMFC was significantly higher than that of CW-MFC system. In addition, the maximum of power density of CW-ACMFC and CW-MFC was 4.21 and 0.005 mW m-2. Notably, the chemical oxygen demand (COD) and NH3-N removal efficiency of CW-ACMFC was slightly higher than that in CW-MFC, which resulted from a higher voltage accelerating the transport of electron donors and the growth of microorganisms and plants. This study possesses a probability of using ACMFC coupled with CW to enhance the pollutant removal performance in CW system.

The Impact on the Ecosystem Services Value of the Ecological Shelter Zone Reconstruction in the Upper Reaches Basin of the Yangtze River in China.

With regional socio-economic development and increasing population, the structure and function of terrestrial ecosystem environments on the earth's surface have changed markedly. Ecological shelter zone reconstruction (ESZR) is an ecosystem restoration and conservation project, which aims to ensure the safety of the ecological environments of-regions and basins. We selected the upper reaches of the Yangtze River (from Yibin to Chongqing) as the study area and determined the connotation of ESZR. At the same time, the planning scope and construction content of the ecological barrier in this specific region have been preliminarily explored. Meanwhile, a set of related planning methods was proposed, the ecological effects of which were quantitatively assessed and confirmed through the calculation of ESVs. Compared with the conditions in 2005, the study showed that the value of the services of the whole ecosystem augmented significantly under the slope classification, increasing by 103.23%. At the same time, the land use pattern has been optimized, and the vegetation coverage has been enhanced. The ESZR can effectively improve the ecosystem service function of slope land (mainly slope > 25°) and the regional ecological environment, solve the rocky desertification of the study area and provide an effective decision in relation to supporting regional green sustainable development.

Bioelectricity generation, contaminant removal and bacterial community distribution as affected by substrate material size and aquatic macrophyte in constructed wetland-microbial fuel cell.

Integrating microbial fuel cell with constructed wetland (CW-MFC) is a novel way to harvest bioelectricity during wastewater treatment. In this study, the bioelectricity generation, containment removal and microbial community distribution in CW-MFC as affected by substrate material sizes and aquatic macrophyte were investigated. The planted CW-MFC with larger filler size showed a significant promotion of the relative abundance of electrochemically active bacteria (beta-Proteobacteria), which might result in the increase of bioelectricity generation in CW-MFC (8.91mWm-2). Additionally, a sharp decrease of voltage was observed in unplanted CW-MFC with smaller filler size in Cycle eight. However, the peak COD (86.7%) and NO3-N (87.1%) removal efficiencies were observed in planted CW-MFC with smaller filler size, which was strongly related to the biodiversity of microorganisms. Generally, the acclimation of exoelectrogens as dominant microbes in the anode chamber of planted CW-MFC with larger filler size could promote the bioelectricity generation during wastewater treatment.