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Focusing on the problems such as adjustment of planting structure, imbalance of water supply and serious over-extraction of groundwater in Jinghui Canal Irrigation District, a multi-objective water regulation model was established for finding coordinate development among ecological benefits, social benefits and economic benefits to seek the reasonable program of water resource utilization and agricultural planting. When the ecological benefit was optimal, the total area of crop planting was 6.105 × 104 hm2, the area of grain crops, fruit trees and vegetables planting was 3.073 × 104 hm2, 1.444 × 104 hm2 and 1.592 × 104 hm2 respectively. Under this scenario, the irrigation water requirement was 35986.87 × 104 m3/a. The surface water supply was 32268.42 × 104 m3/a and the compensation of groundwater supply was 3718.45 × 104 m3/a. Therefore, when the social benefit was optimal, the total area of crop planting was 6.57 × 104 hm2, the area of grain crops, fruit trees and vegetables planting was 3.684 × 104 hm2, 1.214 × 104 hm2 and 1.673 × 104 hm2 respectively. Under this scenario, the irrigation water requirement was 39571.20 × 104 m3/a. The surface water supply was 33438.65 × 104 m3/a and the compensation of groundwater supply was 6132.54 × 104 m3/a. The agricultural planting structure between the two can serve as a reasonable control interval, and provide a reasonable resource utilization and agricultural planting scheme for the future development of Jinghui Canal Irrigation District.

Bioretention system can effectively remove polycyclic aromatic hydrocarbons (PAHs) in urban surface runoff through adsorption. However, the accumulation of PAHs may have potential inhibitory effect on microbial growth and activity in the system, and thus influence the overall performance. In this study, laboratory-scale bioretention cells with three different filter media were constructed. Pyrene, a high-molecular-weight PAH with 4 benzene rings, was periodically introduced into the bioretention cells to evaluate its effect on purification of carbon, nitrogen and phosphorus, and related microbial enzyme activities. The results showed that the removal capability of chemical oxygen demand (COD) was significantly influenced by pyrene contamination, which was difficult to recover at high pyrene level of 90 mg/kg. Increased effluent total nitrogen (TN) concentration were observed in the bioretention cells with high pyrene content, while no significant change on effluent total phosphorus (TP) concentration was detected. The soil dehydrogenase enzyme activity decreased with the increase of pyrene level, which might contribute to the decreasing COD removal rate. The urease activities in the bioretention cells were obviously inhibited by the addition of pyrene, probably leading to the decreasing nitrogen removal capacity of the system. In summary, the bioretention cells containing coal ash and lava rock performed better and were more stable under pyrene contamination.

Red tides and eutrophication have been frequently observed over the past two decades in coastal waters around Hong Kong, which are caused by many factors and one of them is the nutrient from nonpoint source pollution (NSP). This paper concentrates on the nutrients carried by river flow from watersheds. Since there are no systematical data sets of nonpoint source pollution in Hong Kong, monthly river water quality measurements, rainfall and river flow data, land uses, and other related information are used to analyze the characteristics of NSP and estimate the nutrient loads for Hong Kong region. Main achievements are as follows: firstly, besides mean concentration for single land use, the concept of integrated mean concentration for mixed land uses was proposed and applied. Secondly, mean concentrations were carried out for different land uses (agriculture, town, grassland, shrubland and woodland), each Water Control Zone, and Hong Kong region. Thirdly, the annual nutrient loads were estimated, for the first time in this paper, with various methods for the whole area of Hong Kong, and about 8,000 tons of TN and 1,500 tons TP are transported into coastal waters from Hong Kong's land in 1998.

A CRISPR/Cas9 gene editing strategy has been remarkable in excising segments of integrated HIV-1 DNA sequences from the genome of latently infected human cell lines and by introducing InDel mutations, suppressing HIV-1 replication in patient-derived CD4+ T-cells, ex vivo . Here, we employed a short version of the Cas9 endonuclease, saCas9, together with a multiplex of guide RNAs (gRNAs) for targeting the viral DNA sequences within the 5′-LTR and the Gag gene for removing critically important segments of the viral DNA in transgenic mice and rats encompassing the HIV-1 genome. Tail-vein injection of transgenic mice with a recombinant Adeno-associated virus 9 (rAAV 9 ) vector expressing saCas9 and the gRNAs, rAAV:saCas9/gRNA, resulted in the cleavage of integrated HIV-1 DNA and excision of a 978 bp DNA fragment spanning between the LTR and Gag gene in the spleen, liver, heart, lung and kidney as well as in the circulating lymphocytes. Retro-orbital inoculation of rAAV 9 :saCas9/gRNA in transgenic rats eliminated a targeted segment of viral DNA and substantially decreased the level of viral gene expression in circulating blood lymphocytes. The results from the proof-of-concept studies, for the first time, demonstrate the in vivo eradication of HIV-1 DNA by CRISPR/Cas9 on delivery by an rAAV 9 vector in a range of cells and tissues that harbor integrated copies of viral DNA.

Chemical probes of epigenetic ‘readers’ of histone post-translational modifications (PTMs) have become powerful tools for mechanistic and functional studies of their target proteins in normal physiology and disease pathogenesis. Here we report the development of the first class of chemical probes of YEATS domains, newly identified ‘readers’ of histone lysine acetylation (Kac) and crotonylation (Kcr). Guided by the structural analysis of a YEATS–Kcr complex, we developed a series of peptide-based inhibitors of YEATS domains by targeting a unique π-π-π stacking interaction at the proteins’ Kcr recognition site. Further structure optimization resulted in the selective inhibitors preferentially binding to individual YEATS-containing proteins including AF9 and ENL with submicromolar affinities. We demonstrate that one of the ENL YEATS-selective inhibitors, XL-13m, engages with endogenous ENL, perturbs the recruitment of ENL onto chromatin, and synergizes the BET and DOT1L inhibition-induced downregulation of oncogenes in MLL-rearranged acute leukemia.

High-resolution measurements of electrons obtained by satellite during the geomagnetic storm of 9 October 2012 together with a data-driven global wave model are analysed to show that scattering by a magnetospheric electromagnetic emission, known as ‘chorus’, can explain the temporal evolution of the observed increase in relativistic electron flux. A local mechanism for magnetic storm A magnetic storm that occurred on 9 October 2012 has been analysed in detail using the array of instruments onboard NASA's two Van Allen probes, launched in August 2012 to study Earth's magnetosphere, including the Van Allen radiation belt. The nature of the force that accelerates electrons trapped in the radiation belts has been a topic of much debate centering on whether the electrons are accelerated locally or by radial diffusive transport between weak and strong magnetic fields. Initial results had favoured a local mechanism and now Richard Thorne et al . report high-resolution electron observations from Van Allen probe A, together with modelling studies that identify the likely source of accelerating energy as chorus scattering, an effect caused locally by structured wave formations. This powerful local acceleration is also likely to be a factor around Jupiter, Saturn and other bodies with significant magnetic fields. Recent analysis of satellite data obtained during the 9 October 2012 geomagnetic storm identified the development of peaks in electron phase space density 1 , which are compelling evidence for local electron acceleration in the heart of the outer radiation belt 2 , 3 , but are inconsistent with acceleration by inward radial diffusive transport 4 , 5 . However, the precise physical mechanism responsible for the acceleration on 9 October was not identified. Previous modelling has indicated that a magnetospheric electromagnetic emission known as chorus could be a potential candidate for local electron acceleration 6 , 7 , 8 , 9 , 10 , but a definitive resolution of the importance of chorus for radiation-belt acceleration was not possible because of limitations in the energy range and resolution of previous electron observations and the lack of a dynamic global wave model. Here we report high-resolution electron observations 11 obtained during the 9 October storm and demonstrate, using a two-dimensional simulation performed with a recently developed time-varying data-driven model 12 , that chorus scattering explains the temporal evolution of both the energy and angular distribution of the observed relativistic electron flux increase. Our detailed modelling demonstrates the remarkable efficiency of wave acceleration in the Earth’s outer radiation belt, and the results presented have potential application to Jupiter, Saturn and other magnetized astrophysical objects.

Accurate repair of DNA double-stranded breaks by homologous recombination preserves genome integrity and inhibits tumorigenesis. Cyclic GMP–AMP synthase (cGAS) is a cytosolic DNA sensor that activates innate immunity by initiating the STING–IRF3–type I IFN signalling cascade 1 , 2 . Recognition of ruptured micronuclei by cGAS links genome instability to the innate immune response 3 , 4 , but the potential involvement of cGAS in DNA repair remains unknown. Here we demonstrate that cGAS inhibits homologous recombination in mouse and human models. DNA damage induces nuclear translocation of cGAS in a manner that is dependent on importin-α, and the phosphorylation of cGAS at tyrosine 215—mediated by B-lymphoid tyrosine kinase—facilitates the cytosolic retention of cGAS. In the nucleus, cGAS is recruited to double-stranded breaks and interacts with PARP1 via poly(ADP-ribose). The cGAS–PARP1 interaction impedes the formation of the PARP1–Timeless complex, and thereby suppresses homologous recombination. We show that knockdown of cGAS suppresses DNA damage and inhibits tumour growth both in vitro and in vivo. We conclude that nuclear cGAS suppresses homologous-recombination-mediated repair and promotes tumour growth, and that cGAS therefore represents a potential target for cancer prevention and therapy. DNA damage induces translocation of cyclic GMP–AMP synthase to the nucleus, where it suppresses homologous recombination by interfering with the formation of the PARP1–Timeless complex.

As a well-known phosphatized Lagerstätte, the Ediacaran Weng'an biota in central Guizhou Province of South China contains diverse acanthomorphic acritarchs, algal thalli, tubular microfossils as well as various spheroidal fossils. These fossils provide crucial palaeontological evidence for the radiation of multicellular eukaryotes after the termination of the Neoproterozoic global glaciation. While the Weng'an biota is generally considered as early Ediacaran in age on the basis of phosphorite Pb–Pb isochron ages ranging from 572 Ma to 599 Ma, the reliability and accuracy of these age data have been questioned and some geologists have proposed that the Weng'an biota may be younger than 580 Ma instead. Here we report a SIMS zircon U–Pb age of 609 ± 5 Ma for a tuffaceous bed immediately above the upper phosphorite unit in the Doushantuo Formation at Zhangcunping, Yichang, South China. Litho-, bio- and chemostratigraphic correlations suggest that the upper phosphorite unit at Zhangcunping can be well correlated with the upper phosphorite unit at Weng'an, which is the main horizon of the Weng'an biota. We therefore conclude that the Weng'an biota could be as old as 609 ± 5 Ma.

Bacterial multidrug resistance poses an urgent challenge for the treatment of critically ill patients developing ventilator-associated pneumonia (VAP). Phage therapy, a potential alternative when conventional antibiotics fail, has been unsuccessful in first clinical trials when used alone. Whether combining antibiotics with phages may enhance effectiveness remains to be tested in experimental models. Here, we use a murine model of Pseudomonas -induced VAP to compare the efficacy of adjunctive phage cocktail for antibiotic therapy to either meropenem or phages alone. Combined treatment in murine VAP results in faster clinical improvement and prevents lung epithelial cell damage. Using human primary epithelial cells to dissect these synergistic effects, we find that adjunctive phage therapy reduces the minimum effective concentration of meropenem and prevents resistance development against both treatments. These findings suggest adjunctive phage therapy represents a promising treatment for MDR-induced VAP, enhancing the effectiveness of both antibiotics and phages while reducing adverse effects. Multidrug-resistant pathogens have become increasingly common in hospital settings. Here, the authors investigate the efficacy of adjunctive antibiotic and phage therapy in a human cell model and a murine model of ventilator-associated pneumonia.

Pulmonary involvement occurs in up to 95% of sarcoidosis cases. In this pilot study, we examine lung compartment-specific protein expression to identify pathways linked to development and progression of pulmonary sarcoidosis. We characterized bronchoalveolar lavage (BAL) cells and fluid (BALF) proteins in recently diagnosed sarcoidosis cases. We identified 4,306 proteins in BAL cells, of which 272 proteins were differentially expressed in sarcoidosis compared to controls. These proteins map to novel pathways such as integrin-linked kinase and IL-8 signaling and previously implicated pathways in sarcoidosis, including phagosome maturation, clathrin-mediated endocytic signaling and redox balance. In the BALF, the differentially expressed proteins map to several pathways identified in the BAL cells. The differentially expressed BALF proteins also map to aryl hydrocarbon signaling, communication between innate and adaptive immune response, integrin, PTEN and phospholipase C signaling, serotonin and tryptophan metabolism, autophagy, and B cell receptor signaling. Additional pathways that were different between progressive and non-progressive sarcoidosis in the BALF included CD28 signaling and PFKFB4 signaling. Our studies demonstrate the power of contemporary proteomics to reveal novel mechanisms operational in sarcoidosis. Application of our workflows in well-phenotyped large cohorts maybe beneficial to identify biomarkers for diagnosis and prognosis and therapeutically tenable molecular mechanisms.