Grass carp (Ctenopharyngodon idellus) SHP2 suppresses IFN I expression via decreasing the phosphorylation of GSK3ß in a non-contact manner.

As a tyrosine phosphatase, Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) serves as an inhibitor in PI3K-Akt pathway. In mammals, SHP2 can phosphorylate GSK3ß at Y216 site to control the expression of IFN. So far, the multiple functions of SHP2 have been reported in mammals. However, little is known about fish SHP2. In this study, we cloned and identified a grass carp (Ctenopharyngodon idellus) SHP2 gene (CiSHP2, MT373151). SHP2 is conserved among different vertebrates by amino acid sequences alignment and the phylogenetic tree analysis. CiSHP2 shared the closest homology with Danio rerio SHP2. Simultaneously, SHP2 was also tested in grass carp tissues and CIK (C. idellus kidney) cells. We found that it responded to poly I:C stimulation. CiSHP2 was located in the cytoplasm just as the same as those of mammals. Interestingly, it inhibited the phosphorylation level of GSK3ß in a non-contact manner. Meanwhile CiGSK3ß interacted with and directly phosphorylated CiTBK1. In addition, we found that CiSHP2 also reduced the phosphorylation level of CiTBK1 by CiGSK3ß, and then it depressed the expression of IFN I via GSK3ß-TBK1 axis. These results suggested that CiSHP2 was involved in CiGSK3ß and CiTBK1 activity but not regulated their transcriptional level. At the same time, we also found that CiSHP2 also influenced the activity of CiIRF3. Therefore, fish SHP2 inhibited IFN I expression through blocking GSK3ß-TBK1 signal axis.

Acid Erosion of Carbonate Fractures and Accessibility of Arsenic-Bearing Minerals: In Operando Synchrotron-Based Microfluidic Experiment.

Underground flows of acidic fluids through fractured rock can create new porosity and increase accessibility to hazardous trace elements such as arsenic. In this study, we developed a custom microfluidic cell for an in operando synchrotron experiment using X-ray attenuation. The experiment mimics reactive fracture flow by passing an acidic fluid over a surface of mineralogically heterogeneous rock from the Eagle Ford shale. Over 48 h, calcite was preferentially dissolved, forming an altered layer 200-500 µm thick with a porosity of 63-68% and surface area >10× higher than that in the unreacted shale as shown by xCT analyses. Calcite dissolution rate quantified from the attenuation data was 3 × 10-4 mol/m2s and decreased to 3 × 10-5 mol/m2s after 24 h because of increasing diffusion limitations. Erosion of the fracture surface increased access to iron-rich minerals, thereby increasing access to toxic metals such as arsenic. Quantification using XRF and XANES microspectroscopy indicated up to 0.5 wt % of As(-I) in arsenopyrite and 1.2 wt % of As(V) associated with ferrihydrite. This study provides valuable contributions for understanding and predicting fracture alteration and changes to the mobilization potential of hazardous metals and metalloids.

Dietary conjugated linoleic acid modulates morphology, selective immune parameters, and gene expressions in the intestine of grass carp.

Conjugated linoleic acid (CLA) has been shown to exhibit anti-inflammatory properties in the intestine in mammals. However, the effect of CLA on intestinal immune response in fish is still unknown. Therefore, a 65-day growth trial was conducted to investigate the effects of dietary conjugated linoleic acid (CLA) on morphology, selective immune parameters, and gene expressions in the intestine of grass carp. Seven isonitrogenous and isolipidic diets were formulated as follows: 0 (control), 0.5 (CLA0.5), 1 (CLA1), 1.5 (CLA1.5), 2 (CLA2), 2.5 (CLA2.5), and 3 (CLA3) g CLA per 100g of feed. RESULTS: showed that dietary supplementation of 1.5-3% CLA significantly (P < 0.05) increased the fold and enterocyte heights in the PI and MI of grass carp. Complement 3 (C3) and immunoglobulin M (IgM) contents in three intestinal segments were significantly (P < 0.05) higher in fish fed with CLA1.5 to CLA2.5 diets compared to fish fed the control diet. CLA1.5 to CLA2.5 diets significantly (P < 0.05) increased the mRNA expression levels of anti-inflammatory cytokines (IL-10 and TGFß1) and significantly (P < 0.05) reduced the mRNA expression levels of pro-inflammatory cytokines (IL-1ß, IL-8, and TNF-α) in the PI, MI, and DI. This improved expression of anti-inflammatory cytokines and the inhibited expression of pro-inflammatory cytokines in the intestine of grass carp, might be mediated via TLR4/NF-κB-signaling pathway. Our results suggested that CLA1.5 to CLA2 diets improved intestinal morphology, increased the expression of anti-inflammatory cytokines, and inhibited the expression of pro-inflammatory cytokines in the intestine of grass carp. In conclusion, dietary supplementation of 1.5%-2% CLA show the anti-inflammatory therapeutic potential in the intestine of grass carp. The anti-inflammatory therapeutic potential of CLA might be mediated via TLR4/NF-κB-signaling pathway.

Reactive Transport Simulation of Fracture Channelization and Transmissivity Evolution.

Underground fractures serve as flow conduits, and they may produce unwanted migration of water and other fluids in the subsurface. An example is the migration and leakage of greenhouse gases in the context of geologic carbon sequestration. This study has generated new understanding about how acids erode carbonate fracture surfaces and the positive feedback between reaction and flow. A two-dimensional reactive transport model was developed and used to investigate the extent to which geochemical factors influence fracture permeability and transmissivity evolution in carbonate rocks. The only mineral modeled as reactive is calcite, a fast-reacting mineral that is abundant in subsurface formations. The X-ray computed tomography dataset from a previous experimental study of fractured cores exposed to carbonic acid served as a testbed to benchmark the model simulation results. The model was able to capture not only erosion of fracture surfaces but also the specific phenomenon of channelization, which produces accelerating transmissivity increase. Results corroborated experimental findings that higher reactivity of the influent solution leads to strong channelization without substantial mineral dissolution. Simulations using mineral maps of calcite in a specimen of Amherstburg limestone demonstrated that mineral heterogeneity can either facilitate or suppress the development of flow channels depending on the spatial patterns of reactive mineral. In these cases, fracture transmissivity may increase rapidly, increase slowly, or stay constant, and for all these possibilities, the calcite mineral continues to dissolve. Collectively, these results illustrate that fluid chemistry and mineral spatial patterns need to be considered in predictions of reaction-induced fracture alteration and risks of fluid migration.

Comparative analysis of cytokinin response factors in Brassica diploids and amphidiploids and insights into the evolution of Brassica species.

BACKGROUND: Cytokinin is a classical phytohormone that plays important roles in numerous plant growth and development processes. In plants, cytokinin signals are transduced by a two-component system, which involves many genes, including cytokinin response factors (CRFs). Although CRFs take vital part in the growth of Arabidopsis thaliana and Solanum lycopersicum, little information of the CRFs in the Brassica U-triangle species has been known yet. RESULTS: We identified and compared 141 CRFs in the diploids and amphidiploids of Brassica species, including B. rapa, B. oleracea, B. nigra, B. napus, and B. juncea. For all the 141 CRFs, the sequence and structure analysis, physiological and biochemical characteristics analysis were performed. Meanwhile, the Ka/Ks ratios of orthologous and paralogous gene pairs were calculated, which indicated the natural selective pressure upon the overall length or a certain part of the CRFs. The expression profiles of CRFs in different tissues and under various stresses were analyzed in B. oleracea, B. nigra, and B. napus. The similarities and differences in gene sequences and expression profiles among the homologous genes of these species were discussed. In addition, AtCRF11 and its ortholog BrCRF11a were identified to be related to primary root growth in Arabidopsis. CONCLUSION: This study performed a genome-wide comparative analysis of the CRFs in the diploids and amphidiploids of the Brassica U-triangle species. Many similarities and differences in gene sequences and expression profiles existed among the CRF homologous genes of these species. In the bioinformatics analysis, we found the close relativity of the CRF homologous genes in the Brassica A and C genomes and the distinctiveness of those in the B genome, and the CRF homologous genes in B subgenome were considerably influenced by the A subgenome of B. juncea. In addition, we identified a new function of the Clade V CRFs related to root growth, which also clarified the functional conservation between Arabidopsis and B. rapa. These results not only offer useful information on the functional analysis of CRFs but also provide new insights into the evolution of Brassica species.

Alteration and Erosion of Rock Matrix Bordering a Carbonate-Rich Shale Fracture.

A novel reactive transport model has been developed to examine the processes that affect fracture evolution in a carbonate-rich shale. An in situ synchrotron X-ray microtomography experiment, flowing CO2 saturated water through a single fracture mini-core of Niobrara Shale provided the experimental observations for the development and testing of the model. The phenomena observed included the development of a porous altered layer, flow channeling, and increasingly limited calcite dissolution. The experimental observations cannot be explained by models that consider only mineral dissolution and development of an altered layer. The difference between the fracture volume change recorded by the microtomography images and what would be expected from mineral dissolution alone suggest that there is erosion of the altered layer as it develops. The numerical model includes this additional mechanism, with the erosion rate based on the thickness of the altered layer, and successfully captures the evolution of the geochemical reactions and morphology of the fracture. The findings imply that the abundance (with a threshold of approximately 35%) and reactivity of the rapidly reacting mineral control the development and erodibility of the altered layer on the fracture surfaces, and therefore fracture opening.

Replacement of fish oil with soybean oil in diets for juvenile Chinese sucker (Myxocyprinus asiaticus): effects on liver lipid peroxidation and biochemical composition.

This study was designed to evaluate the effect of the replacement of fish oil (FO) by soybean oil (SO) on growth performance, liver lipid peroxidation, and biochemical composition in juvenile Chinese sucker, Myxocyprinus asiaticus. Fish (13.7 ± 0.2 g) in triplicate were fed five experimental diets in which 0% (FO as control), 40% (SO40), 60% (SO60), 80% (SO40), and 100% (SO100) FO were replaced by SO. The body weight gain of fish fed SO40, SO60, or SO80 diet was similar to FO group, but diets that have 100% soybean oil as dietary lipid significantly reduced fish growth (P < 0.05). Although the level of SO resulted in increasing crude lipid content of the liver, the level of SO did not significantly alter the hepatosomatic index (HSI). Indicators of peroxidation, such as vitamin E (VE) and thiobarbituric acid-reactive substance (TBARS) contents, were changed as increasing dietary SO. It was shown that the inclusion of SO in the diets increased VE concentrations, but reduced TBARS in the liver and total cholesterol (T-CHO) in the plasma. Linoleic acid (LA) and linolenic acid (LNA) significantly increased in fish liver fed diets that contained SO, but eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and the ratio n-3/n-6 were significantly reduced by the inclusion of dietary SO (P < 0.05). Our results indicated that the inclusion of SO increased the hepatic VE content and reduced lipid peroxidation in fish. However, diet containing 100% SO as dietary lipid could reduce growth performance. Thus, we recommended that 40-80% SO can be used as dietary lipid to replace FO for juvenile Chinese sucker.

A 2.5D Reactive Transport Model for Fracture Alteration Simulation.

Understanding fracture alteration resulting from geochemical reactions is critical in predicting fluid migration in the subsurface and is relevant to multiple environmental challenges. Here, we present a novel 2.5D continuum reactive transport model that captures and predicts the spatial pattern of fracture aperture change and the development of an altered layer in the near-fracture region. The model considers permeability heterogeneity in the fracture plane and updates fracture apertures and flow fields based on local reactions. It tracks the reaction front of each mineral phase and calculates the thickness of the altered layer. Given this treatment, the model is able to account for the diffusion limitation on reaction rates associated with the altered layer. The model results are in good agreement with an experimental study in which a CO2-acidified brine was injected into a fracture in the Duperow Dolomite, causing dissolution of calcite and dolomite that result in the formation of a preferential flow channel and an altered layer. With an effective diffusion coefficient consistent with the experimentally observed porosity of the altered layer, the model captures the progressive decrease in the dissolution rate of the fast-reacting mineral in the altered layer.

The Leakage Risk Monetization Model for Geologic CO2 Storage.

We developed the Leakage Risk Monetization Model (LRiMM) which integrates simulation of CO2 leakage from geologic CO2 storage reservoirs with estimation of monetized leakage risk (MLR). Using geospatial data, LRiMM quantifies financial responsibility if leaked CO2 or brine interferes with subsurface resources, and estimates the MLR reduction achievable by remediating leaks. We demonstrate LRiMM with simulations of 30 years of injection into the Mt. Simon sandstone at two locations that differ primarily in their proximity to existing wells that could be leakage pathways. The peak MLR for the site nearest the leakage pathways ($7.5/tCO2) was 190x larger than for the farther injection site, illustrating how careful siting would minimize MLR in heavily used sedimentary basins. Our MLR projections are at least an order of magnitude below overall CO2 storage costs at well-sited locations, but some stakeholders may incur substantial costs. Reliable methods to detect and remediate leaks could further minimize MLR. For both sites, the risk of CO2 migrating to potable aquifers or reaching the atmosphere was negligible due to secondary trapping, whereby multiple impervious sedimentary layers trap CO2 that has leaked through the primary seal of the storage formation.

The Cu/ligand stoichiometry effect on the coordination behavior of aroyl hydrazone with copper(II): Structure, anticancer activity and anticancer mechanism.

In an effort to better understand the biological efficacy of the tridentate aroyl hydrazone Cu(II) complexes, three Cu(II) complexes of acetylpyridine benzoyl hydrazone (HL), [Cu(L)(NO3) (H2O)]·H2O (C1), [Cu(L)2] (C2) and [Cu(L)(HL)]·(NO3)(Sas) (C3) (Sas=salicylic acid) were synthesized and characterized. X-ray crystal structures and infrared (IR) spectra of the complexes reveal that the L(-) ligand of C1 and C2 are predominantly in the enolate resonance form, while one L(-) ligand in C3 is represented enolate resonance form and the other HL ligand exhibits keto resonance form. All Cu(II) complexes showed significantly more anticancer activity than the ligand alone. Interestingly, the Cu complexes where the ligand/metal ratio was 1:1 (C1) rather than 2:1 (C2 and C3) had higher antitumor efficacy. Moreover, the 1:1 Cu/ligand complex, C1, promotes A549 cell apoptosis possibly through the intrinsic reactive oxygen species (ROS) mediated mitochondrial pathway, accompanied by the regulation of Bcl-2 family proteins.

Synthesis of Dipyridyl Ketone Isonicotinoyl Hydrazone Copper(II) Complex: Structure, Anticancer Activity and Anticancer Mechanism.

In an effort to better understand the biological efficacy of the tridentate aroyl hydrazone Cu(II) complexes, the Cu(II) complex of di-2-pyridyl ketone isonicotinoyl hydrazone ligand (HL), {[Cu(L)(H2O)]·H2O·NO3}n (C1) was synthesized and characterized. Single crystal X-ray study reveals that complex C1 forms 1D zigzag chains in solid state. In water, the hydrolysis of the 1D zigzag chains was observed, and finally formation of monomeric species. In vitro studies revealed that complex C1 showed significantly more anticancer activity than the ligand alone. Investigation of the anticancer mechanisms of C1, confirmed that the Cu(II) complex exhibit a strong capacity to promote productions of reactive oxygen species (ROS), leading to caspase-dependent apoptotic cell death.

Alterations of Fractures in Carbonate Rocks by CO2-Acidified Brines.

Fractures in geological formations may enable migration of environmentally relevant fluids, as in leakage of CO2 through caprocks in geologic carbon sequestration. We investigated geochemically induced alterations of fracture geometry in Indiana Limestone specimens. Experiments were the first of their kind, with periodic high-resolution imaging using X-ray computed tomography (xCT) scanning while maintaining high pore pressure (100 bar). We studied two CO2-acidified brines having the same pH (3.3) and comparable thermodynamic disequilibrium but different equilibrated pressures of CO2 (PCO2 values of 12 and 77 bar). High-PCO2 brine has a faster calcite dissolution kinetic rate because of the accelerating effect of carbonic acid. Contrary to expectations, dissolution extents were comparable in the two experiments. However, progressive xCT images revealed extensive channelization for high PCO2, explained by strong positive feedback between ongoing flow and reaction. The pronounced channel increasingly directed flow to a small region of the fracture, which explains why the overall dissolution was lower than expected. Despite this, flow simulations revealed large increases in permeability in the high-PCO2 experiment. This study shows that the permeability evolution of dissolving fractures will be larger for faster-reacting fluids. The overall mechanism is not because more rock dissolves, as would be commonly assumed, but because of accelerated fracture channelization.

Conjugated linoleic acid alters growth performance, tissue lipid deposition, and fatty acid composition of darkbarbel catfish (Pelteobagrus vachelli).

Fatty liver syndrome is a prevalent problem of farmed fish. Conjugated linoleic acid (CLA) has received increased attention recently as a fat-reducing fatty acid to control fat deposition in mammals. Therefore, the aim of the present study was to determine whether dietary CLA can reduce tissue lipid content of darkbarbel catfish (Pelteobagrus vachelli) and whether decreased lipid content is partially due to alterations in lipid metabolism enzyme activities and fatty acid profiles. A 76-day feeding trial was conducted to investigate the effect of dietary CLA on the growth, tissue lipid deposition, and fatty acid composition of darkbarbel catfish. Five diets containing 0 % (control), 0.5 % (CLA0.5), 1 % (CLA1), 2 % (CLA2), and 3 % (CLA3) CLA levels were evaluated. Results showed that fish fed with 2-3 % CLA diets showed a significantly lower specific growth rate and feed conversion efficiency than those fed with the control diet. Dietary CLA decreased the lipid contents in the liver and intraperitoneal fat with the CLA levels from 1 to 3 %. Fish fed with 2-3 % CLA diets showed significantly higher lipoprotein lipase and hepatic triacylglycerol lipase activities in liver than those of fish fed with the control, and fish fed with 1-3 % CLA diets had significantly higher pancreatic triacylglycerol lipase activities in liver than those of fish fed with the control. Dietary CLA was incorporated into liver, intraperitoneal fat, and muscle lipids, with higher percentages observed in liver compared with other tissues. Liver CLA deposition was at the expense of monounsaturated fatty acids (MUFA). In contrast, CLA deposition appeared to be primarily at the expense of MUFA and n-3 polyunsaturated fatty acids (PUFA) in the intraperitoneal fat, whereas in muscle it was at the expense of n-3 PUFA. Our results suggested that CLA at a 1 % dose can reduce liver lipid content without eliciting any negative effect on growth rate in darkbarbel catfish. This lipid-lowering effect could be in part due to an increment in the activity of lipid metabolism enzymes and an extensive interconversion of fatty acids. Although CLA deposition in muscle (0.66-3.19 % of total fatty acids) are higher than presented in natural sources of CLA, EPA (C20:5n-3) in fish muscle appears simultaneously expendable, when the fish fed with 2-3 % CLA.

Association of sleep traits with male fertility: a two-sample Mendelian randomization study.

Background: Previous observational studies have investigated the association between sleep-related traits and male fertility; however, conclusive evidence of a causal connection is lacking. This study aimed to explore the causal relationship between sleep and male fertility using Mendelian randomisation. Methods: Eight sleep-related traits (chronotype, sleep duration, insomnia, snoring, dozing, daytime nap, oversleeping, and undersleeping) and three descriptors representing male fertility (male infertility, abnormal sperm, and bioavailable testosterone levels) were selected from published Genome-Wide Association Studies. The causal relationship between sleep-related traits and male fertility was evaluated using multiple methods, including inverse variance weighting (IVW), weighted median, Mendelian randomisation-Egger, weighted model, and simple model through two-sample Mendelian randomisation analysis. Mendelian randomisation-Egger regression was used to assess pleiotropy, Cochrane's Q test was employed to detect heterogeneity, and a leave-one-out sensitivity analysis was conducted. Results: Genetically-predicted chronotype (IVW,OR = 1.07; 95%CL = 1.04-1.12; p = 0.0002) was suggestively associated with bioavailable testosterone levels. However, using the IVW method, we found no evidence of a causal association between other sleep traits and male fertility. Conclusion: This study found that chronotype affects testosterone secretion levels. However, further studies are needed to explain this mechanism.

Synthesis of disulfides and diselenides by copper-catalyzed coupling reactions in water.

A simple and efficient protocol for copper-catalyzed coupling reactions between aryl halides and elemental sulfur or selenium has been developed. A variety of disulfides and diselenides can be obtained in moderate to excellent yields up to 96%.

The environmental controls on efficiency of enhanced rock weathering in soils.

Enhanced rock weathering (ERW) in soils is a promising carbon removal technology, but the realistically achievable efficiency, controlled primarily by in situ weathering rates of the applied rocks, is highly uncertain. Here we explored the impacts of coupled biogeochemical and transport processes and a set of primary environmental and operational controls, using forsterite as a proxy mineral in soils and a multiphase multi-component reactive transport model considering microbe-mediated reactions. For a onetime forsterite application of ~ 16 kg/m2, complete weathering within five years can be achieved, giving an equivalent carbon removal rate of ~ 2.3 kgCO2/m2/yr. However, the rate is highly variable based on site-specific conditions. We showed that the in situ weathering rate can be enhanced by conditions and operations that maintain high CO2 availability via effective transport of atmospheric CO2 (e.g. in well-drained soils) and/or sufficient biogenic CO2 supply (e.g. stimulated plant-microbe processes). Our results further highlight that the effect of increasing surface area on weathering rate can be significant-so that the energy penalty of reducing the grain size may be justified-only when CO2 supply is nonlimiting. Therefore, for ERW practices to be effective, siting and engineering design (e.g. optimal grain size) need to be co-optimized.

Cu-catalyzed three-component synthesis of substituted benzothiazoles in water.

Three in one: Copper-catalyzed three-component reactions, involving 2-iodoanilines, aldehydes, and sulfur powder, afford 2-phenylbenzothiazoles in water. A variety of 2-substituted benzothiazoles can be obtained in good to excellent yields of up to 96 % (see scheme).

[Influence of different extracts from persimmon leaves on the antioxidant activity in diabetic mice].

OBJECTIVE: To investigate the antioxidant effect of different solvent extracts from persimmon leaves (PL) in diabetic mice induced by streptozotocin (STZ). METHODS: The total ethanol-extracted fraction of PL was further extracted with chloroform, ethyl acetate and n-butanol, in that order, the residues after ethanol extraction were water-extracted and alcohol-precipitated, and concentrated. The hypoglycemic effects of different solvents extracts from PL were evaluated in diabetic mice induced by STZ. The experimental mice were randomly divided into groups: control group, model group, glibenclamide group, low and high dosage groups of the various solvent extracts. The drugs were administrated to mice in every morning for 15 days. During this time period, the contents of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined. RESULTS: The water-extracted and ethanol-precipitated fractions and the ethyl acetate-extracted fraction markedly reduced the content of MDA and increased the activity of SOD in the livers of STZ-induced diabetic mice (P<0.01 or P<0.05). The chloroform-extracted and n-butanol-extracted fraction did not markedly reduce the content of MDA nor increase the activity of SOD in liver of STZ-induced diabetic mice (P>0.05). CONCLUSION: The ethyl acetate-extracted fraction, water-extracted and ethanol-precipitated fraction of persimmon leaves have potential value in the treatment of diabetes. The mechanism of action of the antioxidant is related to the hypoglycemic effects of extracts from persimmon leaves.