Toward a generic analytical framework for sustainable nitrogen management: application for China

Managing reactive nitrogen (Nr) to achieve a sustainable balance between production of food, feed and fiber, and environmental protection is a grand challenge in the context of an increasingly affluent society. Here, we propose a novel framework for national nitrogen (N) assessments enabling a more consistent comparison of the uses, losses and impacts of Nr between countries, and improvement of Nr management for sustainable development at national and regional scales. This framework includes four key components: national scale N budgets, validation of N fluxes, cost-benefit analysis and Nr management strategies. We identify four critical factors for Nr management to achieve the sustainable development goals: N use efficiency (NUE), Nr recycling ratio (e.g., ratio of livestock excretion applied to cropland), human dietary patterns and food waste ratio. This framework was partly adopted from the European Nitrogen Assessment and now is successfully applied to China, where it contributed to trigger policy interventions toward improvements for future sustainable use of Nr. We demonstrate how other countries can also benefit from the application our framework, in order to include sustainable Nr management under future challenges of growing population, hence contributing to the achievement of some key sustainable development goals (SDGs)

DNA Methylation and Gene Expression of Matrix Metalloproteinase 9 Gene in Deficit and Non-deficit Schizophrenia

The biological pathology of deficit schizophrenia (DS) remains unclear. Matrix metalloproteinase 9 (MMP9) might be associated with neural plasticity and glutamate regulation, involved in schizophrenia pathogenesis. This study explores gene expression and DNA methylation of MMP9 in peripheral blood mononuclear cells (PBMCs) and their relationship with clinical symptoms in DS and non-deficit schizophrenia (NDS). Pyrosequencing was used to determine DNA methylation at CpG sites in exon 4 and exon 5 of MMP9 in 51 DS patients, 53 NDS patients and 50 healthy subjects (HC). RT-qPCR was used to detect MMP9 expression. Clinical symptoms were assessed by BPRS, SANS and SAPS scales. MMP9 expression in PBMCs was significantly higher in DS than NDS and HC subjects. Compared to NDS patients, DS patients had significantly lower DNA methylation at individual CpG sites in exon 4 and exon 5 of MMP9. Correlation analysis showed that DNA methylation in exon 4 was negatively correlated with gene expression in DS group. Positive correlation was found between MMP9 expression and negative symptoms in total schizophrenic patients. The social amotivation factor of SANS and negative syndrome of BPRS was negatively correlated with DNA methylation of CpG5-1 in DS patients but not in NDS patients. DS patients showed a specific abnormality of peripheral MMP9 expression and DNA methylation, indicating a pathological mechanism underlying DS as a specific subgroup of schizophrenia

A Normalized Hysteretic Energy Spectrum for Energy-Based Seismic Design

To disclose the impacts of hysteretic energy (HE) demand on energy-based seismic design, this paper introduces the dimensionless parameter βEH to express the cumulative HE indirectly and establishes the βEH spectrum for energy-based seismic design. After analyzing numerous seismic responses of a single degree-of-freedom (SDOF) system, the author set up a simplified βEH spectral formula based on the genetic algorithm. Then, 750 ground motion records were selected according to Chinese site classification, and used to examine the effects of soil type and damping ratio on the βEH spectra. The results show that the soil type, site group and damping ratio have significant effects on the βEH spectra; the ductility ratio has an impact on the spectral value but not the spectral shape

Concentration Prediction of Polymer Insulation Aging Indicator-Alcohols in Oil Based on Genetic Algorithm-Optimized Support Vector Machines

The predictive model of aging indicator based on intelligent algorithms has become an auxiliary method for the aging condition of transformer polymer insulation. However, most of the current research on the concentration prediction of aging products focuses on dissolved gases in oil, and the concentration prediction of alcohols in oil is ignored. As new types of aging indicators, alcohols (methanol, ethanol) are becoming prevalent in the aging evaluation of transformer polymer insulation. To address this, this study proposes a prediction model for the concentration of alcohols based on a genetic-algorithm-optimized support vector machine (GA-SVM). Firstly, accelerated thermal aging experiments on oil-paper insulation are conducted, and the concentration of alcohols is measured. Then, the data of the past 4 days of aging are used as the input feature of SVM, and the GA algorithm is utilized to optimize the kernel function parameter and penalty factor of SVM. Moreover, the concentrations of methanol and ethanol are predicted, after which the prediction accuracy of other algorithms and GA-SVM are compared. Finally, an industrial software program for predicting the concentration of methanol and ethanol is established. The results show that the mean square errors (MSE) of methanol and ethanol concentration predictions of the model proposed in this paper are 0.008 and 0.003, respectively. The prediction model proposed in this paper can track changes in methanol and ethanol concentrations well, providing a theoretical basis for the field of alcohol concentration prediction in transformer oil

Hematopoietic Stem Cell-Derived Exosomes Promote Hematopoietic Differentiation of Mouse Embryonic Stem Cells in Vitro via Inhibiting the mir126/notch1 Pathway

Cell-derived exosomes (EXs) can modulate target cell differentiation via microRNAs (miRs) that they carried. Previous studies have shown that miR126 is highly expressed in hematopoietic stem cells (HSCs) and plays a role in hematopoiesis via modulating the Notch pathway that participates in progenitors’ cell fate decisions. In this study we investigated whether HSC-derived EXs (HSCEXs) could affect the differentiation of mouse embryonic stem cells (ESCs) into HSCs. We prepared HSC-EXscon, HSC-EXssc and HSCEXsmiR126 from control HSCs and the HSCs transfected with scramble control or miR126 mimics, respectively. HSC-EXs were isolated by ultracentrifugation and analyzed using nanoparticle tracking analysis. We incubated the collected EXs with mouse ESCs over a 10-d differentiation induction period, during which HSC-EXs and a Notch pathway activator (Jagged1, 100 ng/mL) were added to the cultures every 3 d. After the 10-d differentiation period, the expression levels of miR126, SSEA1, CD117, Sca1, Notch1 and Hes1 in ESCs were assessed. The generated HSCs were validated by flow cytometry using antibodies against HSC markers (CD117, CD34 and Sca1). Our results revealed that: (1) transfection with miR126 mimics significantly increased miR126 levels in HSC-EXsmiR126. (2) HSC-EX co-culture promoted mouse ESCs differentiation into HSCs with the most prominent effect found in the HSC-EXsmiR126 co-culture. (3) HSC differentiation was verified by reduced SSEA1 expression and increased CD117 and Sca1 expression. (4) All the effects caused by HSCEXs were accompanied by significant reduction of Notch1 and Hes1 expression, thus inhibition of the Notch1/Hes1 pathway, whereas activation of Notch by Jagged1 abolished the effects of HSC-EXsmiR126. In conclusion, HSC-EXs promote hematopoietic differentiation of mouse ESCs in vitro by inhibiting the miR126/Notch1 pathway

Hematopoietic Stem Cell-Derived Exosomes Promote Hematopoietic Differentiation of Mouse Embryonic Stem Cells In Vitro via Inhibiting the miR126/Notch1 Pathway

Cell-derived exosomes (EXs) can modulate target cell differentiation via microRNAs (miRs) that they carried. Previous studies have shown that miR126 is highly expressed in hematopoietic stem cells (HSCs) and plays a role in hematopoiesis via modulating the Notch pathway that participates in progenitors\u27 cell fate decisions. In this study we investigated whether HSC-derived EXs (HSC-EXs) could affect the differentiation of mouse embryonic stem cells (ESCs) into HSCs. We prepared HSC-EXscon, HSC-EXssc and HSC-EXsmiR126 from control HSCs and the HSCs transfected with scramble control or miR126 mimics, respectively. HSC-EXs were isolated by ultracentrifugation and analyzed using nanoparticle tracking analysis. We incubated the collected EXs with mouse ESCs over a 10-d differentiation induction period, during which HSC-EXs and a Notch pathway activator (Jagged1, 100 ng/mL) were added to the cultures every 3 d. After the 10-d differentiation period, the expression levels of miR126, SSEA1, CD117, Sca1, Notch1 and Hes1 in ESCs were assessed. The generated HSCs were validated by flow cytometry using antibodies against HSC markers (CD117, CD34 and Sca1). Our results revealed that: (1) transfection with miR126 mimics significantly increased miR126 levels in HSC-EXsmiR126. (2) HSC-EX co-culture promoted mouse ESCs differentiation into HSCs with the most prominent effect found in the HSC-EXsmiR126 co-culture. (3) HSC differentiation was verified by reduced SSEA1 expression and increased CD117 and Sca1 expression. (4) All the effects caused by HSC-EXs were accompanied by significant reduction of Notch1 and Hes1 expression, thus inhibition of the Notch1/Hes1 pathway, whereas activation of Notch by Jagged1 abolished the effects of HSC-EXsmiR126. In conclusion, HSC-EXs promote hematopoietic differentiation of mouse ESCs in vitro by inhibiting the miR126/Notch1 pathway

Hematopoietic Stem Cell-Derived Exosomes Promote Hematopoietic Differentiation of Mouse Embryonic Stem Cells in Vitro via Inhibiting the mir126/notch1 Pathway

Cell-derived exosomes (EXs) can modulate target cell differentiation via microRNAs (miRs) that they carried. Previous studies have shown that miR126 is highly expressed in hematopoietic stem cells (HSCs) and plays a role in hematopoiesis via modulating the Notch pathway that participates in progenitors’ cell fate decisions. In this study we investigated whether HSC-derived EXs (HSCEXs) could affect the differentiation of mouse embryonic stem cells (ESCs) into HSCs. We prepared HSC-EXscon, HSC-EXssc and HSCEXsmiR126 from control HSCs and the HSCs transfected with scramble control or miR126 mimics, respectively. HSC-EXs were isolated by ultracentrifugation and analyzed using nanoparticle tracking analysis. We incubated the collected EXs with mouse ESCs over a 10-d differentiation induction period, during which HSC-EXs and a Notch pathway activator (Jagged1, 100 ng/mL) were added to the cultures every 3 d. After the 10-d differentiation period, the expression levels of miR126, SSEA1, CD117, Sca1, Notch1 and Hes1 in ESCs were assessed. The generated HSCs were validated by flow cytometry using antibodies against HSC markers (CD117, CD34 and Sca1). Our results revealed that: (1) transfection with miR126 mimics significantly increased miR126 levels in HSC-EXsmiR126. (2) HSC-EX co-culture promoted mouse ESCs differentiation into HSCs with the most prominent effect found in the HSC-EXsmiR126 co-culture. (3) HSC differentiation was verified by reduced SSEA1 expression and increased CD117 and Sca1 expression. (4) All the effects caused by HSCEXs were accompanied by significant reduction of Notch1 and Hes1 expression, thus inhibition of the Notch1/Hes1 pathway, whereas activation of Notch by Jagged1 abolished the effects of HSC-EXsmiR126. In conclusion, HSC-EXs promote hematopoietic differentiation of mouse ESCs in vitro by inhibiting the miR126/Notch1 pathway

Lipocalin 2 Upregulation Protects Hepatocytes from IL1-β-Induced Stress

Background: Lipocalin 2 (LCN2), a protein primarily produced by hepatocytes, is highly upregulated under various conditions that induce cellular stress, such as intoxication, infection or inflammation. However, the precise biological functions and underlying mechanisms of LCN2 in hepatocytes remains unknown. Methods: Hepatocyte stress was successfully induced by treating Huh7 cells with interleukin-1β (IL-1β). Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and LCN2 levels were measured in IL-1β treated Huh7 cells and supernatant. Additionally, microarray analysis was conducted to identify genes differentially expressed in LCN2-silenced and control Huh7 cells. Results: TNF-α, IL-6 and LCN2 were significantly elevated in Huh7 cells after IL-1β) treatment. In LCN2-silenced Huh7 cells, expression of IL-6 and TNF-α was significantly increased when compared with the expression levels of control Huh7 cells. Furthermore, differentially expressed genes were observed between the LCN2-silenced and control cells. Microarray analysis indicated that LCN2 acted by influencing genes involved in protein metabolism, stress response, cell cycle and proliferation. Conclusions: Our results suggest that LCN2 upregulation protects hepatocytes from IL-1β-induced stress. Additionally, our microarray analysis of LCN2-silenced and control cells provides a better understanding of the mechanisms that may be influenced by LCN2 induction