Urea Production Research Articles

Hepatic Polarization Accelerated by Mechanical Compaction Involves HNF4α Activation.

There remain few data about the role of homeostatic compaction in hepatic polarization. A previous study has found that mechanical compaction can accelerate hepatocyte polarization; however, the cellular mechanism underlying the effect is mostly unclear. Hepatocyte nuclear factor 4 alpha (HNF4α) is crucial for hepatic polarization in liver morphogenesis. Therefore, we sought to identify any possible involvement of HNF4α in the process of hepatocyte polarization accelerated by mechanical compaction. We first verified in the nonhepatic cell model HEK-293T, and the hepatic cell model primary hepatocytes that the mechanical compaction on cell aggregates simulated by using transient centrifugation can directly activate the expression of HNF4α promoters. Moreover, data using primary hepatocytes showed that the HNF4α expression is positively associated with the levels of compaction force: 2.1-folds higher at the mRNA level and 2.1-folds higher at the protein level for 500 g vs. 0 g. Furthermore, activated HNF4α expression is associated with the enhanced biliary canalicular formation and the increased production of albumin and urea. Pretreatment with Latrunculin B, an inhibitor of F-actin, and SHE78-7, an inhibitor of E-cadherin, which both interrupt the pathway of mechanical transduction, partially but significantly reduced the HNF4α expression and production of albumin and urea. In conclusion, HNF4α can be actively involved in the hepatic polarization in the context of environmental mechanical compaction.

Electrochemical urea production directly from N2 and CO2 in ambient aqueous media

Electrochemical urea production directly from N2 and CO2 in ambient aqueous media

Reducing the Formation of Secondary Pollutants in the Process of NonCatalytic Purification of Flue Gases from Nitrogen Oxides

The possibilities of the technology of non-catalytic reduction of nitrogen oxides (SNCR) to reduce the possible formation of secondary pollutants: ammonia, carbon monoxide and nitric oxide (I) are considered. The conditions for the process of reduction of nitrogen oxides by the thermal decomposition products of urea with a minimum formation of the above pollutants are determined.

Generation of Scalable Hepatic Micro-Tissues as a Platform for Toxicological Studies.

Currently, there is an urgent need for scalable and reliable in vitro models to assess the effects of therapeutic entities on the human liver. Hepatoma cell lines, including Huh-7, show weakly resemblance to human hepatocytes, limiting their significance in toxicity studies. Co-culture of hepatic cells with non-parenchymal cells, and the presence of extracellular matrix have been shown to influence the biological behavior of hepatocytes. The aim of this study was to generate the scalable and functional hepatic micro-tissues (HMTs). The size-controllable HMTs were generated through co-culturing of Huh-7 cells by mesenchymal stem cells and human umbilical vein endothelial cells in a composite hydrogel of liver-derived extracellular matrix and alginate, using an air-driven droplet generator. The generated HMTs were functional throughout a culture period of 28days, as assessed by monitoring glycogen storage, uptake of low-density lipoprotein and indocyanine green. The HMTs also showed increased secretion levels of albumin, alpha-1-antitrypsin, and fibrinogen, and production of urea. Evaluating the expression of genes involved in hepatic-specific and drug metabolism functions indicated a significant improvement in HMTs compared to two-dimensional (2D) culture of Huh-7 cells. Moreover, in drug testing assessments, HMTs showed higher sensitivity to hepatotoxins compared to 2D cultured Huh-7 cells. Furthermore, induction and inhibition potency of cytochrome P450 enzymes confirmed that the HMTs can be used for in vitro drug screening. Overall, we developed a simple and scalable method for generation of liver micro-tissues, using Huh-7, with improved hepatic-specific functionality, which may represent a biologically relevant platform for drug studies.

Cystatin C and Sarcopenia Predict Acute on Chronic Liver Failure Development and Mortality in Patients on the Liver Transplant Waiting List.

Cystatin C (CysC) is an early biomarker of renal dysfunction scarcely studied in patients awaiting liver transplantation (LT). Sarcopenia is frequent in cirrhosis and impacts prognosis. We aimed to assess the capability of these factors to predict survival and acute-on-chronic liver failure (ACLF) in patients awaiting LT, as well as early post-LT outcomes. Single-center study that included all cirrhotic patients listed for LT between 2014 and 2017. Competing risk regression analysis was used to evaluate the capability of liver-, kidney-, and global status-related variables at waitlist (WL) inclusion to predict WL mortality and ACLF. Variables associated with post-LT outcomes were evaluated with logistic regression analysis. One-hundred-and-eighty patients were included. Fifty-six (31%) patients developed ACLF, 54 (30%) underwent LT and 35 (19%) died. In the adjusted competing risk regression analysis, CysC ≥ 1.5 mg/L, sarcopenia and MELD-Na were independent predictors of ACLF in the WL, while CysC ≥ 1.5 mg/L, sarcopenia and albumin were independent predictors of mortality. The cumulative incidence of ACLF and mortality at 12 months were 50% and 34% in patients with sarcopenia and CysC ≥1.5 mg/L. An estimated glomerular filtration rate by chronic kidney disease (CKD)-EPI-CysC-creatinine <60 mL/min/1.73 m at WL inclusion was an independent predictor of the need for renal replacement therapy (RRT) in the first month post-LT. Higher levels of CysC and sarcopenia are strongly associated with the ACLF and mortality in WL. The assessment of both risk factors may improve the prognostic evaluation and allow identifying a group of patients with a very high risk of poor outcomes while awaiting LT.

A mechanobiological mathematical model of liver metabolism

The liver plays a complex role in metabolism and detoxification, and better tools are needed to understand its function and to develop liver-targeted therapies. In this study, we establish a mechanobiological model of liver transport and hepatocyte biology to elucidate the metabolism of urea and albumin, the production/detoxification of ammonia, and consumption of oxygen and nutrients. Since hepatocellular shear stress (SS) can influence the enzymatic activities of liver, the effect of SS on the urea and albumin synthesis are empirically modeled through the mechanotransduction mechanisms. The results demonstrate that the rheology and dynamics of the sinusoid flow can significantly affect liver metabolism. We show that perfusate rheology and blood hematocrit can affect urea and albumin production by changing hepatocyte mechanosensitive metabolism. The model can also simulate enzymatic diseases of the liver such as hyperammonemia I, hyperammonemia II, hyperarginemia, citrollinemia, and argininosuccinicaciduria, which disrupt the urea metabolism and ammonia detoxification. The model is also able to predict how aggregate cultures of hepatocytes differ from single cell cultures. We conclude that in vitro perfusable devices for the study of liver metabolism or personalized medicine should be designed with similar morphology and fluid dynamics as patient liver tissue. This robust model can be adapted to any type of hepatocyte culture to determine how hepatocyte viability, functionality, and metabolism are influenced by liver pathologies and environmental conditions.

Energy and nitrogenous waste from glutamate/glutamine catabolism facilitates acute osmotic adjustment in non-neuroectodermal branchial cells

Maintenance of homeostasis is one of the most important physiological responses for animals upon osmotic perturbations. Ionocytes of branchial epithelia are the major cell types responsible for active ion transport, which is mediated by energy-consuming ion pumps (e.g., Na+-K+-ATPase, NKA) and secondary active transporters. Consequently, in addition to osmolyte adjustments, sufficient and immediate energy replenishment is essenttableial for acclimation to osmotic changes. In this study, we propose that glutamate/glutamine catabolism and trans-epithelial transport of nitrogenous waste may aid euryhaline teleosts Japanese medaka (Oryzias latipes) during acclimation to osmotic changes. Glutamate family amino acid contents in gills were increased by hyperosmotic challenge along an acclimation period of 72 hours. This change in amino acids was accompanied by a stimulation of putative glutamate/glutamine transporters (Eaats, Sat) and synthesis enzymes (Gls, Glul) that participate in regulating glutamate/glutamine cycling in branchial epithelia during acclimation to hyperosmotic conditions. In situ hybridization of glutaminase and glutamine synthetase in combination with immunocytochemistry demonstrate a partial colocalization of olgls1a and olgls2 but not olglul with Na+/K+-ATPase-rich ionocytes. Also for the glutamate and glutamine transporters colocalization with ionocytes was found for oleaat1, oleaat3, and olslc38a4, but not oleaat2. Morpholino knock-down of Sat decreased Na+ flux from the larval epithelium, demonstrating the importance of glutamate/glutamine transport in osmotic regulation. In addition to its role as an energy substrate, glutamate deamination produces NH4+, which may contribute to osmolyte production; genes encoding components of the urea production cycle, including carbamoyl phosphate synthetase (CPS) and ornithine transcarbamylase (OTC), were upregulated under hyperosmotic challenges. Based on these findings the present work demonstrates that the glutamate/glutamine cycle and subsequent transepithelial transport of nitrogenous waste in branchial epithelia represents an essential component for the maintenance of ionic homeostasis under a hyperosmotic challenge.

Development of immortalized human hepatocyte-like hybrid cells by fusion of multi-lineage progenitor cells with primary hepatocytes.

Human primary hepatocytes (PHs) are critical to studying liver functions, drug metabolism and toxicity. PHs isolated from livers that are unacceptable for transplantation have limited expansion and culture viability in vitro, in addition to rapidly deteriorating enzymatic functions. The unsuitability of immortalized hepato-carcinoma cell lines for this function has prompted studies to develop hepatocyte-like cells from alternative sources like ESC, iPS, and other stem cell types using differentiation protocols. This study describes a novel technique to produce expandable and functional hepatocyte-like cells from the fusion of an immortalized human umbilical cord blood derived cell line (E12 MLPC) to normal human primary hepatocytes. Multi-lineage progenitor cells (MLPC) comprise a small subset of mesenchymal-like cells isolated from human umbilical cord blood. MLPC are distinguishable from other mesenchymal-like cells by their extended expansion capacity (up to 80 cell doublings before senescence) and the ability to be differentiated into cells representative of endo-, meso- and ectodermal origins. Transfection of MLPC with the gene for telomerase reverse transcriptase (TERT) resulted in clonal cell lines that were capable of differentiation to different cellular outcomes while maintaining their functional immortality. A methodology for the development of immortalized hepatocyte-like hybrid cells by the in vitro fusion of human MLPC with normal human primary hepatocytes is reported. The resultant hybrid cells exhibited homology with hepatocytes by morphology, immunohistochemistry, urea and albumin production and gene expression. A medium that allows stable long-term expansion of hepatocyte-like fusion cells is described.

Differential nitric oxide induced by Mycobacterium bovis and BCG leading to dendritic cells apoptosis in a caspase dependent manner

Dendritic cells (DCs) are critical for both innate and adaptive immunity. Meanwhile, nitric oxide (NO) is a member of reactive nitrogen species (RNS) generally considered to play a key role in the bactericidal process in innate immunity against Mycobacterium tuberculosis complex infection. The present study therefore investigated the mechanism of NO production in murine DCs induced by Mycobacterium bovis (M.bovis) and its attenuated strain Bacillus Calmette-Guérin (BCG) infection. The expression of genes Slc7A1, Slc7A2, iNOS, and ArgI essential to NO synthesis was up-regulated in M.bovis/BCG infected DCs. IFN-γ addition further increased, while the iNOS inhibitor L-NMMA significantly inhibited their expression. Accordingly, the end products of arginine metabolism, NO and urea, were found to be significantly increased. In addition, BCG induced significantly higher levels of apoptosis in DCs compared to M.bovis shown by higher levels of DNA fragmentation using flow cytometry and release of mitochondrial Cytochrome C, and up-regulation of the genes caspase-3, caspase-8, caspase-9 and dffa critical to apoptosis by qRT-PCR detection and western blot analysis. Furthermore, IFN-γ increased, but L-NMMA decreased apoptosis of M.bovis/BCG infected DCs. In addition, mycobacterial intracellular survival was significantly reduced by IFN-γ treatment in BCG infected DCs, while slightly increased by L-NMMA treatment. Taken altogether, our data show that NO synthesis was differentially increased and associated with apoptosis in M.bovis/BCG infected DCs. These findings may significantly contribute to elucidate the pathogenesis of M.bovis.

In vitro Differentiation of Human TERT-Transfected Multi-Lineage Progenitor Cells (MLPC) into Immortalized Hepatocyte-Like Cells.

BackgroundResearch directed towards drug development, metabolism, and liver functions often utilize primary hepatocytes (PH) for preliminary in vitro studies. Variability in the in vitro functionality of PH and the unsuitability of hepatocarcinoma cells for these studies have driven researchers to look to ESC, iPS, and other stem cell types using differentiation protocols to provide more reliable and available cells. This study describes the development of hepatocyte-like cells through the in vitro differentiation of human TERT-immortalized cord blood-derived multi-lineage progenitor cells (MLPC). The E12 clonal cell line derived from polyclonal TERT-transfected cells was used throughout the study.MethodsE12 MLPC were subjected to a three-step differentiation protocol using alternating combinations of growth factors, cytokines, and maturational factors. Cells at various stages of differentiation were analyzed for consistency with PH by morphology, immunohistochemistry, urea production, and gene expression.ResultsE12 MLPC were shown to significantly change morphology with each stage of differentiation. Coincidental with the morphological changes in the cells, immunohistochemistry data documented the differentiation to committed endoderm by the expression of SOX-17 and GATA-4; the progression to committed hepatocyte-like cells by the expression of a large number of markers including α-fetoprotein and albumin; and the final differentiation by the expression of nuclear and cytoplasmic HNF4. Fully differentiated cells demonstrated gene expression, urea production, and immunohistochemistry consistent with PH. A methodology and medium formulation to continuously expand the E12-derived hepatocyte-like cells is described.ConclusionThe availability of immortalized hepatocyte-like cell lines could provide a consistent tool for the study of hepatic diseases, drug discovery, and the development of cellular therapies for liver disorders. Utilization of these techniques could provide a basis for the development of bridge therapies for liver failure patients awaiting transplant.

Body-in-a-Cube: a microphysiological system for multi-tissue co-culture with near-physiological amounts of blood surrogate.

Background:Decreasing the amount of liquid inside microphysiological systems (MPS) can help uncover the presence of toxic drug metabolites. However, maintaining near-physiological volume ratios among blood surrogate and multiple organ mimics is technically challenging. Here, we developed a body cube and tested its ability to support four human tissues (kidney, GI tract, liver, and bone marrow) scaled down from in vivo functional volumes by a factor of 73,000 with 80 μL of cell culture medium (corresponding to ~1/73000th of in vivo blood volume).Methods:GI tract cells (Caco-2), liver cells (HepG2/C3A), bone marrow cells (Meg-01), and kidney cells (HK-2) were co-cultured inside the body cube with 80 μL of common, recirculating cell culture medium for 72 h. The system was challenged with acetaminophen and troglitazone, and concentrations of aspartate aminotransferase (AST), albumin, and urea were monitored over time.Results:Cell viability analysis showed that 95.5%±3.2% of liver cells, 89.8%±4.7% of bone marrow cells, 82.8%±8.1% of GI tract cells, and 80.1%±11.5% of kidney cells were viable in co-culture for 72 h. Both acetaminophen and troglitazone significantly lowered cell viability in the liver chamber as indicated by viability analysis and a temporary increase of AST in the cell culture medium. Both drugs also lowered urea production in the liver by up to 45%.Conclusions:Cell viability data and the production of urea and albumin indicate that the co-culture of GI tract, liver, bone marrow, and kidney tissues with near-physiological volume ratios of tissues to blood surrogate is possible for up to 72 h. The body-cube was capable of reproducing liver toxicity to HepG2/C3A liver cells via acetaminophen and troglitazone. The developed design provides a viable format for acute toxicity testing with near-physiological blood surrogate to tissue volume ratios.

220-LB: Glucagon Promotes Hepatic Autophagy by AMPK-Mediated mTORC1 Inhibition

Glucagon plays an important role in hepatic glucose metabolism as well as protein/amino acid metabolism but detailed knowledge about glucagon’s role in hepatic autophagy is limited. We hypothesized that glucagon regulate hepatic protein metabolism partly through activation of AMP-kinase (AMPK) that in turn lead to inhibition of mammalian target of rapamycin complex1 (mTORC1) and activation of Uncoordinated-51 like autophagy activating kinase-1 (ULK1) resulting in increased autophagy. In order to test this hypothesis, we infused chronically catheterized awake mice with [13C5]-glutamine [0.225 mg/(kg-min)] for 120 min after which a second line was connected infusing somatostatin [4 µg/(kg-min)] and insulin [0.1 mU/(kg-min)], with (n=7) or without glucagon [10 ng/(kg-min)] (n=6) for 90 min. This raised plasma glucagon concentration ~18-fold compared to control. Glucagon infusion increased phosphorylation of hepatic: AMPKThr172, RaptorSer792, ULK1Ser555 (P=0.03, P=0.03, and P=0.06, respectively, compared to control), and resulted in hepatic Microtubule-associated protein 1A/1B-light chain 3 (LC3)-II accumulation (P=0.02), a marker of autophagy, assessed by immunoblotting. Glucagon treatment also increased the 13C enrichment (m+3) in liver glucose (P&amp;lt;0.0001), indicating increased conversion of [13C5]-glutamine to glucose as well as increased plasma urea concentrations (P=0.04). Consistent with these in vivo results, parallel studies performed in liver slices obtained from overnight fasted male rats (n=6) incubated in Krebs-Henseleit bicarbonate buffer supplemented with [3-13C]-alanine (1 mM), glucagon (250 µM) treatment increased: glucose production (P=0.01), urea production (P=0.0005), and intracellular levels of leucine (P=0.045). In conclusion, our data suggest that glucagon promotes hepatic proteolysis and ureagenesis by AMPK-mediated suppression of mTOC1 activity, leading to increased hepatic autophagy. Disclosure K.D. Galsgaard: None. N.J. Wewer Albrechtsen: Research Support; Self; Mercodia, Novo Nordisk A/S, Novo Nordisk Foundation. Speaker’s Bureau; Self; Merck Sharp &amp; Dohme Corp. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research &amp; Development, LLC, Merck &amp; Co., Inc. Advisory Panel; Spouse/Partner; Merck &amp; Co., Inc. Consultant; Self; Novo Nordisk A/S. Consultant; Spouse/Partner; Novo Nordisk A/S. Other Relationship; Self; Gilead Sciences, Inc., iMetabolic Biopharma Corporation. Other Relationship; Spouse/Partner; iMetabolic Biopharma Corporation. Other Relationship; Self; Maze Therapeutics. K. Petersen: Advisory Panel; Spouse/Partner; Merck Sharp &amp; Dohme Corp. Research Support; Self; Merck Sharp &amp; Dohme Corp., National Institute of Diabetes and Digestive and Kidney Diseases. Research Support; Spouse/Partner; National Institute of Diabetes and Digestive and Kidney Diseases. A. Nasiri: Employee; Spouse/Partner; Medtronic. G. Cline: None. X. Zhang: None. J. Lee: None. B.T. Hubbard: None.

Energy- and Resourse-Saving Technologies and Equipment in Urea Production

Energy- and Resourse-Saving Technologies and Equipment in Urea Production

1812-P: Glucagon Resistance and Decreased Susceptibility to Diabetes in a Model of Chronic Hyperglucagonemia

Elevation of glucagon levels and increase in α-cell mass are associated to states of hyperglycemia in diabetes. However, little is known about the mechanisms that control glucagon secretion and α-cell mass expansion in normal or diabetogenic conditions. The current studies investigated the effects of activation of nutrient signaling by conditional deletion of the mTORC1 inhibitor, TSC2, in α-cells (αTSC2KO), we showed that activation of mTORC1 signaling is sufficient to induce chronic hyperglucagonemia as a result of α-cell proliferation, cell size and mass expansion. Hyperglucagonemia in αTSC2KO was associated to increase in glucagon content, enhanced glucagon secretion and defective adaptation to fasting. This model allowed us to identify the beneficial effects of chronic hyperglucagonemia in glucose homeostasis by inducing insulin secretion and resistance to glucagon in the liver. Liver glucagon resistance in αTSC2KO mice was characterized by reduced expression of the glucagon receptor (GCGR), phosphoenolpyruvate carboxykinase (PEPCK) and genes involved in amino acid metabolism and urea production. Surprisingly, hyperglucagonemia in αTSC2KO mice was associated to improved glucose levels in models of Streptozotocin (STZ)-induced β-cell destruction and high fat diet-induced glucose intolerance. Contrary to our current understanding of glucagon action, these studies demonstrate that endogenous chronic hyperglucagonemia improve glucose homeostasis by augmenting insulin secretion and by inducing glucagon resistance in the liver. These novel in vivo findings support the concept that enhancing glucagon action could be used as an alternative strategy to treat hyperglycemia in diabetes. Disclosure C. Lubaczeuski: None. N. Bozadjieva: None. M. Blandino-Rosano: None. E. Bernal-Mizrachi: None. Funding U.S. Department of Veterans Affairs (IBX002728A); Diabetes Research Connection

P0561ACUTE KIDNEY INJURY AS A RISK FACTOR FOR KIDNEY STONES: A PROPENSITY MATCHED ANALYSIS

Abstract Background and Aims Kidney stones affects 6-9% of the population, with an almost 30% risk of reoccurrence. Factors associated with kidney stone formation include male gender, ethnicity, family history and stone type. The underlying pathology of stone formation is complex and includes increased urine saturation, decreased urine stone inhibitors in addition to metabolic factors. Acute kidney injury (AKI) refers to the abrupt decrease in kidney function, resulting in retention of urea and other waste products and the dysregulation of fluid and electrolyte balance. AKI affects 10-15% of the hospitalised population and is associated with long-term outcomes, such as chronic kidney disease, end-stage kidney disease (ESKD), cardiovascular disease, fractures and earlier mortality. There is evidence that AKI may result in long-term renal damage and fibrosis. A potential effect is impairment in urine concentration which would limit kidney stone formation. However there has been no previous investigation about this potential association. We aim to investigate if there is an association between AKI and kidney stone formation. Method Retrospective clinical data available for all adult (≥18 years of age) hospital admissions to a local health district in Australia between January 2008 and December 2017 was used in the analysis. We excluded 1) non-residents, 2) stone diagnosis pre-AKI, 3) death within 1 month of an AKI episode, 4) dialysis dependent ESKD prior to an AKI episode and 5) incomplete patient information. AKI episode was diagnosed from ICD-10 coding and kidney stone from ICD-10 and SNOMED coding. Our outcome was a kidney stone episode. We examined the entire cohort in addition to propensity score matching (PSM) using 1:1 optimal matching, caliper 0.1 and without replacement based on covariates known to be associated with renal calculi and AKI. Balance before and after PSM was assessed between the groups to evaluate quality using standardised means. Baseline characteristics were compared with chi-square and Mann Whitney U. Multivariate analysis was compared using Logistic regression. Results For the cohort of 180,927 patients, after exclusions, 12,338 (6.8%) patients were diagnosed with an AKI and 4,495 (2.5%) patients with a kidney stone. Patients with an AKI (12,338), compared to patients with no AKI (168,523), were more likely to be older (75.0 vs 50.0 years, p&amp;lt;0.001) with more comorbidities such as hypertension (31.8% vs 12.7%, p&amp;lt;0.001), diabetes (21.5% vs 9.4%, p&amp;lt;0.001), coronary artery disease (14.6% vs 7.0%, p&amp;lt;0.001) and peripheral vascular disease (5.4% vs 1.8%, p&amp;lt;0.001). The risk of kidney stone formation for the entire cohort in patients with a history of AKI was lower when compared to the no AKI patients (1.1% vs 2.6%, Hazard ratio 0.42, 95% confidence interval 0.36- 0.52, p&amp;lt;0.001). After PSM 12,336 patients with AKI were matched with 12,336 patients with no AKI with good balance of covariates. Patients with a history of AKI had a lower risk of kidney stone formation when compared to no AKI patients (Hazard ratio 0.57, 95% Confidence Interval 0.36- 0.51, p&amp;lt;0.001) Conclusion Our findings suggest that patients with AKI appear to be at a significantly lower risk of developing subsequent kidney stone formation when compared to patients with no previous AKI episodes. Further analysis on a greater scale are required to confirm these findings and their implications.

Inhibition of p38mapk Reduces Adipose Tissue Inflammation in Aging Mediated by Arginase-II

Background: Adipose tissue inflammation occurs not only in obesity but also in aging and is mechanistically linked with age-associated diseases. Studies show that ablation of the l-arginine-metabolizing enzyme arginase-II (Arg-II) reduces adipose tissue inflammation and improves glucose tolerance in obesity. However, the role of Arg-II in aging adipose tissue inflammation is not clear. Objective: This study investigated the role of Arg-II in age-associated adipose tissue inflammation. Methods: Visceral adipose tissues of young (3–6 months) and old (20–24 months) wild-type (WT) and Arg-II^−/− mice were investigated. Immunofluorescence confocal microscopy was performed for analysis of macrophage accumulation and cellular localization of arginase and cytokines; expression of arginase and cytokines was analyzed by qRT-PCR or immunoblotting or ELISA; activation of mitogen-activated protein kinases in adipose tissues was analyzed by immunoblotting; and arginase activity was measured by colorimetric determination of urea production. Results: In the old WT mice, there is more macrophage accumulation in the visceral adipose tissues than in Arg-II knockout animals. An age-associated increase in arginase activity and Arg-II expression in adipose tissues of WT mice is observed. Arg-II knockout enhances Arg-I expression and activity, but inhibits interleukin (IL)-6 expression and secretion and reduces active p38mapk in aging adipose tissue macrophages and stromal cells. Treatment of aging adipose tissues of WT mice with a specific p38mapk inhibitor SB203580 reduces IL-6 secretion. Conclusions: Arg-II promotes IL-6 production in aging adipose tissues through p38mapk. The results suggest that targeting Arg-II or inhibiting p38mapk could be beneficial in reducing age-associated adipose tissue inflammation.

Environmental benefits of urea production from basic oxygen furnace gas

Basic oxygen furnace gas (BOFG) is a multi-component residual flow from integrated steel mills composed of CO, CO2, O2, N2 and H2. In this study, we use the life cycle assessment method to quantify the environmental impacts of six applications of BOFG: heat for internal use in the steel mill, heat combined with CO2 storage, electricity production, urea production, urea production combined with CO2 storage and flaring. Urea can be produced from solely BOFG components, making use of the sorption enhanced water–gas shift technology. This application of BOFG is described here for the first time. The environmental impacts of these six applications were compared in light of the impacts of their conventional production (‘counterfactual’). Using BOFG for the production of electricity and urea would result in net greenhouse gas emissions of 0.87 tCO2-eq/tBOFG and 0.69 tCO2-eq/tBOFG, respectively. When excess CO2 is transported and stored, net emission savings could be achieved when producing urea (−0.11 tCO2-eq/tBOFG) and heat (−0.12 tCO2-eq/tBOFG) from BOFG, again as compared to their counterfactual of conventional production. Overall environmental impacts were slightly lower for electricity (5.2E−4 DALY/tBOFG, 1.9E−6 species.yr/tBOFG) compared to urea (6.2E−4 DALY/tBOFG, 1.9E−6 species.yr/tBOFG). Sensitivity analysis showed, however, that when replacing cleaner electricity (e.g. under future power decarbonisation), these relative environmental benefits of electricity production from BOFG are diminished. We conclude that urea production, rather than the current practice of electricity production, is the best investigated option to reduce environmental impacts of BOFG, which can lead to net environmental benefits when combined with CO2 storage.

Oxygen vacancies enhanced cooperative electrocatalytic reduction of carbon dioxide and nitrite ions to urea

The electrochemical reduction of carbon dioxide and nitrite ions into value-added chemicals represents one of the most promising approaches to relieve the greenhouse gases, while a critical challenge is to search for a highly effective catalyst with low energy input and high conversion selectivity. In this work, we demonstrated low-valence Cu doped, oxygen vacancy-rich anatase TiO2 (Cu-TiO2) nanotubes as a synergetic catalyst for electrochemical co-reduction of both CO2 and NO2–. The incorporation of Cu dopants in anatase TiO2 facilitated to form abundant oxygen vacancies and bi-Ti3+ defect sites, which allowed for efficient nitrite adsorption and activation. The low-valence Cu dopants also served as effective catalytic centers to reduce CO2 into CO* adsorbate. The close proximity of CO* and NH2* intermediates was beneficial for the subsequent cooperative tandem reaction to form urea via the CN coupling. This oxygen vacancy-rich Cu-TiO2 electrocatalyst enabled excellent urea production rate (20.8 μmol⋅h−1) and corresponding Faradaic efficiency (43.1%) at a low overpotential of –0.4 V versus reversible hydrogen electrode, substantially superior than those of undoped TiO2, thus suggesting an exciting approach for cooperative CO2 and nitrogen fixation.

The consequences of altered microbiota in immune-related chronic kidney disease.

The normal gut microbiome modulates host enterocyte metabolism and shapes local and systemic immunity. Accumulation of urea and other waste products in chronic kidney disease induces gut dysbiosis and intestinal wall inflammation (leaky gut). There are decreased numbers of bacteria that generate short-chain fatty acids, which are an important nutrient source for host enterocytes and also contribute to regulation of the host immune system. Anaerobic proteolytic bacteria that express urease, uricase and indole and p-cresol enzymes, such as Enterobacteria and Enterococci, are increased. Microbial-derived uremic toxins such as indoxyl sulfate and trimethylamine N-oxide contribute to the pathophysiology of immune-related kidney diseases such as diabetic nephropathy, lupus nephritis and immunoglobulin A (IgA) nephropathy. Animal and clinical studies suggest potential benefits of dietary and probiotic interventions in slowing the progression of immune-related kidney diseases.

1,2-Bis(diiso-propyl-phosphan-yl)ethane-κ2 P,P'](2-fluoro-N-{[(2-fluoro-phen-yl)aza-nid-yl]carbon-yl}anilinido-κ2 N,N')nickel(II).

The mol-ecular structure of the title complex, [Ni(C13H8F2N2O)(C14H32P2)] or Ni(oFPU)(dippe), where oFPU is the dianion of bis-(2-fluoro-phen-yl)urea and dippe is 1,2-bis-(di-iso-propyl-phosphino)ethane, comprises an NiII atom with a distorted square-planar coordination environment (geometry index τ4 = 0.195). One of the fluoro-phenyl rings of the oFPU ligand is disordered over two sets of sites in an 0.832 (7):0.168 (7) ratio. The crystal structure displays C-H⋯O and C-H⋯F hydrogen-bonding inter-actions, leading to chains with R 2 2(12) motifs extending parallel to [100]. The title compound might be of inter-est with respect to the production of urea and carbamate derivatives of nickel(II).