Development, Modeling, Analysis, and Optimization of a Novel Inland Desalination with Zero Liquid Discharge for Brackish Groundwaters

Groundwater is considered the major source of domestic water supply in many countries worldwide. In the absence of surface water supplies, the use of groundwater for domestic, agricultural, and even for industrial purposes becomes essential, especially in rural communities. Groundwater supplies typically are of good quality, and the quality is reasonably uniform throughout the year compared to that of surface water, thus making it suitable for direct use, or simple to treat. A disadvantage of groundwater is the content of dissolved salt as many have a moderate-to-high salinity. The high salinity makes water brackish and thus it requires desalination before use. This has led to wide use of groundwater desalination to produce good-quality water in many regions around the world. Nevertheless, a problem of desalination processes is the generation of a concentrate stream, sometimes called brine or reject, which must be properly managed. The management of brine from brackish groundwater desalination is a significant issue if located far from the coast (i.e. inland plants) or far from public channel to discharge such brine. Some options for brine disposal from inland desalination plants are evaporation ponds, deep-well injection, disposal to municipal sewers, and irrigation of plants tolerant to high salinities. Each of these disposal methods may result in many environmental problems such as groundwater contamination, the decline in crop yields from agricultural lands, the formation of eyesores, decreasing the efficiency of biological wastewater treatment, and making treated sewage effluent unsuitable for irrigation. As a result, the brine management from inland desalination of brackish groundwater is very critical, and the need for affordable and environmentally benign inland desalination has become crucial in many regions worldwide. This work aims to develop an efficient and environmentally benign process for inland desalination of brackish groundwater, which approaches zero liquid discharge (ZLD), maximizing the water produced and minimizing the volume of concentrate effluent. The technical approach involves utilization of two-stage reverse osmosis (RO) units with the intermediate chemical treatment of brine stream that is designed to remove most of the scale-forming constituents, which foul membrane surface in RO and limits its water recovery and hence enable further recovery of water in the secondary RO unit. The treatment process proposed in this work is based on advanced lime softening processes, which have the ability to effectively remove scale-forming constituents, in addition to heavy metals and natural organic matters that might be present in the brine. The process has been applied to the brine produced from 1st stage RO i.e. primary brine stream, to minimize the volume of the stream to be treated chemically, which in turn reduces the capacity of the treatment equipment. Analysis of groundwater quality and scale-forming constituents that are present in the brine stream upon desalination of groundwater has been performed. The analysis has revealed that in most cases of brackish groundwater desalination the recovery is limited by scaling due to calcium sulfate i.e. gypsum, and amorphous silica. Thus, the main objective set for the chemical treatment of the brine stream focused on removal of calcium, sulfate, and silica. Advanced lime softening based on high lime doses along with sodium aluminate, as in ultra-high lime with alumina UHLA process, has been proposed for chemical treatment of brine. Bench-scale experiments conducted to evaluate the effectiveness of the proposed chemical treatment for removal of scale-forming constituents, particularly calcium, sulfate, and silica by studying the different factors affecting the removals efficiency from synthetic solutions containing sulfate-only, silica-only, and model brine solution. The results obtained have revealed that the proposed process was very effective and results generally in high and quick removals of calcium, sulfate, and silica of more than 80% within 2 hrs under different experimental conditions. In addition, beneficial uses of different solid byproducts formed are investigated, by analyzing the solids resulted to qualitatively and quantitatively to identify the different solids present. This offers the potential to lower both costs and solid disposal problems of solids formed being considered as added value product rather than solid waste that has to be properly managed. Results have shown that the solid precipitate contains a wide range of solids that generally composed of calcium, magnesium, aluminum along with carbonate, sulfate, and silicate, which have several potential applications as soil sub-grade, and in cement industry. Equilibrium model to simulate the chemical treatment process that is able to predict the required chemical reagents doses, effluent water quality for a given influent water quality and treatment levels has been developed utilizing OLI stream analyzer, the developed model was found to well predict the performance of the chemical treatment at equilibrium conditions. Rigorous membrane separation model has developed in Aspen Custom Modeler to more accurately model RO desalination, which is to be combined with the developed equilibrium model to formulate a complete 1st Stage RO–Chemical Treatment–2nd Stage RO process model. The developed complete and validated model has been then used to fully and accurately simulate the performance of the proposed Zero Liquid Discharge desalination process. The present work results in three novel achievements: first, introducing a very effective intermediate chemical treatment, which efficiently remove sulfate, particularly from brine. Most of the previously proposed intermediate treatment processes remove sulfate as calcium sulfate i.e. gypsum, however in the introduced process, sulfate is removed in calcium-aluminum-sulfate complexes, which has very low solubility, making the brine highly undersaturated with respect to gypsum, and hence lowering the fouling propensity in the secondary RO, leading to maximizing the overall recovery. In addition, the chemical treatment has been successfully modeled for better simulate of its performance for different brine qualities, which are usually encountered in brackish ground desalination due to the high location-specific nature of groundwater quality. Second, the developed membrane model has treated the species present in water as ions, accounting for monovalent and divalent ions separately, and obtaining a different permeability coefficient for their transport through the membrane. This is different from most developed RO models, which simplify the transport through the membranes to only water and salt permeability coefficients. This treatment results in better and more refined modeling and simulation of the RO membrane separation, as the RO membrane interact differently to ions present in water. Third, the complete process model, results from combining the developed equilibrium model of the chemical treatment, and membrane separation model, has revealed very promising results of achieving high recovery desalination of about 93.5% suitable for drinking water purposes, which is higher by about 90% than most of the reported literature, whose result in reducing the brine volume from 25% in conventional desalination to only 6.5% in the proposed process, i.e. brine volume reduction of 74% relative to conventional inland desalination, and 35% relative to other high recovery processes, at reasonable chemical treatment levels

Protein Phosphatase 2A Regulates Xanthine Oxidase-derived ROS Production in Macrophages and Influx of Inflammatory Monocytes in a Murine Gout Model

Background: Gout is a common arthritis, due to deposition of monosodium urate (MSU) crystals which results in IL-1β secretion by tissue-resident macrophages. Xanthine oxidase (XO) catalyzes uric acid (UA) production and in the process, reactive oxygen species (ROS) are generated which contributes to NLRP3 inflammasome activation. Protein phosphatase 2A (PP2A) may be involved in regulating inflammatory pathways in macrophages. The objective of this study was to investigate whether PP2A regulates gout inflammation, mediated by XO activity modulation. We studied UA and ROS generations in MSU stimulated murine bone marrow derived macrophages (BMDMs) in response to fingolimod phosphate, a PP2A activator, and compared its anti-inflammatory efficacy to that of an XO inhibitor, febuxostat. Methods: BMDMs were stimulated with MSU, GM-CSF/IL-1β or nigericin ± fingolimod (2.5 μM) or febuxostat (200 μM) and UA levels, ROS, XO, and PP2A activities, Xdh (XO) expression and secreted IL-1β levels were determined. PP2A activity and IL-1β in MSU stimulated BMDMs ± N-acetylcysteine (NAC) (10 μM) ± okadaic acid (a PP2A inhibitor) were also determined. M1 polarization of BMDMs in response to MSU ± fingolimod treatment was assessed by a combination of iNOS expression and multiplex cytokine assay. The in vivo efficacy of fingolimod was assessed in a murine peritoneal model of acute gout where peritoneal lavages were studied for pro-inflammatory classical monocytes (CMs), anti-inflammatory nonclassical monocytes (NCMs) and neutrophils by flow cytometry and IL-1β by ELISA. Results: Fingolimod reduced intracellular and secreted UA levels (p \u3c 0.05), Xdh expression (p \u3c 0.001), XO activity (p \u3c 0.001), ROS generation (p \u3c 0.0001) and IL-1β secretion (p \u3c 0.0001), whereas febuxostat enhanced PP2A activity (p \u3c 0.05). NAC treatment enhanced PP2A activity and reduced XO activity and PP2A restoration mediated NAC’s efficacy as co-treatment with okadaic acid increased IL-1β secretion (p \u3c 0.05). Nigericin activated caspase-1 and reduced PP2A activity (p \u3c 0.001) and fingolimod reduced caspase-1 activity in BMDMs (p \u3c 0.001). Fingolimod reduced iNOS expression (p \u3c 0.0001) and secretion of IL-6 and TNF-α (p \u3c 0.05). Fingolimod reduced CMs (p \u3c 0.0001), neutrophil (p \u3c 0.001) and IL-1β (p \u3c 0.05) lavage levels while increasing NCMs (p \u3c 0.001). Conclusion: Macrophage PP2A is inactivated in acute gout by ROS and a PP2A activator exhibited a broad anti-inflammatory effect in acute gout in vitro and in vivo

CD44 Receptor Mediates Urate Crystal Phagocytosis by Macrophages and Regulates Inflammation in A Murine Peritoneal Model of Acute Gout

Gout is a chronic arthritis caused by the deposition of poorly soluble monosodium urate monohydrate (MSU) crystals in peripheral joints. Resident macrophages initiate inflammation in response to MSU mediated by NF-κB nuclear translocation and NLRP3 inflammasome activation. We investigated the role of CD44, a transmembrane receptor, in mediating MSU phagocytosis by macrophages. We used an antibody that sheds the extracellular domain (ECD) of CD44 to study the role of the receptor and its associated protein phosphatase 2A (PP2A) in macrophage activation. We also studied the significance of CD44 in mediating MSU inflammation in-vivo. Cd44−/− BMDMs showed reduced MSU phagocytosis, LDH release, IL-1β expression and production compared to Cd44+/+ BMDMs. Elevated CD44 staining was detected intracellularly and CD44 colocalized with α-tubulin as a result of MSU exposure and ECD-shedding reduced MSU phagocytosis in murine and human macrophages. Anti-CD44 antibody treatment reduced NF-κB p65 subunit nuclear levels, IL-1β expression, pro-IL-1β and IL-8 production in MSU stimulated THP-1 macrophages (p \u3c 0.01). The effect of the antibody was mediated by an enhancement in PP2A activity. CD44 ECD-shedding reduced the conversion of procaspase-1 to active caspase-1, caspase-1 activity and resultant generation of mature IL-1β in macrophages. Neutrophil and monocyte influx and upregulated production of IL-1β was evident in wildtype mice. MSU failed to trigger neutrophil and monocyte recruitment in Cd44−/− mice and lower IL-1β levels were detected in peritoneal lavages from Cd44−/− mice (p \u3c 0.01). Anti-CD44 antibody treatment reduced neutrophil and monocyte recruitment and resulted in reduced lavage IL-1β levels in the same model. CD44 plays a biologically significant role in mediating phagocytosis of MSU and downstream inflammation and is a novel target in gout treatment

Fingolimod Phosphate (FTY720-P) Activates Protein Phosphatase 2A in Human Monocytes and Inhibits Monosodium Urate Crystal-Induced Interleukin-1 β Production

Gout is a chronic inflammatory arthritis caused by monosodium urate monohydrate (MSU) crystal deposits in joints of lower limbs. Phagocytic uptake of MSU crystals by joint-resident macrophages and recruited circulating monocytes results in IL-1β expression and production. Current acute gout treatments have serious toxicities and suffer suboptimal clinical outcomes. Protein phosphatase 2A (PP2A) plays an important role in regulating signaling pathways relevant to inflammation. We hypothesized that innate immune danger signals, e.g., lipopolysaccharide (LPS) and soluble uric acid (sUA), prime human monocytes toward MSU crystal phagocytosis and that increased IL-1β production mediated by a reduction in PP2A activity and restoring PP2A activity exerts an anti-inflammatory effect in this setting. Priming monocytes with LPS + sUA increased cytosolic pro-IL-1β and mature IL-1β and enhanced MSU crystal phagocytosis and its downstream IL-1β expression (P \u3c 0.001). A combination of LPS + sUA priming and MSU crystals reduced PP2A activity in monocytes by 60% (P = 0.013). PP2A catalytic subunit gene knockdown reduced PP2A activity and exacerbated MSU crystal–induced IL-1β expression and secretion (P \u3c 0.0001). Fingolimod (FTY720) and its active metabolite, fingolimod phosphate (FTY720-P), were evaluated for their ability to activate PP2A in human monocytes over 24 hours. FTY720 and FTY720-P activated PP2A to a similar extent, and maximal enzyme activity occurred at 24 hours for FTY720 and at 6 hours for FTY720-P. FTY720-P (2.5 μM) reduced pro-IL-1β production and IL-1β secretion in primed and MSU crystal–stimulated monocytes (P \u3c 0.0001) without changing the magnitude of crystal phagocytosis. We conclude that PP2A is a promising new target in acute gout

Activation of Adenylyl Cyclase Reduces TGF-b Profibrotic Response in Osteoarthritic Fibroblast-like Synoviocytes

Purpose: The hallmarks of osteoarthritis (OA) include cartilage degeneration, bone remodeling and synovial fibrosis. Synovial fibrosis is characterized by excessive extracellular matrix (ECM) accumulation due to an imbalance in ECM production, in particular collagen, and its turnover. Transforming growth factor beta (TGF-β) and its associated signaling pathway mediated by ALK5, plays an important role in synovial fibrosis and blocking TGF-β’s effect prevents synovial fibrosis. Increasing intracellular cyclic AMP (cAMP) produces an antifibrotic effect in fibroblasts of multiple origins. Forskolin (FsK) is a naturally occurring diterpene in the roots of the Indian Coleus plant that activates adenylyl cyclase resulting in an elevation in intracellular cAMP levels. We hypothesized that FsK treatment results in an anti-fibrotic effect in TGF-β stimulated fibroblast-like synoviocytes (FLS) from patients with advanced OA. Methods: OA FLS (Cell Applications, USA) were harvested from patients undergoing total knee replacement. Cells were used between the 3rd and 6th passages for all experiments. OA FLS (300,000 cells per well) were treated with TGF-β (1ng/ml; R&D Systems) in the absence or presence of FsK (10μM; Sigma Aldrich) or SB431542, an ALK5 inhibitor (1μM, Sigma Aldrich) for 24 hours followed by RNA extraction using Trizol reagent and RNA concentrations were determined using a NanoDrop ND-2000 spectrophotometer. cDNA was synthesized using iScript Reverse Transcription Supermix for RT-qPCR (Bio-Rad, USA). Quantitative PCR (qPCR) was performed using TaqMan Fast Advanced Master Mix (Lifetechnologies, USA). The cycle threshold (Ct) value of genes of interest were normalized to the Ct value of GAPDH in the same sample, and the relative expression was calculated using the 2−ΔΔCt method. Genes of interest included collagens type 1 (COL1A1) and 3 (COL3A1), α2 smooth muscle actin (ACTA2), proteoglycan-4 (PRG4), matrix metalloproteinases 3, 9 and 13 (MMP3, MMP9 and MMP13), tissue inhibitor of metalloproteinase-1 (TIMP1) and aggrecanase-1 (ADAMTS4). Multiple group comparisons were performed by ANOVA or ANOVA on the ranks followed by pairwise group comparisons using Tukey\u27s test. Data is presented as the average ± S.D. of 3–6 independent experiments. Results:FsK treatment significantly reduced TGF-β induced expression of collagen type I (fig. 1A; p Conclusions: Using a model of TGF-β stimulated OA synovial fibroblasts, FsK treatment resulted in a reduction in the expression of collagen type I, a major component of fibrosis and α2 smooth muscle actin, a marker of fibroblast differentiation to myofibroblasts. To this end, FsK\u27s effect was comparable to the inhibition of intracellular TGF-β signaling. PRG4 regulates synovial proliferation and inflammation and FsK treatment enhanced PRG4 expression by OA fibroblasts. FsK reduced expression of matrix degrading enzymes, especially MMP3 and MMP9 involved in synovial proliferation, and MMP13 and ADAMTS4, involved in cartilage degradation. Increasing intracellular levels of cAMP in synovial fibroblasts may result in antifibrotic and chondroprotective effects in the joint

Intra-Articular Interleukin-1 Receptor Antagonist (IL1-ra) Microspheres for Posttraumatic Osteoarthritis: In Vitro Biological Activity and in Vivo Disease Modifying Effect

Background: Interleukin-1 receptor antagonist (IL-1 ra) can be disease-modifying in posttraumatic osteoarthritis (PTOA). One limitation is its short joint residence time. We hypothesized that IL-1 ra encapsulation in poly (lactide-co-glycolide) (PLGA) microspheres reduces IL-1 ra systemic absorption and provides an enhanced anti-PTOA effect. Methods: IL-1 ra release kinetics and biological activity: IL-1 ra encapsulation into PLGA microsphere was performed using double emulsion solvent extraction. Lyophilized PLGA IL-1 ra microspheres were resuspended in PBS and supernatant IL-1 ra concentrations were assayed. The biological activity of IL-1 ra from PLGA IL-1 ra microspheres was performed using IL-1 induced lymphocyte proliferation and bovine articular cartilage degradation assays. Systemic absorption of IL-1 ra following intra-articular (IA) injection of PLGA IL-1 ra or IL-1 ra: At 1, 3, 6, 12 and 24 h following injection of 50 μl PLGA IL-1 ra (n = 6) or IL-1 ra (n = 6), serum samples were collected and IL-1 ra concentrations were determined. Anterior cruciate ligament transection (ACLT) and IA dosing: ACLT was performed in 8–10 week old male Lewis rats (n = 42). PBS (50 μl; n = 9), IL-1 ra (50 μl; 5 mg/ml; n=13), PLGA IL-1 ra (50 μl; equivalent to 5 mg/ml IL-1 ra; n = 14) or PLGA particles (50 μl; n = 6) treatments were performed on days 7, 14, 21 and 28 following ACLT. Cartilage and synovial histopathology: On day 35, animal ACLT joints were harvested and tibial cartilage and synovial histopathology scoring was performed. Results: Percent IL-1 ra content in the supernatant at 6 h was 13.44 ± 9.27 % compared to 34.16 ± 12.04 %, 47.89 ± 12. 71 %, 57.14 ± 11.71 %, and 93.90 ± 8.50 % at 12, 24, 48 and 72 h, respectively. PLGA IL-1 ra inhibited lymphocyte proliferation and cartilage degradation similar to IL-1 ra. Serum IL-1 ra levels were significantly lower at 1, 3, and 6 h following PLGA IL-1 ra injection compared to IL-1 ra. Cartilage and synovial histopathology scores were significantly lower in the PLGA IL-1 ra group compared to PBS and PLGA groups (p \u3c 0.001). Conclusions: IL-1 ra encapsulation in PLGA microspheres is feasible with no alteration to IL-1 ra biological activity. PLGA IL-1 ra exhibited an enhanced disease-modifying effect in a PTOA model compared to similarly dosed IL-1 ra

Design and Biological Evaluation of Colchicine-CD44-Targeted Peptide Conjugate in an In Vitro Model of Crystal Induced Inflammation

Gout is an inflammatory arthritis due to the joint deposition of monosodium urate (MSU) crystals. Phagocytosis of MSU crystals by tissue macrophages results in the generation of reactive oxygen species (ROS) and production of inflammatory cytokines and chemokines. Colchicine use in gout is limited by severe toxicity. CD44 is a transmembrane glycoprotein that is highly expressed in tissue macrophages and may be involved in gout pathogenesis. The P6 peptide is a 20-amino acid residue peptide that binds to CD44. We hypothesized that the conjugation of colchicine to the P6 peptide would reduce its off-target cytotoxicity while preserving its anti-inflammatory effect. A modified version of P6 peptide and colchicine-P6 peptide conjugate were synthesized using Fmoc/tBu solid-phase and solution-phase chemistry, respectively. A glutaryl amide was used as a linker. The P6 peptide was evaluated for its binding to CD44, association, and internalization by macrophages. Cytotoxic effects of P6 peptide, colchicine, and colchicine-P6 peptide on macrophages were compared and the inhibition of ROS generation and interleukin-8 (IL-8) secretion in MSU-stimulated macrophages treated with P6 peptide, colchicine, or colchicine-P6 peptide was studied. We confirmed that the P6 peptide binds to CD44 and its association and internalization by macrophages were CD44-dependent. Colchicine (1, 10, and 25 µM) demonstrated a significant cytotoxic effect on macrophages while the P6 peptide and colchicine-P6 peptide conjugate (1, 10 and 25 µM) did not alter the viability of the macrophages. The P6 peptide (10 and 25 µM) reduced ROS generation and IL-8 secretion mediated by a reduction in MSU phagocytosis by macrophages. The colchicine-P6 peptide significantly reduced ROS generation and IL-8 secretion compared to the P6 peptide alone at 1 and 10 µM concentrations. Conjugation of colchicine to the P6 peptide reduced the cytotoxic effect of colchicine while preserving its anti-inflammatory activity

Applicable anode based on Co3O4–SrCO3 heterostructure nanorods-incorporated CNFs with low-onset potential for DUFCs

Besides the high-current density, lower onset potential of urea electrooxidation is key parameter which influences the direct urea fuel cell performance. In the present article, low-onset potential has been reported for nickel-free (NF) electrocatalyst in urea electrooxidation. The nickel-free electrocatalyst: Co3O4–SrCO3 heterostructure nanorods-incorporated carbon nanofibers (CNFs) were synthesized by electrospinning technique, followed by calcination of electrospun mat composed of strontium acetate, cobalt acetate, and poly(vinyl alcohol) sol–gel in inert environment at 750 °C. Physiochemical characterizations confirmed the formation of Co3O4–SrCO3 heterostructure nanorods-incorporated CNFs. The electrochemical activity of resultant nickel-free electrocatalyst toward the electrooxidation of urea in alkaline medium is evaluated using cyclic voltammetry measurements (CV). Co3O4–SrCO3 heterostructure nanorods-incorporated CNFs reveals high-current density of 21.33 mA/cm2 at low-fuel concentration. Notably, the low-onset potential has been observed, showing a good application prospect in direct urea fuel cells.This Publication was made possible by NPRP grant # [8-1344-1-246] from the Qatar National Research Fund (a member of Qatar Foundation). The findings achieved herein are solely the responsibility of authors