Studies in animal models suggest that complement activation is crucial in the pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Here we investigate the circulating complement activation profile of 66 patients with active stage AAV compared to that of 54 patients with AAV in remission. Plasma levels of C3a, C5a, soluble C5b-9, and Bb, all determined by enzyme-linked immunosorbent assay, were significantly higher in active stage than in remission of AAV, while plasma levels of properdin were significantly lower in the former than the latter disease stage. There was no significant difference in the plasma levels of C4d between active stage and remission. The plasma level of Bb in patients with active AAV significantly correlated with the proportion of total and cellular crescents in the renal biopsy, the erythrocyte sedimentation rate, and the Birmingham Vasculitis Activity Scores. Thus, systemic activation of complement by the alternative pathway takes place in human AAV. Circulating Bb might be a useful biomarker in assessing disease activity of AAV.

SummaryBackground and objectives Previous study revealed that complement activation products of the alternative pathway could be detected in renal specimens of human ANCA-associated vasculitis. The current study aimed to investigate the clinical and pathologic significance of complement activation products in the urine and kidneys of patients with ANCA-associated vasculitis.Design, setting, participants, & measurements Renal biopsy specimens from 29 patients with ANCA-associated vasculitis diagnosed at Peking University First Hospital from January of 2008 to December of 2010 were randomly collected. Urine samples from 27 of 29 patients in active stage and 22 ANCA-associated vasculitis patients in complete remission who were independent of the above-mentioned 29 patients were collected. Urine samples from 28 patients with lupus nephritis and 25 healthy individuals were also collected. The renal deposition of Bb, C3d, and C5b-9 were detected by immunohistochemistry. The urinary levels of Bb, C3a, C5a, and soluble C5b-9 were determined by ELISA.Results The deposition, measured by the mean optical density of Bb, which is an alternative complement pathway marker, in glomeruli correlated with the proportion of total crescents (r=0.50, P=0.006), the extent of interstitial infiltrate (r=0.59, P=0.001), interstitial fibrosis (r=0.45, P=0.01), and tubular atrophy (r=0.55, P=0.002), whereas it correlated inversely with the proportion of normal glomeruli (r=20.49, P=0.008). The urinary levels of Bb, C3a, C5a, and soluble C5b-9 were all significantly higher in active compared with remission stage. The urinary levels of Bb in patients with active ANCA-associated vasculitis correlated with the serum creatinine (r=0.56, P=0.002) and correlated inversely with the proportion of normal glomeruli in renal specimens (r=20.49, P=0.009). ConclusionsThe present study provides additional evidence that complement activation through the alternative pathway occurred in the development of ANCA-associated vasculitis. The renal deposition of Bb and urinary Bb levels were associated with the severity of renal injury.

IntroductionThe complement system is crucial for the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In particular, C5a plays a central role. In this study, plasma and urinary levels of C5a as well as renal C5a receptors (CD88 and C5L2) expression were investigated in patients with AAV.MethodsTwenty-four patients with AAV in the active phase, 19 patients with AAV in the remission phase, and 20 patients with lupus nephritis (LN) were included. Plasma and urinary levels of C5a were measured with enzyme-linked immunosorbent assay (ELISA). The staining of CD88 and C5L2 in renal specimens was detected with immunohistochemistry.ResultsThe level of plasma C5a was significantly higher in patients with AAV in the active phase than that in patients in remission, that in patients with LN, and that in normal controls. The urinary C5a level was significantly higher in patients with AAV in the active phase than that in patients in remission and that in normal controls, but not significantly different between patients with active AAV and patients with LN. The mean optical density of CD88 staining in the tubulointerstitium was significantly lower in AAV patients than that in normal controls (0.0052 ± 0.0011 versus 0.029 ± 0.0042; P = 0.005). The mean optical density of C5L2 in glomeruli was significantly higher in AAV patients than that in normal controls (0.013 ± 0.0027 versus 0.0032 ± 0.0006; P < 0.001). The mean optical density of CD88 staining closely correlated with the initial eGFR (r = 0.835; P < 0.001) in AAV patients. Double-labeling immunofluorescence assay suggested that CD88 did not express on neutrophils, monocytes, or macrophages, but C5L2 expressed on neutrophils (or monocytes) and macrophages.ConclusionThe elevated plasma and urinary C5a levels indicated complement activation in human AAV. The level of renal CD88 expression could reflect the disease severity of ANCA-associated glomerulonephritis. CD88 expression was downregulated, and C5L2 was upregulated in ANCA-associated glomerulonephritis.

Modelling groundwater uptake provides a powerful tool for examining the tight linkage of phreatophytic vegetation with spatial and temporal variations in groundwater and soil moisture. Here, a physically based modelling framework was developed to simulate groundwater uptake and hydraulic redistribution (HR), as driven by the potential gradients along the groundwater-soilplant-atmosphere continuum. A new water stress function, based on the 'vulnerability curve' theory, was introduced; it integrates the influence of both soil water and groundwater on transpiration. The model was then implemented using a system dynamics approach and applied to simulate groundwater uptake of Quercus douglasii (blue oak) in a California savanna. It showed good agreement with the measured evapotranspiration, soil moisture, and leaf water potential data. The model results indicated that the dominant water source for blue oaks switched from soil water in the wet season to groundwater in the dry season. During the dry period, cavitation led to a hydraulic conductivity loss of approximately 85% in the shallow roots, and groundwater uptake contributed over 80% of transpiration. The dry, shallow soil layers received water from groundwater and deep soil layers at night through HR. The new water stress function performed well when simulating daily transpiration (r 2 = 0·69). The model indicated that blue oaks maintained only a small portion of deep roots (15% of the total) to uptake groundwater and mitigate the impacts of drought. The proposed model framework can be incorporated into coupled climate, hydrological, and ecological models to improve their performance when studying ecohydrological process and climate feedbacks.

ObjectiveDiabetic nephropathy (DN) is a serious complication for patients with diabetes mellitus (DM). Emerging evidence suggests that complement C3a is involved in the progression of DN. The aim of this study was to investigate the effect of C3a Receptor Agonist (C3aRA) on DN and its potential mechanism of action in rats with type 2 diabetes mellitus (T2DM).MethodsT2DM was induced in SD rats by a high fat diet (HFD) plus repeated low dose streptozocin (STZ) injections. T2DM rats were treated with vehicle or C3aRA for 8 weeks. Biochemical analysis, HE and PAS stains were performed to evaluate the renal function and pathological changes. Human renal glomerular endothelial cells (HRGECs) were cultured and treated with normal glucose (NG), high glucose (HG), HG+C3a, HG+C3a+C3aRA and HG+C3a+BAY-11-7082 (p-IKBα Inhibitor) or SIS3 (Smad3 Inhibitor), respectively. Real-time PCR, immunofluorescent staining and western blot were performed to detect the mRNA and protein levels, respectively.ResultsT2DM rats showed worse renal morphology and impaired renal function compared with control rats, including elevated levels of serum creatinine (CREA), blood urea nitrogen (BUN) and urine albumin excretion (UACR), as well as increased levels of C3a, C3aR, IL-6, p-IKBα, collagen I, TGF-β and p-Smad3 in the kidney of T2DM rats and C3a-treated HRGECs. In contrast, C3aRA treatment improved renal function and morphology, reduced CREA, UACR and the intensity of PAS and collagen I staining in the kidney of T2DM rats, and decreased C3a, p-IKBα, IL-6, TGF-β, p-Smad3 and collagen I expressions in HRGECs and T2DM rats.ConclusionC3a mediated pro-inflammatory and pro-fibrotic responses and aggravated renal injury in T2DM rats. C3aRA ameliorated T2DN by inhibiting IKBα phosphorylation and cytokine release, and also TGF-β/Smad3 signaling and ECM deposition. Therefore, complement C3a receptor is a potential therapeutic target for DN.

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A novel water-soluble polymer was prepared by copolymerization and sulfomethylation using acrylamide (AM) and Nallylbenzamide (NABI) as raw materials under mild conditions. The effects of ratio of AM to NABI, initiator concentration, reaction temperature, pH, and monomer concentration on the copolymerization were studied. The sulfonates copolymer was characterized by infrared (IR) spectroscopy, 1 H NMR spectroscopy, elemental analysis, and atomic force microscopy (AFM). It was found that the sulfonates copolymer could achieve up to 25%, 30% retention rate of the viscosity at a high temperature (120 C) and a vigorous shear condition (1000 s À1 ). It was also found that the sulfonates copolymer had moderate salt tolerance (NaCl, CaCl 2 , and MgCl 2 Á6H 2 O) and its viscosity could be restored to the original value when the shear rate changed from 170 to 510 s À1 and 510 to 170 s À1 . At last, the enhanced oil recovery (EOR) of the sulfonates copolymer was tested by core flood, and with up to 10.6% EOR was afforded in presence of 5000 mg/L NaCl brine at 60 C.

Ecosystems which rely on either the surface expression or subsurface presence of groundwater are known as groundwater-dependent ecosystems (GDEs). A comprehensive inventory of GDE locations at an appropriate management scale is a necessary first-step for sustainable management of supporting aquifers; however, this information is unavailable for most areas of concern. To address this gap, this study created a two-step algorithm which analyzed existing geospatial and remote sensing data to identify potential GDEs at both state/province and aquifer/basin scales. At the state/province scale, a geospatial information system (GIS) database was constructed for Texas, including climate, topography, hydrology, and ecology data. From these data, a GDE index was calculated, which combined vegetative and hydrological indicators. The results indicated that central Texas, particularly the Edwards Aquifer region, had highest potential to host GDEs. Next, an aquifer/basin scale remote sensing-based algorithm was created to provide more detailed maps of GDEs in the Edwards Aquifer region. This algorithm used Landsat ETM+ and MODIS images to track the changes of NDVI for each vegetation pixel. The NDVI dynamics were used to identify the vegetation with high potential to use groundwater--such plants remain high NDVI during extended dry periods and also exhibit low seasonal and inter-annual NDVI changes between dry and wet seasons/years. The results indicated that 8% of natural vegetation was very likely using groundwater. Of the potential GDEs identified, 75% were located on shallow soil averaging 45 cm in depth. The dominant GDE species were live oak, ashe juniper, and mesquite.