Urinary Modified C-Reactive Protein is Closely Associated with Tubulointerstitial Lesions in Lupus Nephritis.

Objective: Modified C-reactive protein (mCRP) is known to be involved in the upregulation and amplification of the local inflammatory response. This study investigated the circulating and local levels of mCRP and their relevance to clinicopathological features in patients with lupus nephritis. Methods: Ninety-five patients with renal biopsy-proven lupus nephritis and 30 normal controls were enrolled in this study. Plasma and urinary mCRP were screened by enzyme-linked immunosorbent assay (ELISA). The renal deposition of mCRP was detected by immunohistochemistry and immunofluorescence staining. A human proximal tubular epithelial cell line (HK2 cells) was incubated with purified IgG from lupus nephritis, and the production of CRP by HK2 cells was further evaluated. Results: Plasma and urinary levels of mCRP increased significantly in patients with lupus nephritis compared with normal controls (P = 0.013, P < 0.001, respectively). The urinary mCRP levels were associated with interstitial inflammatory cell infiltration (r = 0.514, P < 0.001) and interstitial fibrosis (r = 0.270, P = 0.008). The ROC-AUC of the urinary mCRP levels for diagnosing tubulointerstitial lesions was 0.766. The urinary mCRP levels were closely associated with poor outcomes (HR: 1.204, 95% CI: 1.029-1.409, P = 0.020). However, no correlations were found of the plasma mCRP levels with clinicopathological data or the prognosis of lupus nephritis. CRP was mostly deposited in the renal tubules in patients with lupus nephritis, and the expression of CRP was significantly correlated with tubulointerstitial lesion indices. Immunofluorescence staining showed that mCRP could colocalize with IgG in tubules. Lupus nephritis-derived IgG could induce CRP production by HK2 cells. Conclusion: Urinary mCRP levels were significantly increased, and urinary mCRP might be a biomarker for tubulointerstitial lesions in patients with lupus nephritis. Renal CRP could be produced by tubular epithelial cells after stimulation by lupus nephritis-derived IgG, and the local presence of mCRP might play a critical role in the development of tubulointerstitial lesions.

Serum IgE anti-dsDNA autoantibodies in patients with proliferative lupus nephritis are associated with tubulointerstitial inflammation.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the overproduction of multiple autoantibodies. Lupus nephritis (LN), the most common cause of morbidity and mortality, requires early detection. However, only a limited number of serum biomarkers have been associated with the disease activity of LN. Serum IgE anti-dsDNA autoantibodies are prevalent in patients with SLE and may be associated with the pathogenesis of LN. In this study, serum samples from 88 patients with biopsy-proven proliferative LN were collected along with complete clinical and pathological data to investigate the clinical and pathological associations of anti-dsDNA IgE autoantibodies using ELISA. This study found that the prevalence of IgE anti-dsDNA autoantibodies in patients with proliferative LN was 38.6% (34/88). Patients with anti-dsDNA IgE autoantibodies were more prone to acute kidney injury (17/34 vs. 14/54; p = .025). Levels of anti-dsDNA IgE autoantibodies were associated with interstitial inflammation (r = 0.962, p = .017). Therefore, anti-dsDNA IgE autoantibody levels are associated with tubulointerstitial inflammation in patients with proliferative LN.

Metagenomic insights into the "window" effect of static magnetic field on nitrous oxide emission from biological nitrogen removal process at low temperature.

This study aimed to explore whether the "window" effect of static magnetic field (SMF) on nitrous oxide (N2O) emission from the biological nitrogen removal process at low temperature existed and reveal its biological mechanism at the gene level. Four sequencing batch reactors (SBRs) with SMFs of 0, 10, 45, and 75 mT were operated continuously for 110 days at 10 °C and the lowest N2O-Gas cumulative emission (5.50 mg N/day) and N2O conversion rate (4.28 %) in 45 mT SMF-SBR verified the existence of the "window" effect. In 45 mT SMF-SBR, nearly all enzymatic activities related to N2O reduction and corresponding functional gene abundances improved significantly. Metagenomic high-throughput sequencing analysis revealed that Alicycliphilus denitricans, Paracoccus denitrificans, Rhodopseudomonas palustris, Pseudomonas stutzeri, and Dechloromonas aromatica, as species related to N2O reduction, could be separately enriched by applying suitable SMF intensity. Gene functions annotation based on KEGG and CAZy databases indicated that SMF not only accelerated the rate of free ammonia into ammonia-oxidizing bacteria and electrons delivered to the corresponding denitrification reductases, but also enhanced the degradation of complex organic matter into smaller molecules, and thus reducing the production of N2O via nitrifier denitrification and incomplete denitrification pathways at 10 °C. These findings provided a guideline and presented a blueprint of ecophysiology for the future application of magnetic field to the reduction of N2O emission in wastewater treatment plants in the cold region.

Anti-pentraxin 3 auto-antibodies might be protective in lupus nephritis: a large cohort study.

OBJECTIVES: Anti-pentraxin 3 (PTX3) auto-antibodies were found to be associated with the absence of renal involvement in systemic lupus erythematosus (SLE). This study is to investigate the prevalence of anti-PTX3 auto-antibodies and their clinical significance based on a large Chinese lupus nephritis cohort. METHODS: One hundred and ninety-six active lupus nephritis patients, 150 SLE patients without clinical renal involvement, and 100 healthy controls were enrolled. Serum anti-PTX3 auto-antibodies and PTX3 levels were screened by enzyme-linked immunosorbent assay (ELISA). The associations between anti-PTX3 auto-antibodies and clinicopathological parameters in lupus nephritis were further analyzed. RESULTS: Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement (19.4% (38/196) versus 40.7% (61/150), p < .001). The serum levels of anti-PTX3 auto-antibodies were negatively correlated with proteinuria in lupus nephritis (r = -.143, p = .047). The levels of proteinuria, serum creatinine, and the prevalence of thrombotic microangiopathy were significantly higher in patients with higher PTX3 levels (≥3.207 ng/ml) and without anti-PTX3 auto-antibodies compared with patients with lower PTX3 levels (<3.207 ng/ml) and with anti-PTX3 auto-antibodies (4.79 (3.39-8.28) versus 3.95 (1.78-7.0), p = .03; 168.84 ± 153.63 versus 101.44 ± 47.36, p = .01; 34.1% (14/41) versus 0% (0/9), p = .04; respectively). CONCLUSION: Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement and associated with less severe renal damage, especially with the combined evaluation of serum PTX3 levels.

Simultaneous efficient removal of tetracycline and mitigation of antibiotic resistance genes enrichment by a modified activated sludge process with static magnetic field.

To address the increasing issue of antibiotic wastewater, this study applied a static magnetic field (SMF) to the activated sludge process to increase the efficiency of tetracycline (TC) removal from swine wastewater and to reveal its enhanced mechanisms. The results demonstrated that the SMF-modified activated sludge process could achieve almost complete TC removal at sludge loading rates of 0.3 mg TC/g MLSS/d. Analysis of zeta potential and extracellular polymeric substances composition of the activated sludge revealed that SMF increased electrostatic interactions between TC and activated sludge and made activated sludge has much more binding sites, finally resulting in the increased TC biosorption. Metagenomic analysis showed that SMF promoted the enrichment of ammonia-oxidizing bacteria, TC-degrading bacteria, and aromatic compounds-degrading bacteria; it also enhanced ammonia monooxygenase- and cytochrome P450-mediated TC metabolism while upregulating functional genes associated with oxidase, reductase, and dehydrogenase - all contributing to increased TC biodegradation. Additionally, SMF mitigated the enrichment and spread of antibiotic resistance genes (ARGs) by decreasing the abundance of potential hosts of ARGs and inhibiting the upregulation of genes encoding ABC transporters and putative transposase. Based on these findings, this study demonstrates that magnetic field is an enhancement strategy with great potential to relieve the harmful impacts of the growing antibiotic wastewater problem on human health and the ecosystem.

The Role of Anti-mCRP Autoantibodies in Lupus Nephritis.

Background: Lupus nephritis is characterized by multiple autoantibodies production. However, there are few autoantibodies associated with disease activity and prognosis. CRP exists in at least two conformationally distinct forms: native pentameric C-reactive protein (pCRP) and modified/monomeric CRP (mCRP). Autoantibodies against mCRP are prevalent in sera of patients with lupus nephritis and are reported to be pathogenic. Summary: The levels of serum anti-mCRP autoantibodies are associated with clinical disease activity, tubulointerstitial lesions, treatment response, and prognosis in patients with lupus nephritis. The key epitope of mCRP was amino acid 35-47. Furthermore, emerging evidence indicated that anti-mCRP autoantibodies could participate in the pathogenesis of lupus nephritis by forming in situ immune complexes or interfering with the biological functions of mCRP, such as binding to complement C1q and factor H. Key Messages: Here, we review the recent advances in the prevalence, clinical-pathological associations, and potential pathogenesis of anti-mCRP autoantibodies in lupus nephritis, which may provide a promising novel therapeutic strategy for lupus nephritis.

Glomerular mTORC1 activation was associated with podocytes to endothelial cells communication in lupus nephritis.

OBJECTIVE: This study was initiated to evaluate the mammalian target of the rapamycin (mTOR) signalling pathway involved in renal endothelial-podocyte crosstalk in patients with lupus nephritis (LN). METHODS: We compared the kidney protein expression patterns of 10 patients with LN with severe endothelial-podocyte injury and 3 patients with non-severe endothelial-podocyte injury on formalin-fixed paraffin-embedded kidney tissues using label-free liquid chromatography-mass spectrometry for quantitative proteomics analysis. Podocyte injury was graded by foot process width (FPW). The severe group was referred to patients with both glomerular endocapillary hypercellularity and FPW >1240 nm. The non-severe group included patients with normal endothelial capillaries and FPW in the range of 619~1240 nm. Gene Ontology (GO) enrichment analyses were performed based on the protein intensity levels of differentially expressed proteins in each patient. An enriched mTOR pathway was selected, and the activation of mTOR complexes in renal biopsied specimens was further verified in 176 patients with LN. RESULTS: Compared with those of the non-severe group, 230 proteins were upregulated and 54 proteins were downregulated in the severe group. Furthermore, GO enrichment analysis showed enrichment in the 'positive regulation of mTOR signalling' pathway. The glomerular activation of mTOR complex 1 (mTORC1) was significantly increased in the severe group compared with the non-severe group (p=0.034), and mTORC1 was located in podocytes and glomerular endothelial cells. Glomerular activation of mTORC1 was positively correlated with endocapillary hypercellularity (r=0.289, p<0.001) and significantly increased in patients with both endocapillary hypercellularity and FPW >1240 nm (p<0.001). CONCLUSIONS: Glomerular mTORC1 was highly activated in patients with both glomerular endocapillary hypercellularity and podocyte injury, which might be involved in podocytes to endothelial cells communication in lupus nephritis.

Urinary sediments could differentiate endocapillary proliferative lupus nephritis and endocapillary proliferative IgA nephropathy.

OBJECTIVE: This study investigated the differences in urinary sediment findings between patients with endocapillary proliferative lupus nephritis (LN) and patients with endocapillary proliferative IgA nephropathy (IgAN) and further evaluated the associations of leukocyturia with disease activity, pathological features and prognosis. METHODS: The urinary sediments of 126 patients, including 92 with LN and 34 with IgAN, with renal-biopsy-proven endocapillary proliferative glomerulonephritis (EPGN) were examined by a standardized method. The urinary elements investigated included various cells, casts and crystals. The associations of leukocyturia with disease activity, pathological features and prognosis were further analyzed. RESULTS: In the patients with EPGN, normal to mild leukocyturia (≤12/HPF) and moderate to severe leukocyturia (>12/HPF) were found in 52 (41.27%) and 74 (58.73%) patients, respectively. The proportion of moderate to severe leukocyturia and the frequencies of urinary white blood cell casts and waxy casts were significantly higher in endocapillary proliferative LN than those in endocapillary proliferative IgAN (P < 0.001, P = 0.020, P = 0.010, respectively). In the endocapillary proliferative LN group, the levels of leukocyturia were significantly correlated with serum creatinine (r = 0.288, P = 0.005), eGFR (r = -0.284, P = 0.006), serum C3 (r = -0.275, P = 0.009), SLEDAI scores (r = 0.383, P ≤ 0.001) and glomerular leukocyte infiltration (r = 0.285, P = 0.002). A multivariate analysis showed that leukocyturia was an independent risk factor for renal outcomes in endocapillary proliferative LN (HR: 1.456, 95% CI: 1.083-1.957, P = 0.013) but not in IgAN. CONCLUSIONS: Urinary sediments of LN with EPGN and IgAN with EPGN differed in many aspects. Leukocyturia could reflect the disease activity and prognosis of EPGN, especially in endocapillary proliferative LN.

Enhancement of static magnetic field on nitrogen removal at different ammonium concentrations in a sequencing batch reactor: Performance and biological mechanism.

This study aimed to investigate the effects and biological mechanism of external static magnetic fields (SMFs) on enhancing nitrogen removal at different influent ammonium nitrogen (NH4+) concentrations. Four sequential batch reactors (SBRs) with SMFs of 0, 15, 30, and 50 mT were operated continuously for 196 days, during which the influent NH4+-N concentration increased stepwise as 50, 100, 350, and 600 mg L-1. The results showed that 50 mT had optimum effects on enhancing nitrogen removal, especially at high NH4+-N concentrations (350 and 600 mg L-1). The biological mechanism by which SMF influences nitrogen removal varies depending on the NH4+ concentration. At low NH4+-N concentrations (50 and 100 mg L-1), a field of 50 mT increased key enzyme activities and corresponding functional gene abundances. Additionally, it further improved functional bacterial abundances, which involved nitrifying and denitrifying bacteria at high NH4+ concentrations. These findings could provide guidance for the selection of optimum SMF intensity at different influent NH4+ concentrations.

[Effect of Acorus tatarinowii schott on ultrastructure and permeability of blood-brain barrier].

OBJECTIVE: To explore the influence of Acorus tatarinowii schott on ultrastructure and permeability of BBB. METHOD: The ultrastructure and permeability of BBB on rats with A. tatarinowii by electron microscope were observed. The even's blue (EB) and sodium phenytoin in brain was determined by UV and HPLC-MS. RESULT: After give A. tatarinowii, tight junctions of the endothelial cell opened in cotex, and the concentration of EB and sodium phenytoin in brain are significant increased. CONCLUSION: A. tatarinowii can increase the permeability of BBB, and show its 'Kaiqiao' effect.

Characterization of aerobic granular sludge of different sizes for nitrogen and phosphorus removal.

Granular size plays a key role in the performance of the aerobic granular sludge (AGS). As the diameter of the granule increases, stratification may begin to appear due to the increase in mass transfer resistance. Aerobic granules harvested from a lab-scale anaerobic-aerobic sequencing batch reactor (AO-SBR) were classified into three categories according to their size: (a) 0.15-0.28 mm, (b) 0.28-0.45 mm and (c) larger than 0.45 mm. In this study, the categories were called small-size, medium-size and large-size granules, respectively. A fraction of the different forms of phosphate and denitrification efficiency was investigated in each category. Results show that small-size granules present much more easily mobile phosphorus than other granules. Moreover, the denitrification performance has been tested by using dumping and trickling patterns for COD and NO3--N feeding. The results demonstrated that the large-size granules exhibit poor denitrification rates, as opposed to the medium-size granules. Therefore, medium-size granules, with a size of 0.28-0.45 mm, are regarded as the most suitable granular size for AGS in this experiment from the perspective of denitrification and phosphorus removal.

Evaluation of robustness of activated sludge using calcium-induced enhancement of respiration.

Robustness of an activated sludge system, describing uncertainty and operational risk, was evaluated using the absence or presence of calcium-induced enhancement of respiration (CaER) effect. Generally, the fast-growing system was susceptible to external environmental variations, of which the sludge exhibited significant CaER effect under normal operational conditions, while the slow growing system showed less significant CaER effect. However, sludge in both systems exhibited CaER effect under stressed conditions of decreasing temperature or ammonia shocking. Therefore, the absence of CaER effect indicates a more robust system, while the presence of CaER effect indicates a susceptible system. Additionally, a method to identify safe and dangerous shocking was established by a hybrid usage of absence or presence of CaER effect and recovery index (RI) curve type. The evaluation of robustness could help determining when adjustment should be really taken to cope with the uncertainty, and thus holds a high promise for field application.

A simple respirogram-based approach for the management of effluent from an activated sludge system.

Managing wastewater treatment plant (WWTP) based on respirometric analysis is a new and promising field. In this study, a multi-dimensional respirogram space was constructed, and an important index Res/t (ratio of in-situ respiration rate to maximum respiration rate) was derived as an alarm signal for the effluent quality control. A smaller Res/t value suggests better effluent. The critical R'es/t value used for determining whether the effluent meets the regulation depends on operational conditions, which were characterized by temperature and biomass ratio of heterotrophs to autotrophs. With given operational conditions, the critical R'es/t value can be calculated from the respirogram space and effluent conditions required by the discharge regulation, with no requirement for calibration of parameters or any additional measurements. Since it is simple, easy to use, and can be readily implemented online, this approach holds a great promise for applications.