A green edge-hosted zinc single-site heterogeneous catalyst for superior Fenton-like activity.

Developing green heterogeneous catalysts with excellent Fenton-like activity is critical for water remediation technologies. However, current catalysts often rely on toxic transitional metals, and their catalytic performance is far from satisfactory as alternatives of homogeneous Fenton-like catalysts. In this study, a green catalyst based on Zn single-atom was prepared in an ammonium atmosphere using ZIF-8 as a precursor. Multiple characterization analyses provided evidence that abundant intrinsic defects due to the edge sites were created, leading to the formation of a thermally stable edge-hosted Zn-N4 single-atom catalyst (ZnN4-Edge). Density functional theory calculations revealed that the edge sites equipped the single-atom Zn with a super catalytic performance, which not only promoted decomposition of peroxide molecule (HSO5-) but also greatly lowered the activation barrier for •OH generation. Consequently, the as-prepared ZnN4-Edge exhibited extremely high Fenton-like performance in oxidation and mineralization of phenol as a representative organic contaminant in a wide range of pH, realizing its quick detoxification. The atom-utilization efficiency of the ZnN4-Edge was ~104 higher than an equivalent amount of the control sample without edge sites (ZnN4), and the turnover frequency was ~103 times of the typical benchmark of homogeneous catalyst (Co2+). This study opens up a revolutionary way to rationally design and optimize heterogeneous catalysts to homogeneous catalytic performance for Fenton-like application.

Sirtuin 6 protects against podocyte injury by blocking the renin-angiotensin system by inhibiting the Wnt1/ß-catenin pathway.

Sirtuins (Sirts) are a family of nicotinamide adenine dinucleotide-dependent protein deacetylases that share diverse cellular functions. Increasing evidence shows that Sirts play a critical role in podocyte injury, which is a major determinant of proteinuria-associated renal disease. Membranous nephropathy (MN) is a typical glomerular disease in which podocyte damage mediates proteinuria development. In this study we investigated the molecular mechanisms underlying the regulatory roles of Sirt in podocyte injury in MN patients, rats with cationic bovine serum albumin (CBSA)-induced MN and zymosan activation serum (ZAS)-stimulated podocytes. Compared with healthy controls, MN patients showed significant reduction in intrarenal Sirt1 and Sirt6 protein expression. In CBSA-induced MN rats, significant reduction in intrarenal Sirt1, Sirt3 and Sirt6 protein expression was observed. However, only significant decrease in Sirt6 protein expression was found in ZAS-stimulated podocytes. MN patients showed significantly upregulated protein expression of Wnt1 and ß-catenin and renin-angiotensin system (RAS) components in glomeruli. CBSA-induced MN rats exhibited significantly upregulated protein expression of intrarenal Wnt1 and ß-catenin and their downstream gene products as well as RAS components. Similar results were observed in ZAS-stimulated podocytes. In ZAS-stimulated podocytes, treatment with a specific Sirt6 activator UBCS039 preserved the protein expression of podocin, nephrin and podocalyxin, accompanied by significant inhibition of the protein expression of ß-catenin and its downstream gene products, including Snail1 and Twist; treatment with a ß-catenin inhibitor ICG-001 significantly preserved the expression of podocyte-specific proteins and inhibited the upregulation of downstream ß-catenin gene products accompanied by significant suppression of the protein expression of RAS components. Thus, we demonstrate that Sirt6 ameliorates podocyte injury by blocking RAS signalling via the Wnt1/ß-catenin pathway. Sirt6 is a specific therapeutic target for the treatment of podocyte damage-associated renal disease.

Fullerene-polysaccharide supramolecular hydrogel displaying antioxidation/antiglycation behavior.

A fullerene-polysaccharide supramolecular hydrogel was constructed by carrying out a co-assembly of fullerene@hydroxypropyl-ß-cyclodextrin, chitosan and bentonite, and displayed good antioxidant and antiglycation properties, and hence showed promising cosmetics applications. Benefitting from the cyclodextrin hydrophobic cavity, hydroxypropyl-ß-cyclodextrin formed a stoichiometric 2 : 1 complex with fullerene, effectively enhancing the water solubility and biological activity of fullerene, and the encapsulation ratio of the prepared fullerene was calculated to be 79%. Results of oxygen radical absorbance capacity and pyrogallol autoxidation experiments showed high antioxidant activity displayed by the fullerene@HP-ß-CD inclusion complex. The supramolecular inclusion was further co-assembled, using multiple hydrogen bonds and electrostatic interactions, with chitosan and bentonite to form a supramolecular hydrogel; this hydrogel was successfully used in antiglycation, with a glycation end products inhibition rate of 43.99% at a 10% sample concentration. Therefore, the fullerene-polysaccharide ternary co-assembly supramolecular hydrogel showed good antioxidant and antiglycation abilities, and the construction of the polysaccharide supramolecular hydrogel provided a new perspective for raw materials to consider in cosmetics applications.

Comparison of the prophylactic antithrombotic effect of indobufen and warfarin in patients with nephrotic syndrome: a randomized controlled trial.

PURPOSE: The risk of thromboembolic events is elevated in patients with nephrotic syndrome, and warfarin use has been associated with an increased risk of bleeding. Indobufen, a selective cyclooxygenase-1 inhibitor, is currently being evaluated for the prevention of thromboembolic events in nephrotic syndrome. This study aimed to compare the efficacy and safety of indobufen with that of warfarin in patients with nephrotic syndrome. MATERIALS AND METHODS: This multicenter, randomized, three-arm, open-label, parallel controlled trial involved a total of 180 adult patients with nephrotic syndrome from four centers in China. Patients were randomly assigned to receive 100 mg indobufen (bid), 200 mg indobufen (bid), and 3 mg warfarin (qd) daily for 12 weeks. The primary endpoints included thromboembolic and bleeding events, while laboratory results and adverse events constituted secondary endpoints. RESULTS: No thromboembolic events occurred in the high-/low-dose indobufen and warfarin groups. Moreover, the use of a low dose of indobufen significantly reduced the risk of minor bleeding events compared with warfarin use (2% versus 18%, p < .05). Finally, adverse events were more frequent in warfarin-treated patients. CONCLUSIONS: This study found that indobufen therapy provided equivalent effects in preventing thromboembolic events compared with warfarin therapy, while low dose of indobufen was associated with a reduced risk of bleeding events, thus it should be recommended for the prevention of thromboembolic events in clinical practice in patients with nephrotic syndrome. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-17013428.

Insights into the Competitive Mechanisms of Per- and Polyfluoroalkyl Substances Partition in Liver and Blood.

Some per- and polyfluoroalkyl substances (PFASs) tend to be accumulated in liver and cause hepatotoxicity. However, the difficulty to directly measure liver concentrations of PFASs in humans hampers our understanding of their hepatotoxicity and mechanisms of action. We investigated the partitioning of 11 PFASs between liver and blood in male CD-1 mice. Although accumulation of the perfluoroalkanesulfonic acids (PFSAs) in mice serum was higher than their carboxylic acids (PFCAs) counterparts as expected, the liver-blood partition coefficients (RL/S) of PFSAs were lower than the PFCAs RL/S, implying a competition between liver and blood. The in vitro experiments further indicated that the partitioning was dominantly determined by their competitive binding between human liver fatty acid binding protein (hL-FABP) and serum albumin (HSA). The binding affinities (Kd) of PFASs to both proteins were measured. The correlations between the RL/S and log Kd (hL-FABP)/log Kd (HSA) were stronger than those with log Kd (hL-FABP) alone, magnifying that the partitioning was dominantly controlled by competitive binding between hL-FABP and HSA. Therefore, the liver concentrations of the selected PFASs in humans could be predicted from the available serum concentrations, which is important for assessing their hepatotoxicity.

Power system load forecasting using mobility optimization and multi-task learning in COVID-19.

Affected by the new coronavirus (COVID-19) pandemic, global energy production and consumption have changed a lot. It is unknown whether conventional short-term load forecasting methods based on single-task, single-region, and conventional indicators can accurately capture the load pattern during the COVID-19 and should be carefully studied. In this paper, we make the following contributions: 1) A mobility-optimized load forecasting method based on multi-task learning and long short-term memory network is innovatively proposed to alleviate the impact of the COVID-19 on short-term load forecasting. The incorporation of mobility data and data sharing layers potentially reduces the difficulty of capturing the load patterns and improves the generalization of the load forecasting models. 2) The real public data collected from multiple agencies and companies in the United States and European countries are used to conduct horizontal and vertical tests. These tests prove the failure of the conventional models and methods in the COVID-19 and demonstrate the high accuracy (error mostly less than 1%) and robustness of the proposed model. 3) The Shapley additive explanations technology based on game theory is innovatively introduced to improve the objectivity of the models. It visualizes that mobility indicators are of great help to the accurate load forecasting. Besides, the non-synchronous relationships between the indicators' correlations and contributions to the load have been proved.

Phosphorus Deficiency Promoted Hydrolysis of Organophosphate Esters in Plants: Mechanisms and Transformation Pathways.

The biotransformation of organophosphate esters (OPEs) in white lupin (Lupinus albus) and wheat (Triticum aestivum L.) was investigated in hydroponic experiments with different phosphorus (P)-containing conditions. The hydrolysis rates of OPEs followed the order of triphenyl phosphate (TPHP) > tri-n-butyl phosphate (TnBP) > tris(1,3-dichloro-2-propyl) phosphate (TDCPP). Hydrolysis of OPEs was accelerated at P-deficient conditions, and faster hydrolysis took place in white lupin than in wheat. Coincidingly, the production of acid phosphatase (ACP) in both plants was promoted, and much higher intracellular and extracellular ACPs were observed in white lupin under P-deficient conditions. In vitro experiments revealed that ACP was a key enzyme to hydrolyze OPEs. The hydrolysis rates of OPEs were significantly correlated with the Hirshfeld charges, calculated by density functional theory, of the oxygen atom in the single P-O bond. Using ultra-high-performance liquid chromatography coupled with Orbitrap Fusion mass spectrometer, 30 metabolites were successfully identified. Some of these metabolites, such as sulfate-conjugated products, hydration of cysteine-conjugated products of TPHP, and reductively dechlorinated metabolites of TDCPP, were observed for the first time in plants. It is noteworthy that OPEs may transform into many hydroxylated metabolites, and special attention should be paid to their potential environmental effects.

Atlantic hurricane surge response to geoengineering.

Devastating floods due to Atlantic hurricanes are relatively rare events. However, the frequency of the most intense storms is likely to increase with rises in sea surface temperatures. Geoengineering by stratospheric sulfate aerosol injection cools the tropics relative to the polar regions, including the hurricane Main Development Region in the Atlantic, suggesting that geoengineering may mitigate hurricanes. We examine this hypothesis using eight earth system model simulations of climate under the Geoengineering Model Intercomparison Project (GeoMIP) G3 and G4 schemes that use stratospheric aerosols to reduce the radiative forcing under the Representative Concentration Pathway (RCP) 4.5 scenario. Global mean temperature increases are greatly ameliorated by geoengineering, and tropical temperature increases are at most half of those temperature increases in the RCP4.5. However, sulfate injection would have to double (to nearly 10 teragrams of SO2 per year) between 2020 and 2070 to balance the RCP4.5, approximately the equivalent of a 1991 Pinatubo eruption every 2 y, with consequent implications for stratospheric ozone. We project changes in storm frequencies using a temperature-dependent generalized extreme value statistical model calibrated by historical storm surges and observed temperatures since 1923. The number of storm surge events as big as the one caused by the 2005 Katrina hurricane are reduced by about 50% compared with no geoengineering, but this reduction is only marginally statistically significant. Nevertheless, when sea level rise differences in 2070 between the RCP4.5 and geoengineering are factored into coastal flood risk, we find that expected flood levels are reduced by about 40 cm for 5-y events and about halved for 50-y surges.

Combined Clinical Phenotype and Lipidomic Analysis Reveals the Impact of Chronic Kidney Disease on Lipid Metabolism.

Chronic kidney disease (CKD) results in significant dyslipidemia and profound changes in lipid and lipoprotein metabolism. The associated dyslipidemia, in turn, contributes to progression of CKD and its cardiovascular complications. To gain an in-depth insight into the disorders of lipid metabolism in advanced CKD, we applied UPLC-HDMS-based lipidomics to measure serum lipid metabolites in 180 patients with advanced CKD and 120 age-matched healthy controls. We found significant increases in the levels of total free fatty acids, glycerolipids, and glycerophospholipids in patients with CKD. The levels of free fatty acids, glycerolipids, and glycerophospholipids directly correlated with the level of serum triglyceride and inversely correlated with the levels of total cholesterol and eGFR. A total of 126 lipid species were identified from positive and negative ion modes. Out of 126, 113 identified lipid species were significantly altered in patients with CKD based on the adjusted FDR method. These results pointed to profound disturbance of fatty acid and triglyceride metabolisms in patients with CKD. Logistic regression analysis showed strong correlations between serum methyl hexadecanoic acid, LPC(24:1), 3-oxooctadecanoic acid, and PC(20:2/24:1) levels with eGFR and serum creatinine levels (R > 0.8758). In conclusion, application of UPLC-HDMS-based lipidomic technique revealed profound changes in lipid metabolites in patients with CKD. The observed increases in serum total fatty acids, glycerolipids, and glycerophospholipids levels directly correlated with increased serum triglyceride level and inversely correlated with the eGFR and triglyceride levels.

Chemotherapy with or without plasmapheresis in acute renal failure due to multiple myeloma: a meta-analysis.

BACKGROUND/AIM: The clinical benefits of plasmapheresis in the management of multiple myeloma-induced acute renal failure remain controversial. In this study, we conducted a meta-analysis to quantitatively evaluate the clinical efficacy of chemotherapy with or without plasmapheresis in the treatment of multiple myeloma patients with renal failure. METHODS: Randomized controlled trials evaluating clinical efficacy of plasmapheresis were identified by searching PubMed (from 1980 to November 2013) and EMBASE (from 1980 to November 2013). Outcomes subjected to meta-analysis were 6-month survival and dialysis-dependent rate. RESULTS: Three randomized controlled studies were selected for meta-analysis. A total of 63 patients received chemotherapy only and 84 patients were given both chemotherapy and plasmapheresis. No difference was observed in 6-month survival rate between plasmapheresis and control group (75% vs. 66.7%; risk ratio, 0.92; 95% CI, 0.76 - 1.11; p = 0.39). 6-month dialysis-dependent ratio was significantly lower in patients treated with both chemotherapy and plasmapheresis than chemotherapy only (15.6% vs. 37.2%; risk ratio, 2.02; 95% CI, 1.03 - 3.96; p = 0.04). CONCLUSION: Our meta-analysis results showed that plasmapheresis used as an adjunct to chemotherapy had a benefit in the management of dialysisdependent multiple myeloma patients with renal failure.

Stabilizing Hypoxia-Inducible Factor to Manage Anemia in Chronic Kidney Disease: From Basic Theory to Clinical Study.

Background: Anemia is one of the common complications of chronic kidney disease (CKD), and its prevalence has been arising globally. The key cause of anemia in CKD patients is the diseased kidney's reduced ability to synthesize endogenous erythropoietin (EPO), yet this is not the sole reason. Inflammatory elements, functional iron deficiency, and uremic toxins together participate in the development of anemia. According to research data, anemia is an independent risk factor for cardiovascular events, all-cause mortality, and worsening renal function and affects the clinical prognosis and quality of life of CKD patients. Regular treatments for anemia in CKD patients include the use of erythropoiesis-stimulating agents (ESAs), iron supplements, and blood transfusions. Summary: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel and small-molecule pharmacological compounds that target the hypoxia-inducible factor (HIF) pathway and are another option for improving anemia in CKD patients. HIF-PHIs simulate hypoxia, stabilize HIF protein, stimulate EPO synthesis, reduce hepcidin level, boost iron utilization, induce the creation of red blood cells, and alleviate anemia. The results of several HIF-PHI phase III trials indicated that HIF-PHIs are similarly effective as ESA at raising hemoglobin concentration. Key Messages: This article summarizes the structure of HIF and the mechanism of stabilizing HIF to improve anemia, discusses the efficacy of HIF-PHIs in CKD patients with or without dialysis, as well as emphasizes the potential safety concerns with HIF-PHIs.

Lactobacillus species ameliorate membranous nephropathy through inhibiting the aryl hydrocarbon receptor pathway via tryptophan-produced indole metabolites.

BACKGROUND AND PURPOSE: Membranous nephropathy (MN) is an immune-mediated glomerular disease in adults. Antibody- and antigen-bonding mechanisms have been largely clarified, but the subepithelium immune complex deposition-mediated downstream molecular mechanisms are currently unresolved. Increasing evidence has suggested that gut microbiota contribute to MN pathogenesis. EXPERIMENTAL APPROACH: In this study, we identified alterations in faecal gut microbiota and serum metabolites that mediate an aryl hydrocarbon receptor (AhR) mechanism in cationic bovine serum albumin (CBSA)-induced MN rats and in patients with idiopathic MN (IMN). KEY RESULTS: Impaired renal function correlated with the relative abundance of reduced faecal probiotics, Lactobacillus and Bifidobacterium, and altered serum levels of tryptophan-produced indole derivatives (TPIDs) in MN rats. Further results showed that reduced relative abundance of five probiotics, namely Lactobacillus johnsonii, Lactobacillus murinus, Lactobacillus vaginalis, Lactobacillus reuteri and Bifidobacterium animalis, positively correlated with decreased levels of indole-3-pyruvic acid, indole-3-aldehyde and tryptamine and negatively correlated with increased levels of indole-3-lactic acid and indole-3-acetic acid in serum of MN rats. Altered five probiotics and five TPIDs also were observed in patients with IMN. Further studies showed that MN rats exhibited a significant increase in intrarenal mRNA expression of AhR and its target genes CYP1A1, CYP1A2 and CYP1B1, which were accompanied by protein expression of down-regulated cytoplasmic AhR, but up-regulated nuclear AhR, in MN rats and IMN patients. CONCLUSION AND IMPLICATIONS: Activation of the intrarenal AhR signalling pathway may involve five TPIDs. These data suggest that gut microbiota could influence MN through TPIDs that engage host receptors.

Oxidative stress and inflammation are mediated via aryl hydrocarbon receptor signalling in idiopathic membranous nephropathy.

Membranous nephropathy (MN) patients are diagnosed by the presence of phospholipase A2 receptor (PLA2R) before they progress to renal failure. However, the subepithelium-like immunocomplex deposit-mediated downstream molecular pathways are poorly understood. The aryl hydrocarbon receptor (AHR), NF-ƙB and Nrf2 pathways play central roles in the pathogenesis and progression of chronic kidney disease. However, their mutual effects on MN require further examination. Thus, we investigated the effect of AHR signalling on the NF-ƙB and Nrf2 pathways in IMN patients, cationic bovine serum albumin (CBSA)-injected rats and zymosan activation serum (ZAS)-treated podocytes. IMN patients show significantly decreased serum total protein and albumin levels, increased urine protein levels and intrarenal IgG4 and PLA2R protein expression in glomeruli compared with controls. IMN patients exhibited increased mRNA expression of intrarenal AHR and its target genes, including CYP1A1, CYP1A2, CYP1B1 and COX-2. This increase was accompanied by significantly upregulated protein expression of CD3, NF-ƙB p65 and COX-2 and significantly downregulated Nrf2 and HO-1 expression. Similarly, CBSA-induced rats showed severe proteinuria and activated intrarenal AHR signalling. This was accompanied by significantly upregulated protein expression of intrarenal p-IκBα, NF-κB p65 and its gene products, including COX-2, MCP-1, iNOS, 12-LOX, p47phox and p67phox, and significantly downregulated protein expression of Nrf2 and its gene products, including HO-1, catalase, GCLC, GCLM, MnSOD and NQO1. These results were further verified in ZAS-induced podocytes. Treatment with the AHR antagonist CH223191 and AHRsiRNA significantly preserved podocyte-specific protein expression and improved the NF-ƙB and Nrf2 pathways in ZAS-induced podocytes. In contrast, similar results were obtained in ZAS-induced podocytes treated with the NF-ƙB inhibitor BAY 11-7082 and NF-κBp65 siRNA. However, neither method had a significant effect on AHR signalling. Collectively, these results indicate that the NF-ƙB pathway is a downstream target of AHR signalling. Our findings suggest that blocking AHR signalling inhibits oxidative stress and inflammation, thereby improving proteinuria and renal injury.

Moshen granule ameliorates membranous nephropathy by regulating NF-ƙB/Nrf2 pathways via aryl hydrocarbon receptor signalling.

Considerable achievements were realized in illuminating underlying pathological mechanisms of patients with idiopathic membranous nephropathy (IMN). Although IMN patients are well diagnosed before they reach renal failure, no currently available drug intervention is effective in halting IMN progression. In this study, we assess Moshen granule (MSG) effect on IMN patients and cationic bovine serum albumin (CBSA)-induced rats. Increasing studies has indicated that activation of aryl hydrocarbon receptor (AHR) was related to oxidative stress and inflammation. We further determine MSG effect on AHR, nuclear factor ƙB (NF-ƙB) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the CBSA-induced rats. MSG markedly reduces proteinuria and improves kidney function in both IMN patients and rats induced by CBSA. MSG markedly inhibits increased mRNA expressions of intrarenal AHR and its four downstream target genes including CYP1A1, CYP1A2, CYP1B1 and COX-2 compared with untreated CBSA-induced rats. This is accompanied by markedly downregulated protein expressions of p-IƙBα and NF-ƙB p65 and its downstream gene products including MCP-1, COX-2, 12-LOX, iNOS, p47phox and p67phox, while markedly preserves protein expressions of Nrf2 and its downstream gene products including catalase, HO-1, GCLM, GCLC, MnSOD and NQO1 in the kidney tissues. These data suggests MSG blunts podocyte damage through inhibiting activation of NF-ƙB/Nrf2 pathway via AHR signaling. This finding may provide a promising therapy for treatment of IMN through oxidative stress and inflammation.

Widely targeted metabolomic profiling combined with transcriptome analysis sheds light on flavonoid biosynthesis in sweet orange 'Newhall' (C. sinensis) under magnesium stress.

Sweet orange 'Newhall' peels (SOPs) are abundant in flavonoids, making them increasingly popular in the realms of nutrition, food, and medicine. However, there is still much unknown about flavonoid components in SOPs and the molecular mechanism of flavonoid biosynthesis when subjected to magnesium stress. The previous experiment conducted by the research group found that the total flavonoid content of Magnesium deficiency (MD) was higher than Magnesium sufficiency (MS) in SOPs. In order to study the metabolic pathway of flavonoids under magnesium stress, an integrative analysis of the metabolome and transcriptome was performed in SOPs at different developmental stages, comparing MS and MD. A comprehensive analysis revealed the identification of 1,533 secondary metabolites in SOPs. Among them, 740 flavonoids were classified into eight categories, with flavones identified as the dominant flavonoid component. The influence of magnesium stress on flavonoid composition was evaluated using a combination of heat map and volcanic map, which indicated significant variations between MS and MD varieties at different growth stages. The transcriptome detected 17,897 differential genes that were significantly enriched in flavonoid pathways. Further analysis was performed using Weighted gene correlation network analysis (WGCNA) in conjunction with flavonoid metabolism profiling and transcriptome analysis to identify six hub structural genes and ten hub transcription factor genes that play a crucial role in regulating flavonoid biosynthesis from yellow and blue modules. The correlation heatmap and Canonical Correspondence Analysis (CCA) results showed that CitCHS had a significant impact on the synthesis of flavones and other flavonoids in SOPs, as it was the backbone gene in the flavonoid biosynthesis pathway. The qPCR results further validated the accuracy of transcriptome data and the reliability of candidate genes. Overall, these results shed light on the composition of flavonoid compounds in SOPs and highlight the changes in flavonoid metabolism that occur under magnesium stress. This research provides valuable insights for improving the cultivation of high-flavonoid plants and enhancing our understanding of the molecular mechanisms underlying flavonoid biosynthesis.

Evaluation of safety, effectiveness and treatment patterns of sodium zirconium cyclosilicate in management of hyperkalaemia in China: a real-world study protocol.

INTRODUCTION: Hyperkalaemia (HK) is a potentially life-threatening electrolyte imbalance associated with several adverse clinical outcomes. The efficacy and negative effects of currently existing treatment options have made HK management questionable. Sodium zirconium cyclosilicate (SZC), a novel highly selective potassium binder, is approved for the treatment of HK. The present study will be aimed to assess the safety, effectiveness and treatment patterns of SZC in Chinese patients with HK in a real-world clinical setting as it is required by China's drug review and approval process. METHODS AND ANALYSIS: This is a multicentre, prospective cohort study which plans to enrol 1000 patients taking SZC or willing to take SZC from approximately 40 sites in China. Patients ≥18 years of age at the time of signing the written informed consent and with documented serum potassium levels ≥5.0 mmol/L within 1 year before study enrolment day will be included. Eligible patients will receive SZC treatment and will be followed up for 6 months from enrolment day. The primary objective will be to evaluate the safety of SZC for the management of HK in Chinese patients in terms of adverse events (AEs), serious AEs as well as discontinuation of SZC. The secondary objectives will include understanding the SZC dosage information in terms of its effectiveness and treatment patterns under real-world clinical practice and assessing effectiveness of SZC during the observational period. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University (approval number: YJ-JG-YW-2020). All the participating sites have received the ethics approval. Results will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05271266.

Membranous nephropathy: Systems biology-based novel mechanism and traditional Chinese medicine therapy.

Membranous nephropathy (MN) is a renal-limited non-inflammatory autoimmune disease in the glomerulus, which is the second or third main cause of end-stage kidney diseases in patients with primary glomerulonephritis. Substantial achievements have increased our understanding of the aetiology and pathogenesis of murine and human MN. The identification of nephritogenic autoantibodies against neutral endopeptidase, phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) antigens provide more specific concept-driven intervention strategies for treatments by specific B cell-targeting monoclonal antibodies to inhibit antibody production and antibody-antigen immune complex deposition. Furthermore, additional antibody specificities for antigens have been discovered, but their pathogenic effects are uncertain. Although anti-PLA2R and anti-THSD7A antibodies as a diagnostic marker is widely used in MN patients, many questions including autoimmune response development, antigenic epitopes, and podocyte damage signalling pathways remain unresolved. This review describes the current available evidence regarding both established and novel molecular mechanisms based on systems biology approaches (gut microbiota, long non-coding RNAs, metabolite biomarkers and DNA methylation) in MN, with an emphasis on clinical findings. This review further summarizes the applications of traditional Chinese medicines such as Tripterygium wilfordii and Astragalus membranaceus for MN treatment. Lastly, this review considers how the identification of novel antibodies/antigens and unresolved questions and future challenges reveal the pathogenesis of MN.

TGF-ß/Smad Signaling Pathway in Tubulointerstitial Fibrosis.

Chronic kidney disease (CKD) was a major public health problem worldwide. Renal fibrosis, especially tubulointerstitial fibrosis, is final manifestation of CKD. Many studies have demonstrated that TGF-ß/Smad signaling pathway plays a crucial role in renal fibrosis. Therefore, targeted inhibition of TGF-ß/Smad signaling pathway can be used as a potential therapeutic measure for tubulointerstitial fibrosis. At present, a variety of targeting TGF-ß1 and its downstream Smad proteins have attracted attention. Natural products used as potential therapeutic strategies for tubulointerstitial fibrosis have the characteristics of acting on multiple targets by multiple components and few side effects. With the continuous research and technique development, more and more molecular mechanisms of natural products have been revealed, and there are many natural products that inhibited tubulointerstitial fibrosis via TGF-ß/Smad signaling pathway. This review summarized the role of TGF-ß/Smad signaling pathway in tubulointerstitial fibrosis and natural products against tubulointerstitial fibrosis by targeting TGF-ß/Smad signaling pathway. Additionally, many challenges and opportunities are presented for inhibiting renal fibrosis in the future.

Research Progress of Chinese Herbal Medicine Intervention in Renal Interstitial Fibrosis.

Chronic kidney diseases usually cause renal interstitial fibrosis, the prevention, delay, and treatment of which is a global research hotspot. However, no definite treatment options are available in modern medicine. Chinese herbal medicine has a long history, rich varieties, and accurate treatment effects. Hitherto, many Chinese herbal medicine studies have emerged to improve renal interstitial fibrosis. This paper reviews the mechanisms of renal interstitial fibrosis and recent studies on the disease intervention with Chinese herbal medicine through literature search, intend to reveal the importance of Chinese herbal medicine in renal interstitial fibrosis. The results show that Chinese herbal medicine can improve renal interstitial fibrosis, and the effects of Chinese herbal medicine on specific pathological mechanisms underlying renal interstitial fibrosis have been explored. Additionally, the limitations and advantages of Chinese herbal medicine in the treatment of renal interstitial fibrosis, possible research directions, and new targets of Chinese herbal medicine are discussed to provide a basis for studies of renal interstitial fibrosis.

Underlying mechanisms for the impacts of molecular structures and water chemistry on the enrichment of poly/perfluoroalkyl substances in aqueous aerosol.

Enrichment of ionic poly/perfluoroalkyl substances (PFASs) in aqueous aerosol (AA) is an important pathway for them to enter atmosphere. In this study, the enrichment behaviors of 12 legacy and emerging PFASs in AA in both single solute and mixed solutions were investigated. The enrichment factors (EF) displayed a general increasing trend with the fluorinated carbon chain length. For the first time, a robust Quantitative Structure-Property Relationship (QSPR) model coupled with partial least-square method was established with fifteen quantum chemical descriptors. Four molecular descriptors, including dipole moment (µ), molecular weight (MW), the maximal value of the molecular surface potential (Vs, max) and molecular volume (V) were identified as the key structural variables affecting the PFASs enrichment. Inorganic salts and humic acid (HA) which are common in seawater, facilitated the PFASs enrichment as a result of enhanced hydrophobicity and the bridging effect caused by divalent cations. The typical cationic and anionic surfactants, cetyltrimethylammonium bromide and sodium dodecyl sulfate, both inhibited the enrichment due to the competition between PFASs and surfactants. It is interesting that 6:2 chlorinated polyfluorinated ether sulfonate (F53B) had the highest EF among the 12 PFASs, implying its strong potential of atmosphere transport.