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BackgroundThere is little research on the relationship between flavonol consumption and chronic kidney disease (CKD). This study aimed to examine the link between flavonol consumption and the risk of CKD among US adults, using data from the 2007–2008, 2009–2010 and 2017–2018 National Health and Nutrition Examination Survey (NHANES).MethodsA cross-sectional approach was used, drawing on data from three NHANES cycles. The flavonol consumption of the participants in this study was assessed using a 48 h dietary recall interview. CKD was diagnosed based on an estimated glomerular filtration rate below 60 mL/min/1.73 m2 or a urine albumin-to-creatinine ratio of 30 mg/g or higher.ResultsCompared to the lowest quartile of flavonol intake (Q1), the odds ratios for CKD were 0.598 (95% CI: 0.349, 1.023) for the second quartile (Q2), 0.679 (95% CI: 0.404, 1.142) for the third quartile (Q3), and 0.628 (95% CI: 0.395, 0.998) for the fourth quartile (Q4), with a p value for trend significance of 0.190. In addition, there was a significant trend in CKD risk with isorhamnetin intake, with the odds ratios for CKD decreasing to 0.860 (95% CI: 0.546, 1.354) in the second quartile, 0.778 (95% CI: 0.515, 1.177) in the third quartile, and 0.637 (95% CI: 0.515, 1.177) in the fourth quartile (p for trend = 0.013).ConclusionOur analysis of the NHANES data spanning 2007–2008, 2009–2010, and 2017–2018 suggests that high consumption of dietary flavonol, especially isorhamnetin, might be linked to a lower risk of CKD in US adults. These findings offer new avenues for exploring strategies for managing CKD.

Abstract Henoch-Schonlein purpura nephritis (HSPN) is a systemic vascular inflammatory disease. Huanglian Decoction (HLD) ameliorates renal injury in nephritis; however, the mechanism of action of HLD on HSPN has not been investigated. This study aimed to investigate the protective mechanism of HLD treatment in HSPN. The effects of HLD on HSPN biochemical indices, kidney injury and NF-κB/NLRP3 signaling pathway were analyzed by biochemical analysis, ELISA, HE and PAS staining, immunohistochemistry, immunofluorescence, and Western Blot. In addition, the effects of HLD on HSPN cells were analyzed. We found that HLD treatment significantly reduced renal tissue damage, decreased the levels of IL-17, IL-18, TNF-α, and IL-1β, and increased the levels of TP and ALB in HSPN mice. It also inhibited the deposition of IgA, IgG, and C3 in kidney tissues and significantly decreased the expression of IκBα, p-IκBα, NLRP3, caspase-1, and IL-1β in kidney tissues and cells. In addition, PMA treatment inhibited the above-mentioned effects of HLD. These results suggested that HLD attenuates renal injury, IgA deposition, and inflammation in HSPN mice and its mechanism of action may be related to the inhibition of the NF-κB/NLRP3 pathway.

Abstract Background Chronic kidney disease (CKD) is a global public health issue. The diagnosis of CKD would be considerably enhanced by discovering novel biomarkers used to determine the glomerular filtration rate (GFR). Small molecule metabolites related to kidney filtration function that might be utilized as biomarkers to measure GFR more accurately could be found via a metabolomics analysis of blood samples taken from individuals with varied glomerular filtration rates. Methods An untargeted metabolomics study of 145 plasma samples was performed using ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS). The 145 samples were divided into four groups based on the patient’s measured glomerular filtration rates (mGFRs) determined by the iohexol plasma clearance rate. The data were analyzed using random forest analyses and six other unique statistical analyses. Principal component analysis (PCA) was conducted using R software. Results A large number of metabolites involved in various metabolic pathways changed significantly between groups with different GFRs. These included metabolites involved in tryptophan or pyrimidine metabolism. The top 30 metabolites that best distinguished between the four groups in a random forest plot analysis included 13 amino acids, 9 nucleotides, and 3 carbohydrates. A panel of metabolites (including hydroxyaparagine, pseudouridine, C-glycosyltryptophan, erythronate, N-acetylalanine, and 7-methylguanidine) for estimating GFR was selected for future testing in targeted analyses by combining the candidate lists with the six other statistical analyses. Both hydroxyasparagine and N,N-dimethyl-proline-proline are unique biomarkers shown to be inversely associated with kidney function that have not been reported previously. In contrast, 1,5-anhydroglucitol (1,5-AG) decreases with impaired renal function. Conclusions This global untargeted metabolomics study of plasma samples from patients with different degrees of renal function identified potential metabolite biomarkers related to kidney filtration. These novel potential metabolites provide more insight into the underlying pathophysiologic processes that may contribute to the progression of CKD, lead to improvements in the estimation of GFR and provide potential therapeutic targets to improve kidney function.

Objective Whether uric acid (UA) has an effect on renal function remains controversial. We aimed to investigate the association between serum UA with the decline in estimated glomerular filtration rate (eGFR) in middle-aged and elderly populations in the China Health and Retirement Longitudinal Study (CHARLS).Design Longitudinal cohort study.Setting This was a second analysis of a public dataset (CHARLS).Participants In this study, 4538 middle-aged and elderly individuals were screened after removing individuals younger than 45 years old, with kidney disease, malignant tumour and missing values.Outcome measures Blood tests were performed both in 2011 and 2015. Decline in eGFR was defined as an eGFR decrease of more than 25% or deterioration of the eGFR stage during the 4-year follow-up period. Logistic models corrected for multiple covariables were used to analyse the association of UA with the decline in eGFR.Results The median (IQR) concentrations of serum UA grouped by quartiles were 3.1 (0.6), 3.9 (0.3), 4.6 (0.4) and 5.7 (1.0) mg/dL, respectively. After multivariable adjustment, the OR of the decline in eGFR was higher for quartile 2 (3.5–

Background: With the development of chronic kidney disease (CKD), there are various changes in metabolites. However, the effect of these metabolites on the etiology, progression and prognosis of CKD remains unclear.Objective: We aimed to identify significant metabolic pathways in CKD progression by screening metabolites through metabolic profiling, thus identifying potential targets for CKD treatment.Methods: Clinical data were collected from 145 CKD participants. GFR (mGFR) was measured by the iohexol method and participants were divided into four groups according to their mGFR. Untargeted metabolomics analysis was performed via UPLC-MS/MSUPLC–MSMS/MS assays. Metabolomic data were analyzed by MetaboAnalyst 5.0, one-way ANOVA, principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) to identify differential metabolites for further analysis. The open database sources of MBRole2.0, including KEGG and HMDB, were used to identify significant metabolic pathways in CKD progression.Results: Four metabolic pathways were classified as important in CKD progression, among which the most significant was caffeine metabolism. A total of 12 differential metabolites were enriched in caffeine metabolism, four of which decreased with the deterioration of the CKD stage, and two of which increased with the deterioration of the CKD stage. Of the four decreased metabolites, the most important was caffeine.Conclusion: Caffeine metabolism appears to be the most important pathway in the progression of CKD as identified by metabolic profiling. Caffeine is the most important metabolite that decreases with the deterioration of the CKD stage.

The linking of ecosystem service flows (ESFs) with urban land management is still in its nascent stage. The spatial process modeling of ESFs plays a crucial role in establishing connections between urban land sustainability and human benefits. However, the spatial processes and driving mechanisms associated with urban cooling services (UCS) remain ambiguous. In this study, we selected the area within the 6th Ring Road of Beijing as the study area, where the population is highly concentrated and the urban greenery is relatively developed. We modeled the spatial processes of cooling service flow (UCSF) in this area and elucidated the contribution of landscape patterns to UCSF. Firstly, the cooling capacity, referred to as UCS, of the urban blue–green landscape, was estimated using the InVEST tool. Subsequently, the UCSF spatial process was simulated by employing a two-dimensional Gaussian function at the pixel level. In order to characterize the landscape features in the study area, eight landscape indices were selected, and Fragstats v4.2 was employed for their calculation. Finally, GeoDetector was utilized to explore the driving mechanisms of landscape patterns on UCSF. The predominant area for both UCS and UCSF lies between the 5th and 6th Ring Road in Beijing, exhibiting a declining trend from the 6th Ring Road toward the city center. The UCSF coverage area, which represents the beneficiary area, accounted for approximately 87.78% of the study area, with the largest increase occurring within the 2nd Ring Road. The Landscape Shape Index demonstrated the strongest individual contribution to UCSF, while its combined bivariate contribution was significant. Geometry exerted a greater influence on UCSF compared to landscape scale and spatial configuration. This study presents novel insights for assessing the omnidirectional flow of ESFs through the modeling of flow functions. The findings of this study can serve as a valuable reference for sustainable urban landscape management and planning.

Objectives Few studies have explored correlations between metabolic syndrome (MetS) alterations and renal deterioration in longitudinal cohorts. We aim to investigate associations between MetS recovery/development and rapid estimated glomerular filtration rate (eGFR) decline in the China Health and Retirement Longitudinal Study (CHARLS).Design Longitudinal cohort study.Setting This study is a secondary analysis of CHARLS.Participants After excluding individuals with age 3 mL/min/1.73 m2. The associations between rapid eGFR decline and MetS recovery/development were analysed using multivariable adjusted logistic models.Results According to MetS baseline status and follow-up, participants were divided into four groups: (1) 2460 (59.4%) in the MetS-free group, (2) 361 (8.7%) in the MetS-developed group, (3) 499 (12.0%) in the MetS recovery group and (4) 822 (19.8%) in the MetS chronic group. When compared with the MetS chronic group, the multivariable adjusted OR of rapid eGFR decline in the MetS recovery group was 0.64 (OR: 0.64; 95% CI 0.45 to 0.90, p=0.01). In contrast, when compared with the MetS-free group, the multivariable adjusted OR of rapid eGFR decline in the MetS-developed group was 1.00 (OR: 1.00; 95% CI 0.73 to 1.38, p=0.98).Conclusions Over the 4-year follow-up period, we found that MetS recovery was associated with a reduced risk of rapid eGFR decline in middle-aged and older adults, while MetS occurrence was not related to rapid eGFR decline. Recovery from MetS appeared to protect against a rapid decline in eGFR.

Introduction: The glomerular filtration rate (GFR) is crucial for chronic kidney disease (CKD) diagnosis and therapy. Various studies have sought to recognize ideal endogenous markers to improve the estimated GFR (eGFR) for clinical practice. To screen out potential novel metabolites related to GFR (mGFR) measurement in CKD patients from the Chinese population, we identified more biomarkers for improving GFR estimation. Methods: Fifty-three CKD participants were recruited from the third affiliated hospital of Sun Yat-sen University in 2020. For each participant, mGFR was evaluated by utilizing the plasma clearance of iohexol and collecting serum samples for untargeted metabolomics analyses by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC–MS/MS). All participants were divided into four groups according to mGFR. The metabolite peak area data were uploaded to MetaboAnalyst5.0 for one-way ANOVA, principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) and confirmed the metabolites whose levels increased or decreased with mGFR and Variable Importance in Projection (VIP) values>1. Metabolites were ranked by correlation with the original values of mGFR, and metabolites with a correlation coefficient>0.8 and VIP >2 were identified. Results: We screened out 198 metabolites that increased or decreased with mGFR decline. After ranking by correlation with mGFR, the top 50 metabolites were confirmed. Further studies confirmed the 10 most highly correlated metabolites. Conclusion: We screened out the metabolites that increased or decreased with mGFR decline in CKD patients from the Chinese population, and 10 of them were highly correlated. They are potential novel metabolites to improve GFR estimation.

Accurate understanding of spatial distribution and variability of soil total nitrogen (TN) is critical for the site-specific nitrogen management. Based on 4337 newly obtained soil observations and 33 covariates, this study applied the random forest (RF) algorithm and modified regression kriging (RF combined with residual kriging: RFK, hereafter) model to spatially predict and map topsoil TN content in agricultural areas of Henan Province, central China. According to the RFK prediction, topsoil TN content ranged from 0.52 to 1.81 g kg−1, and the farmland with the topsoil TN contents of 1.00–1.23 g kg−1 and 0.80–1.23 g kg−1 accounted for 48.2% and 81.2% of the total farmland area, respectively. Spatially, the topsoil TN in the study area was generally higher in the west and lower in the east. By using the Boruta variable selection algorithm, soil organic matter (SOM) and available potassium contents in topsoil, nitrogen deposition, average annual precipitation, livestock discharges, and topsoil pH were identified as the main factors driving the spatial distribution and variation of soil TN in the study area. The RF and RFK models used showed the expected performance and achieved acceptable TN prediction accuracy. In comparison, RFK performed slightly better than the RF model. The R2 and RMSE achieved by the RFK model were improved by 4.5% and 4.5%, respectively, compared with that by the RF model. However, the results suggest that RFK was inferior to the RF model in quantifying prediction uncertainty and thus may have a slight disadvantage in model reliability.

Studies of key metabolite variations and their biological mechanisms in cerebral infarction (CI) have increased our understanding of the pathophysiology of the disease. However, how metabolite variations in different periods of CI influence these biological processes and whether key metabolites from different periods may better predict disease progression are still unknown. We performed a systematic investigation using the metabonomics method. Various metabolites in different pathways were investigated by serum metabolic profiling of 143 patients diagnosed with CI and 59 healthy controls. Phe-Phe, carnitine C18:1, palmitic acid, cis-8,11,14-eicosatrienoic acid, palmitoleic acid, 1-linoleoyl-rac-glycerol, MAG 18:1, MAG 20:3, phosphoric acid, 5α-dihydrotestosterone, Ca, K, and GGT were the major components in the early period of CI. GCDCA, glycocholate, PC 36:5, LPC 18:2, and PA showed obvious changes in the intermediate time. In contrast, trans-vaccenic acid, linolenic acid, linoleic acid, all-cis-4,7,10,13,16-docosapentaenoic acid, arachidonic acid, DHA, FFA 18:1, FFA 18:2, FFA 18:3, FFA 20:4, FFA 22:6, PC 34:1, PC 36:3, PC 38:4, ALP, and Crea displayed changes in the later time. More importantly, we found that phenylalanine metabolism, medium-chain acylcarnitines, long-chain acylcarnitines, choline, DHEA, LPC 18:0, LPC 18:1, FFA 18:0, FFA 22:4, TG, ALB, IDBIL, and DBIL played vital roles in the development of different periods of CI. Increased phenylacetyl-L-glutamine was detected and may be a biomarker for CI. It was of great significance that we identified key metabolic pathways and risk metabolites in different periods of CI different from those previously reported. Specific data are detailed in the Conclusion section. In addition, we also explored metabolite differences of CI patients complicated with high blood glucose compared with healthy controls. Further work in this area may inform personalized treatment approaches in clinical practice for CI by experimentally elucidating the pathophysiological mechanisms.

Abstract Background The performance of previously published glomerular filtration rate (GFR) estimation equations degrades when directly used in Chinese population. We incorporated more independent variables and using complicated non-linear modeling technology (artificial neural network, ANN) to develop a more accurate GFR estimation model for Chinese population. Methods The enrolled participants came from the Third Affiliated Hospital of Sun Yat-sen University, China from Jan 2012 to Jun 2016. Participants with age

Background. Chronic kidney disease (CKD) is a global public health problem. Identifying new biomarkers that can be used to calculate the glomerular filtration rate (GFR) would greatly improve the diagnosis and understanding of CKD at the molecular level. A metabolomics study of blood samples derived from patients with widely divergent glomerular filtration rates could potentially discover small molecule metabolites associated with varying kidney function. Methods. Using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), serum was analyzed from 53 participants with a spectrum of measured GFR (by iohexol plasma clearance) ranging from normal to severe renal insufficiency. An untargeted metabolomics assay (N ¼ 214) was conducted at the Calibra-Metabolon Joint Laboratory. Results. From a large number of metabolomics-derived metabolites, the top 30 metabolites correlated to increasing renal insufficiency according to mGFR were selected by the random forest method. Significant differences in metabolite profiles with increasing stages of CKD were observed. Combining candidate lists from six other unique statistical analyses, six novel, potential metabolites that were reproducibly strongly associated with mGFR were selected, including erythronate, gulonate, C-glycosyltryptophan, N-acetylserine, N6-carbamoylthreonyladenosine, and pseudouridine. In addition, hydroxyasparagine were strongly associated with mGFR and CKD, which were unique to this study. Conclusions. Global metabolite profiling of serum yielded potentially valuable biomarkers of different stages of CKD. Additionally, these potential biomarkers might provide insight into the underlying pathophysiologic processes that contribute to the progression of CKD as well as improve GFR estimation.

Background/Aims: Chronic cerebral hypoperfusion (CCH) is a high-risk factor for vascular dementia and Alzheimer’s disease. Autophagy plays a critical role in the initiation and progression of CCH. However, the underlying mechanisms remain unclear. In this study, we identified the effect of a microRNA (miR) on autophagy under CCH. Methods: A CCH rat model was established by two-vessel occlusion (2VO). Learning and memory abilities were assessed by the Morris water maze. The protein levels of LC3, beclin-1, and mTOR were detected by western blotting and immunofluorescence assays, miR-96 expression was assessed by real-time PCR, luciferase assays were used to determine the effect of miR-96 on the 3′ untranslated region (UTR) of mTOR, and the number of autophagosomes was examined by electron microscopy. Results: The level of miR-96 was significantly increased in 2VO rats, and inhibition of miR-96 ameliorated the cognitive impairment induced by 2VO. Furthermore, the number of LC3- and beclin-1-positive autophagosomes was increased in 2VO rats, and was decreased after miR-96 antagomir injection. However, the protein level of mTOR was reduced in 2VO rats, and it was down-regulated by miR-96 overexpression and up-regulated by miR-96 inhibition in 2VO rats and primary culture cells. Moreover, the luciferase activity of the 3′-UTR of mTOR was suppressed by miR-96, which was relieved by mutation of the miR-96 binding sites. Conclusion: Our study demonstrated that miR-96 may play a key role in autophagy under CCH by regulating mTOR; therefore, miR-96 may represent a potential therapeutic target for CCH.

Soil is an important natural resource. The excessive amount of heavy metals in soil can harm and threaten human health. Therefore, monitoring of soil heavy metal content is urgent. Monitoring soil heavy metals by traditional methods requires many human and material resources. Remote sensing has shown advantages in the field of monitoring heavy metals. Based on 971 heavy metal samples and Sentinel-2 multi-spectral images in Tai Lake, China, we analyzed the correlation between six heavy metals (Cd, Hg, As, Pb, Cu, Zn) and spectral factors, and selected As and Hg as the input factors of inversion model. The correlation coefficient of the best model of As was 0.53 (p < 0.01), and of Hg was 0.318 (p < 0.01). We used the methods of partial least squares regression (PLSR) and back propagation neural network (BPNN) to establish inversion models with different combinations of spectral factors by using 649 measured samples. In addition, 322 measured samples were used for accuracy evaluation. Compared with the PLSR model, the BP neural network builds the model with higher accuracy, and B1-B4 combined with LnB1-LnB4 builds the model with the highest accuracy. The accuracy of the best model was verified, with an average error of 19% for As and 45% for Hg. Analyzing the spatial distribution of heavy metals by using the interpolation method of Kriging and IDW. The overall distribution trend of the two interpolations is similar. The concentration of As elements tends to increase from north to south, and the relatively high value of Hg elements is distributed in the east and west of the study area. The factories in the study area are distributed along rivers and lakes, which is consistent with the spatial distribution of heavy metal enrichment areas. The relatively high-value areas of heavy metal elements are related to the distribution of metal products factories, refractory porcelain factories, tile factories, factories and mining enterprises, etc., indicating that factory pollution is the main reason for the enrichment of heavy metals.

With the contamination of soil heavy metals becoming more and more serious, remediation has become a hot issue, and it is of great significance to study the remediation effects of heavy metal contaminated soil. The heavy metal contaminated soil was leached with water, acetic acid and citric acid, and the pH value of the soil after leaching was adjusted with 2% lime water. Finally, the pH value and conductivity of the soil leacheate were determined. The results showed that the best leacheate was citric acid for the remediation of soil contaminated with heavy metals Cu, Cd and Pb, and the optimum leaching concentration was 1.0, 0.4, 0.7 mol/L, respectively. For the remediation of soil contaminated with Zn, the best leacheate was acetic acid, and the optimal leaching concentration was 1 mol/L. The leaching effect of lime water on heavy metal contaminated soil was positively correlated with the concentration of organic acid, that is, the leaching effect on heavy metals was better at stronger acidic condition. The conductivity of the soil sample treated with lime water increased with the increase of the concentration of organic acid, and at the same concentration, the conductivity was in the order of citric acid > acetic acid. [ABSTRACT FROM AUTHOR]