N-acetyl-β-D-glucosaminidase Research Articles

Deciphering differences in microbial community characteristics and main factors between healthy and root rot-infected Carya cathayensis rhizosphere soils

IntroductionFusarium-induced root rot of Carya cathayensis (C. cathayensis) is a typical soil-borne disease that has severely damaged the Carya cathayensis industry in China. Understanding the interaction among soil microbial communities, soil characteristics, and pathogenic bacteria is very important for the ecological prevention and control of Carya cathayensis root rot.MethodsWe used Miseq Illumina high-throughput sequencing technology to study the microbial community in the rhizosphere soil of healthy and diseased C. cathayensis, quantified the abundance of bacteria, fungi, and pathogenic fungi, and combined these with soil chemistry and enzyme activity indicators to analyze the characteristics of healthy and diseased rhizosphere soils.ResultsWe found that the pH, soil organic carbon(SOC), available nitrogen (AN), available phosphorus (AP), available potassium (AK),N-acetyl-β-D-glucosaminidase (NAG) β-glucosidase (BG), fungal gene copy number, bacterial community diversity and network complexity of the diseased soil were significantly lower (p < 0.05), while Fusarium graminearum copies number levels increased (p < 0.05). Additionally, the study found that healthy soils were enriched with beneficial bacteria such as Subgroup_7 (0.08%), MND1 (0.29%), SWB02 (0.08%), and Bradyrhizobium (0.09%), as well as potential pathogen-suppressing fungi such as Mortierella (0.13%), Preussia (0.03%), and Humicol (0.37%), were found to be associated with the growth and development of C. cathayensis.DiscussionIn summary, this research comprehensively reveals the differences in environmental and biological factors between healthy and diseased soils, as well as their correlations. It provides a theoretical basis for optimal soil environmental regulation and the construction of healthy microbial communities. This foundation facilitates the development of multifaceted strategies for the prevention and control of C. cathayensis root rot.

Nephroprotective effects of the soluble guanylyl cyclase stimulator, riociguat in doxorubicin-induced acute kidney injury in rats

This study aimed to investigate the potential protective effects of riociguat, a soluble guanylyl cyclase (sGC) stimulator, on kidney function and structure in rats with acute kidney injury (AKI) induced by the chemotherapeutic drug doxorubicin (DX). Rats were subjected to a single intraperitoneal injection of DX (13.5 mg/kg) on the 5th day, either alone or in combination with low-dose riociguat (3 mg/kg/day), or high-dose riociguat (10 mg/kg/day) for 8 consecutive days. Various markers related to kidney function, oxidative stress, and inflammation were measured in plasma and urine. Kidney tissues were examined histopathologically. DX-induced nephrotoxicity was characterized by increased plasma urea, creatinine, uric acid and neutrophil gelatinase-associated lipocalin (NGAL). DX also decreased creatinine clearance and albumin levels and increased urinary N-acetyl-β-D-glucosaminidase (NAG) activity. Furthermore, DX increased the inflammatory markers interleukin 1 beta (IL-1 β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α). DX further induced oxidative stress injury evidenced by decreased glutathione reductase (GR) activity, total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase levels and increased malondialdehyde (MDA) levels. Concomitant treatment with riociguat ameliorated these DX-induced changes with parallel histopathological improvements but the effects were more favorable with high-dose riociguat. The observed renoprotective effects of riociguat can be partly attributed to the anti-inflammatory and anti-oxidant properties of this drug.

Multi-omics analysis reveals the protective effects of Chinese yam polysaccharide against cisplatin-induced renal interstitial fibrosis

BackgroundChinese yam polysaccharide (SYDT) has been reported to protect renal function and mitigate renal fibrosis in mice with diabetic nephropathy. Based on a multi-omics analysis, the objectives of this study were to determine the effect of SYDT on cisplatin (CDDP)-induced chronic renal interstitial fibrosis (RIF) and the underlying molecular mechanisms using an in vivo model. MethodsRats were intraperitoneally injected with a single dose of CDDP and then treated with SYDT or amifostine (AMF). The levels of urinary N-acetyl-β-D-glucosaminidase (NAG), blood urea nitrogen (BUN) and serum creatinine (Scr) were detected to assess renal function. Renal tissue damage and fibrosis were evaluated using hematoxylin and eosin (H&E) and Masson's trichrome staining, respectively. In addition, this study applied transcriptomics and metabolomics to predict the possible mechanism of SYDT action, which was verified by several relevant examinations. ResultsSYDT significantly protected the renal function, alleviated renal tissue damage and fibrosis, as well as decreased the protein levels of vimentin, α-SMA and CTGF, whereas SYDT significantly increased MMP-1 protein level in renal tissues from rats treated with CDDP. There were 1130 differently expressed genes (DEGs) between the CDDP model and SYDT-M groups proved by transcriptome analysis, indicating that metabolic pathways were likely the primary targets of relevance. Consistent with the transcriptome analysis, metabolome analysis identified 276 differentially expressed metabolites (DEMs) between the SYDT-M and CDDP model groups, with predominant clustering within glycerophospholipid metabolism. Integrative analysis of the transcriptome and metabolome indicated that SYDT inhibited the glycerophospholipid metabolism pathway by regulating the target genes Gpd2, Gpam, Agpat3, Lcat, and Pla2g4b. Notably, integrative analysis showed that the Phospholipase D (PLD) signaling pathway may be the most relevant target. Moreover, related signaling pathway analysis confirmed that SYDT inhibited CDDP-induced RIF in rats by down-regulating the PLD pathway. ConclusionOur study showed that the alleviation of CDDP-induced RIF in vivo can be achieved through the inhibition of glycerophospholipid metabolism and PLD signaling pathways by SYDT.

Magnetic vagus nerve stimulation ameliorates contrast-induced acute kidney injury by circulating plasma exosomal miR-365-3p

BackgroundContrast-induced acute kidney injury (CI-AKI) is manifested by a rapid decline in renal function occurring within 48–72 h in patients exposed to iodinated contrast media (CM). Although intravenous hydration is currently the effective method confirmed to prevent CI-AKI, it has several drawbacks. Some investigations have demonstrated the nephroprotective effects of vagus nerve stimulation (VNS) against kidney ischemia-reperfusion injury, but no direct research has investigated the use of VNS for treating CI-AKI. Additionally, most current VNS treatment applies invasive electrical stimulator implantation, which is largely limited by the complications. Our recent publications introduce the magnetic vagus nerve stimulation (mVNS) system pioneered and successfully used for the treatment of myocardial infarction. However, it remains uncertain whether mVNS can mitigate CI-AKI and its specific underlying mechanisms. Therefore, we herein evaluate the potential therapeutic effects of mVNS on CM-induced nephropathy in rats and explore the underlying mechanisms.ResultsmVNS treatment was found to significantly improve the damaged renal function, including the reduction of elevated serum creatinine (Scr), blood urea nitrogen (BUN), and urinary N-acetyl-β-D-glucosaminidase (NAG) with increased urine output. Pathologically, mVNS treatment alleviated the renal tissue structure injury, and suppressed kidney injury molecule-1 (KIM-1) expression and apoptosis in renal tubular epithelial cells. Mechanistically, increased circulating plasma exosomal miR-365-3p after mVNS treatment enhanced the autophagy and reduced CM-induced apoptosis in renal tubular epithelial cells by targeting Ras homolog enriched in brain (Rheb).ConclusionsIn summary, we demonstrated that mVNS can improve CI-AKI through enhanced autophagy and apoptosis inhibition, which depended on plasma exosomal miR-365-3p. Our findings highlight the therapeutic potential of mVNS for CI-AKI in clinical practice. However, further research is needed to determine the optimal stimulation parameters to achieve the best therapeutic effects.Graphical abstract

Caffeic acid phenethyl ester ameliorates colistin-induced nephrotoxicity in rats via modulation of FOXO1/Nrf2/Sirt1 axis.

Colistin (Cst) is one of the antimicrobial peptides and is reserved for use against multi-drug-resistant Gram-negative bacteria. However, the clinical value of Cst is limited by its nephrotoxic adverse effects. Caffeic acid phenethyl ester (CAPE) is a honeybee propolis flavonoid recognised for its diverse pharmacological potential. It has demonstrated d antioxidant and anti-inflammatory properties, as well as protective effects against chemically induced toxicity in variuos biological systems. This study aimed to investigate the impact of CAPE on nephrotoxicity induced in rats by Cst. Animals were randomly divided into five groups. Group 1 served as control, group 2 received CAPE (10 mg/kg) orally, group 3 received Cst IP, group 4 received Cst + CAPE (5 mg/kg) and group 5 received Cst + CAPE (10 mg/kg). All treatments were given daily for 10 consecutive days. CAPE notably attenuated Cst-inducednephrotoxicity as shown by reducing urea serum levels, creatinine, cystatin C, urinary protein contents and urinary N-acetyl-β-D-glucosaminidase (NAG). This was confirmed by histological investigations that indicated amelioration of histopathological changes in the kidney architecture as well as the deposition of collagen in renal tissues. CAPE exhibited antioxidant effects supported by the prevention of rise in Cst-induced lipid peroxidation and depletion of superoxide dismutase and catalase enzymatic activities. In addition, CAPE inhibited the expression of the inflammatory markers including tumour necrosis factor-α, nuclear factor kappa B and interleukin-6. These actions were associated with modulation of messenger ribonucleic acid (mRNA) expression of Bax and Bcl-2 in favour of anti-apoptosis. CAPE inhibited Cst-induced rise in forkhead box O1 (FOXO1) expression and downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and Sirtuin 1 (Sirt1) immune-expression. CAPE protects against nephrotoxicity induced by Cst in ratsprimarily through its antioxidant, antiinflammatory and antiapoptotic activities. These pritective effects are mediatedvia modulation of FOXO1/Nrf2/Sirt1 axis.

Dose Effect of Polyethylene Microplastics Derived from Commercial Resins on Soil Properties, Bacterial Communities, and Enzymatic Activity.

Soils are the largest reservoir of microplastics (MPs) on earth. Since MPs can remain in soils for a very long time, their effects are magnified. In this study, different concentrations of polyethylene (PE) MPs derived from commercial resins (0%, 1%, 7%, and 14%, represented as MP_0, MP_1, MP_7, and MP_14) were added to soils to assess the changes in the soils' chemical properties, enzyme activities, and bacterial communities during a 70-day incubation period. The results show that PE MP treatments with low concentrations differed from other treatments in terms of exchangeable Ca and Mg, whereas at high concentrations, the pH and availability of phosphate ions differed. Fluorescein diacetate (FDA), acid phosphatase (ACP), and N-acetyl-β-d-glucosaminidase (NAG) enzyme activities exhibited a dose-related trend with the addition of the PE MPs; however, the average FDA and ACP activities were significantly affected only by MP_14. Changes in the microbial communities were observed at both the phylum and family levels with all PE MP treatments. It was revealed that even a low dosage of PE MPs in soils can affect the functional microbes, and a greater impact is observed on those that can survive in polluted environments with limited resources.

Aminopeptidasic Enzymes as Early Biomarkers of Cardiac Surgery-Associated Acute Kidney Injury and Long-Term Events.

Diagnosis of acute kidney injury (AKI) relies on serum creatinine (SCr) changes. This study investigated if urinary aminopeptidases are early and predictive biomarkers of cardiac surgery-associated AKI (CSA-AKI). Glutamyl aminopeptidase (GluAp), alanyl aminopeptidase (AlaAp), dipeptidyl peptidase-4 (DPP4), proteinuria, albuminuria, N-acetyl-β-D-glucosaminidase (NAG), and neutrophile gelatinase-associated lipocalin (NGAL) were measured in urine samples from 44 patients at arrival in the intensive care unit (ICU) after cardiac surgery. Sensitivity, specificity, and positive and negative predictive value for diagnosis of stages 1, 2, and 3 of AKI were analyzed for the highest quartile of each marker. We also studied the relationship with SCr after surgery, 6- and 12-month glomerular filtration rates (GFRs), and other long-term events over the next 5 years. GluAp diagnosed the maximal number of patients that developed stage 2 or 3 of AKI, increasing diagnostic sensitivity from 0% to 75%. In addition, GluAp and DPP4 were related to the decrease in GFR at 6 or 12 months after surgery. Urinary aminopeptidases are a potential tool for the early diagnosis of CSA-AKI, with GluAp being the most effective marker for diagnosing stage 2 or 3 of AKI at ICU admission. GluAp and DPP4 serve as predictive biomarkers for a decrease in GFR.

Changes in urinary renal injury markers in children with Mycoplasma pneumoniae pneumonia and a prediction model for related early renal injury

BackgroundThis study aims to analyse changes in urinary kidney injury markers in children with Mycoplasma pneumoniae pneumonia (MPP), investigate the risk factors for MPP-related acute kidney injury (AKI) and establish a model to predict MPP-related AKI.MethodsNinety-five children were enrolled based on the study’s inclusion and exclusion criteria. They were divided into a severe MPP (SMPP) group and a non-SMPP group and then into an AKI group and a non-AKI group according to the presence of AKI. A univariate logistic regression analysis was performed to explore the early risk factors for AKI. Based on a multivariate logistic regression analysis and a least absolute shrinkage and selection operator regression analysis, appropriate variables were selected to establish a prediction model, and R 4.2.2 software was used to draw nomograms and generate a dynamic nomogram website.ResultsSeven urinary kidney injury markers were abnormally elevated in the SMPP group and the non-SMPP group: urinary N-acetyl-β-D-glucosaminidase (NAG), β2-microglobulin, α1-microglobulin, retinol-binding protein, urinary immunoglobulin G, urinary transferrin and urinary microalbumin. Sixteen children were identified with AKI during hospitalisation. The AKI group had higher levels of urinary NAG, α1-microglobulin, β2-microglobulin, urinary microalbumin, urinary transferrin and retinol-binding protein than the non-AKI group (P < 0.05). The MPP-related AKI prediction model consists of four indicators (serum immunoglobulin M [IgM], C-reactive protein [CRP], urine NAG and sputum plug presence) and a dynamic nomogram.ConclusionUrinary kidney injury markers are often elevated in children with MPP; urinary NAG is the marker most likely to be elevated, and it is especially evident in severe cases. The nomogram of the prediction model, comprising serum IgM, CRP, urinary NAG and sputum plug presence, can predict the probability of AKI in children with MPP.

Benchmark Dose of Melamine Exposure for a Renal Injury Marker Mediated by Oxidative Stress: Examples in Patients with Urolithiasis and Occupational Workers.

Establishing a safe exposure level from epidemiological studies while providing direct hazard characterization in humans often faces uncertainty in causality, especially cross-sectional data. With advances in molecular epidemiology, it is reasonable to integrate identified intermediate biomarkers into health risk assessment. In this study, by considering the mediation of the oxidative stress marker malondialdehyde (MDA), we explored the exposure threshold of melamine on the early renal injury marker N-acetyl-β-D glucosaminidase (NAG). The benchmark dose (BMD) was derived from model averaging of the composite direct effect of melamine exposure and the indirect effect through the mediation of MDA on NAG levels. As illustrative examples, we analyzed 309 adult patients with calcium urolithiasis and 80 occupational workers for the corresponding exposure thresholds. The derived threshold was subpopulation-dependent, with the one-sided lower bound BMDL10 for the patients with urolithiasis with (without) the mediator MDA for the patients with kidney stones and the occupational workers being 0.88 (0.96) μg/kg_bw/day and 22.82 (18.09) μg/kg_bw/day, respectively. The derived threshold levels, considering the oxidative stress marker MDA, were consistent with those without adjusting for the mediation effect. However, the study outcomes were further supported by the suggested mechanism pathway. The threshold for the patients with urolithiasis was up to two orders lower than the current tolerable daily intake level of 200 μg/kg_bw/day recommended by the WHO (EFSA).

Effects of leguminous green manure-crop rotation on soil enzyme activities and stoichiometry

Abstract As a crucial strategy for sustainable agricultural production, green manure-crop rotation can regulate soil nutrient cycling and decrease the reliance on nitrogen fertilizers. However, we still lack a comprehensive understanding of the changes in soil eco-enzyme activities, microbial metabolism, and nutrient limitations caused by leguminous green manure crop rotation. Here, we conducted field experiments of leguminous green manure-crop rotation across China to analyze soil extracellular enzyme activities, specifically β-glucosidase (BG), N-acetyl-β-D-glucosaminidase (NAG), leucine aminopeptidase (LAP), and acid phosphatase (AP). The study revealed that long-term green manure-crop rotation increased carbon and nitrogen accumulation in farmland, with a significant average increase of 20.1% and 36.4% in BG, AP enzyme activities in topsoil, while showing a decrease in ln(NAG+LAP):ln(AP) ratios. The ratios of ln(BG):ln(NAG+LAP) and ln(NAG+LAP):ln(AP) in soil across various regions were typically below 1:1, indicating that soil microbial activity is more constrained by nitrogen and phosphorus nutrients rather than by carbon. Precipitation, temperature, soil total carbon, and total nitrogen were identified as key environmental factors for extracellular enzyme activities and stoichiometric ratios. Our study highlights that the green manure-crop rotation alleviates nitrogen limitation while enhancing phosphorus limitation, and is closely related to the accumulation of total carbon and nitrogen in the soil.

Urinary N-acetyl-D-glucosaminidase can predict bleeding after a percutaneous kidney biopsy

BackgroundA percutaneous kidney biopsy (PKB) allows nephrologists to make informed decisions for treating various kidney diseases; however, the risk of bleeding complications should be considered, given the vascularity of the kidney. Many studies have reported risk factors for bleeding events after a PKB. However, while urinary N-acetyl-β-D-glucosaminidase (NAG) is a useful biomarker of kidney disease severity, little is known about whether or not urinary NAG is related to the bleeding risk.MethodsMedical records of patients who underwent a PKB at the National Defense Medical College Hospital between October 2018 and October 2023 were retrospectively studied. Hemoglobin (Hb) loss ≥ 1 g/dL was defined as a bleeding event.ResultsOf the 213 patients, 110 (51.6%) were men, and the median age was 56 years old (interquartile range 40–71). The most frequent diagnosis on a PKB was IgA nephropathy (N = 72; 34.0%). Fifty-four patients (25.3%) experienced Hb loss ≥ 1 g/dL after a PKB, and urinary NAG/Cr levels before the biopsy were able to predict a bleeding event, with an area under the receiver operating characteristic curve of 0.65 (p = 0.005). Using the optimal cutoff value of 35 U/gCr, urinary NAG/Cr was found to be an independent risk factor by multiple logistic regression analysis (odds ratio 3.21, 95% confidence interval 1.42–7.27, p = 0.005). Even after adjusting for previously-reported risk factors, the elevated urinary NAG/Cr ratio remained a statistically significant variable. Compared with the pathological findings, only the severity of multilayered elastic laminae of the small muscular artery was associated with both urinary NAG/Cr levels (p = 0.008) and bleeding events (p = 0.03).ConclusionUrinary NAG successfully predicted not only the severity of kidney disorders but also bleeding events after a PKB. Arteriosclerosis in the kidneys may be the mechanism underlying these increased bleeding events.

Tachycardia and Acute Kidney Injury among Critically Ill Patients with Sepsis: A Prospective Observational Study

Introduction: Tachycardia caused by sympathetic overactivity impairs myocardial function and raises septic patients’ mortality. This study examined whether tachycardia is associated with acute kidney injury (AKI) period-prevalence among critically ill patients with and without sepsis. Methods: In 328 patients (119 sepsis and 209 non-sepsis) admitted to our intensive care unit (ICU), we assessed heart rate at ICU admission, plasma neutrophil gelatinase-associated lipocalin (NGAL) and N-terminal pro-B-type natriuretic peptide, and urinary L-type fatty acid-binding protein and N-acetyl-β-d-glucosaminidase (NAG) at 0 and 48 h after admission. Tachycardia was defined as a heart rate above 100 beats/min. Results: Tachycardia was independently correlated with AKI prevalence during the first week after ICU admission in the septic patients, but not in the non-septic patients. A dose-dependent increase in AKI period-prevalence was observed across ascending heart rate ranges. Furthermore, we discovered a dose-dependent increase in renal biomarker-positive patients regarding plasma NGAL and urinary NAG over increasing heart rate ranges 48 h after admission. Conclusion: The findings revealed an independent relationship between tachycardia and AKI prevalence during the first week of ICU in septic patients. Heart rate was found to have a dose-dependent effect on AKI prevalence and renal insult monitored by biomarkers.

#1831 Circulating MiRNA 195-5p may be associated with early renal impairment in patients with prediabetes

Abstract Background and Aims Type 2 diabetes mellitus (DM) is one of the leading causes of chronic kidney disease worldwide. However, there are few data concerning early kidney impairment in prediabetes patients. The aim of the study was to demonstrate early kidney damage in patients with prediabetes by assessing proximal tubule (PT) dysfunction, podocytes injury, and miRNA expression. Method A cohort of 192 individuals were analysed and divided such as follows: 52-normoalbuminuria-, 48-microalbuminuria-, and 50-macroalbuminuria type 2 DM patients, respectively; 12 patients-prediabetes and 30-healthy controls. The miRNA profile was assessed by real-time PCR, while PT dysfunction biomarker, N-acetyl-β-D-glucosaminidase (NAG), and podocyte injury biomarker, podocalyxin, were assessed by ELISA technique. The study was conducted in two distinct stages. In the first part of the study was detected a particular miRNAs profile in serum in patients with prediabetes; subsequently, the expression of the most relevant miRNA in patients with prediabetes was identified. Results i) in prediabetes patients, serum miRNA195-5p was 2.69 fold change as compared to the control group and correlated with NAG (p&amp;lt;0.05) and podocalyxin (p&amp;lt;0.03); ii) in type 2 DM patients, the expression of serum miRNA195-5p was higher and correlated with NAG (p&amp;lt;0.05), podocalyxin (p&amp;lt;0.04), urinary albumin: creatinine ratio (p&amp;lt;0.001) and with eGFR (p&amp;lt;0.001); iii) urinary NAG and urinary podocalyxin were higher in prediabetes patients and type 2 DM patients, even in the normoalbuminuria stage, as compared to controls (p&amp;lt;0.04; p&amp;lt;0.001). Conclusion A panel of molecular biomarkers, such as miRNAs, remain useful tools for the early diagnosis of renal involvement in the course of type 2 DM. MiRNA 195-5p may be associated with PT dysfunction and podocyte damage, and could predict renal dysfunction in both prediabetes and early diabetic kidney disease in type 2 DM patients.

#1554 The association between gut-derived metabolites and biomarkers of renal and cerebro-vascular damage in type 2 diabetes mellitus patients

Abstract Background and Aims Due to its numerous complications, type 2 diabetes mellitus (T2DM) has a major impact on the global economic burden and overall mortality. This condition modifies the metabolic microenvironment in targeted organs, such as the kidney and the brain, by its hyperglycemic nature. Gut microbiota seems to have significant interference with the renal-cerebral axis, especially in a dysbiosis state. The aim of the study was to quantify gut derived metabolites by metabolomic techniques and to evaluate their association with markers of endothelial, podocyte and proximal tubule damage and with cerebro-vascular hemodynamic indices. Method The metabolomic profiling was realized on serum and urine samples originated from 90 T2DM patients, divided into three subgroups, such as the following: 30 normal to mildly-, 30 moderately-, and 30 severely increased albuminuria, respectively, and 20 healthy subjects. The samples were examined by using untargeted and targeted ultra-high performance liquid chromatography coupled with electrospray-ionization quadroupole time-of-flight mass spectrometry (UHPLC-QTOF-ESI+-MS), in order to obtain the metabolic profile. The markers of renal damage such as synaptopodin (SP), podocalyxin (PD), N-acetyl-β-D-glucosaminidase (NAG), kidney injury molecule 1 (KIM-1), monocyte chemotactic protein 1 (MCP-1), and intercellular adhesion molecule 1 (ICAM-1) were assessed by ELISA technique. The hemodynamic cerebro-vascular indices were obtained by high resolution Doppler ultrasound of common carotid arteries (CCAs), internal carotid arteries (ICAs), and middle cerebral arteries (MCAs), bilaterally. The correlations between the metabolites, the markers of renal damage, and neurosonological indices were realized by univariable and multivariable linear regression analyses. Results UHPLC-QTOF-ESI+-MS targeted analysis and subsequent statistical assessments revealed a subset of metabolites with a specific pattern for the normal to mildly increased albuminuria subgroup. The metabolites identified as significant were, in serum: arginine (sArg), hippuric acid (sHA), indoxyl sulfate (sIS), butenoylcarnitine (sBCA), sorbitol (sSorb); and in urine, arginine (uArg), butenoylcarnitine (uBCA), indoxyl sulfate (uIS) and p-cresyl sulfate (uPCS). The univariable linear regression analysis revealed that sArg correlated positively with the breath-holding index (BHI) and negatively with intima media thickness (IMT) in ACI, MCP-1 and ICAM-1; sIS, sSorb, and sBCA correlated inversely with these parametes. The multivariable linear regression analysis displayed the specific correlations between metabolites, markers of endothelial dysfunction, and neurosonological indices, such as follows: sArg correlated with IMT and ICAM-1; sIS followed a predictive pattern along with resistance index (RI) in ACIs and ICAM-1; sBCA correlated with IMT and MCP-1 and sSorb correlated with ICAM-1 and BHI. The urine metabolites were correlated with markers of podocyte and proximal tubule dysfunction: uIS and uBCA were correlated with PD and urinary albumin to-creatinin ratio (uACR), and uPCR correlated with KIM-1 and uACR. Conclusion This study revealed a set of metabolites potentially derived from the intestinal microflora which may act as biomarkers for the early detection of both CMA and DKD in T2DM patients. SArg, sIS and, sBCA are indicators of renal endothelial dysfunction. Moreover, sArg and sIS reflect incipient common and internal carotid artery atherosclerosis, suggesting vascular remodeling at these levels. SSorb correlated with BHI, indicating blood-brain barrier dysfunction and CMA development. In urine, uBCA and uIS are indicators of podocytopathy, whereas uPCS is associated with proximal tubule damage in incipient DKD.

Complex interplay of heavy metals and renal injury: New perspectives from longitudinal epidemiological evidence

BackgroundEpidemiological studies have reported associations between heavy metals and renal function. However, longitudinal studies are required to further validate these associations and explore the interactive effects of heavy metals on renal function and their directional influence. MethodThis study, conducted in Northeast China from 2016 to 2021, included a four-time repeated measures design involving 384 participants (1536 observations). Urinary concentrations of chromium (Cr), cadmium (Cd), manganese (Mn), and lead (Pb) were measured, along with renal biomarkers including urinary microalbumin (umAlb), urinary albumin-to-creatinine ratio (UACR), N-acetyl-β-D-glucosaminidase (NAG), and β2-microglobulin (β2-MG) levels. Estimated glomerular filtration rate (eGFR) was calculated. A Linear Mixed Effects Model (LME) examined the association between individual metal exposure and renal biomarkers. Subsequently, Quantile g-computation and Bayesian Kernel Machine Regression (BKMR) models assessed the overall effects of heavy metal mixtures. Marginal Effect models examined the directional impact of metal interactions in the BKMR on renal function. ResultResults indicate significant impacts of individual and combined exposures of Cr, Cd, Pb, and Mn on renal biomarkers. Metal interactions in the BKMR model were observed, with synergistic effects of Cd-Cr on NAG, umAlb, UACR; Cd-Pb on NAG, UACR; Pb-Cr on umAlb, UACR, eGFR-MDRD, eGFR-EPI; and an antagonistic effect of Mn-Pb-Cr on UACR. ConclusionBoth individual and combined exposures to heavy metals are associated with renal biomarkers, with significant synergistic interactions leading to renal damage. Our findings elucidate potential interactions among these metals, offering valuable insights into the mechanisms linking multiple metal exposures to renal injury.

Environmental risk score of multiple pollutants for kidney damage among residents in vulnerable areas by occupational chemical exposure in Korea

This study aimed to develop an environmental risk score (ERS) of multiple pollutants (MP) causing kidney damage (KD) in Korean residents near abandoned metal mines or smelters and evaluate the association between ERS and KD by a history of occupational chemical exposure (OCE). Exposure to MP, consisting of nine metals, four polycyclic aromatic hydrocarbons, and four volatile organic compounds, was measured as urinary metabolites. The study participants were recruited from the Forensic Research via Omics Markers (FROM) study (n = 256). Beta-2-microglobulin (β2-MG), N-acetyl-β-D-glucosaminidase (NAG), and estimated glomerular filtration rate (eGFR) were used as biomarkers of KD. Bayesian kernel machine regression (BKMR) was selected as the optimal ERS model with the best performance and stability of the predicted effect size among the elastic net, adaptive elastic net, weighted quantile sum regression, BKMR, Bayesian additive regression tree, and super learner model. Variable importance was estimated to evaluate the effects of metabolites on KD. When stratified with the history of OCE after adjusting for several confounding factors, the risks for KD were higher in the OCE group than those in the non-OCE group; the odds ratio (OR; 95% CI) for ERS in non-OCE and OCE groups were 2.97 (2.19, 4.02) and 6.43 (2.85, 14.5) for β2-MG, 1.37 (1.01, 1.86) and 4.16 (1.85, 9.39) for NAG, and 4.57 (3.37, 6.19) and 6.44 (2.85, 14.5) for eGFR, respectively. We found that the ERS stratified history of OCE was the most suitable for evaluating the association between MP and KD, and the risks were higher in the OCE group than those in the non-OCE group.

Organic fertilizer prepared by thermophilic aerobic fermentation technology enhanced soil humus and related soil enzyme activities

AbstractOrganic fertilizer (OF) prepared from chicken manure in a high‐temperature aerobic fermenter contains high levels of nitrogen, phosphorus and potassium. The effect of high‐nutrient OF substitution for chemical fertilizer (CF) on soil organic carbon stability is worth exploring. We used OF to replace CFs for supplying crops, and we set five OF replacement rates as 0, 25%, 50%, 75% and 100% in the black soil zone of Northeast China. We explored the variations in soil humus carbon contents, enzyme activities and nutrient contents (0–10 cm and 10–20 cm). Two‐way ANOVA results showed that interaction between soil depth and OF substitution significantly affected soil pH, total nitrogen, organic carbon, available potassium, water‐soluble carbon substance (WSSC) and activities of soil β‐galactosidase (β‐gal), N‐acetyl‐β‐D‐glucosaminidase (NAG) and cellobiohydrolase. The treatments of OF75 and OF100 increased soil pH, and the content of soil organic carbon, humic acid carbon (HAC), fulvic acid carbon (FAC), WSSC, total phosphorus, available phosphorus (AP), total potassium and available potassium was increased in OF75 and OF100 treatment. Treatments of OF75 and OF100 increased the tested soil enzyme activities except for oxidase activities of 0–10 cm soil layer. There was a positive correlation between HAC and AP contents, and a positive correlation between FAC and soil pH, total nitrogen and available potassium contents. The key influencing factors of soil FAC were the activities of NAG, α‐galactosidase and β‐gal. It can be concluded that OF substitution promoted soil humus carbon accumulation by affecting hydrolase activity related to carbon conversion.

Evaluation of Serum Human Kidney Injury Molecule-1 and N-Acetyl-β-D-Glucosaminidase as Early Markers of Kidney Injury in Patients with β-Thalassemia Major in Diyala Governorate

Thalassemia is a genetic disease identified by a defect in the production of one or more globin chains. This study was aimed at determining the possibility of using "serum kidney injury molecule-1 (KIM-1)" and "N-acetyl-β-D-glucosaminidase (NAG)" in the diagnosis of early renal damage in thalassemia patients. Serum biomarkers (CBC, urea, creatinine, KIM-1, and NAG) were determined in 45 patients with major thalassemia with an age range of 4-45 years who attended Baquba General Hospital. A significant increase in S.KIM-1 and S.NAG levels in patients compared with controls. The level of KIM was positively correlated with that of urea and creatinine in comparison with control. Also, the level of NAG was strongly positively correlated with the level of KIM-1 (p = 0.000) and had a moderately positive correlation with urea and creatinine (p = 0.000). According to ROC, KIM-1 had a sensitivity of 95.56% and a specificity of 88.89%, while NAG had a sensitivity of 100% and a specificity of 75.6%. This study concluded that S.KIM-1 and S.NAG are highly promising biomarkers for the detection of "acute kidney injury" in an early stage before elevated urea and creatinine in thalassemia patients.

Anchoring copper nanoclusters to Al2O3 microsphere for dual-mode analysis of N-acetyl-β-D-glucosaminidase and information encryption

Herein, we attempted to confine copper nanoclusters (CuNCs) with alumina (Al2O3) as the matrix (Al2O3@CuNCs), which effectively circumvented the drawbacks of CuNCs (such as weak photoluminescence and low quantum yield). Al2O3@CuNCs demonstrated sensitive response to p-nitrophenol, the catalytic product of N-acetyl-β-D-glucosaminidase (NAG) on account of the inner filter effect and dynamic quenching effect. In light of this, a novel assay was created to identify NAG, a critical indicator of diabetic nephropathy. Additionally, a portable and instrument-free sensing platform mainly consisting of a smartphone, a cuvette, a cuvette holder, a dark box and a 365 nm UV lamp was developed for the quantitative detection of NAG. The as-prepared material was also utilized in anti-counterfeiting and information encryption based on their excellent optical properties and sensitive response to the catalyzed product of NAG. This work advanced potential applications of CuNCs composites in the areas of portable, multi-mode biosensing, anti-counterfeiting and information encryption.

Effects of different maize residue managements on soil organic nitrogen cycling in different soil layers in northeast China

AbstractA field experiment was conducted in northeast China to examine the response of nitrogen cycling enzymes, that is, protease, N‐acetyl‐β‐D‐glucosaminidase (NAG), amidase, urease, and peptidase, as well soil organic nitrogen (SON) fractions and their relationships to RT (no maize residue application), NT (no tillage with maize residues placed on the surface), TT (plow maize residues into the soil at 0–35 cm depth in the first year, 0–20 cm in the second year, and 0–15 cm in the third year), and PT (plow maize residues into soil at 0–35 cm depth). The results have shown that NT significantly enhanced the activities of protease and NAG at 0–10 cm soil depth in comparison with other treatments. NT and TT significantly enhanced the activities of protease compared to RT and PT at 10–20 cm soil depth. TT significantly enhanced the activities of NAG in comparison with RT at 10–20 cm soil depth. TT and PT significantly enhanced the activities of NAG and peptidase compared to RT and NT at 20–35 cm soil depth. PT significantly increased the activities of protease in comparison with RT at 20–35 cm soil depth. NT, TT, and PT significantly enhanced the activities of peptidase compared to RT at 10–20 cm soil depth. NT significantly increased the concentration of hydrolyzable in comparison with other treatments at 0–10 cm soil depth. PT significantly enhanced the concentration of hydrolyzable and amino acid N compared to other treatments at 20–35 cm soil depth. Redundancy analysis showed that protease played a crucial role in the cycling of SON under RT and NT, whereas peptidase and NAG played a significant role in the cycling of SON under TT and PT, respectively. This study provided a comprehensive understanding of crop residue return methods for regulating soil N cycling.