An outbreak of renal failure in asian dogs due to s-triazine adulteration of pet food raw material: Analysis of unique, green kidney stones formed as a result.

Renoliths were removed at necropsy from dogs that had died from acute kidney injury in Asia in 2004 and submitted to our laboratories for analysis including elemental composition, mass spectrometry, and nuclear magnetic resonance spectroscopy. The presence of a mixed s-triazine matrix comprising melamine, cyanuric acid, and ammelide, but no detectable ammeline, was found in the stone samples we analyzed. The unusual and unique green coloration of these stones was determined to be due to the presence of biliverdin. The occurrence of these green stones distinguished the 2004 incident from another incident in 2007 in the USA and other reported cases. The presence of crystals was reported in renal tubules and collecting ducts in both outbreaks, but no stones were reported in the 2007 incident. This difference suggested a variation in the disease process caused by mixed s-triazine ingestion. Careful monitoring of food additives is warranted to prevent future problems in animals and humans.

Trace level detection of melamine and cyanuric acid extracted from pet liquid food (milk) using a SERS Au nanogap substrate.

This study reported an application of Au nanogap substrates for surface-enhanced Raman scattering (SERS) measurements to quantitatively analyze melamine and its derivative products at trace levels in pet liquid food (milk) combined with a waveband selection approach, namely variable importance in projection (VIP). Six different concentrations of melamine, cyanuric acid, and melamine combined with cyanuric acid were created, and SERS spectra were acquired from 550 to 1620cm-1. Detection was possible up to 200 pM for melamine-contaminated samples, and 400 pM concentration detection for other two groups. The VIP-PLSR models obtained correlation coefficient (R2) values of 0.997, 0.985, and 0.981, with root mean square error of prediction (RMSEP) values of 18.492 pM, 19.777 pM, and 15.124 pM for prediction datasets. Additionally, partial least square discriminant analysis (PLS-DA) was used to classify both pure and different concentrations of spiked samples. The results showed that the maximum classification accuracy for melamine was 100%, for cyanuric acid it was 96%, and for melamine coupled with cyanuric acid it was 95%. The results obtained clearly demonstrated that the Au nanogap substrate offers low-concentration, rapid, and efficient detection of hazardous additive chemicals in pet consuming liquid food.

Environmental exposure to melamine and its derivatives and kidney outcomes in children.

Melamine caused acute nephrotoxicity in a past food adulteration incident, but it is unclear whether and how widespread ambient exposure to melamine and related compounds might affect pediatric kidney health. We assessed cross-sectional associations between childhood exposure to melamine and its derivatives and biomarkers of kidney injury and health and explored potential heterogeneity by sex suggested by sex-dependent differences in renal physiology. We measured melamine and its derivatives ammeline, ammelide, and cyanuric acid (CYA) in spot urine samples collected from 192 children from an urban site (Seattle, WA) and 187 children from a rural site (Yakima, WA) aged 4-8 years in the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Study. In addition, biomarkers of kidney injury were measured in the same urine samples, including albumin, total protein, KIM-1, NAG, NGAL, and EGF. We utilized linear regressions to examine associations between individual chemical exposures and kidney biomarkers. Interaction terms examined association modification by sex, as well as potential interactions between melamine and CYA. Despite comparable exposures, girls had higher levels of many kidney injury biomarkers compared to boys. A ten-fold higher melamine concentration was associated with a 18% (95% CI: 5.6%, 31%) higher EGF in the full sample, while ten-fold higher melamine was associated with a 76% (14.1%, 173%) higher KIM-1 in boys but not in girls (-10.1% (-40.6%, 36.1%), interaction p = 0.026). Melamine exhibited significant negative interactions with CYA in association with total protein and NAG that appeared to be specific to girls. Our results suggest possible associations between melamine exposure and markers of kidney injury that may be more pronounced in boys. These findings provide novel insights into melamine and related derivative compound health effects at low levels of exposure in children and emphasize the role of sex in mediating the relationship between nephrotoxicant exposure and kidney injury.

Cyanuric Acid-Assisted Synthesis of Hierarchical Amorphous Carbon Nitride Assembled by Ultrathin Oxygen-Doped Nanosheets for Excellent Photocatalytic Hydrogen Generation.

Amorphous carbon nitride with typical short-range order arrangement as an effective photocatalyst is worth exploring but remains a great challenge because its disordered structure induces severe recombination of photogenerated charge carriers. Herein, for the first time, we demonstrate that a hierarchical amorphous carbon nitride (HACN) with structural oxygen incorporation can be synthesized via a cyanuric acid-assisted melem hydrothermal process, accompanied by freeze-drying and pyrolysis. The complex composed of melem and cyanuric acid exhibiting a unique 3D self-supporting skeleton and significant phase transformation is responsible for the formation of an interconnected hierarchical framework and amorphous structure for HACN. These features are beneficial to enhance its visible light harvesting by the multiple-reflection effect within the architecture consisting of more exposed porous nanosheets and introducing a long band tail absorption. The well-designed morphology, band tail state, and oxygen doping effectively inhibit rapid band-to-band recombination of the photogenerated electrons and holes and facilitate subsequent separation. Accordingly, the HACN catalyst exhibits exceptional visible light (λ > 420 nm)-driven photoreduction for hydrogen production with a rate of 82.4 µmol h-1, which is 21.7 and 9.5 times higher than those of melem-derived carbon nitride and crystalline nanotube carbon nitride counterparts, respectively, and significantly surpasses those of most reported amorphous carbon nitrides. Our controlling of rearrangement of the in situ supramolecular self-assembly of melem oligomer using cyanuric acid directly instructs the development of highly efficient amorphous photocatalysts for converting solar energy into hydrogen fuel.

Twenty-four-hour temporal trend of melamine and its derivatives in urine in association with meal consumption: a panel study in Shanghai, China.

Timing of sampling is important for the exposure assessment of melamine (MEL) and its derivatives. This study aimed to investigate whether MEL and its derivatives in spot urine can effectively represent individual exposure levels throughout the day in adults and to explore their temporal trend before and after meal consumption for helping understand the timing of sampling and for assessing the potential exposure risk. This is a 2-day panel study with 43 college students being enrolled to provide urine specimens in 24 h (from the morning of the first day to the second day) and to answer a questionnaire on demographic characteristics, physical measurements, and time of having meal. Spearman correlation and Wilcoxon rank-sum test were used to examine the associations of the urinary concentrations of MEL and its derivatives in different sampled times and compare the concentrations' differences before and after meal consumption. Urinary concentrations of MEL and its derivatives (ammeline (AMN), ammelide (AMD), and cyanuric acid (CYA)) in the first-morning urine at the second day and randomly selected spot urine were positively associated with the average concentrations in the previous 24-h urine (all P ≤ 0.002). Urinary MEL concentration increased rapidly after meal consumption, reaching a maximum at approximately 3 h and then decreased gradually towards baseline (P = 0.006). Two subjects (4.65%) had a cumulative daily intake exceeding the severest tolerable daily intake. MEL and its three derivatives in spot urine can effectively represent the average concentrations in the previous 24-h urine in adults. Meal consumption is still a notable source of exposure to MEL for humans. These findings are important for choosing a better sampling strategy of performing exposure assessment. Meanwhile, the acute elevation in urinary MEL concentration following meal consumption may pose a potential health risk.

Investigation of melamine and cyanuric acid concentration in several brands of liquid milk and its non-carcinogenic risk assessment in adults and infants.

In this study, the melamine and cyanuric acid concentration of widely used milk brands and the probability of non-carcinogenic risk of the brands for adults and infants were investigated. These values were 1.37 mg/L, 1.10 mg/L, and 1.09 mg/L, which corresponded to creamy sterilized sample, high-fat (creamy) pasteurized sample, and low-fat (less-creamy) pasteurized sample, respectively. Similarly, the highest amount of cyanuric acid occurred in brand A with the values of 0.79 mg/L, 0.65 mg/L, and 0.64 mg/L, which was reported in the same samples mentioned for melamine. The HQ (Hazard Quotient) of melamine in the brands of A, B, C and D for adults was 0.0025, 0.0011, 0.0006 and 0.0008 respectively. These values for infants were reported as 2.2280, 0.9444, 0.5714 and 0.6714 respectively. The risk probability of melamine for adults was less than 1. However, the HQ in brand A for infants was greater than 1 (2.380), which indicate the high probability of non-carcinogenic risk. Furthermore, the HI (Hazard Index) values of the brands of A, B, C and D for infants were 2.7913, 1.1737, 0.7067 and 0.838, respectively. The simultaneous melamine and cyanuric acid in the brands A and B in for infants increase the non-carcinogenic risk probability by approximately 2.8 and 1.2 times, respectively. The results revealed that the melamine and cyanuric acid concentrations in creamy milk samples (0.5%) were higher than in less-creamy milk samples (2.5%). Moreover, the amount of the compounds in sterilized milk samples was higher than pasteurized. In this study, a conversion factor (0.7) was proposed in order to find out the concentration of cyanuric acid in milk sample with the amount of melamine is known but the cyanuric acid concentration is unknown.

Development of a Colorimetric Paper Sensor for Hg2+ Detection in Water Using Cyanuric Acid-Conjugated Gold Nanoparticles.

Hg2+ is one of the most dangerous pollutants that can cause damage to organs and the immune system. The common detection methods of Hg2+ require sophisticated instrumentation and a long time for analysis. The purpose of this study was to develop a sensor for the detection of Hg2+ using filter paper immobilized by gold nanoparticles (AuNPs) conjugated with cyanuric acid (CA). The clear color change from pink to bluish purple is the response of the CA-AuNPs filter paper sensor to exposure to Hg2+. Detection can be observed visually with the naked eye and/or with imageJ software; the detection limit is 0.05 µM. The colorimetric response of the sensor was also selective towards Hg2+ after testing with different metal ions. In addition, the response from the sensor was also consistent for lake water samples spiked with Hg2+. The results of this research provide a promising basic technology for the development of sensors that are affordable, fast, portable, and easy to use for the detection and monitoring of Hg2+ levels in water.

The Therapeutic Effect of Catechin on Nephrolithiasis Induced by Co-Exposure to Melamine and Cyanuric Acid in Sprague-Dawley Rats.

This study aimed to assess the therapeutic efficacy of catechin against experimentally induced kidney stones resulting from co-exposure to melamine (MEL) and cyanuric acid (CYA) in male Sprague-Dawley rats. To induce nephrolithiasis, a combination of MEL and CYA (1:1 ratio, each at a dose of 31.5 mg/kg bw/day) was administered to the rats for 28 consecutive days. After nephrolithiasis was successfully induced, the rats were randomly divided into two groups: a treatment group and a sham group. The treatment group was given a daily oral dose of 50 mg/kg of catechin for 28 days, while the sham group received no intervention. Urine and blood samples were collected throughout the treatment period, and kidney samples were taken on day 28. Our findings demonstrated that treatment with catechin significantly reduced crystal deposition and pathological damage in the rats from nephrolithiasis. Additionally, renal injury markers were significantly decreased in the treatment group compared to the sham group. These findings suggest that catechin has potential therapeutic benefits in treating nephrolithiasis induced by co-exposure to MEL and CYA.

The Antimicrobial and Antibiofilm Potential of New Water-Soluble Tris-Quaternary Ammonium Compounds.

The invention and innovation of highly effective antimicrobials are always crucial tasks for medical and organic chemistry, especially at the current time, when there is a serious threat of shortages of effective antimicrobials following the pandemic. In the study presented in this article, we established a new approach to synthesizing three novel series of bioactive water-soluble tris-quaternary ammonium compounds using an optimized one-pot method, and we assessed their antimicrobial and antibiofilm potential. Five pathogenic microorganisms of the ESKAPE group, including highly resistant clinical isolates, were used as the test samples. Moreover, we highlighted the dependence of antibacterial activity from the hydrophilic-hydrophobic balance of the QACs and noted the significant performance of the desired products on biofilms with MBEC as low as 16 mg/L against bacteria and 8 mg/L against fungi. Particularly notable was the high activity against Pseudomonas aeruginosa and Acinetobacter baumannii, which are among the most resilient bacteria known. The presented work will provide useful insights for future research on the topic.

Deep Learning-Based Quantitative Assessment of Melamine and Cyanuric Acid in Pet Food Using Fourier Transform Infrared Spectroscopy.

Melamine and its derivative, cyanuric acid, are occasionally added to pet meals because of their nitrogen-rich qualities, leading to the development of several health-related issues. A nondestructive sensing technique that offers effective detection must be developed to address this problem. In conjunction with machine learning and deep learning technique, Fourier transform infrared (FT-IR) spectroscopy was employed in this investigation for the nondestructive quantitative measurement of eight different concentrations of melamine and cyanuric acid added to pet food. The effectiveness of the one-dimensional convolutional neural network (1D CNN) technique was compared with that of partial least squares regression (PLSR), principal component regression (PCR), and a net analyte signal (NAS)-based methodology, called hybrid linear analysis (HLA/GO). The 1D CNN model developed for the FT-IR spectra attained correlation coefficients of 0.995 and 0.994 and root mean square error of prediction values of 0.090% and 0.110% for the prediction datasets on the melamine- and cyanuric acid-contaminated pet food samples, respectively, which were superior to those of the PLSR and PCR models. Therefore, when FT-IR spectroscopy is employed in conjunction with a 1D CNN model, it serves as a potentially rapid and nondestructive method for identifying toxic chemicals added to pet food.

Effects of melamine and cyanuric acid on placental and fetal development in rats.

Melamine or cyanuric acid alone has low toxicity, but combined exposure to melamine and cyanuric acid was reported to cause unexpected toxicological effects. This study investigated the potential effects and toxic mechanism of combined exposure to melamine and cyanuric acid on placental and fetal development in rats. Exposure to melamine and cyanuric acid caused maternal toxicity manifested by increased abnormal symptoms and decreased body weight gain. Developmental toxic effects included a decrease in placental and fetal weights with increased fetal deaths and post-implantation loss. Melamine and cyanuric acid induced oxidative stress in the developing placenta and fetus. The placentas from rats treated with melamine and cyanuric acid showed shortening of the placental layers with histological changes, decreased cell proliferation, increased apoptotic changes, and decreased insulin-like growth factor (IGF)/IGF-binding proteins (IGFBPs) and placental lactogen (PL) expression levels. Fetuses from melamine- and cyanuric acid-treated dams showed increased apoptotic changes and suppressed cellular proliferation in their livers and vertebrae. Consequently, combined exposure to melamine and cyanuric acid resulted in high levels of oxidative stress and impaired placental development associated with impairment of the IGF/IGFBP and PL systems, resulting in increased apoptotic changes and reduced fetal cell proliferation.

Exposure to nitrogenous based flame retardants in Chinese population: Evidence from a national-scale study.

Extensive use of nitrogen-based flame retardants (NFRs) has resulted in their widespread environmental occurrence. To investigate human exposure to NFRs on a national scale, the abundance and spatial distribution of NFRs were assessed in urine specimens collected from 13 cities in China. Six out of eight target NFRs were detectable in more than half of the urine samples, and the total concentrations of NFRs ranged from 3.22 to 880 ng/mL with a median of 46.7 ng/mL. Cyanuric acid was the most abundant chemical, accounting for 66.2%, followed by melamine (16.3%), ammelide (10.8%), and ammeline (6.11%). Regional differences in concentrations and composition profiles of NFRs were observed within China as a result of different production and application profiles. In addition, we found that urinary NFRs levels were much higher than but statistically correlated with that of organophosphates (r2 = 0.69, p < 0.05), another class of phosphorus-based flame retardant, implying similar emission sources and/or human exposure pathways. Furthermore, the estimated daily intakes and hazard quotients revealed that the Chinese population's exposure to NFRs is within safe limits. To the best of our knowledge, this is the first study to document the ubiquitous occurrence and region-specific variations of human exposure to NFRs in China.

Prenatal cyanuric acid exposure induced spatial learning impairments associated with alteration of acetylcholine-mediated neural information flow at the hippocampal CA3-CA1 synapses of male rats.

Cyanuric acid (CA) is reported to induce nephrotoxicity but its toxic effect is not fully known. Prenatal CA exposure causes neurodevelopmental deficits and abnormal behavior in spatial learning ability. Dysfunction of the acetyl-cholinergic system in neural information processing is correlated with spatial learning impairment and was found in the previous reports of CA structural analogue melamine. To further investigate the neurotoxic effects and the potential mechanism, the acetylcholine (ACh) level was detected in the rats which were exposed to CA during the whole of gestation. Local field potentials (LFPs) were recorded when rats infused with ACh or cholinergic receptor agonist into hippocampal CA3 or CA1 region were trained in the Y-maze task. We found the expression of ACh in the hippocampus was significantly reduced in dose-dependent manners. Intra-hippocampal infusion of ACh into the CA1 but not the CA3 region could effectively mitigate learning deficits induced by CA exposure. However, activation of cholinergic receptors did not rescue the learning impairments. In the LFP recording, we found that the hippocampal ACh infusions could enhance the values of phase synchronization between CA3 and CA1 regions in theta and alpha oscillations. Meanwhile, the reduction in the coupling directional index and the strength of CA3 driving CA1 in the CA-treated groups was also reversed by the ACh infusions. Our findings are consistent with the hypothesis and provide the first evidence that prenatal CA exposure induced spatial learning defect is attributed to the weakened ACh-mediated neuronal coupling and NIF in the CA3-CA1 pathway.

Purine catabolism by enterobacteria.

Purines are abundant among organic nitrogen sources and have high nitrogen content. Accordingly, microorganisms have evolved different pathways to catabolize purines and their metabolic products such as allantoin. Enterobacteria from the genera Escherichia, Klebsiella and Salmonella have three such pathways. First, the HPX pathway, found in the genus Klebsiella and very close relatives, catabolizes purines during aerobic growth, extracting all four nitrogen atoms in the process. This pathway includes several known or predicted enzymes not previously observed in other purine catabolic pathways. Second, the ALL pathway, found in strains from all three species, catabolizes allantoin during anaerobic growth in a branched pathway that also includes glyoxylate assimilation. This allantoin fermentation pathway originally was characterized in a gram-positive bacterium, and therefore is widespread. Third, the XDH pathway, found in strains from Escherichia and Klebsiella spp., at present is ill-defined but likely includes enzymes to catabolize purines during anaerobic growth. Critically, this pathway may include an enzyme system for anaerobic urate catabolism, a phenomenon not previously described. Documenting such a pathway would overturn the long-held assumption that urate catabolism requires oxygen. Overall, this broad capability for purine catabolism during either aerobic or anaerobic growth suggests that purines and their metabolites contribute to enterobacterial fitness in a variety of environments.

Small Molecule-Templated DNA Hydrogel with Record Stiffness Integrates and Releases DNA Nanostructures and Gene Silencing Nucleic Acids.

Deoxyribonucleic acid (DNA) hydrogels are a unique class of programmable, biocompatible materials able to respond to complex stimuli, making them valuable in drug delivery, analyte detection, cell growth, and shape-memory materials. However, unmodified DNA hydrogels in the literature are very soft, rarely reaching a storage modulus of 103  Pa, and they lack functionality, limiting their applications. Here, a DNA/small-molecule motif to create stiff hydrogels from unmodified DNA, reaching 105  Pa in storage modulus is used. The motif consists of an interaction between polyadenine and cyanuric acid-which has 3-thymine like faces-into multimicrometer supramolecular fibers. The mechanical properties of these hydrogels are readily tuned, they are self-healing and thixotropic. They integrate a high density of small, nontoxic molecules, and are functionalized simply by varying the molecule sidechain. They respond to three independent stimuli, including a small molecule stimulus. These stimuli are used to integrate and release DNA wireframe and DNA origami nanostructures within the hydrogel. The hydrogel is applied as an injectable delivery vector, releasing an antisense oligonucleotide in cells, and increasing its gene silencing efficacy. This work provides tunable, stimuli-responsive, exceptionally stiff all-DNA hydrogels from simple sequences, extending these materials' capabilities.

Study on the health risk of cyanuric acid in swimming pool water and its prevention and control measures.

Cyanuric acid is a widely used fine chemical intermediate that acts as a free chlorine buffer in swimming pool water, wherein it is often used as a stabilizer to maintain the germicidal efficacy of chlorinated disinfectants. However, it has also been associated with health risks. Herein, we introduced the sources and functions of cyanuric acid in swimming pool water, focusing on potential health risks associated with excessive concentration of the component and the current control standards worldwide. Also, the prevention and control measures were summarized in terms of physical chemistry, biodegradation, and ultraviolet radiation to provide a basis for the development of public health policies for swimming pool management.

Co-exposure of melamine and cyanuric acid as a risk factor for oxidative stress and energy metabolism: Adverse effects on hippocampal neuronal and synaptic function induced by excessive ROS production.

Melamine (MEL) and cyanuric acid (CA) alone have relatively low toxicity, but together they may cause serious damage to multiple organs, including the central nervous system, however, the underlying mechanism is unknown. This study aimed to determine and compare the neurotoxic effects of MEL (20 µg/mL), CA (20 µg/mL) and their combination (10 µg/mL MEL and 10 µg/mL CA) on cultured hippocampal neurons. The cell viability, apoptosis, anti-oxidative and energy metabolic indices were detected following 24 h of incubations. The miniature excitatory postsynaptic currents (mEPSCs), miniature inhibitory postsynaptic currents (mIPSCs) and synaptic plasticity in the hippocampal CA1 neurons were recorded. Moreover, ROS scavenger NAC was co-infused to investigate the potential mechanism. We found the complex of MEL and CA but not their alone caused severe cell death and disturbed energy production through activation caspase-3-mediated apoptosis. Meanwhile, the combination significantly reduced the amplitude, decay time and frequency of mEPSCs but not mIPSCs, indicating the pre- and post-synaptic inhibitory actions on neuronal activity. Paired-pulsed ratio (PPR) and long-term potentiation (LTP) at the Schaffer collateral-CA1 synapses were critically depressed. However, the co-application of NAC could effectively mitigate the cellular apoptosis, energy metabolism dysfunction and the impairments in neuronal and synaptic function. Our findings provide the first evidence that the combination of MEL and CA can exert more prominently neurotoxic effects than their alone and certify that one of the potential mechanisms for neuronal and synaptic dysfunction is the ROS-mediated signaling pathway.

Exposure to melamine cyanuric acid in adult mice caused motor activity and skeletal muscle energy metabolism disorder.

Thyroid hormone has a variety of physiological functions and plays an important role in the development of central nervous system, skeletal muscle and lung, as well as body temperature regulation. Skeletal muscle is a key determinant of basal metabolic rate and systemic energy metabolism. It contains Myopsin (SLN) which plays an important role in muscle heat production and energy metabolism. Melamine cyanuric acid (MCA) is an important component of the new flame retardant, but also a chemical interfering substance that can affect the endocrine in the body. It is mainly distributed in nylon and other flame retardant substances. Therefore, in this study, male mice were exposed to MCA at 10, 20 and 30 mg/kg for four weeks. We explored the effects of MCA exposure on skeletal muscle morphology, thermogenic gene expression and motor activity to explore whether MCA exposure could induce skeletal muscle hyperthermia and energy metabolism disorders and its underlying mechanisms. The results showed that the motor activity of male mice exposed to MCA was decreased, the morphology of skeletal muscle tissue was impaired, and the levels of morphological and thermogenic genes in skeletal muscle were destroyed. These findings are intended to provide a preliminary reference for studying the effects of MCA exposure on thermogenesis and energy metabolism in adult mice.

Prenatal cyanuric acid exposure disrupts cognitive flexibility and mGluR1-mediated hippocampal long-term depression in male rats.

Cyanuric acid is one of the most widely used classes of industrial chemicals and is now well known as food adulterant and contaminant in pet food and infant formula. Previously, it was reported that animals prenatally exposed to cyanuric acid showed neurotoxic effects that impaired memory consolidating and suppressed long-term potentiation (LTP) in the hippocampus. However, it is not clear if prenatal exposure to cyanuric acid induces deficits in reversal learning and long-term depression (LTD), which is required for the developmental reorganization of synaptic circuits and updating learned behaviors. Here, pregnant rats were i.p. injected with cyanuric acid (20 mg/kg) during the whole of gestation, and male offspring were selected to examine the levels of hippocampal mGluR1 and mGluR2/3 in young adulthood. The LTD at the Schaffer collateral-CA1 pathway was induced by low-frequency stimulation (LFS) and recorded. Reversal learning and hippocampus-dependent learning strategy were tested in Morris-water maze (MWM) and T-maze tasks, respectively. To further confirm the potential mechanism, selective agonists of mGluR1 and mGluR2/3 and antagonists of mGluR were intra-hippocampal infused before behavioral and neuronal recording. We found the levels of alkaline phosphatase were markedly increased in the maternal placenta and fetal brain following prenatal exposure. The expression of mGluR1 but not mGluR2/3 was significantly decreased and mGluR1-mediated LTD was selectively weakened. Prenatal cyanuric acid impaired reversal learning ability, without changing place learning strategy. The mGluR1 agonist could effectively enhance LFS-induced LTD and mitigate reversal learning deficits. Meanwhile, the reductions in the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPAR)-mediated spontaneous excitatory postsynaptic currents (sEPSCs) amplitude and frequency of cyanuric acid offspring were simultaneously alleviated by mGluR1 agonist infusions. Therefore, the results indicate the cognitive and synaptic impairments induced by prenatal cyanuric acid exposure are attributed to the disruption of the hippocampal mGluR1 signaling. Our findings provided the first evidence for the deteriorated effects of cyanuric acid on synaptic depression and advanced cognitive performance.

Urinary Excretion of Cyanuric Acid in Association with Urolithiasis: A Matched Case-Control Study in Shanghai Adults.

Melamine (MEL) has raised human concern since the 2008 milk scandal. Co-exposure to MEL and one of its analogues, cyanuric acid (CYA), has been reported to have a synergistic effect on promoting urolithiasis. However, few epidemiological studies have reported urolithiasis in association with exposure to CYA based on our knowledge. We therefore conducted a case-control study to investigate whether cases of urolithiasis had higher excretion of urinary CYA than the controls. Spot urine samples from 70 adult cases and first-morning urine samples from 70 controls (matched by age and sex) were collected for the measurement of MEL, CYA, and other two analogues in urine. The case group also had 2.81-fold higher concentration of urinary CYA than the control group (34.87 versus 12.43 ng/mL, p-value < 0.001). Multivariate conditional logistic regression models adjusting potential confounders of personal characteristics identified the risk factor of urinary CYA as a continuous variable with odds ratio (OR) (95% confidence interval, 95%CI) of 1.11 (1.02−1.21) (p-value = 0.021) and having meals at restaurants with OR of 5.71 (1.01−32.31) (p-value = 0.049). Compared to the participants having the lowest quartile of CYA concentration in urine, participants at the second, third, and fourth quartile groups had ORs of 13.94, 83.69, and 118.65 with p-values of 0.004, <0.001, and <0.001, respectively. The high excretion of urinary CYA in urolithiasis cases might be the sign of stones in patients consisting of CYA, then proving the attribution of CYA exposure in the etiology of urolithiasis. These findings are important since CYA is a degraded by-product of chlorinated isocyanuric acid disinfectants, which are widely used in daily life not only in swimming pool water but also in other scenarios, such as serving as anti-pandemic disinfectants. Risk assessment of CYA serving as a by-product of disinfectants needs to be conducted in future studies.