Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19)1. The development of a vaccine is likely to take at least 12-18 months, and the typical timeline for approval of a new antiviral therapeutic agent can exceed 10 years. Thus, repurposing of known drugs could substantially accelerate the deployment of new therapies for COVID-19. Here we profiled a library of drugs encompassing approximately 12,000 clinical-stage or Food and Drug Administration (FDA)-approved small molecules to identify candidate therapeutic drugs for COVID-19. We report the identification of 100 molecules that inhibit viral replication of SARS-CoV-2, including 21 drugs that exhibit dose-response relationships. Of these, thirteen were found to harbour effective concentrations commensurate with probable achievable therapeutic doses in patients, including the PIKfyve kinase inhibitor apilimod2-4 and the cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825 and ONO 5334. Notably, MDL-28170, ONO 5334 and apilimod were found to antagonize viral replication in human pneumocyte-like cells derived from induced pluripotent stem cells, and apilimod also demonstrated antiviral efficacy in a primary human lung explant model. Since most of the molecules identified in this study have already advanced into the clinic, their known pharmacological and human safety profiles will enable accelerated preclinical and clinical evaluation of these drugs for the treatment of COVID-19.

Occurrence and Ecological Risk of Alkylamine Triazines in Chinese Estuarine Sediments: An Emerging Class of Persistent, Mobile, and Toxic Substances.

Identifying persistent, mobile, and toxic (PMT) substances from synthetic chemicals is critical for chemical management and ecological risk assessment. Inspired by the triazine analogues (e.g., atrazine and melamine) in the original European Union's list of PMT substances, the occurrence and compositions of alkylamine triazines (AATs) in the estuarine sediments of main rivers along the eastern coast of China were comprehensively explored by an integrated strategy of target, suspect, and nontarget screening analysis. A total of 44 AATs were identified, of which 23 were confirmed by comparison with authentic standards. Among the remaining tentatively identified analogues, 18 were emerging pollutants not previously reported in the environment. Tri- and di-AATs were the dominant analogues, and varied geographic distributions of AATs were apparent in the investigated regions. Toxic unit calculations indicated that there were acute and chronic risks to algae from AATs on a large geographical scale, with the antifouling biocide cybutryne as a key driver. The assessment of physicochemical properties further revealed that more than half of the AATs could be categorized as potential PMT and very persistent and very mobile substances at the screening level. These results highlight that AATs are a class of PMT substances posing high ecological impacts on the aquatic environment and therefore require more attention.

Porous poly(bismaleimide-co-divinylbenzene) microspheres as dispersive solid-phase extraction adsorbent coupled to high-performance liquid chromatography for the determination of triazine herbicide residues in vegetable samples.

In this work, monodisperse and nano-porous poly(bismaleimide-co-divinylbenzene) microspheres with large specific surface area (427.6 m2 /g) and rich pore structure were prepared by one-pot self-stable precipitation polymerization of 2,2'-bis[4-(4-maleimidophenoxy) phenyl] propane and divinylbenzene. The prepared poly(bismaleimide-co-divinylbenzene) microspheres were employed as dispersive solid-phase extraction (DSPE) adsorbent for the extraction of triazine herbicides. Under optimized conditions, good linearities were obtained between the peak area and the concentration of triazine herbicides in the range of 1-400 µg/L (R2 ≥ 0.9987) with the limits of detection of 0.12-0.31 µg/L. Triazine herbicides were detected using the described approach in vegetable samples (i.e., cucumber, tomato, and maize) with recoveries of 93.6%-117.3% and relative standard deviations of 0.4%-3.5%. In addition, the recoveries of triazine herbicides remained above 80.7% after being used for nine DSPE cycles, showing excellent reusability of poly(bismaleimide-co-divinylbenzene) microspheres. The adsorption of poly(bismaleimide-co-divinylbenzene) microspheres toward triazine herbicides was a monolayer and chemical adsorption. The adsorption mechanism between triazine herbicides and adsorbents might be a combination of hydrogen bonding, electrostatic interaction, and π-π conjugation. The results confirmed the potential use of the poly(bismaleimide-co-divinylbenzene) microspheres-based DSPE coupled to the high-performance liquid chromatography method for the detection of triazine herbicide residues in vegetable samples.

A nanogold sensor test for tire wear chemicals based on the plasmon ruler approach.

The release of tire wear substances in the environment is raising concerns about potential impacts on aquatic ecosystems. The purpose of this study was to develop a quick and inexpensive screening test for the following tire wear substances: 6-phenylphenyldiamine quinone (6-PPD quinone), hexamethoxymethylmelamine (HMMM), 1-3-diphenylguanidine (1,3-DPG), and melamine. A dual strategy consisting of nanogold (nAu) signal intensity and the plasmonic ruler principle was used based on the spectral shift from the unaggregated free-form nAu from 525 nm to aggregated nAu at higher wavelengths. The shift in resonance corresponded to the relative sizes of the tire wear substances at the surface of nAu: 6-PPD (560 nm), HMMM (590 nm), 1,3-DPG (620 nm), and melamine (660 nm) in a concentration-dependent manner. When present in mixtures, a large indiscriminate band between 550 and 660 nm with a maximum corresponding to the mean intermolecular distance of 0.43 nm from the tested individual substances suggests that all compounds indiscriminately interacted at the surface of nAu. An internal calibration methodology was developed for mixtures and biological extracts from mussels and biofilms and revealed a proportional increase in absorbance at the corresponding resonance line for each test compound. Application of this simple and quick methodology revealed the increased presence of melamine and HMMM compounds in mussels and biofilms collected at urban sites (downstream city, road runoffs), respectively. The data also showed that treated municipal effluent decreased somewhat melamine levels in mussels.

Rapid detection of melamine by DNA Walker mediated SERS sensing technique based on signal amplification function.

A new method is proposed for detecting typical melamine dopants in food using surface-enhanced Raman scattering (SERS) biosensing technology. Melamine specific aptamer was used as the identification probe, and gold magnets (AuNPs@MNPs) and small gold nanoparticles (AuNPs@MBA) were used as the basis for Raman detection. The Raman signal of the detection system can directly detect melamine quantitatively. Under optimized conditions, the detection of melamine was carried out in the low concentration range of 0.001-500 mg/kg, the enhancement factor (EF) was 2.3 × 107, and the detection limit was 0.001 mg/kg. The method is sensitive and rapid, and can be used for the rapid detection of melamine in the field environment.

Melamine-based hyper-cross-linked resin for efficient removal of total petroleum hydrocarbons (C10-C32) from aqueous solutions.

Petroleum hydrocarbons (PHCs) are produced from industrial discharges, storage leakages, accidental spills, and operational failures. The hazardous nature of PHCs causes serious health risks and threatens the entire aquatic habitat. In this research work, the investigation of the removal of total petroleum hydrocarbons (TPHs) from the contaminated water is carried out utilizing a novel hypercross-linked resin, MAICY, which is generated by condensation of commercially available precursors. The chemical structures of MAICY have been examined extensively by FESEM, FT-IR, solid (CP-MAS) 13C-NMR, and TGA. A comprehensive analysis for adsorption parameters of TPHs has been performed, and different models such as Langmuir and Freundlich isotherms have been employed where the Freundlich isotherm was found to be the best fit for removal of THPs (R2= 0.9991). The results revealed that the performance of MAICY for the adsorption of TPHs from contaminated water gives a maximum adsorption capacity (qe) of 146 mg.g-1. The results of various parameters hinted that the contact time (0.25-4 h), the dosage of adsorbent (0.17 g/L), pH (7), and concentration of TPHs (26.5 mg/L) have controlled the overall adsorptive performance. Moreover, the kinetic data of qe(expt.) and qe(calc.) for adsorption of TPHs disclosed the regression values (R2) for pseudo-first order (R2= 0.9921) and pseudo-second order (R2= 0.9891). Additionally, based on CHI factor (X2) error estimations, the data was shown to be more consistent with pseudo-first-order kinetics. Moreover, MAICY demonstrated excellent reusability and recycling properties for up to four consecutive adsorption-desorption cycles.

Understanding Environmental Fate: Soil Variability and Rainfall Influence on Triafamone and Ethoxysulfuron Leaching.

Considering the environmental impact of triafamone and ethoxysulfuron, it is crucial to investigate their leaching behaviour under different geographical conditions. The present study evaluates the effects of application rate, soil properties and rainfall conditions on leaching of these herbicides and their metabolites. Ethoxysulfuron leached up to 50-60 cm with 82.95 to 89.23% detected in leachates while triafamone leached only to 10-20 cm and was < 0.01 µg mL-1 in leachates. Highest leachability was observed in loamy sand followed by sandy loam and clay loam soil. M1 metabolite (N-(2-((4,6-dimethoxy-1,3,5-triazin-2-yl) (hydroxy) methyl) -6-fluorophenyl) -1,1-difluoro-N-methyl methane sulfonamide) was majorly present in 0 to 10 cm soil depth. With increase in rainfall, downward mobility of both parent and M1 increased. Amendment of loamy sand soil with farmyard manure reduced the leachability indicating it could mitigate groundwater pollution. However, the effect of different exogenous OM amendments on leaching behaviour of herbicides needs to be evaluated.

Melamine in Iranian foodstuffs: A systematic review, meta-analysis, and health risk assessment of infant formula.

The presence of melamine in food is one of the most significant threats to consumer health and food safety now confronting the communities. The goal of this systematic review and meta-analysis was to determine the melamine content of different food products available on the Iranian market. The pooled melamine concentration (95% confidence interval) on 484 samples of animal-based foodstuffs was as follows: 0.22 (0.08, 0.36 mg kg-1) for milk, 0.39 (0.25, 0.53 mg kg-1) for coffee mate, 1.45 (1.36, 1.54 mg kg-1) for dairy cream, 0.90 (0.50, 1.29 mg kg-1) for yoghurt, 1.25 (1.20, 1.29 mg kg-1) for cheese, 0.81 (-0.16, 1.78 mg kg-1) for hen eggs, 1.28 (1.25, 1.31 mg kg-1) for poultry meat, 0.58 (0.35, 0.80 mg kg-1) for chocolates, and 0.98 (0.18, 1.78 mg kg-1) for infant formula. Based on the results of health risk assessment study on toddlers under 2 years old who ingested infant formula (as a melamine-sensitive group), all groups of toddlers are at an acceptable level of non-carcinogenic risk (THQ ≤ 1). Toddlers were classified according to their ILCR (carcinogenic risk) levels due to infant formula consumption as follows: under 6 months (0.0000056), 6-12 months (0.0000077), 12-18 months (0.0000102), and 18-24 months (0.0000117). The melamine carcinogenicity in infant formula for children had an ILCR value of 0.000001-0.0001 in the investigation, which was considerable risk. According to the findings, Iranian food products (notably infant formula) should be analyzed for melamine contamination on a regular basis.

Bioinformatics analysis of the potential mechanisms of Alzheimer's disease induced by exposure to combined triazine herbicides.

BACKGROUND: The development of Alzheimer's disease (AD) is promoted by a combination of genetic and environmental factors. Notably, combined exposure to triazine herbicides atrazine (ATR), simazine (SIM), and propazine (PRO) may promote the development of AD, but the mechanism is unknown. AIM: To study the molecular mechanism of AD induced by triazine herbicides. METHODS: Differentially expressed genes (DEGs) of AD patients and controls were identified. The intersectional targets of ATR, SIM, and PRO for possible associations with AD were screened through network pharmacology and used for gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis. The binding potentials between the core targets and herbicides were validated by molecular docking and molecular dynamics. RESULTS: A total of 1,062 DEGs were screened between the AD patients and controls, which identified 148 intersectional targets of herbicides causing AD that were screened by network pharmacology analysis. GO and KEGG enrichment analysis revealed that cell cycling and cellular senescence were important signalling pathways. Finally, the core targets EGFR, FN1, and TYMS were screened and validated by molecular docking and molecular dynamics. CONCLUSION: Our results suggest that combined exposure to triazine herbicides might promote the development of AD, thereby providing new insights for the prevention of AD.

Spatial and seasonal distribution of pesticides in the waters of Azagny area (Grand Lahou, Cote d'Ivoire).

This study provides comprehensive data on the seasonal variation and distribution of pesticides in the waters bordering Azagny National Park (ANP). Forty-six (46) samples of water from the Azagny area were analyzed using high-performance liquid chromatography (HPLC) coupled with a UV/visible detector to assess the level of thirty-one pesticide molecules divided into six families. These include triazines, phenylureas, organophosphates, carbamates, chloroacetanilides, dicarboximides, and crimidine, which are regularly used in this area. The respective average concentrations of pesticides are 54.54 µg//L, 20.93 µg/L, 18.24 µg/L, 3.06 µg/L, and 16.52 µg/L in the Bandama, Azagny Canal, ANP, mangroves, and estuarine environment. The analyses also showed that herbicides were the most abundant pesticides in the three waters, Bandama, Azagny Canal, and Azagny Park, with levels of 100%, 63%, and 59%, respectively, followed by insecticides with a levels of 0%, 37%, and 41%, respectively. However, rodenticides (76%) were more frequently detected than herbicides (24% in the mangroves). Regarding seasonal variation, high levels of pesticides were detected in the Bandama River, the Azagny Canal, and the mangroves during the dry season, while multiple pesticide residues were detected during the rainy season. The waters bordering Azagny National Park (ANP) are contaminated with pesticide residues (triazines, phenylureas, organophosphates, carbamates, and chloroacetanilides). As a result, policymakers should implement measures to regularly monitor pesticide levels in plantations surrounding the Azagny region's waters in order to better preserve biodiversity.

Hydrophobic microporous extraction on polyurethane sponges for convenient and sensitive analysis of organic molecules in water.

RATIONALE: Various solvent supports have been developed to overcome solvent instability during liquid-phase microextraction. The hydrophobic polyurethane sponge (PS) possesses numerous cross-linked internal microchannels and terminal micropores that can facilitate steady solvent storage capacity, high extraction efficiency, extractant loading, and recycling convenience. METHODS: In this study, an easy, convenient, and efficient PS-supported liquid-phase microextraction (PS-LPME) coupled with gas chromatography-mass spectrometry (GC-MS) method was developed for the trace analysis of different organic compounds in aqueous solutions. Different extraction solvents, PS dosages, stirring speeds, and extraction times were first investigated by extracting eight polycyclic aromatic hydrocarbons (PAHs: naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, and pyrene), and then applied for the analysis of triazines, amides, chloroacetamides, and organophosphorus compounds. RESULTS: High enrichment factors (approximately 208-439) were observed for the monitored PAHs. Good linearities, with determination coefficients (r2 ) greater than 0.9992, were achieved in the concentration range of 0.01-50 µg L-1 . Low limits of detection and quantification were found in the ranges of 0.3-3 ng L-1 and 1-10 ng L-1 , respectively. At three spiked concentrations (0.1, 1, and 10 µg L-1 ), good recoveries were obtained in the range of 91.6-118.5% with intra- and inter-day relative standard deviations of less than 6.4% and 11.7%, respectively. CONCLUSIONS: The developed PS-LPME method coupled with GC-MS was successfully applied in the analysis of different organic compounds in aqueous solutions and has shown great convenience and satisfactory enrichment performance in microextraction analysis.

Silica gel impregnated with deep eutectic solvent-based matrix solid-phase dispersion followed by high-performance liquid chromatography for extraction and detection of triazine herbicides in brown sugar.

A novel method was developed to determine six triazine herbicides from brown sugar samples using matrix solid-phase dispersion (MSPD) based on silica gel impregnated with deep eutectic solvent (DES) followed by high-performance liquid chromatography with photodiode array detector (HPLC/PDA). Several factors involved in the MSPD procedure such as DES type, DES content in impregnated silica gel, adsorbent-to-sample mass ratio, type and volume of washing solvent, type and volume of eluent, and grinding time were screened using single-factor experiments and then optimized using Box-Behnken design to accomplish the highest recoveries. The above method demonstrated a good linear range (20-1000 µg kg-1) with a determination coefficient exceeding 0.9962, low limits of determination (1.59-3.77 µg kg-1), acceptable limits of quantifications, and acceptable spiking recoveries (95.0-101.7%) for six triazines under optimized conditions. The proposed MSPD-HPLC/PDA method is a convenient, effective, and sensitive method for rapidly isolating and quantifying six triazines from brown sugar.

13C NMR detection of non-protein nitrogen substance adulteration in animal feed.

Illegal adulteration of melamine in animal feed and food has been widely studied. However, the risk of using substitute non-protein nitrogen substances still exists. In this study, we developed the 13C NMR method for the detection of non-protein nitrogen substance adulteration in animal feed. Three compounds, i.e., urea, melamine, and biuret, were used for method development. We found that the chemical shifts of the characteristic peaks in the carbon spectra of high-nitrogen adulterants were all between 150 and 170 ppm, whereas the chemical shifts of real protein peptide bonds (-CO-NH-) were between 170 and 180 ppm, demonstrating a good distinction between non-protein nitrogen and authentic protein. The method for analyzing melamine, urea, and biuret was validated. The R2 values were all above 0.99 within the calibration range of 0.05-2% (w/w). The limits of quantification of urea, melamine, and biuret were 0.0120%, 0.0660%, and 0.0806%, respectively. This method involves simple sample pretreatment and rapid detection while also providing high accuracy. All the sample information obtained by NMR detection does not require strict impurity removal. Compared with a previously reported 1H NMR method, the developed 13C NMR method does not require strict moisture removal to avoid active hydrogen exchange, and the interfering peak overlap is mitigated.

Extraction of parabens by melamine sponge with determination by high-performance liquid chromatography.

In the present study, we propose a novel method for the extraction of parabens in personal care products. A new, simple adsorptive material was obtained by combining metal-organic frameworks and melamine sponges using the adhesive property of polyvinylidene fluoride. This new material, metal-organic frameworks/melamine sponges, was found to be particularly suitable for solid-phase extraction. The structural characteristics of metal-organic frameworks/melamine sponges were first analyzed by scanning electron microscopy. Subsequently, solid-phase extraction was performed on sample solutions, and the extracted substances were then analyzed by high-performance liquid chromatography. Following optimization of important experimental conditions, excellent recovery rates were obtained. Our novel method was then applied to the extraction of four parabens (methylparahydroxybenzoates, ethylparahydroxybenzoates, propylparahydroxybenzoates, and butylparahydroxybenzoates) from real samples. The results yielded limits of detection of 0.26-0.41 ng/mL. The inter- and intra-day recoveries were 104.0-109.7% and 91.2-98.1%, respectively (relative standard deviation, <13.8%).

Magnetic phenolic resin core-shell structure derived carbon microspheres for ultrafast magnetic solid-phase extraction of triazine herbicides.

In this study, monodisperse magnetic carbon microspheres were successfully synthesized through the carbonization of phenolic resin encapsulated Fe3 O4 core-shell structures. The magnetic carbon microspheres showed high performance in ultrafast extraction and separation of trace triazine herbicides from environmental water samples. Under optimized conditions, both the adsorption and desorption processes could be achieved in 2 min, and the maximum adsorption capacity for simazine and prometryn were 387.6 and 448.5 µg/g. Coupled with high-performance liquid chromatography-ultraviolet detection technology, the detection limit of triazine herbicides was in the range of 0.30-0.41 ng/mL. The mean recoveries ranged from 81.44 to 91.03% with relative standard deviations lower than 7.47%. The excellent magnetic solid-phase extraction performance indicates that magnetic carbon microspheres are promising candidate adsorbents for the fast analysis of environmental contaminants.

Evaluation of 2-hydroxyethyl methacrylate as comonomer in the preparation of water-compatible molecularly imprinted polymers for triazinic herbicides.

In this work, the preparation and evaluation of water-compatible molecularly imprinted polymers for triazines using 2-hydroxyethyl methacrylate and methacrylic acid as comonomers is described. Four sets of molecularly imprinted and non-imprinted polymers for propazine were prepared at varying monomer molar ratios (from 4:0 to 1:3), and evaluated for the recognition of several triazines directly in aqueous media. The evaluation was performed by loading 1 mL of an aqueous solution containing 500 ng of each selected triazine, washing with 500 µL of acetonitrile, and eluting with 500 µL of methanol followed by 2 × 500 µL of a solution of methanol containing 10% of acetic acid. Final determinations were performed by high-performance liquid chromatography-ultraviolet detection. Improvement in molecular recognition of triazines in water was obtained on those molecularly imprinted polymers incorporating 2-hydroxyethyl methacrylate in 3:1 or 2:2 molar ratios, being the former selected as optimum providing recoveries for propazine up to 80%. A molecularly imprinted solid-phase extraction protocol was developed to ensure that triazines-selective recognition takes place inside selective binding sites in pure water media. Finally, the developed method was successfully applied to the determination of the selected triazines in environmental waters providing limits of detection from 0.16 and the 0.5 µg/L concentration range.

Combination of microwave-assisted solvent extraction and effervescence-assisted deep eutectic solvent-based in-syringe dispersive liquid-liquid microextraction and its application in the extraction of triazine pesticides from apple samples.

In the current study, a combination of microwave-assisted solvent extraction combined with effervescence-assisted deep eutectic solvent-based in-syringe dispersive liquid-liquid microextraction has been developed as a new sample pretreatment method. The offered method was used for the extraction of five triazine pesticides (atrazine, propazine, cyanazine, ametryn, and simazine) from apple samples before their determination by gas chromatography-flame ionization detection. For this purpose, briefly, the apple sample was contacted with a suitable acidified extraction solvent and the mixture was exposed to microwave irradiations. Then, the supernatant was taken and mixed with a few microliters of a low-density deep eutectic solvent. The supernatant phase containing the extracted analytes was injected into a sodium bicarbonate solution filled into a syringe. Consequently, the effervescence reaction occurs and the analytes were extracted into the fine droplets of extractant dispersed throughout the solution. Afterward, an aliquot of this phase was analyzed by the chromatographic system. Satisfactory outcomes include high enrichment factors (228-261) and extraction recoveries (67-87%), good repeatability (relative standard deviations equal to or less than 3.2% and 5.3% for intra- and inter-day precisions), and low limits of detection (0.4-0.7 ng/g) and quantification (1.4-2.3 ng/g) were acquired under the best experimental situations.

Natural dynamics and residues of pymetrozine for typical rice-growing areas of China.

Pymetrozine has replaced toxic organophosphate pesticides previously used for controlling pests of rice crops in China. Existing data on its environmental behavior are usually related to studies on artificial plots that do not adequately address the natural dynamics and residues in actual field conditions. Therefore, studies under field conditions were carried out to investigate the natural dynamics and residues of pymetrozine in two typical rice-growing areas in China - Hunan and Guangxi provinces. Samples of paddy soil and water were collected in relation to spraying events in the study areas. The quick, easy, cheap, effective, rugged and safe (QuEChERS) method was used to extract pymetrozine residues from the samples by a Waters ACQUITY UPLC (Milford, MA, USA) system interfaced with a triple-quadrupole mass spectrometer (Xevo TQ-D, Waters Corp., USA). The initial deposition of pymetrozine in paddy soils was higher than in paddy waters in both areas. The decay of pymetrozine followed an exponential trend consistent with the first order kinetics. The half-life of pymetrozine in paddy water was determined to be 3.0 and 3.8 days, whereas the half-life in soil was 3.8 and 3.5 days in the Guangxi and Hunan samples, respectively. The decline rates of pymetrozine in paddy soil and paddy water in this field study were faster than those conducted under non-field conditions reported in previous studies. Compared to other pesticides used in China as reported in previous studies, the environmental persistence of pymetrozine in both paddy water and soils in Guangxi and Hunan provinces is very low. This has important implications for the use of pymetrozine in agricultural systems globally.

Exposure to melamine and its derivatives in Chinese adults: The cumulative risk assessment and the effect on routine blood parameters.

Melamine (MEL) and its derivatives, ammeline (AMN), ammelide (AMD), cyanuric acid (CYA) are widely existed in environmental media. Animal studies have reported the cumulative risk assessment (CRA) of simultaneous exposure to MEL and its derivatives and explored the associations between exposure and routine blood parameters. Such information is largely unknown in human studies. In this study, we detected the urinary concentrations of MEL and its derivatives in 239 Chinese adults to conduct the CRA by evaluating their hazard quotients (HQ) and hazard Index (HI), and also explored the possible associations between exposure and measured routine blood parameters in study population. The detectable frequencies of MEL, AMN, AMD and CYA were 96.65%, 41.00%, 97.91% and 97.07%, respectively. The median values of creatinine (Cr)-adjusted MEL, AMN, AMD, CYA and the total concentrations of MEL and its derivatives (∑MEL) were 11.41 µg/g Cr, not detected (ND), 2.64 µg/g Cr, 15.30 µg/g Cr, 35.02 µg/g Cr, respectively. There were 9 (3.77%) participants with estimated daily intakes (EDIs) of CYA exceeding the tolerable daily intake (TDI) of 2500 ng/kg bw/day, and 12 (5.02%) participants with HI of ∑MEL exposure exceeding 1 based on the strictest TDI value. Urinary concentrations of MEL and its derivatives were positively associated with specific routine blood parameters, including hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, white blood cell, neutrophil count (P < 0.05). Meanwhile, exposure to MEL and its derivatives increased the risk of red blood cell abnormality (P < 0.05). Our study is the first study to provide evidence-based data on the CRA of exposure to MEL and its derivatives in Chinese adults, and to propose a possible association between such exposure and routine blood parameters in human.

Application of a Screen-Printed Sensor Modified with Carbon Nanofibers for the Voltammetric Analysis of an Anticancer Disubstituted Fused Triazinone.

In this paper, we propose the first analytical procedure-using a screen-printed carbon electrode modified with carbon nanofibers (SPCE/CNFs)-for the detection and quantitative determination of an electroactive disubstituted fused triazinone, namely 4-Cl-PIMT, which is a promising anticancer drug candidate. The electrochemical performances of the sensor were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and square-wave adsorptive stripping voltammetry (SWAdSV). The presence of carbon nanofibers on the sensor surface caused a decrease in charge-transfer resistance and an increase in the active surface compared to the bare SPCE. Under the optimised experimental conditions, the proposed voltammetric procedure possesses a good linear response for the determination of 4-Cl-PIMT in the two linear ranges of 0.5-10 nM and 10-100 nM. The low limits of detection and quantification were calculated at 0.099 and 0.33 nM, respectively. In addition, the sensor displays high reproducibility and repeatability, as well as good selectivity. The selectivity was improved through the use of a flow system and a short accumulation time. The SWAdSV procedure with SPCE/CNFs was applied to determine 4-Cl-PIMT in human serum samples. The SWAdSV results were compared to those obtained by the ultra-high-performance liquid chromatography coupled with electrospray ionization/single-quadrupole mass spectrometry (UHPLC-ESI-MS) method.