The selective enrichment of trace hydrophilic peptides from complex biological matrices remains a pivotal challenge in biomarker discovery. To address this, we developed a high-throughput and environmentally friendly electromembrane extraction-liquid chromatograph/mass spectrometry (EME-LC/MS) method for the analysis of 21 hydrophilic endogenous peptides in urine. Two different liquid membranes were optimized: P1, a conventional organic liquid membrane consisting of 2-nitrophenyl octyl ether (NPOE) and carvacrol (2:1, v/v) with 2% di(2-ethylhexyl) phosphate (DEHP); and P2, a deep eutectic solvent (DES)-based membrane composed of camphor and decanoic acid (1:1, w/w) with 0.5% DEHP. Mechanistic studies revealed that P1 extraction relies on cation-t[, t[-t[ stacking, and ion-pair interactions, enriching 13 peptides within 20 min at 30 V. In contrast, P2 operates via hydrogen bonding and ionic interactions, achieving more rapid extraction of 14 peptides within only 10 min at 30 V, along with a broader operational window and enhanced green solvent potential. Importantly, we established a log P-charge dual-factor model, demonstrating that peptide electromigration was co-determined by lipophilicity (log P) and net charge under operational buffer, with its predictive reliability confirmed by external validation. Implemented in a 96-well format, the EME method was high-throughput, solvent-minimized, and environmentally friendly with AGREEprep score of 0.72. Beyond providing a robust analytical tool, this work established a fundamental mechanistic framework for the design of electromembrane extraction systems, advancing both biomarker analysis and the understanding of transmembrane transfer for polar biomolecules.

Phthalic acid esters (PAEs) exhibit ubiquitous contamination across aquatic systems, yet their spatiotemporal dynamics and associated risks remain poorly characterized. To address this, this study measured the concentrations of 13 PAEs in river samples collected from various locations along the Jinjiang River in Chengdu at different times, as well as in tap water samples from five different floors of a building and bottled water from five brands. Additionally, ecological risks were assessed using SSD curves, and health risks were evaluated based on USEPA-validated health risk models. The results indicated that surface water ∑PAEs ranged from 0.016 to 9.36 μg/L, with DBP (9.36 ± 2.46 μg/L) and DIBP (5.66 ± 1.49 μg/L) being the primary contributors, and significantly higher concentrations were observed upstream (most p < 0.05). Bottled and tap water ∑PAEs ranged from 0.015 to 7.42 and 0.019 to 7.79 μg/L, respectively, both dominated by DBP (bottled: 7.41 ± 0.35; tap: 7.79 ± 0.35 μg/L). Natural mineral bottled water showed the highest ∑PAEs, whereas ∑PAEs in tap water decreased with increasing building floor height. Furthermore, ecological risks to shellfish were identified, yet human health risks (oral/dermal) for adults/children remained low across all water types. Despite the high detection rates of PAEs, the dangers of population exposure were minimal. However, natural mineral bottled water and tap water from lower floors require prioritized monitoring due to higher PAE levels in surface water associated with human activities.

ObjectiveDue to the high global prevalence of silicosis and the ongoing challenges in its diagnosis, this pilot study aims to screen biomarkers from routine blood parameters and develop a multi-biomarker model for its early detection.MethodsA case-control study was conducted to screen biomarkers for the diagnosis of silicosis using LASSO regression, SVM and RF. A sample of 612 subjects (half cases and half controls) were randomly divided into training and test groups in a 2:1 ratio. Logistic regression analysis and receiver operating characteristic (ROC) curves were used to construct a multiple biomarker-based model for the diagnosis of silicosis, which was applied to both the training and the testing datasets.ResultsThe training cohort revealed significant statistical differences (P < 0.05) in multiple hematologic parameters between silicosis patients and healthy individuals. Based on machine learning, eight silicosis biomarkers were screened and identified from routine blood cell, biochemical and coagulation parameters. D-dimer (DD), Albumin/Globulin (A/G), lactate dehydrogenase (LDH) and white blood cells (WBC) were selected for constructing the logistic regression model for silicosis diagnostics. This model had a satisfactory performance in the training cohort with an area under the ROC curve (AUC) of 0.982, a diagnostic sensitivity of 95.4%, and a specificity of 92.2%. In addition, the model had a prediction accuracy of 0.936 with an AUC of 0.979 in the independent test cohort. Moreover, the diagnostic accuracies of the logistic model in silicosis stages 1, 2, and 3 were 88.0, 95.4, and 94.3% with an AUC of 0.968, 0.983, and 0.990 for silicosis, respectively.ConclusionA diagnostic model based on DD, A/G, LDH and WBC is successfully proposed for silicosis diagnostics. It is cheap, sensitive, specific, and preliminarily offers a potential strategy for the large-scale screening of silicosis.

Objective:To assess the exposure levels of heavy metals, including lead, arsenic, mercury, and cadmium, in the local population in Sichuan and Chongqing, China, to compare and analyze the differences in reference intervals (RIs) obtained from direct and indirect sampling methods, and to explore the interchangeability and limitations of these two sampling methods. Methods:RIs were obtained by the direct sampling method and the indirect sampling method. In the direct sample method, the levels of blood arsenic, urinary cadmium, urinary mercury, and blood lead levels of 5562 healthy participants aged 22-50 years in Sichuan and Chongqing, China were measured by atomic absorption spectrometry and inductively coupled plasma-mass spectrometry. Using the human biomonitoring (HBM) data, we established RIs for the population by a nonparametric method. On the other hand, in the indirect sampling method, RIs were established via a nonparametric method based on data from the laboratory information system (LIS) of a local hospital after stratifying healthy individuals using a Gaussian mixture model (GMM). Comparative analysis of the RIs derived from the two sampling methods were then conducted. Results:The RI for blood arsenic was 0.11-1.3 μmol/L. The RI for urinary cadmium was 0.51-2.80 μmol/mol creatine for adults aged 22 to under 43 years and 0.66-2.96 μmol/mol creatine for adults aged 43-50 years. The RI for urinary mercury was 0.12-1.10 μmol/mol creatine. The RI for blood lead was 14.00-47.00 μg/L for adults aged 22 to under 41 year, 16.00-53.38 μg/L for males aged 41-50 year, and 15.00-51.02 μg/L for females aged 41-50 year. Most of the RIs established by the direct sampling method had a narrower range compared to those established by the indirect sampling method, and the RIs established by both sampling methods were partially biased. Conclusions:The RIs for blood arsenic, urine cadmium, urine mercury, and blood lead in healthy individuals aged 22-50 years in Sichuan and Chongqing, China were established using both direct and indirect sampling methods, which contributes to a better understanding of environmental exposure to metals in the general population and provides a reference for metal poisoning. For data from the same lab, the GMM-based indirect sampling method demonstrated relatively consistent performance in establishing RIs compared with the direct sampling method.

BACKGROUND:Environmental metal pollution poses a potential threat to public health, and reference intervals (RIs) are crucial tools for assessing exposure levels. AIMS:Our study was the first to systematically establish RIs for lead, arsenic, mercury, and cadmium in a population in southwest China, examining differences across genders and ages. The study also compared the differences between RIs obtained by two sampling techniques, including direct and indirect sampling, to assess the substitutability and limitations between the two techniques. MATERIALS AND METHODS:Direct sampling employed atomic absorption spectrometry (AAS) and inductively coupled plasma-mass spectrometry (ICP-MS) on human biomonitoring (HBM) data, while indirect sampling utilized a Gaussian Mixture Model (GMM) applied to a local Laboratory Information System (LIS) database. RIs were determined using the nonparametric method for both approaches. RESULTS:RIs were established for each metal, with variations observed across age groups for cadmium and lead, and across genders for lead in certain age groups. Most of the RIs established by the direct sampling technique had a narrower range compared to that established by GMM, and the RIs established by the two techniques were partially biased. DISCUSSION AND CONCLUSION:These RIs offer a vital baseline for assessing environmental metal exposure and identifying metal poisoning in Southwest China. Additionally, this study highlights the potential of the GMM-based indirect sampling technique as a viable alternative to the traditional direct sampling technique, with the dual-technique comparison enhancing our understanding of their substitutability and limitations, thus opening new avenues for environmental health research.

7-Ethyl-10-hydroxycamptothecin (SN38), the bioactive metabolite of irinotecan (CPT-11), has been shown to be 100-1000 times more effective than CPT-11. However, the poor water solubility and bioavailability of SN38 constrained its clinical application. In this study, we synthesized a novel SN38-glucose conjugate (FSY04) to address this issue. Our in vitro studies indicated that FSY04 had a potent inhibitory ability against colorectal cancer (CRC) cell lines of SW-480 and HCT-116 compared to the inhibitory capacity of CPT-11. Interestingly, FSY04 possessed lower cytotoxicity against normal cell lines of LO2 and 293T in contrast with CPT-11. Moreover, FSY04 is more active than CPT-11 in inducing apoptosis, inhibiting migration, and invasion. In vivo experiments suggested that half of the equivalent of FSY04 inhibited the growth of SW480 in the xenograft tumor model better than one equivalent of CPT-11. Our data demonstrated FSY04 to be a promising agent in CRC therapy.

Tetracycline antibiotics (TCs) are among the most common broad spectrum antibiotic. Since 1940s, they have been widely used to prevent and treat human and animal infections, as well as growth promoters in animal feed. However, antibiotics are a double-edged sword. TCs can accumulate in humans and animals through the food chain, affecting human health and developing drug resistance. Therefore, TCs in food and environmental samples must be accurately analysed. In this review, analytical methods of TCs in various samples are summarised, focusing on novel sample pretreatment and detection techniques.

Abstract Objectives To explore the value of a logistic regression model based on haematological parameters for the early diagnosis of silicosis by comparing the differences in haematological parameters between silicosis patients and healthy physical examiners.Methods A total of 390 individuals, including 195 silicosis patients and 195 normal participants were included in the training cohort. Then, 65 silicosis patients and 65 healthy individuals were enrolled in the validation cohort. Whole blood samples were collected from all participants, and hematological indicator characteristics were determined. Features with statistical significance in the univariate analysis of the training cohort and reported significant features were included in the logistic regression analysis to determine the independent factors influencing the diagnosis of silicosis and to construct a logistic diagnostic model. A receiver operating characteristic (ROC) curve was plotted to evaluate the accuracy of the model in diagnosing silicosis.Results In the training cohort, several hematological indicators were significantly different in silicosis patients, including Hematocrit(HCT), Hemoglobin(HGB), Mean corpuscular volume(MCV), Red Blood Cell Count(RBC), White blood cell count (WBC), Mon#, Mon%, Neu#, Neu%, Red blood cell distribution width coefficient of variation(RDW_CV), C-reactive protein(CRP), Hydroxybutyrate dehydrogenase (HBDH), Lactate dehydrogenase(LDH), Prothrombin time(PT), International normalized ratio(INR), Fibrinogen(FIB), and D-Dimer(DD) levels, all with statistical significance (P < 0.05). The silicosis diagnostic model performed well in the training cohort (Area Under Curve, AUC = 0.943) and had high diagnostic sensitivity (83.1%) and specificity (92.3%). The diagnostic model also effectively distinguished between silicosis patients and the control cohort in the validation cohort (AUC = 0.936).Conclusions This study confirmed that Age, CRP, LDH, Macro%, and INR were independent factors influencing the diagnosis of silicosis, and the logistic regression model based on these indicators could provide a reliable basis for predicting silicosis diagnosis.

Background: Polycyclic aromatic hydrocarbons (PAHs) have attracted worldwide attention due to their carcinogenic, teratogenic, and mutagenic effects, environmental persistence, and bioaccumulation characteristics. Therefore, the sensitive, reliable, and rapid detection of PAHs in sediment is of great importance. Objective: To develop a high-performance liquid chromatography (HPLC) with fluorescence and ultraviolet detection after Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) treatment for simultaneous determination of 16U.S. Environmental Protection Agency priority PAHs in sediment samples. Method: The samples were ultrasonically extracted with acetone and then the supernatant was purified with a modified QuEChERS method. After centrifugation, the supernatant was injected into the HPLC system for analysis. The separation was accomplished on a ZORBAX Eclipse PAH column (150x4.6mm, 3.5 mu m) and the column temperature was set at 30 degrees C. The flow rate of the mobile phase consisting of water and acetonitrile in gradient elution mode was fixed at 0.9mL/min. Detection was conducted on an ultraviolet detector and a fluorescence detector simultaneously. The qualitative analysis was based on retention time and the quantification was based on standard curves. Results: Under the optimal conditions, this method showed good linearities in the range of 10-200 mu g/L with correlation coefficients greater than 0.9993. The method had LODs ranging from 0.00108 to 0.314ng/g. The mean recoveries ranged from 78.4 to 117% with intra-day and inter-day RSDs of 0.592-10.7% and 1.01-13.0%, respectively. The proposed method was successfully applied to the detection of 16 PAHs in sediment samples collected from the Funan River in Chengdu, China with total contents of 431-2143ng/g.dw. Conclusions: The established method is simple, rapid, environmentally friendly, and cost-effective. It can be applied to the analysis of 16 PAHs in sediment samples. Highlights: A method of QuEChERS with ultrasound-assisted extraction combined with HPLC has been established for the analysis of 16 PAHs in sediment samples and the proposed method has been successfully applied to the analysis PAHs in real sediment samples.

Background: The wide usage of tetracyclines in livestock farming may result in drug residues in foods. Therefore, it is necessary to develop reliable methods for the determination of tetracyclines in foods. Objective: A dispersive liquid-liquid microextraction (DLLME) combined with HPLC method was developed for the analysis of six tetracyclines in eggs and chicken. Methods: After deproteinization, tetracyclines in acidic solutions were concentrated by vortex-assisted DLLME. After the addition of NaCl (35% for eggs and 20% for chicken), a mixture of ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate and ethyl acetate (300 mu L-50 mu L for eggs and 200 mu L-60 mu L for chicken) was used as the extractant. After centrifugation, the extract was collected for HPLC analysis. Results: The developed method showed good linear relationships (10.0-500 mu g/kg), low method detection limits (0.219-1.42 mu g/kg) and quantification limits (0.731-4.72 mu g/kg), and satisfactory relative recoveries (87.1-104%), with intra-day and inter-day RSDs in the ranges of 0.853-8.62% and 1.65-11.8%, respectively. The established method was successfully applied for the determination of six tetracyclines in eggs and different parts of chicken. The contents of tetracyclines in all samples were lower than their maximum residue limits. Conclusion: A DLLME-HPLC method has been developed for the analysis of six tetracyclines in animal-derived foods using ionic liquid and ethyl acetate as the extractant. Highlights: The developed method is simple, sensitive, cost-effective, and has strong anti-interference abilities. This method has been successfully applied to the analysis of six tetracyclines in eggs and chicken.

A novel ionic liquid-based air-assisted dispersive liquid–liquid microextraction combined with high-performance liquid chromatographic method was developed for the simultaneous analysis of oxytetracycline, tetracycline, demeclocycline, metacycline, chlortetracycline and doxycycline in honey. Tetracyclines in samples were extracted with ethyl acetate-[Bmim]PF6 under acidic condition with the assistance of air. The analytes were separated on a C18 column thermostated at 20 °C under gradient condition with a mobile phase consisted of methanol and oxalic acid. Parameters for the extraction (pH, dilution buffer, ionic strength, volumes of ionic liquid and ethyl acetate, assistance techniques and extraction time) were evaluated. The developed method showed good linearities over the range of 10.0–500 μg/L (R2 > 0.999). The enrichment factors were 16.6–41.2. The detection limits and quantification limits were 0.434–0.919 μg/kg and 1.45–3.06 μg/kg, respectively. The recoveries were 89.5–116%. The intra-day and inter-day RSDs were 0.644–6.44% and 2.35–15.9%, respectively. The developed method is sensitive, accurate, rapid, convenient, and is applicable for the determination of six tetracyclines in honey.

Background: Vitamin E deficiencies are prevalent around the world and have become one of the major public health issues. It is necessary to determine their levels in human serum for routine clinical practice. Objective: In this study, a simple and green ionic liquid-based (IL)vortex-assisted (VA) liquid-liquid microextraction (LLME) combined with HPLC was developed for simultaneous determination of eight vitamin E isomers in human serum. Methods: The IL, 1-octyl-methylimidazolium trifluoromethanesulfonate ([OMIM]OTf), was added into the diluted sample and vortexed to form a cloudy solution. After centrifugation, the IL phase was collected for HPLC analysis. The separation was accomplished on a Phenomenex Luna-C18 column (250 mm x 4.6 mm, 5 mu m) and the column temperature was 30 degrees C. The mobile phase was methanol/acetonitrile (80+20, v/v) and the flow rate was 0.7 mL/min. A fluorescence detector was used for the simultaneous detection of eight vitamin E isomers, and the detection wavelength was set at 290/327 nm. The LLME procedure can be completed within 10 min without using any organic solvent. The parameters affecting the extraction efficiencies were optimized, including the type and volume of the ILs, dispersive solvent, vortex time, and salt addition. Results: Under the optimal conditions, limits of detection were 0.857-4.16 ng/mL. Acceptable recoveries ranging from 80.1% to 103% were achieved, with relative standard deviations less than 13.0%. The proposed method was successfully applied to the detection of eight vitamin E isomers in human serum samples. Conclusions: This method is simple, fast, environment-friendly, cheap, and has similar linear ranges, sensitivities, accuracy, and precision as those reported chromatographic methods. Highlights: The IL, [OMIM]OTf, was chosen as the green extractant of LLME for vitamin E extraction because of its strong adsorption property for vitamin E isomers. An IL-VA-LLME method has been developed for the analysis of 8 vitamin E isomers. The established method was successfully applied to the analysis of 8 vitamin E isomers in human serum samples.

Environmental endocrine-disrupting chemicals (EDCs) are a large category of chemicals that can disrupt normal endocrine functions of organisms. They can enter the environment and foodstuffs in different ways and bring great threat to human health. Phenolic environmental estrogens (PEEs) are the typical representatives of EDCs and include bisphenols, alkylphenols, and others such as dibromophenol, dichlorophenol, 4-nitrophenononylphenol, etc. Even trace amounts of PEEs can cause serious damage to the human reproductive, nervous, and immune systems; therefore, it is very important to develop accurate and sensitive methods for their determination in different matrixes. At the present, there are still many challenges in the determination of PEEs in the samples with complex matrixes, and the sample treatment is one of the key issues. This review deals with the recent advances in sample treatment methods for the analysis of PEEs in foods and drinking water, including improved and newly developed liquid-liquid extraction, solid-phase extraction (SPE), magnetic SPE, matrix solid-phase dispersion with new adsorbent materials, and stir-bar sorptive extraction. In addition, the challenges and perspectives are also briefly discussed.

Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) are derivatives of polycyclic aromatic hydrocarbons (PAHs). They are trace pollutants commonly found in the environment and have been widely detected in various matrices. Nitro-PAHs are direct mutagens and carcinogens to humans, so they have attracted increasing public attention. In order to accurately assess the adverse effects of nitro-PAHs on human health, it is necessary to analyze them in different samples. In this review, the sources, toxicity, contamination status, physicochemical properties, especially, the advances of their sample preparation and quantification methods in various matrices in the past decade are summarized.

Polycyclic aromatic hydrocarbons (PAHs) are a large category of ubiquitous persistent environmental pollutants, some of them have strong carcinogenicity to human and animals. These pollutants can easily enter the river through multiple ways including rainfall, dry deposition and water washout, and deposit in the sediment. However, it is easy for them to re-enter the river water and pollute water sources, as well as aquatic animals and plants, bringing potential harm to human health. Therefore, it is requisite to accurately analyze the PAHs in sediment. In this review, the analytical methods of PAHs in sediment, focused on the methods of sample extraction, purification, concentration and determination, are summarized. (C) 2019 Elsevier B.V. All rights reserved.

Vitamin D plays an important role in decreasing the risk of various musculoskeletal diseases and chronic illnesses by participating in the calcium, phosphate absorption, bone metabolism and many other metabolic pathways. Vitamin D deficiency among populations of different ages is common throughout the world, even in the developed countries. Accurate vitamin D analysis is crucial for quality control in pharmaceuticals and foods and assessment of human vitamin D nutritional status. This review briefly introduces the existing forms in different matrices, synthesis and metabolism process in humans of vitamin D, as well as the related diseases caused by its deficiency. The emphases are focused on the recent advances of sample pretreatment and analytical techniques of vitamin D and its analogues in pharmaceuticals, foods and biological samples in the last five years.

OBJECTIVE:To develop a method for the simultaneous determination of 67 pesticides in water by solid phase extration(SPE) disk extraction-gas chromatography-tandem mass spectrometry(GC-MS/MS).METHODS:Pesticides in water were extracted and cleaned-up with SPE disk, then eluted with dichloromethane-n-ethyl acetate(7∶3, V/V). After the eluent being concentrated to 1 mL under nitrogen blow at 40 ℃, the supernatant was injected into GC-MS/MS for analysis. The GC separation was performed on a DB-5 MS capillary column(30 m×0. 25 mm×0. 25 μm). The pesticides were detected by MS/MS in multiple reaction monitoring(MRM) mode and quantified by working curve method.RESULTS:The linear range of the method for most of the pesticides were in the range of 0. 05-5 μg/L with correlation coefficients of 0. 9924-0. 9999. The quantitative limits(S/N=10) of the method were in the range of 1. 0×10~(-5)-0. 059 μg/L. The recoveries for pesticides were 81. 0%-125. 0% with relative standard deviations of 1. 5%-21. 4%(n=6).CONCLUSION:The method is sensitive, simple, environmentally friendly and suitable to the determination of pesticides in drinking water for rapid screening and quantitative analysis.

Background: Beverages can be easily contaminated by phthalate esters (PAEs) during the production, bottling, and transportation processes. It is necessary to determine the contamination level in beverages for assessment of human exposure. Objective: In this study, magnetic solid-phase extraction (MSPE) was combined with HPLC for the determination of 11 PAEs in beverages. Methods: Self-synthesized magnetic multiwalled carbon nanotubes (m-MWCNTs) were used as the adsorbent for PAE extraction. To extract the PAEs, an appropriate amount of m-MWCNTs and NaCl was added to the beverage sample. The mixture was mixed on a vortex mixer, the magnetic sorbent was collected with the aid of a magnet, and the supernatant was removed. Then, the analytes were eluted with n-hexane-acetone (1+1, v/v). Finally, the eluent was analyzed by the HPLC method. The separation was accomplished on a Phenomenex Luna-C18 column (250 × 4.6 mm, 5 μm), and the detection wavelength was set at 225 nm. Results: The linear ranges of the method were 2-300 μg/L with correlation coefficients greater than 0.9981. The LOD and LOQ were in the range of 0.659-5.33 × 10-2 μg/L and 2.20-17.8 × 10-2 μg/L, respectively. The recoveries of the method ranged from 79.8 to 114%, with the relative SDs less than 15.8%. The established method has been successfully applied for the determination of 11 PAEs in mineral water, carbonated soft drink, tea beverage, and fruit juice samples. PAEs were detected at 0.246-34.3 μg/L in these samples. Conclusions: The m-MWCNTs are the satisfactory sorbent for MSPE because of their strong adsorption capacity for PAEs. The established MSPE-HPLC method is rapid, easy, sensitive, green, and cost-effective. It can be applied to the analysis of trace PAEs in plastic bottled beverages. Highlights: Three magnetic nanoparticles (MNPs), including Fe₃O₄ MNPs, m-MWCNTs, and magnetic graphene oxide, were synthesized, and m-MWCNTs were chosen as the sorbent of MSPE for PAE extraction because of their strong adsorption capacity for PAEs. An MSPE-HPLC method has been developed for the analysis of 11 phthalates in plastic bottled beverages. The established method was successfully applied to the analysis of 11 phthalates in four types of beverage samples.

本文将从能否反映真理这一角度来理解在古希腊时期的诗与哲学之争.在西方思想史上,诗与哲学之争一直是一个或隐或现的话题,从诗先于哲学而产生,到哲学对诗的驱逐,都推动着诗与哲学各自的发展,甚至是文学理论的发展.回到公元前五世纪的希腊爱琴海畔去了解二者的产生、发展和争论的背景,为世界本质和秩序的话语权的争夺奠定一个基础.

古文理论发展到姚鼐的手中,有吸取各方面优势并加以综合的趋势,但是同时也需要探讨他在理论与实际创作中出现的差距.一方面,这一差距难以弥合;另一方面,姚鼐在古文上的实践使后来者有可能形成对文学形式审美特征的认识,坚持道统、文以载道的桐城派反而在内容与形式、审美特征等方面促进了后来的桐城支派对文学作品的认识.