Exploring the optimal lower blood pressure boundary during endovascular thrombectomy in patients with large vessel occlusion.

BACKGROUND: Current guidelines advocate for maintaining BP level below 180/105 mmHg during EVT, determining the safe lower boundary remains primarily consensus-driven by experts. This study aims to delve into the correlation between various targets of lower boundary for systolic and diastolic BP (SBP and DBP) during EVT and 3-month functional outcomes. METHODS: A cohort study was conducted across two EVT-capable centers, enrolling patients with large artery occlusion undergoing EVT within 8 h of stroke onset. Mean BP values during EVT were meticulously recorded, and logistic regression models were utilized to evaluate the correlation between outcomes and diverse lower boundary targets for SBP and DBP. Additionally, logistic regression models investigated the relationship between periprocedural BP variability and subsequent outcomes. RESULTS: Among the 201 patients included, having a SBP higher than 130 or 140 mmHg showed an independent association with increased good functional outcomes at 3 months (adjusted odds ratio, aOR 2.80, 95% Cis, 1.26-6.39 for 140 mmHg; aOR 2.34, 95% Cis, 1.03-5.56 for 130 mmHg). Additionally, an SBP exceeding 130 mmHg was correlated with decreased 3-month mortality (aOR, 0.24, 95% CI 0.07-0.74). No significant relationship was observed between DBP and functional outcomes. Patients with higher periprocedural SBP coefficient variance exhibited a decreased rate of good functional outcomes at 3 months (aOR, 0.42, 95% CI, 0.18-0.96). CONCLUSIONS: A SBP range above 130-140 mmHg could potentially serve as a safe lower boundary during EVT, while minimizing BP fluctuations may correlate with improved post-EVT functional outcomes.

A simple, organized web-based system improved the transfer efficiency and patient outcomes for endovascular thrombectomy in regional stroke network.

BACKGROUND: Endovascular thrombectomy (EVT) is a time-sensitive treatment for acute ischemic stroke with large vessel occlusion. To optimize transfer efficiency, a web-based platform was introduced in the Tainan Stroke Network (TSN). We assessed its application and effectiveness in regional stroke care. METHOD: This new web-based platform containing a questionnaire-style interface was introduced on October 1, 2021. To assess the transfer efficiency and patient outcomes, acute stroke patients transferred from PSCs to CSC for EVT from April 01, 2020, to December 30, 2022, were enrolled. The patients were classified into the traditional transferal pathway (TTP) group and the new transferal pathway (NTP) group depending on mode of transfer. Patient characteristics, time segments after stroke onset and outcome were compared between groups. RESULT: A total of 104 patients were enrolled, with 77 in the TTP group and 27 in the NTP group. Compared to the TTP group, the NTP group had a significantly shorter onset-to-CSC door time (TTP vs. NTP: 267 vs. 198 min; p = 0.041) and a higher EVT rate (TTP vs. NTP: 18.2% vs. 48.1%, p = 0.002). Among EVT patients, those in the NTP group had a significantly shorter CSC door-to-puncture time (TTP vs. NTP: 131.5 vs. 110 min; p = 0.029). The NTP group had a higher rate of good functional outcomes at 3 months (TTP vs. NTP: 21% vs. 61.5%; p = 0.034). CONCLUSION: This new web-based EVT transfer system provides notable improvements in clinical outcomes, transfer efficiency, and EVT execution for potential EVT candidates without markedly changing the regional stroke care paradigm.

Simple, efficient, and eco-friendly sample preparation for simultaneous determination of paracetamol and chloramphenicol in meat.

We have developed and validated a simple, eco-friendly, and reliable method to simultaneously determine paracetamol and chloramphenicol in meat with ultra performance liquid chromatography and tandem mass spectrometry. The samples were firstly extracted with ethylenediaminetetraacetic acid-McIlvaine's buffer and then purified by solid-phase extraction by using a novel core-shell polyaniline/polyacrylonitrile nanofibers mat. Compared with existing methods for the two analytes, the proposed method was simplified greatly with much fewer sample preparation steps, consumed much less time (< 2 min per sample) and organic solvent (0.7 mL per sample). Low detection levels (0.15-0.20 µg/kg for paracetamol, 0.01 µg/kg for chloramphenicol) with good precision and recoveries of the target compounds were obtained. The proposed method was applied to determine the residual paracetamol and chloramphenicol in pork, chicken, and beef samples, and the test results were consistent with those using the Chinese national standard methods, which demonstrates the reliability and practicality of the new method.

The essential role of CYP2E1 in metabolism and hepatotoxicity of N,N-dimethylformamide using a novel Cyp2e1 knockout mouse model and a population study.

N,N-Dimethylformamide (DMF) is a widespread contaminant of leather factories and their surrounding environment. There is a lack of direct in vivo evidence supporting CYP2E1 as a primary enzyme responsible for DMF metabolism and hepatotoxicity. In this study, a novel Cyp2e1 knockout (KO) mouse model was generated and used to assess whether DMF metabolism and hepatotoxicity is CYP2E1 dependent using an acute toxicity protocol with a single dose of 1500 mg DMF/kg. An epidemiological study in 698 DMF-exposed workers and 188 non-DMF-exposed controls was conducted to investigate the associations between functional polymorphisms of CYP2E1 (rs6413432/rs2031920) and DMF metabolite (N-methylcarbmoylated-hemoglobin [NMHb]). We successfully established Cyp2e1 KO mice with evidence from DNA sequence analysis, which showed 1-bp insertion at 65 bp (C) site of Cyp2e1 Exon 1. In addition, western blot and in vivo pharmacokinetic study also showed a complete absence of CYP2E1 protein and a 92% and 88% reduction in CYP2E1 activity among males and females, respectively. DMF metabolism as evidenced by increased blood NMHb, and hepatotoxicity as evidenced by elevated liver/body weight ratio, activity of liver enzymes and massive liver necrosis were detected in wild-type (WT) mice but were completely abrogated in KO mice, strongly supporting a CYP2E1-dependent pattern of DMF metabolism and hepatotoxicity. Moreover, variant allele of CYP2E1-rs6413432 was also significantly associated with higher NMHb levels in DMF-exposed workers (P = 0.045). The increase of glucose-regulated protein 94 detected in WT mice but not in KO mice suggested CYP2E1-dependent endoplasmic reticulum stress may be a key mechanism underlying DMF-induced hepatotoxicity.

Prepared Reticulated Nickel Hydroxide for Sensing Urea by Differential Pulse Voltammetry.

A urea sensor base on reticulated nickel hydroxide is prepared by hydrothermal way and operated by differential pulse voltammetry method. The reticulated nickel hydroxide has been successfully synthesized by a hydrothermal method and has been characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). The Ni(OH)2 sensor exhibits a higher sensor response (S) of 7.1 than NiO and Au sensing materials to 0.05 M urea concentration at 0.62 V. Various concentration of urea from 0.1 mM to 50 mM are performed on Ni(OH)2, and the sensor response are increased from 1.1 to 7.1 by differential pulse voltammetry (DPV) method. The urea detection limit is measured as 0.1 µM in this system. In addition, the Ni(OH)2 sensor exhibited good reproducibility and short term stability, and the response exhibits no obvious changes after 20 days tests. A possible sensing mechanism of Ni(OH)2 urea sensor is presented.

Fertility: Store-Operated Ca2+ Entry in Germ Cells: Role in Egg Activation.

At the time of fertilization, the sperm activates the egg and induces embryonic development by triggering an elevation in the egg's intracellular free Ca2+ concentration. In mammals the initial Ca2+ rise is followed by a series of repetitive Ca2+ transients (known as oscillations) that last for several hours. Although the source of Ca2+ during the signaling process is primarily the egg's smooth endoplasmic reticulum, the oscillations stop in the absence of extracellular Ca2+ indicating that a Ca2+ influx across the plasma membrane is essential to sustain them. Depletion of the intracellular stores using specific inhibitors generates a Ca2+ entry across the plasma membrane of eggs of various species, and a continuous influx of Ca2+ has been linked to the sperm-induced Ca2+ oscillations in the mouse; these data indicate that store-operated Ca2+ entry (SOCE) operates in eggs and may be the mechanism that maintains the long-lasting Ca2+ signal at fertilization. Recent findings suggest that the signaling proteins STIM1 and Orai1 are present in eggs; they are responsible for mediating SOCE, and their functions are essential for proper Ca2+ signaling at fertilization to support normal embryo development.

The effects of permeating cryoprotectants on intracellular free-calcium concentrations and developmental potential of in vitro-matured feline oocytes.

Embryos produced from vitrified feline oocytes have resulted in pregnancies, but the efficiency of oocyte vitrification in cats is still low. Our objectives were to evaluate the effects of exposing feline oocytes to ethylene glycol (EG), propanediol (PrOH) and dimethyl sulfoxide (DMSO) on changes in intracellular free-calcium concentrations ([Ca(2+)]i), the time needed for enzymatic digestion of the zona pellucida (ZP), the incidence of parthenogenetic activation and degeneration and embryonic development following in vitro fertilisation (IVF). All of the chemicals tested altered [Ca(2+)]i, but changes in [Ca(2+)]i, resistance of the ZP to enzymatic digestion and the incidence of parthenogenetic activation (<5% for all treatments) were not affected (P>0.05) by extracellular Ca(2+). Exposure to EG (>44.1%) and DMSO (19.7%) increased (P<0.05) oocyte degeneration compared with control oocytes and oocytes exposed to PrOH (≤2.5%). Following exposure to a combination of PrOH and DMSO (10% v/v each), blastocyst development (per cleaved embryo; 52.1%) was similar (P>0.05) to control oocytes (64.4%). When oocytes were vitrified with PrOH and DMSO, 28.3% of surviving (intact plasma membrane) oocytes cleaved following IVF, but no blastocyst developed. When a non-permeating cryoprotectant (galactose, 0.25M) was added to the vitrification medium, 47.7% of surviving oocytes cleaved and 14.3% developed to the blastocyst stage.

Store-Operated Ca2+ Entry Sustains the Fertilization Ca2+ Signal in Pig Eggs.

The role of store-operated Ca(2+) entry (SOCE) in the maintenance of sperm-induced Ca(2+) oscillations was investigated in porcine eggs. We found that 10 µM gadolinium (Gd(3+)), which is known to inhibit SOCE, blocked Ca(2+) entry that was triggered by thapsigargin-induced store depletion and also caused an abrupt cessation of the fertilization Ca(2+) signal. In a similar manner 3,5-bis(trifluoromethyl)pyrazole 2 (20 µM), and tetrapandin-2 (10 µM), potent SOCE inhibitors, also blocked thapsigargin-stimulated Ca(2+) entry and disrupted the Ca(2+) oscillations after sperm-egg fusion. The downregulation of Stim1 or Orai1 in the eggs did not alter the Ca(2+) content of the intracellular stores, whereas co-overexpression of these proteins led to the generation of irregular Ca(2+) transients after fertilization that stopped prematurely. We also found that thapsigargin completely emptied the endoplasmic reticulum, and that the series of Ca(2+) transients stopped abruptly after the addition of thapsigargin to the fertilized eggs, indicating that the proper reloading of the intracellular stores is a prerequisite for the maintenance of the Ca(2+) oscillations. These data strengthen our previous findings that in porcine eggs SOCE is a major signaling cascade that is responsible for sustaining the repetitive Ca(2+) signal at fertilization.

Using bio-functionalized magnetic nanoparticles and dynamic nuclear magnetic resonance to characterize the time-dependent spin-spin relaxation time for sensitive bio-detection.

In this work, we report the use of bio-functionalized magnetic nanoparticles (BMNs) and dynamic magnetic resonance (DMR) to characterize the time-dependent spin-spin relaxation time for sensitive bio-detection. The biomarkers are the human C-reactive protein (CRP) while the BMNs are the anti-CRP bound onto dextran-coated Fe3O4 particles labeled as Fe3O4-antiCRP. It was found the time-dependent spin-spin relaxation time, T2, of protons decreases as time evolves. Additionally, the ΔT2 of of protons in BMNs increases as the concentration of CRP increases. We attribute these to the formation of the magnetic clusters that deteriorate the field homogeneity of nearby protons. A sensitivity better than 0.1 µg/mL for assaying CRP is achieved, which is much higher than that required by the clinical criteria (0.5 mg/dL). The present MR-detection platform shows promise for further use in detecting tumors, viruses, and proteins.

[Effect of N, N-dimethylformamide on oxidation or antioxidation status among occupational exposed workers].

OBJECTIVE: To explore the effect of N,N-dimethylformamide (DMF) on oxidation or antioxidation status among occupational exposed workers. METHODS: A total of 104 DMF exposed workers and 101 controls were recruited in this study in May 2012. The information of occupational history, age, gender, smoking and alcohol habits of all subjects were collected by questionnaire. DMF concentration in the air of workplace was tested. N-methyl-carbamoylated haemoglobin adduct (NMHb) in blood was chosen as an inner-dose biomarker, which was expressed as 3-methyl-5-isopropylhydantoin(MVH), the degeneration product of NMHb. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels were detected to reflect liver function. Serum superoxide dismutase (SOD) activity, glutathione-S-transferase (GST) activity, malondialdehyde (MDA) levels, 3- nitrotyrosine (3-NT) levels were detected to reflect oxidative/antioxidative status. RESULTS: DMF concentration in workplace air was within the range of 3.3-12.4 mg/m(3), which did not exceed our national standard. The MVH level in exposed workers was (19.69 ± 12.52) mg/kg, but was not detectable in control group. The activity of SOD in exposed workers ((125.30 ± 21.23) U/ml) was significantly higher than the control group ((118.35 ± 18.48) U/ml, t = -2.47, P = 0.014). However, the activity of SOD showed different trends with the increasing of MVH level. When MVH ≤ 24 mg/kg, the SOD activity increased with the increasing of MVH level (r = 0.356, P = 0.002). However, when MVH> 24 mg/kg, SOD activity expressed decreasing trend with the increasing of MVH level (r = -0.260, P = 0.150). No significant differences were observed in GST, MDA, 3-NT, ALT, AST levels among the two groups. CONCLUSION: DMF exposure might have stimulatory effect on antioxidation system of the body under low concentration; within the range of compensatory defense, DMF exposure did not cause obvious lipid and/or protein peroxidative damage.

Simultaneous monitoring of multiple prohibited drugs in various aquatic products.

Both sedative and antipathogenic drugs are often found to be illegally used in aquaculture, but there is a lack of simultaneous monitoring methods. A method for simultaneously monitoring multiple prohibited drugs in various aquatic product samples was developed in this work, including fish, shrimp, crab, and shellfish. Sulfonic acid-functionalized magnetic graphitic carbon nitride (S-MGCN) was synthesized and validated to efficiently co-extract all targets (adsorption efficiency over 90.07%) through various adsorption mechanisms such as electrostatic interaction, hydrogen bonding, and π-π interaction while demonstrating good sample matrix purification ability (matrix effect below 13.60%). A new magnetic solid-phase extraction method based on S-MGCN was subsequently established. Coupled with UPLC-MS/MS, the detection limits were 0.030.075 µg /kg, and the recoveries ranged from 88.76% to 111.74% with the RSDs lower than 14.60%, indicating that the developed method has good sensitivity, accuracy, and precision. Further validation of its practicality was achieved through actual sample analysis.

STIM1 is required for Ca2+ signaling during mammalian fertilization.

During fertilization in mammals, a series of oscillations in the oocyte's intracellular free Ca(2+) concentration is responsible for oocyte activation and stimulation of embryonic development. The oscillations are associated with influx of Ca(2+) across the plasma membrane that is probably triggered by the depletion of the intracellular stores, a mechanism known as store-operated Ca(2+) entry. Recently, STIM1 has been identified in oocytes as a key component of the machinery that generates the Ca(2+) influx after store depletion. In this study, the involvement of STIM1 in the sperm-induced Ca(2+) oscillations and its significance in supporting subsequent embryo development were investigated. Downregulation of STIM1 levels in pig oocytes by siRNA completely inhibited the repetitive Ca(2+) signal triggered by the fertilizing sperm. In addition, a significantly lower percentage of oocytes cleaved or formed blastocysts when STIM1 was downregulated prior to fertilization compared to the control groups. Restoring STIM1 levels after fertilization in such oocytes by means of mRNA injection could not rescue embryonic development that in most cases was arrested at the 2-cell stage. On the other hand, STIM1 overexpression prior to fertilization did not alter the pattern of sperm-induced Ca(2+) oscillations and development of these fertilized oocytes up to the blastocyst stage was also similar to that registered in the control group. Finally, downregulation of STIM1 had no effect on oocyte activation when activation was stimulated artificially by inducing a single large elevation in the oocyte's intracellular free Ca(2+) concentration. These findings suggest that STIM1 is essential for normal fertilization as it is involved in the maintenance of the long-lasting repetitive Ca(2+) signal.

Orai1 mediates store-operated Ca2+ entry during fertilization in mammalian oocytes.

The presence of the store-operated Ca(2+) entry channel Orai1 and its function in signal transduction during fertilization have been investigated in mammalian oocytes using the pig as a model. RT-PCR cloning and sequence analysis revealed that Orai1 is expressed in the oocytes with a coding sequence of 921bp. After indirect immunocytochemistry or the overexpression of EGFP-tagged Orai1, the fluorescent signal was present primarily in the cell cortex consistent with plasma membrane localization of the protein. Western blot and real-time PCR results showed that Orai1 expression decreases during oocyte maturation; this is associated with the oocytes gaining the ability to generate a large Ca(2+) influx after store depletion. Downregulation of Orai1 expression by siRNA microinjection blocked Ca(2+) influx after store depletion and subsequent Ca(2+) add-back; the Ca(2+) oscillations induced by the fertilizing sperm were also inhibited in oocytes with downregulated Orai1 levels. At the same time, overexpression of Orai1 in the oocytes also modified store-operated Ca(2+) entry and had an inhibitory effect on the fertilization Ca(2+) signal. The abnormal Ca(2+) signaling due to Orai1 downregulation had a strong negative impact on subsequent embryo development. Co-overexpression of Orai1 and STIM1 on the other hand, led to a dramatic increase in Ca(2+) entry after store depletion. The findings indicate that Orai1 is a plasma membrane-resident Ca(2+) channel that is responsible for mediating Ca(2+) entry after the mobilization of intracellular Ca(2+) in oocytes. Orai1 and a functional store-operated Ca(2+) entry pathway are required to maintain the Ca(2+) oscillations at fertilization and to support proper embryo development.

Calcium influx in mammalian eggs.

Calcium (Ca(2)(+)) signals are involved in the regulation of oocyte maturation and play a critical role during fertilization. In the egg, Ca(2)(+) is stored in the lumen of the endoplasmic reticulum and a signal is generated when the stored Ca(2)(+) is released through specialized channels in the membrane of the endoplasmic reticulum to elevate the free Ca(2)(+) concentration in the cytoplasm. Extracellular Ca(2)(+) is also important, indicated by the fact that the mobilization of luminal Ca(2)(+) is typically followed by Ca(2)(+) entry across the plasma membrane. The transmembrane Ca(2)(+) flux replenishes the endoplasmic reticulum, and thus, it is essential to sustain prolonged Ca(2)(+) signals. It also seems to be responsible for the stimulation of important signaling cascades required for complete egg activation. Characterization of the pathway that mediates Ca(2)(+) entry implies that its major components include STIM1, a protein that senses the filling status of the stores, and ORAI1, a channel protein located in the plasma membrane. Defining the mechanism and functions of Ca(2)(+) entry will not only lead to a better understanding of egg physiology but may also help improving the efficiency of a number of assisted reproductive technologies.

Efficient adsorptive removal of aminoglycoside antibiotics from environmental water.

Aminoglycoside antibiotics (AGs) in environmental water are emerging pollutants that must be removed to protect human health and the ecosystem. However, removing AGs from environmental water remains a technical challenge due to high polarity, stronger hydrophilicity and unique characteristics of polycation. Herein, a thermal-crosslinked polyvinyl alcohol electrospun nanofiber membrane (T-PVA NFsM) is synthesized and firstly leveraged as the adsorptive removal of AGs from environmental water. The thermal crosslinking strategy is demonstrated to enhance both the water resistance and hydrophilicity of T-PVA NFsM, thereby effectively interacting with AGs with high stability. Experimental characterizations and analog calculations indicate that T-PVA NFsM utilizes multiple adsorption mechanisms, including electrostatic and hydrogen bonding interactions with AGs. As a result, the material achieves 91.09%-100% adsorption efficiencies and a maximum adsorption capacity of 110.35 mg g-1 in less than 30 min. Furthermore, the adsorption kinetics follow the pseudo-second-order model. After eight consecutive adsorption-desorption cycles, T-PVA NFsM with a simplified recycling process maintains a sustainable adsorption capability. Compared with other forms of adsorption materials, T-PVA NFsM has significant advantages such as less consumption of adsorbent, high adsorption efficiency and fast removal speed. Therefore, T-PVA NFsM-based adsorptive removal holds promise for eliminating AGs from environmental water.

Polyvinyl alcohol electrospun nanofiber membrane based solid-phase extraction for monitoring administered aminoglycoside antibiotics in various animal-derived foods.

This work aims to develop a widely applicable method to monitor administered AGs in various animal-derived food samples to ensure food safety. A polyvinyl alcohol electrospun nanofiber membrane (PVA NFsM) was synthesized and employed as solid-phase extraction (SPE) sorbent, in combination with UPLC-MS/MS, for the simultaneous detection of ten AGs in nine types of animal-derived food samples. PVA NFsM exhibited excellent adsorption performance for the targets (with an adsorption rate of over 91.09%), good matrix purification ability (with a reduction of 7.65%-77.47% in matrix effect after SPE), and good recyclability (can be reused 8 times). The method displayed a linear range of 0.1-25000 µg/kg and attained limits of detection for AGs were 0.03-15 µg/kg. Spiked samples demonstrated a recovery of 91.72%-100.04% with a precision of<13.66%. The practicality of the developed method was verified by testing multiple actual samples.

Simultaneous determination of multiple mycotoxins in corn and wheat by high efficiency extraction and purification based on polydopamine and ionic liquid bifunctional nanofiber mat.

Due to the universality and harmfulness of mycotoxin co-contamination in cereals, it is of great significance to simultaneously monitor various mycotoxins co-polluted to ensure food safety and public health. In this work, a nanofiber mat modified by polydopamine and ionic liquid (PDA-IL-NFsM) was prepared and utilized as a solid-phase extraction (SPE) adsorbent for the simultaneous quantitative detection of multiple mycotoxins in corn and wheat. The PDA-IL-NFsM can form multiple retention mechanisms with the targets through hydrogen bond, π-π interaction, electrostatic or hydrophobic interaction, it shows favorable simultaneous adsorption performance (adsorption efficiency mostly higher than 88.27%) for fifteen mycotoxins in seven classes. Moreover, it can significantly reduce the matrix effect (lower than -13.69%), showing a good purification effect on the sample matrix. Based on the superior performance of PDA-IL-NFsM, a simple sample preparation method was established. The sample extract is simply diluted with water for SPE, and the eluent can be directly collected for ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analysis. The detection limit can reach 0.04-4.21 µg kg-1, the recovery was 80.09%-113.01%, and the relative standard deviations of intra-day and inter-day precision were 2.80%-14.81% and 0.68%-13.80% respectively. The results show that the proposed method has good sensitivity, accuracy and precision, and has practical application potential.

[Sulfonated magnetic graphite carbon nitride solid-phase extraction-ultra performance liquid chromatography-tandem mass spectrometry for screening malachite green and leucomalachite green in freshwater fish].

Malachite green (MG) and its metabolite, leucomalachite green (LMG), exert toxic effects on the human body. The use of these dyes is illegal, but they are still detected in aquatic products. Freshwater fish are aquatic products with the high non-qualified rates. Therefore, the sensitive screening of MG and LMG in freshwater fish is of great importance to ensure the safety of aquatic products. Owing to the low contents of MG and LMG in fish and the complex matrix of actual samples, sample preparation is required before detection to purify impurities and enrich the target compounds. Graphite carbon nitride (GCN), a polymer material composed of C, N, and H, has good chemical and thermal stability, a large specific surface area, and a large number of active sites. It has a wide range of application prospects in adsorption and can be used in food safety testing when compounded with Fe3O4 to form magnetic graphite carbon nitride (MGCN). In this study, sulfonated magnetic graphite carbon nitride (S-MGCN) was prepared by further functionalizing MGCN with sulfonic acid. After characterization by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and vibrating sample magnetometry (VSM), a magnetic solid-phase extraction (MSPE) method based on S-MGCN was established to extract MG and LMG from freshwater fish. The targets were screened using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Following sulfonic acid functionalization, S-MGCN showed increased electrostatic interactions based on the MGCN adsorption mechanism, which includes hydrogen bonds and π-π interactions; thus, its adsorption efficiency was significantly improved. The matrix effects were -42.21% and -33.77% before functionalization, -11.40% and -7.84% after functionalization, thus confirming that S-MGCN has significant matrix removal ability. Given that S-MGCN demonstrated excellent efficiency as an MSPE adsorbent, the adsorption conditions for S-MGCN were optimized. The optimal conditions were as follows: adsorbent dosage, 15 mg; adsorption time, 2 min; solution pH, 5; and ionic strength, not adjusted. Under these conditions, the adsorption efficiency of S-MGCN could reach 94.2%. Different organic solvents were used to elute adsorbed MG and LMG, and the desorption efficiency peaked when 1%(v/v) ammonia acetonitrile was used as the elution solvent. The elution volume was also optimized, and a maximum desorption efficiency of 93.2% was obtained when 1 mL of 1%(v/v) ammonia acetonitrile was added to S-MGCN. The limits of detection (LODs) and quantification (LOQs) of the two targets were determined at signal-to-noise ratios (S/N) of 3 and 10, respectively. The LODs and LOQs were 0.075 µg/kg and 0.25 µg/kg, respectively. The linear ranges of the two target compounds were 0.25-20.0 µg/kg with correlation coefficients (r) greater than 0.998. To assess accuracy and precision, we prepared spiked samples at three levels (low, medium, and high) with six parallel samples per level (n=6). The recoveries ranged from 88.8% to 105.9%. The intra- and inter-day relative standard deviations were 5.4%-13.7% (n=6) and 3.3%-11.1% (n=3), respectively. Compared with the national standard method, the proposed method features simpler sample pretreatment procedures, less use of organic reagents (5 mL), and a shorter extraction time (2 min); moreover, the method does not require complicated elution steps, and the eluent can be directly analyzed by UPLC-MS/MS. The test results of actual samples were consistent with those obtained via the national standard method, thus confirming the practical feasibility of the developed method. The proposed MSPE method based on S-MGCN is an efficient and environmentally friendly method that could provide a new methodological reference for the sensitive screening of MG and LMG in actual samples.

The relationships between plasma advanced glycation end products level and cognitive function in middle-aged and elderly Chinese subjects.

OBJECTIVES: To determine the relationships between circulating representative advanced glycation end products (AGEs) and cognitive performance in middle-aged and elderly Chinese adults. METHOD: A cross-sectional study with 1834 participants were included. Cognitive performance was assessed using the Mini-Mental State Examination (MMSE). Plasma free AGEs including Nε-carboxymethyl-L-lysine (CML), Nε-(1-carboxyethyl) lysine (CEL), S-carboxymethyl-L-cysteine (CMC) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were measured by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Multivariate adjusted linear and logistic regression analysis were used to explore the associations between plasma AGEs and cognitive function. RESULTS: The prevalence of mild cognitive impairment (MCI) was 17.94%. Plasma CMC and MG-H1 level were negatively associated with MMSE score (ß = -0.42, p < 0.001 for all) in the multivariate linear regression analysis. In the multivariate logistic regression analysis, compared to the lowest tertile, participants within the highest tertile of CMC and MG-H1 had increased risk of MCI [ORs (95% CI): 1.62 (1.21-2.17), P trend <0.001, and ORs (95% CI): 1.30 (0.97-1.76), P trend = 0.069, respectively]. In addition, the weighted quantile sum (WQS) index was negatively associated with MMSE (ß = -0.48, P < 0.001) and increased risk of MCI [ORs (95% CI): 1.35 (1.20-1.52), P < 0.001]. CONCLUSION: Combined exposure of plasma free AGEs including CML, CEL, CMC and MG-H1 were associated with increased risk of cognitive impairment. Plasma CMC and MG-H1 might the main contributors for cognitive impairment, while further longitudinal studies are required to verify the associations.