Metabolic profiling of a new synthetic cannabinoid receptor agonist, ADMB-FUBIATA, with human liver microsomes, human primary hepatocytes and human recombinant CYP450 enzymes using LC-quadrupole-orbitrap MS.

A novel synthetic cannabinoid receptor agonist (SCRA), ADMB-FUBIATA, featuring an acetamide-linked structure, has emerged on the illicit drug market. To provide dependable verification of its consumption and identify reliable biomarkers, we investigated an in vitro metabolism study of ADMB-FUBIATA incubated with human primary hepatocytes (HPHs) for the first time and correlated our findings with those from human liver microsomes (HLMs). In this work, ADMB-FUBIATA (10 µM) was incubated with HLM and HPH for 1 and 5 h, respectively, and then subjected to LC-quadrupole-orbitrap MS. A total of 25 metabolites across 8 metabolic pathways were identified after incubation with HLM and HPH, respectively. Monohydroxylation and N-dealkylation were the major metabolic pathways, and formation to ketone was first identified. In addition, the metabolism of ADMB-FUBIATA were found to be mediated by multiple CYP450 enzymes, predominantly CYP2C19, 2D6, and 3A4. This research also initially characterized the fragmentation patterns of the metabolites of ADMB-FUBIATA, elaborating on their structural relationship with ADMB-FUBIATA analogs. To effectively monitor ADMB-FUBIATA abuse, metabolites M4 and M1 were proposed as reliable biomarkers by cross-validating the HLM and HPH incubation results.

Exploring the topic structure and abuse trends of new psychoactive Substance since the 21st century from a bibliometric perspective.

Nowadays, NPS abuse are continuing to expand in terms of harm and scope, due to its cheap and easy to manufacture anywhere in the world. This study reviewed articles related to seven heavily abused NPS to analyze the structure and trends of NPS abuse. A total of 2476 articles were retrieved based on the search strategy for bibliometric analysis. A significant trend of research in recent years was the increasing number of research on synthetic opioids and designer benzodiazepines, but synthetic cannabinoid and synthetic cathinone still dominate, which were mainly concerned with the development of metabolic models and determining methods as well as their abuse characteristics and reasons. However, with the introduction of class-wide ban on synthetic cannabinoid in China and a series of enhancements in other countries, the abuse of it might decrease to some extent, but more than 20 kinds of synthetic cannabinoid beyond the scope of ban in China still reminded researchers of their potential threats. As for synthetic cathinone, an important phenomenon was some of the drugs first identified during certain period might be more widely distributed in the future. Besides, several problems such as the regulation and prevention mode of emerging NPS, development of testing technologies as well as the interpretation and identification of multiple NPS combinations were also worth paying attention to. This study could help entrants better understand the structure of NPS abuse and provided direction for future research in forensic toxicology.

Application of terahertz Time-Domain spectroscopy and chemometrics-based whale optimization algorithm in PDE5 inhibitor detection.

Combating the illicit use of PDE5 inhibitor drugs is a focal point in forensic science research. In order to achieve rapid identification of such drugs, this study applies terahertz time-domain spectroscopy combined with chemometrics to establish a fast and accurate detection method for PDE5 inhibitors. The optimal detection method is determined by comparing the spectral performance of three optical parameters, namely absorption coefficient, refractive index, and dielectric constant. Linear discriminant models based on different spectral parameters, whale optimization algorithm optimized extreme learning machine models, and whale optimization algorithm optimized random forest models are established. The effectiveness and performance of principal component analysis and competitive adaptive reweighted sampling algorithm for spectral feature data selection are also investigated. The PDE5 inhibitor identification model based on the competitive adaptive reweighted sampling - whale optimization algorithm - random forest (CARS-WOA-RF) model achieves an accuracy of 98.61%, and the identification model for two concentrations of Sildenafil achieves 100% accuracy. The results demonstrate that terahertz time-domain spectroscopy combined with chemometrics can effectively detect various common types of PDE5 inhibitor drugs and different concentrations.

[Determination of four amide synthetic cannabinoid isomers by ultra-high performance liquid chromatography-high resolution mass spectrometry].

Isomerization commonly occurs in synthetic cannabinoids (SCs). Owing to the few differences in their structure and properties, it is difficult to simultaneously separate and identify them. Thus, the identification of synthetic cannabinoids is challenging, posing a threat to public security. This study aims to separate and identify four SCs, which are 2-[1-(5-fluoropentyl)-1H-indole-3-formylamino]-3,3-dimethylbutyrate methyl ester (5F-MDMB-PICA), 2-[1-(5-fluoropentyl)-1H-indole-3-formylamino]-3-methylbutyrate ethyl ester (5F-EMB-PICA), N-(1-amino-2,2-dimethyl-1-oxobutyl-2-yl)-1-butyl-1H-indazole-3-formamide (ADB-BINACA), N-(1-carbamoyl-2-methylpropyl)-1-pentyl indazole-3-formamide (AB-PINACA).Supercritical fluid chromatography-mass spectroscopy (SFC-MS) can realize the effective separation of some cannabinoid isomers. However, most laboratories are not equipped with SFC-MS systems. Ultra-high performance liquid chromatography-high resolution mass spectroscopy (UHPLC-HRMS) effectively combines the excellent efficient separation characteristics of liquid chromatography and the powerful qualitative ability of mass spectrometry. It is a commonly used technical method for the detection of amide synthetic cannabinoids and their metabolites in vivo and in vitro because of its advantages of high accuracy and efficiency. Liquid chromatography allows the separation of tested components by exploiting the difference in the partition coefficients between the mobile and stationary phases. When the two phases are in relative motion, the tested components are divided between the two phases, facilitating the separation and analysis of each component. Although the difference in the polarities of the tested amide synthetic cannabinoid isomeric substances is extremely small, liquid chromatography can induce a strong separation effect. The advantages of UHPLC-HRMS include high resolution imparted by mass spectrometry and high sensitivity, allowing its application in the qualitative analysis of various substances. Through UHPLC-HRMS, trace analytes at the nanogram scale as well as pure drugs and their metabolites in biosamples can be detected. This study proposed a method for the determination of two pairs of amide synthetic cannabinoid isomers-5F-EMB-PICA and 5F-MDMB-PICA, ADB-BINACA and AB-PINACA-through UHPLC-HRMS. A Hypersil GOLD C18 column (100 mm×2.1 mm, 1.9 µm) was selected for separation via liquid chromatography, and gradient elution was performed with methanol containing 0.1% formic acid and a 0.1% formic acid aqueous solution containing 10 mmol/L ammonium formate. Full scan/data-dependent secondary mass spectrometry (Full MS/dd-MS2) was conducted in the positive ion mode for detection. The results indicated that the four synthetic cannabinoid isomers could be accurately detected under the abovementioned conditions. The resolution between 5F-EMB-PICA and 5F-MDMB-PICA was 2.06, while that between ADB-BINACA and AB-PINACA was 1.22, indicating the effective separation and detection of both pairs. Furthermore, method validation was conducted to ensure the accuracy of the proposed method. The relationship of the four amide synthetic cannabinoid isomers exhibited excellent linearity. The correlation coefficients (R2) were >0.99. Moreover, the matrix effects of the four SCs in hair samples were between 88.67% and 111.76% and the recoveries were 96.23%-105.11%. The intra-day and inter-day precisions (RSDs) were <10%. The proposed method was used to identify the case materials. AB-PINACA was detected in a hair sample at a content of 0.73 µg/g. 5F-MDMB-PICA was detected in a tobacco sample at a content of 11.3 mg/g. The results indicate that the proposed method can be used for the examination of practical samples conducted by public security organizations. This study provides a reference method for the identification of synthetic cannabinoid isomers.

Rapid detection of 10 benzodiazepines and metabolites in blood and urine using DART-MS/MS.

Benzodiazepines are essential screening targets for common sleeping and sedative drugs used in forensic toxicology. Direct analysis in real-time tandem mass spectrometry was used to rapidly identify 10 benzodiazepines and related metabolites in the blood and urine. The related direct analysis in real-time tandem mass spectrometry parameters were optimized. A liquid-liquid extraction method using ethyl acetate as the extraction solvent was used for sample preparation. The established method was validated and tested on case specimens. The limits of detection of this method ranged from 0.2 to 20 ng/mL and the limits of quantification from 1 to 50 ng/mL. The recoveries ranged from 78.8% to 114%, and the matrix effects were in the range of -21.2% to 17.9%. The precision and repeatability at high and medium concentrations did not exceed 14.6%, and the limit of quantification did not exceed 18.2%, indicating a desirable linear relationship. The established method was used to determine blood and urine specimens from authentic cases, and promising results were obtained.

Evaluation of Monochromatic Excitation X-ray Fluorescence Spectrometry for Rapid Thallium Detection in Biological Samples Using Animal Models.

Monochromatic excitation X-ray fluorescence (ME-XRF) spectrometry is a novel technique for trace element analysis, characterized by its simplicity, rapidity, and low cost. The objective of this study was to evaluate the applicability of ME-XRF technique for the measurement of thallium in biological samples. Acute and subacute thallium poisoning experiments were conducted to simulate various scenarios, with blood, urine, and 10 distinct organs collected. Detection was initially performed using ME-XRF technique, followed by validation with inductively coupled plasma mass spectrometry (ICP-MS). Excellent agreement between ME-XRF and ICP-MS values was demonstrated by means of paired sample t-tests and intraclass correlation coefficients. Subsequently, the practical implementation of the proposed technique was demonstrated through an actual case study. In conclusion, this study validates ME-XRF as a suitable alternative to ICP-MS for the measurement of trace heavy metals in biological samples. These efforts promote the development of simpler and faster techniques for heavy metal detection, thereby presenting novel avenues for the prevention and diagnosis of heavy metal poisoning.

Enhancing solar photothermal conversion and energy storage with titanium carbide (Ti3C2) MXene nanosheets in phase-change microcapsules.

We propose to enhance photothermal conversion via doping titanium carbide (Ti3C2) MXene nanosheets on the surfaces of phase-change microcapsules consisted of the n-Octadecane core and styrene divinylbenzene copolymer shell. Detected by scanning electron microscopy, the microcapsules showed a usually circular form with an appropriate dispersion. The thermal properties of the microcapsules were characterized using the differential scanning calorimetry and thermal conductivity instruments, realizing an excellent phase-change enthalpy of around 140 J/g, high encapsulation ratio of over 64 %, good heat transfer of 0.294 ± 0.003 W/(m·K), and great thermal reliability. More importantly, the microcapsules doped with Ti3C2 MXene nanosheets reach a solar-to-heat conversion efficiency of 85 ± 7 %, a substantial enhancement by 240 % in comparison with non-doping sample. The Ti3C2 MXene-doped microcapsules with excellent heat storage and solar-to-heat conversion capabilities offer great potential for high-efficiency solar energy utilization and can be applied to thermal energy storage systems and direct absorption solar collectors.

Metabolic Profile Analysis of Designer Benzodiazepine Etizolam in Zebrafish and Human Liver Microsomes.

As one of the most widely abused designer benzodiazepines worldwide, Etizolam is characterized by its high addiction potential, low production cost, and difficulty in detection. Due to the rapid metabolism of Etizolam in the human body, the probability of detecting the Etizolam parent drug in actual case samples by forensic personnel is low. Therefore, without detecting the parent drug, analysis of Etizolam metabolites can help forensic personnel provide references and suggestions on whether the suspect has taken Etizolam. This study simulates the objective metabolic process of the human body. It establishes a zebrafish in vivo metabolism model and a human liver microsome in vitro metabolism model to analyze the metabolic characteristics of Etizolam. A total of 28 metabolites were detected in the experiment, including 13 produced in zebrafish, 28 produced in zebrafish urine and feces, and 17 produced in human liver microsomes. The UPLC-Q-Exactive-MS technology was used to analyze the structures and related metabolic pathways of Etizolam metabolites in zebrafish and human liver microsomes, and a total of 9 metabolic pathways were identified, including monohydroxylation, dihydroxylation, hydration, desaturation, methylation, oxidative deamination to alcohol, oxidation, reduction acetylation, and glucuronidation. Among them, metabolites involving hydroxylation reactions (including monohydroxylation and dihydroxylation) accounted for 57.1% of the total number of potential metabolites, indicating that hydroxylation may be the major metabolic pathway of Etizolam. Based on the response values of each metabolite, monohydroxylation (M1), desaturation (M19), and hydration (M16) were recommended as potential biomarkers for Etizolam metabolism. The experimental results provide reference and guidance for forensic personnel in identifying Etizolam use in suspects.

Fluorescence and Thermal Regulation Using Low-Supercooling Inorganic Microencapsulated Phase-Change Materials.

High supercooling and single functionalization are the main barriers to the large-scale application of microencapsulated phase-change materials (PCMs) in the construction industry. To address these issues, we propose a new inorganic microencapsulated PCM, PW@CaWO4, which was synthesized via the in situ polymerization method using inorganic CaWO4 as shell and phase-change paraffin wax (PW) as core. We investigated the effects of different emulsifiers and core-to-shell ratios on microcapsule properties and found that the PW@CaWO4 microcapsules have regular spherical topography and good uniformity in particle size. During the synthesis process, the CaWO4 shell provides convenient conditions for heterogeneous nucleation of PW and effectively reduces the supercooling degree. The minimum supercooling degree of the PW@CaWO4 microcapsules is only 1.00 ± 0.08 °C, which is 3.41 °C lower than that of PW. Moreover, the PW@CaWO4 microcapsules can absorb ultraviolet radiation and exhibit fluorescence, which originates from the peculiar WO42- structure in the CaWO4 shell, eliminating the need for doping other light-activating ions into the shell. The newly prepared microcapsules possess several advantages, including suitable particle size, low supercooling, good heat storage, high thermal conductivity, good short-wave ultraviolet absorption, peculiar fluorescence, excellent proof of leakage, and so on. The microcapsules can be applied to fluorescent architectural energy-saving coatings.

Direct analysis in real-time tandem mass spectrometry method for the rapid screening of 11 new psychoactive substances in blood and urine.

RATIONALE: With the continuous renewal of new psychoactive substances (NPS), the abuse of NPS has seriously harmed social security and public safety. The number of deaths from the abuse of NPS is increasing year by year. Therefore, there is an immediate need to develop an effective method for detecting NPS. METHODS: Direct analysis in real-time tandem mass spectrometry (DART-MS/MS) was used to detect 11 NPS in blood and urine. The temperature of the ion source was optimized and set to 400°C. The mixture solvent of acetonitrile/methanol (4:1, v/v) was used as the precipitant. SKF-525 (2-(diethylamino)ethyl 2,2-diphenylpentanoate) was selected as the internal standard for quantification. After the pretreatment of the analytes in blood or urine, the supernatant was prepared for instrumental analysis. RESULTS: The results indicated that the correlation coefficients (r2 ) of all analytes ranged from 0.99 to 1 in the linear range. The recoveries of 11 analytes at three spiked levels ranged between 83.4% and 110.4% in blood and between 81.7% and 108.5% in urine. The matrix effects of 11 analytes ranged between 79.5% and 109.5% in blood and between 85.0% and 109.4% in urine. The relative standard deviations of intra-day and inter-day precisions and repeatability were lower than 12.4%, 14.1%, and 14.3% in blood and lower than 11.4%, 13.9%, and 14.3% in urine, respectively. CONCLUSION: The method established for the detection of 11 NPS could meet the needs for the rapid screening of NPS samples. The DART-MS/MS method has the advantages of being efficient, fast, and green. Therefore, it may become a promising technology for the detection of NPS in the future.

Metabolic profiles and screening tactics for MDMB-4en-PINACA in human urine and serum samples.

MDMB-4en-PINACA (Methyl 3,3-dimethyl-2-[1-(pent-4-en-1-yl)-1H-indazole-3-carboxamido] butanoate) is a potent agonist of the CB1 receptor. In 2021, it was one of the most common synthetic cannabinoid receptor agonists (SCRAs) seized by the Beijing Drug Control Agency. MDMB-4en-PINACA can be hard to detect in biological specimens because of ester hydrolysis. In this work, a highly sensitive liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method was developed for the detection of MDMB-4en-PINACA metabolites in urine, serum, and hair samples. Metabolites from authentic samples were compared with those from human liver microsomes (HLMs) in vitro and in zebrafish in vivo. A total of 75 metabolites, including 44 previously unreported metabolites, were identified from urine samples. We found that 11 metabolic pathways were involved in MDMB-4en-PINACA metabolism, including acetylation, a novel metabolic pathway for SCRAs. Our results revealed that ester hydrolysis and hydroxylation were to the major metabolic pathways involved in MDMB-4en-PINACA metabolism. Using serum samples, we detected 9 metabolites along with the parent drug. Only the parent drug was detected using hair samples. The existence of ADB-4en-PINACA makes the currently used biomarkers for MDMB-4enPINACA not very specific for the intake of MDMB-4en-PINACA. Therefore, based on the identified metabolites and their structural features, we propose more sensitive screening tactics for MDMB-4en-PINACA using urine and serum samples.

Asymmetric synthesis of aryl/vinyl alkyl carbinol esters via Ni-catalyzed reductive arylation/vinylation of 1-chloro-1-alkanol esters.

We report herein an asymmetric Ni-catalyzed cross-electrophile coupling approach to prepare enantioenriched aryl/vinyl alkyl carbinol esters through arylation/vinylation of easily accessible racemic 1-chloro-1-alkanol esters with aryl/vinyl electrophiles. The method features a broad substrate scope as demonstrated by more than 60 examples including the challenging chiral allylic esters. It tolerates a wide array of functional groups including alkenyl, carbonyl and free hydroxyl groups that may not survive in conventional carbonyl reduction and addition methods. The synthetic utility of the present work was showcased by facile preparation of a few key intermediates and the modification of chiral drugs and naturally occurring compounds. Finally, we describe an efficient one-pot procedure for this method.

[Simultaneous determination of 36 hypotensive drugs in fingerprints by ultra performance liquid chromatography-triple quadrupole composite linear ion trap mass spectrometry].

Fingerprints contain important information such as the ingredients ingested by the donor. By analyzing the characteristic components in fingerprints, the donor can be characterized, which would provide insights for investigation of a given case. This approach can also be used in the qualitative monitoring of drug intake. Therefore, the examination of hypotensive drugs in fingerprints has significant value in practical application. This study established a method based on ultra performance liquid chromatography-triple quadrupole composite linear ion trap mass spectrometry (UPLC-Q-TRAP/MS) for the simultaneous determination of 36 hypotensive drugs in fingerprints. The pre-treatment method was based on protein precipitation. A 3×3 cm filter paper was cut into pieces and placed in a 2 mL plastic centrifuge tube after fingerprint collection. Then, 0.50 mL methanol was added, followed by vortex mixing for 1 min and ultrasonic oscillation for 3 min. The filter paper was centrifuged at 12000 r/min for 5 min, and the supernatant was withdrawn for sample analysis. An ACQUITY UPLC® BEH C18 chromatographic column (100 mm×3.0 mm, 1.7 µm) was selected, with 0.01% aqueous formic acid and methanol as mobile phases for gradient elution. MS analysis involved scheduled multiple reaction monitoring-information dependent acquisition-enhanced product ion (SMRM-IDA-EPI) scanning. This method could be used to retrieve library researching during high-sensitivity analysis, which could increase the accuracy of qualitative results. The calibration curves showed good linearity in the range of 0.05-50.00 ng/fingerprint, with correlation coefficients (r) greater than 0.99 for all 36 analytes. The limits of detection and limits of quantification of the 36 hypotensive drugs were 0.001-0.045 ng/fingerprint and 0.002-0.050 ng/fingerprint, respectively. At spiked levels of 0.25, 2.50, 25.00 ng/fingerprint, the matrix effects, recoveries, intra-day precisions, and inter-day precisions of the 36 hypotensive drugs were 79.0%-119.2%, 79.3%-116.2%, 0.2%-18.3%, and 1.6%-19.1%, respectively. This method was used to detect hypotensive drugs in the fingerprints of 87 hypertensive patients, and hypotensive drug intakes were accurately detected in most cases. The established method is operationally simple, with high sensitivity and good selectivity, and it is suitable for screening and testing hypotensive drugs in fingerprints.

Quantitative analysis of 17 hypoglycemic drugs in fingerprints using ultra-high-performance liquid chromatography/tandem hybrid triple quadrupole linear ion trap mass spectrometry.

RATIONALE: The objective of this study was to develop, optimize, and validate a method for the determination and quantification of 17 hypoglycemic drugs in fingerprints using ultra-high-performance liquid chromatography/tandem hybrid triple quadrupole linear ion trap mass spectrometry (UHPLC/QTRAP-MS/MS). We also aimed to apply the present method to the fingerprints collected from patients with hyperglycemia. METHODS: The scheduled multiple reaction monitoring information-dependent acquisition-enhanced product ion (SMRM-IDA-EPI) scanning mode was utilized. The chromatographic system consisted of an Acquity UHPLC® BEH C18 column (3.0 × 100 mm, 1.7 µm) and a mobile phase of 0.01% (v/v) formic acid in water and methanol. Analytes were extracted via a precipitation protein procedure. The method was validated in accordance with the US Food and Drug Administration (FDA) guidance and applied to the analysis of fingerprint deposits from subjects who had taken the drugs. RESULTS: The limits of detection (LODs) and the lower limits of quantification (LLOQs) of 17 hypoglycemic drugs were 0.001 to 0.020 and 0.002 to 0.050 ng/fingerprint, respectively. The correlation coefficients (r) for the calibration curves were > 0.99 in the range of 0.050-50.000 ng/fingerprint. The matrix effect and recovery of 17 hypoglycemic drugs at three concentrations ranged from 81.1 to 117.3% and 80.0 to 109.6%, respectively. The validation data (intra- and inter-day combined) for accuracy ranged from 85.5 to 117.2%, the CV (%) data were ≤19.7%. All analytes were found to be stable stored in the autosampler (4°C) for 24 h. This validated method was successfully applied to detect hypoglycemic drugs in fingerprints from patients with hyperglycemia. CONCLUSIONS: A quantification method for hypoglycemic drugs in fingerprints was developed, optimized, and validated. This sensitive method could be used for drug monitoring and providing reference information in forensic investigations.

Rapid detection of nine synthetic cathinones in blood and urine by direct analysis in real-time-tandem mass spectrometry.

RATIONALE: Designer drugs of cathinone, a kind of hallucinogen, were abused in the recent years. They were also known as bath salts, plant fertilizers, and zombie potions in drug market. The abuse of synthetic cathinones caused many bad effects on social order. Rapid detection of synthetic cathinones became an important subject of study in forensic science. METHODS: Direct analysis in real-time-tandem mass spectrometry (DART-MS/MS) was used to develop an effective method on nine synthetic cathinones in human whole blood and urine. The reference materials with 100 ng/mL were prepared for mass spectrometry optimization with electrospray ionization (ESI) probe tandem QTRAP 4000 mass spectrometer. The temperature of DART ion source was optimized to 400°C. The volumes of 4/1 (v/v) MeCN/MeOH with 0.69 mL were selected for the preparation of 0.31 mL blood and urine samples, respectively. Then the spiked analytes were prepared for detection by the DART 12Dip-it autosampler module. RESULTS: The results showed that the linearities range between 0.1 and 5 µg/mL, the correlation coefficients (r2 ) ranged from 0.99 to 1, the limits of detection (LODs) were all between 0.5 and 50 ng/mL, and the relative standard deviations (RSDs) of repeatability, intra-day and inter-day precisions were all below 13% and 14% in blood and urine, respectively. CONCLUSION: The results indicated that the method could meet the needs of rapid screening of samples that may contain synthetic cathinones. In addition, the method developed has many advantages, such as efficient, fast sample preparation, and environmental protection. Therefore, the DART-MS/MS method would provide effective data support for rapid screening of synthetic cathinones in forensic science.

Fisetin Alleviates Neointimal Hyperplasia via PPARγ/PON2 Antioxidative Pathway in SHR Rat Artery Injury Model.

The phenotypic transformation of proliferation and migration in vascular smooth muscle cells (VSMCs) from media to intima is the basic pathology of neointimal hyperplasia after angioplasty in hypertensive patients. Angiotensin II (AngII) stimulates oxidative stress in VSMC, inducing VSMC proliferation and migration, which is a critical factor in both developments of hypertension and angioplasty-induced arterial restenosis. Fisetin, a plant flavonoid polyphenol, has been reported to be antioxidative and potent senolytic. It is unknown whether fisetin would inhibit neointimal hyperplasia. Therefore, we investigated the role of fisetin in neointimal formation in vitro and in vivo. The rat thoracic aortic smooth muscle cells (A10 cells) stimulated by AngII were used as the in vitro neointimal hyperplasia model, where AngII significantly induced the proliferation and migration in A10 cells. We found that fisetin could dose-dependently inhibit the effect of AngII via inducing the expression of an antioxidant, paraoxonase-2 (PON2), whose overexpression could inhibit the proliferation and migration of A10 cells and downexpression by siRNA had the opposite effect. Furthermore, we found the mechanism of fisetin's inducing PON2 expression involved PPARγ. Rosiglitazone, a PPARγ agonist, could increase PON2 expression in A10 cells, while the PPARγ inhibitor prevented the effect of fisetin on PON2. The in vivo neointimal hyperplasia model was established 2 weeks after the carotid artery balloon injury in SHR rats. Administration of fisetin (ip 3 mg/kg daily for 2 weeks) right after the injury significantly increased PON2 expression in the artery, inhibiting ROS production, and efficiently reduced carotid neointimal hyperplasia. These results indicate that fisetin increases the expression of antioxidant PON2 via activation of PPARγ, reducing oxidative stress, inhibiting VSMC proliferation and migration, and alleviates neointimal hyperplasia after intimal injury. PON2 may be a potential therapeutic target to reduce arterial remodeling after angioplasty in hypertensive patients.

Simultaneous determination and quantitation of hypolipidemic drugs in fingerprints by UPLC-Q-TRAP/MS.

An ultra-performance liquid chromatography tandem triple quadrupole compound linear ion trap mass spectrometry (UPLC-Q-TRAP/MS) method was developed and validated for the detection of hypolipidemic drugs in fingerprints. 13 hypolipidemic drugs were well separated by the gradient elution of 0.01% formic acid in water and methanol at a flow rate of 0.4 mL/min within 11 min. The analytes were detected in positive (ESI+) and negative (ESI-) modes and scanned using scheduled multiple reaction monitoring-information dependent acquisition-enhanced product ion (SMRM-IDA-EPI) for best selectivity and sensitivity. The calibration curves showed good linearity in the range of 0.050-50.000 ng/patch with coefficients (r2) higher than 0.9904 for all analytes. Meantime, the LODs and LLOQs were in ranges of 0.001-0.034 and 0.003-0.050 ng/patch. The accuracies, intra-day and inter-day precision ranged from -13.3 to 0.3%, 1.1-10.4% and 3.7-14.5%, respectively. The recoveries ranged from 79.9 to 114.8%, while the absolute and relative matrix effects were in the range of 83.0-107.2% and 2.2-9.7%. By comparing the non-spiked fingerprints from healthy volunteers with the fingerprints obtained from patients, demonstrated that the method was competent for determination and quantitation of hypolipidemic drugs in fingerprints.

Rapid Identification of MDMB-CHMINACA Metabolites Using Zebrafish and Human Liver Microsomes as the Biotransformation System by LC-QE-HF-MS.

MDMB-CHMINACA is a newly synthetic cannabinoid, which scoped in NMS Lab, USA. Since there are currently no published data on MDMB-CHMINACA metabolism, we aimed to identify its biotransformation pathways and major metabolites. Liquid chromatography Q-exactive HF hybrid quadrupole-orbitrap mass spectrometry (LC-QE-HF-MS) using full scan positive ion mode and targeted MS-MS (ddms2) techniques with accurate mass measurement were employed to analyze the metabolic sites and pathways. An in vivo metabolic animal model of zebrafish was established to verify the metabolic pathways of MDMB-CHMINACA obtained from human liver microsomal experiment in vitro. The results showed that 29 metabolites were generated in the zebrafish animal model and human liver microsomes model. Biotransformations mainly occurred at the cyclohexylmethyl tail of the compound, minor reactions also occurred at the tert-butyl chain and no reaction was analyzed at the indazole ring. We recommend M1 group (MDMB-CHMINACA ester hydroxylation) and M2 group (MDMB-CHMINACA monohydroxylation) as the potential poisoning markers to document MDMB-CHMINACA intake in clinical and forensic cases. Additionally, this study provides preliminary information regarding the metabolism of MDMB-CHMINACA that will guide analytical standard manufacturers to better provide suitable references for further studies on newly encountered designer drugs.

Differentiation of white architectural paints by microscopic laser Raman spectroscopy and chemometrics.

A feasible, effective and non-destructive method that could be used to differentiate architectural paints was proposed by Microscopic laser Raman spectroscopy and chemometrics. A total of 252 white architectural paints from 7 different manufacturers were prepared for evaluating the potential of differentiating them. 5th Newton interpolation polynomial combined with Savitzky-Golay 7-point and 1st or 2nd polynomial smoothing under the 1st-order derivative were considered as the optimal pre-processing method for MLRM data. The Bayes discriminant analysis model realized 100% accuracy based on discriminant functions Z1, Z2 and Z3, which was the more useful and practical method for differentiating white architectural paints than that of multilayer perceptron and radial basis function neural network models. All samples were differentiated exactly, which was rapid and non-destructive. The designed method demonstrated the potential of Microscopic Laser Raman spectroscopy in combination with pre-processing and chemometrics as a universal, confirmatory, and accurate method for the white architectural paint differentiation in forensic science.

A rapid and nondestructive approach for forensic identification of car bumper splinters using attenuated total reflectance Fourier transform infrared spectroscopy and chemometrics.

The proper identification of car bumper splinters at hit-and-run crime scenes is imperative to forensic investigations, as splinters yield crucial pieces of vehicle information that can lead to subsequent investigation resolution and criminal justice. A method based on attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) combined with Fisher discriminant analysis (FDA) and support vector machine (SVM) is reported to classify car bumper splinters. The FDA and SVM models were constructed based on full spectrum, fingerprint spectrum, and characteristic spectrum data from 156 car bumper splinter samples. The characteristic spectrum data were extracted by principal component analysis. The classification results for different types of data were compared, and the classification models were analyzed. In the FDA, the model based on the spectral data of the characteristic spectrum yielded the highest classification accuracy, and the classification accuracy based on 10 brands was 88.5%. For polypropylene type; polypropylene, talcum powder, and calcium carbonate type; and polypropylene and talcum powder type bumper samples, the classification accuracy rate reached 97.4%. The classification results were ideal for the SVM, for 10 brands and 3 types of samples, the classification accuracy of the model constructed based on both full spectrum and characteristic spectrum data reached 100%. The results suggest that the SVM model is superior to the FDA model. The SVM model is also suitable for the classification of high-dimensional data. ATR-FTIR combined with the chemometrics methods of FDA and SVM is a rapid, nondestructive, and accurate method for the differentiation of car bumper splinters.