STNGS: a deep scaffold learning-driven generation and screening framework for discovering potential novel psychoactive substances.

The supervision of novel psychoactive substances (NPSs) is a global problem, and the regulation of NPSs was heavily relied on identifying structural matches in established NPSs databases. However, violators could circumvent legal oversight by altering the side chain structure of recognized NPSs and the existing methods cannot overcome the inaccuracy and lag of supervision. In this study, we propose a scaffold and transformer-based NPS generation and Screening (STNGS) framework to systematically identify and evaluate potential NPSs.

Direct injection UPLC-MS/MS method for analysing 77 compounds including human biomarkers, illicit drugs, new psychoactive substances and metabolites in wastewater.

Wastewater analysis technology has emerged as a promising tool for monitoring illicit drug consumption. However, the current reliance on the solid-phase extraction (SPE) pre-treatment method presents significant challenges for widespread adoption and high-throughput monitoring, as it consumes a large amount of time and labor as well as requires specialized instruments. This study has developed a direct injection (DI) technique for UPLC-MS/MS, enabling the detection of 77 compounds encompassing metabolites of human biomarkers, illicit drugs, and new psychoactive substances.

Improved entropy-CRITIC population model based on temporal and spatial variability: Construction and application in wastewater epidemiology.

Numerous factors contribute to the uncertainty inherent in conducting wastewater-based epidemiology (WBE), with shifting populations exerting a significant influence. However, traditional single- and multi-parameter population models suffer from certain limitations. This study employs an evaluation model framework to construct a model (EC model) based on data characteristics.

CBMAFF-Net: An Intelligent NMR-Based Nontargeted Screening Method for New Psychoactive Substances.

With the proliferation and rapid evolution of new psychoactive substances (NPSs), traditional database-based search methods face increasing challenges in identifying NPS seizures with complex compositions, thereby complicating their regulation and early warning. To address this issue, CBMAFF-Net (CNN BiLSTM Multistep Attentional Feature Fusion Network) is proposed as an intelligent screening method to rapidly classify unknown confiscated substances using C nuclear magnetic resonance (NMR) and H NMR data. Initially, we utilize the synergy of a convolutional neural network (CNN) and bidirectional long short-term memory network (BiLSTM) to extract the global and local features of the NMR data.

Establishment of Broad-Specificity Monoclonal Antibody-Based Immunoassay for Rapid Detection of Indole-Type and Indazole-Type Synthetic Cannabinoids and Metabolites.

Synthetic cannabinoids (SCs) have emerged as one of the most severely abused categories of new psychoactive substances (NPS), exacerbating the global drug problem and posing significant threats to public health. Presently, a class of new amide-type SCs featuring an indazole or indole core has been identified in numerous cases of illegal drug use, but there is still a lack of comprehensive analysis methods of SC detection. Herein, monoclonal antibodies (mAbs) and targeting 36 indole-type and indazole-type SCs and their metabolites with IC ranging from 0.

Assessment of pharmacological effects and abuse potential of 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201 in mice.

Rationale: The newly emerging synthetic cannabinoids (SCs) 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201 have been observed to produce effects by activating cannabinoid type 1 (CB1) receptors. Nevertheless, the pharmacological effects and potential for abuse of these three substances remain to be studied. These substances have yet to be regulated in many countries.

Isobutyryl-carfentanyl has strong acute toxicity and analgesic effects with high addiction potential.

Rationale: Isobutyryl-carfentanyl is the most recently discovered fentanyl analogue with a chemical structure that is similar to that of carfentanyl. Its analogue, carfentanyl, is regarded as one of the most lethal drugs in the world, with a potency of 10,000 times that of morphine. Therefore, isobutyryl-carfentanyl may possess a comparably high potency and its harmful effects cannot be ignored.

Feature-Based Molecular Network-Assisted Cannabinoid and Flavonoid Profiling of Leaves and Their Antioxidant Properties.

() leaves are rich in cannabinoids and flavonoids, which play important antioxidant roles. Since the environmental factors may influence the accumulation of antioxidants in herbal medicines, which affects their activity, this study aimed to investigate the correlation between the chemical composition of leaves and their geographical origin and antioxidant activity. Firstly, a high-resolution mass spectrometry method assisted by semi-quantitative feature-based molecular networking (SQFBMN) was established for the characterization and quantitative analysis of leaves from various regions.

Preparation of amphiphilic poly(divinylbenzene--vinylpyrrolidone)-functionalized polydopamine magnetic nanoadsorbents for enrichment of synthetic cannabinoids in wastewater.

Concerns have been raised about synthetic cannabinoids (SCs), which are among the most often trafficked and used illegal substances. An analytical method that holds promise for determining illicit drug use in the general population is wastewater-based epidemiology (WBE). Unfortunately, the concentration of SCs in wastewater is often extremely low on account of their hydrophobic nature, thus presenting a significant obstacle to the accurate detection and quantification of SCs using WBE.

Development of fentanyl-specific monoclonal antibody (mAb) to antagonize the pharmacological effects of fentanyl.

Fentanyl, a critical component of opioid analgesics, poses a severe threat to public health, exacerbating the drug problem due to its potential fatality. Herein, we present two novel haptens designed with different attachment sites conjugated to keyhole limpet hemocyanin (KLH), aiming to develop an efficacious vaccine against fentanyl. KLH-Fent-1 demonstrated superior performance over KLH-Fent-2 in antibody titer, blood-brain distribution, and antinociceptive tests.

Wastewater-based estimation of diabetes mellitus prevalence in 237 cities: A cross-China study.

Diabetes mellitus, a metabolic disease characterized by hyperglycemia, has been witnessed as a rapidly escalating worldwide health crisis. China currently had 140.9 million diabetic population in 2021, which was the largest globally.

Estimation of the spatial pattern of gout prevalence across China by wastewater-based epidemiology.

Gout is a metabolic arthritis caused by hyperuricemia. In recent years, the prevalence of gout has been increased significantly in China due to the improvement of the living standards, and gout has become another common metabolic disease following diabetes mellitus. Gout severely affects the health status and life quality of human.

N-Isopropylbenzylamine-induced conditioned place preference, sensitization behaviour and self-administration in rodents.

N-Isopropylbenzylamine (N-ipb), a chain isomer of methamphetamine (METH) with similar physical properties, has been used as a substitute for METH in seized drug samples. However, the abuse potential of N-ipb remains unclear. Therefore, this study aimed to evaluate the abuse potential of N-ipb in comparison to METH, by using conditioned place preference (CPP), locomotor sensitization and intravenous self-administration tests.

Comparative pharmacokinetic and intracerebral distribution of MDMB-4F-BICA in mice following inhalation ('vapor') and subcutaneous injection.

MDMB-4F-BICA, also known as 4F-MDMB-BICA, is a new psychoactive substance that emerged in 2020. It is often illegally added to electronic cigarette oil for inhalation abuse, leading to serious adverse symptoms and even death. There are significant differences in pharmacokinetics between inhalation administration and conventional drug delivery methods.

The NLRP3 inflammasome: a vital player in inflammation and mediating the anti-inflammatory effect of CBD.

Background: The NLRP3 inflammasome is a vital player in the emergence of inflammation. The priming and activation of the NLRP3 inflammasome is a major trigger for inflammation which is a defense response against adverse stimuli. However, the excessive activation of the NLRP3 inflammasome can lead to the development of various inflammatory diseases.

In-sample stability and postsampling analysis of 21 illicit drugs, their metabolites and cotinine in wastewater.

A thorough understanding of the degradation of chemical biomarkers in wastewater after the sampling is critical in the surveillance of illicit drug use based on the back-calculation technique. Herein, three temperatures, eight groups of matrices, and acidification were applied to simulate the preservation condition of 21 illicit drugs, their metabolites, and cotinine for a 240-day stability study. It was proved that the temperature, matrices, and acidification play vital roles in their stability in wastewater.

Estimating the prevalence of dyslipidemia by measuring fenofibrate in 33 cities in China.

Dyslipidemia, recognized as a predominant risk factor for atherosclerotic cardiovascular disease (CVD), remains a pressing health concern worldwide, particularly in China with nearly 40 % of the population adversely suffering. Fenofibrate, as one of the most commonly used drugs for dyslipidemia therapy, excreted as the format of fenofibrate-acid, which showed considerable stability in sewage samples and could be detected as WBE-biomarkers to monitor the prevalence of dyslipidemia. In this work, we reported the first research on estimating the prevalence of dyslipidemia by WBE approach.

Metabolism of four novel structural analogs of ketamine, 2-FXE [2-(ethylamino)-2-(2-fluorophenyl) cyclohexan-1-one], 2-MDCK [2-(methylamino)-2-(o-tolyl) cyclohexan-1-one], 3-DMXE [2-(ethylamino)-2-(m-tolyl) cyclohexan-1-one], and 2-DMXE [2-(ethylamino)-2-(o-tolyl) cyclohexan-1-one], in human liver microsomes based on ultra-performance liquid chromatography-high-resolution tandem mass spectrometry.

New psychoactive substances are constantly emerging, among which ketamine analogs with the core structure of 2-amino-2-phenylcyclohexanone have attracted global attention due to their continued involvement in acute intoxications. The monitoring of these substances largely relies on the acquisition of metabolic data. However, the lack of in vitro human metabolism information for these emerging structural analogs presents significant challenges to drug control efforts.

Design and development of a lanthanide-labeled immunochromatographic strip for simultaneous detection of morphine, methamphetamine and ketamine in hair.

Colloidal gold immunoassay is the most widely used method in the field of drug detection. However, this method often has poor quantitative identification ability and low analytical sensitivity, which is not suitable for the analysis of hair poisoning ingredients. In order to solve these limitations, we developed an immunochromatographic test strip for simultaneously screening multiple drugs in this study.

Magnetic Liposomes Infused with GPCR-Expressing Cell Membrane for Targeted Extraction Using Minimum Organic Solvent: An Investigative Study of Trace THC in Sewage.

Trace analysis of lipophilic substances in complex environmental, food, or biological matrices has proven to be a challenge, on account of their high susceptibility to adsorption by particulate matter and liquid-solid interfaces. For this purpose, liquid-liquid extraction (LLE) is often employed as the separation method, which uses water-immiscible organic solvents. As an alternative, magnetic solid-phase extraction (MSPE) allows for adsorption, separation, and recovery of analytes from large volumes of aqueous samples with minimum usage of organic solvents.

Application of wastewater-based epidemiology to estimate the usage of beta-agonists in 31 cities in China.

The illegal use of beta-agonists could cause severe problems to human health. In this study, the usage of beta-agonists in 31 cities across China was estimated using wastewater-based epidemiology (WBE). The proposed method is based on solid-phase extraction (SPE) and LC-MS/MS and was developed and validated to determine the concentration of seven beta-agonists in wastewater.

A comprehensive analytical strategy based on characteristic fragments to detect synthetic cannabinoid analogs in seized products and hair samples.

Synthetic cannabinoids, one of the most widely abused new psychoactive substances (NPS), are now placed under national control generally in China. Due to continuous modification of synthetic cannabinoid structure, an ongoing dilemma in the forensic laboratory is that newly emerging substances cannot be detected by established methods. Thus, the screening methods for simultaneous detection of known or unknown substances have become research hotspots.

Nail analysis for the assessment of caffeine abuse in Northwest China: A population-based study.

Caffeine is the most widely consumed psychoactive agent worldwide and has the potential for abuse, but studies monitoring caffeine abuse in China are scarce. This study aims to estimate the prevalence of caffeine abuse in northwest China and investigate the correlation between caffeine and other drugs in hair and nails using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Fingernail clippings were collected from 376 participants in northwest China to detect caffeine and 13 other illicit psychoactive drugs and their metabolites.

Preparation of poly(methacrylic acid-co-ethylene glycol dimethacrylate)-functionalized magnetic polydopamine nanoparticles for the extraction of six cannabinoids in wastewater followed by UHPLC-MS/MS.

Phytocannabinoids and their synthetic analogs (natural and synthetic cannabinoids) are illicit drugs that are widely abused worldwide. Wastewater-based epidemiology (WBE) is an objective approach for the estimation of population-level exposure to a wide range of substances, especially drugs of abuse. However, the concentrations of cannabinoids in wastewater are extremely low (frequently at the levels of nanograms per liter), and the existing pretreatment procedures for wastewater have the disadvantages of time-consumption or low extraction recoveries.