Determination of 13 potential anti-obesity agents in hair by dispersive liquid-liquid microextraction-assisted UHPLC-MS/MS.

As the adulteration of dietary supplements with synthetic drugs remains a prevalent issue, the inclusion of anti-obesity agents may pose health risks, potentially leading to central nervous system or cardiovascular diseases. However, surveillance studies on the use of anti-obesity agents by the Chinese population are limited. This study aims to establish an efficient and rapid hair pretreatment method using dispersive liquid-liquid microextraction (DLLME) combined with high-speed grinding and develop a sensitive and accurate analytical method employing ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for detecting 13 potential anti-obesity agents in hair samples. Herein, hair samples were washed sequentially with 0.1% sodium dodecyl sulfate (SDS), water and acetone, and then ground at high speed using 1 mL of an extraction solution (internal standard solution-n-butanol-1.2 mol/L Na2HPO4, pH10.0, 100:400:500, v/v/v for procaterol; internal standard solution-ethyl acetate-1.2 mol/L Na2HPO4, pH8.0, 100:300:600, v/v/v for other 12 anti-obesity agents) while simultaneously performing DLLME. The developed method successfully detected 13 anti-obesity agents within 11 min, including bambuterol, clenbuterol, ractopamine, clorprenaline, formoterol, salbutamol, terbutaline, procaterol, phentermine, bupropion, sibutramine, desmethyl sibutramine, and N,N-didesmethyl sibutramine, which improved the screening efficiency. The calibration curves exhibited good linearity of 0.025-5 ng/mg, achieving correlation coefficients of r ≥ 0.99. The lower limits of quantification (LLOQs) for the analytes were 0.025 ng/mg, demonstrating acceptable levels of accuracy and precision. Recovery rates ranged between 73.30% and 107.47% across the three concentrations of 0.075, 0.375, and 3.75 ng/mg. The validated method was successfully applied to 369 real cases and detected six analytes, including bambuterol, salbutamol, terbutaline, sibutramine, desmethyl sibutramine, and N,N-didesmethyl sibutramine. This method offers several advantages, including simple pretreatment, high extraction efficiency, rapid extraction, solvent economy, and pollution mitigation, making it highly suitable for large-scale surveillance of usage of added anti-obesity agents.

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. Consequently, we immunized mice with KLH-Fent-1 to generate fentanyl-specific monoclonal antibodies (mAbs) using the hybridoma technique to compensate for the defects of active immunization in the treatment of opioid overdose and addiction. The mAb produced by hybridoma 9D5 exhibited the ability to recognize fentanyl and its analogs with a binding affinity of 10-10 M. Subsequently, we developed a human IgG1 chimeric mAb to improve the degree of humanization. Pre-treatment with murine and chimeric mAb significantly reduced the analgesic effect of fentanyl and altered its blood-brain biodistribution in vivo. Furthermore, in a mouse model of fentanyl-induced respiratory depression, the chimeric mAb effectively reversed respiratory depression promptly and maintained a certain level during the week. The development of high-affinity chimeric mAb gives support to combat the challenges of fentanyl misuse and its detrimental consequences. In conclusion, mAb passive immunization represents a viable strategy for addressing fentanyl addiction and overdose.

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. In order to monitor the near real-time prevalence of gout, a wastewater-based epidemiology (WBE) approach was carried out in 257 Chinese cities using febuxostat as the biomarker. Febuxostat in wastewater was measured by a LC-MS/MS method with satisfactory results of method validation. The average concentration of febuxostat in wastewater was 53.05 ± 31.76 ng/L, with the estimated per capita consumption of 124.40 ± 73.37 mg/day/1000 inhabitant. The calculated prevalence of febuxostat was 0.41 % ± 0.24 %, and the prevalence of gout was finally estimated to be 1.30 % ± 0.77 % (0.60 % to 2.11 %), which was nearly consistent with value of 1.10 % obtained from the Guideline for the diagnosis and management of hyperuricemia and gout in China (2019). The results indicated that the febuxostat-based WBE approach might be reasonable to assess the near real-time gout prevalence in China.

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. DM has witnessed a significant surge in the past few decades, leading to an alarming rise in the overall burden caused by this disease. To monitor the near real-time DM prevalence and the consumption of first-line anti-diabetic drugs, a wastewater-based epidemiology (WBE) approach based on the back-calculation of metformin concentration was implemented in 237 cities in China. The quantitative analysis of metformin in wastewater was conducted by LC-MS/MS with satisfactory results of method validation. The average concentration of metformin in wastewater was 14.07 ± 13.16 µg/L, and the per capita consumption was 5.16 ± 2.08 mg/day/inh, ranging from 0.90 to 10.36 ± 4.63 mg/day/inh. The calculated metformin prevalence was found to be 0.52 % ± 0.28 %, and the final estimated DM prevalence was 11.33 % ± 4.99 %, which was nearly consistent with the result of the International Diabetes Federation survey of 9.98 %. The results suggested that metformin might be one of the suitable WBE biomarkers in DM monitoring and WBE strategy could potentially enable the estimation of DM prevalence in most of Chinese cities after reasonable correction of associated parameters.

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. Cannabidiol, as the second-most abundant component in cannabis, has a variety of pharmacological properties, particularly anti-inflammation. Unlike tetrahydrocannabinol, cannabidiol has a lower affinity for cannabinoid receptors, which may be the reason why it is not psychoactive. Notably, the mechanism by which cannabidiol exerts its anti-inflammatory effect is still unclear. METHODS: We have performed a literature review based on published original and review articles encompassing the NLRP3 inflammasome and cannabidiol in inflammation from central databases, including PubMed and Web of Science. RESULTS AND CONCLUSIONS: In this review, we first summarize the composition and activation process of the NLRP3 inflammasome. Then, we list possible molecular mechanisms of action of cannabidiol. Next, we explain the role of the NLRP3 inflammasome and the anti-inflammatory effect of cannabidiol in inflammatory disorders. Finally, we emphasize the capacity of cannabidiol to suppress inflammation by blocking the NLRP3 signaling pathway, which indicates that cannabidiol is a quite promising anti-inflammatory compound.

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. Most of them demonstrated high stability (transformation rates < 20%) during room temperature for 45 days, and the transformation rates decreased while the storage temperature reduced. The stability of the target compounds such as cocaine (COC), 6-monoacetylmorphine (6-MAM), and amphetamine (AM) is influenced by matrices. Acidification prevented the majority of analytes from transforming, making it a feasible solution for preservation after sampling. A model that combined the effects of temperature and matrix was developed to back-calculate the concentration of target compounds during the postsampling process. The feasibility of this model was validated by correcting the loss of COC and 6-MAM from 24.2% and 16.2% to 2.98% and 2.77%. This study simulated a typical large-scale sampling and storage scenario. The effect of the temperature, pH, and matrix on in-sample stability and the postsampling analysis of selected target compounds was investigated for the first time in this study.

Development of new matrix reference materials for quantitative urine analysis in drug tests.

Accurate quantitative analyses require standardized methods to control and improve the analytical process in the laboratory. The availability of urine reference materials (RMs) may offer a feasible option to improve the accuracy of urine analysis and to control matrix effects. This paper presents the complete process of the development of matrix RMs in urine, including sample preparation, homogeneity, and stability studies, as well as uncertainty assessment. A freeze-drying process was developed, and freeze-dried human and pig urine samples were prepared and verified to have comparable homogeneity to liquid samples and higher stability than liquid human, pig, and artificial urine samples at 4℃ or room temperature and under extreme conditions. A total of 21 authentic urine samples from August 2022 were measured with freeze-dried RMs and spiked urine samples, and the reliability of the quantification of the RMs was compared. The freeze-dried human urine matrix RM appeared to be an excellent tool for daily quality control, as it showed high stability and gave the most consistent results with spiked samples.

A mini-invasive surgical technique for Carlevale IOL implantation: case series study and description of concomitant surgery.

PURPOSE: To examine the feasibility and outcomes of a modified technique for the implantation of scleral fixated Carlevale intraocular lens (IOL) (I71 FIL SSF. Soleko IOL Division, Pontecorvo, Italy), and to analyze the occurrence of adverse events. METHODS: This is a retrospective observational study conducted revising patients charts from 2018 to 2023. Thirty-five eyes of 33 patients were included. Patients requiring IOL explantation had either IOL dislocation or opacification. The implantation of the Carlevale IOL was performed with the subconjunctival positioning of the anchors without any scleral flap. All maneuvers were performed transconjunctivally. The anatomical outcomes considered were IOL positioning, and the absence of postoperative complications. The functional outcomes analyzed were best correctedvisual acuity (BCVA) and refraction. RESULTS: In all the cases, the IOL was well positioned and centered postoperatively. No cases of conjunctival erosion were recorded. The best corrected visual acuity (BCVA) was 0.9±0.6 logMar (mean±standard deviation) preoperatively and 0.5±0.5 logMar (mean±standard deviation) postoperatively. The mean preoperative spherical equivalent was +6.8±7.7 dioptres, while postoperatively it was -1.1±1.6 dioptres. The most frequent procedure associated to secondary IOL implantation was posterior vitrectomy (25 eyes, 71.4%), which was performed with 25-gauge transconjunctival cannulas in the ciliary sulcus. The follow-up period was 24.5±16.9 months (mean±standard deviation). CONCLUSION: The described mini-invasive technique for Carlevale IOL implantation is safe and effective. It can be recommended either as a stand-alone operation or associated to concurrent surgical procedures.

Simple and rapid detection of three amatoxins and three phallotoxins in human body fluids by UPLC-MS-MS and its application in 15 poisoning cases.

Amatoxins and phallotoxins are toxic cyclopeptides found in the genus Amanita and are among the predominant causes of foodborne sickness and poisoning-related fatalities in China. This study introduces and validates a simple, rapid and cost-effective ultra-performance liquid chromatography-mass spectrometry method for the simultaneous determination and quantification of α-amanitin, ß-amanitin, γ-amanitin, phallisacin, phallacidin and phalloidin in human blood and urine. Quick therapeutic decision-making is supported by a 9 min chromatographic separation performed on a Waters Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 µm) using a gradient of high-performance liquid chromatography (HPLC)-grade water and methanol:0.005% formic acid. The analyte limit of quantification was 1-3 ng/mL in blood and 0.5-2 ng/mL in urine. Calibrations curves, prepared by spiking drug-free blood and urine, demonstrated acceptable linearity with mean correlation coefficients (r) greater than 0.99 for all phallotoxins and amatoxins. Acceptable intraday and interday precision (relative standard deviation <15%) and accuracy (bias, -4.8% to 13.0% for blood and-9.0% to 14.7% for urine) were achieved. The validated method was successfully applied to analyze 9 blood samples and 2 urine samples testing positive for amatoxins and/or phallotoxins. Amatoxins and/or phallotoxins were identified in each whole blood sample at a range of 1.12-5.63 ng/mL and in two urine samples from 1.01-9.27 ng/mL. The method has the benefits of simple sample preparation (protein precipitation) and wide analyte coverage, making it suitable for emergency quantitative surveillance toxicological analysis in clinics and forensic poisoning practice.

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. 527 sewage samples from 33 cities in China were extracted by solid phase and analyzed by LC-MS/MS. The detected concentration of fenofibrate acid in sewage was on an average of 120.5 ± 59.9 ng/L, and the reverse-calculated consumption of fenofibrate based on fenofibrate acid was 77.8 ± 25.0 mg/day/1000inh. Detailed analysis unveiled an average prevalence of fenofibrate at 0.056 % ± 0.018 %, and the dyslipidemia prevalence among the population aged over 15 was ultimately estimated to be 37.9 % ± 9.3 % and was in accordance with the China Cardiovascular research result of 40.4 %, which proves that WBE is a substitutable approach of traditional epidemiological investigation methods due to its timeliness and cost-effectiveness. This study demonstrated that estimating dyslipidemia prevalence by WBE with metabolite fenofibrate acid as a biomarker is feasible in most Chinese cities.

Resolving D-Amino Acid Containing Peptides Using Ion Mobility-Mass Spectrometry: Challenges and Recent Developments.

Peptides and proteins having D-amino acids in their sequences are now believed to be widespread among different living organisms. Their significance is attributed to the diverse functions of these molecules, such as having a certain pathological implication or enhancing biological activity. Indeed, some peptide molecules with D-amino acids in their structure have already found their way to clinical use such as the antibacterial gramicidin and the antidiabetic nateglinide. Ion mobility mass spectrometry (IM-MS) added an additional dimension of separation as it depends on ions mobility in the space, which is dependent on their shapes, and the shape depends on the orientation of atoms. Thus, D-amino acids containing peptides (DAACPs) will have different mobility and collision cross-section values than those with L-amino acids. Eventually, this will lead to baseline separation of the two peptides. Additionally, ion mobility can precisely locate the position of D-amino acids by analyzing the difference in the arrival times of the fragment ions. The importance of DAACPs, as well as the difficulties in discovering them, were addressed in this review. Similarly, we emphasized how recent developments in IM-MS have improved their detection and analysis. Consequently, the LC-IM-MS/MS platform appears to be promising in isomeric mixture analysis.

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. This hand-held test strip used fluorescent nanoparticles loaded with lanthanide chelates as the signal carrier of fluorescence reading, and conducted quantitative testing of various drugs based on the competitive immune reaction between the analyte and antigen. Under the optimal conditions, the competition curves of morphine (MOP), methamphetamine (MET) and ketamine (KET) were obtained on a single band. The detection limit (LOD) of this analytical method was 100-1000 times lower than that of colloidal gold test strips. The detection limits of MOP, MET and KET were 0.06 ng mL-1, 0.1 ng mL-1 and 1.0 ng mL-1, respectively. No cross-reaction was observed when morphine, methamphetamine and ketamine were tested simultaneously with this method. And 184 hair samples were tested simultaneously, and the detected amount was very close to the results of LC-MS. The immunochromatographic strip showed good stability in repeated tests, and the coefficient of variation was less than 15%. Fluorescence immunochromatography strips and handheld strip readers have the characteristics of portability, speed, ease of operation and high sensitivity, and may become powerful tools for screening drug abuse in hair in forensic medicine.

Mechanisms of NLRP3 inflammasome activation and the development of peptide inhibitors.

The Nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3), a member of the nucleotide-binding oligomerization domain (NOD) like receptors (NLRs) family, plays an important role in the innate immune response against pathogen invasions. NLRP3 inflammasome consisting of NLRP3 protein, the adapter protein apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD) (ASC), and the effector protein pro-caspase-1, is central to this process. Upon activation, NLRP3 inflammasome initiates the release of inflammatory cytokines and triggers a form of cell death known as pyroptosis. Dysregulation or inappropriate activation of NLRP3 has been implicated in various human diseases, including type 2 diabetes, colitis, depression, and gout. Consequently, understanding the mechanism underlying NLRP3 inflammasome activation is critical for the development of therapeutic drugs. In the pursuit of potential therapeutic agents, peptides present several advantages over small molecules. They offer higher selectivity, increased potency, reduced toxicity, and fewer off-target effects. The advancements in molecular biology have expanded the opportunities for applying peptides in medicine, unlocking their vast medical potential. This review begins by providing a comprehensive summary of recent research progress regarding the mechanisms governing NLRP3 inflammasome activation. Subsequently, we offer an overview of current peptide inhibitors capable of modulating the NLRP3 inflammasome activation pathway.

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. However, the poor selectivity hampers its performance in various scenarios, especially in sewage samples where complicated and unpredictable interference exists, resulting in block of the active adsorption sites of the sorbent. To this end, we propose receptor-affinity MSPE employing magnetic liposomes decorated with cell membranes expressing G-protein-coupled receptor as the sorbents. Application of the novel sorbent CM@Lip@Fe infused with CB1 cannabinoid receptors was demonstrated for the targeted extraction and enrichment of tetrahydrocannabinol from sewage matrix. Thanks to the high affinity and molecular selectivity of the ligand-receptor interactions, a limit of quantitation of 5.17 ng/L was achieved coupled with HPLC-MS/MS in unfiltered raw sewage, featuring minimum usage of organic solvents, fivefold enhanced sensitivity, low sorbent dosage (75 mg/L of sewage), and high efficiency as major advantages over conventional LLE. This work establishes a framework for efficient separation of specific molecules from complex media, thus promising to extend and refine standard LLE as the clean-up procedure for trace analysis.

Recent advances in the treatment of IBD: Targets, mechanisms and related therapies.

Inflammatory bowel disease (IBD), as a representative inflammatory disease, currently has multiple effective treatment options available and new therapeutic strategies are being actively explored to further increase the treatment options for patients with IBD. Furthermore, biologic agents and small molecule drugs developed for ulcerative colitis (UC) and Crohn's disease (CD) have evolved toward fewer side effects and more accurate targeting. Novel inhibitors that target cytokines (such as IL-12/23 inhibitors, PDE4 inhibitors), integrins (such as integrin inhibitors), cytokine signaling pathways (such as JAK inhibitors, SMAD7 blocker) and cell signaling receptors (such as S1P receptor modulator) have become the preferred treatment choice for many IBD patients. Conventional therapies such as 5-aminosalicylic acid, corticosteroids, immunomodulators and anti-tumor necrosis factor agents continue to demonstrate therapeutic efficacy, particularly in combination with drug therapy. This review integrates research from chemical, biological and adjuvant therapies to evaluate current and future IBD therapies, highlighting the mechanism of action of each therapy and emphasizing the potential of development prospects.

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. This study aimed to propose a novel poly (methacrylic acid-co-ethylene glycol dimethacrylate)-functionalized polydopamine-coated Fe3O4 nanoparticle (Fe3O4@PDA@poly (MAA-co-EGDMA)) as an adsorbent, and provide a highly sensitive quantitative analytical technique for the detection of five synthetic cannabinoids (SCs: 5 F-EDMB-PINACA, FUB-APINACA, MDMB-4en-PINACA, MDMB-FUBINACA, and PB-22) and one cannabis-related human metabolite (THC-COOH) in wastewater. The magnetic adsorbents were fully characterized by transmission electron microscopy (TEM), infrared spectroscopy (IR), vibrating sample magnetometry (VSM) and X-ray photoelectron spectroscopy (XPS). Subsequently, an MSPE-UHPLC-MS/MS method was developed and validated for the determination of six trace analytes in wastewater. The validation results showed that the method has limits of quantification as low as 0.1-1.0 ng/L. Additionally, the recoveries ranged from 62.81 to 124.02%, and the relative standard deviations (RSDs) of intraday and interday precision were less than 15%. This MSPE-UHPLC-MS/MS method was successfully applied to real wastewater samples, and the whole analytical process of one sample from pretreatment to the obtained quantitative results was completed in less than 30 min. Thus, the proposed method based on Fe3O4@PDA@poly (MAA-co-EGDMA) is a convenient, rapid, sensitive and reliable method for the determination of trace psychoactive drugs in wastewater.

Development of an LC-MS/MS method for the determination of multiple mycotoxins in human urine.

A sensitive liquid chromatography-tandem mass spectrometry method was developed for the determination of 17 mycotoxins in human urine. The method incorporates a two-step liquid-liquid extraction with ethyl acetate:acetonitrile (7:1), which had good extraction recovery. The LOQs of all mycotoxins ranged from 0.1 to 1 ng/mL. Intra-day accuracy ranged from 94 to 106%, and intra-day precision ranged from 1 to 12% for all mycotoxins. Inter-day accuracy and precision were 95-105% and 2-8%, respectively. The method was successfully applied to investigate the urine levels of 17 mycotoxins from 42 volunteers. Deoxynivalenol (DON, 0.97-9.88 ng/mL) was detected in 10 (24%) urine samples and zearalenone (ZEN, 0.13-1.11 ng/mL) in 2 (5%) urine samples.

A Bio-Inspired Decision-Making Method of UAV Swarm for Attack-Defense Confrontation via Multi-Agent Reinforcement Learning.

The unmanned aerial vehicle (UAV) swarm is regarded as having a significant role in modern warfare. The demand for UAV swarms with the capability of attack-defense confrontation is urgent. The existing decision-making methods of UAV swarm confrontation, such as multi-agent reinforcement learning (MARL), suffer from an exponential increase in training time as the size of the swarm increases. Inspired by group hunting behavior in nature, this paper presents a new bio-inspired decision-making method for UAV swarms for attack-defense confrontation via MARL. Firstly, a UAV swarm decision-making framework for confrontation based on grouping mechanisms is established. Secondly, a bio-inspired action space is designed, and a dense reward is added to the reward function to accelerate the convergence speed of training. Finally, numerical experiments are conducted to evaluate the performance of our method. The experiment results show that the proposed method can be applied to a swarm of 12 UAVs, and when the maximum acceleration of the enemy UAV is within 2.5 times ours, the swarm can well intercept the enemy, and the success rate is above 91%.

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. Paired hair and nail samples were collected from 39 participants to investigate the correlation between caffeine and other drugs in hair and nails. The samples were decontaminated, pulverized, and extracted by a high-throughput nail sample preparation method and analyzed by UPLC-MS/MS. The results showed a risk of caffeine abuse in northwest China, with concentrations ranging from 0.43 to 10.6 ng/mg for healthy volunteers, 0.49-246 ng/mg for caffeine abusers, and 0.25-363 ng/mg for drug addicts in community rehabilitation centers. Caffeine was detected together with other illicit psychoactive drugs and their metabolites. Furthermore, positive detection correlations were found between hair and nail samples. This study provides a current perspective on caffeine abuse in northwest China and demonstrates the practical use of UPLC-MS/MS for the simultaneous detection of caffeine and 13 illicit psychoactive drugs and their metabolites in hair and nails. The results highlight the potential of nails as a supplementary matrix when hair samples are unavailable and emphasize the need for handling caffeine carefully given its potential for abuse.

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 population model based on cotinine (COT), NH4-N and the flow volume was constructed to estimate the population equivalents for different wastewater treatment plants (WWTPs). Clenbuterol and ractopamine are banned in China for both animal husbandry and medical use, but were nevertheless detected in some wastewater samples at rates of 6.2 % and 4.7 %, respectively (n = 339). The WBE-based consumption of clenbuterol and ractopamine were compared with the acceptable daily intake (ADI) and the health risks were assessed by their hazard quotients (0.26-6.62 for clenbuterol and 9.27 × 10-4-0.05 for ractopamine). Salbutamol, clorprenaline and terbutaline were observed in practically all wastewater samples at concentrations of up to several ng/L, whereas the formoterol and bambuterol concentrations were below the detection limit in all samples. Salbutamol consumption (7.35 ± 4.14 mg/1000 inh/day) was highest among the examined beta-agonists and varied regionally. Beta-agonist consumption based on WBE was higher in some cities than that based on medical survey data, indicating potential illegal use. These results show that WBE can be a straightforward and supplementary method for monitoring beta-agonist usage at the population level and spatially.