Application research of radiomics in colorectal cancer: A bibliometric study.

BACKGROUND: Radiomics has shown great potential in the clinical field of colorectal cancer (CRC). However, few bibliometric studies have systematically analyzed existing research in this field. The purpose of this study is to understand the current research status and future development directions of CRC. METHODS: Search the English documents on the application of radiomics in the field of CRC research included in the Web of Science Core Collection from its establishment to October 2023. VOSviewer and CiteSpace software were used to conduct bibliometric and visual analysis of online publications related to countries/regions, authors, journals, references, and keywords in this field. RESULTS: A total of 735 relevant documents published from Web of Science Core Collection to October 2023 were retrieved, and a total of 419 documents were obtained based on the screening criteria, including 376 articles and 43 reviews. The number of publications is increasing year by year. Among them, China publishes the most relevant documents (n = 238), which is much higher than Italy (n = 69) and the United States (n = 63). Tian Jie is the author with the most publications and citations (n = 17, citations = 2128), GE Healthcare is the most productive institution (n = 26), Frontiers in Oncology is the journal with the most publications (n = 60), and European Radiology is the most cited journal (n = 776). Hot spots for the application of radiomics in CRC include magnetic resonance, neoadjuvant chemoradiotherapy, survival, texture analysis, and machine learning. These directions are the current hot spots for the application of radiomics research in CRC and may be the direction of continued development in the future. CONCLUSION: Through bibliometric analysis, the application of radiomics in CRC has been increasing year by year. The application of radiomics improves the accuracy of preoperative diagnosis, prediction, and prognosis of CRC. The results of bibliometrics analysis provide a valuable reference for the research direction of radiomics. However, radiomics still faces many challenges in the future, such as the single nature of the data source which may affect the comprehensiveness of the results. Future studies can further expand the data sources and build a multicenter public database to more comprehensively reflect the research status and development trend of CRC radiomics.

From cradle to grave: Deciphering sex-specific disruptions of the nervous and reproductive systems through interactions of 4-methylbenzylidene camphor and nanoplastics in adult zebrafish.

4-methylbenzylidene camphor (4-MBC) and micro/nanoplastics (MNPs) are common in personal care and cosmetic products (PCCPs) and consumer goods; however, they have become pervasive environmental contaminants. MNPs serve as carriers of 4-MBC in both PCCPs and the environment. Our previous study demonstrated that 4-MBC induces estrogenic effects in zebrafish larvae. However, knowledge gaps remain regarding the sex- and tissue-specific accumulation and potential toxicities of chronic coexposure to 4-MBC and MNPs. Herein, adult zebrafish were exposed to environmentally realistic concentrations of 4-MBC (0, 0.4832, and 4832 µg/L), with or without polystyrene nanoplastics (PS-NPs; 50 nm, 1.0 mg/L) for 21 days. Sex-specific accumulation was observed, with higher concentrations in female brains, while males exhibited comparable accumulation in the liver, testes, and brain. Coexposure to PS-NPs intensified the 4-MBC burden in all tested tissues. Dual-omics analysis (transcriptomics and proteomics) revealed dysfunctions in neuronal differentiation, death, and reproduction. 4-MBC-co-PS-NP exposure disrupted the brain histopathology more severely than exposure to 4-MBC alone, inducing sex-specific neurotoxicity and reproductive disruptions. Female zebrafish exhibited autism spectrum disorder-like behavior and disruption of vitellogenesis and oocyte maturation, while male zebrafish showed Parkinson's-like behavior and spermatogenesis disruption. Our findings highlight that PS-NPs enhance tissue accumulation of 4-MBC, leading to sex-specific impairments in the nervous and reproductive systems of zebrafish.

Mulberry Leaf Dietary Supplementation Can Improve the Lipo-Nutritional Quality of Pork and Regulate Gut Microbiota in Pigs: A Comprehensive Multi-Omics Analysis.

Mulberry leaves, a common traditional Chinese medicine, represent a potential nutritional strategy to improve the fat profile, also known as the lipo-nutrition, of pork. However, the effects of mulberry leaves on pork lipo-nutrition and the microorganisms and metabolites in the porcine gut remain unclear. In this study, multi-omics analysis was employed in a Yuxi black pig animal model to explore the possible regulatory mechanism of mulberry leaves on pork quality. Sixty Yuxi black pigs were divided into two groups: the control group (n = 15) was fed a standard diet, and the experimental group (n = 45) was fed a diet supplemented with 8% mulberry leaves. Experiments were performed in three replicates (n = 15 per replicate); the two diets were ensured to be nutritionally balanced, and the feeding period was 120 days. The results showed that pigs receiving the diet supplemented with mulberry leaves had significantly reduced backfat thickness (p < 0.05) and increased intramuscular fat (IMF) content (p < 0.05) compared with pigs receiving the standard diet. Lipidomics analysis showed that mulberry leaves improved the lipid profile composition and increased the proportion of triglycerides (TGs). Interestingly, the IMF content was positively correlated with acyl C18:2 and negatively correlated with C18:1 of differential TGs. In addition, the cecal microbiological analysis showed that mulberry leaves could increase the abundance of bacteria such as UCG-005, Muribaculaceae_norank, Prevotellaceae_NK3B31_group, and Limosilactobacillus. Simultaneously, the relative levels of L-tyrosine-ethyl ester, oleic acid methyl ester, 21-deoxycortisol, N-acetyldihydrosphingosine, and mulberrin were increased. Furthermore, we found that mulberry leaf supplementation significantly increased the mRNA expression of lipoprotein lipase, fatty acid-binding protein 4, and peroxisome proliferators-activated receptor γ in muscle (p < 0.01). Mulberry leaf supplementation significantly increased the mRNA expression of diacylglycerol acyltransferase 1 (p < 0.05) while significantly decreasing the expression of acetyl CoA carboxylase in backfat (p < 0.05). Furthermore, mulberry leaf supplementation significantly upregulated the mRNA expression of hormone-sensitive triglyceride lipase and peroxisome proliferator-activated receptor α (p < 0.05) in backfat. In addition, mulberry leaf supplementation led to increased serum leptin and adiponectin (p < 0.01). Collectively, this omic profile is consistent with an increased ratio of IMF to backfat in the pig model.

Acidification induce chemical and microbial variation in tea plantation soils and bacterial degradation of the key acidifying phenolic acids.

Camellia sinensis is an important economic plant grown in southern subtropical hilly areas, especially in China, mainly for the production of tea. Soil acidification is a significant cause of the reduction of yield and quality and continuous cropping obstacles in tea plants. Therefore, chemical and microbial properties of tea growing soils were investigated and phenolic acid-degrading bacteria were isolated from a tea plantation. Chemical and ICP-AES investigations showed that the soils tested were acidic, with pH values of 4.05-5.08, and the pH negatively correlated with K (p < 0.01), Al (p < 0.05), Fe and P. Aluminum was the highest (47-584 mg/kg) nonessential element. Based on high-throughput sequencing, a total of 34 phyla and 583 genera were identified in tea plantation soils. Proteobacteria and Acidobacteria were the main dominant phyla and the highest abundance of Acidobacteria was found in three soils, with nearly 22% for the genus Gp2. Based on the functional abundance values, general function predicts the highest abundance, while the abundance of amino acids and carbon transport and metabolism were higher in soils with pH less than 5. According to Biolog Eco Plate™ assay, the soil microorganisms utilized amino acids well, followed by polymers and phenolic acids. Three strains with good phenolic acid degradation rates were obtained, and they were identified as Bacillus thuringiensis B1, Bacillus amyloliquefaciens B2 and Bacillus subtilis B3, respectively. The three strains significantly relieved the inhibition of peanut germination and growth by ferulic acid, p-coumaric acid, p-hydroxybenzoic acid, cinnamic acid, and mixed acids. Combination of the three isolates showed reduced relief of the four phenolic acids due to the antagonist of B2 against B1 and B3. The three phenolic acid degradation strains isolated from acidic soils display potential in improving the acidification and imbalance in soils of C. sinensis.

MCD-LightGBM System for Intelligent Analyzing Heterogeneous Clinical Drug Therapeutic Effects.

Causal effect estimation of individual heterogeneity is a core issue in the field of causal inference, and its application in medicine poses an active and challenging problem. In high-risk decision-making domain such as healthcare, inappropriate treatments can have serious negative impacts on patients. Recently, machine learning-based methods have been proposed to improve the accuracy of causal effect estimation results. However, many of these methods concentrate on estimating causal effects of continuous outcome variables under binary intervention conditions, and give less consideration to multivariate intervention conditions or discrete outcome variables, thus limiting their scope of application. To tackle this issue, we combine the double machine learning framework with Light Gradient Boosting Machine (LightGBM) and propose a double LightGBM model. This model can estimate binary causal effects more accurately and in less time. Two cyclic structures were added to the model. Data correction method was introduced and improved to transform discrete outcome variables into continuous outcome variables. Multivariate Cyclic Double LightGBM model (MCD-LightGBM) was proposed to intelligently estimate multivariate treatment effects. A visual human-computer interaction system for heterogeneous causal effect estimation was designed, which can be applied to different types of data. This paper reports that the system improved the Logarithm of the Minimum Angle of Resolution (LogMAR) of visual acuity change after Vascular Endothelial Growth Factor (anti-VEGF) treatment in patients with diabetic macular degeneration. The improvement was observed in two clinical problems, from 0.05 to 0.33, and the readmission rate of diabetic patients after cure was reduced from 48.4% to 10.5%. The results above demonstrate the potential of the proposed system in predicting heterogeneous clinical drug treatment effects.

Endocrine disrupting effects of parabens in zebrafish (Danio rerio): New insights from transcriptomics, metabolomics, and molecular dynamics simulation.

Parabens (PBs), a group of widely used synthetic preservatives with potential endocrine disrupting activity, have been detected with increasing frequency in organisms and environmental matrices. This study assessed the hormone interference effects of four typical PBs, namely methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP), in zebrafish and elucidated the probable underlying mechanisms. Transcriptomic and metabolomic analyses showed that the differentially expressed genes and metabolites were associated with the tyrosine metabolism, arachidonate metabolism, and glycerophospholipid metabolism, indicating they were essential precursors of steroid hormone biosynthesis and metabolism. Histopathological analysis revealed impaired gonad development in the zebrafish exposed to PBs, as evidenced by the significantly increased vitellogenin (VTG) and estradiol (E2) levels. Furthermore, molecular dynamics simulation suggested that the four PBs could preferentially activate the zebrafish estrogen receptor, zfERß2, to regulate the downstream pathways. Disruption of the amino acid metabolism and lipid metabolism, and activation of zfERß2 signaling pathway were found to be the key mechanisms for the endocrine disrupting effects of PBs. The hormone interference effects of PBs were apparently dependent on the shared oxybenzene on their structures, with the degree of interference determined largely by the length of their alkyl chains. These findings provide new insights into the endocrine disrupting effects of PBs and could help better assess their risk to human health.

Comprehensive lipidomic analysis revealed the effects of fermented Morus alba L. intake on lipid profile in backfat and muscle tissue of Yuxi black pigs.

Mulberry leaf is a widely used protein feed and is often used as a strategy to reduce feed costs and improve meat quality in the livestock industry. However, to date, there is a lack of research on the improvement of meat quality using mulberry leaves, and the exact mechanisms are not yet known. The results showed that fermented mulberry leaves significantly reduced backfat content but had no significant effect on intramuscular fat (IMF). Lipidomic analysis showed that 98 and 303 differential lipid molecules (p < 0.05) were identified in adipose and muscle tissues, respectively, including triglycerides (TG), phosphatidylcholine, phosphatidylethanolamine, sphingolipids, and especially TG; therefore, we analysed the acyl carbon atom number of TG. The statistical results of acyl with different carbon atom numbers of TG in adipose tissue showed that the acyl group containing 13 carbon atoms (C13) in TG was significantly upregulated, whereas C15, C16, C17, and C23 were significantly downregulated, whereas in muscle tissue, the C12, C19, C23, C25, and C26 in TG were significantly downregulated. Acyl changes in TG were different for different numbers of carbon atoms in different tissues. We found that the correlations of C (14-18) in adipose tissue were higher, but in muscle tissue, the correlations of C (18-26) were higher. Through pathway enrichment analysis, we identified six and four metabolic pathways with the highest contributions of differential lipid metabolites in adipose and muscle tissues respectively. These findings suggest that fermented mulberry leaves improve meat quality mainly by inhibiting TG deposition by downregulating medium- and short-chain fatty acids in backfat tissue and long-chain fatty acids in muscle tissue.

Developmental toxicity, immunotoxicity and cardiotoxicity induced by methidathion in early life stages of zebrafish.

Methidathion is a highly effective organophosphorus pesticide and is extensively utilized for the control of insects in agricultural production. However, there is little information on the adverse effects and underlying mechanisms of methidathion on aquatic organisms. In this work, embryonic zebrafish were exposed to methidathion at concentrations of 4, 10, and 25 mg/L for 96 h, and morphological changes and activities of antioxidant indicators alterations were detected. In addition, the locomotor behavioral abilities of zebrafish exposed to methidathion were also measured. To further explore the mechanism of the toxic effects of methidathion, gene expression levels associated with cardiac development, cell apoptosis, and the immune system were tested through qPCR assays. The findings revealed that methidathion exposure could induce a decrease in survival rate, hatchability, length of body, and increase in abnormality of zebrafish, as well as cardiac developmental toxicity. The LC50 value of methidathion in zebrafish embryos was determined to be about 30.72 mg/L at 96 hpf. Additionally, methidathion exposure triggered oxidative stress in zebrafish by increasing SOD activity, ROS, and MDA content. Acridine orange (AO) staining indicated that methidathion exposure led to apoptosis, which was mainly distributed in the pericardial region. Furthermore, significant impairments of locomotor activity in zebrafish larvae were induced by methidathion exposure. Lastly, the expression of pro-inflammatory factors including IFN-γ, IL-6, IL-8, CXCL-clc, TLR4, and MYD88 significantly up-regulated in exposed zebrafish. Taken together, the results in this work illustrated that methidathion caused developmental toxicity, cardiotoxicity, and immunotoxicity in embryogenetic zebrafish.

Hyoscyamine induces developmental toxicity by disrupting metabolism in zebrafish embryo (Danio rerio).

Hyoscyamine is a kind of tropane alkaloids, which exists in several plants of the family Solanaceae. However, the mechanism underlying such hyoscyamine toxic effects during early development remains unclear. In this study, an untargeted metabolomics approach was used to investigate the toxic mechanisms of hyoscyamine in zebrafish embryos. The LC10 and MNLC of hyoscyamine in zebrafish embryos were determined to be 350 and 313 µg/mL, respectively. Moreover, hyoscyamine exposure increased the accumulation of ROS and MDA, and altered the activity of antioxidant enzymes (CAT, SOD, and GSH) in zebrafish embryos. After exposure, the embryos were extracted, derivatized and analyzed by UHPLC-Q-Orbitrap-HRMS for 3551 metabolites to identify 38 significantly changed metabolites based on the VIP, p value, and fold change results. Metabolic pathways associated with those metabolites were identified using MetaboAnalyst 5.0 as follows: pyrimidine metabolism, purine metabolism, histidine metabolism, beta-Alanine metabolism, and glutathione metabolism. These results suggested that hyoscyamine exposure to zebrafish embryos exhibited marked metabolic disturbance. Such significant perturbations of important metabolites within crucial biochemical pathways may have biologically hazardous effects on zebrafish embryos induced by hyoscyamine.

Molecular, morphological and behavioral alterations of zebrafish (Danio rerio) embryos/larvae after clorprenaline hydrochloride exposure.

Chlorprenaline hydrochloride (CLOR) is a typical representative of ß-adrenergic agonists that may be used illegally as a livestock feed additive and may have adverse impacts on the environment. In the present study, zebrafish embryos were exposed to CLOR to investigate its developmental toxicity and neurotoxicity. The results demonstrated that CLOR exposure led to adverse effects on developing zebrafish, such as morphological changes, a high heart rate, and increased body length, resulting in developmental toxicity. Moreover, the up-regulation of activities of superoxide dismutase (SOD) and catalase (CAT) and the enhancement of malondialdehyde (MDA) content illustrated that CLOR exposure activated oxidative stress in exposed zebrafish embryos. Meanwhile, CLOR exposure also caused alterations in locomotive behavior in zebrafish embryos, including an increase in acetylcholinesterase (AChE) activity. Quantitative polymerase chain reaction (QPCR) results showed that the transcription of genes related to the central nervous system (CNS) development, namely, mbp, syn2a, α1-tubulin, gap43, shha, and elavl3, indicated that CLOR exposure could lead to neurotoxicity in zebrafish embryos. These results showed that CLOR exposure could cause developmental neurotoxicity in the early stages of zebrafish development and that CLOR might induce neurotoxicity by altering the expression of neuro-developmental genes, elevating AChE activity, and activating oxidative stress.

High fried food consumption impacts anxiety and depression due to lipid metabolism disturbance and neuroinflammation.

Western dietary patterns have been unfavorably linked with mental health. However, the long-term effects of habitual fried food consumption on anxiety and depression and underlying mechanisms remain unclear. Our population-based study with 140,728 people revealed that frequent fried food consumption, especially fried potato consumption, is strongly associated with 12% and 7% higher risk of anxiety and depression, respectively. The associations were more pronounced among male and younger consumers. Consistently, long-term exposure to acrylamide, a representative food processing contaminant in fried products, exacerbates scototaxis and thigmotaxis, and further impairs exploration ability and sociality of adult zebrafish, showing anxiety- and depressive-like behaviors. Moreover, treatment with acrylamide significantly down-regulates the gene expression of tjp2a related to the permeability of blood-brain barrier. Multiomics analysis showed that chronic exposure to acrylamide induces cerebral lipid metabolism disturbance and neuroinflammation. PPAR signaling pathway mediates acrylamide-induced lipid metabolism disorder in the brain of zebrafish. Especially, chronic exposure to acrylamide dysregulates sphingolipid and phospholipid metabolism, which plays important roles in the development of anxiety and depression symptoms. In addition, acrylamide promotes lipid peroxidation and oxidation stress, which participate in cerebral neuroinflammation. Acrylamide dramatically increases the markers of lipid peroxidation, including (±)5-HETE, 11(S)-HETE, 5-oxoETE, and up-regulates the expression of proinflammatory lipid mediators such as (±)12-HETE and 14(S)-HDHA, indicating elevated cerebral inflammatory status after chronic exposure to acrylamide. Together, these results both epidemiologically and mechanistically provide strong evidence to unravel the mechanism of acrylamide-triggered anxiety and depression, and highlight the significance of reducing fried food consumption for mental health.

Toxic effects of isofenphos-methyl on zebrafish embryonic development.

Isofenphos-methyl (IFP) is widely used as an organophosphorus for controlling underground insects and nematodes. However, excessive use of IFP may pose potential risks to the environment and humans, but little information is available on its sublethal toxicity to aquatic organisms. To address this knowledge gap, the current study exposed zebrafish embryos to 2, 4, and 8 mg/L IFP within 6-96 h past fertilization (hpf) and measured mortality, hatching, developmental abnormalities, oxidative stress, gene expressions, and locomotor activity. The results showed that IFP exposure reduced the rates of heart and survival rate, hatchability, and body length of embryos and induced uninflated swim bladder and developmental malformations. Reduction in locomotive behavior and inhibition of AChE activity indicated that IFP exposure may induce behavioral defects and neurotoxicity in zebrafish larvae. IFP exposure also led to pericardial edema, longer venous sinus-arterial bulb (SV-BA) distance, and apoptosis of the heart cells. Moreover, IFP exposure increased the accumulation of reactive oxygen species (ROS) and the content of malonaldehyde (MDA), also elevated the levels of antioxidant enzymes of superoxide dismutase (SOD) and catalase (CAT), but decreased glutathione (GSH) levels in zebrafish embryos. The relative expressions of heart development-related genes (nkx2.5, nppa, gata4, and tbx2b), apoptosis-related genes (bcl2, p53, bax, and puma), and swim bladder development-related genes (foxA3, anxa5b, mnx1, and has2) were significantly altered by IFP exposure. Collectively, our results indicated that IFP induced developmental toxicity and neurotoxicity to zebrafish embryos and the mechanisms may be relevant to the activation of oxidative stress and reduction of acetylcholinesterase (AChE) content.

Methyl Parathion Exposure Induces Development Toxicity and Cardiotoxicity in Zebrafish Embryos.

Methyl parathion (MP) has been widely used as an organophosphorus pesticide for food preservation and pest management, resulting in its accumulation in the aquatic environment. However, the early developmental toxicity of MP to non-target species, especially aquatic vertebrates, has not been thoroughly investigated. In this study, zebrafish embryos were treated with 2.5, 5, or 10 mg/L of MP solution until 72 h post-fertilization (hpf). The results showed that MP exposure reduced spontaneous movement, hatching, and survival rates of zebrafish embryos and induced developmental abnormalities such as shortened body length, yolk edema, and spinal curvature. Notably, MP was found to induce cardiac abnormalities, including pericardial edema and decreased heart rate. Exposure to MP resulted in the accumulation of reactive oxygen species (ROS), decreased superoxide dismutase (SOD) activity, increased catalase (CAT) activity, elevated malondialdehyde (MDA) levels, and caused cardiac apoptosis in zebrafish embryos. Moreover, MP affected the transcription of cardiac development-related genes (vmhc, sox9b, nppa, tnnt2, bmp2b, bmp4) and apoptosis-related genes (p53, bax, bcl2). Astaxanthin could rescue MP-induced heart development defects by down-regulating oxidative stress. These findings suggest that MP induces cardiac developmental toxicity and provides additional evidence of MP toxicity to aquatic organisms.

Developmental toxicity induced by brodifacoum in zebrafish (Danio rerio) early life stages.

OBJECTIVES: The present study mainly focused on the assessment of developmental toxicity induced by exposure to brodifacoum (BDF) in zebrafish at early life stages. MATERIAL AND METHODS: Zebrafish embryos were exposed to 0.2, 0.4, and 0.8 mg/L of BDF from 6 to 96 hr post-fertilization (hpf), and the toxic effects of BDF on early embryonic development were investigated in terms of morphological changes, oxidative stress, and alterations in heart development-related genes. RESULTS: The experimental results showed that BDF significantly decreased the heart rate, survival rate, body length, and spontaneous movements of zebrafish embryos at 0.8 mg/L, and the morphological developmental abnormalities were also observed at 96 hpf. In addition, exposure to BDF significantly increased oxidative stress levels in zebrafish embryos by increasing the enzymatic activities of catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels, and decreased glutathione (GSH) levels. Furthermore, BDF treatment-induced alterations in the expression levels of the heart development-related genes (gata4, sox9b, tbx2b, and nppa). CONCLUSION: Results from this study indicated that exposure to BDF could lead to marked growth inhibition and significantly alter the activities of antioxidant enzymes in zebrafish embryos. Moreover, BDF exposure exhibited severe cardiotoxicity and significantly disrupted heart development-related genes. The results indicated that BDF could induce developmental and cardiac toxicity in zebrafish embryos.

Lasso-Logistic regression model for the identification of serum biomarkers of neurotoxicity induced by strychnos alkaloids.

As a traditional Chinese medicine, strychnos alkaloids have wide effects including antitumor, analgesic, and anti-inflammatory. However, the therapeutic window of strychnos alkaloids is quite narrow due to potential neurotoxicity. Therefore, it is necessary to explore some efficient biomarkers to identify and predict the neurotoxicity induced by strychnos alkaloids and find a therapy to prevent the neurotoxicity of strychnos alkaloids. Based on the previous studies of our research team, 21 endogenous substances related to neurotoxicity were monitored in rats' serum with HPLC-MS/MS and ELISA. Starting from these fundamentals, a Lasso-Logistic regression model was used to select efficient biomarkers from 21 endogenous substances to predict brain injury and verify the neuroprotective effect of peonies. Under the processing of the Lasso-Logistic regression model, 12 biomarkers were identified from 21 endogenous substances to predict the neurotoxicity induced by strychnos alkaloids. At the same time, the neuroprotective effect of peonies was further confirmed by evaluating the level of 12 biomarkers. The results indicated that the development of the Lasso-Logistic regression model would provide a new, simple and efficient method for the prediction and diagnosis of the neurotoxicity induced by strychnos alkaloids.

Comparative analysis of the metabolites and biotransformation pathways of fentanyl in the liver and brain of zebrafish.

The rise of fentanyl has introduced significant new challenges to public health. To improve the examination and identification of biological samples in cases of fentanyl misuse and fatalities, this study utilized a zebrafish animal model to conduct a comparative investigation of the metabolites and biotransformation pathways of fentanyl in the zebrafish's liver and brain. A total of 17 fentanyl metabolites were identified in the positive ion mode using ultra-high-pressure liquid chromatography Q Exactive HF Hybrid Quadrupole-Orbitrap mass spectrometry (UHPLC-QE HF MS). Specifically, the zebrafish's liver revealed 16 fentanyl metabolites, including 6 phase I metabolites and 10 phase II metabolites. Conversely, the zebrafish's brain presented fewer metabolites, with only 8 detected, comprising 6 phase I metabolites and 2 phase II metabolites. Notably, M'4, a metabolite of dihydroxylation, was found exclusively in the brain, not in the liver. Through our research, we have identified two specific metabolites, M9-a (monohydroxylation followed by glucuronidation) and M3-c (monohydroxylation, precursor of M9-a), as potential markers of fentanyl toxicity within the liver. Furthermore, we propose that the metabolites M1 (normetabolite) and M3-b (monohydroxylation) may serve as indicators of fentanyl metabolism within the brain. These findings suggest potential strategies for extending the detection window and enhancing the efficiency of fentanyl detection, and provide valuable insights that can be referenced in metabolic studies of other new psychoactive substances.

Embryonic exposure to fentanyl induces behavioral changes and neurotoxicity in zebrafish larvae.

The use of fentanyl during pregnancy, whether by prescription or illicit use, may result in high blood levels that pose an early risk to fetal development. However, little is known regarding the neurotoxicity that might arise from excessive fentanyl exposure in growing organisms, particularly drug-related withdrawal symptoms. In this study, zebrafish embryos were exposed to fentanyl solutions (0.1, 1, and 5 mg/L) for 5 days post fertilization (dpf), followed by a 5-day recovery period, and then the larvae were evaluated for photomotor response, anxiety behavior, shoaling behavior, aggression, social preference, and sensitization behavior. Fentanyl solutions at 1 and 5 mg/L induced elevated anxiety, decreased social preference and aggressiveness, and behavioral sensitization in zebrafish larvae. The expression of genes revealed that embryonic exposure to fentanyl caused substantial alterations in neural activity (bdnf, c-fos) and neuronal development and plasticity (npas4a, egr1, btg2, ier2a, vgf). These results suggest that fentanyl exposure during embryonic development is neurotoxic, highlighting the importance of zebrafish as an aquatic species in research on the neurobehavioral effects of opioids in vertebrates.

Metal-free synthesis of 3-trifluoromethyl-1,2,4-triazoles via multi-component reaction of trifluoroacetimidoyl chlorides, hydrazine hydrate and benzene-1,3,5-triyl triformate.

A convenient approach for the construction of pharmaceutically valuable 3-trifluoromethyl-1,2,4-triazoles has been developed, which employs the readily available trifluoroacetimidoyl chlorides, hydrazine hydrate and benzene-1,3,5-triyl triformate (TFBen) as starting materials. The multi-component reaction features broad substrate scope, high efficiency, and scalability, providing a facile and straightforward route to the biologically important 3-trifluoromethyl-1,2,4-triazole scaffolds in moderate to good yields. Considering its broad-spectrum pharmaceutical activity, the method offers the opportunity for the further study towards the toxicity risk assessment and structure-activity relationship of the pharmaceuticals containing trifluoromethyl-1,2,4-triazole cores.

Scopoletin Induced Metabolomic Profile Disturbances in Zebrafish Embryos.

Scopoletin, a typical example of a coumarin compound, exists in several Artemisia species and other plant genera. However, the systemic metabolic effects induced by scopoletin remain unclear. In the present study, we evaluated the metabolic profiles in scopoletin-exposed zebrafish embryos using UHPLC-Q-Obitrap-HRMS combined with multivariate analysis. Compared with the control group, 33 metabolites in scopoletin group were significantly upregulated, while 27 metabolites were significantly downregulated. Importantly, scopoletin exposure affected metabolites mainly involved in phosphonate and phosphinate metabolism, vitamin B6 metabolism, histidine metabolism, sphingolipid metabolism, and folate biosynthesis. These results suggested that scopoletin exposure to zebrafish embryos exhibited marked metabolic disturbance. This study provides a perspective of metabolic impacts and the underlying mechanism associated with scopoletin exposure.

Fentanyl Induces Novel Conditioned Place Preference in Adult Zebrafish, Disrupts Neurotransmitter Homeostasis, and Triggers Behavioral Changes.

Abuse of new psychoactive substances increases risk of addiction, which can lead to serious brain disorders. Fentanyl is a synthetic opioid commonly used in clinical practice, and behavioral changes resulting from fentanyl addiction have rarely been studied with zebrafish models. In this study, we evaluated the rewarding effects of intraperitoneal injections of fentanyl at concentrations of 10, 100, and 1000 mg/L on the group shoaling behavior in adult zebrafish. Additional behavioral tests on individual zebrafish, including novel tank, novel object exploration, mirror attack, social preference, and T-maze memory, were utilized to evaluate fentanyl-induced neuro-behavioral toxicity. The high doses of 1000 mg/L fentanyl produced significant reward effects in zebrafish and altered the neuro-behavioral profiles: reduced cohesion in shoaling behavior, decreased anxiety levels, reduced exploratory behavior, increased aggression behavior, affected social preference, and suppressed memory in an appetitive associative learning task. Behavioral changes in zebrafish were shown to be associated with altered neurotransmitters, such as elevated glutamine (Gln), gamma-aminobutyric acid (GABA), dopamine hydrochloride (DA), and 5-hydroxytryptamine (5-HT). This study identified potential fentanyl-induced neurotoxicity through multiple neurobehavioral assessments, which provided a method for assessing risk of addiction to new psychoactive substances.