JOURNAL OF HAZARDOUS MATERIALS
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2024
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IF 12.2
Ya Zhu,Lan Li,Shaokui Yi,Rui Hu,Jianjun Wu,Jinqian Xu,Junguang Xu,Qinnan Zhu,Shijia Cen,Yuxuan Yuan,Da Sun,Waqas Ahmad,Huilan Zhang,Xuan Cao,Jingjuan Ju
Water pollution poses a significant risk to the environment and human health, necessitating the development of innovative detection methods. In this study, a series of representative psychoactive compounds were selected as model pollutants, and a new approach combining zebrafish embryo behavioral phenotyping with deep learning was used to identify and classify water pollutants. Zebrafish embryos were exposed to 17 psychoactive compounds at environmentally relevant concentrations (1 and 10 μg/L), and their locomotor behavior was recorded at 5 and 6 days post-fertilization (dpf). We constructed six distinct zebrafish locomotor track datasets encompassing various observation times and developmental stages and evaluated multiple deep learning models on these datasets. The results demonstrated that the ResNet101 model performed optimally on the 1-min track dataset at 6 dpf, achieving an accuracy of 65.35 %. Interpretability analyses revealed that the model effectively focused on the relevant locomotor track features for classification. These findings suggest that the integration of zebrafish embryo behavioral analysis with deep learning can serve as an environmentally friendly and economical method for detecting water pollutants. This approach offers a new perspective for water quality monitoring and has the potential to assist existing chemical analytical techniques in detection, thereby advancing environmental toxicology research and water pollution control efforts.
研究领域:
环境科学
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毒理学
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计算生物学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2022
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IF 10.753
Jiawen Ji,Jinze Huang,Niannian Cao,Xianghong Hao,Yanhua Wu,Yongqiang Ma,Dong An,Sen Pang,Xuefeng Li
The typical tire manufacturing additive 6PPD, its metabolites 6PPDQ and 4-Hydroxy should be monitored because of their ubiquitous presence in the environment and the high toxicity of 6PPDQ to coho salmon. The toxic effect of 6PPD and its metabolites have been revealed superficially, especially on behavioral characteristics. However, the behavioral indicators explored so far are relatively simple and the toxic causes are poorly understood. With this in mind, our work investigated the toxic effects of 6PPD, 6PPDQ and 4-Hydroxy on adult zebrafish penetratingly through machine vision, and the meandering, body angle, top time and 3D trajectory are used for the first time to show the abnormal behaviors induced by 6PPD and its metabolites. Moreover, neurotransmitter changes in the zebrafish brain were measured to explore the causes of abnormal behavior. The results showed that high-dose treatment of 6PPD reduced the velocity by 42.4% and decreased the time at the top of the tank by 91.0%, suggesting significant activity inhibition and anxiety. In addition, γ-aminobutyric acid and acetylcholine were significantly impacted by 6PPD, while dopamine exhibited a slight variation, which can explain the bradykinesia, unbalance and anxiety of zebrafish and presented similar symptoms as Huntingdon's disease. Our study explored new abnormal behaviors of zebrafish induced by 6PPD and its metabolites in detail, and the toxic causes were revealed for the first time by studying the changes of neurotransmitters, thus providing an important reference for further studies of the biological toxicity of 6PPD and its metabolites.
研究领域:
环境毒理学
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神经科学
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水生生物学
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行为科学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Jinyu Wang,Aijuan Zheng,Fei Lin,Xiaozhuo Zhang,Kaifang Shi,Tingxu Yan,Ying Jia
Background Schisandra chinensis lignan (SCL), a major active component of the traditional functional Chinese medicine Schisandra chinensis , has been reported to have antidepressant effects. Its mechanisms include alleviating intestinal barrier injury (IBI) by resolving intestinal microflora, anti-inflammation, and neuroprotection. SCL also regulates endogenous cannabinoid system, and it is closely related to the onset and development of depression. Purpose We investigated a new treatment strategy for depression, i.e., alleviating IBI by regulating the endogenous cannabinoid system for antidepressant effects, as well as conducted in-depth research to explore the specific mechanism. Methods Behavioral analysis was conducted to detect the occurrence of depressive-like behavior in C57BL/6 mice. We used hematoxylin-eosin staining, periodic acid-Schiff staining, and immunofluorescence to evaluate IBI. Network pharmacology and Western blotting (WB) were used to predict and confirm that the amelioration effect of SCL was associated with anti-inflammation and anti-apoptosis. Combined with the levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG), we conducted the Pearson analysis between the AEA, 2-AG levels and the major targets identified and validated by network pharmacology and WB. Subsequently, URB-597, a fatty acid amide hydrolase (FAAH) antagonist with an AEA hydrolase-inhibiting effect, was administered to the mice, and behavioral analysis and apoptotic proteins were verified. Plasma endocannabinoid levels after URB-597 supplementation were measured via 6470 Triple Quadrupole LC/MS. Finally, the cannabinoid receptor type 2 (CB2R) antagonist AM630 was administered to mice, and immunofluorescence and WB were performed to assess the proteins of IBI and anti-inflammation. Results The study demonstrated that SCL alleviated depressive-like behaviours and ameliorated IBI. Network pharmacology and WB confirmed that the improvement of IBI was related to the anti-inflammatory and anti-apoptotic pathways. Pearson results showed that AEA levels were positively correlated with inflammation and apoptosis, with a greater contribution to apoptosis. In-depth studies validated that the URB-597 administration reversed the positive effects of SCL on depressive-like behavior and anti-apoptosis. Similarly, URB-597 counteracted AEA levels reduced by SCL and decreased 2-AG levels. Furthermore, AM630 supplementation antagonized SCL's effect of improving IBI by reactivating the MAPK/NF-κB inflammation pathway. Conclusion Overall, SCL, in collaboration with the endogenous cannabinoid system regulated by SCL, alleviates depression associated IBI. The specific mechanism involes SCL decreasing AEA levels to inhibit colon tissue cell apoptosis by up-regulating FAAH. Simultaneously, it directly triggers CB2R to reduce inflammation responses, further alleviating IBI.
研究领域:
药理学
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神经科学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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2019
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IF 4.027
Yu-Heng Hu,Jie Yang,Yun Zhang,Ke-Chun Liu,Teng Liu,Jie Sun,Xiao-Jing Wang
The work is focused on the design of drugs that prevent and treat Alzheimer’s disease (AD) and its complications. A series of 3–(4-aminophenyl)-coumarin derivatives designed, synthesised, fully characterised and evaluated in vitro/vivo. The biological assay experiments showed that some compounds displayed a clearly selective inhibition for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among all compounds, compound 4m exhibited the highest AChE inhibition with an IC50 value of 0.091 ± 0.011 µM and compound 4k exhibited the highest BuChE inhibition with an IC50 value of 0.559 ± 0.017 µM. A zebrafish behaviour analyser (Zebrobox) was used to determine the behavioural effects of the active compound on the movement distance of the aluminium chloride-induced zebrafish. Compound 4m offered a potential drug design concept for the development of therapeutic or preventive agents for AD and its complications.
研究领域:
药理学
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神经科学
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药物设计
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DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2024
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IF 8.2
Chenyang Rao,Fuhao Chu,Fang Fang,Dongfang Xiang,Bo Xian,Xiaying Liu,Shaopan Bao,Tao Fang
The ubiquity of amino antioxidants (AAOs) in the environment has attracted increasing attention, given their potential toxicity. This investigation represents a pioneering effort, systematically scrutinizing the toxicological effects of four distinct AAOs across the developmental spectrum of zebrafish, encompassing embryonic, larvae, and adult stages. The results indicate that four types of AAO exhibit varying degrees of cell proliferation toxicity. Although environmentally relevant concentrations of AAOs exhibit a comparatively circumscribed impact on zebrafish embryo development, heightened concentrations (300 μg/L) of N -(1,3-dimethylbutyl)- N′ -phenyl- p -phenylenediamine (6PPD) and N -isopropyl- N′ -phenyl- p -phenylenediamine (IPPD) distinctly evoke developmental toxicity. Behavioral analysis results indicate that at concentrations of 20 and 300 μg/L, the majority of AAOs significantly reduced the swimming speed and activity of larvae. Moreover, each AAO triggers the generation of reactive oxygen species (ROS) in larvae, instigating diverse levels of oxidative stress. The study delineates parallel toxicological patterns in zebrafish exposed to 300 μg/L of 6PPD and IPPD, thereby establishing a comparable toxicity profile. The comprehensive toxicity effects among the four AAOs is as follows: IPPD >6PPD > N -Phenyl-1-naphthylamine (PANA) > diphenylamine (DPA). These findings not only enrich our comprehension of the potential hazards associated with AAOs but also provide data support for structure-based toxicity prediction models.
研究领域:
环境毒理学
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水生毒理学
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发育生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
ARCHIV DER PHARMAZIE
·
2024
·Vol. 357
·期 5
·2300693
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IF 4.3
Jingfang Zhai,Canhua Hao,Xiaojing Wang,Yuexing Cao,Yinbo Pan,Min Zhou,Jie Sun,Chuanyou Li
Aβ 1−42 and acetylcholinesterase (AChE) are two key therapeutic targets for Alzheimer's disease (AD). The purpose of this study is to develop a dual-target inhibitor that inhibits both of these targets by fusing the chemical structure of baicalein and donepezil. Among them, we modified the structure of baicalein to arylcoumarin, synthesized three kinds of structural compounds, and evaluated their biological activities. The results showed that compound 3b had the strongest inhibitory effect on AChE (IC 50 = 0.05 ± 0.02 µM), which was better than those of donepezil and baicalein. In addition, compound 3b has a strong ability to inhibit the aggregation of Aβ 1−42 and protect nerve cells, and it can also penetrate the blood–brain barrier well. Using a zebrafish behavioral analyzer test, it was found that compound 3b can alleviate the behavioral effects of AlCl 3 -induced zebrafish larval movement retardation, which has a certain guiding significance for simulating the movement disorders of AD patients. In summary, compound 3b is expected to become a multifunctional agent for treating and alleviating the symptoms of AD patients.
研究领域:
药理学
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神经科学
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药物设计
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生物化学
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DOI
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
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2024
·Vol. 68
·期 8
·2300671
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IF 4.5
Hui Zhou,Ziyi Chen,Jingbin Li,Rongjin Wang,Hongshi Bu,Chengjiang Ruan
Scope Cerebral ischemia-reperfusion (IR) injury stands as a prominent global contributor to disability and mortality. Nervonic acid (NA), a bioactive elongated monounsaturated fatty acid, holds pivotal significance in human physiological well-being. This research aims to explore the prophylactic effects and fundamental mechanisms of NA in a rat model of cerebral IR injury. Methods and results Through the induction of middle cerebral artery occlusion, this study establishes a rat model of cerebral IR injury and comprehensively assesses the pharmacodynamic impacts of NA pretreatment. This evaluation involves behavioral analyses, histopathological examinations, and quantification of serum markers. Detailed mechanisms of nervonic acid's prophylactic effects are revealed through fecal metabolomics and 16S rRNA sequencing analyses. Our findings robustly support nervonic acid's capacity to ameliorate neurological impairments in rats afflicted with cerebral IR injury. Beyond its neurological benefits, NA demonstrates its potential by rectifying metabolic perturbations across diverse pathways, particularly those pertinent to unsaturated fatty acid metabolism. Additionally, NA emerges as a modulator of gut microbiota composition, notably by selectively enhancing vital genera like Lactobacillus . Conclusion These comprehensive findings highlight the potential of incorporating NA as a functional component in dietary interventions aimed at targeting cerebral IR injury.
研究领域:
神经科学
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药理学
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微生物学
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代谢组学
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病理学
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产品关联
DOI
PubMed
高影响因子
Neural Regeneration Research
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2022
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IF 6.058
Ting-Ting Cao,Huan Chen,Mao Pang,Si-Si Xu,Hui-Quan Wen,Bin Liu,Li-Min Rong,Mang-Mang Li
Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate for spinal cord injury (SCI) repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources. However, modest clinical efficacy hampered the progression of these cells to clinical translation. This discrepancy may be due to many variables, such as cell source, timing of implantation, route of administration, and relevant efficacious cell dose, which are critical factors that affect the efficacy of treatment of patients with SCI. Previously, we have evaluated the safety and efficacy of 4 × 10 6 hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models. To search for a more accurate dose range for clinical translation, we compared the effects of three different doses of hUC-MSCs – low (0.25 × 10 6 cells/kg), medium (1 × 10 6 cells/kg) and high (4 × 10 6 cells/kg) – on subacute SCI repair through an elaborate combination of behavioral analyses, anatomical analyses, magnetic resonance imaging-diffusion tensor imaging (MRI-DTI), biotinylated dextran amine (BDA) tracing, electrophysiology, and quantification of mRNA levels of ion channels and neurotransmitter receptors. Our study demonstrated that the medium dose, but not the low dose, is as efficient as the high dose in producing the desired therapeutic outcomes. Furthermore, partial restoration of the γ-aminobutyric acid type A (GABA A ) receptor expression by the effective doses indicates that GABA A receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord. Overall, this study revealed that intrathecal implantation of 1 × 10 6 hUC-MSCs/kg is an alternative approach for treating subacute SCI.
研究领域:
干细胞治疗
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神经科学
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脊髓损伤
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细胞生物学
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医学影像
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产品关联
DOI
PubMed
高影响因子
Journal of Oral & Facial Pain and Headache
·
2024
·Vol. 38
·期 1
·77
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IF 1.9
Zhiheng Feng,Mingcai Chen,Jue Zhang,Xin Peng
Pain assessment in trigeminal neuralgia (TN) mouse models is essential for exploring its pathophysiology and developing effective analgesics. However, pain assessment methods for TN mouse models have not been widely studied, resulting in a critical gap in our understanding of TN. With the rapid advancement of deep learning, numerous pain assessment methods based on deep learning have emerged. Nonetheless, these methods have some limitations: (1) insufficiently objective supervision signals for training, (2) failure to account for the dynamic behavioral characteristics of mouse models in the constructed models and (3) inadequate generalization ability of the models. In this study, we initially constructed an objective pain grading dataset as the ground truth for model training, which remedy the limitations of prior studies that relied on subjective evaluation as supervisory signals. Then we proposed a novel deep neural network, named trigeminal neuralgia pain assessment network (TNPAN), which fuses the static texture characteristics and dynamic behavioral characteristics of mouse facial expressions. The promising experimental results demonstrate that TNPAN exhibits exceptional accuracy and generalization capability in pain assessment.
研究领域:
神经科学
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疼痛研究
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深度学习
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医学影像
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行为分析
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
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