AQUATIC TOXICOLOGY
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2023
·
IF 4.5
Ferry Saputra,Michael Edbert Suryanto,Gilbert Audira,Cao Thang Luong,Chih-Hsin Hung,Marri Jmelou Roldan,Ross D. Vasquez,Chung-Der Hsiao
Daphnia magna is one species of water flea that has been used for a long time for ecotoxicity studies. In addition, Daphnia has a myogenic heart that is very useful for cardiotoxicity studies. Previous attempts to calculate the cardiac parameter endpoints in Daphnia suffer from the drawback of tedious operation and high variation due to manual counting errors. Even the previous method that utilized deep learning to help the process suffer from either overestimation of parameters or the need for specialized equipment to perform the analysis. In this study, we utilized DeepLabCut software previously used for animal pose tracking and demonstrated that ResNet_152 was the best fit for training the network. The trained network also showed comparable results with ImageJ and Kymograph, which was mostly done manually. In addition to that, several macro scripts in either Excel or Python format were developed to help summarize the data for faster analysis. The trained network was then challenged to analyze the potential cardiotoxicity of imidacloprid and pendimethalin in D. magna , and it showed that both pesticides cause alteration in their cardiac performance. Overall, this method provides a simple and automatic method to analyze the cardiac performance of Daphnia by utilizing DeepLabCut . The method proposed in this paper can contribute greatly to scientists conducting fast and accurate cardiotoxicity measurements when using Daphnia as a model.
研究领域:
生态毒理学
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计算生物学
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心血管研究
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PubMed
高影响因子
Micromachines
·
2022
·Vol. 13
·期 3
·488
·
IF 3.523
Yun Wang,Mixia Wang,Yuchuan Dai,Yilin Song,Yiding Wang,Botao Lu,Yinghui Li,Xinxia Cai
Research on the intracerebral mechanism of insomnia induced by serotonin (5-HT) deficiency is indispensable. In order to explore the effect of 5-HT deficiency-induced insomnia on brain regions related to memory in rats, we designed and fabricated a microelectrode array that simultaneously detects the electrical activity of the dorsal raphe nucleus (DRN) and hippocampus in normal, insomnia and recovery rats in vivo. In the DRN and hippocampus of insomnia rats, our results showed that the spike amplitudes decreased by 40.16 and 57.92%, the spike repolarization slope decreased by 44.64 and 48.59%, and the spiking rate increased by 66.81 and 63.40%. On a mesoscopic scale, the increased firing rates of individual neurons led to an increased δ wave power. In the DRN and hippocampus of insomnia rats, the δ wave power increased by 57.57 and 67.75%. Furthermore, two segments’ δ wave slopes were also increased in two brain regions of the insomnia rats. Our findings suggest that 5-HT deficiency causes the hyperactivity of neurons in the hippocampus and DRN; the DRN’s firing rate and the hippocampal neuronal amplitude reflect insomnia in rats more effectively. Further studies on alleviating neurons affected by 5-HT deficiency and on achieving a highly effective treatment for insomnia by the microelectrode array are needed.Keywords:microelectrode array;insomnia;electrophysiology;dorsal raphe nucleus;serotonin
研究领域:
神经科学
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电生理学
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生物医学工程
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PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2024
·
IF 3.7
Jiaying Lin,Fengjiao Bu,Dan Wu,Pin Jiang,Qingfeng He,Dongsheng Yang,Xiao Zhu,Yixue Wang,Xiaoqiang Xiang
Exploiting a convenient and highly bioavailable ocular drug delivery approach is currently one of the hotspots in the pharmaceutical industry. Eyelid topical application is seen to be a valuable strategy in the treatment of chronic ocular diseases . To further elucidate the feasibility of eyelid topical administration as an alternative route for ocular drug delivery, pharmacokinetic and pharmacodynamic studies of pilocarpine were conducted in rabbits. Besides, a novel physiologically based pharmacokinetic (PBPK) model describing eyelid transdermal absorption and ocular disposition was developed in rabbits. The PBPK model of rabbits was extrapolated to human by integrating the drug-specific permeability parameters and human physiological parameters to predict ocular pharmacokinetic in human. After eyelid topical application of pilocarpine, the concentration of pilocarpine in iris peaked at 2 h with the value of 18,724 ng/g and the concentration in aqueous humor peaked at 1 h with the value of 1,363 ng/mL. Significant miotic effect were observed from 0.5 h to 4.5 h after eyelid topical application of pilocarpine in rabbits, while that were observed from 0.5 h to 3.5 h after eyedrop instillation. The proposed eyelid PBPK model was capable of reasonably predicting ocular exposure of pilocarpine after application on the eyelid skin and based on the PBPK model, the human ocular concentration was predicted to be 10-fold lower than that in rabbits. And it was suggested that drugs applied on the eyelid skin could transfer into the eyeball through corneal pathway and scleral pathway. This work could provide pharmacokinetic and pharmacodynamic data for the development of eyelid drug delivery, as well as the reference for clinical applications.
研究领域:
药理学
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药物代谢动力学
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眼科医学
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PubMed
高影响因子
Journal of Fungi
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2022
·Vol. 8
·期 12
·1310
·
IF 5.724
Ai-Ai Zhou,Rong-Yu Li,Fei-Xu Mo,Yi Ding,Ruo-Tong Li,Xue Guo,Ke Hu,Ming Li
Background: Natural products are often favored in the study of crop pests and diseases. Previous studies have shown that citronellal has a strong inhibition effect onMagnaporthe oryzae. The objective of this study was to clarify its mechanism of action againstM. oryzae. Results: Firstly, the biological activity of citronellal againstM. oryzaewas determined by direct and indirect methods, and the results show that citronellal had a strong inhibition effect onM. oryzaewith EC50values of 134.00 mg/L and 70.48 μL/L air, respectively. Additionally, a preliminary study on its mechanism of action was studied. After citronellal treatment, electron microscopy revealed that the mycelium became thin and broken; scanning electron microscopy revealed that the mycelium was wrinkled and distorted; and transmission electron microscopy revealed that the mycelium cell wall was invaginated, the mass wall of mycelium was separated, and the organelles were blurred. The mycelium was further stained with CFW, and the nodes were blurred, while the mycelium was almost non-fluorescent after PI staining, and there was no significant difference in the relative conductivity of mycelium. In addition, chitinase was significantly enhanced, and the expression of chitin synthesis-related genes was 17.47-fold upregulated. Finally, we found that the efficacy of citronellal against the rice blast was as high as 82.14% according to indoor efficacy tests. Conclusion: These results indicate that citronellal can affect the synthesis of chitin inM. oryzaeand damage its cell wall, thereby inhibiting the growth of mycelium and effectively protecting rice from rice blasts.Keywords:magnaporthe oryzae;citronellal;cell wall;physiology;cytotoxicity
研究领域:
植物病理学
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真菌学
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农药科学
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PubMed
高影响因子
Interdisciplinary Materials
·
2024
·Vol. 3
·期 5
·775-790
·
IF 24.5
Xiaoxue Lin,Zeping Ou,Xuewei Wang,Can Wang,Yunfei Ouyang,Ibrahim M. Mwakitawa,Feng Li,Rui Chen,Yaru Yue,Jihe Tang,Wei Fang,Shanshan Chen,Bing Guo,Jianyong Ouyang,Tatyana Shumilova,Yongli Zhou,Liang Wang,Chengwu Zhang,Kuan Sun
Long-term biopotential monitoring requires high-performance biocompatible wearable dry electrodes. But currently, it is challenging to establish a form-preserving fit with the skin, resulting in high interface impedance and motion artifacts. This research aims to present an innovative solution using an all-green organic dry electrode that eliminates the aforementioned challenges. The dry electrode is prepared by introducing biocompatible maltitol into the chosen conductive polymer, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate). Thanks to the secondary doping and plasticizer effect of maltitol, the dry electrode exhibits good stretchability (62%), strong self-adhesion (0.46 N/cm), high conductivity (102 S/cm), and low Young's modulus (7 MPa). It can always form a conformal contact with the skin even during body movements. Together with good electrical properties, the electrode enables a lower skin contact impedance compared to the current standard Ag/AgCl gel electrode. Consequently, the application of this dry electrode in bioelectrical signal measurement (electromyography, electrocardiography, electroencephalography) and long-term biopotential monitoring was successfully demonstrated.
研究领域:
生物医学工程
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材料科学
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DOI
高影响因子
Metabolites
·
2025
·Vol. 15
·期 9
·625
·
IF 3.7
Hai Zhao,Kangwei Shen,Wei Fan,Mengjie Li,Xuejun Kang
Purpose: To explore the potential relationship between salivary amino acid concentrations and 8 km running performance in male undergraduate students. Methods: Thirty male undergraduate students were recruited. Participants completed an 8 km run while wearing smart bracelets. Saliva samples were collected before, immediately after, and 24 h after the run. Ultra-High Performance Liquid Chromatography (UHPLC) was used to quantify salivary amino acids. Results: The fast group (average speed > 12.80 km/h) had a significantly shorter running time (35.66 ± 1.30 min,p< 0.001) and higher speed (13.59 ± 0.46 km/h,p< 0.001) than the slow group. Before the run, salivary serine concentration (20.19 µg/mL,p= 0.013) was higher in the fast group. After 24 h, salivary glutamine concentration (6.65 µg/mL,p= 0.047) was lower in the fast group. Salivary threonine concentration was positively correlated with running speed. For every 1 µg/mL increase in salivary threonine concentration, average running speed increased by 0.011 km/h, and this correlation persisted after adjusting for age and heart rate. Conclusions: This study found a positive correlation between salivary threonine and 8 km running speed, along with differences in serine and glutamine concentrations among runners with different speeds. These findings provide preliminary evidence for the relationship between salivary amino acid concentrations and running performance, though further research with larger samples and diverse exercise types is needed.
研究领域:
运动医学
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生理学
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生物化学
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营养学
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代谢组学
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转化医学
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DOI
PubMed
高影响因子
ANALYTICAL LETTERS
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2018
·
IF 1.206
Shuangyang Chen,Jiajia Xu,Guitang Chen,Qiuhui Hu,Liyan Zhao
Humans are exposed to arsenic by inhalation and ingestion and are therefore may be affected by its toxicity. Arsenic may enter the human body by inhalation and ingestion. Cooking may alter the contents and chemical forms of arsenic. The determination of arsenic species in Lentinus edodes after microwave blanching was performed by high-performance liquid chromatography–inductively coupled plasma–mass spectrometry. Using a physiologically based extraction, the bioaccessibility of arsenic species in raw L. edodes and microwave blanching treated L. edodes were determined after the simulated gastrointestinal digestion. The arsenate (AsV), arsenite (AsIII), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), arsenobetaine, and arsenocholine did not undergo decomposition and transformation in this study. Furthermore, the total contents of arsenic in L. edodes samples were in the range of 0.1378 ± 0.0044–0.2347 ± 0.0144 mg/kg. Approximately 3.38–43.27% were released from samples into the blanching water after various microwave blanching treatments. The oxidation of AsIII and demethylation of DMA and MMA were observed in L. edodes during digestion, increasing the likelihood of arsenic toxicity in the liver. The health risk for arsenic in L. edodes was decreased after microwave blanching because the potentially available arsenic in microwave blanching treatments L. edodes samples (83.78 ± 0.9103%) were lower than those in raw L. edodes samples (88.33 ± 0.7983%). L. edodes subjected to microwave blanching prior to consumption significantly decreased the total arsenic content and the risk of arsenic exposure to consumers (p < 0.05).
研究领域:
食品科学
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环境化学
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毒理学
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DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2022
·
IF 12.545
Enhui He,You Zhou,Jinping Luo,Shihong Xu,Kui Zhang,Yilin Song,Mixia Wang,Shengwei Xu,Yuchuan Dai,Gucheng Yang,Jingyu Xie,Zhaojie Xu,Wanwan Zhu,Yu Deng,Qi Xu,Xinxia Cai
Clinical transplantation of human embryonic stem cells derived dopaminergic neurons (hESC-DDNs) is expected to be a potential therapy for treating neurodegenerative diseases. However, the assessment of the physiological functions, including electrophysiology and dopamine (DA) vesicular exocytosis of hESC-DDNs are not impeccable currently, which deeply limits the clinical application of hESC-DDNs. To overcome this challenge, we developed a multifunctional microelectrode array (MEA) which can detect both electrophysiological signals and DA vesicular exocytosis. The reduced oxidation graphene, poly(3,4-ethylenedioxythiophene) and poly (sodium-4-styrenesultanate) nanocomposites (rGO/PEDOT:PSS) were electrochemically deposited on the MEAs to improve their electrical characterizations with low impedance and small phase delay, and electrochemical characterizations with low oxidation potential, low detection limit, high sensitivity, wide linear range and high sensitivity. In the hESC-DDNs experiment, the modified MEA could detect electrophysiological signals with low noise (25 μV) and high signal-to-noise ratio (>5.4), and the weak current signals generated by DA vesicular exocytosis with high sensitivity (∼pA), high time resolution (sub-millisecond) and low noise (3 pA). Moreover, due to increased accuracy, the MEA could clearly distinguish two typical kinds of exocytosis spike events (“Spikes with foot” and “Spikes without foot”) and found that the slow and low release through the fusion pore was an important mode of DA vesicular exocytosis in hESC-DDNs. Our work proved that the hESC-DDNs had the basic physiological functions as human dopaminergic neurons, which would be beneficial to the clinical application of the hESC-DDNs.
研究领域:
神经科学
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再生医学
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生物工程
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PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 21
·7417
·
IF 4.6
Wei Yang,Wenping Wang,Song Cai,Peng Li,Die Zhang,Jinhua Ning,Jin Ke,Anguo Hou,Linyun Chen,Yunshu Ma,Wenbin Jin
Malignant cardiac arrhythmias with high morbidity and mortality have posed a significant threat to our human health. Scutellarein, a metabolite of Scutellarin which is isolated fromScutellaria altissimaL., presents excellent therapeutic effects on cardiovascular diseases and could further be metabolized into methylated forms. A series of 22 new scutellarein derivatives with hydroxyl-substitution based on the scutellarin metabolite in vivo was designed, synthesized via the conjugation of the scutellarein scaffold with pharmacophores of FDA-approved antiarrhythmic medications and evaluated for their antiarrhythmic activity through the analyzation of the rat number of arrhythmia recovery, corresponding to the recovery time and maintenance time in the rat model of barium chloride-induced arrhythmia, as well as the cumulative dosage of aconitine required to induce VP, VT, VF and CA in the rat model of aconitine-induced arrhythmia. All designed compounds could shorten the time of the arrhythmia continuum induced by barium chloride, indicating that 4′-hydroxy substituents of scutellarein had rapid-onset antiarrhythmic effects. In addition, nearly all of the compounds could normalize the HR, RR, QRS, QT and QTc interval, as well as the P/T waves’ amplitude. The most promising compound10eshowed the best antiarrhythmic activity with long-term efficacy and extremely low cytotoxicity, better than the positive control scutellarein. This result was also approved by the computational docking simulation. Most importantly, patch clamp measurements on Nav1.5 and Cav1.2 channels indicated that compound10ewas able to reduce the INa and ICa in a concentration-dependent manner and left-shifted the inactivation curve of Nav1.5. Taken together, all compounds were considered to be antiarrhythmic. Compound10eeven showed no proarrhythmic effect and could be classified as Ib Vaughan Williams antiarrhythmic agents. What is more, compound10edid not block the hERG potassium channel which highly associated with cardiotoxicity.Keywords:antiarrhythmic;scutellarein derivatives;Nav1.5 channel blockers;Cav1.2 channel blockers;electrophysiology
研究领域:
药理学
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心脏病学
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药物化学
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DOI
PubMed
高影响因子
Marine Drugs
·
2023
·Vol. 21
·期 5
·286
·
IF 5.4
Jianying Dong,Panpan Zhang,Junjie Xie,Ting Xie,Xiaopeng Zhu,Dongting Zhangsun,Jinpeng Yu,Sulan Luo
α4/6-conotoxin TxID, which was identified fromConus textile, simultaneously blocks rat (r) α3β4 and rα6/α3β4 nicotinic acetylcholine receptors (nAChRs) with IC50values of 3.6 nM and 33.9 nM, respectively. In order to identify the effects of loop2 size on the potency of TxID, alanine (Ala) insertion and truncation mutants were designed and synthesized in this study. An electrophysiological assay was used to evaluate the activity of TxID and its loop2-modified mutants. The results showed that the inhibition of 4/7-subfamily mutants [+9A]TxID, [+10A]TxID, [+14A]TxID, and all the 4/5-subfamily mutants against rα3β4 and rα6/α3β4 nAChRs decreased. Overall, ala-insertion or truncation of the 9th, 10th, and 11th amino acid results in a loss of inhibition and the truncation of loop2 has more obvious impacts on its functions. Our findings have strengthened the understanding of α-conotoxin, provided guidance for further modifications, and offered a perspective for future studies on the molecular mechanism of the interaction between α-conotoxins and nAChRs.Keywords:α-conotoxin TxID;α3β4 nAChR;loop size modification;electrophysiology;CD spectra
研究领域:
药理学
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神经科学
·
生物化学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2018
·
IF 6.434
Rongyan Liu,Ruiwen He,Xinyi Cui,Lena Q. Ma
Contaminants, such as polycyclic aromatic hydrocarbons (PAHs), can be absorbed on the particles of indoor dust, which may pose potential health risks. In this study, indoor dust samples were collected and sieved into 6 size fractions (i.e., <43 μm, 43–63 μm, 63–100 μm, 100–150 μm, 150–200 μm, and 200–2000 μm). Ingestion bioaccessibility of PAHs was measured by physiologically based extraction test. Bioaccessibility in fractions of 200–2000 μm was generally higher than those in other particle sizes. Daily uptake doses based on benzo(a)pyrene toxic equivalency quantity were 1.09–15.0 ng/d/kg, and peaked at fractions of <43 μm, while doses considering bioaccessibility ranged from 0.02 to 0.21 ng/d/kg, and peaked at fractions with relatively larger particle size. Cell toxicity was also investigated by human normal liver cell line viability through exposure to organic extracts of indoor dust fractions with various particle sizes. Our results indicated that it is crucial to consider dust particle size and bioaccessibility during risk assessment.
研究领域:
环境科学
·
毒理学
·
公共卫生
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PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2022
·
IF 11.357
Yu Wang,Leilei Xiang,Fang Wang,Ziquan Wang,Yongrong Bian,Chenggang Gu,Xin Wen,Fredrick Orori Kengara,Andreas Schäffer,Xin Jiang,Baoshan Xing
Microplastics (MPs) can enter plants through the foliar pathway and are potential hazards to ecosystems and human health. However, studies related to the molecular mechanisms underlying the impact of foliar exposure to differently charged MPs to leafy vegetables are limited. Because the surfaces of MPs in the environment are often charged, we explored the uptake pathways, accumulation concentration of MPs, physiological responses, and molecular mechanisms of lettuce foliarly exposed to MPs carrying positive (MP+) and negative charges (MP–). MPs largely accumulated in the lettuce leaves, and stomatal uptake and cuticle entry could be the main pathways for MPs to get inside lettuce leaves. More MP+ entered lettuce leaves and induced physiological, transcriptomic, and metabolomic changes, including a decrease in biomass and photosynthetic pigments, an increase in reactive oxygen species and antioxidant activities, a differential expression of genes, and a change of metabolite profiles. In particular, MP+ caused the upregulation of circadian rhythm-related genes, and this may play a major role in the greater physiological toxicity of MP+ to lettuce, compared to MP–. These findings provide direct evidence that MPs can enter plant leaves following foliar exposure and a molecular-scale perspective on the response of leafy vegetables to differently charged MPs.
研究领域:
环境科学
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植物生理学
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分子生物学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）