MOLECULAR IMAGING AND BIOLOGY
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2021
·Vol. 23
·期 5
·733-744
·
IF 3.488
Cao Shanshan,Tang Jie,Liu Chunyi,Fang Yi,Ji Linyang,Xu Yingjiao,Chen Zhengping
Purpose The dopamine transporter (DAT) is a marker of the occurrence and development of Parkinson’s disease (PD) and other diseases with nigrostriatal degeneration. 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[ 18 F]-fluoroethyl)nortropane ([ 18 F]FECNT), an 18 F-labelled tropane derivative, was reported to be a useful positron-emitting probe for DAT. However, the rapid formation of brain-penetrating radioactive metabolites is an impediment to the proper quantitation of DAT in PET studies with [ 18 F]FECNT. Deuterium-substituted analogues have presented better in vivo stability to reduce metabolites. This study aimed to synthesize a deuterium-substituted DAT radiotracer, [ 18 F]FECNT- d 4 , and to make a preliminary investigation of its properties as a DAT tracer in vivo . Procedures The ligand [ 18 F]FECNT- d 4 was obtained by one-step radiolabelling reaction. The lipophilicity was measured by the shake-flask method. Binding properties of [ 18 F]FECNT- d 4 were estimated by in vitro binding assay, biodistribution, and microPET imaging in rats. In vivo stability of [ 18 F]FECNT- d 4 was estimated by radio-HPLC. Results [ 18 F]FECNT- d 4 was synthesized at an average activity yield of 46 ± 17 % ( n = 15) and the molar activity was 67 ± 12 GBq/μmol. The deuterated tracer showed suitable lipophilicity and the ability to penetrate the blood-brain barrier (brain uptake of 1.72 % ID at 5 min). [ 18 F]FECNT- d 4 displayed a high binding affinity for DAT comparable to that of [ 18 F]FECNT in rat striatum homogenates. Biodistribution results in normal rats showed that [ 18 F]FECNT- d 4 exhibited a higher ratio of the target to non-target (striatum/cerebellum) at 15 min post administration (5.00 ± 0.44 vs 3.84 ± 0.24 for [ 18 F]FECNT- d 4 vs [ 18 F]FECNT). MicroPET imaging studies of [ 18 F]FECNT- d 4 in normal rats showed that the ligand selectively localized to DAT-rich striatal regions and the accumulation could be blocked with DAT inhibitor. Furthermore, in the unilateral PD model rat, a significant reduction of the signal was found in the lesioned side relative to the unlesioned side. Striatal standardized uptake value of [ 18 F]FECNT- d 4 remained ~4.02 in the striatum between 5 and 20 min, whereas that of [ 18 F]FECNT fell rapidly from 4.11 to 2.95. Radio-HPLC analysis of the plasma demonstrated better in vivo stability of [ 18 F]FECNT- d 4 than [ 18 F]FECNT. Conclusion The deuterated compound [ 18 F]FECNT- d 4 may serve as a promising PET imaging agent to assess DAT-related disorders.
研究领域:
神经科学
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医学影像学
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放射化学
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DOI
PubMed
高影响因子
Animal Diseases
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2021
·Vol. 1
·期 1
·1-13
·
IF 0
Yang Xiaoqi,Fu Yang,Wu Lianfeng,Li Antong,Ji Luyao,Li Hao,Peng Yuxuan,Zhang Jiabin,Zhou Donghai,Zhou Huiping
The major cause of pulmonary vascular remodeling in broilers is abnormal proliferation of vascular smooth muscle cells (VSMCs), and one of the main causes of pulmonary hypertension syndrome (PHS) in broilers is pulmonary artery vascular remodeling. Forty Arbor Acres (AA) broilers were randomly divided into four groups ( n = 10): a control group (deionized water, 0 g/L NaCl), a freshwater group (FW, deionized water + 1 g/L NaCl), highly salinized freshwater group 1 (H-SFW-1, deionized water + 2.5 g/L NaCl) and highly salinized freshwater group 2 (H-SFW-2, deionized water + 5 g/L NaCl). The results of in vivo experiments showed that vascular smooth muscle of the broilers could be significantly proliferated by intake of high-salinity fresh water (H-SFW-1 & H-SFW-2), which significantly increased the content of angiotensin II (Ang II) and the expression of angiotensin II type 1 (AT1) receptor protein. Meanwhile, it significantly decreased the expression of dopamine receptor D4 (DRD4) protein. The results of in vitro experiments showed that exogenous Ang II induced the proliferation of primary VSMCs in broilers, which could be significantly inhibited by DRD4 agonists (D4A, HY-101384A) and enhanced by DRD4 inhibitors (D4I, HY-B0965). In addition, the results of immunoblotting and fluorescence quantitative PCR showed that AT1 receptors could be negatively regulated by DRD4 in VSMCs of broilers, either at the transcriptional or translational level. At the same time, the expression of AT1 receptor could be increased by DRD4 inhibition by D4I and decreased by DRD4 activation by D4A. The negative regulatory effect of DRD4 on AT1 receptor occurred in a dose-dependent manner. These results indicate that long-term intake of highly salinized fresh water can cause PHS in broilers, accompanied by varying degrees of proliferation of pulmonary artery smooth muscle. This mechanism may involve response of its receptor being induced by increased Ang II, while DRD4 can negatively regulate it.
研究领域:
兽医学
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生理学
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分子生物学
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药理学
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DOI
Sensors & Diagnostics
·
2023
·Vol. 3
·期 1
·79-86
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IF 0
Min Shen,Tingting Pan,Yonghao Chen,Juewei Ning,Fengyu Su,Yanqing Tian
Ammonium ions (NH4+) are one of the important metabolic products and are closely related to human health. Currently, many NH4+ detection methods are inevitably disturbed by amino acids, K+, or other substituted amines (such as trimethylamine). To alleviate this problem, a new sensor was designed in this study, which consisted of the fluorescent indicator KS, hydrogel medium D4, and a hydrophobic membrane. In this sensing system, NH4+ and NH3 coexisted in equilibrium; NH3 could pass through a suitable hydrophobic film and transform into NH4+, which complexed with KS, resulting in a change of the probe's fluorescence intensity. By adjusting the internal composition of the sensing matrix, an excellent NH4+ sensor NS-1 was obtained; it demonstrated effective detection of NH4+ in the range 0.3–15.6 mM with a limit of detection (LOD) of 258 μM, and it was not disturbed by K+ or other substituting amines.
研究领域:
生物化学
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分析化学
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DOI
MOLECULES
·
2023
·Vol. 28
·期 7
·3102
·
IF 4.6
Xin Gao,Jinbao Liu,Bo Li,Jing Xie
The destructive effect and mode of action of lemon verbena essential oil on cells were investigated, taking the isolatedPseudosciaena D4as the research object. The extracellular absorbance of thePseudosciaena D4increased at OD260 and OD280 after being treated with lemon verbena essential oil, which destroyed the integrity ofPseudosciaena D4cells, showing a significant effect on preventing biomembrane formation and destroying the formed biomembrane. With an increased concentration of lemon verbena essential oil, extracellular polysaccharide showed a significant decrease in content and a significant increase in inhibition rate, indicating that the secretion of extracellular polysaccharide byPseudosciaena D4cells could be inhibited by lemon verbena essential oil during the process of biomembrane formation. Cell introcession and shrinkage appeared after the treatment with essential oil, and a transparent cavity was formed by the out-flowed cell content. Lemon verbena essential oil destroyed the cell wall, resulting in an enhanced permeability of the cell membrane and leakage of the contents, thereby causing cell death.Keywords:lemon verbena essential oil;antibacterial activity;antibacterial mechanism;Pseudosciaena crocea
研究领域:
微生物学
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植物化学
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DOI
PubMed
高影响因子
EJNMMI Research
·
2024
·Vol. 14
·期 1
·1-16
·
IF 3.1
Tang Jie,Liu Congjin,Liu Chunyi,Hu Qianyue,Fang Yi,Chen Zhengping
Background Parkinson’s disease (PD) is a prevalent neurodegenerative disorder worldwide, diagnosed based on classic symptoms like motor dysfunction and cognitive impairments. With the development of various radioactive ligands, positron emission tomography (PET) imaging combined with specific radiolabelling probes has proven to be effective in aiding clinical PD diagnosis. Among these probes, 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[ 18 F]-fluoroethyl) nortropane ([ 18 F]FECNT) has been utilized as a PET tracer to image dopamine transporter (DAT) integrity in striatal presynaptic dopaminergic terminals. However, the presence of brain-penetrant radioactive metabolites produced by [ 18 F]FECNT may impact the accuracy of PET imaging. In previous research, we developed 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[ 18 F]-fluoroethyl-1,1,2,2-d4) nortropane ([ 18 F]FECNT-d 4 ), a deuterated derivative with enhanced stability in plasma and the striatum, along with a slower washout rate. In this study, we further investigated the potential of [ 18 F]FECNT-d 4 to detect dopaminergic neuron degeneration in Parkinson’s disease. This involved PET imaging in unilaterally-lesioned PD model rats and in vitro autoradiography conducted on postmortem brain sections. Results PET images revealed reduced specific uptake in the ipsilateral striatum of rats stereotactically injected with 6-hydroxydopamine hydrochloride (6-OHDA). Compared to the sham group, the ratio of standardized uptake value (SUV) in the ipsilateral to contralateral striatum decreased by 13%, 23%, and 63% in the mild, moderate, and severe lesioned groups, respectively. Dopaminergic denervation observed in PET imaging was further supported by behavioral assessments, immunostaining, and monoamine concentration tests. Moreover, the microPET results exhibited positive correlations with these measurements, except for the apomorphine-induced rotational behavior test, which showed a negative correlation. Additionally, [ 18 F]FECNT-d 4 uptake was approximately 40% lower in the postmortem striatal sections of a PD patient compared to a healthy subject. Furthermore, estimated human dosimetry (effective dose equivalent: 5.06 E-03 mSv/MBq), extrapolated from rat biodistribution data, remained below the current Food and Drug Administration limit for radiation exposure. Conclusion Our findings demonstrate that [ 18 F]FECNT-d 4 accurately estimates levels of dopaminergic neuron degeneration in the 6-OHDA-induced PD rat model and effectively distinguishes between PD patients and healthy individuals. This highly sensitive and safe PET probe holds promising potential for clinical application in the diagnosis and monitoring of Parkinson’s disease.
研究领域:
神经科学
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医学影像学
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药理学
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DOI
PubMed
高影响因子
Andrology
·
2023
·
IF 4.5
Pan Gao,Xi Liu,Tianle Zhu,Rui Gao,Jingjing Gao,Yao Zhang,Hui Jiang,Houbao Huang,Xiansheng Zhang
Background Recently, dapoxetine has been widely accepted to treat premature ejaculation by fast-inhibiting 5-hydroxytryptamine reuptake. However, dapoxetine is not suitable for all premature ejaculation patients in clinical treatment. We need to investigate and reveal the mechanism deeply to solve this problem. Objectives To investigate and reveal the function of dopamine D4 receptor in dapoxetine medicated premature ejaculation treatment. Materials and methods A rat model was used to screen rapid ejaculators. The molecular mechanisms of histone serotonylation-mediated regulation of dopamine D4 receptor were demonstrated by chromatin immunoprecipitation, DNA pull-down, mass spectrometry analysis, and coimmunoprecipitation experiments. The biological function of dopamine D4 receptor was investigated through in vivo experiments by intrathecal injection of shDRD4 to knockdown dopamine D4 receptor. Results In this study, we found that dapoxetine increased expression of 5-hydroxytryptamine and dopamine D4 receptor. We demonstrated that dapoxetine increased levels of 5-hydroxytryptamine, which promoted histone serotonylation (H3K4me3Q5ser) and transcription factor myeloid zinc-finger 1 complex binding on the dopamine D4 receptor promoter, upregulated the expression of dopamine D4 receptor and thus delayed ejaculation. Discussion In this study, we demonstrated that dapoxetine increased the levels of 5-hydroxytryptamine, which promoted histone serotonylation and myeloid zinc-finger 1 complex binding to the dopamine D4 receptor promoter and upregulated the expression of dopamine D4 receptor, thus delaying ejaculation. Conclusion It is a novel mechanism that dapoxetine take effect of premature ejaculation treatment through upregulating the dopamine D4 receptor, which indicated that upregulated dopamine D4 receptor would enhance the dapoxetine effect in premature ejaculation treatment. This may lead to the development of novel therapeutic interventions for premature ejaculation.
研究领域:
药理学
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神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
SHOCK
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2024
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IF 2.7
Liu Lijuan,Wang Ruoyu,Pu Xuexue,Zha Yutao,Yang Xiao,Fang Xiao,Liu Yong,Shao Min,Zhu Ling,Ren Xiaoou,Deng Guoqing,Yang Ke
Background Sepsis, a systemic inflammation syndrome initiated by infection, poses significant challenges due to its intricate pathophysiology. T cells play a crucial role in combating infections during sepsis. Despite previous observations indicating T cell dysfunction in sepsis, reliable in-vitro detection methods were lacking, and the factors influencing these impairments remained unclear. Methods We developed a novel method using the D 4 -Chip to assess sepsis T cell migration function. This microfluidic platform enabled precise analysis of migration function under controlled conditions. Additionally, We explored the impact of the plasma microenvironment on T cell behavior, along with the redox environment in sepsis, and assessed the potential efficacy of Mitoquinone mesylate (MitoQ), a mitochondrial-targeted drug. Results Our findings revealed impaired migration function in sepsis T cells compared to healthy controls. Interestingly, sepsis plasma enhanced the migration of healthy T cells, yet incubation with healthy plasma did not fully restore migration impairments in sepsis T cells. Subsequent investigations uncovered a significant increase in NADH/NAD+ levels in sepsis T cells, with healthy T cells exposed to various sepsis plasma conditions also showing elevated NADH/NAD+ levels. Importantly, MitoQ normalized abnormal intracellular NADH/NAD+ levels and enhanced the migration ability of T cells. Conclusions Short-term incubation with sepsis plasma does not directly inhibit T cell migration but instead affects T cell function by disrupting the intracellular redox environment. Improving the intracellular redox environment of sepsis patients contributes to restoring impaired migration and proliferation, with MitoQ demonstrating therapeutic potential.
研究领域:
免疫学
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传染病学
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药理学
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细胞生物学
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DOI
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
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2015
·Vol. 132
·期 22
·
IF 1.768
Junjie Yuan,He Qian
The film-forming polyacrylate/silica core–shell nanocomposite particles with octamethylcyclotetrasiloxane (D 4 ) were successfully synthesized via aqueous emulsion polymerization in the presence of a glycerol-functionalized nano silica sol. The ring-opening polymerization of D 4 and the reaction with the glycerol-functionalized nano silica particles before emulsion polymerization was the key procedure in this process. Transmission electron microscopy results showed that more nano silica particles tended to coat on the polyacrylate particles surface after the nano silica sols were modified with D 4 . The silica aggregation efficiency was increased from 90.9 to 98.6% when the amount of D 4 used in the system was varied from 0 to 8.0 wt %. The transparency of the nanocomposite films was not compromised after D 4 was incorporated into the system. The films of the nanocomposite particles with or without D 4 both exhibited superior abrasive resistance. Furthermore, the water resistance and hydrophobicity of the films of these particles with D 4 were also improved significantly. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132 , 42003.
研究领域:
材料科学
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化学工程
✓ 已验证
DOI
高影响因子
Journal of Macromolecular Science Part A-Pure and Applied Chemistry
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2019
·
IF 1.163
Fengfu Li,Changhui Li,Chunda Ji,Xiaoyong Hu,Yunwei He,Yu Sun,Zhi Yun
A series of MoO3/ZrO2 catalysts were prepared by impregnation method, and characterized by X-ray diffraction (XRD), specific surface area (BET) and temperature-programmed desorption of NH3 (NH3-TPD). The polydimethylsiloxane (PDMS) was prepared by ring-opening polymerization from D4 and MM with MoO3/ZrO2 catalysts. The effects of MoO3/ZrO2 catalysts preparation conditions on PDMS molecular weight and reaction conversion rate were discussed. Moreover, the effects of reaction conditions on the ring-opening polymerization were also studied. During the preparation of PDMS, the molecular weight of the product can be controlled by adjusting the mass ratio of D4:MM. The MoO3/ZrO2 catalyst was compared with other catalysts during the ring-opening process, and the repeated times of MoO3/ZrO2 catalysts were also studied. The results showed that MoO3/ZrO2 catalyst had more excellent catalytic performance, for ring-opening process, and when the repeated times was more than 5, the catalytic activity decreased significantly. In addition, the kinetics of D4 ring-opening polymerization with the MoO3/ZrO2 catalyst was investigated.
研究领域:
催化化学
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高分子化学
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材料科学
·
化学工程
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DOI
高影响因子
Separations
·
2022
·Vol. 9
·期 12
·388
·
IF 3.344
Yulin You,Dongxiao Guo,Weiliang Cui,Zhifan Wang,Chunguo Yang,Yongqiang Lin,Shuqi Wang
Matrix-assisted diffusion-ordered spectroscopy (MA DOSY) technology enables efficient the virtual separation of components in a mixture according to their coefficients (D). In the current research, MA DOSY technology was applied for the analysis of a flavonoid mixture. To establish the method, five representative active flavonoid ingredients, including baicalein, baicalin, quercetin, puerarin and rutinum, were selected for the mixture model. The effects of the type and concentration of the matrix, solvent polarity, and nuclear magnetic resonance (NMR) experimental conditions on the resolution of the DOSY spectrum were investigated. It turned out that sodium dodecyl sulfate (SDS) showed the best performance in increasing the resolution of different analytes, which initially increased to the peak below the added amount of 9 mg, and decreased upon the addition of more SDS. In addition, the five flavonoids showed higher resolution in DMSO–d6than in MeOD. Experimental parameters of DOSY, including the number of scans (NS), dummy scans (DS), and value of the FID data points (TD), were also optimized. Finally, the above optimized method was used for the qualitative analysis of the total flavonoid mixture extracted fromScutellaria baicalensisGeorgi. A total of nine compounds were identified and confirmed by comparing them with mass spectrometry data, which further verifies the practical value of this method upon analyzing flavonoid mixtures and provides some reference significance for the follow-up research.Keywords:NMR;MA-DOSY;flavonoids;mixture separation
研究领域:
分析化学
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药学
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天然产物化学
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产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
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2020
·
IF 6.785
Shu-Jian Zheng,Jie Zheng,Cai-Feng Xiong,Hua-Ming Xiao,Shi-Jie Liu,Yu-Qi Feng
Identification of metabolites at the trace level in complex samples is still one of the major challenges in untargeted metabolomics. One formula in the metabolomic database is always corresponding to more than one candidate, which increases the difficulty and cost in the subsequent process of standard compound matching. In this study, we developed an effective method for amine metabolite identification by hydrogen–deuterium scrambling (HDS) based on chemical isotope labeling coupled with liquid chromatography–mass spectrometry (HDS–CIL–LC–MS). After d4-4-(N,N-dimethylamino)phenyl isothiocyanate (d4-DMAP) labeling, the labeled amine metabolites can produce HDS under collision-induced dissociation (CID). The HDS can effectively reflect the number of labile hydrogen atoms in amine metabolites and thus distinguish amine isomers with different functional groups. The developed HDS–CIL–LC–MS method was applied to the determination of amine metabolites in mice feces, in which the amine candidates obtained by the database based on chemical formula searching were reduced by 64% on average, which greatly reduces the cost of standard compound matching. Taken together, the developed HDS–CIL–LC–MS analysis was demonstrated to be a promising method for untargeted metabolomics and a novel strategy for deciphering tandem mass spectrometry (MS2) spectra.
研究领域:
分析化学
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代谢组学
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质谱
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产品关联
DOI
PubMed
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
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2025
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IF 9
Zhenfan Wu,Jing Chen,Zezhi Chen,Huijuan Gong,Xiaofeng Guo,Lu Chen
Membrane separation, a green and efficient gas purification method, has been underexplored for removing volatile methyl siloxanes (VMS) from biogas. This study investigates the feasibility of removing VMS from biogas through polydimethylsiloxane (PDMS) membranes. Permeation tests revealed that PDMS membranes exhibit exceptional permeability to D4 (octamethylcyclotetrasiloxane, a representative VMS compound), with a permeance of 1492.37 GPU, significantly higher than for CH 4 and CO 2 . The selectivity values for D4/CH 4 and CO 2 /CH 4 were 75.26 and 9.80, respectively, demonstrating the membrane’s dual potential for D4 removal and CH 4 recovery. The permeation mechanism of D4 in PDMS was elucidated using density functional theory (DFT) calculations and molecular dynamics (MD) simulations. The results revealed that D4 permeation in PDMS is driven by favorable solubility compatibility, with dissolution being the rate-limiting step. Furthermore, the 40-hour continuous permeation test demonstrated the long-term stability of the PDMS membrane. Process simulation using PRO II software evaluated the engineering application of PDMS membranes for biogas purification, identifying a trade-off between maximizing D4 removal and minimizing CH 4 loss. To address this challenge, an optimized strategy was proposed through PDMS layer thickening. By increasing the thickness of the PDMS layer from 3.32 μm to 15.27 μm, the selectivity of the PDMS membrane for D4/CH 4 was enhanced. PRO II simulation results demonstrated that the thickened membrane could reduce the D4 concentration in simulated biogas from 50 mg/m 3 to 0.79 mg/m 3 , with a CH 4 loss rate of only 3.39 %, meeting the requirements for engineering applications. This study provides a novel and sustainable approach for removing siloxane from biogas, highlighting its potential for practical applications and future research.
研究领域:
膜科学
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环境工程
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化学工程
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材料科学
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可再生能源
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）