ACTA PHARMACOLOGICA SINICA
·
2024
·
IF 6.9
Wang Fei,Wang Yu,Zhang Qing-yang,Hu Ke-yu,Song Ying-jie,Yang Lin,Fei Fan,Xu Ceng-lin,Cui Sun-liang,Ruan Ye-ping,Wang Yi,Chen Zhong
Status epilepticus (SE), a serious and often life-threatening medical emergency, is characterized by abnormally prolonged seizures. It is not effectively managed by present first-line anti-seizure medications and could readily develop into drug resistance without timely treatment. In this study, we highlight the therapeutic potential of CZL80, a small molecule that inhibits caspase-1, in SE termination and its related mechanisms. We found that delayed treatment of diazepam (0.5 h) easily induces resistance in kainic acid (KA)-induced SE. CZL80 dose-dependently terminated diazepam-resistant SE, extending the therapeutic time window to 3 h following SE, and also protected against neuronal damage. Interestingly, the effect of CZL80 on SE termination was model-dependent, as evidenced by ineffectiveness in the pilocarpine-induced SE. Further, we found that CZL80 did not terminate KA-induced SE in Caspase-1 −/− mice but partially terminated SE in IL1R1 −/− mice, suggesting the SE termination effect of CZL80 was dependent on the caspase-1, but not entirely through the downstream IL-1β pathway. Furthermore, in vivo calcium fiber photometry revealed that CZL80 completely reversed the neuroinflammation-augmented glutamatergic transmission in SE. Together, our results demonstrate that caspase-1 inhibitor CZL80 terminates diazepam-resistant SE by blocking glutamatergic transmission. This may be of great therapeutic significance for the clinical treatment of refractory SE.
研究领域:
神经科学
·
药理学
·
神经炎症
·
癫痫
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DOI
PubMed
高影响因子
Nano Research
·
2024
·
IF 9.5
Zhu Shengjie,Huang Danqing,Luan Qichen,Li Yang,Gan Jingjing,Zhao Yuanjin,Sun Lingyun
Macrophages play a pivotal role in systemic lupus erythematosus (SLE) therapy. Efforts have been made to develop multifunctional drug delivery systems capable of directing macrophage polarization. Here, we present a novel hyaluronic acid methacrylate (HAMA) hydrogel microparticle encapsulating multiple cytokines for SLE remission though enhancing macrophage functions. The HAMA microparticles loaded with monocyte chemotactic protein-1 (MCP-1) and interleukin-4 (IL-4) were fabricated by using a microfluidic technology. The released MCP-1 facilitates the aggregation of inflammatory macrophages, after which IL-4 induces the macrophage phenotype shift from inflammatory M1 to immune-protective M2, thus restoring immune balance. We have demonstrated in MRL/lpr mice that the hydrogel microparticles could improve their efficacy of intraperitoneal drug delivery, modulate immune function, and attenuate the disease symptoms. These results suggest that our proposed microparticles delivery platform has potential clinical value for treating autoimmune diseases.
研究领域:
药理学
·
免疫学
·
生物医学工程
·
药物递送系统
·
自身免疫疾病
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DOI
高影响因子
PLANT PHYSIOLOGY AND BIOCHEMISTRY
·
2023
·
IF 6.5
Qingwei Jia,Yuqing Yin,Shuting Gai,Lu Tian,Zhihao Zhu,Lei Qin,Yong Wang
Cryptochromes (CRYs), as blue-light photoreceptors, play a crucial role in regulating flowering time and hypocotyl and cotyledon development. Their physiological functions have been extensively studied in various plant species. However, research on onions remains limited. In this study, we identified AcCRY1 and conducted preliminary investigations into its function. Our results demonstrate that AcCRY1 possesses a conserved domain typical of cryptochromes with high homology to those found in monocots. Furthermore, we examined the expression level of AcCRY1 in onion. The green tissues is significantly higher compared to non-green tissues, and it exhibits a significant response to blue-light induction. AcCRY1 demonstrates cytoplasmic localization under blue-light conditions, while it localizes in the nucleus during darkness, indicating a strong dependence on blue-light for its subcellular distribution. In comparison to cry1 , overexpression of AcCRY1 leads to a significant shorten in seedling hypocotyl length, notable expansion of cotyledons, and acceleration of flowering time. The yeast two-hybrid experiment demonstrated the in vitro interaction between AcCRY1, AcCOP1, and AcSPA1. Additionally, BIFC analysis confirmed their interaction in Onion epidermis. Notably, under blue-light conditions, a significantly enhanced binding activity was observed compared to dark conditions. These findings establish a functional foundation for the regulatory role of AcCRY1 in important physiological processes of onion and provide initial insights into the underlying molecular mechanisms.
研究领域:
植物生物学
·
分子生物学
·
遗传学
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DOI
PubMed
高影响因子
Journal of Cell Communication and Signaling
·
2024
·
IF 3.6
Le Cao,Weilu Gao,Haitao Yang,Ran Zeng,Zongsheng Yin
Inflammation promotes the degradation of the extracellular matrix, which contributes to the development of osteoarthritis (OA). Adipocyte enhancer binding protein 1 (AEBP1) participates in multiple pathological processes related to inflammatory diseases. However, the role of AEBP1 in OA development is unknown. We found a higher AEBP1 expression in articular cartilage of OA patients ( n = 20) compared to their normal controls ( n = 10). Thus, we inferred that AEBP1 might affect OA progression. Then mice with destabilization of the medial meniscus (DMM) surgery and chondrocytes with IL-1β treatment (10 ng/mL) were used to mimic OA. The increased AEBP1 expression was observed in models of OA. AEBP1 knockdown in chondrocytes reversed IL-1β-induced inflammation and extracellular matrix degradation, which was mediated by the inactivation of NF-κB signaling pathway and the increased IκBα activity. Co-immunoprecipitation assay indicated the interaction between AEBP1 and IκBα. Importantly, IκBα knockdown depleted the protective role of AEBP1 knockdown in OA. Moreover, AEBP1 knockdown in mice with OA showed similar results to those in chondrocytes. Collectively, our findings suggest that AEBP1 knockdown alleviates the development of OA, providing a novel strategy for OA treatment.
研究领域:
风湿病学
·
分子生物学
·
细胞生物学
·
病理学
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DOI
PubMed
高影响因子
JOURNAL OF ELECTROANALYTICAL CHEMISTRY
·
2018
·
IF 3.235
Yang Yuan,Jiaxin Wang,Xinjiong Ni,Yuhua Cao
A biosensor for determination of 3-chloro-1, 2-propandiol (3-MCPD) was developed based on the electrochemically catalytic reduction by hemoglobin (Hb). Hb was concentrated and immobilized with magnetic molecularly imprinted nanoparticles (MMIPs NPs). The MMIP NPs had a core-shell structure, with magnetic Fe 3 O 4 NPs as the core and SiO 2 as the shell. MMIPs NPs were modified on the surface of a magnetic electrode to constitute the Hb enzyme-like sensor. The biosensor could catalyze the electrochemical reduction of 3-MCPD, and a direct electrochemical determination of 3-MCPD could be achieved for the first time. The biosensor, where Hb immobilized with MMIPs NPs had high electrochemical response for 3-MCPD, increased by 37.5% compared with Hb immobilized with magnetic non-imprinted nanoparticle (MNIPs NPs). The biosensor increased the response by 19.56% again under an external magnetic field . The reduction peak current had a linear relationship with 3-MCPD concentration ranging from 1.0 mg·L −1 to 160 mg·L −1 with a detection limit (S/N = 3) of 0.25 mg·L −1 . The biosensor was applied to the determination of 3-MCPD in soy sauce samples successfully with recoveries between 97.4% and 99.6%.
研究领域:
生物传感器
·
分析化学
·
食品科学
·
电化学
·
分子生物学
·
纳米医学
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DOI
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2015
·
IF 2.037
Xiaopo Wang,Xiaojie Wang,Bo Song
Experimental density and viscosity data for binary mixtures of 2,2,4-trimethylpentane with 1-propanol, 1-pentanol, 1-hexanol, and 1-heptanol at atmospheric pressure over the entire composition range at temperatures from (298.15 to 323.15) K are reported. Excess molar volumes and viscosity deviations of the mixtures were calculated from the experimental data and correlated using the Redlich–Kister equation. The optimized sets of parameters of the equation at each temperature were obtained by the least-squares method.
研究领域:
热力学
·
化学工程
·
物理化学
·
流体混合物
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DOI
高影响因子
Energy Storage Materials
·
2021
·
IF 17.789
Weibo Huang,Yan Wang,Linze Lv,Wei Wang,Chengchang Jin,Guobin Zhu,Qiang Shi,Qunting Qu,Chao Jin,Honghe Zheng
Fluoroethylene carbonate (FEC) is an important electrolyte additive in silicon (Si) anodes. However, it is easily defluorinated by Lewis acids (PF 5 − ) to form harmful corrosive substances (HF). To overcome this problem, 1-Hydroxyethylidene-1, 1-diphosphonic acid (HEDP), a novel multifunctional surface modifier is developed on the Si surface. It can not only consume HF, but also participate in the formation of a solid electrolyte interphase (SEI) film with excellent electrochemical stability, high lithium conductivity, and good thermal stability. In addition, Si@HEDP anode with polyvinylidene fluoride (PVDF) binder exhibits much improved electrochemical performance. After 500 cycles at 30 °C, a high reversible capacity of 1831.8 mAh g − 1 is obtained; and after 200 cycles at 60 °C, it still maintains 2163.8 mAh g − 1 ; which are in sharp contrast to the reference Si anode of almost zero capacity after 25 cycles. This work overcomes the fundamental challenges of using FEC electrolyte additive and PVDF binder in Si-based batteries.
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产品关联
DOI
高影响因子
EMBO JOURNAL
·
2020
·Vol. 39
·期 16
·e103631
·
IF 9.889
Xianping Wang,Jihong Gong,Le Zhu,Shen Wang,Xiaoyu Yang,Yuanyuan Xu,Xiaofei Yang,Cong Ma
Priming of synaptic vesicles involves Munc13-catalyzed transition of the Munc18-1/syntaxin-1 complex to the SNARE complex in the presence of SNAP-25 and synaptobrevin-2; Munc13 drives opening of syntaxin-1 via the MUN domain while Munc18-1 primes SNARE assembly via domain 3a. However, the underlying mechanism remains unclear. In this study, we have identified a number of residues in domain 3a of Munc18-1 that are crucial for Munc13 and Munc18-1 actions in SNARE complex assembly and synaptic vesicle priming. Our results showed that two residues (Q301/K308) at the side of domain 3a mediate the interaction between the Munc18-1/syntaxin-1 complex and the MUN domain. This interaction enables the MUN domain to drive the opening of syntaxin-1 linker region, thereby leading to the extension of domain 3a and promoting synaptobrevin-2 binding. In addition, we identified two residues (K332/K333) at the bottom of domain 3a that mediate the interaction between Munc18-1 and the SNARE motif of syntaxin-1. This interaction ensures Munc18-1 to persistently associate with syntaxin-1 during the conformational change of syntaxin-1 from closed to open, which reinforces the role of Munc18-1 in templating SNARE assembly. Taken together, our data suggest a mechanism by which Munc13 activates the Munc18-1/syntaxin-1 complex and enables Munc18-1 to prime SNARE assembly.
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DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2020
·
IF 4.831
Shiyang Zhou,Gangliang Huang
In this study, a series of novel 7 H -benzo [ c ] [1,3] dioxolo [4, 5- f ] chromen-7-one derivatives were obtained by structural modification of the lead compounds with Fissitungfine B. A total 15 compounds were designed, synthesized and evaluated as inhibitors of tumor. These target compounds have the novel chemical structures that named three six-membered rings including one lactone six-membered ring. In vitro assay, the results showed that the target compounds have a broad spectrum and strong of anti-tumor activity. Such as the target compound 4n to MCF-7 was IC 50 = 0.35 ± 0.01 μM, to A-549 was IC 50 = 0.37 ± 0.01 μM, to Hela was IC 50 = 0.56 ± 0.02 μM, to MDC-803 was IC 50 = 0.53 ± 0.02 μM and COLO-205 was IC 50 = 0.50 ± 0.02 μM in vitro . At the same time, in vivo anti-tumor activity assay results showed that the target compounds had a good inhibitory effect on tumor growth. Among them, the target compound 4n had the best anti-tumor activity, it could inhibit tumor growth well at a low dose. The target compound 4n could be used as a candidate drug for further research and development, in order to be used as early as application in the clinical treatment of tumors.
研究领域:
药物化学
·
肿瘤学
·
有机合成
✓ 已验证
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART B-ATOMIC SPECTROSCOPY
·
2018
·
IF 2.854
Bingshan Zhao,Man He,Beibei Chen,Hongrun Xu,Bin Hu
In this study, poly(1-vinylimidazole) functionalized gold ion imprinted polymer coated magnetic nanoparticles (MNPs@PVIM-Au-IIP) were prepared and characterized. The adsorption behaviors of the prepared MNPs@PVIM-Au-IIP toward gold ions (Au(III)) were studied, it was found that MNPs@PVIM-Au-IIP has good selectivity, high adsorption capacity (185.4 mg g −1 ) and fast adsorption kinetic for Au(III). Based on it, a new method of ion imprinted magnetic solid phase extraction (II-MSPE) coupled with graphite furnace atomic absorption spectrometry (GFAAS) detection was proposed for the analysis of trace Au(III) in real samples with complicated matrix. Factors affecting MSPE including sample pH, desorption reagent, elution concentration and volume, elution time, sample volume and adsorption time were optimized. With high enrichment factor of 100-fold, the detection limit of the proposed method is 7.9 ng L −1 for Au(III) with the relative standard deviation of 7.4% (c = 50 ng L −1 , n = 7). In order to validate the accuracy of the proposed method, the Certified Reference Material of GBW07293 geological sample (platinpalladium ore) was analyzed, and the determined value was in good agreement with the certified value. The proposed II-MSPE-GFAAS method is simple, fast, selective, sensitive and has been successfully applied in the determination of trace Au in ore, sediment, environmental water and human urine samples with satisfactory results.
研究领域:
分析化学
·
环境科学
·
材料科学
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DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2016
·
IF 3.926
Qingxiang Zhou,Man Lei,Jing Li,Kuifu Zhao,Yongli Liu
Magnetic Fe@MgAl-layered double hydroxides (MgAl-LDHs) composite was firstly synthesized by coating MgAl-layered double hydroxides on the surface of the dispersed nanoscale zero valent irons with co-precipitation method and characterized by transmission electron microscopy and X-ray diffraction techniques. The synthesized Fe@MgAl-LDHs nanoparticles were investigated for magnetic solid phase extraction (MSPE) of 1-naphthol and 2-naphthol from the water samples. The elutent containing 1-naphthol and 2-naphthol was analyzed by high performance liquid chromatography with variable wavelength detection (HPLC–UV). Under optimal conditions, there is good linear relationship between the concentration and the peak area in the range of 0.5–200 μg L −1 with the correlation coefficients ( r 2 ) above 0.998 for 1-naphthol and 2-naphthol. The limits of detection were 0.22 μg L −1 and 0.19 μg L −1 for 1-naphthol and 2-naphthol, respectively, and precisions were both below 2.5% ( n = 6). The real water analysis demonstrated that the spiked recoveries were in the range of 79.2–80.9% ( n = 3). All these results indicated that the developed MSPE–HPLC–UV method was proved to be an efficient tool for the analysis of naphthols.
研究领域:
环境科学
·
分析化学
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DOI
高影响因子
Russian Journal of Physical Chemistry A
·
2026
·Vol. 100
·期 7
·1360-1365
·
IF 0.7
Xiaoru Pan,Kong Xiangyan,Li Dan
In this experiment, the viscosities and densities of binary systems consisting of cyclohexene oxide with 1-butanol, 1-pentanol, 1-hexanol, 1-heptanol were measured at different temperatures ranging from 298.15 to 313.15 K. Based on these data, excess molar volumes and viscosity deviations were calculated. The excess properties were correlated using the Redlich–Kister equation.
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）