World Journal of Clinical Cases
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2021
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IF 1.337
Shi-Hao Mao,Dan-Dan Feng,Xi Wang,Yi-Hui Zhi,Shu Lei,Xi Xing,Rong-Lin Jiang,Jian-Nong Wu
BACKGROUND Sepsis is a major medical challenge. Magnolol is an active constituent of Houpu that improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects, but the mechanism by which it reduces intestinal inflammation in sepsis is yet unclear. AIM To assess the protective effect of magnolol on intestinal mucosal epithelial cells in sepsis and elucidate the underlying mechanisms. METHODS Enzyme-linked immunosorbent assay was used to measure tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and regulated on activation, normal T-cell expressed and secreted (RANTES) levels in serum and ileal tissue in animal studies. The histopathological changes of the ileal mucosa in different groups were observed under a microscope. Cell Counting Kit-8 and cell permeability assays were used to determine the concentration of drug-containing serum that did not affect the activity of Caco2 cells but inhibited lipopolysaccharide (LPS)-induced decrease in permeability. Immunofluorescence and Western blot assays were used to detect the levels of RANTES, inhibitor of nuclear factor kappa-B kinase β (IKKβ), phosphorylated IKKβ (p-IKKβ), inhibitor of nuclear factor kappa-B kinase α (IκBα), p65, and p-p65 proteins in different groups in vitro . RESULTS In rats treated with LPS by intravenous tail injection in the presence or absence of magnolol, magnolol inhibited the expression of proinflammatory cytokines, IL-1β, IL-6, and TNF-α in a dose-dependent manner. In addition, magnolol suppressed the production of RANTES in LPS-stimulated sepsis rats. Moreover, in vitro studies suggested that magnolol inhibited the increase of p65 nucleation, thereby markedly downregulating the production of the phosphorylated form of IKKβ in LPS-treated Caco2 cells. Specifically, magnolol inhibited the translocation of the transcription factor nuclear factor-kappa B (NF-κB) from the cytosol into the nucleus and down-regulated the expression level of the chemokine RANTES in LPS-stimulated Caco2 cells. CONCLUSION Magnolol down-regulates RANTES levels by inhibiting the LPS/NF-κB signaling pathways, thereby suppressing IL-1β, IL-6, and TNF-α expression to alleviate the mucosal barrier dysfunction in sepsis.
研究领域:
药理学
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免疫学
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病理学
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PubMed
高影响因子
JOURNAL OF THE ELECTROCHEMICAL SOCIETY
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2024
·Vol. 171
·期 4
·047503
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IF 3.1
Zhengjie Zhang,Yiheng Zhang,Yangchun Li,Yurong Wang
An electrochemical sensor for the simultaneous detection of magnolol (MAG) and honokiol (HON) was constructed based on the metal-organic framework, UIO-66-NH2, and electroreduced carboxylated graphene oxide (ErGO-GOOH). The UIO-66-NH2@ErGO-COOH coating was characterized by scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. Cyclic voltammetry was applied to investigate the electrochemical behavior of MAG and HON on UIO-66-NH2@ErGO-COOH/GCE. The electroanalytical method for the simultaneous determination of MAG and HON was established using linear sweep voltammetry. Under optimal experimental conditions, a linear range of 0.05 ∼ 8 μM and limits of detection of 16 and 7.0 nm for MAG and HON, respectively, were obtained. The sensor exhibited good repeatability, reproducibility, stability and anti-interference ability. The sensor was successfully applied to the simultaneous detection of MAG and HON in urine and serum samples with good recovery.
研究领域:
分析化学
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电化学
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纳米材料
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生物传感器
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高影响因子
ACS Applied Materials & Interfaces
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2021
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IF 9.229
Xiao Wang,Huan Gu,Huan Zhang,Jing Xian,Jingjing Li,Chaomei Fu,Chen Zhang,Jinming Zhang
Although magnolol (Mag), an anti-inflammatory natural compound, has been demonstrated to play protective effects on ulcerative colitis (UC), its application as an alternative therapeutic reagent for UC treatment is still greatly impeded due to its poor stability in the gastrointestinal tract and insufficient accumulation in the inflamed colon lesion. Nano-/microsized drug delivery systems can potentially overcome some challenges regarding the oral administration of phytochemicals, which still confront premature early drug release, degradation of NPs, or the sustained drug release of MPs. In this study, we primarily loaded Mag into the core–shell zein-based nanoparticles with chondroitin sulfate coating (Mag@CS-Zein NPs) with an average size of 142.27 ± 5.11 nm, showing significant macrophage-targeting and enhanced colon epithelial cellular uptake capacity. Then, we embedded Mag@CS-Zein NPs into hydrogel microspheres via an electrospraying technology. The Mag@CS-Zein NPsinMPs presented a uniform-sized sphere with an average size of 164.36 ± 6.29 μm and sustained drug-release profiles. Compared to CS-Zein NPs, the developed CS-Zein NPsinMPs exhibited prolonged colon retention on the inflammatory surface, as seen from ex vivo and in vivo imaging fluorescence adhesion experiments. Based on the advantage of the combination of hybrid nanoparticles-in-microparticles, oral administration of Mag@CS-Zein NPsinMPs significantly alleviated colitis symptoms in DSS-treated mice by regulating the expression levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) and anti-inflammatory cytokines (IL-10) and factor accelerated colonic mucosal barrier repair via upregulating the expression of ZO-1 and occludin. This study provides great insights into the oral drug delivery of natural compounds for UC therapy.
研究领域:
药学
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纳米技术
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胃肠病学
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材料科学
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2018
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IF 3.118
Jie Cheng,Shuqi Dong,Litao Yi,Di Geng,Qing Liu
Magnolol , the main constituent of Magnolia officinalis , has been shown to produce antidepressant-like effect in rodents. Growing evidence shows that neuroinflammation , oxidative stress and neuroendocrine contribute to the pathogenesis of major depression . Here, the aim of this present study was to determine whether magnolol affected these systems in mice exposed to chronic mild stress (CMS). The ameliorative effect of magnolol on depressive-like symptoms was investigated through behavioral tests, including the classical sucrose preference and forced swimming tests . The behavioral evaluation showed that magnolol reversed the depressive-like deficits both in sucrose preference test and forced swimming test. The elevation of prefrontal cortex pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was decreased by magnolol. Consistently, the microglia activation by CMS was also alleviated by magnolol. In addition, the hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis induced by CMS was attenuated by magnolol. Moreover, the increased lipid peroxidation such as malonaldehyde (MDA) and decreased antioxidant defense enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) induced by CMS were also reversed by magnolol. These findings suggest that administration of magnolol could alleviate depressive-like behaviors in CMS mice that are mediated by suppressing neuroinflammation and oxidative stress in the prefrontal cortex.
研究领域:
神经科学
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药理学
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行为科学
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PubMed
高影响因子
ACS Nano
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2023
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IF 17.1
Xi Fan,Zhuangzhuang Zhang,Wenxia Gao,Qingqing Pan,Kui Luo,Bin He,Yuji Pu
Colonic epithelial damage and dysregulated immune response are crucial factors in the progression and exacerbation of inflammatory bowel disease (IBD). Nanoenabled targeted drug delivery to the inflamed intestinal mucosa has shown promise in inducing and maintaining colitis remission, while minimizing side effects. Inspired by the excellent antioxidative and anti-inflammatory efficacy of naturally derived magnolol (Mag) and gut homeostasis regulation of microbiota-derived butyrate, we developed a pH/redox dual-responsive butyrate-rich polymer nanoparticle (PSBA) as an oral Mag delivery system for combinational therapy of IBD. PSBA showed a high butyrate content of 22% and effectively encapsulated Mag. The Mag-loaded nanoparticles (PSBA@Mag) demonstrated colonic pH and reduction-responsive drug release, ensuring efficient retention and adhesion in the colon of colitis mice. PSBA@Mag not only normalized the level of reactive oxygen species and inflammatory effectors in inflamed colonic mucosa but also restored the epithelial barrier function in both ulcerative colitis and Crohn’s disease mouse models. Importantly, PSBA promoted the migration and healing ability of intestinal epithelial cells in vitro and in vivo, sensitizing the therapeutic efficacy of Mag in animal models. Moreover, transcriptomics and metabolism analyses revealed that PSBA@Mag mitigated inflammation by suppressing the production of pro-inflammatory cytokines and chemokines and restoring the lipid metabolism. Additionally, this nanomedicine modulated the gut microbiota by inhibiting pathogenic Proteus and Escherichia-Shigella and promoting the proliferation of beneficial probiotics, including Lachnoclostridium, Lachnospiraceae_NK4A136_group and norank_f_Ruminococcaceae. Overall, our findings highlight the potential of butyrate-functionalized polymethacrylates as versatile and effective nanoplatforms for colonic drug delivery and mucosa repair in combating IBD and other gastrointestinal disorders.
研究领域:
药学
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纳米技术
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胃肠病学
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免疫学
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DOI
PubMed
高影响因子
Bioengineered
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2021
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IF 3.269
Ting Chen,Lan Shou,Xiaowen Guo,Mingyang Wei,Hui Zheng,Tao Tao
In this study, we aimed to investigate the effect of Magnolol on Alzheimer’s disease (AD). After the model of streptozotocin-induced AD mice with brain insulin resistance was established, the mice were treated with Magnolol or miR-200c antagomiR. The abilities of ambulations, rearings, discrimination, spatial learning, and memory were evaluated by open-field test (OFT), novel object recognition (NOR), and morris water maze (MWM) tests. The levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), and miR-200c in the mice hippocampus were evaluated by enzyme-linked immunosorbent assay, Western blot, or Quantitative real-time Polymerase Chain Reaction. In AD mice model, streptozotocin induced the locomotor impairment and cognitive deficit, up-regulated levels of MDA, TNF-α, IL-6, and CRP, while down-regulated levels of GSH, SOD, and miR-200c. Magnolol increased the rearings numbers and discrimination index of AD mice in OFT and NOR tests. Magnolol increased the number of entries in the target quadrant and time spent in the target quadrant and decreased the escape latency of AD mice in the MWM test. Magnolol also down-regulated the levels of MDA, TNF-α, IL-6, and CRP, and up-regulated the levels of GSH, SOD, and miR-200c in the hippocampus tissues of AD mice. However, miR-200c antagomiR did the opposite and further offset the effects of the Magnolol on AD mice. Magnolol attenuated the locomotor impairment, cognitive deficit, and neuroinflammatory in AD mice with brain insulin resistance via up-regulating miR-200c.
研究领域:
神经科学
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药理学
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分子生物学
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PubMed
高影响因子
Frontiers in Veterinary Science
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2023
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IF 3.2
Tong Yin-Chao,Zhang Yi-Ning,Li Peng-Cheng,Cao Ya-Li,Ding Dong-Zhao,Yang Yang,Lin Qing-Yi,Gao Yi-Nuo,Sun Shao-Qiang,Fan Yun-Peng,Liu Ying-Qiu,Qing Su-Zhu,Ma Wu-Ren,Zhang Wei-Min
Background: The development of antimicrobial resistance in the opportunistic pathogen Escherichia coli has become a global public health concern. Due to daily close contact, dogs kept as pets share the same E. coli with their owners. Therefore, the detection of antimicrobial resistance in canine E. coli is important, as the results could provide guidance for the future use of antibiotics. This study aimed to detect the prevalence of antibiotic-resistance of canine origin E. coli in Shaanxi province and to explore the inhibition effect of magnolol combined with cefquinome on MDR E. coli, so as to provide evidence for the use of antibiotics.Methods: Canine fecal samples were collected from animal hospitals. The E. coli isolates were separated and purified using various indicator media and polymerase chain reaction (PCR). Drug-resistance genes [aacC2, ant(3')-I, aph(3')-II, aac(6')-Ib-cr, aac(3')-IIe, blaKPC, blaIMP−4, blaOXA, blaCMY, blaTEM−1, blaSHV, blaCTX−M−1, blaCTX−M−9, Qnra, Qnrb, Qnrs, TetA, TetB, TetM, Ermb] were also detected by PCR. The minimum inhibitory concentration (MIC) was determined for 10 antibiotics using the broth-microdilution method. Synergistic activity of magnolol and cefquinome against multidrug-resistant (MDR) E. coli strains was investigated using checkerboard assays, time-kill curves, and drug-resistance curves.Results: A total of 101 E. coli strains were isolated from 158 fecal samples collected from animal hospitals. MIC determinations showed that 75.25% (76/101) of the E. coli strains were MDR. A total of 22 drug-resistance genes were detected among the 101 strains. The blaTEM−1gene exhibited the highest detection rate (89.77%). The TetA and Sul gene also exhibited high detection rate (66.34 and 53.47%, respectively). Carbapenem-resistant E. coli strains were found in Shangluo and Yan'an. Additionally, in MDR E. coli initially resistant to cefquinome, magnolol increased the susceptibility to cefquinome, with an FICI (Fractional Inhibitory Concentration Index) between 0.125 and 0.5, indicating stable synergy. Furthermore, magnolol enhanced the killing effect of cefquinome against MDR E. coli. Resistance of MDR E. coli to cefquinome decreased markedly after treatment with magnolol for 15 generations.Conclusion: Our study indicates that antibiotic-resistance E. coli has been found in domestic dogs. After treatment with magnolol extracted from the Chinese herb Houpo (Magnolia officinalis), the sensitivity of MDR E. coli to cefquinome was enhanced, indicating that magnolol reverses the resistance of MDR E. coli. The results of this study thus provide reference for the control of E. coli resistance.
研究领域:
兽医学
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微生物学
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药理学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2020
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IF 4.545
Zhishen Xie,Jianping Zhao,Hui Wang,Yali Jiang,Qiaoling Yang,Yu Fu,Huahui Zeng,Christian Hölscher,Jiangyan Xu,Zhenqiang Zhang
This study aims to investigate whether magnolol (MG), a natural neolignane compound, can prevent AD induced by beta-amyloid (Aβ) and the possible mechanisms involved. MG dose-dependently reduces Aβ deposition, toxicity and memory impairment caused by Aβ in transgenic C. elegans . More importantly, these effects are reversed by GW9662, a selective peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist. MG is more effective in enhancing PPAR-γ luciferase levels than honokiol (HK). Meanwhile, MG has the potential to bind with the ligand binding domain of PPAR-γ (PPAR-γ-LBD). As expected, MG inhibited the luciferase activity of NF-κB and its target genes of inflammatory cytokines, and this effect was blocked by GW9662. The luciferase activity of Nrf2-ARE expression can be activated by MG and decreased Aβ-induced reactive oxygen species (ROS). The target gene LXR of PPAR-γ is activated by MG, which upregulates ApoE and promotes microglia phagocytosis and the degradation of Aβ, and these effects were also reversed by GW9662. In summary, MG can attenuate Aβ-induced AD and the underlying mechanism is the reduction of inflammation and promotion of phagocytosis and degradation of Aβ, which is dependent on PPAR-γ.
研究领域:
神经科学
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药理学
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分子生物学
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PubMed
高影响因子
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
·
2016
·Vol. 120
·期 6
·560-570
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IF 3.097
Hongjun Zhang,Baoling Ju,Xiaoli Zhang,Yanfei Zhu,Ying Nie,Yuanhong Xu,Qiuxia Lei
Magnolol is a pharmacological biphenolic compound extracted from Chinese herb Magnolia officinalis , which displays anti-inflammatory and antioxidant effects. This study was aimed at exploring the potential effect of magnolol on immune-related liver fibrosis. Herein, BALB/c mice were injected with concanavalin A (ConA, 8 mg/kg/week) up to 6 weeks to establish hepatic fibrosis, and magnolol (10, 20, 30 mg/kg/day) was given to these mice orally throughout the whole experiment. We found that magnolol preserved liver function and attenuated liver fibrotic injury in vivo . In response to ConA stimulation, the CD4 + T cells preferred to polarizing towards CD4 + T helper 17 (Th17) cells in liver. Magnolol was observed to inhibit Th17 cell differentiation in ConA-treated liver in addition to suppressing interleukin (IL)-17A generation. Hepatic stellate cells were activated in fibrotic liver as demonstrated by increased alpha smooth muscle actin (α-SMA) and desmin. More transforming growth factor (TGF)-β1 and activin A were secreted into the serum. Magnolol suppressed this abnormal HSC activation. Furthermore, the phosphorylation of Smad3 in its linker area (Thr179, Ser 204/208/213) was inhibited by magnolol. In vitro , the recombinant IL-17A plus TGF-β1 or activin A induced activation of human LX2 HSCs and promoted their collagen production. Smad3/Smad4 signalling pathway was activated in LX2 cells exposed to the fibrotic stimuli, as illustrated by the up-regulated phospho-Smad3 and the enhanced interaction between Smad3 and Smad4. These alterations were suppressed by magnolol. Collectively, our study reveals a novel antifibrotic effect of magnolol on Th17 cell-mediated fibrosis.
研究领域:
药理学
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免疫学
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肝病学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
·
IF 8.5
Safdar Ali Amur,Quratulain Khuhro,Najaf Ali Soomro,Bharat Prasad Sharma,Ahmed Nadeem,Muhammad Tariq,Hao Liang
ZIF-8 has strong potential for biomedical applications due to its excellent biocompatibility. In this study, 89.67 % of natural drug magnolol (Mag) was loaded in ZIF-8 to form Mag@ZIF-8, which was subsequently modified with chitosan (CS) to obtain Mag@ZIF-8/CS. The prepared materials were characterized using the UV–Vis spectroscopy, FTIR, XRD, DLS, SEM and TEM techniques. Thermal stability of materials was analyzed using Thermos Gravimetric Analysis system. PDI and Z -average hydrodynamic sizes of Mag@ZIF-8/CS and Mag@ZIF-8 were increased compared to ZIF-8. Similarly, Mag@ZIF-8 revealed higher zeta potential (+17.5 ± 2.3 mV) than ZIF-8 (+9.8 ± 0.5 mV), but Mag@ZIF-8/CS exposed 3.2 ± 0.9 mV, in water; however, at pH 4 it was changed to +5 mV. Pure ZIF-8 and Mag@ZIF-8 exhibited a hexagonal morphology, while Mag@ZIF-8/CS had a rotund, flat-like structure, with mean particle size of 101 nm, 123 nm and 343 nm, respectively. Density Functional Theory (DFT) analysis offered a deeper insight into the electronic properties and binding interactions of the composites. Under acidic conditions, drug release from Mag@ZIF-8 was higher (86.4 %) and faster than from Mag@ZIF-8/CS (74 %), when tested at physiological pH 7.4 and 37 °C. This, suggests that CS modification of Mag@ZIF-8 is crucial for achieving prolonged and sustained drug release. Mag@ZIF-8 and Mag@ZIF-8/CS depicted a two-fold increase in antibacterial activity against E. coli and S. aureus , demonstrating a synergistic effect. The MIC value for E. coli and S. aureus were, 35 μg/mL and 20 μg/mL, respectively, confirming the enhanced antibacterial efficacy of the composites. Molecular docking analysis provided deeper insights into the binding interactions between the materials and the E. coli protein 5AZC.
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高影响因子
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