Stem Cell Research & Therapy
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2020
·Vol. 11
·期 1
·1-15
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IF 5.116
Shen Ying-Shan,Chen Xiao-Jun,Wuri Sha-Na,Yang Fan,Pang Feng-Xiang,Xu Liang-Liang,He Wei,Wei Qiu-Shi
Objectives Polydatin (PD), extracted from Polygonum cuspidatum , has shown potential therapeutic applications due to its antiosteoporotic and anti-inflammatory activities. Our previous study suggested that PD promotes the osteogenesis of human bone marrow stromal cells (hBMSCs) via the BMP2-Wnt/β-catenin pathway. The aim of our present study was to further explore the role of PD-mediated regulation of Tafazzin (TAZ), a transcriptional coactivator with a PDZ-binding motif, in osteogenesis. Materials and methods hBMSCs were isolated and treated with PD at various concentrations. Alizarin red staining and RT-qPCR were performed to identify calcium complex deposition in hBMSCs as well as the expression of specific osteoblast-related markers, respectively, in each group. Next, TAZ-silenced hBMSCs were generated by lentivirus-produced TAZ shRNA. After treatment with PD, the osteogenic abilities of the TAZ-silenced and control hBMSCs were estimated by ALP activity assay, and expression of the TAZ protein was detected by Western blot analysis and immunofluorescence staining. In vitro, an ovariectomized (OVX) mouse model was established and used to evaluate the effect of PD on bone destruction by micro-CT, immunohistochemistry, and ELISA. Results In vitro, 30 μM PD significantly improved the proliferation and calcium deposition of hBMSCs and markedly stimulated the expression of the mRNAs RUNX2 , Osteopontin , DLX5 , β-catenin , TAZ , and Osteocalcin ( OCN ). Osteogenic differentiation induced by PD was blocked by lentivirus-mediated TAZ shRNA. Furthermore, Noggin (a regulator of bone morphogenic protein 2 (BMP2)) and DKK1 (an inhibitor of the Wnt/β-catenin pathway) were found to inhibit the increase in TAZ expression induced by PD. In vivo, PD prevented estrogen deficiency-induced bone loss in the OVX mouse model. Conclusion Taken together, our findings suggest that PD improved the osteogenic differentiation of hBMSCs and maintained the bone matrix in the OVX mouse model through the activation of TAZ, a potential target gene of the BMP2-Wnt/β-catenin pathway.
研究领域:
药理学
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干细胞生物学
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骨骼生物学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yinghan Wang,Pengyu Xue,Liang Gao,Xuefei Wang,Shilin Zhou,Xiaochen Wu,Chuanlong Guo
Cisplatin induced acute kidney injury (AKI) is clinically prevalent, with a complex pathogenesis and a lack of effective therapeutic drugs. Polydatin (Po) has excellent biological activity, but its low solubility and bioavailability limit its application. In this study, fucoidan (Fu) and carboxymethyl chitosan (Cs) self-assembled into nanoparticles through electrostatic interactions/hydrogen bonding and loaded Po (Fu/Cs Po NPs). In vitro studies found that Fu/Cs Po NPs protected human renal tubular epithelial (HK-2) cells from cisplatin induced damage and accumulation of reactive oxygen species (ROS). Mechanistic studies showed that Fu/Cs Po NPs inhibited cisplatin induced DNA damage and activation of cyclic guanosine monophosphate synthase (cGAS) and intron gene stimulator (STING) pathways. In vivo studies showed that Fu/Cs Po NPs treatment alleviated cisplatin induced AKI symptoms, including elevated blood urea nitrogen (BUN) and serum creatinine (SCr), as well as pathological damage to kidney tissues. In vivo mechanism studies also showed that Fu/Cs Po NPs treatment inhibited cisplatin induced DNA damage and activation of the cGAS-STING pathway. The pharmacokinetic and tissue distribution results demonstrated that the Fu/Cs delivery system enhanced the bioavailability and kidney accumulation of Po in vivo . In summary, our study provided potential drugs for the treatment of cisplatin induced AKI.
研究领域:
药理学
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肾病学
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药物递送系统
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Sustainable Chemistry and Pharmacy
·
2023
·
IF 6
Chen-Xi He,Yu-Shi Shen,Mei-Yan Ling,Xiao-Hui Yao,Tao Chen,Wei-Guo Zhao,Dong-yang Zhang
Continuous fluid catalysis technology is widely used in industry as traditional fluid reactors have unstable reaction efficiency and poor production conversion. Herein, a continuous fluid reactor with porous directional channel was prepared from natural wood (xylem reactor). When the reactor was used for continuous fluid catalysis, fluid from adjacent channels collided through the pores in the inner walls of the directional channels, creating fluid disturbances that caused full contact between the fluid and enzymes in the reactor. Thus, the porous directional channel structure improved mass transfer and catalytic efficiency, which led to a high biological conversion rate. The xylem reactor exhibited satisfactory catalytic performance and catalyzed the hydrolysis of polydatin at 60 °C for 4 h with an optimum conversion of 99.44%. Additionally, the xylem reactor prevented pressure buildup (0.34 kPa) and displayed cycling stability. The xylem reactor with porous directional channel structure exhibited excellent application potential suitable for sustainable development and green chemistry owing to its low preparation cost, minimal environmental impact and high efficiency.
研究领域:
生物工程
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绿色化学
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产品关联
DOI
高影响因子
LIFE SCIENCES
·
2023
·
IF 6.1
Kang Du,Qun Zhou,Ziwen Wang,Chou Mo,Wanwen Dong,Ning Wei,Wenshen Zhong,Yuejiao You,Yifei Wang,Zhiping Wang
Aims Polygonum cuspidatum Sieb. et Zucc is one of the commonly used herbs for the treatment of gouty arthritis, and polydatin is one of its main effective components. This study evaluated the therapeutic potential of polydatin for the treatment of gout. Main methods The ankle joint of C57BL/6 mice were injected with MSU suspensions to simulate human gouty arthritis, and oral treatment with polydatin (25, 50, and 100 mg/kg body weight) was performed at 1 h after MSU crystal injection. The effect of polydatin on model mice was evaluated by measuring ankle swelling, gait, histopathological analysis, proinflammatory cytokine expression, as well as the contents of NO, MDA and GSH. The targets of polydatin were explored by Real-Time PCR and IHC. Key findings Treatment with polydatin inhibited ankle swelling, improved abnormal gait, and reduced ankle lesions dose-dependently. Moreover, polydatin decreased pro-inflammatory cytokine expression, and promoted expression of anti-inflammatory cytokine. In addition, polydatin inhibited MSU-induced oxidative stress by decreasing oxidative product (NO, MDA) generation and promote the antioxidant (GSH). Further, we found that polydatin reduced inflammation by decreasing the expression of NLRP3 inflammasome component via activating PPAR-γ. Moreover, polydatin can protect against iron overload and attenuate oxidative stress by promoting the activation of ferritin. Significance Our findings indicates that polydatin ameliorates MSU-induced inflammation and oxidative stress by regulating PPAR-γ and ferritin activation in gouty arthritis model mice, and this research result suggests that polydatin has therapeutic potential for the treatment of gout in humans through multiple targets.
研究领域:
药理学
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免疫学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2018
·Vol. 9
·期 3
·1701-1712
·
IF 3.289
Shangkun Tang,Qian Tang,Jialei Jin,Gang Zheng,Jianchen Xu,Wu Huang,Xiaobin Li,Ping Shang,Haixiao Liu
Osteoarthritis (OA), which is characterized by progressive degradation of the articular cartilage, is the most prevalent form of human arthritis. Accumulating evidence has shown that polydatin (PD) exerts special biological functions in a variety of diseases. However, whether it protects against OA development has remained unknown. Here, we investigated the anti-inflammatory and chondroprotective effects of PD on interleukin (IL)-1β-induced human osteoarthritic chondrocytes and in the surgical destabilization of medial meniscus mouse (DMM) OA models. In vitro, PD treatment completely suppressed the over-production of pro-inflammatory mediators, including prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), nitric oxide (NO), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and IL-6 in IL-1β-induced human OA chondrocytes. Moreover, PD exerted a suppressive effect on the expression of matrix-degrading proteases, including matrix metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS-5), which leads to the degradation of the extracellular matrix (ECM). Meanwhile, specific inhibition of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) level by short-interfering RNA (siRNA) strongly reversed the anti-inflammatory and chondroprotective effects of PD in human OA chondrocytes. The protective effects of PD were also observed in vivo. In conclusion, our studies demonstrate that PD holds novel therapeutic potential for the development of OA.
研究领域:
风湿病学
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药理学
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炎症
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骨科
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2026
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IF 6.2
Zhengming Xu,Bingbing Song,Shiyi Ou,Zhengang Zhao
Phenolic glycoside monolaurate derivatives synthesized in our previous work exhibit significantly enhanced biological activities and improved intestinal absorption compared with their parent compounds. However, their in vivo functions and underlying mechanisms remain largely unclear, which limits their potential applications in nutrition and health. In this study, Caenorhabditis elegans was employed as an in vivo model to investigate the antioxidant and anti-aging activities of phenolic glycosides and their monolaurate derivatives. The results demonstrated that both phenolic glycosides and their monolaurate derivatives exhibited strong ROS-scavenging activity in C. elegans . Polydatin and polydatin monolaurate prolonged the mean lifespan of wild-type C. elegans by 10.5% and 14.9%, respectively, without exerting any adverse impacts on the body length or reproductive capacity of C. elegans . Both compounds reduced the accumulation of lipofuscin and malondialdehyde (MDA) in C. elegans , enhanced superoxide dismutase (SOD) activity, and strengthened the tolerance of C. elegans to oxidative stress, heat shock, and ultraviolet (UV)-induced damage. Furthermore, they effectively facilitated the nuclear translocation of the transcription factor DAF-16 in C. elegans . Gene expression profiling and mutant strain validation experiments confirmed that the lifespan-extending effects of these two compounds on wild-type C. elegans are mediated through the insulin/insulin-like growth factor 1 signaling (IIS) pathway and the c-Jun N-terminal kinase (JNK) signaling pathway. Specifically, the compounds suppress the IIS pathway and activate the JNK pathway to promote DAF-16 nuclear translocation, thereby regulating the expression of downstream target genes and exerting anti-aging effects.
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产品关联
DOI
高影响因子
Materials Advances
·
2024
·
IF 5.2
Kepei Zhang,Junlan Chen,Faisal Raza,Hajra Zafar,Ye Xu,Ran Li,Kamran Hidayat Ullah,Shigao Zhou
Polydatin, a monomer derived from the dried roots and stems of traditional Chinese medicinal herb, Polygonum cuspidatum, boasts extensive pharmacological activities. Existing nanocarriers of polydatin have not been able to prolong the circulation time for enhanced antidiabetic potential of the stilbenoid polyphenol. This study aims to improve the sustained release and antidiabetic potential of polydatin by fabricating long circulating liposomes (PLLs) via a membrane dispersion method. An orthogonal optimized PLL composed of lecithin, DSPE-PEG2000, and cholesterol was produced, wherein evaluation of the physical properties showed that the prepared PLL had a spherical shape with uniform size, small particle size, and even distribution as well as high encapsulation efficiency and drug loading, along with good physical stability at 4 and 25 °C for 30 days. In vivo release experiments in different buffers via the dialysis bag method suggested that the PLL provided a sustained release of polydatin. Also, in vitro cell uptake and in vivo pharmacokinetics studies of the PLL respectively demonstrated improved cellular uptake and prolonged in vivo circulation time and bioavailability. Using a high-fat diet-induced obese type 2 diabetes mellitus (T2DM) mouse model, it was observed that the PLL could lower blood sugar, improve weight loss, reduce antioxidant stress, lower blood lipids, and ameliorate liver, spleen, and pancreatic tissue damage. This study successfully prepared long-circulating liposomes of polydatin, which sustained in vitro release of polydatin, improved bioavailability in vivo, and enhanced the activity of the drug in treating obese diabetic mice.
研究领域:
药理学
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纳米医学
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代谢疾病研究
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产品关联
DOI
高影响因子
Antioxidants
·
2022
·Vol. 11
·期 4
·666
·
IF 7.675
Yanan Chen,Yue Li,Peilu Jia,Shuli Ji,Hao Zhang,Tian Wang
The present study investigated the potential of polydatin to protect against liver injury and the mitochondrial dysfunction of weanling piglets suffering from intra-uterine growth retardation (IUGR). Thirty-six normal birth weight weanling piglets and an equal number of IUGR littermates were given a basal diet with or without polydatin (250 mg/kg) from 21 to 35 d of age. Plasma and liver samples were collected to measure biochemistry parameters at 35 d of age. IUGR caused hepatic apoptosis, mitochondrial dysfunction, and oxidative damage, along with a lower efficiency of energy metabolism and inferior antioxidant ability. Polydatin decreased apoptotic rate, improved the features of mitochondrial damage, inhibited mitochondrial swelling and superoxide anion formation, and preserved mitochondrial membrane potential in the liver. Concurrently, polydatin promoted mitochondrial biogenesis, increased sirtuin 1 activity, and upregulated the expression levels of several genes related to mitochondrial function and fitness. Polydatin also facilitated mitochondrial oxidative metabolism with a beneficial outcome of increased energy production. Furthermore, polydatin mitigated the IUGR-induced reduction in manganese superoxide dismutase activity and prevented the excessive accumulation of oxidative damaging products in the liver. These findings indicate that polydatin confers protection against hepatic injury and mitochondrial dysfunction in the IUGR piglets by improving energy metabolism and redox balance.Keywords:energy metabolism;intra-uterine growth retardation;liver injury;mitochondrial dysfunction;weanling piglet;polydatin;redox balance
研究领域:
动物科学
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营养学
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生理学
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药理学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2024
·
IF 7.6
Zhaoli Su,Yuanyuan Tang,Gejing Li,Junping Zhu,Yini He,Junlan Zhang,Feng Zhang,Ye Lin,Bin Liu,Xiong Cai
Rheumatoid arthritis (RA) is a chronic and refractory autoimmune disease that primarily affects the synovium of diarthrodial joints. Inflammatory macrophages and fibroblast-like synoviocytes (FLS) in the synovial microenvironment produce pathogenic mediators such as cytokines and proteases that perpetuate immune-mediated inflammation and contribute to the destruction of cartilage and bone. Polydatin (PD), a natural active compound, has demonstrated potential anti-inflammatory and anti-arthritic effects. However, drug development and delivery of PD is still a great challenge owing to its low solubility, short half-life, and high dose requirement. In order to overcome these drawbacks, we developed a novel nanodrug system named HA-M@PB@Ag@PD NPs. This system is composed of hybrid membrane (M), hyaluronic acid (HA), Prussian blue nanoparticles (PB NPs), PD, and Chi-Ag. In vitro experiments demonstrated that HA-M@PB@Ag@PD NPs effectively cleared ROS, promoted the repolarization of inflammatory macrophages, and induced apoptosis of RA-FLS. Using a rat model of RA, HA-M@PB@Ag@PD NPs markedly suppressed joint inflammation, inhibited synovial hyperplasia, and protected joints against destruction of cartilage and bone. Moreover, HA-M@PB@Ag@PD NPs significantly improved the synovial microenvironment of arthritic rats by reducing the number of FLS and inflammatory macrophages, and facilitating the repolarization of inflammatory macrophages.
研究领域:
药理学
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纳米技术
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免疫学
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风湿病学
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产品关联
DOI
高影响因子
Food & Function
·
2024
·
IF 5.1
Zhengming Xu,Kseniya Hileuskaya,Aliaksandr Kraskouski,Yujiao Yang,Zhe Huang,Zhengang Zhao
A diet containing natural active compounds that can inhibit the hydrolytic activity of α-glucosidase on carbohydrates and intestinal glucose absorption is an effective means of controlling postprandial hyperglycemia. Phlorizin and polydatin as phenolic glycosides had a high affinity to the catalytic site of α-glucosidase, but exhibited unsatisfactory competitive inhibitory capacity, with IC50 of 0.97 and > 2 mM, respectively. However, dodecyl-acylated derivatives of phlorizin and polydatin exerted α-glucosidase inhibitory capacity, with IC50 of 55.10 and 70.95 µM, respectively, which were greatly enhanced and much stronger than that of acarbose with IC50 of 2.46 mM. Both dodecyl phlorizin and dodecyl polydatin reduced the catalytic ability of α-glucosidase by reversible noncompetitive and uncompetitive mixed inhibition, which bind noncovalently to the allosteric site 2 through hydrogen bonds and hydrophobic interactions, thereby inducing the secondary structure unfolding and intrinsic fluorescence quenching of α-glucosidase. Confocal microscopy detection visually showed the significant inhibitory effects on FITC-labeled glucose uptake in intestinal Caco-2 cells by phlorizin, polydatin, dodecyl phlorizin and dodecyl polydatin. In addition, based on the differentiated Caco-2 cell monolayer model, dodecyl phlorizin and dodecyl polydatin suppressed intestinal glucose transport more effectively than phlorizin and polydatin, suggesting that they were promising in vivo hypoglycemic active compounds.
研究领域:
药理学
·
生物化学
·
分子生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2020
·
IF 3.004
Dandan Wang,Xinxin Luo,Min Wang,Kai Zhou,Zhining Xia
Molecularly imprinted polymers (MIPs) based on polydatin were prepared by precipitation polymerization method. Synthesis process of MIPs was optimized by discussion of functional monomers, porogens and the molar ratio of template- functional monomer-cross linker. Then, MIPs were prepared with polydatin as the template, 4-vinyl pyridine as the functional monomer, ethylene glycol dimethyl acrylate as the cross linker, acetonitrile as the porogen and the molar ratio of template-monomer-cross linker at 1:10:20. Scanning electron microscopy and Fourier transform infrared spectrometer were used to inspect macroscale and chemical bond of MIPs. Adsorption capability and selectivity of MIPs to polydatin were investigated by carrying out the static, dynamic and selective experiments. The results showed MIPs performed high adsorption ability and selectivity to polydatin, indicating MIPs could be used to separate and enrich polydatin from the complex systems. Finally, MIPs were applied as the adsorbent for isolation and purification of polydatin from the extract of Polygoni Cuspidati Rhizoma et Radix , rats' plasma and urine samples. MIPs were successfully used to separate polydatin from the Polygoni Cuspidati Rhizoma et Radix and recovery ranged from 89.2% to 91.6%. The maximum concentration of polydatin in rats' plasma and urine samples was 2.84 ± 0.0748 µg mL −1 and 2.64 ± 0.485 µg mL −1 , respectively. Moreover, to compare with the MIPs method, organic solvent methods were used to analyze the polydatin in rats' plasma and urine samples. The results illustrated MIPs method was effective and selective for enrichment of polydatin from the medicinal plants and biological samples.
研究领域:
药物化学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Zhao Guangshan,Yang Lian,Zhong Wenshen,Hu Yuze,Tan Yu,Ren Zhe,Ban Qiuyan,Yang Chung S.,Wang Yifei,Wang Zhiping
Resveratrol (RES) is considered to be an activator of AMP-activated protein kinase (AMPK) with many reported health benefits. Polydatin (POD) is a natural precursor and glycosylated form of RES. The glycoside structure of POD alters the bioactivity. Overnutrition-stimulated reactive oxygen species (ROS) promote the AMPK suppression and metabolic dysregulation. The present work compared the effects of POD and RES in ameliorating energy homeostasis imbalance in mice fed a high-fructose diet and elucidated the underlying mechanisms of action. Our results showed that POD elevated the fecal levels of valeric acid and caproic acid via modification of gut microbiota, while RES did not significantly influence the levels of fecal short-chain fatty acids (SCFAs). Both POD and RES markedly decreased the oxidative stress and activated the AMPK signaling pathways in the liver. POD and RES exerted a similar effect in alleviating glucose dysmetabolism, but POD was more effective in ameliorating lipid dysmetabolism than RES. Furthermore, valeric acid and caproic acid alone can activate the AMPK and ameliorate hypercholesterolemia, and enhance the effects of POD on improving lipid metabolism in mice. Overall, for the first time, we demonstrated that POD administration elevated the fecal levels of valeric acid and caproic acid by modifying gut microbiota, thus promoting AMPK activation may be the underlying mechanism that POD is superior to RES in alleviating the lipid dysmetabolism. Our results suggest that POD may be an alternative for RES as an AMPK activator.
研究领域:
药理学
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营养学
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代谢性疾病
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胃肠病学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子