JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2025
·
IF 3.5
Ze-Rui Sun,Hui-Zhen Peng,Mao-Si Fan,Dong Chang,Ming-Yue Wang,Meng-Fei An,Li-Juan Zhang,Rui Zan,Jun Sheng,Yun-Li Zhao,Xuan-Jun Wang
BACKGROUND Hyperuricemia (HUA) is a chronic disease caused by abnormal purine metabolism with high prevalence. Dihydromyricetin (DMY) is a natural flavonoid that is abundant in plants, such as vine tea, grapes and bayberry. DMY has been shown to possess multiple biological properties, but its anti-HUA effect remains underexplored. In the present study, the regulatory effects of DMY on HUA and its complications and mechanism were investigated. RESULTS DMY (10 and 20 μmol L −1 ) treatment significantly reduced xanthine oxidase (XOD) expression and uric acid (UA) synthesis in normal human liver cell strain cells, and intraperitoneal administration of DMY (100 mg kg −1 ) also significantly reduced serum UA and the expression of hepatic XOD in HUA mice. After DMY treatment for 12 consecutive days, the uricosuric protein, ATP-binding cassette subfamily G member 2, was upregulated, and reabsorption proteins, including urate transporter 1 and glucose transporter 9, were downregulated, which was consistent with the results of monosodium urate-induced HUA in human renal tubular epithelial cell line and human colon adenocarcinoma cell line cell models. In addition, DMY significantly ameliorated HUA-induced renal injury, and foot edema induced by monosodium urate. The nucleotide-binding oligomerization domain-like receptor family containing pyrin domain 3 (NLRP3) inflammasome was activated in HUA mice as evidenced by upregulation of NLRP3, caspase-1, ACS, TNF- α and IL-1 β in the kidney and foot, which was significantly suppressed by DMY treatment. CONCLUSION Collectively, these findings suggested that DMY may play important roles in experimental HUA. © 2025 Society of Chemical Industry.
研究领域:
药理学
·
代谢疾病
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Qiyue Sun,Ronghua Zhao,Shuran Li,Weiqin Zhou,Jingsheng Zhang,Bo Pang,Shilan Ding,Lei Bao,Zihan Geng,Rui Xie,Dan Xie,Xiaolan Cui,Shanshan Guo,Jing Sun
Background Coronavirus has caused high-mortality viral pneumonia worldwide. The pathogenesis is characterized by hyperinflammatory reactions resulting from immune homeostasis dysregulation. Verbenalin, an iridoid glucoside derived from Verbena officinalis L ., is widely used in Traditional Chinese Medicine (TCM) clinical practice for its antioxidant, anti-inflammatory and antiviral properties. Purpose This study aimed to investigate the pharmacological effects and underlying mechanisms of verbenalin on coronavirus pneumonia both in vivo and in vitro. Methods A coronavirus pneumonia mouse model and macrophage injury models, including mouse alveolar macrophage cell line (MH-S) cells and primary macrophages, were established to initially confirm the antiviral effects of verbenalin. Time-resolved proteomic were then employed to uncover proteomic changes and identify potential therapeutic targets for coronavirus treatment. Subsequently, flow cytometry and Western blot were employed to investigate verbenalin's effects on NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome pathway. Additionally, the targeting regulation of phosphatase and tensin homolog-induced putative kinase 1 (PINK1) / E3 ubiquitin ligase Parkin (Parkin) pathway by verbenalin was validated through molecular docking, surface plasmon resonance (SPR), immunofluorescent staining, RNA interference (RNAi), and mitophagy inhibition both in vivo and in vitro. Results Verbenalin reduced cell injury and inflammation in Human coronavirus 229E (HCoV-229E)-infected macrophages and improved lung inflammation in mice. Proteomics analysis highlighted the roles of nucleotide-binding oligomerization domain (NOD)-like receptor signaling and mitophagy pathways in coronavirus pneumonia. Verbenalin bound strongly to PINK1 and Parkin proteins, increased mitochondrial membrane potential (MMP), decreased mitochondrial reactive oxygen species (mtROS) levels, reduced the opening of mitochondrial permeability transition pore (MPTP), maintained mitochondrial mass, promoted mitophagy flux, upregulated the expression of PINK1, Parkin, and microtubule-associated protein 1A/1B-light chain 3BII (LC3BII). Additionally, verbenalin inhibited the activation of the NLRP3 inflammasome and downregulated the expression of Interleukin-1 beta (IL-1β), cysteine aspartate-specific protease 1 (caspase-1), and gasdermin D (GSDMD) both in vivo and in vitro. Furthermore, treatment with a mitophagy inhibitor and RNAi attenuated the inhibitory effects of verbenalin on NLRP3 activation, confirming the involvement of the PINK1/Parkin/NLRP3 pathway in verbenalin's protective effects. Conclusion Verbenalin enhances PINK1/Parkin-mediated mitophagy to suppress NLRP3 activation, thereby promoting immune homeostasis and mitigating HCoV-229E-induced inflammation.
研究领域:
药理学
·
免疫学
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Kai Yu,Lidan Fu,Yu Chao,Xiaodong Zeng,Yonggang Zhang,Yuanyuan Chen,Jialu Gao,Binchun Lu,Hua Zhu,Lijuan Gu,Xiaoxing Xiong,Zhenhua Hu,Xuechuan Hong,Yuling Xiao
Small interfering RNA (siRNA) targeting the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has emerged as a promising therapeutic strategy to mitigate infarct volume and brain injury following ischemic stroke. However, the clinical translation of siRNA-based therapies is significantly hampered by the formidable blood-brain barrier (BBB), which restricts drug penetration into the central nervous system. To address this challenge, we have developed an innovative long-circulating near-infrared II (NIR-II) nanoparticle platform YWFC NPs, which is meticulously engineered to enhance BBB transcytosis and enable efficient delivery of siRNA targeting NLRP3 (siNLRP3@YWFC NPs) in preclinical models of ischemic stroke. Furthermore, we integrated advanced deep learning neural network algorithms to optimize in vivo NIR-II imaging of the cerebral infarct penumbra, achieving an improved signal-to-background ratio at 72 h poststroke. In vivo studies employing middle cerebral artery occlusion (MCAO) mouse models demonstrated that image-guided therapy with siNLRP3@YWFC NPs, guided by prolonged NIR-II imaging, resulted in significant therapeutic benefits.
研究领域:
神经科学
·
药理学
·
医学影像学
✓ 已验证
DOI
PubMed
高影响因子
TISSUE & CELL
·
2025
·
IF 2.5
Minhui Wang,Daojun Chen,Daofa Zhang,Hui Han,Maowei Xie,Ying Zhang,Yun Cao,Jiali Wei
Background Renal fibrosis (RF) is a common histopathological feature of chronic kidney disease (CKD) and is closely associated with persistent inflammation and regulated cell death. However, the underlying molecular mechanisms of pyroptosis in RF are unclear. Methods Pyroptosis-related hub genes in RF were identified through bioinformatics analysis. Granzyme B ( GZMB ) was knocked down in transforming growth factor (TGF-β)-stimulated HK-2 cells and in a folic acid (FA)-induced nephropathy mouse model. Western blot and enzyme-linked immunosorbent assays were performed to detect the expression of fibrosis and pyroptosis-related markers. Cell viability was assessed by the Cell Counting Kit-8 assay. Hematoxylin and eosin (HE) and Masson's staining were used to evaluate tubular injury and collagen deposition in renal tissues. Results GZMB was identified as a pyroptosis-associated hub gene. It was significantly upregulated in RF and exhibited high diagnostic performance. In TGF-β-stimulated HK-2 cells, GZMB knockdown enhanced cell viability and reduced lactate dehydrogenase release. In vivo , GZMB silencing ameliorated tubular injury, reduced collagen deposition, and improved renal function. The expression levels of pyroptosis-related proteins, including the N-terminal fragment of gasdermin D, cleaved caspase-1, and NOD-like receptor family pyrin domain containing 3 (NLRP3), as well as fibrotic markers alpha-smooth muscle actin and collagen type I, were downregulated after GZMB knockdown. Mechanically, GZMB knockdown inhibited NLRP3 inflammasome activation and suppressed the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway. Conclusion GZMB deficiency inhibits pyroptosis and dampens the JAK2/STAT3 pathway, representing a potential approach for RF treatment.
研究领域:
肾脏病学
·
分子生物学
·
细胞信号传导
·
炎症
·
纤维化研究
✓ 已验证
DOI
PubMed
高影响因子
Bioresources and Bioprocessing
·
2025
·Vol. 12
·期 1
·139
·
IF 5.1
Jia Yan,Shi Yuxin,Wang Jie,Liu Honghui,Wang Hanyue,Huang Yilin,Liu Ya,Chen Peiyan,Peng Jie
Background Acute pancreatitis (AP) has caused great concern worldwide due to its serious threat to human health. Astragalin is a bioactive natural flavonoid compound with several pharmacological activities, but it remains unclear about its effect on AP. The objective of this experiment was to explore the mitigating efficacy of astragalin on caerulein-induced AP model and examine the underlying mechanisms. Methods Following the assessment of astragalin’s direct effects on pancreatic acinar cells using an in vitro AP model, an in vivo mouse model was established to further validate its efficacy and elucidate the underlying mechanisms. Pancreatic histopathology, amylase, and lipase levels of mice were observed to determine the optimal therapeutic dose of astragalin. The network pharmacology and RNA sequencing technology were used to reveal the possible targets and pathways. Subsequent molecular docking and western blot were conducted to validate the association between astragalin and key target molecules, as well as the NLRP3 signaling pathway. Combined with metagenomics and metabolomics analysis, the astragalin effective gut microbiota-metabolite-gene network was constructed. Moreover, fecal microbiota transplantation experiments were performed to clarify the importance of gut microbiota in astragalin-mediated alleviation of AP. Results The results showed that astragalin attenuated caerulein-induced injury in AR42J cells in vitro. Consistent with these findings, in vivo experiments revealed that astragalin treatment significantly improved pancreatic pathological injury, cell apoptosis, and systemic inflammatory response in AP mice, particularly at high doses. The integrated analysis of network pharmacology and transcriptomics revealed that the NLRP3 signaling pathway was a key molecular pathway, which was further validated using western blot. Docking analysis showed that 12 target genes had good docking activity with astragalin. More intriguingly, it was found that astragalin could reverse gut microbiota dysbiosis by restoring microbial diversity, altering bacterial community composition, and modulating key metabolic pathways. Specifically, astragalin-effective correlation networks were constructed with Lachnoclostridium sp. YL32, Roseburia intestinalis , Ruminococcus gnavus , Lachnospiraceae bacterium Choco86, Anaerobutyricum hallii , etc. as the core strains, 22 metabolites, including 5-Methoxytryptophan, D-Serine, L-Tryptophan, L-Methionine, etc. as core metabolites, and NLRP3 pathway-related genes as the main regulatory targets. Furthermore, fecal microbiota transplantation experiments confirmed the involvement of gut microbiota in AP remission. Conclusion Collectively, these findings identify astragalin as a promising therapeutic agent for AP, targeting both the NLRP3 signaling cascade and gut microbial homeostasis. Graphical
研究领域:
药理学
·
分子生物学
·
胃肠病学
·
微生物组研究
·
天然产物
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Huimin Li,Jingya Ruan,Jiayan Huang,Yijin Wu,Jiaming Cheng,Ongher Kouye,Yi Zhang,Tao Wang
Background Ulcerative colitis (UC) therapy remains challenging due to limited options. Pomegranate peel, rich in bioactive compounds, shows potential, but its key components and mechanisms underlying its action against UC are unclear. Purpose The present investigation was undertaken to assess the therapeutic efficacy of 70 % ethanolic (PPEE) and aqueous extracts (PPWE) derived from pomegranate peel, determine the primary active component, and clarify the underlying molecular mechanism. Study design and methods The anti-UC effects of PPEE and PPWE extracts were first assessed in DSS-induced mice. Differential constituents underlying their efficacy disparities were identified using LC-MS/UHPLC and chemometric analyses. Key bioactive compounds were screened via a model of Caco-2/THP-1 co-culture evaluating intestinal barrier function. The action mechanisms were further elucidated through molecular docking, surface plasmon resonance (SPR), co-immunoprecipitation (Co-IP), and other assays, validated across inflammatory cell models, DSS-induced mice, and human UC colon tissues. Results PPEE showed superior efficacy over PPWE, as evidenced by enhanced intestinal barrier function and suppressed inflammation and NLRP3 inflammasome activation. Ellagic acid (EA) was identified as the core active constituent, which directly targeted AKR1B1/AKR1B3, thereby inhibiting NLRP3-ASC oligomerization and subsequent cleavage of caspase-1 and IL-1 β . Conclusion This study unveils a novel pathogenic mechanism in UC, namely the AKR1B1/AKR1B3-NLRP3 axis, and identifies EA as its effective inhibitor. These results demonstrate the potential of pomegranate peel extracts and offer a novel therapeutic approach for UC.
研究领域:
药理学
·
胃肠病学
·
分子生物学
·
天然产物研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
METABOLIC BRAIN DISEASE
·
2025
·Vol. 40
·期 8
·324
·
IF 3.5
Tian Lei,Su Pan,Feng Gang,Peng Shuaijun,Liu Liming,Yan Xiangli,Liu Xianghua,Li Yucheng,Bai Ming,Wang Baoying,Xu Erping
Modified Xiaoyao San (MXYS) is a well-established clinical prescription for the treatment of depression in China. While MXYS shows considerable promise for the development of new antidepressants, its pharmacological mechanisms remain poorly understood. This study aims to investigate the antidepressant potential and underlying mechanisms of MXYS in lipopolysaccharide (LPS)-induced depression-like behaviors in mice. Behavioral assessments (sucrose preference test, tail suspension test, open field test) demonstrated that MXYS significantly ameliorated LPS-induced anhedonia and behavioral despair. Histopathological and molecular analyses revealed that MXYS mitigated LPS-induced neuronal damage in the prefrontal cortex (PFC), restored dendritic spine density, and rebalanced neuroinflammatory cytokines by reducing the pro-inflammatory IL-1β and elevating the anti-inflammatory IL-10. Moreover, MXYS promoted microglial polarization toward the anti-inflammatory M2 phenotype (CD206⁺) while suppressing the pro-inflammatory M1 phenotype (CD68⁺). Mechanistically, MXYS inhibited NLRP3 inflammasome activation and pyroptosis through the upregulation of the E3 ubiquitin ligase TRIM31, which facilitated NLRP3 degradation. Transmission electron microscopy confirmed that MXYS inhibited LPS-induced microglial pyroptosis, as evidenced by reduced Gasdermin D (GSDMD) expression and preserved cellular ultrastructure. In vitro validation using LPS-stimulated BV2 microglia further corroborated the MXYS-mediated suppression of NLRP3 inflammasome activity, pyroptosis, and inflammatory cytokine dysregulation, alongside enhanced TRIM31 expression. Collectively, these findings demonstrate that MXYS exerts antidepressant effects by modulating neuroinflammation through TRIM31-dependent NLRP3 ubiquitination, microglial phenotype switching, and the inhibition of pyroptosis, providing novel insights into its therapeutic potential for the treatment of depression. Graphical
研究领域:
药理学
·
神经科学
·
免疫学
·
中医中药
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Open Medicine
·
2025
·Vol. 20
·期 1
·20251198
·
IF 1.6
Fei Yu,Guangxue Wang,Xingyi Chen,Yanfei Zhang,Cheng Yang,Hui Hu,Liang Wei
We aimed to investigate the protective effect of luteolin against neuron injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R), and to further elucidate the roles of NLRP3 in luteolin-mediated regulation of neuron injury. Using Schwann (SW) 10 cells, an OGD/R-induced neuron injury model was established, and six experimental groups were designated. Subsequently, cell viability and apoptosis were respectively detected by cell counting kit 8 and flow cytometry. Reactive oxygen species (ROS) levels were measured via flow cytometry with a ROS assay kit. Moreover, the expression of interleukin (IL)-6, IL-1β, NLRP3, and MMP9 was examined by real-time quantitative PCR and Western blot. Compared with control cells, OGD/R significantly reduced cell viability and increased apoptosis, ROS levels, and the mRNA levels of IL-6 , IL-1β , NLRP3 , and MMP9 . Luteolin significantly enhanced OGD/R-induced cell viability and alleviated apoptosis in SW10 cells ( P < 0.05). Additionally, luteolin suppressed ROS levels, along with the expression of IL-1β, IL-6, NLRP3, and MMP9 induced by OGD/R. Furthermore, BMS-986299 significantly decreased the cell viability and increased the expression of inflammatory factors in OGD/R-induced SW10 cells treated with luteolin. This inhibitory effect was reversed by NLRP3 knockdown. In conclusion, luteolin may exert a protective effect on OGD/R-induced nerve injury by inhibiting the NLRP3/IL-1β signaling pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2025
·
IF 4.1
Jun Chen,Shengchen Ding,Huabing Yang,Yi Dai,Zhigang Zhang,Tianxiang Zhu,Lu Cao,Baifei Hu,Hongtao Liu
Purpose: Dihydromyricetin (DMY) is known for its wide range of pharmacological effects and has been approved as a dietary supplement. This study aimed to investigate the therapeutic effects of DMY on dextran sulfate sodium (DSS)-induced disruption of intestinal homeostasis in mice and to explore the underlying molecular mechanisms.Methods: To establish a model of colitis, mice were treated with a 3% DSS solution, followed by gavage administration of DMY for therapeutic intervention. Techniques such as histomorphology, RT-qPCR, 16S rRNA sequencing, and Western blot analysis were used.Results: DMY alleviated several physiological symptoms in colitis mice, including a reduction in the disease activity index (DAI) and spleen index, as well as decreases in the numbers of white blood cells, lymphocytes, and monocytes. Additionally, DMY helped repair the intestinal mucosal barrier function, reshaped the composition of gut microbiota, and regulated intestinal immune responses. These effects collectively contributed to the partial restoration of intestinal homeostasis in colitis mice. Furthermore, experiments with NLRP3−/− mice and pseudo-germ-free mice confirmed that DMY exerts its anti-colitis effects through the gut microbiota-NLRP3 inflammasome axis.Conclusion: DMY helps regulate intestinal homeostasis in colitis mice by suppressing the NLRP3 inflammasome via the gut microbiota. Our study provides new evidence supporting DMY as a potential therapeutic agent for colitis.
研究领域:
药理学
·
胃肠病学
·
免疫学
·
微生物组研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Ziyi Song,Yucheng Gao,Jiangkai Yu,Yang Zhang,Wenbin Xuan,Yijun Rong,Youheng Zhang,Zengxin Gao
This study investigates the role of calreticulin (CRT) in intervertebral disc degeneration (IVDD) and elucidates its underlying mechanisms. CRT expression was markedly reduced in degenerated disc tissues, implicating its involvement in IVDD pathogenesis. Both in vitro and in vivo experiments were conducted to assess the effects of CRT on nucleus pulposus cell (NPC) pyroptosis, apoptosis, and mitochondrial function. Functional analyses demonstrated that CRT overexpression alleviated disc degeneration, inhibited pyroptotic cell death, and preserved mitochondrial integrity. Mechanistically, CRT promoted the clearance of damaged mitochondria through PINK1/Parkin-mediated mitophagy, restoring mitochondrial homeostasis and suppressing ROS accumulation and NLRP3 inflammasome activation. In vivo studies using an IVDD animal model further validated these protective effects, showing reduced disc degeneration and maintenance of extracellular matrix integrity. Recent studies have demonstrated the protective effect of CRT in IVDD. This study builds on these findings and investigates a novel mechanism through which CRT mediates its protective effects in IVDD. Specifically, our study identifies the involvement of PINK1/Parkin-mediated mitophagy in CRT's ability to preserve mitochondrial function and mitigate inflammation in NPCs, offering new insights into the molecular pathways underlying CRT's protective role in IVDD.
研究领域:
分子生物学
·
细胞生物学
·
骨科学
·
炎症研究
✓ 已验证
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2022
·Vol. 43
·期 8
·2016-2025
·
IF 7.169
Wang Jin-cheng,Shi Qi,Zhou Qian,Zhang Lu-lu,Qiu Yue-ping,Lou Da-yong,Zhou Li-qin,Yang Bo,He Qiao-jun,Weng Qin-jie,Wang Jia-jia
Macrophages play a critical role in the pathogenesis of acetaminophen (APAP)-induced liver injury (AILI), a major cause of acute liver failure or even death. Sapidolide A (SA) is a sesquiterpene lactone extracted from Baccaurea ramiflora Lour., a folk medicine used in China to treat inflammatory diseases. In this study, we investigated whether SA exerted protective effects on macrophages, thus alleviated the secondary hepatocyte damage in an AILI. We showed that SA (5–20 μM) suppressed the phosphorylated activation of NF-κB in a dose-dependent manner, thereby inhibiting the expression and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and pyroptosis in LPS/ATP-treated mouse bone marrow-derived primary macrophages (BMDMs). In human hepatic cell line L02 co-cultured with BMDMs, SA (10 μM) protected macrophages from the pyroptosis induced by APAP-damaged L02 cells. Moreover, SA treatment reduced the secondary liver cell damage aggravated by the conditioned medium (CM) taken from LPS/ATP-treated macrophages. The in vivo assessments conducted on mice pretreated with SA (25, 50 mg/kg, ip) then with a single dose of APAP (400 mg/kg, ip) showed that SA significantly alleviated inflammatory responses of AILI by inhibiting the expression and activation of the NLRP3 inflammasome. In general, the results reported herein revealed that SA exerts anti-inflammatory effects by regulating NLRP3 inflammasome activation in macrophages, which suggests that SA has great a potential for use in the treatment of AILI patients.
研究领域:
药理学
·
免疫学
·
肝病学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 6.5
Cheng Fu,Tianyi Hu,Xiangli Zhao,Yahui Huang,Jiang zhang,Lan Zhu,Jun Yang,Gang Chen
Rhein, an anthraquinone-derivative monomer isolated from the rhubarb plant, is the active ingredient of the drug Diacerein® (generic name: diacetylrhein), which possesses anti-inflammatory and antioxidant properties. It has been reported that rhein is effective in protecting against cerebral and retinal ischemia–reperfusion injury (IRI), but whether it can protect against renal IRI remains unknown. Here, a lethal renal IRI model was established with a 100 % mortality rate in untreated mice. Treatment with 100 mg/kg of rhein for 5 consecutive days before ischemia resulted in 100 % survival, maximal preservation of renal function, and a significant reduction in pathological damage, apoptosis and inflammation. In addition, rhein pretreatment significantly inhibited the upregulation of NLRP3, caspase-1, IL-1β and NGAL seen in the IRI control group. Through a series of experiments (including Co-Immunoprecipitation (Co-IP), pull-down, molecular dynamics simulation and surface plasmon resonance (SPR)), we confirmed that rhein has a strong binding affinity with PPARγ. By using the specific inhibitor T0070907 to block PPARγ, the protective effect of rhein on renal IRI in vivo and the protective effect on cell damage in the NLRP3 inflammasome activation model induced by (LPS + Nig) in vitro can be largely eliminated. We demonstrate here that rhein can potently protect against lethal renal IRI in mice. This protection is mainly achieved by targeting and enhancing the expression of PPARγ, thereby inhibiting the activation of the NLRP3 inflammasome. Thus, rhein may be therapeutically useful for the clinical prevention and treatment of renal IRI.
✓ 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）