Acta Biomaterialia
·
2025
·
IF 9.6
Chunxia Liu,Mengjing Lin,Jing Dai,Binglin Chen,Jiali Wang,Jingyi Li,Xiaoyun Li,Ziyun Jiang,Miao Xiao,Mingliang Tang
Vascular calcification (VC) is a critical pathological hallmark of cardiovascular diseases but current therapeutic options remain inadequate. Nitric oxide (NO) homeostasis plays a vital role in endothelial function and phenotypic transformation of vascular smooth muscle cells (VSMCs), two key pathological processes in VC. In this study, Fe₃O₄@PDA@BNN6 (FPB) nanoparticles were prepared for directional and controllable NO therapy. Magnetic field enriched the nanoparticles to the site of VC and ultrasound triggered the controllable release of NO to regulate the homeostasis of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS), further activated sGC-cGMP-PKG signaling pathway. Both in the rat and in vitro VC models, the innovative therapy inhibited osteogenic like transformation of VSMCs, alleviated endothelial inflammatory response, regulated eNOS/iNOS homeostasis, and effectively improved VC. By ensuring optimal NO bioavailability for vascular homeostasis, this magneto-ultrasonically controlled strategy overcomes limitations of conventional NO-based therapies and paves the way for precision NO-mediated interventions in cardiovascular diseases. Statement of Significance Engineering innovation: Dual-modality nanoparticle system for precision NO delivery: Magnetic guidance directs the FPB to calcified lesions, reducing systemic off-target effects. Ultrasound-triggered release of NO to ensure on-demand delivery at VC sites. Mechanistic innovation: Restoring eNOS/iNOS homeostasis as a therapeutic axis: Directional and controllable NO therapy uniquely modulates eNOS/iNOS homeostasis, further activating the sGC-cGMP-PKG signaling pathway.
研究领域:
心血管医学
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纳米医学
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分子治疗
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生物医学工程
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氧化还原生物学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Yang Zheng,Jiaru Wang,Tiejian Zhao,Lei Wang,Jiahui Wang
Ethnopharmacological relevance Curcuma is a common Chinese herbal medicine that is used in the clinical treatment of chronic liver disease . Studies have found that curcumol is the main active ingredient of curcuma and has good hepatoprotective and anti-inflammatory effects. However, there are few reports on the molecular mechanism underlying the anti-liver fibrosis effect of curcumol. Aim To explore the effect of curcumol on liver angiogenesis, and to reveal the mechanism of curcumol against liver fibrosis . Materials and methods We used liver collagenase perfusion combined with Percoll density gradient sedimentation to separate primary liver sinusoidal endothelial cells, and then applied a leptin-activated cell pathological model. The cells were divided into four treatment groups as follows: blank group, model group, curcumol group, and solafini group. MTT was used to detect the cell proliferation rate in each group, and RT-PCR and western blotting were used to detect the expressions of VEGF, AKT, eNOS , CD31, and vWF. A fluorescent probe was used to detect NO expression, and scanning electron microscopy was used to observe changes in the cell fenestration structure. Angiogenesis assays were used to observe blood vessel formation in each group. Results The results of the MTT test found that the proliferation rate of each group was higher. The results of the molecular biology tests found that curcumol inhibited the activity of the VEGF/AKT/eNOS pathway, thereby increasing fenestration of sinusoidal endothelial cells and inhibiting liver angiogenesis. These differences were statistically significant compared with the model group. Conclusions Curcumol inhibits the activity of the VEGF/AKT/eNOS signaling pathway, regulates the structure of hepatic sinusoidal endothelial cells, and inhibits liver angiogenesis, which together may explain its anti-liver fibrosis mechanism.
研究领域:
药理学
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分子生物学
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肝病学
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民族药理学
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PubMed
高影响因子
INFLAMMOPHARMACOLOGY
·
2024
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IF 4.6
Iqbal Urooj,Malik Abdul,Sial Nabeela Tabassum,Mehmood Malik Hassan,Nawaz Shoaib,Papadakis Marios,Fouad Dalia,Ateyya Hayam,Welson Nermeen N.,Alexiou Athanasios,Batiha Gaber El-Saber
Background The current study aimed to evaluate the anti-inflammatory, anti-oxidant, and pronounced gastro-protective activities of β- Citronellol using in vitro , in vivo assays and in silico approaches. Methods In vitro assays, denaturation of bovine serum albumin, egg protein, and human Red Blood Cells (RBCs) membrane stabilization were performed, using Piroxicam as standard. For in vivo assessment, Histamine (0.1 ml from 1% w/v) and Formaldehyde (0.1 ml from 2% v/v) were used to mediate inflammation. In silico molecular docking and network pharmacology were employed to probe the possible target genes mediating gastroprotective effect of β-Citronellol at 25, 50, and 100 mg/kg, using indomethacin-induced (25 mg/kg i.p) gastric ulcer in rats. Moreover, Gastric tissues were evaluated for morphological, histopathological, and bio-chemical analysis of PGE 2, COX-I, COX-II, 5-LOX, eNOS, ICAM-1, oxygen-free radical scavengers (SOD, CAT), and oxidative stress marker (MDA). Results β - Citronellol prevented denaturation of proteins and RBCs membrane stabilization with maximum effect observed at 6,400 µg/mL. Citronellol decreased rat’s paw edema. Network pharmacology and docking studies revealed gastro-protective potential of Citronellol possibly mediated through arachidonic acid pathways by targeting COX-I, COX-II, PGE 2 , and 5-LOX. Citronellol reduced the ulcer indices, and histopathological changes. Further, β - Citronellol (50 and 100 mg/kg) increased gastric PGE 2, COX-1, and eNOS; while suppressing COX-2, 5-LOX and ICAM-1. Citronellol markedly enhanced the oxidative balance in isolated rat stomach tissues. Conclusions The anti-inflammatory, anti-oxidant, and gastro-protective effects of β - Citronellol against indomethacin-induced gastric ulcer model in rats through mediating COX-I, COX-II, PGE 2, 5-LOX, eNOS, and ICAM-1 inflammatory markers. Graphical abstract
研究领域:
药理学
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炎症
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胃肠病学
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分子生物学
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生物化学
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PubMed
高影响因子
Molecular Medicine Reports
·
2021
·Vol. 24
·期 4
·1-7
·
IF 2.952
Yongpan Huang,Xiaodong Han,Jiayu Tang,Xian Long,Xiaoye Wang
Homocysteine (Hcy) was discovered to be an independent risk factor for the development of atherosclerosis (AS). Moreover, endothelial‑mesenchymal transition (EndMT) was found to be one of main mechanisms contributing to the pathogenesis of AS. Salidroside (SAL) has diverse pharmacological activities, including anti‑inflammatory, anti‑cancer, anti‑oxidative and anti‑fibrosis properties. However, whether SAL serves a beneficial role in Hcy‑induced EndMT remains unknown. The present study aimed to investigate whether SAL exerted its effects on Hcy‑induced EndMT via the Kruppel‑like factor 4 (KLF4)/endothelial nitric oxide (NO) synthase (eNOS) signaling pathway. HUVECs were pretreated with high and low doses (10 or 50 µmol/l) of SAL for 2 h, followed by 1 mmol/l Hcy for 48 h to induce EndMT. Western blotting was used to analyze the protein expression levels of the endothelial marker, VE‑cadherin, the mesenchymal cell marker, α‑smooth muscle actin (SMA), and the nuclear transcription factors, KLF4 and eNOS. Wound healing assays were used to determine the cell migratory ability, and the levels of NO in the cell culture supernatants were measured using a nitrate reductase assay. Cellular immunofluorescence was used to analyze the expression and localization of KLF4. Small interfering (si)RNA targeting KLF4 (siKLF4) was used to knock down KLF4 expression in HUVECs. The results of the present study revealed that treatment with SAL upregulated the expression levels of VE‑cadherin, downregulated the expression levels of α‑SMA, reduced cell migration and activated the eNOS/NO signaling axis, as well as downregulated KLF4 expression and translocation to the nucleus. Compared with the SAL + siKLF4 co‑administration group, no significant differences were observed in the expression levels of the phenotypic markers in the SAL or siKLF4 groups. In conclusion, the findings of the present study revealed that SAL may inhibit Hcy‑induced EndMT via regulation of the KLF4/eNOS signaling pathway.
研究领域:
心血管疾病
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分子生物学
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药理学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 23
·16756
·
IF 5.6
Mengyuan Wang,Xingfang Zhang,Juan Guo,Shangze Yang,Fang Yang,Xingjuan Chen
Acute lung injury (ALI) is characterized by endothelial barrier disruption and associated inflammatory responses, and transient receptor potential cation channel 6 (TRPC6)—mediated Ca2+influx is critical for endothelial hyperpermeability. In this study, we investigated the role of TRPC6 in LPS—induced ALI, analyzed gene expression inWTandTRPC6-/-lungs using RNA sequencing, and explored the effects of TRPC6 in the LPS—induced hyperpermeability in human umbilical vein endothelial cells (HUVECs) to elucidate the underlying mechanisms. Intratracheal instillation of LPS caused edema in the mouse lungs. Deletion of TRPC6 reduced LPS—induced lung edema and decreased cell infiltration. RNA sequencing analysis suggested that downregulated cell adhesion molecules inTRPC6-/-lungs may be responsible for their resistance to LPS—induced injury. In addition, downregulation of TRPC6 significantly alleviated the LPS—induced decrease in eNOS expression in lung tissue as well as in HUVECs. Moreover, inhibition of TRPC6 with the channel antagonist larixyl led to a decrease in LPS—induced hyperpermeability and ROS production in HUVECs, which could be reversed by blocking eNOS. Our findings suggest that inhibition of TRPC6 ameliorates LPS—induced ALI, which may be achieved by acting on the cell adhesion molecule signaling pathway and participating in the regulation of eNOS levels in endothelial cells.Keywords:acute lung injury;TRPC6;eNOS;endothelial cells
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高影响因子
BMC Complementary and Alternative Medicine
·
2019
·Vol. 19
·期 1
·1-10
·
IF 2.479
Fan Yuyan,Fan Hongyu,Zhu Bin,Zhou Yilun,Liu Qingshan,Li Ping
Background Astragaloside IV (AS-IV) was reported to play a role in improving diabetic nephropathy (DN), however, the underlying mechanisms still remain unclear. The aim of the present study is to investigate whether AS-IV ameliorates DN via the regulation of endothelial nitric oxide synthase (eNOS).Methods DN model was induced in Sprague-Dawley (SD) male rats by intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Rats in the AS-IV treatment group were orally gavaged with 5 mg/kg/day or 10 mg/kg/day AS-IV for eight consecutive weeks. Body weight, blood glucose, blood urea nitrogen (BUN), Serum creatinine (Scr), proteinuria and Glycosylated hemoglobin (HbA1c) levels were measured. Hematoxylin-Eosin (HE) and Periodic Acid-Schiff (PAS) staining were used to detect the renal pathology. The apoptosis status of glomerular cells was measured by TUNEL assay. The phosphorylation and acetylation of eNOS were detected by western blot. The effects of AS-IV on high-glucose (HG)-induced apoptosis and eNOS activity were also investigated in human renal glomerular endothelial cells (HRGECs) in vitro.Results Treatment with AS-IV apparently reduced DN symptoms in diabetic rats, as evidenced by reduced BUN, Scr, proteinuria, HbA1c levels and expanding mesangial matrix. AS-IV treatment also promoted the synthesis of nitric oxide (NO) in serum and renal tissues and ameliorated the phosphorylation of eNOS at Ser 1177 with decreased eNOS acetylation. Moreover, HG-induced dysfunction of HRGECs including increased cell permeability and apoptosis, impaired eNOS phosphorylation at Ser 1177, and decreased NO production, were all reversed by AS-IV treatment.Conclusion sThese novel findings suggest that AS-IV ameliorates functional abnormalities of DN through inhibiting acetylation of eNOS and activating its phosphorylation at Ser 1177. AS-IV could be served as a potential therapeutic drug for DN.
研究领域:
药理学
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糖尿病
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肾病学
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分子生物学
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PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2017
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IF 4.593
Hui Zhou,Baocai Fu,Bo Xu,Xiangquan Mi,Gang Li,Chengjun Ma,Jianxin Xie,Ji Li,Zhenhua Wang
Endothelial dysfunction is the key player in the development and progression of vascular events. Oxidative stress is involved in endothelial injury. Rosmarinic acid (RA) is a natural polyphenol with antioxidative, antiapoptotic, and anti-inflammatory properties. The present study investigates the protective effect of RA on endothelial dysfunction induced by hydrogen peroxide (H2O2). Compared with endothelium-denuded aortic rings, the endothelium significantly alleviated the decrease of vasoconstrictive reactivity to PE and KCl induced by H2O2. H2O2 pretreatment significantly injured the vasodilative reactivity to ACh in endothelium-intact aortic rings in a concentration-dependent manner. RA individual pretreatment had no obvious effect on the vasoconstrictive reaction to PE and KCl, while its cotreatment obviously mitigated the endothelium-dependent relaxation impairments and the oxidative stress induced by H2O2. The RA cotreatment reversed the downregulation of AMPK and eNOS phosphorylation induced by H2O2 in HAEC cells. The pretreatment with the inhibitors of AMPK (compound C) and eNOS (L-NAME) wiped off RA’s beneficial effects. All these results demonstrated that RA attenuated the endothelial dysfunction induced by oxidative stress by activating the AMPK/eNOS pathway.
研究领域:
药理学
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心血管研究
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分子生物学
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PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 10
·期 4
·607-624
·
IF 6.331
Andy Wijaya,Yi Wang,Dan Tang,Yuan Zhong,Boyan Liu,Meng Yan,Quhui Jiu,Wei Wu,Guixue Wang
Nitric oxide (NO) is an exceptional endogenous biological gas that mediates and regulates physiological and pathological processes in the human body. However, its synthesis process is impaired during athero-progression and formation. Hence, a strategy to boost NO production and target endothelial nitric oxide synthase (eNOS) is crucial and intriguing in atherosclerosis (AS) management. Herein, we prepare L-arginine (LA) and lovastatin (LV) co-loaded PLGA nanomedicine to achieve sustainable release for enhancing NO production. The utilization of LA reveals that LA has dual contributions, acting as a NO donor and enhancing the solubility of LV by stabilizing PLGA NPs. PLGA-LA/LV demonstrated its potential to boost NO in vitro and in vivo confirmed using DAF-FM DA, augment eNOS and p-eNOS mRNA and protein levels, and suppress the ki67 proliferation marker in VSMCs; in addition, it lowers the total cholesterol level of blood plasma in C57BL/6 mice. Moreover, PLGA can protect the compound delivered and enhance the bioavailability to reach and get released in the blood circulation after oral administration. Collectively, our results endow a safe and efficient nanomedicine outcome, specifically with potential for AS management.
研究领域:
药学
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心血管疾病
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纳米技术
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分子生物学
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PubMed
高影响因子
PHYTOMEDICINE
·
2026
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IF 11.3
Deyu Zuo,Dingyi Lv,Guozhi Zhao,Yanliang Chen,Zhesheng Chen,Lili Pu,Minghao Luo,Ming Tang,Ming Wang,An He,Weijian Xiong,Xunjia Li
Background Vascular endothelial dysfunction is a core pathological feature of diabetes-associated vascular complications, primarily driven by impaired nitric oxide (NO) bioavailability due to dysregulated endothelial nitric oxide synthase (eNOS) activity. While pharmacological strategies targeting the eNOS pathway have shown promise, the discovery of natural compounds capable of restoring endothelial function through novel molecular targets remains an important research direction. Purpose The aim of this study was to investigate the targets and molecular mechanisms of Chikusetsusaponin V (CsV) in regulating vascular endothelial function in diabetes mellitus (DM). Methods The DM models were constructed using db/db mice and high-glucose cultured human aortic endothelial cells (HAECs). The vasodilatory function was investigated using techniques such as metal wire microvascular tension measurement and ultrasonography after intervention with CsV. Modern techniques such as affinity chromatography, mass spectrometry, molecular docking and microscale thermophoresis (MST) test were used to identify the direct targets of CsV. The key pathways and downstream transcription factors involved in the improvement of vasodilatory function of CsV were screened using RNA-Seq. Subsequent validation was performed using a dual luciferase assay. Knockdown adenoviral vectors, quantitative polymerase chain reaction (qPCR), and Western blot (WB) were used to elucidate the molecular mechanism of CsV in regulating the vasodilatory function in DM. Results The results showed that CsV down-regulated blood glucose and increased the expression of eNOS and p-eNOS (S1177), which improved vasodilatation and reduced vascular stiffness in DM mice. Additionally, CsV increased NO release and tube-forming capacity of HAECs. CsV can directly bind to the membrane protein ITGB1. In vivo and in vitro experiments showed that administration of CsV after knockdown of ITGB1 or inhibiting PI3K significantly down-regulated the expression of p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, NR4A3, PURA, and p-eNOS (S1177)/eNOS, decreased NO levels, and affected angiogenesis and endothelial cell function. In contrast, overexpression of ITGB1 produced the opposite results. Moreover, knockdown NR4A3 inhibited NR4A3/PURA/eNOS expression and affected endothelial function, whereas overexpression produced the opposite result. Conclusions CsV improves endothelial function in DM vasculature by targeting ITGB1, enhancing eNOS phosphorylation via the PI3K/AKT pathway, and promoting PURA/eNOS expression through PI3K/AKT/mTOR/NR4A3. These findings support CsV's potential use for improving diabetes vascular function. CsV Targets ITGB1 to Improve Endothelial Function via activating PI3K/AKT/mTOR/NR4A3/eNOS Pathway - present study vs. previous study. Download: Download high-res image (224KB) Download: Download full-size image
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高影响因子
PeerJ
·
2022
·
IF 3.061
Jinhuang Shen,Xinhua Ma,Yubin He,Yanjun Wang,Tianhua Zhong,Yonghong Zhang
Background Ulcerative colitis is a unique inflammatory bowel disease with ulcerative lesions of the colonic mucosa. Melianodiol (MN), a triterpenoid, isolated from the fruits of the Chinese medicinal plant Melia azedarach , possesses significant anti-inflammatory properties. Objective The present study investigated the protective effects of MN on lipopolysaccharide (LPS)-induced macrophages and DSS-mediated ulcerative colitis in mice. Methods In the study, mice were given MN (50, 100, and 200 mg/kg) and 5-ASA (500 mg/kg) daily for 9 days after induction by DSS for 1 week. The progress of the disease was monitored daily by observation of changes in clinical signs and body weight. Results The results showed that MN effectively improved the overproduction of inflammatory factors (IL-6, NO, and TNF- α ) and suppressed the activation of the NF- κ B signalling cascade in LPS-mediated RAW264.7 cells. For DSS-mediated colitis in mice, MN can reduce weight loss and the disease activity index (DAI) score in UC mice, suppress colon shortening, and alleviate pathological colon injury. Moreover, MN treatment notably up regulated the levels of IL-10 and down regulated those of IL-1 β and TNF- α , and inhibited the protein expression of p-JAK2, p-STAT3, iNOS, NF- κ B P65, p-P65, p-IKK α/β , and p-I κ B α in the colon. After MN treatment, the levels of MDA and NO in colonic tissue were remarkably decreased, whereas the levels of GSH, SOD, Nrf-2, Keap-1, HO-1, I κ B α , and eNOS protein expression levels were significantly increased. Conclusion These results indicate that MN can activate the Nrf-2 signalling pathway and inhibit the JAK/STAT, iNOS/eNOS, and NF- κ B signalling cascades, enhance intestinal barrier function, and effectively reduce the LPS-mediated inflammatory response in mouse macrophages and DSS-induced intestinal injury in UC.
研究领域:
药理学
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免疫学
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胃肠病学
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PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2021
·Vol. 45
·期 9
·1926-1934
·
IF 3.612
Yan Li,Zhongjie Qin,Lin Zhou,Khawar Ali Shahzad,Delin Xia
In the treatment of cardiovascular diseases, vascular scaffold materials play an extremely important role. The appropriate substrate chemistries and 15 dynes/cm 2 physiological fluid shear stress (FSS) are both required to ensure normal physiological activity of human umbilical vein endothelial cells (HUVECs). The present study reported the collective influence of substrate chemistries and FSS on HUVECs in the sense of its biological functions. The CH 3 , NH 2 , and OH functional groups were adopted to offer a variety of substrate chemistries on glass slides by the technology of self-assembled monolayers, whereas FSS was generated by a parallel-plate fluid flow system. Substrate chemistries on its own by no means had noticeable effects on eNOS, ATP, NO, and PGI 2 expressions, while FSS stimuli enhanced their production. While substrate chemistries, as well as FSS, were both exerted, the releases of ATP, NO, and PGI 2 were dependent on substrate chemistries. Study of F-actin organization and focal adhesions (FAs) formation of HUVECs before FSS exposure proves that F-action organization and FAs formation followed similar chemistry-dependence. Hereby proposed a feasible mechanism, that is, the F-actin organization and FAs formation of HUVECs are controlled by substrate chemistries, further advancing the modulation of FSS-triggered responses of HUVECs.
研究领域:
生物医学工程
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细胞生物学
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组织工程
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Lei Wu,Wenqing Cheng,Haoke Xiang,Yaping Zhu,Yiran Jiang,Zixuan Wei,Mengqi Shao,Liyuan Tian,Yan Sun,Chao Lu
Chaihu Shugan San produces rapid antidepressant-like effects within 2 h in female CRS-exposed mice. • The rapid effect is comparable in onset to ketamine in female chronically stressed mice. • Hippocampal TC2N is a negative regulator of the rapid antidepressant-like action of CSS. • TC2N down-regulation is associated with hippocampal ERβ–eNOS–CaMKII–BDNF signaling. • The estrogen receptor β-linked mechanism was demonstrated in female mice and requires validation in males. Ethnopharmacological relevance Chaihu Shugan San (CSS), a classical seven-herb formula from the Ming-dynasty text Jing-Yue Quanshu, is widely prescribed for depressive disorders in China. Previous preclinical studies reported antidepressant-like effects only after weeks of repeated administration, mostly in male animals. Whether a single dose of CSS can produce rapid antidepressant-like effects in female animals, and through what mechanism, remains unclear. Aim of the study To determine whether a single administration of CSS produces rapid antidepressant-like effects in female mice exposed to chronic restraint stress (CRS), and to explore the underlying hippocampal mechanism. Methods and materials CSS quality was controlled by HPLC quantification of four index components. Female CRS mice received a single dose of CSS (1, 2 or 4 g/kg, i. g.) or ketamine (10 mg/kg, i. p.), followed by behavioral testing (tail suspension, forced swimming, sucrose preference and open field tests) within 2–24 h. Hippocampal RNA sequencing, RT-qPCR, Western blotting and ELISA were used to identify and validate candidate targets; hippocampal AAV-mediated TC2N overexpression and pretreatment with the ERβ antagonist acolbifene or the CaMKII inhibitor KN-93 were used for interventional validation. Results Batch-to-batch variation of the four index components was below 10% (RSDs 3.51–5.66%), with naringin (313.07 ± 11.16 μg/mL) and hesperidin (196.40 ± 11.11 μg/mL) as the major constituents. Acute administration of CSS (2 and 4 g/kg), like ketamine, shortened immobility time in the tail suspension test at 2 h and in the forced swimming test at 12 h, and restored sucrose preference at 24 h, without affecting locomotor activity. Hippocampal transcriptomics identified Tc2n as up-regulated by CRS and down-regulated by CSS, with Esr2, Nos3 and Camk2a showing the opposite pattern; these changes were confirmed at the mRNA and protein levels within 2 h. Hippocampal TC2N overexpression or pretreatment with acolbifene or KN-93 abolished the rapid behavioral effects of CSS and the associated changes in ERβ–eNOS–CaMKII–BDNF signaling. Conclusion CSS produces rapid, ketamine-comparable antidepressant-like behavioral effects in female CRS-exposed mice, accompanied by down-regulation of hippocampal TC2N and involvement of ERβ, eNOS, CaMKII and BDNF. Because only female mice were studied, these findings are specific to females and support an estrogen-linked mechanism that warrants confirmation in male animals and further translational study. Download: Download high-res image (318KB) Download: Download full-size image
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高影响因子
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