Chemosensors
·
2025
·Vol. 13
·期 2
·32
·
IF 3.7
Yang Dai,Xiuran Mao,Maimaiti A. Abulaiti,Qianyu Wang,Zhihao Bai,Yifeng Ding,Shuangcan Zhai,Yang Pan,Yue Zhang
Monitoring of immune factors, including interferon-gamma (IFN-γ), holds great importance for understanding immune responses and disease diagnosis. Wearable sensors enable continuous and non-invasive detection of immune markers in sweat, drawing significant attention to their potential in real-time health monitoring and personalized medicine. Among these, electrochemical sensors are particularly advantageous, due to their excellent signal responsiveness, cost-effectiveness, miniaturization, and broad applicability, making them ideal for constructing wearable sweat sensors. In this study, we present a flexible and sensitive wearable platform for the detection of IFN-γ, utilizing a DNA hydrogel with favorable loading performance and sample collection capability, and the application of mobile software achieves immediate data analysis and processing. This platform integrates three-dimensional DNA hydrogel functionalized with IFN-γ-specific aptamers for precise target recognition and efficient sweat collection. Signal amplification is achieved through target-triggered catalytic hairpin assembly (CHA), with DNA hairpins remarkably enhancing sensitivity. Ferrocene-labeled reporting strands immobilized on a screen-printed carbon electrode are displayed via CHA-mediated strand displacement, leading to a measurable reduction in electrical signals. These changes are transmitted to a custom-developed mobile application via a portable electrochemical workstation for real-time data analysis and recording. This wearable sensor platform combines the specificity of DNA aptamers, advanced signal amplification, and the convenience of mobile data processing. It offers a high-sensitivity approach to detecting low-abundance targets in sweat, paving the way for new applications in point-of-care diagnostics and wearable health monitoring.
研究领域:
生物传感器
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电化学
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纳米技术
·
生物医学工程
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健康监测
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即时检测
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产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Zhang Huaiyu,Zhang Jiayu,Liu Yilun,Jiang Yang,Li Zhongmin
Molecular targeted therapy has been proved effective in treatment of rectal cancer. Up-regulated expression of programmed death ligand-1 (PD-L1) was observed after the management of molecular targeted therapy, which made the therapeutic effect discounted. Tumors with higher PD-L1 expression were more sensitive and responsive to treatment of PD-L1 inhibitor. Therefore, the combination of molecular targeted therapy and immune checkpoint blockade makes sense. In this study, the copolymers of poly (ethylene glycol)-block-poly (L-leucine) (PEG-PLLeu) were synthesized as a thermosensitive hydrogel composite for consecutive release of regorafenib (REG) and BMS202. The mechanical properties of PEG-PLLeu were investigated, confirming that PEG-PLLeu (5 wt.%) was suitable for in situ injection as drug-delivery composite at low temperature and stable after sol-gel transition at body temperature. Importantly, the double drug loaded hydrogel showed superior antitumour activity over single drugs in an orthotopic rectal cancer model (CT26-Luc). Further analysis of the tumor tissues suggested that REG upregulated the expression of PD-L1 in tumor tissues. In addition, the immunosuppressive tumor microenvironment of CT26-Luc tumor was distinctly relieved under the effect of BMS202, as characterized by increased infiltration of CD8+ T cells in tumors and enhanced secretion of antitumour cytokines (IFN-γ and TNF-α). Moreover, the drug-loaded composite showed no obvious toxicity in histological analysis. Taken together, the administration of REG and BMS202 in the PEG-PLLeu composite could induce a synergistic effect in in situ treatment of rectal cancer without obvious toxicity, and thus represented a potential strategy for enhanced in situ therapeutic modality.
研究领域:
肿瘤学
·
药学
·
材料科学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2022
·
IF 5.589
Qiangwei Liang,Yang Lan,Yifan Li,Yongjin Cao,Juan Li,Yanhua Liu
Chemotherapeutic agents can trigger the immune response via inducing immunogenic cell death (ICD), but the weak ICD effect induced by chemotherapy alone limits its lasting antitumor immunotherapy effect. A Cro polymerized prodrug carriers (POEG- b -PCro) with immunostimulatory by ICD induction was developed and co-delivered DOX to generate synergistic ICD induction for chemo-immunotherapy on breast cancer. DOX/POEG- b -PCro micelles displayed prolonged circulation in blood, efficient accumulation in tumors, internalization and then co-released DOX&Cro in tumor cells. Moreover, the DOX/POEG- b -PCro micelles synergistically triggered ICD induction by releasing the nuclear high mobility group box 1 (HMGB1) and down-regulation of c-Met level for generating chemo-immune anti-tumor actions. Importantly, the DOX/POEG- b -PCro micelles synergistically enhanced the tumor cytotoxic T lymphocytes infiltration , concomitant decreasing the immunosuppressive regulatory T (Treg) cells, accompanied with the increased cytokines secretion of IFN-γ and TNF-α, consequently displaying an improved anti-tumor activity in 4 T1 breast cancer mice. Overall, POEG- b -PCro prodrug micelles co-delivered DOX could be served as a promising nano drug delivery system for synergistic ICD induction on breast cancer chemo-immunotherapy.
研究领域:
药学
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肿瘤学
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免疫治疗
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Zhang Nan,Gao Xiaochen,Zhang Weijia,Xiong Junyao,Cao Xiaojian,Fu Zhen F.,Cui Min
Japanese encephalitis virus (JEV) is one of the most important members of the flavivirus family. It is a typical zoonotic pathogen that has caused substantial social and economic losses worldwide. The relation between JEV-induced immunosuppression and inflammatory responses has not been thoroughly investigated. In this study, cells infiltrating the brain tissue of JEV-infected mice were mainly identified as monocytic myeloid-derived suppressor cells (M-MDSCs), which subsequently differentiated into CD3+ macrophages. Co-culture with T cells showed that both splenic M-MDSCs and brain infiltrated M-MDSCs isolated from JEV-infected mice inhibited T cell proliferation through ARG1 and iNOS. The splenectomy model revealed that JEV-induced M-MDSCs were mainly derived from bone marrow and migrated to the spleen and central nervous system (CNS). The results of the transcriptome analysis and IRF7-deficient mice indicated that the ZBP1-IRF7 signaling pathway stimulated by JEV RNA played a central role in the induction of M-MDSCs. M-MDSCs migrated into the CNS through the chemokine CCL2/N-CCL2 derived from astrocytes and brain infiltrated M-MDSCs differentiated into CD3+ macrophages through a mechanism mediated by M-CSF, IL-6 and IFN-γ in the brain microenvironment. These findings provide evidence for the mechanism that JEV regulates the differentiation of M-MDSCs and thereby exacerbates pathogenicity, which represents a potential therapeutic target for Japanese encephalitis (JE).
研究领域:
免疫学
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神经病毒学
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病毒学
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致病机制
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产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2022
·
IF 14.903
Yunting Zhang,Min Jiang,Guangsheng Du,Xiaofang Zhong,Chunting He,Ming Qin,Yingying Hou,Rong Liu,Xun Sun
The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN- γ secretion than free antigen and adjuvants. In vivo , MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.
研究领域:
癌症免疫学
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纳米技术
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药学
·
免疫疗法
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yu Tian,Hongshu Jing,Quan Wang,Suxian Hu,Zhihua Wu,Yourong Duan
Immune checkpoint blockade, especially the programmed cell death ligand 1 (PD-L1) blockade, has revolutionized the treatment of melanoma . However, PD-1/PD-L1 monotherapy leads to unsatisfactory therapeutic outcomes. The immunotherapy of melanoma could be improved by adding doxorubicin (DOX), which triggers immunogenic cell death (ICD) effect to activate anti-tumor immunity. Additionally, microneedles, especially dissolving microneedles (dMNs), can further enhance outcomes of chemo-immunotherapy due to the physical adjuvant effect of dMNs. Herein, we developed the dMNs-based programmed delivery system that incorporated pH-sensitive and melanoma-targeting liposomes to co-deliver DOX and siPD-L1, achieving enhanced chemo-immunotherapy of melanoma (si/ [email protected] dMNs). The incorporated si/ [email protected] LPs demonstrated uniform particle size, pH-sensitive drug release, high in vitro cytotoxicity and targeting ability. Besides, si/ [email protected] LPs effectively downregulated the expression of PD-L1, induced tumor cell apoptosis and triggered ICD effect. The si/ [email protected] LPs also showed deep penetration (approximately 80 μm) in 3D tumor spheroids. Moreover, si/ [email protected] dMNs dissolved rapidly into the skin and had sufficient mechanical strength to penetrate skin, reaching a depth of approximately 260 μm in mice skin. In mice model of melanoma tumor, si/ [email protected] dMNs exhibited better anti-tumor efficacy than monotherapy by dMNs and tail intravenous injection at the same dose. This was due to the higher cytotoxic CD8 + T cells and the secreted cytotoxic cytokine IFN-γ evoked by si/ [email protected] dMNs, thereby eliciting strong T-cell mediated immune response and resulted in enhanced anti-tumor effects. In conclusion, these findings suggested that si/ [email protected] dMNs provided a promising and effective strategy for enhanced chemo-immunotherapy of melanoma.
研究领域:
肿瘤学
·
药学
·
免疫学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
NEURON
·
2024
·
IF 14.7
Bin Wu,Ling Meng,Yan Zhao,Junjie Li,Qiuyun Tian,Yayan Pang,Chunguang Ren,Zhifang Dong
Social creatures must attend to threat signals from conspecifics and respond appropriately, both behaviorally and physiologically. In this work, we show in mice a threat-sensitive immune mechanism that orchestrates psychological processes and is amenable to social modulation. Repeated encounters with socially cued threats triggered meningeal neutrophil (MN) priming preferentially in males. MN activity was correlated with attenuated defensive responses to cues. Canonical neutrophil-specific activation marker CD177 was upregulated after social threat cueing, and its genetic ablation abrogated male behavioral phenotypes. CD177 signals favored meningeal T helper (Th)1-like immune bias, which blunted neural response to threatening stimuli by enhancing intrinsic GABAergic inhibition within the prelimbic cortex via interferon-gamma (IFN-γ). MN signaling was sensitized by negative emotional states and governed by socially dependent androgen release. This male-biased hormone/neutrophil regulatory axis is seemingly conserved in humans. Our findings provide insights into how immune responses influence behavioral threat responses, suggesting a possible neuroimmune basis of emotional regulation.
研究领域:
神经科学
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免疫学
·
行为科学
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产品关联
DOI
PubMed
高影响因子
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
·
2025
·Vol. 66
·期 5
·21-21
·
IF 4.7
Xianyang Liu,Hangjia Zuo,Chao Wu,Na Li,Qian Zhou,Fan Cao,Baorui Chu,Shuhao Zeng,Hui Feng,Yakun Wang,Fengyang Lei,Ke Hu,Shengping Hou
Purpose:Uveitis is an immune-mediated ocular disorder that poses a significant threat to vision, particularly among young and middle-aged adults. The treatment of uveitis is complicated by the presence of the blood-retinal barrier (BRB), which restricts the passage of large molecular drugs into the eye, thus limiting effective therapeutic options. The primary objective of this study is to identify a novel therapeutic agent capable of treating uveitis and explore its underlying mechanism.Methods:In this study, we used a mouse model of experimental autoimmune uveitis (EAU) induced by interphotoreceptor retinoid-binding protein (IRBP) and lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-induced inflammatory BV2 cells. Evans blue and fundus fluorescein angiography (FFA) experiments were performed to evaluate the destruction of BRB. Silt lamp and hematoxylin and eosin (H&E) staining were conducted to evaluate the inflammatory response. In vivo proteomics and Western blot were carried to investigate the underlying mechanisms.Results:Our study reveals that Muscone significantly alleviates EAU and restores the integrity of BRB. Moreover, Muscone treatment markedly downregulated inflammatory factors within the retinas and BV2 cells. In vivo proteomic combined with liquid chromatography-mass spectrometry (LC-MS) has elucidated that Muscone exerts its anti-inflammatory effects by modulating the PI3K-AKT signaling pathway. Moreover, by using LY294002 to specifically inhibit PI3K, we observed a marked decrease in inflammatory phenotype and BRB destruction of EAU.Conclusions:In summary, this study establishes the protective efficacy of Muscone against the progression of EAU and provides insights into the molecular mechanisms responsible for its therapeutic action.
研究领域:
免疫学
·
眼科学
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药理学
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分子生物学
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神经炎症
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2024
·Vol. 43
·期 1
·1-20
·
IF 11.4
Xu Wenjing,Li Yingqiu,Liu Lumei,Xie Jing,Hu Zongren,Kuang Shida,Fu Xinying,Li Bonan,Sun Tiansong,Zhu Congxu,He Qinghu,Sheng Wen
Background Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa. Methods A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development. Results After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3 + CD8 + IFN-γ, CD3 + CD8 + Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2. Conclusions ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.
研究领域:
肿瘤学
·
免疫学
·
微生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2016
·
IF 5.886
Wei Li,Wei Jiang,Shuang Dai,Lei Wang
Cytokines play important roles in the immune system and have been regarded as biomarkers. While single cytokine is not specific and accurate enough to meet the strict diagnosis in practice, in this work, we constructed a multiplexed detection method for cytokines based on dual bar-code strategy and single-molecule counting. Taking interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) as model analytes, first, the magnetic nanobead was functionalized with the second antibody and primary bar-code strands, forming a magnetic nanoprobe. Then, through the specific reaction of the second antibody and the antigen that fixed by the primary antibody, sandwich-type immunocomplex was formed on the substrate. Next, the primary bar-code strands as amplification units triggered multibranched hybridization chain reaction (mHCR), producing nicked double-stranded polymers with multiple branched arms, which were served as secondary bar-code strands. Finally, the secondary bar-code strands hybridized with the multimolecule labeled fluorescence probes, generating enhanced fluorescence signals. The numbers of fluorescence dots were counted one by one for quantification with epi-fluorescence microscope. By integrating the primary and secondary bar-code-based amplification strategy and the multimolecule labeled fluorescence probes, this method displayed an excellent sensitivity with the detection limits were both 5 fM. Unlike the typical bar-code assay that the bar-code strands should be released and identified on a microarray, this method is more direct. Moreover, because of the selective immune reaction and the dual bar-code mechanism, the resulting method could detect the two targets simultaneously. Multiple analysis in human serum was also performed, suggesting that our strategy was reliable and had a great potential application in early clinical diagnosis.
研究领域:
生物化学
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免疫学
·
分子生物学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Li Zhang,Shuai Cui,Ning Ding,Jing Zhang,Enna Cui,Qian Xiang,Zhenghao Zhou,Bo Sun,Yinan Wang,Hao Hong,Yunsu Ma,Dongzhi Yang
Tumor-associated macrophages (TAMs) play a critical role in tumor progression and metastasis. Modulation of TAM polarization is one of the most effective strategies to change the immunosuppressive tumor microenvironment (TME). In this study, organic polymer nanoparticles (CPHT) were prepared using hyaluronic acid (HA)-conjugated disulfide-bonded polyethylene imide (PEIS) as a carrier through a self-assembly strategy. These nanoparticles were modified by transferrin (Tf) and loaded with chlorin e6 (Ce6). The results showed that CPHT had good dispersion with a particle size of about 30 nm. CPHT gradually disintegrated under the exposure with a high concentration of glutathione (GSH) in tumor cells, proving the possibility for the controlled release of Ce6 and photodynamic therapy. An in vitro test showed that the uptake of CPHT in tumor cells was mediated by both HA and Tf, indicating the active tumor-targeting capacity of CPHT. CPHT significantly downregulated the ratio of CD206/CD86 and triggered the upregulation of immune factors such as TNF-α and iNOS, suggesting the repolarization of TAMs. We also found that CPHT effectively induced ferroptosis in tumor cells through lipid peroxide accumulation, GSH depletion, and downregulation of lipid peroxidase (GPX4) expression. Animal experiments confirmed that CPHT not only effectively inhibited the growth of tumors in situ but also significantly decelerated the growth of the distal tumor. Elevated levels of CD86 and IFN-γ and decreased expression of CD206 were observed at the tumor sites post CPHT treatment. These results confirmed the value of CPHT as a multifunctional nanoplatform that can tune the TME and provide new hope for tumor treatment.
研究领域:
癌症生物学
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纳米技术
·
药学
·
免疫学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ORAL PATHOLOGY & MEDICINE
·
2021
·Vol. 51
·期 1
·74-85
·
IF 4.253
Jing-Ya Yang,Fang Wang,Gang Zhou
Background Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory disease with uncertain aetiology. Mucosal-associated invariant T (MAIT) cells and γδT cells are unconventional, innate-like T cells with immunoregulatory capacity. This study aimed to investigate the potential effects of MAIT and γδT cells on the pathogenesis of OLP. Methods Circulating MAIT cells and γδT cells were identified using flow cytometry. Surface proteins including CD4, CD8, CD69, CD103, CD49d, programmed death-1 (PD-1) and its ligand PD-L1 were assessed. Cytokines containing interleukin (IL)-4, IL-17, interferon (IFN)-γ, granzyme B and tumour necrosis factor (TNF)-α released by MAIT and γδT cells were measured following PMA and ionomycin stimulation. Results Circulating MAIT and γδT cells were deficient in OLP. The percentage of CD4 + , CD69 + , CD103 + and PD-1 + MAIT cells was increased in OLP, while that of CD8 + and CD49d + MAIT cells was decreased. The percentage of CD103 + , PD-1 + and PD-L1 + γδT cells was upregulated in OLP. Both the MAIT and γδT cells in OLP produced less IL-4 than controls. The granzyme B-producing MAIT cells were increased, while γδT cells secreting granzyme B and TNF-α were reduced in OLP. IL-17 and IFN-γ in OLP MAIT and γδT cells were not significantly different from that in controls. The frequency of OLP MAIT cells and the MAIT/γδT rate were positively associated with the disease severity. Conclusion The deficient MAIT and γδT cells expressing functional proteins and releasing cytokines may play an immunoregulatory role in the pathogenesis of OLP.
研究领域:
免疫学
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炎症
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口腔疾病
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
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