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学者姓名：张静
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Abstract ：
As ubiquitous transport nanovesicles in cell biology, plant exosome-like vesicles (PELVs) have enormous potential to deliver drugs safely and effectively. Drug encapsulation and mechanical stability of vesicles are key limitations influencing their delivery efficiency. However, common methods (i.e., ultrasound, electroporation) for drug loading inevitably affect the inherent vesicle characteristics, which influence their stability, leakproof nature, cellular internalization, and tumor penetration. Herein, in order to balance this contradiction, we put forward a strategy to skillfully remodel aloe exosome-like vesicles (AELVs) through indocyanine green (ICG)-induced hypotonic stress during endogenous drug loading. We observe that the rigidity of AELVs is enhanced with the accumulation of long hydrocarbon chain lipids under ICG-induced hypotonic stress. Synchronously, ICG is also loaded into AELVs (ICG/AELVs, IAs), which effectively prevents secondary damage during drug loading. More interestingly, we find that hypotonic stress promotes IA secretion with less intravesicular protein, which is beneficial to enlarge their inner space for more drug loading. The IAs show great storage stability, leakproof, and antidegradation performance. Compared with control AELVs, IAs with higher rigidity are more liable to penetrate into the tumor. IAs further modifying with the AS1411 aptamer (AS1411-IAs, AIAs) exhibit high tumor targeting in vivo. After intravenous administration, the 4T1 tumor is obviously inhibited by AIAs plus NIR irradiation, which effectively improves the survival rate of tumor-bearing mice. Overall, we systematically explore the effects of drug-induced osmotic stress on PELVs during endogenous drug loading and achieve efficient tumor therapy. This work simplifies the process of drug loading in PELVs and enhances their plasticity, which provides a promising perspective for PELV-based drug delivery and clinical application.
Keyword ：
aloe exosome-like vesicles aloe exosome-like vesicles endogenous drug loading endogenous drug loading hypotonic stress hypotonic stress targeted cancer therapy targeted cancer therapy vesicle mechanical stability vesicle mechanical stability
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| GB/T 7714 | Zeng, Lupeng , Shi, Wanhua , Chen, Kewen et al. Indocyanine Green Aggregation-Induced Hypotonic Stress to Remodel Aloe Exosome-like Vesicles for Enhanced Tumor Penetration and Phototherapy [J]. | ACS NANO , 2025 , 19 (16) : 15425-15443 . |
| MLA | Zeng, Lupeng et al. "Indocyanine Green Aggregation-Induced Hypotonic Stress to Remodel Aloe Exosome-like Vesicles for Enhanced Tumor Penetration and Phototherapy" . | ACS NANO 19 . 16 (2025) : 15425-15443 . |
| APA | Zeng, Lupeng , Shi, Wanhua , Chen, Kewen , Wang, Kun , Dai, Yaping , Cheng, Xin et al. Indocyanine Green Aggregation-Induced Hypotonic Stress to Remodel Aloe Exosome-like Vesicles for Enhanced Tumor Penetration and Phototherapy . | ACS NANO , 2025 , 19 (16) , 15425-15443 . |
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To overcome the low efficacy of conventional monotherapeutic approaches that use a single drug, functional nanocarriers loaded with an amalgamation of anticancer drugs have been promising in cancer therapy. Herein, aloe-derived nanovesicles (gADNVs) are modified with an active integrin-targeted peptide (Arg-Gly-Asp, RGD) by the postinsertion technique to deliver indocyanine green (ICG) and doxorubicin (DOX) for efficient breast cancer therapy. We presented for the first time that the pi-pi stacking interaction can turn the "competitive" relationship of ICG and DOX inside gADNVs into a "cooperative" relationship and enhance their loading efficiency. The dual-drug codelivery nanosystem, denoted as DIARs, was well stable and leakproof, exhibiting high tumor-targeting capability both in vitro and in vivo. Meanwhile, this nanosystem showed significant inhibition of cell growth and migration and induced cell apoptosis with the combination of phototherapy and chemotherapy. Intravenous administration of DIARs exhibited high therapeutic efficacy in a 4T1 tumor-bearing mouse model and exhibited no obvious damage to other organs. Overall, our DIAR nanosystem constitutively integrated the natural and economical gADNVs, pi-pi stacking interaction based on efficient drug loading, and tumor-targeted RGD modification to achieve an effective combination therapy for breast cancer.
Keyword ：
aloe-derived nanovesicles aloe-derived nanovesicles breast cancer therapy breast cancer therapy pi-pi stacking interaction pi-pi stacking interaction stable and leakproof stable and leakproof targeted drug delivery targeted drug delivery
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| GB/T 7714 | Zeng, Lupeng , Shi, Wanhua , Wang, Huaying et al. Codelivery of π-π Stacked Dual Anticancer Drugs Based on Aloe-Derived Nanovesicles for Breast Cancer Therapy [J]. | ACS APPLIED MATERIALS & INTERFACES , 2022 , 14 (24) : 27686-27702 . |
| MLA | Zeng, Lupeng et al. "Codelivery of π-π Stacked Dual Anticancer Drugs Based on Aloe-Derived Nanovesicles for Breast Cancer Therapy" . | ACS APPLIED MATERIALS & INTERFACES 14 . 24 (2022) : 27686-27702 . |
| APA | Zeng, Lupeng , Shi, Wanhua , Wang, Huaying , Cheng, Xin , Chen, Tingting , Wang, Liang Liang et al. Codelivery of π-π Stacked Dual Anticancer Drugs Based on Aloe-Derived Nanovesicles for Breast Cancer Therapy . | ACS APPLIED MATERIALS & INTERFACES , 2022 , 14 (24) , 27686-27702 . |
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It remains a huge challenge to integrate the sensitivity, stability, reproducibility, and anti-fouling ability of electrochemical biosensors for practical applications. Herein, we propose a self-assembled electrode combining hexanethiol (HT),poly-adenine (poly-A), and cholesteryl-modified DNA to meet this challenge. HT can tightly pack at the electrode interface to form a hydrophobic self-assembled monolayer (SAM), effectively improving the stability and signal-to-noise ratio (SNR) of electrochemical detection. Cholesteryl-modified DNA was immobilized at theelectrode through the hydrophobic interaction with HT to avoidthe competition between the SAM and the DNA probe on the goldsite. Thus, the assembly efficiency and uniformity of the DNAprobe as well as the detection reproducibility were increasedremarkedly. Poly-A was added on the HT assembled electrode to occupy the unreacted sites of gold to further enhance the anti-fouling ability. The combination of HT and poly-A allows the electrode to ensure favorable anti-fouling ability without sacrificing the detection performance. On this basis, we proposed a dual-signal amplification electrochemical biosensor for the detection of exosomal microRNAs, which showed excellent sensitivity with a detection limit down to 1.46 aM. Importantly, this method has been successfully applied to detect exosomal microRNA-21 in cells and human serum samples, proving its potential utility in cancer diagnosis.
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| GB/T 7714 | Chen, Guanyu , Chen, Wenqian , Xu, Lilan et al. Sensitive, Highly Stable, and Anti-Fouling Electrode with Hexanethiol and Poly-A Modification for Exosomal microRNA Detection [J]. | ANALYTICAL CHEMISTRY , 2022 , 94 (13) : 5382-5391 . |
| MLA | Chen, Guanyu et al. "Sensitive, Highly Stable, and Anti-Fouling Electrode with Hexanethiol and Poly-A Modification for Exosomal microRNA Detection" . | ANALYTICAL CHEMISTRY 94 . 13 (2022) : 5382-5391 . |
| APA | Chen, Guanyu , Chen, Wenqian , Xu, Lilan , Jin, Huixuan , Sun, Weiming , Lan, Jianming et al. Sensitive, Highly Stable, and Anti-Fouling Electrode with Hexanethiol and Poly-A Modification for Exosomal microRNA Detection . | ANALYTICAL CHEMISTRY , 2022 , 94 (13) , 5382-5391 . |
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Purpose: In recent years, a variety of nanoparticles with excellent anticancer and delivery properties have emerged for cancer therapy. However, potential toxicity, high production cost and complex preparation procedures have been obstacles to their use in biomedicine. Here, we obtained cucumber-derived nanovesicles (CDNVs) at high yield and low cost by simple juicing and ultracentrifugation. The anticancer effects of CDNVs were evaluated in vitro and in vivo. Methods: Transmission electron microscope, nanoparticle tracking analysis and laser particle size analysis were used to characterize the morphology, diameter and zeta potential of CDNVs, respectively. The anticancer effects of CDNVs in vitro were evaluated by MTT and apoptosis assays. The mechanism was further explored by measuring the protein levels of signal transducer and activator of transcription 3 pathway, reactive oxygen species, cell cycle distribution and caspase activity. In-vivo anticancer efficacy was evaluated by measuring tumor volume and weight of mice in three different treatment groups (CDNVs, cucurbitacin B and PBS). Results: CDNVs inhibited proliferation of human non-small cell lung cancer cells by suppressing signal transducer and activator of transcription 3 activation, generating reactive oxygen species, promoting cell cycle arrest, and activating the caspase pathway. These CDNVs exhibited strong anticancer effects both in vitro and in vivo, and reduced the rate of tumor growth without obvious toxicity to mouse visceral organs. Compared with an equivalent dose of cucurbitacin B, CDNVs exerted stronger anticancer effects in vitro and in vivo. Conclusion: These results demonstrate that CDNVs suppress tumor growth. This study addresses the development of cancer therapeutic drugs using plant-derived nanovesicles that are cost-efficient, simple to produce in high yields, and provide an alternative approach to drug isolation that may help advance sustainability of medicinal plants.
Keyword ：
anticancer anticancer cucurbitacin B cucurbitacin B ROS ROS STAT3 STAT3
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| GB/T 7714 | Chen, Tingting , Ma, Bingxiang , Lu, Shi et al. Cucumber-Derived Nanovesicles Containing Cucurbitacin B for Non-Small Cell Lung Cancer Therapy [J]. | INTERNATIONAL JOURNAL OF NANOMEDICINE , 2022 , 17 : 3583-3599 . |
| MLA | Chen, Tingting et al. "Cucumber-Derived Nanovesicles Containing Cucurbitacin B for Non-Small Cell Lung Cancer Therapy" . | INTERNATIONAL JOURNAL OF NANOMEDICINE 17 (2022) : 3583-3599 . |
| APA | Chen, Tingting , Ma, Bingxiang , Lu, Shi , Zeng, Lupeng , Wang, Huaying , Shi, Wanhua et al. Cucumber-Derived Nanovesicles Containing Cucurbitacin B for Non-Small Cell Lung Cancer Therapy . | INTERNATIONAL JOURNAL OF NANOMEDICINE , 2022 , 17 , 3583-3599 . |
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Exosomal miRNAs, as potential biomarkers in liquid biopsy for cancer early diagnosis, have aroused widespread concern. Herein, an electrochemical biosensor based on DNA "nano-bridge" was designed and applied to detect exosomal microRNA-21 (miR-21) derived from breast cancer cells. In brief, the target miR-21 can specifically open the hairpin probe 1(HP1) labeled on the gold electrode (GE) surface through strand displacement reaction. Thus the exposed loop region of HP1 can act as an initiator sequence to activate the hybridization chain reaction (HCR) between two kinetically trapped hairpin probes: HP2 immobilized on the GE surface and biotin labeled HP3 in solution. Cascade HCR leads to the formation of DNA "nano-bridge" tethered to the GE surface with a great deal of "piers". Upon addition of avidin-modified horseradish peroxidase (HRP), numerous HRP were bound to the formed "nano-bridge" through biotinavidin interaction to arouse tremendous current signal. In theory, only a single miR-21 is able to trigger the continuous HCR between HP2 and HP3 until all of the HP2 are exhausted. Therefore the proposed biosensor achieved ultrahigh sensitivity toward miR-21 with the detection limit down to 168 amol/L, as well as little cross-hybridization even at the single-base-mismatched level. Successful attempts were also made in the detection of exosomal miR-21 obtained from the MCF-7 of breast cancer cell line. To our knowledge, this is the first attempt to built horizontal DNA nano-structure on the electrode surface for exosomal miRNAs detection. In a word, the high sensitivity, selectivity, low cost make the proposed method hold great potential application for early point-of-care (POC) diagnostics of cancer. (C) 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Keyword ：
DNA "nano-bridge" DNA "nano-bridge" Electrochemical biosensor Electrochemical biosensor Exosomal miRNAs Exosomal miRNAs Hybridization chain reaction Hybridization chain reaction Signal amplification reaction Signal amplification reaction
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| GB/T 7714 | Zhang, Jing , Hou, Meifeng , Chen, Guanyu et al. An electrochemical biosensor based on DNA "nano-bridge" for amplified detection of exosomal microRNAs [J]. | CHINESE CHEMICAL LETTERS , 2021 , 32 (11) : 3474-3478 . |
| MLA | Zhang, Jing et al. "An electrochemical biosensor based on DNA "nano-bridge" for amplified detection of exosomal microRNAs" . | CHINESE CHEMICAL LETTERS 32 . 11 (2021) : 3474-3478 . |
| APA | Zhang, Jing , Hou, Meifeng , Chen, Guanyu , Mao, Huifang , Chen, Wenqian , Wang, Wenshen et al. An electrochemical biosensor based on DNA "nano-bridge" for amplified detection of exosomal microRNAs . | CHINESE CHEMICAL LETTERS , 2021 , 32 (11) , 3474-3478 . |
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Background Cancer is one of the devastating diseases in the world. The development of nanocarrier provides a promising perspective for improving cancer therapeutic efficacy. However, the issues with potential toxicity, quantity production, and excessive costs limit their further applications in clinical practice. Results Herein, we proposed a nanocarrier obtained from aloe with stability and leak-proofness. We isolated nanovesicles from the gel and rind of aloe (gADNVs and rADNVs) with higher quality and yield by controlling the final centrifugation time within 20 min, and modulating the viscosity at 2.98 mPa S and 1.57 mPa S respectively. The gADNVs showed great structure and storage stability, antioxidant and antidetergent capacity. They could be efficiently taken up by melanoma cells, and with no toxicity in vitro or in vivo. Indocyanine green (ICG) loaded in gADNVs (ICG/gADNVs) showed great stability in both heating system and in serum, and its retention rate exceeded 90% after 30 days stored in gADNVs. ICG/gADNVs stored 30 days could still effectively damage melanoma cells and inhibit melanoma growth, outperforming free ICG and ICG liposomes. Interestingly, gADNVs showed prominent penetrability to mice skin which might be beneficial to noninvasive transdermal administration. Conclusions Our research was designed to simplify the preparation of drug carrier, and reduce production cost, which provided an alternative for the development of economic and safe drug delivery system.
Keyword ：
Aloe derived nanovesicles Aloe derived nanovesicles Cancer therapy Cancer therapy Drug carriers Drug carriers Indocyanine green Indocyanine green Stability Stability
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| GB/T 7714 | Zeng, Lupeng , Wang, Huaying , Shi, Wanhua et al. Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy [J]. | JOURNAL OF NANOBIOTECHNOLOGY , 2021 , 19 (1) . |
| MLA | Zeng, Lupeng et al. "Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy" . | JOURNAL OF NANOBIOTECHNOLOGY 19 . 1 (2021) . |
| APA | Zeng, Lupeng , Wang, Huaying , Shi, Wanhua , Chen, Lingfan , Chen, Tingting , Chen, Guanyu et al. Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy . | JOURNAL OF NANOBIOTECHNOLOGY , 2021 , 19 (1) . |
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Abstract ：
Exosomal miRNAs,as potential biomarkers in liquid biopsy for cancer early diagnosis,have aroused widespread concern.Herein,an electrochemical biosensor based on DNA "nano-bridge" was designed and applied to detect exosomal microRNA-21 (miR-21) derived from breast cancer cells.In brief,the target miR-21 can specifically open the hairpin probe 1(HP1) labeled on the gold electrode (GE) surface through strand displacement reaction.Thus the exposed loop region of HP1 can act as an initiator sequence to ac-tivate the hybridization chain reaction (HCR) between two kinetically trapped hairpin probes:HP2 immo-bilized on the GE surface and biotin labeled HP3 in solution.Cascade HCR leads to the formation of DNA"nano-bridge" tethered to the GE surface with a great deal of "piers".Upon addition of avidin-modified horseradish peroxidase (HRP),numerous HRP were bound to the formed "nano-bridge" through biotin-avidin interaction to arouse tremendous current signal.In theory,only a single miR-21 is able to trigger the continuous HCR between HP2 and HP3 until all of the HP2 are exhausted.Therefore the proposed biosensor achieved ultrahigh sensitivity toward miR-21 with the detection limit down to 168 amol/L,as well as little cross-hybridization even at the single-base-mismatched level.Successful attempts were also made in the detection of exosomal miR-21 obtained from the MCF-7 of breast cancer cell line.To our knowledge,this is the first attempt to built horizontal DNA nano-structure on the electrode surface for exosomal miRNAs detection.In a word,the high sensitivity,selectivity,low cost make the proposed method hold great potential application for early point-of-care (POC) diagnostics of cancer.
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| GB/T 7714 | Jing Zhang , Meifeng Hou , Guanyu Chen et al. An electrochemical biosensor based on DNA "nano-bridge" for amplified detection of exosomal microRNAs [J]. | 中国化学快报（英文版） , 2021 , 32 (11) : 3474-3478 . |
| MLA | Jing Zhang et al. "An electrochemical biosensor based on DNA "nano-bridge" for amplified detection of exosomal microRNAs" . | 中国化学快报（英文版） 32 . 11 (2021) : 3474-3478 . |
| APA | Jing Zhang , Meifeng Hou , Guanyu Chen , Huifang Mao , Wenqian Chen , Wenshen Wang et al. An electrochemical biosensor based on DNA "nano-bridge" for amplified detection of exosomal microRNAs . | 中国化学快报（英文版） , 2021 , 32 (11) , 3474-3478 . |
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The detection of exosomal microRNAs (miRNAs) derived from cancer cells with sensitive and selective methods has stimulated increasing interest due to its potential utility in the application of tumor diagnosis. Here, we developed a ratiometric electrochemical DNA biosensor based on a locked nucleic acid (LNA)-modifled "Y" shape-like structure for the detection of exosomal miRNA-21 (miR-21). When miR-21 is present, the LNA-assisted strand displacement reaction on the "Y" shape-like structure is activated, leading to a structure change and augmentation of the signal ratio, which reflects the different distances between the electrode surface and two electroactive molecules labeled on the "Y" shape-like structure. With this dual signal ratiometric method, the biosensor shows high accuracy and sensitivity with a limit of detection as low as 2.3 fM. Moreover, because of the logarithm of the signal ratio displays a linear relationship with the logarithm of the miR-21 concentration, the biosensor is stable enough to be used in the detection of miR-21 in MCF-7 cell-derived exosomes. In addition, the biosensor shows good selectivity even in the detection of even a single base-mismatched target due to the LNA-assisted strand displacement reaction. Notably, the sensor is both regenerative and robust. In brief, the high sensitivity and selectivity, combined with the low cost of the glassy carbon electrode, make this biosensor a promising tool for the development of point-of-care testing in cancer.
Keyword ：
Exosomal microRNA Exosomal microRNA Locked nucleic acid Locked nucleic acid Ratiometric electrochemical DNA biosensor Ratiometric electrochemical DNA biosensor Strand displacement reaction Strand displacement reaction
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| GB/T 7714 | Luo, Lipei , Wang, Liangliang , Zeng, Lupeng et al. A ratiometric electrochemical DNA biosensor for detection of exosomal MicroRNA [J]. | TALANTA , 2020 , 207 . |
| MLA | Luo, Lipei et al. "A ratiometric electrochemical DNA biosensor for detection of exosomal MicroRNA" . | TALANTA 207 (2020) . |
| APA | Luo, Lipei , Wang, Liangliang , Zeng, Lupeng , Wang, Yuru , Weng, Yunping , Liao, Yijuan et al. A ratiometric electrochemical DNA biosensor for detection of exosomal MicroRNA . | TALANTA , 2020 , 207 . |
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As non-invasive biomarkers, exosomes are of great significance to diseases diagnosis. However, sensitive and accurate detection of exosomes still remains technical challenges. Herein, inspired by nature's "one-to-many" concept, we design a biosensor mimicking the cactus with numerous thorns to detect exosomes. The biosensor is composed of CD63 antibodies, resembling the roots of cactus, to capture exosomes, and the exosomes resemble the stems. Cholesterol-labeled DNA (DNA anchor) binding to streptavidin modified horseradish peroxidase (HRP) can insert into exosomes membrane, which seems the thorns. The readout signal is produced through HRP-catalyzed hydrogen peroxide (H2O2) mediated oxidation of 1,4-phenylenediamine (PPD) to form 2,5-diamino-NN'-bis-(p-aminophenyl)-1,4-benzoquinone di-imine (PPDox). The PPDox can quench fluorescence of fluorescein through inner filter effect (IFE), which provides fluorescent signal for exosomes detection. Based on this principle, the obtained exosomes solution is qualitatively and quantitatively analyzed by our biosensor, with the comparison to current standard methods by nanoparticle tracking analysis (NTA) and commercial enzymelinked immunosorbent assay (ELISA) kit. The linear range is from 1.0 x 10(4) to 5.0 x 10(5) particles mu L-1 with the limit of detection 3.40 x 10(3) particles mu L-1 and 3.12 x 10(3) particles mu L-1 for colorimetric and fluorescent assays, respectively. Meanwhile, our biosensor exhibits good selectivity, and can eliminate the interference from proteins. This dual-modal biosensor shows favorable performance towards analytical application in clinic samples, pushing one step further towards practical clinical use.
Keyword ：
Colorimetric and fluorescent biosensor Colorimetric and fluorescent biosensor DNA anchor DNA anchor Exosomes Exosomes Nature-inspired Nature-inspired
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| GB/T 7714 | Xia, Yaokun , Chen, Tingting , Chen, Guanyu et al. A nature-inspired colorimetric and fluorescent dual-modal biosensor for exosomes detection [J]. | TALANTA , 2020 , 214 . |
| MLA | Xia, Yaokun et al. "A nature-inspired colorimetric and fluorescent dual-modal biosensor for exosomes detection" . | TALANTA 214 (2020) . |
| APA | Xia, Yaokun , Chen, Tingting , Chen, Guanyu , Weng, Yunping , Zen, Lupeng , Liao, Yijuan et al. A nature-inspired colorimetric and fluorescent dual-modal biosensor for exosomes detection . | TALANTA , 2020 , 214 . |
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Compared with plenty of single-functional molecules, multifunctional molecules are scarce and have high demand in further research. In this work, a multifunctional molecule called 10-methyl-2-amino-acridone (MAA) is presented. Interestingly, MAA simultaneously features electrochemistry, two-photon fluorescence, visible-light-induced oxidase mimic, and photoelectrochemistry (PEC) activity, and the related properties are studied in detailed. Multiple functions integrated into one molecule allow MAA to become a versatile signal probe. Therefore, the MAA acted as an electrochemical indicator to detect exosomal total protein with high sensitivity at first. In addition, MAA is used for one- or two-photon fluorescence imaging in vitro and in vivo, including cells, three-dimensional (3D) tumor spheroids, zebrafish, and exosomes. The results suggest that MAA not only possesses favorable photostability, but it is also suitable for imaging in deep tissue. Furthermore, the visible-light-induced oxidase mimic and photoelectrochemical activities of MAA are selectively inhibited by Cu2+, and the relevant mechanism is carefully analyzed. On the basis of this phenomenon, we develop a dual-modal detection strategy for detection of Cu2+ in river water. Compared with a single signal readout model, this strategy is able to avoid false positive and negative detection through two series of data mutually validating each other. Therefore, our study shows that the "multiple-in-one" MAA provides a blueprint for the investigation and application of a multifunctional organic molecule.
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| GB/T 7714 | Xia, Yaokun , He, Wenhui , Li, Juan et al. Acridone Derivate Simultaneously Featuring Multiple Functions and Its Applications [J]. | ANALYTICAL CHEMISTRY , 2019 , 91 (13) : 8406-8414 . |
| MLA | Xia, Yaokun et al. "Acridone Derivate Simultaneously Featuring Multiple Functions and Its Applications" . | ANALYTICAL CHEMISTRY 91 . 13 (2019) : 8406-8414 . |
| APA | Xia, Yaokun , He, Wenhui , Li, Juan , Zeng, Lupeng , Chen, Tingting , Liao, Yijuan et al. Acridone Derivate Simultaneously Featuring Multiple Functions and Its Applications . | ANALYTICAL CHEMISTRY , 2019 , 91 (13) , 8406-8414 . |
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