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1.
Herein, a versatile and sensitive colorimetric sensor for Hg2+ based on aptamer–target specific binding and target‐mediated growth of AuNPs is reported. The 15 T bases are first designed to detect Hg2+ through T–Hg2+–T coordination. Aptamer–target binding results in the desorption of the aptamer from AuNP surface, the remaining aptamers adsorbed on AuNP surface trigger the growth of AuNPs with morphologically varied nanostructures, and then different colored solutions are formed. On this occasion, the limit of detection (LOD) of 9.6 × 10?9m is obtained. The other two aptamer strands (25‐ and 59‐mer) are designed by increasing A bases on either side and both sides of 15 T, respectively. The interaction of the binding domain and Hg2+ makes desorption of 15 T from AuNP surface, whereas excess bases not committed to the binding domain still adsorbed on AuNP surface. These excess bases control the growth of AuNPs, and enhance the sensitivity. The LODs are 4.05 and 3 × 10?9m for 25‐ and 59‐mer aptamers, respectively. In addition, the 59‐mer aptamer system is applied to identify Hg2+ in real river samples, the LOD of 6.2 × 10?9m is obtained.  相似文献   

2.
A number of studies have demonstrated that MWCNTs induce granuloma formation and fibrotic responses in vivo, and it has been recently reported that MWCNT‐induced macrophage activation and subsequent TGF‐β secretion contribute to pulmonary fibrotic responses. However, their direct effects against alveolar type‐II epithelial cells and fibroblasts and the corresponding underlying mechanisms remain largely unaddressed. Here, MWCNTs are reported to be able to directly promote fibroblast‐to‐myofibroblast conversion and the epithelial–mesenchymal transition (EMT) through the activation of the TGF‐β/Smad signaling pathway. Both of the cell transitions may play important roles in MWCNT‐induced pulmonary fibrosis. Firstly, in‐vivo and in‐vitro data show that long MWCNTs can directly interact with fibroblasts and epithelial cells, and some of them may be uptaken into fibroblasts and epithelial cells by endocytosis. Secondly, long MWCNTs can directly activate fibroblasts and increase both the basal and TGF‐β1‐induced expression of the fibroblast‐specific protein‐1, α‐smooth muscle actin, and collagen III. Finally, MWCNTs can induce the EMT through the activation of TGF‐β/Smad2 signaling in alveolar type‐II epithelial cells, from which some fibroblasts involved in pulmonary fibrosis are thought to originate. These observations suggest that the activation of the TGF‐β/Smad2 signaling plays a critical role in the process of the fibroblast‐to‐myofibroblast transition and the EMT induced by MWCNTs.  相似文献   

3.
The chemotherapy of glioblastoma is severely hindered by the immunosuppressive tumor microenvironment, especially the tumor growth factor β (TGF‐β), an immunosuppressive cytokine. In this study, it is proposed to employ RNAi‐based immunomodulation to modify the tumor immune microenvironment and improve the effect of chemotherapy. Herein, a nanotheranostic system (Angiopep LipoPCB(Temozolomide+BAP/siTGF‐β), ALBTA) with dual targeting and ROS response is established for intracranial glioblastoma treatment. The traceable nanoparticles exhibit strong siRNA condensation, high drug loading efficiency, good serum stability, and magnetic property. They can efficiently cross the blood–brain barrier and target to glioblastoma cells via receptor‐mediated transcytosis. The zwitterionic lipid (distearoyl phosphoethanol‐amine‐polycarboxybetaine lipid) in ALBTA promotes endosomal/lysosomal escape, and thus enhances the cytotoxicity of temozolomide and improves gene silencing efficiency of siTGF‐β. ALBTA significantly improves the immunosuppressive microenvironment and prolongs the survival time of glioma‐bearing mice. Moreover, ALBTA can be accurately traced by MRI in brain tumors. The study indicates that this immunochemotherapeutic platform can serve as a flexible and powerful synergistic system for treatment with brain tumors as well as other brain diseases in central nervous system.  相似文献   

4.
A tumor‐responsive nanoprobe based on a conjugated polyelectrolyte and gold nanoparticle (AuNP) hybrid was designed to response to the low pH extracellular microenvironment in tumor with light‐up fluorescence. AuNPs with positive surface charges were prepared by direct reducing Au salt with sodium borohydride and stabilized by cystamine. A pH triggered charge‐reversible polymer and a water‐soluble cationic conjugated polyelectrolyte (CPE) were sequentially deposited onto the AuNP surface through electrostatic interaction. The obtained hybrid probe is monodispersed with an average diameter of 68.3 nm by dynamic light scattering measurement. In physiological conditions (pH ≈ 7.4), the hybrid probe is almost non‐fluorescent due to the super‐quenching of CPE by AuNPs via energy/charge transfer and efficient exciton migration along the polymer backbone. When exposed to acidic extracellular microenvironments in tumor (pHe ≈ 6.5), the acid‐labile amides hydrolyze into primary amines. The generated amine groups result in strong electrostatic repulsion between CPE and AuNPs, leading to recovered probe fluorescence. The fluorescence turn‐on is further utilized for tumor extracellular acidic microenvironment imaging. In addition, under in vivo conditions, the nanosized hybrid probe exhibits specific accumulation in tumor tissue with light‐up fluorescence, which provides new opportunities for easy tumor imaging and identification.  相似文献   

5.
The assembly of plasmonic metal nanoparticles into hot spot surface‐enhanced Raman scattering (SERS) nanocluster probes is a powerful, yet challenging approach for ultrasensitive biosensing. Scaffolding strategies based on self‐complementary peptides and proteins are of increasing interest for these assemblies, but the electronic and the photonic properties of such hybrid nanoclusters remain difficult to predict and optimize. Here, split‐green fluorescence protein (sGFP) fragments are used as molecular glue and the GFP chromophore is used as a Raman reporter to assemble a variety of gold nanoparticle (AuNP) clusters and explore their plasmonic properties by numerical modeling. It is shown that GFP seeding of plasmonic nanogaps in AuNP/GFP hybrid nanoclusters increases near‐field dipolar couplings between AuNPs and provides SERS enhancement factors above 108. Among the different nanoclusters studied, AuNP/GFP chains allow near‐infrared SERS detection of the GFP chromophore imidazolinone/exocyclic C?C vibrational mode with theoretical enhancement factors of 108–109. For larger AuNP/GFP assemblies, the presence of non‐GFP seeded nanogaps between tightly packed nanoparticles reduces near‐field enhancements at Raman active hot spots, indicating that excessive clustering can decrease SERS amplifications. This study provides rationales to optimize the controlled assembly of hot spot SERS nanoprobes for remote biosensing using Raman reporters that act as molecular glue between plasmonic nanoparticles.  相似文献   

6.
The majority of cancer mortality is associated with cancer metastasis. Epithelial‐to‐mesenchymal transition (EMT) is a process by which cells attain migratory and invasive properties, eventually leading to cancer metastasis. Here, it is shown that titanium dioxide nanoparticles (nano‐TiO2), a common food additive, can induce the EMT process in colorectal cancer cells. Nano‐TiO2 exposure is observed to activate transforming growth factor‐β (TGF‐β)/mitogen‐activated protein kinase (MAPK) and wingless (Wnt) pathways, and drive the EMT process. Similarly, silica nanoparticles (nano‐SiO2) and hydroxyapatite nanoparticles (nano‐HA), as food‐based additives, can be ingested and accumulated in the stomach, and are found to be able to induce the EMT progression. The implication of this work can be profound for colorectal cancer patients where these food additives may unknowingly and unnecessarily hasten the progression of their cancers.  相似文献   

7.
Gold nanoparticles (AuNPs) are promising vehicles for cancer immunotherapy, with demonstrated efficacy in immune delivery and innate cell stimulation. Nevertheless, their potential has yet to be assessed in the in vivo application of peptide cancer vaccines. In this study, it is hypothesized that the immune distribution and adjuvant qualities of AuNPs could be leveraged to facilitate delivery of the ovalbumin (OVA) peptide antigen and the CpG adjuvant and enhance their therapeutic effect in a B16‐OVA tumor model. AuNP delivery of OVA (AuNP‐OVA) and of CpG (AuNP‐CpG) enhanced the efficacy of both agents and induced strong antigen‐specific responses. In addition, it is found that AuNP‐OVA delivery alone, without CpG, is sufficient to promote significant antigen‐specific responses, leading to subsequent anti‐tumor activity and prolonged survival in both prophylactic and therapeutic in vivo tumor models. This enhanced therapeutic efficacy is likely due to the adjuvant effect of peptide coated AuNPs, as they induce inflammatory cytokine release when cultured with bone marrow dendritic cells. Overall, AuNP‐mediated OVA peptide delivery can produce significant therapeutic benefits without the need of adjuvant, indicating that AuNPs are effective peptide vaccine carriers with the potential to permit the use of lower and safer adjuvant doses during vaccination.  相似文献   

8.
Chemical regulation of enzyme‐mimic activity of nanomaterials is challenging because it requires a precise understanding of the surface chemistry and mechanism, and rationally designed applications. Herein, Ag+‐gated peroxidase activity is demonstrated by successfully modulating surface chemistry of cetyltrimethylammonium bromide‐capped gold nanoparticles (CTAB‐AuNPs). A surface blocking effect of long‐chain molecules on surfaces of AuNPs that inhibit peroxidase activity of AuNPs is found. Ag+ ions can selectively bind on the surfaces of AuNPs and competitively destroy CTAB membrane forming Ag+@CTAB‐AuNPs complexes to result in enhanced peroxidase activity. Ag+@CTAB‐AuNPs show the highest peroxidase activity compared to similar‐sized citrate‐capped and ascorbic acid‐capped AuNPs. Ag+@CTAB‐AuNPs can potentially develop into analyte‐responsive systems and exhibit advantages in the optical sensing field. For example, the Ag+@CTAB‐AuNPs system shows an enhanced sensitivity and selectivity for acetylcholinesterase activity sensing compared to other methods.  相似文献   

9.
Pancreatic cancer is a highly aggressive malignancy that strongly resists extant treatments. The failure of existing therapies is majorly attributed to the tough tumor microenvironment (TME) limiting drug access and the undruggable targets of tumor cells. The formation of suppressive TME is regulated by transforming growth factor beta (TGF‐β) signaling, while the poor response and short survival of almost 90% of pancreatic cancer patients results from the oncogenic KRAS mutation. Hence, simultaneously targeting both the TGF‐β and KRAS pathways might dismantle the obstacles of pancreatic cancer therapy. Here, a novel sequential‐targeting strategy is developed, in which antifibrotic fraxinellone‐loaded CGKRK‐modified nanoparticles (Frax‐NP‐CGKRK) are constructed to regulate TGF‐β signaling and siRNA‐loaded lipid‐coated calcium phosphate (LCP) biomimetic nanoparticles (siKras‐LCP‐ApoE3) are applied to interfere with the oncogenic KRAS. Frax‐NP‐CGKRK successfully targets the tumor sites through the recognition of overexpressed heparan sulfate proteoglycan, reverses the activated cancer‐associated fibroblasts (CAFs), attenuates the dense stroma barrier, and enhances tumor blood perfusion. Afterward, siKras‐LCP‐ApoE3 is efficiently internalized by the tumor cells through macropinocytosis and specifically silencing KRAS mutation. Compared with gemcitabine, this sequential‐targeting strategy significantly elongates the lifespans of pancreatic tumor‐bearing animals, hence providing a promising approach for pancreatic cancer therapy.  相似文献   

10.
Synthetic unmethylated cytosine–guanine (CpG) oligodeoxynucleotides (CpG ODNs) possess high immunostimulatory activity and have been widely used as a therapeutic tool for various diseases including infection, allergies, and cancer. A variety of nanocarriers have been developed for intracellular delivery of CpG ODNs that are otherwise nonpermeable through the cellular membrane. For example, previous studies showed that gold nanoparticles (AuNPs) could efficiently deliver synthetic thiolated CpG ODNs into cultured cells and induce expression of proinflammatory cytokines. Nevertheless, the necessity of using thiolated CpG ODNs for the modification of AuNPs inevitably complicates the synthesis of the nanoconjugates and increases the cost. A new approach is demonstrated for facile assembly of AuNP‐CpG nanoconjugates for cost‐effective drug delivery. It is found that non‐thiolated, diblock ODNs containing a CpG motif and a poly‐adenine (polyA) tail can readily self‐assemble on the surface of AuNPs with controllable and tunable density. Such nanoconjugates are efficiently delivered into RAW264.7 cells and induce immune response in a Toll‐like receptor 9 (TLR9)‐dependent manner. Under optimal conditions, polyA‐CpG‐AuNPs show significantly higher immunostimulatory activity than their thiolated counterpart. In addition, the immunostimulatory activity of CpG‐AuNPs can be modulated by varying the length of the polyA tail. In vivo induction of immune responses in mice is demonstrated by using polyA‐tailed CpG‐AuNP nanoconjugates.  相似文献   

11.
Telomerase is over‐expressed in over 85% of all known human tumors. This renders the enzyme a valuable biomarker for cancer diagnosis and an important therapeutic target. The most widely used telomeric repeat amplification protocol (TRAP) assay has been questioned for telomerase detection. It is reported that human telomerase activity can be visualized by using primer‐modified Au nanoparticles. The working principle is based on the elongated primers conjugated to the gold nanoparticle (AuNP) surface, which can fold into a G‐quadruplex to protect the AuNPs from the aggregation. The developed simple and sensitive colorimetric assay can measure telomerase activity down to 1 HeLa cell µL?1. More importantly, this assay can be easily extended to high‐throughput and automatic format. The AuNP‐TS method is PCR‐free and therefore avoids the amplification‐related errors and becomes more reliable to evaluate telomerase activity. This assay has also been used for initial screening of telomerase inhibitors as anticancer drug agents.  相似文献   

12.
Multiwall carbon nanotubes (MWCNTs) have been widely used in many disciplines due to their unique physical and chemical properties, but have also raised great concerns about their possible negative health impacts, especially through occupational exposure. Although recent studies have demonstrated that MWCNTs induce granuloma formation and/or fibrotic responses in the lungs of rats or mice, their cellular and molecular mechanisms remain largely unaddressed. Here, it is reported that the TGF‐β/Smad signaling pathway can be activated by MWCNTs and play a critical role in MWCNT‐induced pulmonary fibrosis. Firstly, in vivo data show that spontaneously hypertensive (SH) rats administered long MWCNTs (20–50 μm) but not short MWCNTs (0.5–2 μm) exhibit increased fibroblast proliferation, collagen deposition and granuloma formation in lung tissue. Secondly, the in vivo experiments also indicate that only long MWCNTs can significantly activate macrophages and increase the production of transforming growth factor (TGF)‐β1, which induces the phosphorylation of Smad2 and then the expression of collagen I/III and extracellular matrix (ECM) protease inhibitors in lung tissues. Finally, the present in vitro studies further demonstrate that the TGF‐β/Smad signaling pathway is indeed necessary for the expression of collagen III in fibroblast cells. Together, these data demonstrate that MWCNTs stimulate pulmonary fibrotic responses such as fibroblast proliferation and collagen deposition in a TGF‐β/Smad‐dependent manner. These observations also suggest that tube length acts as an important factor in MWCNT‐induced macrophage activation and subsequent TGF‐β1 secretion. These in vivo and in vitro studies further highlight the potential adverse health effects that may occur following MWCNT exposure and provide a better understanding of the cellular and molecular mechanisms by which MWCNTs induce pulmonary fibrotic reactions.  相似文献   

13.
Understanding the molecular mechanisms governing nanoparticle–membrane interactions is of prime importance for drug delivery and biomedical applications. Neutron reflectometry (NR) experiments are combined with atomistic and coarse‐grained molecular dynamics (MD) simulations to study the interaction between cationic gold nanoparticles (AuNPs) and model lipid membranes composed of a mixture of zwitterionic di‐stearoyl‐phosphatidylcholine (DSPC) and anionic di‐stearoyl‐phosphatidylglycerol (DSPG). MD simulations show that the interaction between AuNPs and a pure DSPC lipid bilayer is modulated by a free energy barrier. This can be overcome by increasing temperature, which promotes an irreversible AuNP incorporation into the lipid bilayer. NR experiments confirm the encapsulation of the AuNPs within the lipid bilayer at temperatures around 55 °C. In contrast, the AuNP adsorption is weak and impaired by heating for a DSPC–DSPG (3:1) lipid bilayer. These results demonstrate that both the lipid charge and the temperature play pivotal roles in AuNP–membrane interactions. Furthermore, NR experiments indicate that the (negative) DSPG lipids are associated with lipid extraction upon AuNP adsorption, which is confirmed by coarse‐grained MD simulations as a lipid‐crawling effect driving further AuNP aggregation. Overall, the obtained detailed molecular view of the interaction mechanisms sheds light on AuNP incorporation and membrane destabilization.  相似文献   

14.
The emergence of multidrug resistant bacteria, especially biofilm‐associated Staphylococci, urgently requires novel antimicrobial agents. The antibacterial activity of ultrasmall gold nanoparticles (AuNPs) is tested against two gram positive: S. aureus and S. epidermidis and two gram negative: Escherichia coli and Pseudomonas aeruginosa strains. Ultrasmall AuNPs with core diameters of 0.8 and 1.4 nm and a triphenylphosphine‐monosulfonate shell (Au0.8MS and Au1.4MS) both have minimum inhibitory concentration (MIC) and minimum bactericidal concentration of 25 × 10?6m [Au]. Disc agar diffusion test demonstrates greater bactericidal activity of the Au0.8MS nanoparticles over Au1.4MS. In contrast, thiol‐stabilized AuNPs with a diameter of 1.9 nm (AuroVist) cause no significant toxicity in any of the bacterial strains. Ultrasmall AuNPs cause a near 5 log bacterial growth reduction in the first 5 h of exposure, and incomplete recovery after 21 h. Bacteria show marked membrane blebbing and lysis in biofilm‐associated bacteria treated with ultrasmall AuNP. Importantly, a twofold MIC dosage of Au0.8MS and Au1.4MS each cause around 80%–90% reduction in the viability of Staphylococci enveloped in biofilms. Altogether, this study demonstrates potential therapeutic activity of ultrasmall AuNPs as an effective treatment option against staphylococcal infections.  相似文献   

15.
This study reveals the antibacterial and catalytic activity of biogenic gold nanoparicles (AuNPs) synthesised by biomass of Trichoderma harzianum. The antibacterial activity of AuNPs was analysed by the means of growth curve, well diffusion and colony forming unit (CFU) count methods. The minimum inhibitory concentration of AuNPs was 20 µg/ml. AuNPs at 60 µg/ml show effective antibacterial activity as optical absorption was insignificant. The well diffusion and CFU methods were also applied to analyse the effect of various concentration of AuNPs. Further, the catalytic activity of AuNPs was analysed against methylene blue (MB) as a model pollutant in water. MB was degraded 39% in 30 min in the presence of AuNPs and sodium borohydrate and the rate constant (k) was found to be 0.2 × 10−3 s−1. This shows that the biogenic AuNP is an effective candidate for antibacterial and catalytic degradation of toxic pollutants.Inspec keywords: antibacterial activity, catalysis, nanoparticles, gold, nanofabrication, biomedical materials, nanomedicine, renewable materials, surface diffusion, dyes, water pollution, reaction rate constants, toxicologyOther keywords: antibacterial activity, catalytic activity, biogenic gold nanoparticles, Trichoderma harzianum, biomass, growth curve, diffusion, colony forming unit count methods, minimum inhibitory concentration, optical absorption, CFU methods, methylene blue, water pollutant, catalytic degradation, toxic pollutants, sodium borohydrate, rate constant, Au  相似文献   

16.
Bacterial type IV pili (T4P) are polymeric protein nanofibers that have diverse biological roles. Their unique physicochemical properties mark them as a candidate biomaterial for various applications, yet difficulties in producing native T4P hinder their utilization. Recent effort to mimic the T4P of the metal‐reducing Geobacter sulfurreducens bacterium led to the design of synthetic peptide building blocks, which self‐assemble into T4P‐like nanofibers. Here, it is reported that the T4P‐like peptide nanofibers efficiently bind metal oxide particles and reduce Au ions analogously to their native counterparts, and thus give rise to versatile and multifunctional peptide–metal nanocomposites. Focusing on the interaction with Au ions, a combination of experimental and computational methods provides mechanistic insight into the formation of an exceptionally dense Au nanoparticle (AuNP) decoration of the nanofibers. Characterization of the thus‐formed peptide–AuNPs nanocomposite reveals enhanced thermal stability, electrical conductivity from the single‐fiber level up, and substrate‐selective adhesion. Exploring its potential applications, it is demonstrated that the peptide–AuNPs nanocomposite can act as a reusable catalytic coating or form self‐supporting immersible films of desired shapes. The films scaffold the assembly of cardiac cells into synchronized patches, and present static charge detection capabilities at the macroscale. The study presents a novel T4P‐inspired biometallic material.  相似文献   

17.
Gold nanoparticles (AuNP) have been widely used for drug delivery and have recently been explored for applications in cancer immunotherapy. Although AuNPs are known to accumulate heavily in the spleen, the particle distribution within immune cells has not been thoroughly studied. Here, cellular distribution of Cy5 labeled 50 nm AuNPs is characterized within the immune populations of the spleen from naïve and tumor bearing mice using flow cytometry. Surprisingly, approximately 30% of the detected AuNPs are taken up by B cells at 24 h, with about 10% in granulocytes, 18% in dendritic cells, and 8% in T cells. In addition, 3% of the particles are detected within myeloid derived suppressor cells, an immune suppressive population that could be targeted for cancer immunotherapy. Furthermore, it is observed that, over time, the particles traveled from the red pulp and marginal zone to the follicles of the spleen. Taking into consideration that the particle cellular distribution does not change at 1, 6 and 24 h, it is highly suggestive that the immune populations carry the particles and migrate through the spleen instead of the particles migrating through the tissue by cell‐cell transfer. Finally, no difference is observed in particle distribution between naïve and tumor bearing mice in the spleen, and nanoparticles are detected within 0.7% of dendritic cells of the tumor microenvironment. Overall, these results can help inform and influence future AuNP delivery design criteria including future applications for nanoparticle‐mediated immunotherapy.  相似文献   

18.
Early detection of cancer is likely to be one of the most effective means of reducing the cancer mortality rate. Hence, simple and ultra‐quick methods for noninvasive detection of early‐stage tumors are highly sought‐after. In this study, a nanobiosensing platform with a rapid response time of nearly 30 s is introduced for the detection of matrilysin—the salivary gland cancer biomarker—with a limit of detection as low as 30 nm . This sensing platform is based on matrilysin‐digestible peptides that bridge gold nanoparticle (AuNPs) cores (≈30–50 nm) and carbon quantum dot (CDs) satellites (≈9 nm). A stepwise synthesis procedure is used for self‐assembly of AuNP‐peptide‐CDs, ensuring their long‐term stability. The AuNP‐peptide‐CDs produce ideal optical signals, with noticeable fluorescence quenching effects. Upon peptide cleavage by matrilysin, CDs leave the surface of AuNPs, resulting in ultra‐fast detectable violet and visible fluorescent signals.  相似文献   

19.
A new gold‐nanoparticle (AuNP)‐based strategy to dynamically modulate the activity of DNA polymerases and realize a hot‐start (HS)‐like effect in the polymerase chain reaction (PCR) is reported, which effectively prevents unwanted nonspecific amplification and improves the performance of PCRs. A high‐fidelity Pfu DNA polymerase is employed as the model system. Interestingly, AuNPs inactivate the polymerase activity of Pfu at low temperature, thus resembling an antibody‐based HS PCR. This inhibition effect of AuNPs is demonstrated for the preamplification polymerization activity of the PCR, which largely suppresses nonspecific amplification at temperatures between 30 and 60 °C and leads to highly specific and sensitive PCR amplification with Pfu. Significantly, the fidelity of Pfu is not sacrificed in the presence of AuNPs. Therefore, this AuNP‐based HS strategy provides a straightforward and potentially versatile approach to realize high‐performance PCR amplification.  相似文献   

20.
We investigate the sliding friction of HUVEC monolayers cultured on PNaSS gel, intending to elucidate the role of glycocalyx on the surface of ECs in friction reduction. Three sets of HUVEC monolayers are investigated: an as‐cultured HUVEC monolayer; a HUVEC monolayer treated with TGF‐β1, which increases the glycocalyx by 148%; and a HUVEC monolayer treated with heparinase I, which reduces the glycocalyx by 57%. When being slid on a flat, glass surface, the frictional stress of the HUVEC monolayer decreases in the order: heparinase‐I‐treated > as‐cultured > TGF‐β1‐treated samples. The results suggest that glycocalyx may play a role in reducing the friction of endothelial cell monolayer.  相似文献   

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