PAMAM

PAMAM
  • 文章类型: Journal Article
    纳米技术带来了药物设计的重大进步,预防革命,诊断,治疗各种疾病。纳米技术的战略利用,以提高药物负荷,delivery,释放引起了越来越多的关注,利用这些系统提供的增强的物理和化学性质。聚酰胺胺(PAMAM)树枝状聚合物在药物递送中至关重要,然而,还有进一步加强的空间。在这项研究中,我们将PAMAM树枝状聚合物与壳聚糖(CS)缀合以增强肿瘤细胞的细胞内化。具体来说,最初将多柔比星(DOX)加载到PAMAM树枝状聚合物中以通过分子间力形成DOX加载的PAMAM(DOX@PAMAM)复合物。随后,将CS连接到负载DOX的PAMAM树枝状聚合物上,以通过希夫碱反应通过戊二醛交联产生负载DOX的CS缀合的PAMAM(DOX@CS@PAMAM)。使用傅里叶变换红外(FTIR)光谱对所得DOX@CS@PAMAM配合物进行了全面表征,透射电子显微镜(TEM),和动态光散射(DLS)。值得注意的是,而在酸性环境中DOX@CS@PAMAM的药物释放曲线不如DOX@PAMAM,DOX@CS@PAMAM证明了有效的酸响应药物释放,在25小时内累积释放70%归因于亚胺键。最重要的是,与DOX@PAMAM相比,DOX@CS@PAMAM表现出显著的选择性细胞内化速率和抗肿瘤功效,通过细胞活力试验验证,荧光成像,和流式细胞术分析。总之,DOX@CS@PAMAM与未结合的PAMAM树枝状聚合物相比,具有优异的抗肿瘤作用,从而扩大了基于树枝状聚合物的纳米药物的范围,具有增强的治疗功效和在癌症治疗中的有希望的应用。
    Nanotechnology has ushered in significant advancements in drug design, revolutionizing the prevention, diagnosis, and treatment of various diseases. The strategic utilization of nanotechnology to enhance drug loading, delivery, and release has garnered increasing attention, leveraging the enhanced physical and chemical properties offered by these systems. Polyamidoamine (PAMAM) dendrimers have been pivotal in drug delivery, yet there is room for further enhancement. In this study, we conjugated PAMAM dendrimers with chitosan (CS) to augment cellular internalization in tumor cells. Specifically, doxorubicin (DOX) was initially loaded into PAMAM dendrimers to form DOX-loaded PAMAM (DOX@PAMAM) complexes via intermolecular forces. Subsequently, CS was linked onto the DOX-loaded PAMAM dendrimers to yield CS-conjugated PAMAM loaded with DOX (DOX@CS@PAMAM) through glutaraldehyde crosslinking via the Schiff base reaction. The resultant DOX@CS@PAMAM complexes were comprehensively characterized using Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Notably, while the drug release profile of DOX@CS@PAMAM in acidic environments was inferior to that of DOX@PAMAM, DOX@CS@PAMAM demonstrated effective acid-responsive drug release, with a cumulative release of 70% within 25 h attributed to the imine linkage. Most importantly, DOX@CS@PAMAM exhibited significant selective cellular internalization rates and antitumor efficacy compared to DOX@PAMAM, as validated through cell viability assays, fluorescence imaging, and flow cytometry analysis. In summary, DOX@CS@PAMAM demonstrated superior antitumor effects compared to unconjugated PAMAM dendrimers, thereby broadening the scope of dendrimer-based nanomedicines with enhanced therapeutic efficacy and promising applications in cancer therapy.
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  • 文章类型: Journal Article
    核酸检测是临床诊断的重要工具。样品的纯化是核酸检测过程中最耗时的步骤,会影响检测结果。这里,我们开发了一种基于表面修饰的核酸纯化方法,并设计了一套随附的离心设备和芯片,以将核酸纯化的步骤整合在一个平台上。以HeLa细胞和HPV16型为样品的实验结果表明,该方法具有良好的核酸纯化能力,配套设备大大简化了实验人员在整个过程中的操作。总的来说,我们的设备可以提高核酸纯化的效率,适用于更大规模的临床检测。
    Nucleic acid detection is an important tool for clinical diagnosis. The purification of the sample is the most time-consuming step in the nucleic acid testing process and will affect the results of the assay. Here, we developed a surface modification-based nucleic acid purification method and designed an accompanying set of centrifugation equipment and chips to integrate the steps of nucleic acid purification on a single platform. The results of experiments with HeLa cells and HPV type 16 as samples showed that the mentioned method had good nucleic acid purification capability and the accompanying equipment greatly simplified the operation of the experimenters in the whole process. Overall, our equipment can improve the efficiency of nucleic acid purification and is suitable for application in larger-scale clinical assays.
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  • 文章类型: Journal Article
    对曲霉毒素A(OTA)的灵敏检测是重要且必不可少的,因为OTA可能对人类和动物健康构成风险。这里,我们开发了一种用于OTA分析的电化学aptasensor,使用聚酰胺胺(PAMAM)树枝状聚合物作为信号放大器。作为承运人,PAMAM具有许多可与硫醇化互补链DNA(cDNA)偶联的伯氨基,允许它识别与辣根过氧化物酶(HRP)修饰的金纳米颗粒(AuNP)表面结合的适体,从而提高了aptasensor的灵敏度。当监测阳性样本时,OTA通过特异性识别被固定在HRP缀合的AuNP表面上的适体捕获,之后,形成的OTA-适体缀合物从电极表面脱离,最终降低通过差分脉冲伏安法监测的电化学信号。新型aptasensor实现了5至105ngL-1的宽线性检测范围,低检测限为0.31ngL-1。拟议的aptasensor已成功应用于红葡萄酒的OTA分析,回收率为94.15%至106%。此外,aptasensor还表现出良好的特异性和储存稳定性。因此,设计的aptasensor代表一个敏感的,实用可靠的农产品OTA监测工具,也可以适应其他霉菌毒素。
    Sensitive detection of ochratoxin A (OTA) is significant and essential because OTA may pose risks to human and animal health. Here, we developed an electrochemical aptasensor for OTA analysis using polyamidoamine (PAMAM) dendrimers as a signal amplifier. As a carrier, PAMAM has numerous primary amino groups that can be coupled with thiolated complementary strand DNA (cDNA), allowing it to recognize aptamers bound to the surface of horseradish peroxidase (HRP)-modified gold nanoparticles (AuNPs), thereby improving the sensitivity of the aptasensor. When monitoring the positive samples, OTA was captured by the aptamer fixed on the HRP-conjugated AuNP surface by specific recognition, after which the formed OTA-aptamer conjugates were detached from the electrode surface, ultimately decreasing the electrochemical signal monitored by differential pulse voltammetry. The novel aptasensor achieved a broad linear detection range from 5 to 105 ng L-1 with a low detection limit of 0.31 ng L-1. The proposed aptasensor was successfully applied for OTA analysis in red wine, with recovery rates ranging from 94.15 to 106%. Furthermore, the aptasensor also exhibited good specificity and storage stability. Therefore, the devised aptasensor represents a sensitive, practical and reliable tool for monitoring OTA in agricultural products, which can also be adapted to other mycotoxins.
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  • 文章类型: Journal Article
    在这项研究中,构建了一种新型的电化学适配体传感器,用于检测曲霉毒素A(OTA)。首先,通过电化学沉积制备了金铜合金膜,以恒电位模式选择性溶解铜,获得纳米多孔金修饰的丝网印刷碳电极(NPG/SPCE)。然后,将2-巯基乙胺滴在NPG/SPCE表面上,并形成Au-S共价键以固定金属。加入戊二醛作为交联剂,这导致PAMAM通过脱水缩合反应固定并连接到2-巯基乙胺上。在准备过程中,通过SEM对纳米多孔金和PAMAM修饰层进行了表征,XRD,和红外光谱,分别。表征结果表明,纳米多孔金和PAMAM复合薄膜被成功修饰。最后,通过戊二醛将OTA适体与PAMAM交联以完成Apt/PAMAM/NPG/SPCE传感器的构建。用DPV方法在曲霉毒素A溶液中测试了该传感器的电化学性能。结果表明,该传感器的重现性,稳定性,特异性很好。红酒的加标回收率在99.65%~101.6%之间,线性范围为0.5ng/mL~20ng/mL,最低检测限为0.141ng/mL。因此,这种新型生物传感器可能为OTA的痕量检测提供有前途的工具。
    In this study, a novel electrochemical aptamer sensor for detecting ochratoxin A (OTA) was constructed. First, a gold-copper alloy film was prepared via electrochemical deposition, and copper was selectively dissolved in constant potential mode for obtaining the nano-porous gold modified screen-printed carbon electrodes (NPG/SPCE). Then, 2-mercaptoethylamine was dropped on the NPG/SPCE surface and Au-S covalent bonds were formed for immobilizing the metal. Glutaraldehyde as cross-linking agent was added, which resulted in immobilization and attachment of PAMAM to the 2-mercaptoethylamine through the dehydration condensation reaction. During the preparation process, the nano-porous gold and PAMAM-modified layers were characterized by SEM, XRD, and IR spectroscopy, respectively. The characterization results showed that the nano-porous gold and PAMAM composite films were successfully modified. Finally, the OTA aptamer was cross-linked with PAMAM by glutaraldehyde to complete construction of the Apt/PAMAM/NPG/SPCE sensor. The electrochemical performance of this sensor was tested in ochratoxin A solutions with the DPV method. The results showed that the sensor\'s reproducibility, stability, and specificity were good. The spiked recoveries in red wine ranged from 99.65%∼101.6%, with a linear range of 0.5 ng/mL∼20 ng/mL and a minimum detection limit of 0.141 ng/mL. Thus, the novel biosensor may provide a promising tool for the trace detection of OTA.
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  • 文章类型: Journal Article
    Ferroptosis作为程序性细胞死亡在癌症研究中受到了相当大的关注。最近,研究已经将铁死亡与光动力疗法(PDT)相关联,因为PDT促进谷胱甘肽(GSH)缺失,谷胱甘肽过氧化物酶4(GPX4)降解,和脂质过氧化物积累。然而,PDT诱导的铁凋亡可能被铁凋亡抑制蛋白1(FSP1)阻止,一种新发现的铁凋亡抑制剂.为了解决这个限制,在这里,通过抑制PDT和FSP1引发铁凋亡的新策略被开发出来.为了加强这一战略,光响应纳米复合物,BODIPY改性PAMAM(BMP)自组装,用于稳定地包封FSP1(iFSP1)和二氢氯e6(Ce6)的抑制剂。纳米系统促进细胞内递送,穿透力,和铁凋亡诱导剂在光照射下在肿瘤中的积累。纳米系统在体外和体内表现出铁凋亡和免疫原性细胞死亡(ICD)的高性能触发。重要的是,纳米颗粒增加了CD8+T细胞的肿瘤浸润,并进一步增强了抗PD-L1免疫治疗的疗效.该研究表明,光响应性纳米复合物在癌症免疫治疗中的光增强协同诱导铁凋亡的巨大潜力。本文受版权保护。保留所有权利。
    Ferroptosis as programmed cell death received considerable attention in cancer research. Recently, studies have associated ferroptosis with photodynamic therapy (PDT) because PDT promotes glutathione (GSH) deletion, glutathione peroxidase 4 (GPX4) degradation, and lipid peroxide accumulation. However, PDT-induced ferroptosis may be potentially prevented by ferroptosis suppressor protein 1 (FSP1). To address this limitation, herein, a novel strategy is developed to trigger ferroptosis by PDT and FSP1 inhibition. For enhancement of this strategy, a photoresponsive nanocomplex, self-assembled by BODIPY-modified poly(amidoamine) (BMP), is utilized to stably encapsulate the inhibitor of FSP1 (iFSP1) and chlorin e6 (Ce6). The nanosystem promotes intracellular delivery, penetration, and accumulation of ferroptosis inducers in tumors with light irradiation. The nanosystem presents high-performance triggering of ferroptosis and immunogenic cell death (ICD) in vitro and in vivo. Importantly, the nanoparticles increase tumor infiltration of CD8+ T cells and further enhance the efficacy of anti-PD-L1 immunotherapy. The study suggests the potential of photo-enhanced synergistic induction of ferroptosis by the photoresponsive nanocomplexes in cancer immunotherapy.
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  • 文章类型: Journal Article
    壳聚糖原位生长的聚酰胺胺(CTS-GxPAMAM(x=0,1,2,3))气凝胶通过简单的一步冷冻干燥方法制备,戊二醛作为交联剂。气凝胶的三维骨架结构提供了许多吸附位点,并加速了污染物的有效传质。两种阴离子染料的吸附动力学和等温线研究符合伪二阶和Langmuir模型,表明玫瑰红(RB)和日落黄(SY)的去除是单层化学吸附过程。RB和SY的最大吸附量分别达到370.28mg/g和343.31mg/g,分别。在五个吸附-解吸循环后,两种阴离子染料的吸附量分别达到初始吸附量的81.10%和84.06%,分别。利用傅里叶变换红外光谱系统研究了气凝胶与染料的主要作用机理,X射线光电子能谱,扫描电子显微镜,和能量色散光谱分析,确认静电相互作用,氢键和范德华相互作用是优越吸附性能的主要驱动力。此外,CTS-G2PAMAM气凝胶具有良好的过滤和分离性能。总的来说,新型气凝胶吸附剂对阴离子染料的纯化具有良好的理论指导和实际应用潜力。
    Chitosan in situ grown polyamidoamine (CTS-Gx PAMAM (x = 0, 1, 2, 3)) aerogels were fabricated by a facile one-step freeze-drying method, with glutaraldehyde serving as a crosslinker. The three-dimensional skeletal structure of aerogel provided numerous adsorption sites and accelerated the effective mass transfer of pollutants. The adsorption kinetics and isotherm studies of the two anionic dyes were consistent with the pseudo-second-order and Langmuir models, indicating that the removal of rose bengal (RB) and sunset yellow (SY) was a monolayer chemisorption process. The maximum adsorption capacity of RB and SY reached 370.28 mg/g and 343.31 mg/g, respectively. After five adsorption-desorption cycles, the adsorption capacities of the two anionic dyes reached 81.10% and 84.06% of the initial adsorption capacities, respectively. The major mechanism between the aerogels and dyes was systematically investigated based on using Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and energy-dispersive spectroscopy analyses, confirming that electrostatic interaction, hydrogen bonding and van der Waals interactions were the main driving forces for the superior adsorption performance. Furthermore, the CTS-G2 PAMAM aerogel exhibited good filtration and separation performance. Overall, the novel aerogel adsorbent possesses excellent theoretical guidance and practical application potential for the purification of anionic dyes.
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  • 文章类型: Journal Article
    谷物中脱氧雪腐镰刀菌烯醇(DON)的污染已引起广泛关注。迫切需要开发一种用于DON高通量筛选的高灵敏度和稳健的测定法。在聚(酰胺基胺)树枝状聚合物(PAMAM)的支架下,借助于蛋白G在免疫磁珠的表面定向组装针对DON的抗体。DON-辣根过氧化物酶(HRP)通过共价连接在AuNP/PAMAM的外围以形成DON-HRP/AuNP/PAMAM。优化了基于DON-HRP/AuNPs/PAMAM的磁免疫分析,并采用基于DON-HRP/AuNPs和DON-HRP的磁免疫分析作为比较。检测限(LODs)为0.447ng/mL,基于DON-HRP的磁性免疫测定为0.127ng/mL和0.035ng/mL,DON-HRP/Au和DON-HRP/Au/PAMAM,分别。基于DON-HRP/AuNP/PAMAM的磁性免疫测定对DON显示出更高的特异性,并用于分析谷物样品。谷物样品中加标DON的回收率为90.8-116.2%,该方法与UPLC/MS具有良好的相关性。发现DON的浓度在ND-3.76ng/mL的范围内。该方法允许将具有信号放大特性的树枝状聚合物-无机NP整合在食品安全分析中。
    Contamination of deoxynivalenol (DON) in grains has attracted widespread concern. It is urgently needed to develop a highly sensitive and robust assay for DON high-throughput screening. Antibody against DON was assembled on the surface of immunomagnetic beads orientationally by the aid of Protein G. AuNPs were obtained under the scaffolding of poly(amidoamine) dendrimer (PAMAM). DON-horseradish peroxidase (HRP) was combined on the periphery of AuNPs/PAMAM by a covalent link to develop DON-HRP/AuNPs/PAMAM. Magnetic immunoassay based on DON-HRP/AuNPs/PAMAM was optimized and that based on DON-HRP/AuNPs and DON-HRP was adopted as comparison. The limits of detection (LODs) were 0.447 ng/mL, 0.127 ng/mL and 0.035 ng/mL for magnetic immunoassays based on DON-HRP, DON-HRP/Au and DON-HRP/Au/PAMAM, respectively. Magnetic immunoassay based on DON-HRP/AuNPs/PAMAM displayed higher specificity towards DON and was utilized to analyze grain samples. The recovery for the spiked DON in grain samples was 90.8-116.2% and the method presented a good correlation with UPLC/MS. It was found that the concentration of DON was in the range of ND-3.76 ng/mL. This method allows the integration of dendrimer-inorganic NPs with signal amplification properties for applications in food safety analysis.
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  • 文章类型: Journal Article
    宽带隙无机CsPbI2Br钙钛矿材料提供与室内光谱高度匹配的吸收范围,有望用于制造高效室内光伏电池(IPV)和自供电低功耗物联网(IoT)传感器。然而,导致非辐射复合和离子迁移的缺陷被认为形成泄漏损失通道,导致对IPV的开路电压(VOC)和填充因子(FF)的严重影响。在这里,我们引入具有多个钝化位点的聚(酰胺胺)(PAMAM)树枝状聚合物,以完全修复器件中的泄漏通道,考虑到IPV对非辐射复合和分流电阻极其敏感的特性。优化后的IPV在荧光光源(1000勒克斯)下表现出35.71%的有前途的PCE,VOC从0.99V提高到1.06V,FF从75.21提高到84.39%。本工作提供了对钙钛矿在全阳光和室内光线下的光伏机理的见解,为具有产业化前景的钙钛矿光伏技术提供指导。
    The wide-band-gap inorganic CsPbI2Br perovskite material provides a highly matched absorption range with the indoor light spectrum and is expected to be used in the fabrication of highly efficient indoor photovoltaic cells (IPVs) and self-powered low-power Internet of Things (IoT) sensors. However, the defects that cause nonradiative recombination and ion migration are assumed to form leakage loss channels, resulting in a severe impact on the open-circuit voltage (VOC) and the fill factor (FF) of IPVs. Herein, we introduce poly(amidoamine) (PAMAM) dendrimers with multiple passivation sites to fully repair the leakage channels in the devices, taking into account the characteristics of IPVs that are extremely sensitive to nonradiative recombination and shunt resistance. The as-optimized IPVs demonstrate a promising PCE of 35.71% under a fluorescent light source (1000 lux), with VOC increased from 0.99 to 1.06 V and FF improved from 75.21 to 84.39%. The present work provides insight into the photovoltaic mechanism of perovskites under full sun and indoor light, which provides guidance for perovskite photovoltaic technology with industrialization prospects.
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  • 文章类型: Journal Article
    自修复藻酸盐水凝胶由于其生物相容性和裂解后恢复能力而在生物领域发挥重要作用。该领域研究人员的主要目标之一是提高自我修复速度。海藻酸钠被氧化,在链上产生醛基,然后通过席夫碱反应通过聚(氨基)胺(PAMAM)交联。在这项工作中,将树枝状结构引入到藻酸盐水凝胶中,这应该促进分子间的相互作用,加速自我修复过程。结果表明,水凝胶(ADA-PAMAM)在2.5分钟内形成凝胶,具有稳定的流变性能。在25分钟内,水凝胶在室温下恢复。此外,通过多角度激光散射和紫外(UV)吸收的凝胶渗透色谱表征了不同氧化程度的海藻酸盐二醛的醛度。通过傅里叶变换红外光谱和紫外-可见光谱表征了水凝胶的化学结构。SEM和激光扫描共聚焦显微镜(CLSM)显示了ADA-PAMAM与10-7CFU微生物在室温下孵育2h时对金黄色葡萄球菌和大肠杆菌的抗菌能力。这项工作提出了通过形成树枝状动态交联网络来促进水凝胶自修复的策略。
    Self-healing alginate hydrogels play important roles in the biological field due to their biocompatibility and ability to recover after cracking. One of the primary targets for researchers in this field is to increase the self-healing speed. Sodium alginate was oxidized, generating aldehyde groups on the chains, which were then crosslinked by poly(amino) amine (PAMAM) via Schiff base reaction. The dendritic structure was introduced to the alginate hydrogel in this work, which was supposed to promote intermolecular interactions and accelerate the self-healing process. Results showed that the hydrogel (ADA-PAMAM) formed a gel within 2.5 min with stable rheological properties. Within 25 min, the hydrogel recovered under room temperature. Furthermore, the aldehyde degree of alginate dialdehyde with a different oxidation degree was characterized through gel permeation chromatograph aligned with multi-angle laser light scattering and ultraviolet (UV) absorption. The chemical structure of the hydrogel was characterized through Fourier transform infrared spectroscopy and UV-vis spectra. The SEM and laser scanning confocal microscope (CLSM) presented the antibiotic ability of ADA-PAMAM against both S. aureus and E. coli when incubated with 10-7 CFU microorganism under room temperature for 2 h. This work presented a strategy to promote the self-healing of hydrogel through forming a dendritic dynamic crosslinking network.
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  • 文章类型: Journal Article
    智能水凝胶,由于其特殊的粘弹性和可变形的能力,以响应环境刺激的温度和pH值,已成功应用于油田的目的,如水和/或气体关闭处理。然而,低渗透油藏的CO2突破问题尚未得到很好的解决。在这项工作中,采用基于流变方法的Avrami动力学模型和Dickinson动力学模型研究了热/pH双敏感PEG/PAMAM纳米凝胶的动态凝胶化过程,以进一步了解其凝胶化的微观结构和针对性的封堵应用。通过在三个破裂的低渗透率岩心上交替注入CO2和水凝胶溶液,进行了封堵实验,背压为13MPa。纳米凝胶呈现从三维到一维的二次生长模式,从微米到纳米大小,形态从球形转变为不规则的椭圆形或圆盘形。相变温度为50°C,相变pH为10。如果两者或两者都低于这些值,水凝胶膨胀;否则,它缩小了。封堵结果表明,封堵效率高于99%。最大突破压力为19.93MPa,对于10mD的岩心,相应的残余压力保持在17.64MPa,具有良好的封堵性能和被CO2击穿后的高残余阻力。
    Smart hydrogels, owing to their exceptional viscoelastic and deformable capacity in response to environmental stimulation involving temperature and pH, have been successfully applied in oilfields for purposes such as water and/or gas shutoff treatments. However, the CO2 breakthrough problem in low permeability reservoirs has not been well solved. In this work, a rheological method-based Avrami dynamics model and Dickinson dynamics model were employed to investigate the dynamic gelation process of thermo-/pH-dual-sensitive PEG/PAMAM nanogels to further our understanding of the microstructure of their gelation and pertinence plugging application. Plugging experiments were performed by alternating injections of CO2 and hydrogel solution in a slug type on three fractured low permeability cores with a backpressure of 13 MPa. The nanogels presented a secondary growth pattern from three to one dimension from micrometer to nanometer size with a morphological transformation from a sphere to an irregular ellipsoid or disk shape. The phase transition temperature was 50 °C, and the phase transition pH was 10. If both or either were below these values, the hydrogel swelled; otherwise, it shrank. Plugging results show that the plugging efficiency was higher than 99%. The maximum breakthrough pressure was 19.93 MPa, and the corresponding residual pressure remained 17.64 MPa for a 10 mD core, exhibiting great plugging performance and high residual resistance after being broken through by CO2.
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