phospholipid

磷脂
  • 文章类型: Journal Article
    苯乙烯-马来酸(SMA)共聚物因其优异的增溶特性而备受关注。在这项工作中,首次开发并开发了基于SMA共聚物刷的色谱固定相。首先,通过活性/受控可逆加成-断裂链转移(RAFT)聚合方法在球形二氧化硅表面原位生长SMA共聚物刷。随后,作为概念验证演示,该共聚物被二甘醇单-2-乙基己基醚(DGME)和2-(2-乙基己氧基)乙醇(EHOE)酯化,分别。用透射电子显微镜对所得的Sil-SMA-DGME和Sil-SMA-EHOE共聚物-刷色谱固定相进行了表征,傅里叶变换红外光谱仪,X射线光电子能谱,和热重分析,分别。色谱保留机制表明,两个填充柱都表现出亲水/反向混合模式保留模式。最大色谱柱效率高达71,000N/m。色谱分离性能评价表明,该新型固定相对亲水,疏水性化合物和磷脂标准。此外,结合质谱鉴定,Sil-SMA-DGME柱进一步用于分离和鉴定人肺癌细胞中的磷脂。完全正确,成功鉴定了9类,包括186种磷脂。结果表明,新型SMA共聚物刷式色谱固定相具有广阔的应用前景。
    Styrene-maleic acid (SMA) copolymer has received much attention for its excellent solubilization characteristics. In this work, SMA copolymer brush-based chromatographic stationary phases were exploited and developed for the first time. First, SMA copolymer brush was in situ grown on the surface of spherical silica via living/controlled reversible addition-fragmentation chain transfer (RAFT) polymerization method. Subsequently, as a proof-of-concept demonstration, the copolymer was esterified by diethylene glycol mono-2-ethylhexyl ether (DGME) and 2-(2-ethylhexyloxy) ethanol (EHOE), respectively. The obtained Sil-SMA-DGME and Sil-SMA-EHOE copolymer-brush chromatographic stationary phases were characterized by transmission electron microscopy, Fourier transform infrared spectrometer, X-ray photoelectron spectroscopy, and thermogravimetric analysis, respectively. The chromatographic retention mechanism indicated that both the two packed columns exhibited hydrophilic/reverse mixed-mode retention modes. The maximum column efficiency was up to 71,000 N/m. The chromatographic separation performance evaluation indicated that the novel kind of stationary phases had excellent separation capabilities for hydrophilic, hydrophobic compounds and phospholipid standards. In addition, by combination with mass spectrometry identification, the Sil-SMA-DGME column was further exploited for separation and identification of phospholipids in human lung cancer cells. Totally, 9 classes including 186 phospholipid species were successfully identified. The results demonstrated the promising application prospects of the novel kind of SMA copolymer-brush chromatographic stationary phases.
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  • 文章类型: Journal Article
    人乳磷脂(HMPL)在婴儿的神经发育和生长中起着不可或缺的作用。在这项研究中,从人乳和其他天然磷脂来源(包括5种动物来源和2种植物来源)共检测到37种磷脂脂肪酸(PLFA)和139种磷脂分子.此外,建立了HMPL的相似性评价模型,包括磷脂类,PLFA,和磷脂分子种类,评估它们的天然替代品。HMPL替代品在这三个维度中最接近的分数是0.89、0.72和0.77,属于马奶,山羊奶,还有骆驼奶,分别。骆驼奶的综合相似度得分最高,为0.75,而大豆磷脂得分最低(0.22)。因此,这些结果不仅监测了HMPL及其替代品的立体化学结构,也进一步为婴儿配方食品的发展提供了新的见解。
    Human milk phospholipids (HMPLs) play an indispensable role in the neurodevelopment and growth of infants. In this study, a total of 37 phospholipid fatty acid (PLFA) species and 139 phospholipid molecular species were detected from human milk and other natural phospholipid sources (including 5 animal-derived species and 2 plant species). Moreover, a similarity evaluation model for HMPLs was established, including phospholipid classes, PLFAs, and phospholipid molecular species, to evaluate their natural substitutes. The closest scores for HMPL substitute in these three dimensions was 0.89, 0.72, and 0.77, which belonged to mare milk, goat milk, and camel milk, respectively. The highest comprehensive similarity score was obtained by camel milk at 0.75, while the lowest score was observed in soybean phospholipid (0.22). Therefore, these results not only monitored the stereochemical structure of HMPLs and their substitutes, but also further provided new insights for the development of infant formulae.
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  • 文章类型: Journal Article
    背景:急性胰腺炎(AP)的特征是全身性炎症,对诊断和预后评估提出了挑战。脂质代谢异常,尤其是三酰甘油(TAG)水平,据报道,表明它们作为急性胰腺炎生物标志物的潜力。然而,TAG周期的性能,包括磷脂和甘油脂代谢,在AP患者中尚未报道。
    方法:本研究纳入了91例急性胆源性胰腺炎(ABP)患者,27患有高脂血症性急性胰腺炎(HLAP),和58个健康对照(HCs),他们的血浆磷脂和甘油脂水平通过液相色谱-质谱分析。首先收集AP患者血浆的磷脂和甘油脂含量,第三,还测量了住院的第七天。正交偏最小二乘判别分析模型用于区分ABP,HLAP和HC组,通过测试集和验证集的受试者工作特征曲线评估潜在诊断性脂质。使用Spearman方法对临床数据与血脂之间的相关性进行分析。通过“mfuzz”R包和Kruskal-WallisH检验进行聚类以监测住院期间的变化。
    结果:与HC相比,磷脂酰胆碱(PC)的水平,磷脂酰乙醇胺(PE),AP患者中磷脂酸(PA)较低,而磷脂酰肌醇(PI)和磷脂酰甘油(PG)的水平则显示出相反的趋势。有趣的是,ABP患者TAG水平与白细胞计数呈正相关,和含有44-55个碳原子的TAG与HLAP患者的血浆TAG水平高度相关。磷脂水平与AP标志物呈负相关,与甘油脂相比,与这些标记呈正相关。此外,PE(O-16:0/20:4)和PE(18:0/22:6)成为潜在的生物标志物,因为它们能够区分ABP和HLAP患者与HCs,曲线下面积(AUC)值分别为0.932和0.962。PG(16:0/18:2),PG(16:0/20:4),PE(P-16:0/20:2),PE(P-18:2/18:2),PE(P-18:1/20:3),PE(P-18:1/20:4),PE(O-16:0/20:4),改善的ABP患者的TAG(56:6/FA18:0)明显改变。对于HLAP患者,PC(18:0/20:3),标签(48:3/FA18:1),PE(P-18:0/16:0),和TAG(48:4/FA18:2)在患者中显示出不同的改善和恶化趋势,这可能用于预后。
    结论:发现磷脂和甘油脂是急性胰腺炎的潜在生物标志物,这为这种疾病提供了新的诊断和治疗见解。
    BACKGROUND: Acute pancreatitis (AP) is characterized as a systemic inflammatory condition posing challenges in diagnosis and prognosis assessment. Lipid metabolism abnormalities, especially triacylglycerol (TAG) levels, have been reported, indicating their potential as biomarkers in acute pancreatitis. However, the performance of the TAG cycle, including phospholipid and glycerolipid metabolism, in AP patients has not yet been reported.
    METHODS: This study enrolled 91 patients with acute biliary pancreatitis (ABP), 27 with hyperlipidaemic acute pancreatitis (HLAP), and 58 healthy controls (HCs), and their plasma phospholipid and glycerolipid levels were analyzed through liquid chromatography‒mass spectrometry. The phospholipid and glycerolipid contents of plasma collected from AP patients on the first, third, and seventh days of hospitalization were also measured. An orthogonal partial least squares discriminant analysis model served to differentiate the ABP, HLAP and HC groups, and potentially diagnostic lipids were evaluated via receiver operating characteristic curves in both the test and validation sets. Correlations between clinical data and lipids were conducted using Spearman\'s method. Clustering via the \'mfuzz\' R package and the Kruskal‒Wallis H test were conducted to monitor changes during hospitalization.
    RESULTS: Compared with those in HCs, the levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidic acid (PA) were lower in AP patients, whereas the levels of phosphatidylinositol (PI) and phosphatidylglycerol (PG) showed the opposite trend. Interestingly, TAG levels were positively correlated with white blood cell counts in ABP patients, and TAGs containing 44-55 carbon atoms were highly correlated with plasma TAG levels in HLAP patients. Phospholipid levels exhibited an inverse correlation with AP markers, in contrast to glycerolipids, which demonstrated a positive correlation with these markers. Additionally, PE (O-16:0/20:4) and PE (18:0/22:6) emerged as potential biomarkers because of their ability to distinguish ABP and HLAP patients from HCs, showing area under the curve (AUC) values of 0.932 and 0.962, respectively. PG (16:0/18:2), PG (16:0/20:4), PE (P-16:0/20:2), PE (P-18:2/18:2), PE (P-18:1/20:3), PE (P-18:1/20:4), PE (O-16:0/20:4), and TAG (56:6/FA18:0) were significantly changed in ABP patients who improved. For HLAP patients, PC (18:0/20:3), TAG (48:3/FA18:1), PE (P-18:0/16:0), and TAG (48:4/FA18:2) showed different trends in patients with improvement and deterioration, which might be used for prognosis.
    CONCLUSIONS: Phospholipids and glycerolipids were found to be potential biomarkers in acute pancreatitis, which offers new diagnostic and therapeutic insights into this disease.
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  • 文章类型: Journal Article
    我们重点介绍邱等人的最新作品。关于具有两个多不饱和脂肪酰尾巴的稀有磷脂(PL-PUFA2s)诱导铁死亡的核心机制,已在Cell上发表。长期以来,人们一直认为含有一个PUFA尾部的PL(PL-PUFA1s)在铁凋亡过程中作为磷脂过氧化的底物,由于它们对体内氧化和流行的敏感性。然而,作者指出,PL-PUFA2s,而不是PL-PUFA1s,代表参与促铁蛋白过程的关键脂质类别。外源性磷脂酰胆碱-PUFA2s在线粒体中积累,并在电子传递链中与复合物I结合,从而可能导致线粒体活性氧水平的升高。然后,这些线粒体过氧化物促使内质网内的过氧化物大量积累,最终导致铁中毒。这些发现揭示了膳食PL-PUFA2诱导铁凋亡的潜在分子机制,并为评估细胞铁死亡敏感性和癌症治疗提供了新的见解。本文将对论文进行更全面的阐述,并促进读者对潜在机制的理解。
    We highlight the latest work of Qiu et al. on the core mechanism of ferroptosis induced by rare phospholipids with two polyunsaturated fatty acyl tails (PL-PUFA2s), which has been published in Cell. It has long been acknowledged that PLs containing one PUFA tail (PL-PUFA1s) serve as substrates for phospholipid peroxidation during the process of ferroptosis, owing to their susceptibility to oxidation and prevalence in vivo. However, the authors note that PL-PUFA2s, rather than PL-PUFA1s, represent critical lipid classes involved in the pro-ferroptosis process. Exogenous phosphatidylcholine-PUFA2s accumulate in mitochondria and combine with Complex I within the electron transport chain, thereby potentially resulting in an elevation of mitochondrial reactive oxygen species levels. Then, these mitochondrial peroxides prompt the substantial accumulation of peroxides within the endoplasmic reticulum, ultimately culminating in ferroptosis. These findings shed light on the potential molecular mechanisms underlying the induction of ferroptosis by dietary PL-PUFA2s and offer novel insights for both the evaluation of cellular iron death sensitivity and the treatment of cancer. This article will provide a more comprehensive elucidation of the paper and facilitate an enhanced understanding of the underlying mechanisms for readers.
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  • 文章类型: Journal Article
    牛奶磷脂有多种健康益处,但是乳制品中详细磷脂谱的缺乏给乳制品磷脂的摄入量计算和功能评估带来了障碍。在目前的研究中,在207个牛奶中鉴定并定量了306个磷脂分子种类,酸奶和奶油产品使用HILIC-ESI-Q-TOFMS和HILIC-ESI-QQQMS。五种哺乳动物乳的磷脂谱表明骆驼乳含有最丰富的磷脂酰乙醇胺,磷脂酰丝氨酸和鞘磷脂;牛,牦牛和山羊奶有相似的磷脂体,而水牛奶中含有丰富的磷脂酰肌醇。在超高温(UHT)灭菌牛奶中发现了比巴氏杀菌牛奶更少的疟原虫,但更多的溶血甘油磷脂,在奶油和脱脂/半脱脂牛奶中观察到的溶血甘油磷脂/总磷脂比例高于全脂牛奶,表明UHT和撇脂过程改善了甘油磷脂的降解和磷脂营养损失。同时,更多的二酰基甘油磷脂和更少的降解产物使酸奶成为比全脂牛奶更好的磷脂资源。
    Milk phospholipids have multiple health benefits, but the deficiency of detailed phospholipid profiles in dairy products brings obstacles to intake calculation and function evaluation of dairy phospholipids. In present study, 306 phospholipid molecular species were identified and quantified among 207 milk, yogurt and cream products using a HILIC-ESI-Q-TOF MS and a HILIC-ESI-QQQ MS. The phospholipid profiles of five mammals\' milk show that camel milk contains the most abundant phosphatidylethanolamine, phosphatidylserine and sphingomyelin; cow, yak and goat milk have similar phospholipidomes, while buffalo milk contains abundant phosphatidylinositol. Fewer plasmalogens but more lyso-glycerolphospholipids were found in ultra-high-temperature (UHT) sterilized milk than in pasteurized milk, and higher proportions of lyso-glycerolphospholipid/total phospholipid were observed in both cream and skimmed/semi-skimmed milk than whole milk, indicating that UHT and skimming processes improve glycerolphospholipid degradation and phospholipid nutrition loss. Meanwhile, more diacyl-glycerolphospholipids and less of their degradation products make yogurt a better phospholipid resource than whole milk.
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  • 文章类型: Journal Article
    由于磷脂对大小有重要影响,脂质体的表面电势和硬度决定了它们吸入后的体内命运,本研究系统评价了磷脂对脂质体肺部给药的影响。在这项研究中,由中性饱和/不饱和磷脂组成的脂质体,构建了阴离子和阳离子磷脂,以研究表面电势和脂肪酸链的饱和度如何在体外和体内决定其粘液和上皮渗透性。我们的研究结果清楚地表明,由饱和中性和阴离子磷脂组成的脂质体具有很高的稳定性和渗透性,与由不饱和磷脂和阳离子磷脂组成的脂质体相比。此外,进行了荧光标记脂质体的体内成像和脂质体中包封的丹酚酸B(SAB)的生物分布,以评估磷脂对吸入脂质体的肺暴露和滞留的影响.最后,吸入SAB脂质体通过抑制炎症和调节凝血-纤溶系统,在博来霉素诱导的特发性肺纤维化小鼠模型中显示出增强的治疗效果.这些发现将有益于开发用于治疗呼吸道疾病的可吸入的基于脂质的纳米药物递送系统,其中吸入是优选的施用途径。
    Since phospholipids have an important effect on the size, surface potential and hardness of liposomes that decide their in vivo fate after inhalation, this research has systematically evaluated the effect of phospholipids on pulmonary drug delivery by liposomes. In this study, liposomes composed of neutral saturated/unsaturated phospholipids, anionic and cationic phospholipids were constructed to investigate how surface potential and the degree of saturation of fatty acid chains determined their mucus and epithelium permeability both in vitro and in vivo. Our results clearly indicated that liposomes composed of saturated neutral and anionic phospholipids possessed high stability and permeability, compared to that of liposomes composed of unsaturated phospholipids and cationic phospholipids. Furthermore, both in vivo imaging of fluorescence-labeled liposomes and biodistribution of salvianolic acid B (SAB) that encapsulated in liposomes were performed to estimate the effect of phospholipids on the lung exposure and retention of inhaled liposomes. Finally, inhaled SAB-loaded liposomes exhibited enhanced therapeutic effects in a bleomycin-induced idiopathic pulmonary fibrosis mice model via inhibition of inflammation and regulation on coagulation-fibrinolytic system. Such findings will be beneficial to the development of inhalable lipid-based nanodrug delivery systems for the treatment of respiratory diseases where inhalation is the preferred route of administration.
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  • 文章类型: Journal Article
    锌(Zn)是一种必需的微量元素,是必需的各种生物功能,但是过度接触锌与许多疾病甚至疾病有关。然而,长期高浓度锌暴露对健康的影响和潜在机制仍不清楚.在本研究中,我们调查了职业锌暴露与工人肝功能指标(如丙氨酸转氨酶(ALT))之间的关联.我们发现工人的锌暴露与ALT水平呈正相关。与血锌含量较低(5969.30(989.26)μg/L)的工人相比,血锌含量较高(7735.65(1159.15)μg/L)的工人的ALT水平增加了30.4%。此外,我们探索了磷脂(PLs)及其代谢对ALT水平的影响,并发现工人的锌暴露与PL水平和代谢的变化有关。这对工人ALT水平的增加有进一步的影响。这项研究提供了对职业锌暴露与肝功能之间关系的见解,强调了长期暴露于高浓度锌的风险,为了解锌暴露对人体健康的潜在机制铺平了道路。
    Zinc (Zn) is an essential trace element that is required for various biological functions, but excessive exposure to Zn is associated with many disorders and even diseases. However, the health effects and underlying mechanisms of long-term and high concentration exposure of Zn remain to be unclear. In the present study, we investigated the association between occupational exposure to Zn and liver function indicators (like alanine aminotransferase (ALT)) in workers. We found a positive association between Zn exposure and ALT level in workers. Workers having higher blood Zn (7735.65 (1159.15) μg/L) shows a 30.4 % increase in ALT level compared to those with lower blood Zn (5969.30 (989.26) μg/L). Furthermore, we explored the effects of phospholipids (PLs) and their metabolism on ALT level and discovered that Zn exposure in workers was associated with changes in PL levels and metabolism, which had further effects on increased ALT levels in workers. The study provides insights into the relationship between occupational Zn exposure and liver function, highlights the risk of long-term exposure to high concentrations of Zn, and paves the way for understanding the underlying mechanisms of Zn exposure on human health.
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  • 文章类型: Journal Article
    饮食蛋氨酸限制(MR)与一系列促进健康的益处有关。有利于预防慢性病和延长寿命,MR可以激活新陈代谢的综合反应,转录,和生理水平。然而,MR的线粒体如何影响代谢表型仍然难以捉摸。这里,我们提供了蛋氨酸代谢的细胞功能的总结和目前对MR效应机制的理解的概述,重点关注线粒体介导的反应。我们认为线粒体可以通过脂化的调节作用来感知和响应MR,由MR致敏的线粒体蛋白质修饰。
    Dietary methionine restriction (MR) is associated with a spectrum of health-promoting benefits. Being conducive to prevention of chronic diseases and extension of life span, MR can activate integrated responses at metabolic, transcriptional, and physiological levels. However, how the mitochondria of MR influence metabolic phenotypes remains elusive. Here, we provide a summary of cellular functions of methionine metabolism and an overview of the current understanding of effector mechanisms of MR, with a focus on the aspect of mitochondria-mediated responses. We propose that mitochondria can sense and respond to MR through a modulatory role of lipoylation, a mitochondrial protein modification sensitized by MR.
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  • 文章类型: Journal Article
    多年来,在药物递送领域中,对PEG化的基于脂质的纳米载体存在显著的兴趣。纳米载体和血浆蛋白之间不可避免的相互作用在其体内生物命运中起着关键作用。了解影响基于脂质的纳米载体和蛋白质冠相互作用的因素在这些纳米载体的设计和临床转化中至关重要。在这里,制备了由具有不同脂质尾部和头部基团的不同磷脂组成的盘状脂质纳米盘(sND)。我们研究了磷脂成分对sND和血清蛋白之间相互作用的影响,粒子稳定性,和生物分布。结果表明,所有这些脂质纳米盘在15天的储存期内保持稳定,而它们在血清中的稳定性表现出显著差异。由POPG组成的sND由于其强大的补体激活能力而表现出最低的稳定性,导致快速的血液清除。此外,补体激活能力与血清稳定性呈负相关。药代动力学和生物分布实验表明,磷脂组成不影响sND逃避加速血液清除现象的能力。sND上的补体沉积与曲线下面积成反比。此外,所有脂质纳米盘都表现出对载脂蛋白的显性吸附。值得注意的是,基于POPC的脂质纳米盘显示出明显更高的载脂蛋白E沉积,有助于明显的大脑分布,这为脑靶向药物递送提供了有希望的工具。
    Over the years, there has been significant interest in PEGylated lipid-based nanocarriers within the drug delivery field. The inevitable interplay between the nanocarriers and plasma protein plays a pivotal role in their in vivo biological fate. Understanding the factors influencing lipid-based nanocarrier and protein corona interactions is of paramount importance in the design and clinical translation of these nanocarriers. Herein, discoid-shaped lipid nanodiscs (sNDs) composed of different phospholipids with varied lipid tails and head groups were fabricated. We investigated the impact of phospholipid components on the interaction between sNDs and serum proteins, particle stability, and biodistribution. The results showed that all of these lipid nanodiscs remained stable over a 15 day storage period, while their stability in the blood serum demonstrated significant differences. The sND composed of POPG exhibited the least stability due to its potent complement activation capability, resulting in rapid blood clearance. Furthermore, a negative correlation between the complement activation capability and serum stability was identified. Pharmacokinetic and biodistribution experiments indicated that phospholipid composition did not influence the capability of sNDs to evade the accelerated blood clearance phenomenon. Complement deposition on the sND was inversely associated with the area under the curve. Additionally, all lipid nanodiscs exhibited dominant adsorption of apolipoprotein. Remarkably, the POPC-based lipid nanodisc displayed a significantly higher deposition of apolipoprotein E, contributing to an obvious brain distribution, which provides a promising tool for brain-targeted drug delivery.
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  • 文章类型: Journal Article
    血红素蛋白及其衍生物在培根干燥过程中诱导脂质氧化产生挥发性化合物中起重要作用。这项研究调查了血红素蛋白及其衍生物(血红蛋白,肌红蛋白,亚硝基肌红蛋白,血红素,Fe2+,和Fe3)对洗涤猪肌肉(WPM)模型中的脂质和挥发物谱的影响。研究结果表明,诱导剂主要引起甘油磷脂的氧化。此外,血红蛋白和肌红蛋白的影响最为显著,它们的潜在底物可能包括PE(O-18:2/20:4),PE(O-18:1/20:4),PC(16:0/18:1),和PE(O-18:2/18:2)。硝基血红蛋白具有有限的促进脂质氧化的能力并且可以保护醚磷脂免受氧化。对模型中挥发物的分析表明,血红素蛋白及其衍生物具有诱导关键香气化合物产生的能力。诱导芳香化合物产生的有效性的降序如下:血红蛋白,肌红蛋白,血红素,和亚硝基肌红蛋白.Fe2+和Fe3+的效力类似于亚硝基肌红蛋白。
    Heme proteins and their derivatives play important roles in inducing lipid oxidation to produce volatile compounds during bacon drying. This study investigated the effects of heme proteins and their derivatives (hemoglobin, myoglobin, nitrosylmyoglobin, hemin, Fe2+, and Fe3+) on lipid and volatiles profiles in the washed pig muscle (WPM) model. The results of the study indicated that the inducers primarily caused the oxidation of glycerophospholipids. Furthermore, hemoglobin and myoglobin had the most significant impact, and their potential substrates may include PE (O-18:2/20:4), PE (O-18:1/20:4), PC (16:0/18:1), and PE (O-18:2/18:2). Nitrosomyoglobin has limited ability to promote lipid oxidation and may protect ether phospholipids from oxidation. The analysis of the volatiles in the model revealed that heme proteins and their derivatives have the ability to induce the production of key aroma compounds. The descending order of effectiveness in inducing the production of aroma compounds is as follows: hemoglobin, myoglobin, hemin, and nitrosylmyoglobin. The effectiveness of Fe2+ and Fe3+ is similar to that of nitrosylmyoglobin.
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