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STATs signaling pathways in dendritic cells: As potential therapeutic targets? 树突状细胞中的STATs信号通路:作为潜在的治疗靶点?
IF 5 4区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2023-10-27 DOI: 10.1080/08830185.2023.2274576
Sepideh Sohrabi, Javad Masoumi, Bahar Naseri, Farid Ghorbaninezhad, Shiva Alipour, Tohid Kazemi, Javad Ahmadian Heris, Leili Aghebati Maleki, Pedram Basirjafar, Raziyeh Zandvakili, Mohammad Amin Doustvandi, Behzad Baradaran

Dendritic cells (DCs) are professional antigen-presenting cells (APCs), including heterogenous populations with phenotypic and functional diversity that coordinate bridging innate and adaptive immunity. Signal transducer and activator of transcriptions (STAT) factors as key proteins in cytokine signaling were shown to play distinct roles in the maturation and antigen presentation of DCs and play a pivotal role in modulating immune responses mediated by DCs such as differentiation of T cells to T helper (Th) 1, Th2 or regulatory T (Treg) cells. This review sheds light on the importance of STAT transcription factors' signaling pathways in different subtypes of DCs and highlights their targeting potential usages for improving DC-based immunotherapies for patients who suffer from cancer or diverse autoimmune conditions according to the type of the STAT transcription factor and its specific activating or inhibitory agent.

树突状细胞(DC)是专业的抗原呈递细胞(APC),包括具有表型和功能多样性的异质群体,协调先天免疫和适应性免疫。信号转导子和转录激活子(STAT)因子作为细胞因子信号传导中的关键蛋白,在DC的成熟和抗原呈递中发挥着不同的作用,并在调节DC介导的免疫反应中发挥着关键作用,如T细胞分化为T辅助细胞(Th)1、Th2或调节性T细胞(Treg)。这篇综述阐明了STAT转录因子信号通路在不同亚型DC中的重要性,并强调了其靶向潜在用途,根据STAT转录因素的类型及其特异性激活或抑制剂,改善癌症或多种自身免疫疾病患者的DC基免疫疗法。
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引用次数: 0
RNA methylation: A potential therapeutic target in autoimmune disease. RNA甲基化:自身免疫性疾病的潜在治疗靶点
IF 4.3 4区 医学 Q2 IMMUNOLOGY Pub Date : 2024-05-01 Epub Date: 2023-11-17 DOI: 10.1080/08830185.2023.2280544
Lele Li, Xiaoping Xia, Tian Yang, Yuchao Sun, Xueke Liu, Wei Xu, Mei Lu, Dawei Cui, Yingping Wu

Autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD) are caused by the body's immune response to autoantigens. The pathogenesis of autoimmune diseases is unclear. Numerous studies have demonstrated that RNA methylation plays a key role in disease progression, which is essential for post-transcriptional regulation and has gradually become a broad regulatory mechanism that controls gene expression in various physiological processes, including RNA nuclear output, translation, splicing, and noncoding RNA processing. Here, we outline the writers, erasers, and readers of RNA methylation, including N6-methyladenosine (m6A), 2'-O-methylation (Nm), 2'-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytidine (m5C) and N7-methylguanosine (m7G). As the role of RNA methylation modifications in the immune system and diseases is explained, the potential treatment value of these modifications has also been demonstrated. This review reports the relationship between RNA methylation and autoimmune diseases, highlighting the need for future research into the therapeutic potential of RNA modifications.

自身免疫性疾病如类风湿关节炎(RA)、系统性红斑狼疮(SLE)和炎症性肠病(IBD)是由机体对自身抗原的免疫反应引起的。自身免疫性疾病的发病机制尚不清楚。大量研究表明,RNA甲基化在疾病进展中起着关键作用,对转录后调控至关重要,并逐渐成为控制RNA核输出、翻译、剪接、非编码RNA加工等多种生理过程中基因表达的广泛调控机制。在这里,我们概述了RNA甲基化的书写器、擦除器和读取器,包括n6 -甲基腺苷(m6A)、2'- o -甲基化(Nm)、2'- o -二甲基腺苷(m6Am)、n1 -甲基腺苷(m1A)、5-甲基胞苷(m5C)和n7 -甲基鸟苷(m7G)。随着RNA甲基化修饰在免疫系统和疾病中的作用被解释,这些修饰的潜在治疗价值也被证明。这篇综述报道了RNA甲基化与自身免疫性疾病之间的关系,强调了未来研究RNA修饰治疗潜力的必要性。
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引用次数: 0
Macrophage: A key player in neuropathic pain. 巨噬细胞神经性疼痛的关键角色
IF 5 4区 医学 Q1 Medicine Pub Date : 2024-04-25 DOI: 10.1080/08830185.2024.2344170
Ying Ye, Hao Cheng, Yan Wang, Yan Sun, Li-Dong Zhang, Jun Tang
Research on the relationship between macrophages and neuropathic pain has flourished in the past two decades. It has long been believed that macrophages are strong immune effector cells that play well-established roles in tissue homeostasis and lesions, such as promoting the initiation and progression of tissue injury and improving wound healing and tissue remodeling in a variety of pathogenesis-related diseases. They are also heterogeneous and versatile cells that can switch phenotypically/functionally in response to the micro-environment signals. Apart from microglia (resident macrophages of both the spinal cord and brain), which are required for the neuropathic pain processing of the CNS, neuropathic pain signals in PNS are influenced by the interaction of tissue-resident macrophages and BM infiltrating macrophages with primary afferent neurons. And the current review looks at new evidence that suggests sexual dimorphism in neuropathic pain are caused by variations in the immune system, notably macrophages, rather than the neurological system.
近二十年来,有关巨噬细胞与神经病理性疼痛之间关系的研究蓬勃发展。长期以来,人们一直认为巨噬细胞是一种强大的免疫效应细胞,在组织稳态和病变中发挥着公认的作用,如促进组织损伤的发生和发展,改善各种发病机制相关疾病的伤口愈合和组织重塑。它们也是异质性和多功能细胞,可根据微环境信号进行表型/功能转换。中枢神经系统的神经病理性疼痛处理需要小胶质细胞(脊髓和大脑的常驻巨噬细胞),除此之外,中枢神经系统的神经病理性疼痛信号还受到组织常驻巨噬细胞和BM浸润巨噬细胞与初级传入神经元相互作用的影响。本综述研究的新证据表明,神经性疼痛的性双态性是由免疫系统(尤其是巨噬细胞)的变化而非神经系统的变化引起的。
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引用次数: 0
Cerebral malaria pathogenesis: Dissecting the role of CD4+ and CD8+ T-cells as major effectors in disease pathology 脑疟疾发病机制:剖析 CD4+ 和 CD8+ T 细胞作为主要效应因子在疾病病理学中的作用
IF 5 4区 医学 Q1 Medicine Pub Date : 2024-04-15 DOI: 10.1080/08830185.2024.2336539
Indu Sharma, Poonam Kataria, Jyoti Das
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum (P. falciparum) infection, with complex pathogenesis involving multiple factors, including the host’s immunological response....
脑疟疾(CM)是恶性疟原虫(P. falciparum)感染的一种严重并发症,发病机制复杂,涉及多种因素,包括宿主的免疫反应....。
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引用次数: 0
The emerging role of T helper 9 (Th9) cells in immunopathophysiology: A comprehensive review of their effects and responsiveness in various disease states. T 辅助细胞 9 (Th9) 在免疫病理生理学中的新作用:全面回顾它们在各种疾病状态中的作用和反应。
IF 4.3 4区 医学 Q2 IMMUNOLOGY Pub Date : 2024-01-01 Epub Date: 2024-06-12 DOI: 10.1080/08830185.2024.2364586
Manoj Khokhar, Purvi Purohit

Th9 cells, a subset of T-helper cells producing interleukin-9 (IL-9), play a vital role in the adaptive immune response and have diverse effects in different diseases. Regulated by transcription factors like PU.1 and IRF4, and cytokines such as IL-4 and TGF-β, Th9 cells drive tissue inflammation. This review focuses on their emerging role in immunopathophysiology. Th9 cells exhibit immune-mediated cancer cell destruction, showing promise in glioma and cervical cancer treatment. However, their role in breast and lung cancer is intricate, requiring a deeper understanding of pro- and anti-tumor aspects. Th9 cells, along with IL-9, foster T cell and immune cell proliferation, contributing to autoimmune disorders. They are implicated in psoriasis, atopic dermatitis, and infections. In allergic reactions and asthma, Th9 cells fuel pro-inflammatory responses. Targeting Foxo1 may regulate innate and adaptive immune responses, alleviating disease symptoms. This comprehensive review outlines Th9 cells' evolving immunopathophysiological role, emphasizing the necessity for further research to grasp their effects and potential therapeutic applications across diseases.

Th9细胞是产生白细胞介素-9(IL-9)的T辅助细胞亚群,在适应性免疫反应中发挥着重要作用,并对不同疾病产生不同影响。在 PU.1 和 IRF4 等转录因子以及 IL-4 和 TGF-β 等细胞因子的调控下,Th9 细胞驱动组织炎症。本综述将重点讨论它们在免疫病理生理学中新出现的作用。Th9 细胞具有免疫介导的癌细胞破坏作用,在胶质瘤和宫颈癌治疗中大有可为。然而,Th9 细胞在乳腺癌和肺癌中的作用错综复杂,需要对其促癌和抗癌方面有更深入的了解。Th9细胞与IL-9一起促进T细胞和免疫细胞增殖,导致自身免疫性疾病。它们与牛皮癣、特应性皮炎和感染有关。在过敏反应和哮喘中,Th9 细胞会助长促炎反应。靶向 Foxo1 可调节先天性和适应性免疫反应,减轻疾病症状。这篇全面的综述概述了 Th9 细胞不断演变的免疫病理生理学作用,强调了进一步研究的必要性,以掌握它们在各种疾病中的作用和潜在治疗应用。
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引用次数: 0
STAT4 and STAT6, their role in cellular and humoral immunity and in diverse human diseases. STAT4 和 STAT6,它们在细胞和体液免疫以及各种人类疾病中的作用。
IF 4.3 4区 医学 Q2 IMMUNOLOGY Pub Date : 2024-01-01 Epub Date: 2024-08-26 DOI: 10.1080/08830185.2024.2395274
Manlio Tolomeo, Antonio Cascio

Signal transducer and activator of transcription (STAT) 4 and STAT6 play a crucial role in immune cells by transducing signals from specific cytokine receptors, and inducing transcription of genes involved in cell-mediated and humoral immunity. These two different defense mechanisms against pathogens are regulated by two specific CD4+ T helper (Th) cells known as Th1 and Th2 cells. Many studies have shown that several diseases including cancer, inflammatory, autoimmune and allergic diseases are associated with a Th1/Th2 imbalance caused by increased or decreased expression/activity of STAT4 or STAT6 often due to genetic and epigenetic aberrances. An altered expression of STAT4 has been observed in different tumors and autoimmune diseases, while a dysregulation of STAT6 signaling pathway is frequently observed in allergic conditions, such as atopic dermatitis, allergic asthma, food allergy, and tumors such as Hodgkin and non-Hodgkin lymphomas. Recently, dysregulations of STAT4 and STAT6 expression have been observed in SARS-CoV2 and monkeypox infections, which are still public health emergencies in many countries. SARS-CoV-2 can induce an imbalance in Th1 and Th2 responses with a predominant activation of STAT6 in the cytosol and nuclei of pneumocytes that drives Th2 polarization and cytokine storm. In monkeypox infection the virus can promote an immune evasion by inducing a Th2 response that in turn inhibits the Th1 response essential for virus elimination. Furthermore, genetic variations of STAT4 that are associated with an increased risk of developing systemic lupus erythematosus seem to play a role in defense against SARS-CoV-2 infection.

信号转导和激活转录(STAT)4 和 STAT6 在免疫细胞中发挥着至关重要的作用,它们从特定的细胞因子受体转导信号,并诱导参与细胞介导免疫和体液免疫的基因转录。这两种针对病原体的不同防御机制是由两种被称为 Th1 和 Th2 细胞的特定 CD4+ T 辅助(Th)细胞调控的。许多研究表明,包括癌症、炎症性疾病、自身免疫性疾病和过敏性疾病在内的多种疾病都与 Th1/Th2 失衡有关,而这种失衡是由 STAT4 或 STAT6 的表达/活性增高或降低(通常是由于遗传和表观遗传失常造成的)引起的。在不同的肿瘤和自身免疫性疾病中观察到 STAT4 表达的改变,而在过敏性疾病(如特应性皮炎、过敏性哮喘、食物过敏)和肿瘤(如霍奇金淋巴瘤和非霍奇金淋巴瘤)中经常观察到 STAT6 信号通路的失调。最近,在SARS-CoV2和猴痘感染中观察到STAT4和STAT6表达失调,这两种疾病在许多国家仍是突发公共卫生事件。SARS-CoV-2 可诱导 Th1 和 Th2 反应失衡,STAT6 在肺炎细胞的细胞膜和细胞核中被激活,从而推动 Th2 极化和细胞因子风暴。在猴痘感染中,病毒可通过诱导 Th2 反应促进免疫逃避,而 Th2 反应反过来又会抑制消除病毒所必需的 Th1 反应。此外,STAT4 基因变异会增加患系统性红斑狼疮的风险,这种变异似乎在抵御 SARS-CoV-2 感染方面发挥了作用。
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引用次数: 0
Orchestration of immune response by innate lymphoid cell subtype 2 at various tumor microenvironment, a suitable target for cancer immunotherapy. 先天性淋巴细胞亚型 2 在各种肿瘤微环境中协调免疫反应,是癌症免疫疗法的合适靶点。
IF 5 4区 医学 Q1 Medicine Pub Date : 2024-01-01 Epub Date: 2023-08-21 DOI: 10.1080/08830185.2023.2247021
Rajdeep Roy, Tanmoy Das, Nabendu Biswas

Innate lymphoid cells are a mixed population of cells and critical regulators of our innate immune system. According to recent scientific literature, tissue resident innate lymphoid cell subtype 2 has been recognized as an important player of type 2 inflammatory responses, involved in different human malignancies like pancreatic, lung, acute myeloid leukemia, gastrointestinal tract cancer, etc. The current reports have revealed that, among the three main ILC sub types, subtype 2 (ILC 2), as the key regulator of initiating the type 2 inflammatory responses at the tumor microenvironment (TME). This activation of ILC-2 is a very important step for the specific downstream functioning of ILC-2. Priming of ILC-2 with different chemokines involves different cytokine secretion from the activated ILC-2 like IL-4, IL-5, IL-13, IL-9 which induce type 2 inflammatory responses involved in the complex interaction with other immune cells like NK cell, Cytotoxic T cell, MDSC and Treg cell. At the initial stage, ILC-2 activation through IL-33 may induce the anti-tumorigenic effect mediated by ILC-2/eosinophil axis. However, it is also evident that PDG2 (Prostaglandin D2)-mediated activation of ILC-2 induces the ILC-2/MDSC immune suppressive pro-tumorigenic niche at the TME. Here, in this review, we have summarized the function of ILC-2 on cancer immunity based on recent scientific work which indicates ILC-2 plays a dual role and orchestrates the immune responses toward type 2 immunity in different cancer settings.

先天性淋巴细胞是一种混合细胞群,也是先天性免疫系统的关键调节因子。根据最近的科学文献,组织常驻先天性淋巴细胞亚型 2 被认为是第二类炎症反应的重要参与者,参与了胰腺癌、肺癌、急性髓性白血病、胃肠道癌等不同人类恶性肿瘤的治疗。目前的报告显示,在三种主要的 ILC 亚型中,亚型 2(ILC 2)是在肿瘤微环境(TME)中启动 2 型炎症反应的关键调节因子。激活 ILC-2 是 ILC-2 发挥特定下游功能的重要步骤。用不同的趋化因子激活 ILC-2,活化的 ILC-2 会分泌不同的细胞因子,如 IL-4、IL-5、IL-13、IL-9,从而诱发 2 型炎症反应,并与 NK 细胞、细胞毒性 T 细胞、MDSC 和 Treg 细胞等其他免疫细胞发生复杂的相互作用。在初期阶段,ILC-2 通过 IL-33 激活可能会诱导 ILC-2/ 嗜酸性粒细胞轴介导的抗肿瘤作用。然而,PDG2(前列腺素 D2)介导的 ILC-2 激活在 TME 诱导 ILC-2/MDSC 的免疫抑制促致癌龛也是显而易见的。在本综述中,我们根据最近的科学研究总结了ILC-2在癌症免疫中的功能,这些研究表明ILC-2在不同的癌症环境中扮演着双重角色,并协调着对2型免疫的免疫反应。
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引用次数: 0
Cholesterol: A friend to viruses. 胆固醇病毒的朋友
IF 5 4区 医学 Q1 Medicine Pub Date : 2024-01-01 Epub Date: 2024-02-19 DOI: 10.1080/08830185.2024.2314577
Yingchun Wang, Lifen Gao

Cholesterol is a key life-sustaining molecule which regulates membrane fluidity and serves as a signaling mediator. Cholesterol homeostasis is closely related to various pathological conditions including tumor, obesity, atherosclerosis, Alzheimer's disease and viral infection. Viral infection disrupts host cholesterol homeostasis, facilitating their own survival. Meanwhile, the host cells strive to reduce cholesterol accessibility to limit viral infection. This review focuses on the regulation of cholesterol metabolism and the role of cholesterol in viral infection, specifically providing an overview of cholesterol as a friend to promote viral entry, replication, assembly, release and immune evasion, which might inspire valuable thinking for pathogenesis and intervention of viral infection.

胆固醇是一种维持生命的关键分子,它能调节膜的流动性并充当信号介质。胆固醇平衡与各种病理状况密切相关,包括肿瘤、肥胖、动脉粥样硬化、阿尔茨海默病和病毒感染。病毒感染会破坏宿主细胞的胆固醇平衡,从而促进宿主细胞的生存。与此同时,宿主细胞努力降低胆固醇的可及性,以限制病毒感染。本综述侧重于胆固醇代谢的调控和胆固醇在病毒感染中的作用,特别是概述了胆固醇作为促进病毒进入、复制、组装、释放和免疫逃避的朋友,这可能会启发人们对病毒感染的发病机制和干预进行有价值的思考。
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引用次数: 0
Natural and genetically-modified animal models to investigate pulmonary and extrapulmonary manifestations of COVID-19. 研究 COVID-19 肺部和肺外表现的天然和基因改造动物模型。
IF 5 4区 医学 Q1 Medicine Pub Date : 2024-01-01 Epub Date: 2022-06-25 DOI: 10.1080/08830185.2022.2089666
Shikha Tiwari, Garima Goel, Ashok Kumar

Coronavirus disease-19 (COVID-19), a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is a primarily respiratory tract disease. Suitable animal models for COVID-19 are required to study various aspects of pathogenesis, drug discovery, effective and safe vaccine development. Several laboratory animals including, non-human primates, hamsters, ferrets, transgenic mice, and zebrafish, have been used and proven their significance experimentally. Currently available animal models of SARS-CoV-2 can be broadly classified into two categories 1) natural animal models 2) genetically-modified that exhibit different degrees of susceptibility of SARS-CoV-2, tissue damage in respiratory and other organ systems. Not all the available animal models mimic COVID-19-like phenotype completely. Therefore, understanding various aspects of COVID-19 requires different animal models. In this review article, we provide an update on the immune response and clinical manifestations observed in naturally occurring and genetically-modified animals of COVID-19. We then review the transmission, viral replication, lung pathology, immunological aspects, and extrapulmonary phenotypes observed in various animal models. In the end, we put forth our perspective on the anticipated uses, disadvantages, and limitations of each type of animal model.

冠状病毒病-19(COVID-19)是由严重急性呼吸系统综合征冠状病毒-2(SARS-CoV-2)引起的大流行病,主要是一种呼吸道疾病。需要针对 COVID-19 建立合适的动物模型,以研究发病机制、药物发现、有效和安全疫苗开发等各个方面。一些实验动物,包括非人灵长类动物、仓鼠、雪貂、转基因小鼠和斑马鱼,都已被使用并通过实验证明了其重要性。目前可用的 SARS-CoV-2 动物模型大致可分为两类:1)天然动物模型;2)基因改造动物模型,这些动物模型对 SARS-CoV-2 有不同程度的易感性,对呼吸系统和其他器官系统造成不同程度的组织损伤。并非所有现有的动物模型都能完全模拟 COVID-19 的表型。因此,了解 COVID-19 的各个方面需要不同的动物模型。在这篇综述文章中,我们将介绍在 COVID-19 的自然发生动物和基因改造动物中观察到的免疫反应和临床表现的最新情况。然后,我们回顾了在各种动物模型中观察到的传播、病毒复制、肺部病理、免疫学方面和肺外表型。最后,我们就每种动物模型的预期用途、缺点和局限性提出了自己的观点。
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引用次数: 3
Chemokines: A key driver for inflammation in protozoan infection. 趋化因子:原生动物感染炎症的关键驱动因素。
IF 5 4区 医学 Q1 Medicine Pub Date : 2024-01-01 Epub Date: 2023-11-19 DOI: 10.1080/08830185.2023.2281566
Rubika Chauhan, Mrinalini Tiwari, Amrendra Chaudhary, Reva Sharan Thakur, Veena Pande, Jyoti Das

Chemokines belong to the group of small proteins within the cytokine family having strong chemo-attractant properties. In most cases, the strong immuno-modulatory role of chemokines is crucial for generating the immune response against pathogens in various protozoan diseases. In this review, we have given a brief update on the classification, characterization, homeostasis, transcellular migration, and immuno-modulatory role of chemokines. Here we will evaluate the potential role of chemokines and their regulation in various protozoan diseases. There is a significant direct relationship between parasitic infection and the recruitment of effector cells of the immune response. Chemokines play an indispensable role in mediating several defense mechanisms against infection, such as leukocyte recruitment and the generation of innate and cell-mediated immunity that aids in controlling/eliminating the pathogen. This process is controlled by the chemotactic movement of chemokines induced as a primary host immune response. We have also addressed that chemokine expressions during infection are time-dependent and orchestrated in a systematic pattern that ultimately assists in generating a protective immune response. Taken together, this review provides a systematic understanding of the complexity of chemokines profiles during protozoan disease conditions and the rationale of targeting chemokines for the development of therapeutic strategies.

趋化因子属于细胞因子家族中的一组小蛋白,具有很强的趋化特性。在大多数情况下,趋化因子的强大免疫调节作用对于产生针对各种原生动物疾病病原体的免疫应答至关重要。在这篇综述中,我们简要介绍了趋化因子的分类、特征、稳态、跨细胞迁移和免疫调节作用。在这里,我们将评估趋化因子及其调控在各种原生动物疾病中的潜在作用。寄生虫感染与免疫应答效应细胞的募集之间存在着重要的直接关系。趋化因子在介导几种抵抗感染的防御机制中发挥着不可或缺的作用,例如白细胞募集和先天免疫和细胞介导免疫的产生,有助于控制/消除病原体。这一过程是由趋化因子的趋化运动所控制的,这是一种主要的宿主免疫反应。我们还指出,趋化因子在感染期间的表达是时间依赖性的,并以一种系统的模式进行编排,最终有助于产生保护性免疫反应。综上所述,本综述提供了对原虫疾病条件下趋化因子谱复杂性的系统理解,以及针对趋化因子制定治疗策略的基本原理。
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引用次数: 0
期刊
International Reviews of Immunology
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