Bioengineering

生物工程
  • 文章类型: Journal Article
    限制入侵物种的负面影响,比如日本雷诺虫,已经成为科学家的挑战和管理者的必需品。生态相关,技术上可行,必须建立可持续的控制方法,以减少粳稻在生态系统中的发展或传播。我们研究的目的是在为期三年的田间试验中,调查与植物竞争相关的每月割草如何影响粳稻的发育。在测量的植物性状中,粳稻的高度生长受影响最大;在存在竞争植物的情况下,它会大大降低。联合割草和与恢复植物的竞争对粳稻的生长直径产生负面影响。大多数竞争性播种物种在限制粳稻的发育方面都很成熟和互补。植物群落表现出年际动态,其中粳稻逐渐下降。本研究采用的恢复方法使管理者能够做出适当的决定,以减少粳稻对生态系统的影响。
    Limiting the negative effects of an invasive species, such as Reynoutria japonica, has become a challenge for scientists and a necessity for managers. Ecologically relevant, technically feasible, and sustainable control methods must be created to reduce the development or spread of R. japonica in ecosystems. The objective of our study was to investigate how monthly mowing in association with plant competition affects the development of R. japonica over a three-year field experiment. Among the plant traits measured, the height growth of R. japonica was the most affected; it was strongly reduced in the presence of competing plants. Combined mowing and competition with restoration plants negatively affected the growth diameter of R. japonica. Most competitive sown species were well established and complementary in limiting the development of R. japonica. The plant communities showed interannual dynamics in which R. japonica declined progressively. The restoration methodology adopted in this study allows managers to make appropriate decisions to reduce the impact of R. japonica on ecosystems.
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  • 文章类型: Journal Article
    移植物与移植物一致证明了免疫系统根除白血病细胞的潜力。allo-HSCT和供体白细胞输注后发生的白血病效应。各种免疫治疗方法,从抗体的使用,抗体-药物缀合物,双特异性T细胞衔接者,嵌合抗原受体(CAR)T细胞,和NK细胞的治疗性输注,因此,目前正在接受有希望的测试,但相互矛盾,结果。这篇综述将集中在临床前和临床发展中的各种类型的免疫疗法,从临床血液学家的角度来看。最有希望的临床翻译疗法是使用双特异性T细胞衔接剂和针对谱系限制性抗原的CAR-T细胞。其中,在一小部分严重预处理的难治性或复发性白血病患者中,总体缓解率(ORR)可达到20%至40%。毒性主要表现在细胞因子释放综合征的发生,通过逐步加药,这在很大程度上是可以控制的,早期使用细胞因子阻断剂和皮质类固醇,和骨髓抑制。各种细胞因子增强的自然杀伤产品也在测试中,主要作为同种异体现成的疗法,具有良好的耐受性和有希望的结果(ORR:小型试验中为20-37.5%)。T淋巴细胞和NK细胞通过抑制其免疫检查点的体内激活也产生了有趣的,但有限,结果(ORR:33-59%),但与严重移植的风险增加移植患者的宿主病。因此,在这些新化合物的广泛临床应用之前,仍有几个障碍需要克服。
    The potential of the immune system to eradicate leukemic cells has been consistently demonstrated by the Graft vs. Leukemia effect occurring after allo-HSCT and in the context of donor leukocyte infusions. Various immunotherapeutic approaches, ranging from the use of antibodies, antibody-drug conjugates, bispecific T-cell engagers, chimeric antigen receptor (CAR) T-cells, and therapeutic infusions of NK cells, are thus currently being tested with promising, yet conflicting, results. This review will concentrate on various types of immunotherapies in preclinical and clinical development, from the point of view of a clinical hematologist. The most promising therapies for clinical translation are the use of bispecific T-cell engagers and CAR-T cells aimed at lineage-restricted antigens, where overall responses (ORR) ranging from 20 to 40% can be achieved in a small series of heavily pretreated patients affected by refractory or relapsing leukemia. Toxicity consists mainly in the occurrence of cytokine-release syndrome, which is mostly manageable with step-up dosing, the early use of cytokine-blocking agents and corticosteroids, and myelosuppression. Various cytokine-enhanced natural killer products are also being tested, mainly as allogeneic off-the-shelf therapies, with a good tolerability profile and promising results (ORR: 20-37.5% in small trials). The in vivo activation of T lymphocytes and NK cells via the inhibition of their immune checkpoints also yielded interesting, yet limited, results (ORR: 33-59%) but with an increased risk of severe Graft vs. Host disease in transplanted patients. Therefore, there are still several hurdles to overcome before the widespread clinical use of these novel compounds.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    骨质疏松症是由骨吸收和骨形成之间的不平衡引起的全身性骨骼疾病。目前的治疗主要涉及全身药物和激素治疗。然而,这些系统治疗缺乏方向性,对局部严重的骨质疏松症通常无效。具有复杂不良反应的可能性。因此,使用生物活性材料或外部干预的治疗策略已成为最有前途的方法.这篇综述提出了12个骨质疏松症相关病理变化的微环境治疗目标,包括炎症因子和活性氧(ROS)的局部积累,线粒体动力学失衡,胰岛素抵抗,破坏骨细胞自噬,骨细胞凋亡失衡,神经分泌物的变化,骨细胞的老化,增加局部骨组织血管破坏,减少再生。此外,本文综述了基于这些微环境治疗目标的有效或潜在的生物物理和生化刺激的研究现状,并总结了不同生物工程刺激的优势和最佳参数,以支持骨质疏松症治疗和骨再生的临床前和临床研究。最后,该综述解决了当前的挑战和未来的研究前景。
    Osteoporosis is a systemic skeletal disease caused by an imbalance between bone resorption and formation. Current treatments primarily involve systemic medication and hormone therapy. However, these systemic treatments lack directionality and are often ineffective for locally severe osteoporosis, with the potential for complex adverse reactions. Consequently, treatment strategies using bioactive materials or external interventions have emerged as the most promising approaches. This review proposes twelve microenvironmental treatment targets for osteoporosis-related pathological changes, including local accumulation of inflammatory factors and reactive oxygen species (ROS), imbalance of mitochondrial dynamics, insulin resistance, disruption of bone cell autophagy, imbalance of bone cell apoptosis, changes in neural secretions, aging of bone cells, increased local bone tissue vascular destruction, and decreased regeneration. Additionally, this review examines the current research status of effective or potential biophysical and biochemical stimuli based on these microenvironmental treatment targets and summarizes the advantages and optimal parameters of different bioengineering stimuli to support preclinical and clinical research on osteoporosis treatment and bone regeneration. Finally, the review addresses ongoing challenges and future research prospects.
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  • 文章类型: Journal Article
    长期重建造血干细胞(LT-HSC)用于通过干细胞移植治疗血液疾病。LT-HSC的极低丰度及其在体外培养过程中的快速分化阻碍了其临床应用。以前使用基质饲养层的发展,定义的培养基鸡尾酒,生物工程使HSC在培养中得以扩展,但主要是短期的HSC和祖细胞群,以幼稚的LT-HSC为代价。这里,我们报告了一个生物工程LT-HSC维持生态位的创建,重建生理细胞外基质组织,使用柔软的I型胶原水凝胶驱动血管周围基质细胞(PerSC)中的巢蛋白表达。我们证明了Nestin,由支持HSC的骨髓基质细胞表达,是细胞保护的,通过调节新陈代谢,对于PerSC中HIF-1α的表达是重要的。当将CD34+veHSC添加到包含表达巢蛋白/HIF-1α的PerSC的生物工程生态位中时,LT-HSC数量保持正常克隆和体内重建潜力,没有媒体补充。我们提供了概念证明,我们的生物工程生态位可以支持CRISPR编辑的HSC的存活。LT-HSC离体的成功编辑可以对血液疾病的治疗具有潜在影响。
    Long-term reconstituting haematopoietic stem cells (LT-HSCs) are used to treat blood disorders via stem cell transplantation. The very low abundance of LT-HSCs and their rapid differentiation during in vitro culture hinders their clinical utility. Previous developments using stromal feeder layers, defined media cocktails, and bioengineering have enabled HSC expansion in culture, but of mostly short-term HSCs and progenitor populations at the expense of naive LT-HSCs. Here, we report the creation of a bioengineered LT-HSC maintenance niche that recreates physiological extracellular matrix organisation, using soft collagen type-I hydrogels to drive nestin expression in perivascular stromal cells (PerSCs). We demonstrate that nestin, which is expressed by HSC-supportive bone marrow stromal cells, is cytoprotective and, via regulation of metabolism, is important for HIF-1α expression in PerSCs. When CD34+ve HSCs were added to the bioengineered niches comprising nestin/HIF-1α expressing PerSCs, LT-HSC numbers were maintained with normal clonal and in vivo reconstitution potential, without media supplementation. We provide proof-of-concept that our bioengineered niches can support the survival of CRISPR edited HSCs. Successful editing of LT-HSCs ex vivo can have potential impact on the treatment of blood disorders.
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  • 文章类型: Journal Article
    慢性伤口是一个巨大的全球负担,数百万人患有令人衰弱的并发症。尽管标准护理,由于持续的炎症和受损的组织再生等因素,受损的愈合持续存在。间充质干细胞(MSC)衍生的细胞外囊泡(EV)提供了一种创新的再生医学方法,在工程纳米级递送系统中递送干细胞衍生的治疗货物。这篇综述探讨了开创性的生物工程策略,以将MSC-EV设计成用于慢性伤口的精密纳米疗法。CRISPR基因编辑等新兴技术,微流体制造,仿生递送系统因其增强MSC-EV靶向的潜力而被强调,优化治疗性货物富集,并确保一致的临床级生产。然而,关键的障碍仍然存在,包括批次可变性,对潜在致瘤性进行严格的安全性评估,免疫原性,和生物分布分析。至关重要的是,协调监管科学与生物工程和患者倡导的协作框架是加快全球临床翻译的关键。通过克服这些挑战,工程MSC-EV可以催化现成的再生疗法的新时代,为数百万受无法愈合的伤口折磨的人恢复希望和愈合。
    Chronic wounds represent a significant global burden, afflicting millions with debilitating complications. Despite standard care, impaired healing persists due to factors like persistent inflammation and impaired tissue regeneration. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) offer an innovative regenerative medicine approach, delivering stem cell-derived therapeutic cargo in engineered nanoscale delivery systems. This review examines pioneering bioengineering strategies to engineer MSC-EVs into precision nanotherapeutics for chronic wounds. Emerging technologies like CRISPR gene editing, microfluidic manufacturing, and biomimetic delivery systems are highlighted for their potential to enhance MSC-EV targeting, optimize therapeutic cargo enrichment, and ensure consistent clinical-grade production. However, key hurdles remain, including batch variability, rigorous safety assessment for potential tumorigenicity, immunogenicity, and biodistribution profiling. Crucially, collaborative frameworks harmonizing regulatory science with bioengineering and patient advocacy hold the key to expediting global clinical translation. By overcoming these challenges, engineered MSC-EVs could catalyze a new era of off-the-shelf regenerative therapies, restoring hope and healing for millions afflicted by non-healing wounds.
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  • 文章类型: Journal Article
    海湾战争疾病(GWI)的特征是广泛的症状,主要表现为胃肠道症状。在这些胃肠道症状中,运动障碍非常普遍,表现为慢性便秘,胃痛,消化不良,腹泻,以及其他严重影响GWI退伍军人生活质量的疾病。然而,尽管这些退伍军人中胃肠道损伤的患病率很高,大多数研究注意力都集中在神经系统疾病上。这一观点提供了当前体内研究进展的全面概述,阐明了GWI中胃肠道疾病的潜在机制。一般来说,这些体内和体外模型表明,神经炎症改变肠道运动,并驱动GWI中报道的胃肠道症状。此外,这种观点突出了体外生物工程模型的潜力和挑战,这可能是理解和治疗胃肠道相关GWI病理的关键因素。
    Gulf War Illness (GWI) is characterized by a wide range of symptoms that manifests largely as gastrointestinal symptoms. Among these gastrointestinal symptoms, motility disorders are highly prevalent, presenting as chronic constipation, stomach pain, indigestion, diarrhea, and other conditions that severely impact the quality of life of GWI veterans. However, despite a high prevalence of gastrointestinal impairments among these veterans, most research attention has focused on neurological disturbances. This perspective provides a comprehensive overview of current in vivo research advancements elucidating the underlying mechanisms contributing to gastrointestinal disorders in GWI. Generally, these in vivo and in vitro models propose that neuroinflammation alters gut motility and drives the gastrointestinal symptoms reported in GWI. Additionally, this perspective highlights the potential and challenges of in vitro bioengineering models, which could be a crucial contributor to understanding and treating the pathology of gastrointestinal related-GWI.
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  • 文章类型: Journal Article
    在时空组织的背景下理解组织微环境(TiME)的分子和物理复杂性仍然是一个持久的挑战。工程和数据科学的最新进展现在有望研究结构,功能,和TiME的动态以前所未有的细节;然而,许多进步仍然发生在筒仓中,这些筒仓很少整合信息来研究TiME的全部细节。这篇综述提供了化学基础工程原理的综合概述,光学,电气,机械,和计算科学来探索,感觉,模型,制造TiME。在个别章节中,我们首先总结了基本原理,能力,以及新兴技术的范围,每种技术和最近的突破性发现,有前途的创新。我们提供了这些进步在回答有关TiME及其在各种疾病和发育过程中的作用的关键问题方面的潜力的观点。最后,我们提出了一种综合观点,赞赏TiME研究中的主要科学和教育方面。
    Understanding the molecular and physical complexity of the tissue microenvironment (TiME) in the context of its spatiotemporal organization has remained an enduring challenge. Recent advances in engineering and data science are now promising the ability to study the structure, functions, and dynamics of the TiME in unprecedented detail; however, many advances still occur in silos that rarely integrate information to study the TiME in its full detail. This review provides an integrative overview of the engineering principles underlying chemical, optical, electrical, mechanical, and computational science to probe, sense, model, and fabricate the TiME. In individual sections, we first summarize the underlying principles, capabilities, and scope of emerging technologies, the breakthrough discoveries enabled by each technology and recent, promising innovations. We provide perspectives on the potential of these advances in answering critical questions about the TiME and its role in various disease and developmental processes. Finally, we present an integrative view that appreciates the major scientific and educational aspects in the study of the TiME.
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  • 文章类型: Journal Article
    周围神经损伤很普遍,其治疗存在重大挑战。在各种重建方案中,神经导管和包裹是受欢迎的选择。生物工程和再生医学的进步导致了新的生物相容性材料和植入物设计的开发,这些材料和植入物设计提供了增强神经恢复的潜力。成本,神经损伤类型,在决定理想的重建方案时,必须考虑植入物的大小。
    Peripheral nerve injuries are prevalent and their treatments present significant challenges. Among the various reconstructive options, nerve conduits and wraps are popular choices. Advances in bioengineering and regenerative medicine have led to the development of new biocompatible materials and implant designs that offer the potential for enhanced neural recovery. Cost, nerve injury type, and implant size must be considered when deciding on the ideal reconstructive option.
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  • 文章类型: Journal Article
    植物免疫受体的生物工程已成为产生新的抗病性状的关键策略,以抵消植物病原体对全球粮食安全的不断扩大的威胁。然而,目前的方法受到植物病原体在田间的快速进化的限制,并且在部署时可能缺乏耐久性。这里,我们表明水稻的核苷酸结合,可以对富含亮氨酸的重复序列(NLR)免疫受体Pik-1进行工程改造,以响应来自多宿主原始真菌病原体稻瘟病菌的保守效应子家族。通过安装假定的宿主靶标,我们将PikNLR的效应子结合和响应谱从其同源稻瘟病效应子AVR-Pik转换为对哭泣loveggrass2(Pwl2)的宿主决定因子致病性,OsHIPP43代替天然整合的重金属相关域(生成Pikm-1OsHIPP43)。这种嵌合受体也对来自不同母细胞分离株的其他PWL等位基因有反应。Pwl2/OsHIPP43复合物的晶体结构显示出多面性,不容易被诱变破坏的强大界面,因此可以提供耐用的,在现场对携带PWL效应物的爆炸隔离物具有广泛的抵抗力。我们的发现强调了如何将病原体效应子的宿主靶标用于生物工程识别特异性,这些特异性与自然进化的抗病基因相比具有更强大的特性。
    Bioengineering of plant immune receptors has emerged as a key strategy for generating novel disease resistance traits to counteract the expanding threat of plant pathogens to global food security. However, current approaches are limited by rapid evolution of plant pathogens in the field and may lack durability when deployed. Here, we show that the rice nucleotide-binding, leucine-rich repeat (NLR) immune receptor Pik-1 can be engineered to respond to a conserved family of effectors from the multihost blast fungus pathogen Magnaporthe oryzae. We switched the effector binding and response profile of the Pik NLR from its cognate rice blast effector AVR-Pik to the host-determining factor pathogenicity toward weeping lovegrass 2 (Pwl2) by installing a putative host target, OsHIPP43, in place of the native integrated heavy metal-associated domain (generating Pikm-1OsHIPP43). This chimeric receptor also responded to other PWL alleles from diverse blast isolates. The crystal structure of the Pwl2/OsHIPP43 complex revealed a multifaceted, robust interface that cannot be easily disrupted by mutagenesis, and may therefore provide durable, broad resistance to blast isolates carrying PWL effectors in the field. Our findings highlight how the host targets of pathogen effectors can be used to bioengineer recognition specificities that have more robust properties compared to naturally evolved disease resistance genes.
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