bioengineering

生物工程
  • 文章类型: Journal Article
    生物能源开发对于实现碳中和至关重要。来自农业的生物质残留物,森林,和牲畜粪便在中国提供了大量的生物能源资源,但是他们的可用性,气候,经济影响尚未得到系统评估。在这里,我们评估生物质的可持续性,生物能源潜力,减少温室气体排放(GHG),和使用集成数据建模方法的成本效益。在全国范围内,只有27%的生物质可以用于可持续的生物能源生产,但可以通过优化区域利用来显著缓解气候变化。生物能源的年度温室气体减排量可达到1.0GtCO2e,或1.4GtCO2e用于具有碳捕获和储存的生物能源(BECCS),与中国陆地生态系统碳汇总量相当。减排成本因地区而异,但低于许多其他碳去除技术。我们的发现揭示了有助于碳中和的特定区域生物能源途径,并鼓励未来评估,以探索包括技术进步和碳市场在内的因素。
    Bioenergy development is critical for achieving carbon neutrality. Biomass residues from agriculture, forest, and livestock manure provide substantial bioenergy resources in China, but their availability, climate, and economic impacts have not been evaluated systematically. Here we assess biomass sustainability, bioenergy potential, greenhouse gas emissions (GHG) reduction, and cost-effectiveness using an integrated data-modeling approach. Nationally, only 27% of biomass can be used for sustainable bioenergy production, but can contribute to significant climate change mitigation with optimized regional utilization. The annual GHG reduction can reach 1.0 Gt CO2e for bioenergy, or 1.4 Gt CO2e for bioenergy with carbon capture and storage (BECCS), which is comparable to total terrestrial ecosystem carbon sinks in China. The abatement cost varies regionally but is lower than many other carbon removal technologies. Our findings reveal region-specific bioenergy pathways that contribute to carbon neutrality, and encourage future assessments to explore factors including technological advances and carbon markets.
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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
    从牙锥束计算机断层扫描(CBCT)精确分割牙源性囊性病变(OCL)对于有效的牙科诊断至关重要。尽管监督学习方法在分割各种疾病方面已经显示出实际的诊断结果,它们分割涵盖不同亚类品种的OCL的能力尚未得到广泛研究。
    在这项研究中,我们提出了一种新的监督学习方法,称为OCL-Net,它结合了多尺度U-Net模型,以及经过联合监督损失训练的自动适应机制。回顾性收集了一家医院的匿名CBCT图像。为了评估我们的模型提高颌面外科医生诊断效率的能力,我们进行了一项诊断评估,包括7名临床医生在有或没有自动分段面罩辅助的情况下进行诊断.
    我们收集了300张匿名CBCT图像,这些图像被手动注释以用于分割掩模。大量实验证明了我们的OCL-Net对CBCTOCL分割的有效性,实现88.84%的整体骰子得分,IoU得分为81.23%,AUC评分为92.37%。通过我们的诊断评估,我们发现,当临床医生得到来自OCL-Net的分割标签的辅助时,他们的平均诊断准确率从53.21%提高到55.71%,而平均花费时间从101s显著减少到47s(P<0.05)。
    这些发现证明了我们的方法作为CBCT图像中OCL的鲁棒自动分割系统的潜力,而分段面罩可用于进一步提高OCLs牙科诊断效率。
    UNASSIGNED: Precise segmentation of Odontogenic Cystic Lesions (OCLs) from dental Cone-Beam Computed Tomography (CBCT) is critical for effective dental diagnosis. Although supervised learning methods have shown practical diagnostic results in segmenting various diseases, their ability to segment OCLs covering different sub-class varieties has not been extensively investigated.
    UNASSIGNED: In this study, we propose a new supervised learning method termed OCL-Net that combines a Multi-Scaled U-Net model, along with an Auto-Adapting mechanism trained with a combined supervised loss. Anonymous CBCT images were collected retrospectively from one hospital. To assess the ability of our model to improve the diagnostic efficiency of maxillofacial surgeons, we conducted a diagnostic assessment where 7 clinicians were included to perform the diagnostic process with and without the assistance of auto-segmentation masks.
    UNASSIGNED: We collected 300 anonymous CBCT images which were manually annotated for segmentation masks. Extensive experiments demonstrate the effectiveness of our OCL-Net for CBCT OCLs segmentation, achieving an overall Dice score of 88.84%, an IoU score of 81.23%, and an AUC score of 92.37%. Through our diagnostic assessment, we found that when clinicians were assisted with segmentation labels from OCL-Net, their average diagnostic accuracy increased from 53.21% to 55.71%, while the average time spent significantly decreased from 101s to 47s (P<0.05).
    UNASSIGNED: The findings demonstrate the potential of our approach as a robust auto-segmentation system on OCLs in CBCT images, while the segmented masks can be used to further improve OCLs dental diagnostic efficiency.
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  • 文章类型: Journal Article
    考虑到生物技术专业传统的制造过程学习方法中存在的问题,本文介绍了“重组人红细胞生成制造过程虚拟仿真实验”课程的开发和实施过程。该实验结合了现代生物制造技术和三维信息技术,以重组人红细胞生成药物为焦点。本文阐述了教学理念,目标,内容,实施方法,实验程序,互动的步骤,和实验中使用的评估标准。通过创新性实验方案设计,教学方法,和评估系统,本课程旨在培养学生在生物制药工程领域的分析和解决问题的能力,同时也拓宽了学生的视野和视野。
    Considering the issues present in traditional learning methods of manufacturing process for biotechnology majors, this paper presents the development and implementation process of the course entitled \"Virtual Simulation Experiment of Recombinant Human Erythropoiesis Manufacturing Process\". The experiment combines modern biological manufacturing technology and three-dimensional information technology, with recombinant human erythropoiesis drug serving as the focal point. This paper elaborates on the teaching concepts, objectives, contents, implementation methods, experimental procedures, interactive steps, and assessment criteria used in the experiment. Through innovative experimental scheme design, teaching methodologies, and evaluation systems, this course aims to cultivate students\' analytical and problem-solving skills in the field of biopharmaceutical engineering, while also broadening students\' perspective and expanding their vision.
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  • 文章类型: Journal Article
    单纯疱疹病毒-1(HSV-1)感染可引起各种疾病,并且目前的疗法具有有限的功效。小干扰RNA(siRNA)疗法是通过直接靶向病毒mRNA来对抗感染性疾病的有希望的方法。最近,我们采用了一种新型的tRNA支架来生产具有少量天然转录后修饰的重组siRNA试剂。在这项研究中,我们的目的是通过生物工程技术开发一种基于siRNA治疗的抗HSV-1感染的特异性前药。我们筛选并发现HSV-1基因组的UL8是基于RNAi的理想抗病毒靶标。接下来,我们使用一种新的生物工程方法在大肠杆菌中制备具有高纯度和活性的重组UL8-siRNA(r/si-UL8)。将r/si-UL8选择性地加工成成熟的si-UL8,并显着减少了人细胞中感染性病毒体的数量。通过柔性纳米脂质体递送的r/si-UL8显着降低了皮肤中的病毒载量,并提高了预防性小鼠带状疱疹样模型的存活率。此外,r/si-UL8还有效抑制3D人类表皮皮肤模型中的HSV-1感染。一起来看,我们的研究结果突出表明,新的siRNA生物工程技术是传统siRNA治疗方法的独特补充,而r/si-UL8可能是治疗HSV-1感染的有前景的前药.
    Herpes simplex virus-1 (HSV-1) infection can cause various diseases and the current therapeutics have limited efficacy. Small interfering RNA (siRNA) therapeutics are a promising approach against infectious diseases by targeting the viral mRNAs directly. Recently, we employed a novel tRNA scaffold to produce recombinant siRNA agents with few natural posttranscriptional modifications. In this study, we aimed to develop a specific prodrug against HSV-1 infection based on siRNA therapeutics by bioengineering technology. We screened and found that UL8 of the HSV-1 genome was an ideal antiviral target based on RNAi. Next, we used a novel bio-engineering approach to manufacture recombinant UL8-siRNA (r/si-UL8) in Escherichia coli with high purity and activity. The r/si-UL8 was selectively processed to mature si-UL8 and significantly reduced the number of infectious virions in human cells. r/si-UL8 delivered by flexible nano-liposomes significantly decreased the viral load in the skin and improved the survival rate in the preventive mouse zosteriform model. Furthermore, r/si-UL8 also effectively inhibited HSV-1 infection in a 3D human epidermal skin model. Taken together, our results highlight that the novel siRNA bioengineering technology is a unique addition to the conventional approach for siRNA therapeutics and r/si-UL8 may be a promising prodrug for curing HSV-1 infection.
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  • 文章类型: Journal Article
    巨噬细胞是免疫系统的核心,几乎存在于所有组织中。最近,基于巨噬细胞的疗法的发展引起了极大的兴趣。这些疗法利用巨噬细胞在免疫中的关键作用,他们驾驭生物屏障的能力,以及它们在肿瘤中积聚的趋势。这篇综述探讨了基于巨噬细胞的治疗的进展。我们讨论了巨噬细胞的生物工程,以改善抗肿瘤作用,使用CAR巨噬细胞治疗靶向癌细胞,和巨噬细胞作为治疗递送的载体。此外,我们检查工程巨噬细胞产品,像细胞外囊泡和膜包被的纳米颗粒,它们在精确和毒性较小的肿瘤治疗中的潜力。还强调了将这些疗法从研究转移到临床实践的挑战。目的是简明扼要地总结现状,挑战,以及工程巨噬细胞在癌症治疗中的未来方向。
    Macrophages are central to the immune system and are found in nearly all tissues. Recently, the development of therapies based on macrophages has attracted significant interest. These therapies utilize macrophages\' key roles in immunity, their ability to navigate biological barriers, and their tendency to accumulate in tumors. This review explores the advancement of macrophage-based treatments. We discuss the bioengineering of macrophages for improved anti-tumor effects, the use of CAR macrophage therapy for targeting cancer cells, and macrophages as vehicles for therapeutic delivery. Additionally, we examine engineered macrophage products, like extracellular vesicles and membrane-coated nanoparticles, for their potential in precise and less toxic tumor therapy. Challenges in moving these therapies from research to clinical practice are also highlighted. The aim is to succinctly summarize the current status, challenges, and future directions of engineered macrophages in cancer therapy.
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  • 文章类型: Journal Article
    随着对微生物的全面认识以及理化工程和生物工程技术的快速发展,在临床疾病管理中,科学家们正在推进合理工程的细菌作为治疗各种疾病的新兴药物。工程细菌特别是指先进的物理化学或遗传技术与尖端纳米技术或物理技术相结合,它们已经被证实在裂解肿瘤中起着重要的作用,调节免疫力,影响代谢途径,等。然而,目前还没有具体的评论同时涵盖物理化学和基因工程细菌及其衍生物,更不用说它们独特的设计原则以及各种功能和应用了。在这里,物理化学和基因工程细菌的应用,并对重大突破进行分类和讨论,重点是针对癌症以外的不同特定用途和疾病的特定设计原则和工程方法。基于这些物理化学和基因工程细菌或细菌衍生物开发体内生物治疗剂的组合策略,并阐明了它们如何抑制癌症和其他疾病。此外,讨论了临床翻译面临的挑战和未来的发展方向。这篇综述有望为物理化学和基因工程细菌提供总体印象,并启发更多的研究人员。
    With the comprehensive understanding of microorganisms and the rapid advances of physiochemical engineering and bioengineering technologies, scientists are advancing rationally-engineered bacteria as emerging drugs for treating various diseases in clinical disease management. Engineered bacteria specifically refer to advanced physiochemical or genetic technologies in combination with cutting edge nanotechnology or physical technologies, which have been validated to play significant roles in lysing tumors, regulating immunity, influencing the metabolic pathways, etc. However, there has no specific reviews that concurrently cover physiochemically- and genetically-engineered bacteria and their derivatives yet, let alone their distinctive design principles and various functions and applications. Herein, the applications of physiochemically and genetically-engineered bacteria, and classify and discuss significant breakthroughs with an emphasis on their specific design principles and engineering methods objective to different specific uses and diseases beyond cancer is described. The combined strategies for developing in vivo biotherapeutic agents based on these physiochemically- and genetically-engineered bacteria or bacterial derivatives, and elucidated how they repress cancer and other diseases is also underlined. Additionally, the challenges faced by clinical translation and the future development directions are discussed. This review is expected to provide an overall impression on physiochemically- and genetically-engineered bacteria and enlighten more researchers.
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  • 文章类型: Journal Article
    稀土元素的特殊性质有效地拓宽了其应用领域。如何准确识别和有效分离具有相似半径和化学性质的目标稀土离子仍然是一个巨大的挑战。这里,我们使用石墨烯氧化(GO)层之间的工程大肠杆菌膜构建了精确的二维(2D)异质通道。异质通道中Lanmodulin(LanM)与稀土离子之间的结合能力和相应构象变化的差异允许精确识别和筛分scan离子(Sc3)。工程大肠杆菌膜不仅可以保护LanM的结构和功能的完整性,丰富的脂质和糖,还通过相互作用帮助大肠杆菌膜紧密贴在GO纳米片上,防止膨胀和控制层间间距精确到亚纳米。显然,2D异质通道对三价离子表现出优异的选择性(SFFe3+/Sc3+≈3),特别是对于稀土元素中的Sc3离子具有高选择性(SFCe/Sc≈167,SFLa/Sc≈103)。长期稳定性和拉伸应变测试验证了膜的出色稳定性。因此,这个简单的,高效,和具有成本效益的工作提供了一个建议,为构建二维夹层异质通道进行精确筛分,并为Sc的高效提取提出了有价值的策略。本文受版权保护。保留所有权利。
    The special properties of rare earth elements (REE) have effectively broadened their application fields. How to accurately recognize and efficiently separate target rare earth ions with similar radii and chemical properties remains a formidable challenge. Here, precise two-dimensional (2D) heterogeneous channels are constructed using engineered E. coli membranes between graphene oxide (GO) layers. The difference in binding ability and corresponding conformational change between Lanmodulin (LanM) and rare earth ions in the heterogeneous channel allows for precisely recognizing and sieving of scandium ions (Sc3+). The engineered E. coli membranes not only can protect the integrity of structure and functionality of LanM, the rich lipids and sugars, but also help the Escherichia coli (E. coli) membranes closely tile on the GO nanosheets through interaction, preventing swelling and controlling interlayer spacing accurately down to the sub-nanometer. Apparently, the 2D heterogeneous channels showcase excellent selectivity for trivalent ions (SFFe /Sc≈3), especially for Sc3+ ions in REE with high selectivity (SFCe/Sc≈167, SFLa/Sc≈103). The long-term stability and tensile strain tests verify the membrane\'s outstanding stability. Thus, this simple, efficient, and cost-effective work provides a suggestion for constructing 2D interlayer heterogeneous channels for precise sieving, and this valuable strategy is proposed for the efficient extraction of Sc.
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  • 文章类型: Journal Article
    1型糖尿病(T1D)发展的一个重要因素是抑制性免疫检查点配体的缺乏,特异性程序性细胞死亡配体1(PD-L1)和半乳糖凝集素-9(Gal-9),在β细胞中。因此,外源性PD-L1或Gal-9对胰腺浸润T淋巴细胞的调节是治疗新发T1D的理想方法。在这里,我们对巨噬细胞进行基因工程改造,生成过表达PD-L1和Gal-9的人工细胞外囊泡(aEVs),这可以限制胰岛自身反应性T淋巴细胞并保护β细胞免受破坏.有趣的是,过表达Gal-9刺激巨噬细胞极化为具有免疫抑制属性的M2表型。或者,PD-L1和Gal-9呈递aEV(PD-L1-Gal-9aEV)均通过程序性细胞死亡蛋白1(PD-1)/PD-L1或T细胞免疫球蛋白粘蛋白3(TIM-3)/Gal-9的相互作用有利地粘附于T细胞.此外,PD-L1-Gal-9aEV在体外显着促进效应T细胞凋亡和脾调节性T细胞(Treg)细胞分化。实际上,PD-L1-Gal-9aEV有效逆转了NOD小鼠的新发高血糖,阻止T1D进展,浸润胰腺的CD4+和CD8+T细胞的比例和活化显著下降,它们共同有助于保留残留的β细胞存活和减轻高血糖。
    An important factor in the development of type 1 diabetes (T1D) is the deficiency of inhibitory immune checkpoint ligands, specifically programmed cell death ligand 1 (PD-L1) and galectin-9 (Gal-9), in β-cells. Therefore, modulation of pancreas-infiltrated T lymphocytes by exogenous PD-L1 or Gal-9 is an ideal approach for treating new-onset T1D. We genetically engineered macrophage cells to generate artificial extracellular vesicles (aEVs) overexpressing PD-L1 and Gal-9, which could restrict islet autoreactive T lymphocytes and protect β-cells from destruction. Intriguingly, overexpression of Gal-9 stimulated macrophage polarization to the M2 phenotype with immunosuppressive attributes. Alternatively, both PD-L1- and Gal-9-presenting aEVs (PD-L1-Gal-9 aEVs) favorably adhered to T cells via the interaction of programmed cell death protein 1/PD-L1 or T-cell immunoglobulin mucin 3/Gal-9. Moreover, PD-L1-Gal-9 aEVs prominently promoted effector T-cell apoptosis and splenic regulatory T (Treg) cell formation in vitro. Notably, PD-L1-Gal-9 aEVs efficaciously reversed new-onset hyperglycemia in NOD mice, prevented T1D progression, and decreased the proportion and activation of CD4+ and CD8+ T cells infiltrating the pancreas, which together contributed to the preservation of residual β-cell survival and mitigation of hyperglycemia.
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  • 文章类型: Journal Article
    胸主动脉瘤(TAA)是一种威胁生命的血管疾病,通常与潜在的遗传原因有关。对人类TAA发病机制的理解不足突出了对更好的疾病模型的需求。这里,我们通过结合人诱导多能干细胞(hiPSCs)在动物宿主中建立了功能性人TAA模型,生物工程血管移植物(BVGs),基因编辑我们从等基因对照hiPSC衍生的血管平滑肌细胞(SMC)和突变SMC基因编辑以携带Loeys-Dietz综合征(LDS)相关致病变体(TGFBR1A230T)产生了BVG。我们还使用来自患有LDS的患者的细胞(PatientA230T/+)和使用遗传校正的细胞(患者+/+)产生了hiPSC衍生的BVG。然后将对照和实验性BVG植入裸鼠的颈总动脉中。TGFBR1A230T变体导致BVG的机械性能受损,导致较低的爆裂压力和缝线保留强度。携带变体的BVGs随时间在体内扩张,类似于人类TAA的形成。空间转录组学分析显示,与患者+/+BVG相比,PatientA230T/+BVG中的细胞外基质(ECM)形成基因表达缺陷。组织学分析和蛋白质分析验证了PatientA230T/BVGs和患者组织中的定量和定性ECM缺陷,包括降低胶原羟基化。血管收缩测试证实,PatientA230T/BVG中的SMC组织也受损。用小干扰RNA沉默胶原修饰酶减少SMC来源的组织构建体中的胶原脯氨酸羟基化。这些研究证明了BVG在动物宿主中模拟人TAA形成的实用性,并强调了降低的胶原蛋白修饰酶活性在人TAA形成中的作用。
    Thoracic aortic aneurysm (TAA) is a life-threatening vascular disease frequently associated with underlying genetic causes. An inadequate understanding of human TAA pathogenesis highlights the need for better disease models. Here, we established a functional human TAA model in an animal host by combining human induced pluripotent stem cells (hiPSCs), bioengineered vascular grafts (BVGs), and gene editing. We generated BVGs from isogenic control hiPSC-derived vascular smooth muscle cells (SMCs) and mutant SMCs gene-edited to carry a Loeys-Dietz syndrome (LDS)-associated pathogenic variant (TGFBR1A230T). We also generated hiPSC-derived BVGs using cells from a patient with LDS (PatientA230T/+) and using genetically corrected cells (Patient+/+). Control and experimental BVGs were then implanted into the common carotid arteries of nude rats. The TGFBR1A230T variant led to impaired mechanical properties of BVGs, resulting in lower burst pressure and suture retention strength. BVGs carrying the variant dilated over time in vivo, resembling human TAA formation. Spatial transcriptomics profiling revealed defective expression of extracellular matrix (ECM) formation genes in PatientA230T/+ BVGs compared with Patient+/+ BVGs. Histological analysis and protein assays validated quantitative and qualitative ECM defects in PatientA230T/+ BVGs and patient tissue, including decreased collagen hydroxylation. SMC organization was also impaired in PatientA230T/+ BVGs as confirmed by vascular contraction testing. Silencing of collagen-modifying enzymes with small interfering RNAs reduced collagen proline hydroxylation in SMC-derived tissue constructs. These studies demonstrated the utility of BVGs to model human TAA formation in an animal host and highlighted the role of reduced collagen modifying enzyme activity in human TAA formation.
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