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Human Adipose Tissue-Derived Stromal Cells Ameliorate Adriamycin-Induced Nephropathy by Promoting Angiogenesis. 人脂肪组织衍生基质细胞通过促进血管生成改善阿霉素诱发的肾病
IF 1.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-31 Epub Date: 2024-05-26 DOI: 10.1080/15476278.2024.2356339
Xiaodi Zhao, Chengyan Ma, Lijie Li, Yuemei Yang, Sen Zhang, Xiaoli Wang

This study is to investigate the therapeutical effect and mechanisms of human-derived adipose mesenchymal stem cells (ADSC) in relieving adriamycin (ADR)-induced nephropathy (AN). SD rats were separated into normal group, ADR group, ADR+Losartan group (20 mg/kg), and ADR + ADSC group. AN rats were induced by intravenous injection with adriamycin (8 mg/kg), and 4 d later, ADSC (2 × 105 cells/mouse) were administrated twice with 2 weeks interval time (i.v.). The rats were euthanized after the 6 weeks' treatment. Biochemical indicators reflecting renal injury, such as blood urea nitrogen (BUN), neutrophil gelatinase alpha (NGAL), serum creatinine (Scr), inflammation, oxidative stress, and pro-fibrosis molecules, were evaluated. Results demonstrated that we obtained high qualified ADSCs for treatment determined by flow cytometry, and ADSCs treatment significantly ameliorated renal injuries in DN rats by decreasing BUN, Scr and NGAL in peripheral blood, as well as renal histopathological injuries, especially protecting the integrity of podocytes by immunofluorescence. Furthermore, ADSCs treatment also remarkably reduced the renal inflammation, oxidative stress, and fibrosis in DN rats. Preliminary mechanism study suggested that the ADSCs treatment significantly increased renal neovascularization via enhancing proangiogenic VEGF production. Pharmacodynamics study using in vivo imaging confirmed that ADSCs via intravenous injection could accumulate into the kidneys and be alive at least 2 weeks. In a conclusion, ADSC can significantly alleviate ADR-induced nephropathy, and mainly through reducing oxidative stress, inflammation and fibrosis, as well as enhancing VEGF production.

本研究旨在探讨人源脂肪间充质干细胞(ADSC)对缓解阿霉素(ADR)诱导的肾病(AN)的治疗效果和机制。将SD大鼠分为正常组、ADR组、ADR+洛沙坦组(20 mg/kg)和ADR+ADSC组。通过静脉注射阿霉素(8 毫克/千克)诱导 AN 大鼠,4 天后注射 ADSC(2 × 105 个细胞/只小鼠)两次,每次间隔 2 周(静脉注射)。大鼠在治疗 6 周后安乐死。评估反映肾损伤的生化指标,如血尿素氮(BUN)、中性粒细胞明胶酶α(NGAL)、血清肌酐(Scr)、炎症、氧化应激和促纤维化分子。结果表明,通过流式细胞仪测定,我们获得了高质量的 ADSCs 用于治疗,ADSCs 治疗显著改善了 DN 大鼠的肾损伤,降低了外周血中的 BUN、Scr 和 NGAL,也减轻了肾组织病理学损伤,尤其是通过免疫荧光检测保护了荚膜细胞的完整性。此外,ADSCs 治疗还显著减轻了 DN 大鼠的肾脏炎症、氧化应激和纤维化。初步机理研究表明,ADSCs 治疗可通过促进血管内皮生长因子(VEGF)的产生,显著增加肾脏新生血管。利用体内成像技术进行的药效学研究证实,ADSCs 经静脉注射可在肾脏内蓄积并存活至少 2 周。总之,ADSC 能显著缓解 ADR 引起的肾病,主要是通过减少氧化应激、炎症和纤维化,以及促进血管内皮生长因子的产生。
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引用次数: 0
Does DNA extraction affect the specificity of a PCR method claiming the specific detectability of a genome-edited plant? DNA 提取是否会影响声称具有基因组编辑植物特异性检测能力的 PCR 方法的特异性?
IF 4.5 2区 农林科学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-31 Epub Date: 2024-11-14 DOI: 10.1080/21645698.2024.2423441
Sophia Edelmann, Christian Savini, Dominik Moor, Jörn Lämke, Kathrin Lieske, Marco Mazzara, Hendrik Emons, Joachim Mankertz, Christopher Weidner

Under current EU legislation, genetically modified organisms (GMOs) and derived food and feed products must be authorized as GM food, feed, or seed and appropriate detection methods must be made available for use in official controls. A Real-Time PCR method has recently been published by Chhalliyil et al. claiming to be specific for the detection and identification of genome-edited oilseed rape (OSR) lines commercialized in North America. In a previous study, we have independently assessed this method in three reference laboratories for sensitivity, specificity, and robustness. We found that the method does not meet all the minimum performance requirements (MPR) for GMO testing in the EU, which contradicts the claims of the method developer. Here we show, in addition to the previously published method assessment study that a modified DNA extraction is not the reason for the contradictory findings and does not affect the specificity of the method. We also discuss the procedures recently proposed by the method developers for interpreting PCR results with high Cq values.

根据欧盟现行法律,转基因生物 (GMO) 及其衍生食品和饲料产品必须被授权为转基因食品、饲料或种子,并且必须提供适当的检测方法用于官方控制。Chhalliyil 等人最近发表了一种实时 PCR 方法,声称该方法可特异性地检测和鉴定北美商业化的基因组编辑油菜(OSR)品系。在之前的一项研究中,我们在三个参考实验室对该方法的灵敏度、特异性和稳健性进行了独立评估。我们发现,该方法不符合欧盟转基因生物检测的所有最低性能要求(MPR),这与方法开发者的说法相矛盾。在此,除了之前公布的方法评估研究外,我们还表明,修改 DNA 提取方法并不是产生矛盾结论的原因,也不会影响该方法的特异性。我们还讨论了方法开发者最近提出的解释高 Cq 值 PCR 结果的程序。
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引用次数: 0
Consumers' response to genetically modified food: an Italian case study. 消费者对转基因食品的反应:意大利案例研究。
IF 4.5 2区 农林科学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-31 Epub Date: 2024-11-06 DOI: 10.1080/21645698.2024.2417473
Federica DeMaria, Simona Romeo Lironcurti, Federica Morandi, Alessandra Pesce, Laura Gazza, Francesca Nocente

The agricultural sector could benefit from biotechnologies in addressing challenges such as pests, droughts, and food supply issues. Genetically modified (GM) crops have been developed to offer not only economic advantages to farmers but also to contribute positively to the environment, human health, and consumer well-being. However, consumers' hesitancy in buying GM food may stem from societal reactions to how biotechnologies in agriculture have been regulated so far. The legislative debate that led, in early 2024, to the approval of Commission's proposal (COM(2023) 411 final) - aimed at simplifying the authorization process for plants obtained with certain new genomic techniques (NGTs) - has sparkled public discussion in the European Union on the application of biotechnologies in agriculture. This work aims to investigate Italian consumers' acceptance toward GM food. Through data collected from an original survey (N = 564), we tested a) their level of knowledge of GM techniques; b) if they are aware of differences between established techniques based on classical approaches of crossing and selection and more precise biotechnological techniques; c) their propensity to buy GM food, with a specific focus on food safety and environmental sustainability issues. By using a Multinomial Logit Model (MNL), starting from three hypotheses, the study highlights a gap in knowledge transfer and, in general, the communication process. This results in widespread misinformation that hinders informed consumer choices. The study also emphasizes consumers' sensitivity to food safety, including environmental issues, but still related to food safety issues.

在应对虫害、干旱和粮食供应问题等挑战方面,农业部门可以从生物技术中受益。转基因作物的开发不仅为农民带来了经济利益,也为环境、人类健康和消费者福祉做出了积极贡献。然而,消费者对购买转基因食品的犹豫不决可能源于社会对迄今为止农业生物技术监管方式的反应。2024 年初,欧盟委员会的提案(COM(2023) 411 final)旨在简化通过某些新基因组技术(NGTs)获得的植物的授权程序,该提案的立法辩论引发了欧盟关于生物技术在农业中的应用的公开讨论。这项工作旨在调查意大利消费者对转基因食品的接受程度。通过原始调查收集的数据(N = 564),我们测试了 a) 消费者对转基因技术的了解程度;b) 消费者是否了解基于经典杂交和选择方法的成熟技术与更精确的生物技术之间的差异;c) 消费者购买转基因食品的倾向,特别关注食品安全和环境可持续性问题。通过使用多项式对数模型(MNL),从三个假设出发,该研究强调了知识传播和一般传播过程中的差距。这导致了广泛的错误信息,阻碍了消费者做出明智的选择。研究还强调了消费者对食品安全的敏感性,包括环境问题,但仍与食品安全问题有关。
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引用次数: 0
Laser-based directed energy deposition of Monel K-500 and Stellite 6 multi-materials 基于激光的定向能沉积 Monel K-500 和 Stellite 6 复合材料
IF 10.6 1区 工程技术 Q1 ENGINEERING, MANUFACTURING Pub Date : 2024-12-31 DOI: 10.1080/17452759.2024.2399789
Ze Chen, Zhongji Sun, Yang Qi, Wei Fan, Verner Soh Qun Liang, Sastry Yagnanna Kandukuri, Paulo Jorge Da Silva Bartolo, Kun Zhou
Laser-based directed energy deposition (L-DED) offers significant advantages for repairing metal structures, particularly in the marine and offshore industry where corrosion-resistant materials like Monel K-500 (a Ni-Cu alloy) lack strength and wear resistance. This study addresses this issue by producing Monel K-500 with high-strength Stellite 6 (a Co-Cr alloy). Two types of multi-material samples were created using L-DED: interlayered and mixed powder samples. The interlayered samples experienced cracking at the material interface, while the mixed powder samples were crack-free and exhibited improved mechanical properties, with yield strength increasing from 208.3 MPa to 490.2 MPa and ultimate tensile strength from 429.7 MPa to 887.0 MPa compared to single Monel K-500 samples. This research demonstrated the potential of in-situ alloying during the L-DED process to enhance alloy properties and highlighted the challenges of abrupt compositional changes leading to cracking, suggesting mitigation strategies for successful production.
激光定向能沉积技术(L-DED)在修复金属结构方面具有显著优势,尤其是在海洋和近海工业领域,因为在这些领域,像 Monel K-500(一种镍铜合金)这样的耐腐蚀材料缺乏强度和耐磨性。本研究通过在 Monel K-500 中加入高强度 Stellite 6(一种 Co-Cr 合金)来解决这一问题。使用 L-DED 制作了两种类型的多材料样品:夹层样品和混合粉末样品。与单一 Monel K-500 样品相比,夹层样品在材料界面处出现了裂纹,而混合粉末样品则没有裂纹,并显示出更好的机械性能,屈服强度从 208.3 兆帕增加到 490.2 兆帕,极限拉伸强度从 429.7 兆帕增加到 887.0 兆帕。这项研究证明了在 L-DED 过程中原位合金化在提高合金性能方面的潜力,并强调了成分突变导致开裂所带来的挑战,提出了成功生产的缓解策略。
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引用次数: 0
Risk assessment of homologous variants of biotech trait proteins using a bridging approach. 采用桥接法对生物技术性状蛋白的同源变体进行风险评估。
IF 4.5 2区 农林科学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-31 Epub Date: 2024-11-09 DOI: 10.1080/21645698.2024.2420412
Cunxi Wang, Jennifer Calcaterra, Beverly Anderson, Timothy Rydel, Rong Wang, Lieselot Bertho, Scott A Saracco, Kimberly Hodge-Bell, Luis Burzio, Tommi White, Bin Li

A transgenic protein is frequently expressed as different homologous variants in genetically modified crops due to differential processing of targeting peptides or optimization of activity and specificity. The aim of this study was to develop a science-based approach for risk assessment of homologous protein variants using dicamba mono-oxygenase (DMO) as a case study. In this study, DMO expressed in the next-generation dicamba-tolerant maize, sugar beet and soybean crops exhibited up to 27 amino acid sequence differences in the N-terminus. Structure modeling using AlphaFold, ESMFold and OpenFold demonstrates that these small N-terminal extensions lack an ordered secondary structure and do not disrupt the DMO functional structure. Three DMO variants were demonstrated to have equivalent immunoreactivity and functional activity ranging from 214 to 331 nmol/min/mg. Repeated toxicity studies using each DMO variant found no test substance-related adverse effects. These results support that homologous protein variants, which have demonstrated physicochemical and functional equivalence, can leverage existing safety data from one variant without requiring additional de novo safety assessments.

在转基因作物中,由于靶向肽的不同加工或活性和特异性的优化,转基因蛋白质经常表现为不同的同源变体。本研究的目的是以麦草畏单氧化酶(DMO)为案例,开发一种基于科学的同源蛋白变体风险评估方法。在这项研究中,在耐麦草畏的下一代玉米、甜菜和大豆作物中表达的 DMO 在 N 端表现出多达 27 个氨基酸序列差异。使用 AlphaFold、ESMFold 和 OpenFold 进行的结构建模表明,这些小的 N 端延伸缺乏有序的二级结构,不会破坏 DMO 的功能结构。研究证明,三种 DMO 变体具有同等的免疫活性和功能活性,范围在 214 至 331 nmol/min/mg 之间。使用每种 DMO 变体进行的重复毒性研究均未发现与试验物质相关的不良反应。这些结果证明,已证明理化和功能等效的同源蛋白质变体可以利用一种变体的现有安全性数据,而无需进行额外的全新安全性评估。
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引用次数: 0
Progress in the Application of Organoids-On-A-Chip in Diseases. 器官芯片在疾病中的应用进展。
IF 1.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-31 Epub Date: 2024-08-10 DOI: 10.1080/15476278.2024.2386727
Qiao Geng, Yanyan Xu, Yang Hu, Lu Wang, Yi Wang, Zhimin Fan, Desong Kong

With the rapid development of the field of life sciences, traditional 2D cell culture and animal models have long been unable to meet the urgent needs of modern biomedical research and new drug development. Establishing a new generation of experimental models and research models is of great significance for deeply understanding human health and disease processes, and developing effective treatment measures. As is well known, long research and development cycles, high risks, and high costs are the "three mountains" facing the development of new drugs today. Organoids and organ-on-chips technology can highly simulate and reproduce the human physiological environment and complex reactions in vitro, greatly improving the accuracy of drug clinical efficacy prediction, reducing drug development costs, and avoiding the defects of drug testing animal models. Therefore, organ-on-chips have enormous potential in medical diagnosis and treatment.

随着生命科学领域的飞速发展,传统的二维细胞培养和动物模型早已不能满足现代生物医学研究和新药开发的迫切需要。建立新一代的实验模型和研究模型,对于深入了解人类健康和疾病过程、开发有效的治疗措施具有重要意义。众所周知,研发周期长、风险大、成本高是当今新药研发面临的 "三座大山"。器官组织和片上器官技术可以在体外高度模拟和再现人体的生理环境和复杂反应,大大提高药物临床疗效预测的准确性,降低药物研发成本,避免药物试验动物模型的缺陷。因此,器官芯片在医学诊断和治疗方面具有巨大的潜力。
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引用次数: 0
Biotechnology executive order opens door for regulatory reform and social acceptance of genetically engineered microbes in agriculture. 生物技术行政命令为农业转基因微生物的监管改革和社会接受打开了大门。
IF 4.5 2区 农林科学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-31 Epub Date: 2024-07-27 DOI: 10.1080/21645698.2024.2381294
Jabeen Ahmad, Amy Grunden, Jennifer Kuzma

In the United States, regulatory review of genetically engineered microbes for agriculture falls under the Coordinated Framework for the Regulation of Biotechnology (CFRB). However, the lack of a centralized regulatory pathway and multiple oversight authorities can lead to uncertainty in regulatory review. Using three microbial-based technologies for agriculture as illustrative examples, this commentary identifies the weaknesses and challenges associated with the CFRB by assessing the current system and proposed changes to the system under a multi criteria decision analysis framework. In addition, it discusses opportunities for regulatory reform to improve clarity, efficiency, and public acceptance of genetically engineered microbes in agriculture under the CHIPS and Science Act and the 2022 Executive Order on the Bioeconomy.

在美国,农业转基因微生物的监管审查属于《生物技术监管协调框架》(CFRB)的管辖范围。然而,缺乏集中监管途径和多个监督机构会导致监管审查的不确定性。本评论以三种基于微生物的农业技术为例,通过在多标准决策分析框架下评估现行制度和拟议的制度改革,指出了与生物技术协调监管框架相关的不足和挑战。此外,它还讨论了根据《CHIPS 和科学法案》以及 2022 年《生物经济行政命令》进行监管改革的机会,以提高农业基因工程微生物的清晰度、效率和公众接受度。
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引用次数: 0
Risk-appropriate regulations for gene-editing technologies. 基因编辑技术的风险适当监管。
IF 3.9 2区 农林科学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-31 Epub Date: 2024-01-12 DOI: 10.1080/21645698.2023.2293510
Graham Brookes, Stuart J Smyth

This paper explores the scope for the newly emerging technologies, based on gene editing (GE) contributing to addressing the global challenges that we face. These challenges relate to food security, climate change and biodiversity depletion. In particular, it examines the science and evidence behind the most appropriate forms of agricultural production to meet these challenges, the targets set in the Global Biodiversity Framework (GBF) agreed to at the end of 2022 and the possible role of GE technologies in contributing to meeting these targets. It then examines the most risk-appropriate regulatory environment required to best facilitate the adoption of GE technology, drawing on the experiences of the impact of regulatory systems for other innovations used in agricultural and food production systems such as genetically modified organisms (GMOs).

本文探讨了基于基因编辑(GE)的新兴技术在应对我们面临的全球挑战方面的应用范围。这些挑战涉及粮食安全、气候变化和生物多样性枯竭。本文特别探讨了应对这些挑战的最合适的农业生产形式背后的科学和证据、2022 年底商定的全球生物多样性框架(GBF)中设定的目标,以及基因编辑技术在促进实现这些目标方面可能发挥的作用。然后,本报告借鉴转基因生物 (GMO) 等其他农业和食品生产系统创新监管制度的影响经验,探讨了最有利于采用 GE 技术所需的风险最适当的监管环境。
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引用次数: 0
Regulatory framework for genetically modified organisms in the Kingdom of Eswatini. 埃斯瓦提尼王国转基因生物监管框架。
IF 4.5 2区 农林科学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-12-31 Epub Date: 2024-07-04 DOI: 10.1080/21645698.2024.2375664
Bongani Z Nkhabindze, Cebisile N Magagula, Diana Earnshaw, Calsile F Mhlanga, Sipho N Matsebula, Isaac G Dladla

The Kingdom of Eswatini is a Party to the Convention on Biological Diversity and to the Cartagena Protocol on Biosafety. As Party, Eswatini has domesticated these agreements by passing the Biosafety Act, of 2012 to provide for the safe handling, transfer, and use of living modified organisms (LMOs) in the country. The Act regulates living modified organisms to be used for confined field trials, commercial release, import, export, and transit, and for food, feed, and processing. Guidance is provided for prospective applicants before any application is made to the Competent Authority. This framework also provides for the regulation of emerging technologies such as synthetic biology and genome editing. The regulatory framework for living modified organisms aims to provide an enabling environment for the precautionary use of modern biotechnology and its products in the country in order to safeguard biological diversity and human health.

斯威士兰王国是《生物多样性公约》和《卡塔赫纳生物安全议定书》的缔约国。作为《公约》的缔约国,斯威士兰通过了2012年《生物安全法》,将这些协定纳入国内法,规定在国内安全处理、转让和使用改性活生物体(LMOs)。该法对用于封闭田间试验、商业释放、进口、出口和转运以及用于食品、饲料和加工的改性活生物体进行了规范。在向主管当局提出申请之前,将为潜在申请人提供指导。该框架还规定了对合成生物学和基因组编辑等新兴技术的监管。改性活生物体监管框架旨在为在该国预防性使用现代生物技术及其产品提供有利环境,以保护生物多样性和人类健康。
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引用次数: 0
Effects of path patterns on residual stresses and deformations of directed energy deposition-arc built blocks 路径模式对定向能沉积弧形构件残余应力和变形的影响
IF 10.6 1区 工程技术 Q1 ENGINEERING, MANUFACTURING Pub Date : 2024-12-31 DOI: 10.1080/17452759.2023.2296128
Donghong Ding, Rong Huang, Tao Liu, Lei Yuan, Chuan Liu
Deposition path patterns play an important role in controlling residual stresses and deformation in direct energy deposition-arc (DED-arc) process. In this paper, the effects of various path patterns on the evolution of the temperature history, residual stress distribution, and substrate deformations are investigated through experiments and finite element analysis. The predicted results of temperature fields and substrate deformations are verified experimentally by the infrared thermal imager and the laser profile scanner, respectively. It is found that the path patterns have significant effects on the stress distribution in the first few layers, and the minimum substrate deformation is obtained by the zigzag path along the short edge of the block. The proposed finite element method and measuring method are confirmed to be effective and feasible, providing valuable insight into the residual stresses and deformations control in the DED-arc process.
沉积路径模式在控制直接能量沉积-电弧(DED-arc)工艺中的残余应力和变形方面发挥着重要作用。本文通过实验和有限元分析研究了各种路径模式对温度历史演变、残余应力分布和基底变形的影响。红外热成像仪和激光轮廓扫描仪分别对温度场和基底变形的预测结果进行了实验验证。结果发现,路径模式对前几层的应力分布有显著影响,沿块体短边的之字形路径可获得最小的基底变形。所提出的有限元方法和测量方法被证实是有效和可行的,为 DED 电弧工艺中的残余应力和变形控制提供了有价值的见解。
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引用次数: 0
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