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Chemical reservoir computation in a self-organizing reaction network 自组织反应网络中的化学储层计算
Pub Date : 2023-11-14 DOI: 10.21203/rs.3.rs-3487081/v1
Wilhelm Huck, Mathieu Baltussen, Thijs de Jong, Quentin Duez, William Robinson
Abstract The flow of information is as crucial to life as the flow of energy1,2. Chemical reaction networks such as those found in metabolism and signalling pathways enable cells to process information from their environment3,4. Current approaches to molecular information processing and computation typically pursue digital computation paradigms and require extensive molecular-level engineering5. Despite significant advances, these approaches have not reached the level of information processing capabilities seen in living systems. Here, we report on the discovery and implementation of a chemical reservoir computer based on the formose reaction6. We demonstrate how this complex, self-organizing chemical reaction network can perform multiple non-linear classification tasks in parallel, of predicting the dynamics of other complex systems, and of time series forecasting. This in chemico information processing system provides proof-of-principle for the emergent computational capabilities of complex chemical reaction networks, paving the way for a new class of biomimetic information processing systems.
信息的流动和能量的流动一样对生命至关重要。代谢和信号通路中的化学反应网络使细胞能够处理来自环境的信息3,4。目前分子信息处理和计算的方法通常追求数字计算范式,需要广泛的分子水平工程5。尽管取得了重大进展,但这些方法还没有达到生命系统中所见的信息处理能力水平。在这里,我们报告了一个基于福尔摩斯反应的化学储层计算机的发现和实现。我们展示了这个复杂的、自组织的化学反应网络如何并行地执行多个非线性分类任务,预测其他复杂系统的动态,以及时间序列预测。这在化学信息处理系统中为复杂化学反应网络的新兴计算能力提供了原理证明,为一类新的仿生信息处理系统铺平了道路。
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引用次数: 0
Risk assessment of antimony-arsenic contaminated soil remediated using zero-valent iron at different pH values combined with freeze-thaw cycles 不同pH值零价铁结合冻融循环修复锑砷污染土壤的风险评价
Pub Date : 2023-11-14 DOI: 10.21203/rs.3.rs-3485701/v1
Erping Hei, Mingjiang He, Enze Zhang, Hua Yu Yu, Kun Chen Chen, Yusheng Qin Qin, Xiangzhong Zeng, Zijun Zhou, Hongzhu Fan, Shangguan Yuxian, Luying Wang
Abstract Soil in mining wastelands is seriously polluted with heavy metals. Zero-valent iron (ZVI) is widely used for remediation of heavy metal-polluted soil because of its excellent adsorption properties; however, the remediation process is affected by complex environmental conditions, such as acid rain and freeze-thaw cycles. In this study, the effects of different pH values and freeze-thaw cycles on remediation of antimony (Sb)- and arsenic (As)-contaminated soil by ZVI were investigated in laboratory simulation experiments. The stability and human health risk of the remediated soil were evaluated. The results showed that different pH values coupled with freeze-thaw cycles could promote stabilization remediation of Sb- and As-contaminated soil by ZVI. Among them, ZVI significantly reduced the leaching toxicity and bioavailability of Sb and As in soil (both about 60.00%) after 32 rounds of freeze-thaw cycle treatment under water sample conditions of pH=1 (F1). However, Compared with soil not treated with freeze-thaw cycles, freeze-thaw cycles increased the leaching concentration of unstable forms of As. Bioavailability calculations based on Sb and As in remediated soil that alkaline soil there were no health or carcinogenic risks for children and adults, but the health risks and carcinogenic risks of Sb in acidic soil remained high for children. These findings provide a theoretical basis for the remediation of Sb- and As-contaminated soil using ZVI, and also highlight the importance of considering pH and freeze-thaw conditions in the remediation process to ensure effective and safe treatment.
矿山废弃地土壤重金属污染严重。零价铁(Zero-valent iron, ZVI)因其优异的吸附性能被广泛应用于重金属污染土壤的修复;然而,修复过程受到酸雨和冻融循环等复杂环境条件的影响。在室内模拟实验中,研究了不同pH值和冻融循环对ZVI修复锑(Sb)-和砷(As)污染土壤的影响。对修复后土壤的稳定性和人体健康风险进行了评价。结果表明,不同pH值配合冻融循环可促进ZVI对Sb和as污染土壤的稳定修复。其中,在pH=1 (F1)的水样条件下,经过32轮冻融循环处理后,ZVI显著降低了土壤中Sb和As的浸出毒性和生物利用度(均约为60.00%)。但与未冻融循环处理的土壤相比,冻融循环增加了不稳定形态砷的淋滤浓度。基于修复土壤中Sb和As的生物利用度计算表明,碱性土壤中Sb对儿童和成人没有健康风险和致癌风险,但酸性土壤中Sb对儿童的健康风险和致癌风险仍然很高。这些研究结果为利用ZVI修复Sb和as污染土壤提供了理论依据,也强调了在修复过程中考虑pH和冻融条件的重要性,以确保有效和安全的处理。
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引用次数: 0
Variables related to soil fertility in successional agroforestry systems – Serras do Sudeste, RS, Brazil 演替农林复合系统中与土壤肥力相关的变量——苏德斯特山脉,RS,巴西
Pub Date : 2023-11-14 DOI: 10.21203/rs.3.rs-3581731/v1
Daniel Hanke, Shirley Grazieli da Silva Nascimento, Déborah Pinheiro Dick, Renan Costa Beber Vieira, Leonardo Paz Deble
Abstract Successional agroforestry systems have the capacity to increase soil fertility and restore degraded ecosystems. The objective of this study was to investigate the influence of agroforestry systems, at different stages of ecological succession, on the dynamics of chemical and physical soil fertility attributes in the Brazil South region. Soil samples were collected under five different conditions: i) Control (T) = initial system (without agroforestry); ii) SAF1 = agroforestry with 1 year of development; iii) SAF3 = agroforestry with 3 years of development; iv) SAF7 = agroforestry with 7 years of development; and v) reference system (naturally regenerating forest with 30 years). Subsequently, determinations/calculations were carried out for chemical attributes/parameters (exchangeable Ca + 2 , Mg + 2 , K + , Na + , P, Al + 3 , H + , sum of bases, effective and potential cation exchange capacity, cation exchange saturation with bases and Al + 3 ), physical attributes (soil bulk density, particle density, total porosity, and moisture), and soil physicochemical properties (pH H 2 O, pH in saline solutions, and SMP method), as well as chemical element stocks were calculated based on soil mass in each sampled layer. Results indicated an increase in pH, total porosity, and nutrient stocks with the systems' development time, accompanied by a decrease in acidity components. The change in soil fertility is directly related to the increase in soil organic matter content.
演替农林复合系统具有提高土壤肥力和恢复退化生态系统的能力。本研究的目的是调查农林业系统在不同生态演替阶段对巴西南部地区土壤化学和物理肥力属性动态的影响。土壤样品在五种不同条件下采集:i)控制(T) =初始系统(不含农林业);ii) SAF1 =发展1年的农林业;SAF3 = 3年发展的农林业;SAF7 =发展7年的农林业;参考系统(30年自然再生森林)。随后,决定/化学属性的计算进行了参数(可交换的Ca + 2毫克+ 2 K +、Na + P + 3, H +,基地,有效的和潜在的阳离子交换能力,阳离子交换饱和与基地和基地+ 3),物理属性(土壤容重、粒子密度、总孔隙度、水分),和土壤理化性质(酸碱H 2 O,在盐的解决方案,和SMP方法),并根据各采样层的土壤质量计算化学元素储量。结果表明,随着体系发育时间的延长,pH值、总孔隙度和养分储量均有所增加,而酸度成分则有所减少。土壤肥力的变化与土壤有机质含量的增加有直接关系。
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引用次数: 0
The microalga Volvox carteri as a cell supportive building block for tissue engineering 微藻作为组织工程的细胞支持构件
Pub Date : 2023-11-14 DOI: 10.21203/rs.3.rs-3484389/v1
Mathilde STRICHER, Pascale Vigneron, Frédéric Delbecq, Claude-Olivier Sarde, Christophe Egles
Abstract Background V. carteri f. nagariensis constitutes, in its most simplified form, a cellularized spheroid built around and stabilised by a form of primitive extracellular matrix (ECM). Methods Based on its structure and its ability to support surface cell adhesion most likely induced by the composition of its algal ECM, we have developed a modular approach to soft tissue engineering by compact-stacking of V. carteri –based living building blocks. Results A primary biocompatibility assessment demonstrated the algal suspension cytocompatibility, its histogenesis promoting properties, and that it did not induce an inflammatory response in vitro . These results allowed us to consider the use of such algal suspension for soft tissue augmentation and to initiate the study of its in vivo biocompatibility. V. carteri exhibited cellular fate-directing properties, causing fibroblasts to take on an alkaline phosphatase + stem-cell-like phenotype and both human adipose-derived stem cells and mouse embryonic stem cells to differentiate into preadipocytes to adipocytes. The ability of V. carteri to support histogenesis and adipogenesis was also observed in vivo by subcutaneous tissue augmentation of athymic mice, highlighting the potential of V. carteri to support or influence tissue regeneration. Conclusions Our conclusion present for the first time V. carteri as an innovative and inspiring biomaterial for tissue engineering and soft tissue regeneration. Its strategies in terms of shape, structure and composition can be central in the design of a new generation of bio-inspired heterogeneous biomaterials recapitulating more appropriately the complexity of the body tissues when guiding their regeneration.
在其最简化的形式中,narariensis构成一个围绕原始细胞外基质(ECM)构建并稳定的细胞化球体。方法基于其结构和支持表面细胞粘附的能力(很可能是由其藻类ECM的组成引起的),我们开发了一种模块化方法,通过紧凑堆叠基于V. carteri的活构建块来实现软组织工程。结果初步生物相容性评价表明,藻悬液具有细胞相容性和促进组织发生的特性,且在体外不引起炎症反应。这些结果使我们可以考虑使用这种藻类悬浮液进行软组织增强,并开始研究其体内生物相容性。V. carteri表现出细胞命运导向特性,使成纤维细胞呈现碱性磷酸酶+干细胞样表型,使人脂肪源性干细胞和小鼠胚胎干细胞分化为前脂肪细胞到脂肪细胞。通过对胸腺发育不全的小鼠进行皮下组织增强实验,也观察到牛角弧菌支持组织发生和脂肪形成的能力,强调了牛角弧菌支持或影响组织再生的潜力。结论本研究结果首次揭示了V. carteri在组织工程和软组织再生方面是一种具有创新意义的生物材料。它在形状、结构和组成方面的策略可以成为新一代生物启发异质生物材料设计的核心,在指导其再生时更恰当地概括了身体组织的复杂性。
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引用次数: 0
The Phyllosphere of Nigerian Medicinal Plants Euphorbia lateriflora and Ficus thonningii is inhabited by a specific Microbiota 尼日利亚药用植物红叶大戟(Euphorbia lateriflora)和无花果(Ficus thonningii)的层层圈由一种特定的微生物群居住
Pub Date : 2023-11-14 DOI: 10.21203/rs.3.rs-3586450/v1
Anderson O Oaikhena, Morenike E Coker, Dorothy Cyril-Okoh, Gabriele Berg, Iruka N Okeke
Abstract Background Medicinal plant microbiota is highly specific and can contribute to medicinal activity. However, the majority of plant species have not yet been studied. Here, we investigated the phyllosphere composition of two common Nigerian medicinal plants, Euphorbia lateriflora and Ficus thonningii , by a polyphasic approach combining analyses of metagenomic DNA and isolates. Results Microbial abundance estimated via qPCR using specific marker gene primers showed that all leaf samples were densely colonized with up to 10 8 per gram of leaf with higher bacterial and fungal abundance than Archaea. While no statistically significant differences between both plant species were found for abundance, amplicon sequencing of 16S rRNA and ITS genes revealed a distinct microbiota composition, and only seven of the 27 genera isolated were represented on both plants. We observed dominance of Sphingomonas spp. on both plants, and members of Xanthomonadaceae and Enterobacteriaceae were also found in high numbers. The most dominant fungal families on both plants were Cladosporiaceae, Mycosphaerellaceae and Trichosphaeriaceae . In addition, 225 plant-specific isolates were identified, with Pseudomonadota and Enterobacteriaceae being dominant. Interestingly, 29 isolates are likely species previously unknown, and 14 of these belong to Burkholderiales . However, a high proportion, 56% and 40% of the isolates from E. lateriflora and F. thonningii , respectively, were characterized as various Escherichia coli . The growth of most of the bacterial isolates was not influenced by extractable secondary metabolites of plants. Conclusions Our results suggest that a specific and diverse microbial community inhabits the leaves of both plants, including potentially new species and producers of antimicrobials.
摘要背景药用植物微生物群具有高度的特异性,可以促进药用活性。然而,大多数植物物种尚未被研究过。本文采用多相方法结合宏基因组DNA和分离株分析,对尼日利亚两种常见药用植物大戟(Euphorbia lateriflora)和无花果(Ficus thonningii)的层球组成进行了研究。结果利用特异标记基因引物进行qPCR估计,所有叶片样品的微生物丰度都很密集,每克叶片的细菌和真菌丰度均高于古生菌。虽然两种植物之间的丰度没有统计学上的显著差异,但16S rRNA和ITS基因的扩增子测序显示了不同的微生物群组成,并且分离的27个属中只有7个在两种植物上都有代表。两种植物均以鞘氨单胞菌属占优势,黄单胞菌科和肠杆菌科的成员数量也较多。两种植物的优势真菌科分别为枝孢菌科、霉孢菌科和毛孢菌科。此外,还鉴定出225株植物特异性分离株,以假单胞菌和肠杆菌科为主。有趣的是,29个分离株可能是以前未知的物种,其中14个属于伯克霍尔德里亚门。然而,较高比例的分离物(分别为56%和40%)被鉴定为多种大肠杆菌。大多数分离菌株的生长不受可提取的植物次生代谢物的影响。结论这两种植物的叶片中都存在一个特定且多样的微生物群落,包括潜在的新物种和抗菌素的产生者。
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引用次数: 0
Tribological properties of PTFE/PI-PAI composite coatings filled by GO/ ZrO2 on the surfaces of different micro-textures 氧化石墨烯/氧化锆填充PTFE/PI-PAI复合涂层在不同微织构表面的摩擦学性能
Pub Date : 2023-11-14 DOI: 10.21203/rs.3.rs-3585659/v1
Peng Xiang, Jun Cao, Qihua Long, Shiming Wang, Jinxing Wu, Zeshan Abbas
Abstract Three different PTFE/PI-PAI composite coatings filled by GO/ZrO 2 were designed to improve the tribological properties of engine bearing. The pentagonal and triangular textures were prepared on the surface of copper alloy by laser processing. The designed coatings were prepared on the surfaces of textures and smooth substrates by liquid spraying. The results indicated that the coating with 0.25 wt.% of GO and 4.75 wt.% of ZrO 2 has the best tribological properties at room temperature and 75°C. The coating has the better mechanical and tribological performances on the surface of the pentagonal textures. The mechanical simulation showed that the contact stress and deformation of the coating on the pentagonal texture is less than that of the triangular texture.
设计了3种不同的氧化石墨烯/氧化锆填充PTFE/PI-PAI复合涂层,以改善发动机轴承的摩擦学性能。采用激光加工技术在铜合金表面制备了五边形和三角形织构。采用液体喷涂的方法在纹理和光滑基底表面制备了所设计的涂层。结果表明:氧化石墨烯含量为0.25 wt.%、氧化锆含量为4.75 wt.%的涂层在室温和75℃下具有最佳的摩擦学性能;该涂层在五边形织构表面具有较好的力学性能和摩擦学性能。力学模拟结果表明,涂层在五边形织构上的接触应力和变形小于三角形织构。
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引用次数: 0
Reactive oxygen and nitrogen species (RONS) solubility controlled activation of water by atmospheric pressure air spark discharge 活性氧和氮(RONS)溶解度通过大气压空气火花放电控制水的活化
Pub Date : 2023-11-14 DOI: 10.21203/rs.3.rs-3581789/v1
Zhiguo Zhao, Guoqiang Liu, Guofeng Li, Weiyuan Ni, Dongping Liu
Abstract The activation of water by the atmospheric pressure air plasma is involved in the diffusion of reactive oxygen and nitrogen species (RONS) in air and water, their gas-phase and liquid-phase reactions, and their dissolution and evaporation. In this study, by generating the air spark discharge over the surface of water, we have evaluated the chemical and biological reactivities of direct–plasma treatment (DPT) and remote–plasma treatment (RPT) plasma-activated water (PAW) at different water temperatures. We have found that DPT-PAW is much more effective in increasing both the chemical and biological reactivities of PAW than RPT-PAW, and decreasing the water temperature from 40°C to 6°C leads to rapid activation of water. Our analysis shows that when the water temperature varies from 6°C to 40°C, the activation of water by the air discharge is RONS solubility controlled, and the gas-phase and liquid-phase RONS diffusion and chemical reactions are not the controlling steps during the activation of water. The direct plasma treatment of water at a relatively low temperature contributes to an obvious increase in the RONS solubility, thus a rapid activation of DPT-PAW.
常压空气等离子体对水的活化涉及活性氧和活性氮在空气和水中的扩散、气相和液相反应、溶解和蒸发。在本研究中,我们通过在水面产生空气火花放电,评估了直接等离子体处理(DPT)和远程等离子体处理(RPT)等离子体活化水(PAW)在不同水温下的化学和生物反应性。我们发现DPT-PAW在提高PAW的化学和生物活性方面比RPT-PAW更有效,并且将水温从40°C降低到6°C会导致水的快速活化。我们的分析表明,当水温在6℃~ 40℃范围内变化时,空气排放对水的活化是由RONS溶解度控制的,气相和液相的RONS扩散和化学反应不是水活化过程中的控制步骤。在相对较低的温度下直接等离子体处理水,可以明显提高RONS的溶解度,从而快速激活DPT-PAW。
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引用次数: 0
Transfer and extension of experience from urban heavy rain flood risk warning 城市暴雨洪水风险预警经验的传递与推广
Pub Date : 2023-11-14 DOI: 10.21203/rs.3.rs-3398604/v1
Thomas Einfalt, Alrun Jasper-Tönnies, Bruno Castro
Abstract The high variability of local intense rainfall events and the short response time of flow in urban catchments demand improved methods in flood warning systems. A key aspect of success is the improvement of short-term forecasts of heavy rainfall by combining ensembles of radar nowcasts with numerical weather prediction ensembles. This paper presents results from this approach in the context of the urban fluvial water management and flood warning system in Hamburg since 2019 and extends its conclusions to other application fields. New challenges from this operational context are being investigated in another research project focusing on the city of Hanover. The topics of improved spatial rainfall data resolution, use of ensemble information from radar nowcasts for pluvial flood warning in connection with sewer load and possible solutions for real-time applications in the urban context are tackled. Experiences from both projects illustrate the importance of applying real-time measurements and ensemble forecasts in connection with a clear open information strategy. Data quality and resolution are crucial aspects in this context, making the combination of different data sources potentially significant for improving the outcome.
局地强降雨事件的高变异性和城市集水区流量的短响应时间要求改进洪水预警系统的方法。成功的一个关键方面是通过将雷达临近预报集合与数值天气预报集合相结合来改进强降雨的短期预报。本文以汉堡自2019年以来的城市河流水管理和洪水预警系统为例,介绍了该方法的结果,并将其结论扩展到其他应用领域。另一个以汉诺威市为重点的研究项目正在调查这一业务背景下的新挑战。本文讨论了提高空间降雨数据分辨率、利用雷达临近预报的集合信息进行与下水道负荷有关的暴雨洪水预警以及在城市环境中实时应用的可能解决方案等主题。这两个项目的经验说明了将实时测量和集合预报与明确的公开信息战略结合起来的重要性。在这种情况下,数据质量和分辨率是至关重要的方面,这使得不同数据源的组合对改善结果具有潜在的重要意义。
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引用次数: 0
Vascular E-Learning in Mainland China: results of the e-Learning during the COVID-19 pandemic (EL-COVID) study 中国大陆血管电子学习:新冠肺炎大流行(EL-COVID)研究期间的电子学习结果
Pub Date : 2023-11-14 DOI: 10.21203/rs.3.rs-3407554/v1
Oana Bartos, Nikolaos Patelis, Zaiping Jing, Jiaxuan Feng, Matthias Trenner, Paulo Eduardo Ocke Reis, Nyityasmono Tri Nugroho, Stephane Elkouri, Lamisse Karam, Mihai Ionac, Marton Berczeli, Vincent Jongkind, Kak Khee Yeung, Athanasios Katsargyris, Efthymios Avgerinos, Demetrios Moris, Andrew Choong, Jun Jie Ng, Ivan Cvjetko, George A. Antoniou, Phillipe Ghibu, Alexei Svetlikov, Fernando Gallardo Pedrajas, Harm Ebben, Hubert Stepak, Sviatoslav Kostiv, Stefano Ancetti, Akli Mekkar, Leonid Magnitskiy, Liliana Fidalgo Domingos
Abstract Purpose: With the onset of the COVID 19 pandemic, digitalization came to the forefront of education delivery and continuous professional development took place predominantly online. We investigate the relevance of e-Learning in the vascular surgery community in mainland People’s Republic of China (PRC) and address the regional variability in comparison with the international community Methods: The international EL-COVID survey took place online from June 15, 2020 to October 15, 2020. We subtracted and analyzed the data from the PRC participants. Results: From 84 different countries, PRC had the largest contribution to the EL-COVID study (n = 109, 12.7%). Most of the Chinese responders were experienced vascular surgeons (73.39% vs. 53.81%; p=0.0001) and attended more than four eL activities (52.29% vs. 54.08%; not significant). Female vascular surgeons were underrepresented: 7.33% vs. 23.15%; p=0.0002. While participation at international activities did not vary, attendance at national eL activities was reduced (27.52% vs. 73.62%, p<0.0001). Obtaining official accreditation/CME points was relevant in choosing what eL opportunities to attend. Employers were less supportive of participation during working hours (17.43% vs. 46.52%; p<0,0001). eL opportunities were mainly promoted on social media (44.04% vs. 27.17%; p=0.0003) and to a lesser degree through direct contact from national/international societies (27.52% vs. 39.49%; p=0.016). Conclusion: As in other countries, eL is gaining relevance in the vascular surgery community of PRC. Adequate support as well as improving the dissemination strategy of national societies are needed to meet the demands of the modern vascular surgeon.
摘要目的:随着新冠肺炎疫情的爆发,数字化成为教育交付的前沿,持续的专业发展以在线为主导。我们调查了电子学习在中华人民共和国大陆血管外科社区的相关性,并与国际社会进行了比较,解决了区域差异。方法:国际EL-COVID调查于2020年6月15日至2020年10月15日在线进行。我们减去并分析了来自中国参与者的数据。结果:在84个不同的国家中,中国对EL-COVID研究的贡献最大(n = 109, 12.7%)。大多数中国应答者为经验丰富的血管外科医生(73.39% vs. 53.81%;p=0.0001),参加4次以上eL活动(52.29% vs. 54.08%;不显著)。女性血管外科医生的比例不足:7.33% vs. 23.15%;p = 0.0002。虽然参加国际活动的人数没有变化,但参加国内eL活动的人数减少了(27.52% vs. 73.62%, p<0.0001)。获得官方认证/CME积分与选择参加何种eL机会有关。雇主不太支持员工在工作时间参与工作(17.43% vs. 46.52%;术;0,0001)。eL机会主要通过社交媒体进行推广(44.04% vs. 27.17%);P =0.0003),在较小程度上通过国家/国际协会的直接接触(27.52% vs. 39.49%;p = 0.016)。结论:与其他国家一样,eL在中国血管外科领域越来越重要。为了满足现代血管外科医生的需求,需要适当的支持以及改进国家学会的传播策略。
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引用次数: 0
Acute Venous Thromboembolism Plasma and Red Blood Cell Metabolomic Profiling Reveals Potential New Early Diagnostic Biomarkers: observational clinical study 急性静脉血栓栓塞血浆和红细胞代谢组学分析揭示潜在的新的早期诊断生物标志物:观察性临床研究
Pub Date : 2023-11-14 DOI: 10.21203/rs.3.rs-3507783/v1
Claudia Febra, Joana Saraiva, Fátima Vaz, Joao Macedo, Hamza Mohammad Al-Hroub, Mohammad H Semreen, Rui Maio, Vitor Gil, Nelson Soares, Deborah Penque
Abstract Background:Venous thromboembolism(VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is still based on complex imaging exams due to the lack of biomarkers. Moreover, studies assessing the diagnostic capacity of novel metabolomics biomarkers in VTE are scarce. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile from plasma and red blood cells (RBCs). Methods: This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis (DVT) or pulmonary embolism (PE) admitted to the emergency room (ER). After gold standard imaging exams, we analysed the plasma and RBCs from 50 acute VTE and 12 nonacute VTE patients. We performed a metabolomics study and used mixed-effects modelling to compare the differences in metabolites. Results:The plasma metabolome had a suboptimal capability for differentiating between the presence or absence of acute VTE, with 23 significantly different molecules, but with ‘good’ performance for the best ROC curves. The metabolic pathway of D-glutamine and D-glutamate had the strongest impact on the acute VTE phenotype ( p = 0.001, false discovery rate = 0.06). RBCs revealed a consistent metabolomic signature of acute VTE. Among the 23 differentially abundant metabolites, we found 3 high-performance ROC curves with an area under the curve (AUC) higher than 0.9, including adenosine 3',5'-diphosphate (0.983), glutathione (0.923), and adenine (0.91). The metabolic set most impacting the differences observed was purine metabolism ( p = 0.000354, false discovery rate = 0.68). Conclusions:Our findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.
背景:静脉血栓栓塞(VTE)是导致心血管疾病死亡的主要原因。由于缺乏生物标志物,急性静脉血栓栓塞的诊断仍然基于复杂的影像学检查。此外,评估新型代谢组学生物标志物在静脉血栓栓塞中的诊断能力的研究很少。我们的目的是确定急性静脉血栓栓塞患者的血浆和红细胞代谢组学特征是否存在差异。方法:本观察性试验纳入62例临床疑似急性深静脉血栓形成(DVT)或肺栓塞(PE)的急诊室(ER)患者。在金标准影像学检查后,我们分析了50例急性静脉血栓栓塞患者和12例非急性静脉血栓栓塞患者的血浆和红细胞。我们进行了一项代谢组学研究,并使用混合效应模型来比较代谢物的差异。结果:血浆代谢组在区分急性静脉血栓栓塞存在与否方面的能力不佳,有23个显著不同的分子,但在最佳ROC曲线上表现“良好”。d -谷氨酰胺和d -谷氨酸的代谢途径对急性VTE表型的影响最大(p = 0.001,假发现率= 0.06)。红细胞显示一致的代谢组学特征急性静脉血栓栓塞。在23个差异丰度代谢物中,我们发现3′,5′-二磷酸腺苷(0.983)、谷胱甘肽(0.923)、腺嘌呤(0.91)3条曲线下面积(AUC)大于0.9的高性能ROC曲线。影响差异最大的代谢组是嘌呤代谢(p = 0.000354,错误发现率= 0.68)。结论:我们的研究结果表明,急性静脉血栓栓塞患者和非急性静脉血栓栓塞患者在早期入住急诊室时存在代谢物差异。从红细胞中获得的三种潜在生物标志物在急性静脉血栓栓塞诊断中表现出很高的性能。进一步的研究应该探索可获得的实验室方法,以便在未来的日常实践中,这些代谢物对急诊急性静脉血栓栓塞的早期诊断有用。
{"title":"Acute Venous Thromboembolism Plasma and Red Blood Cell Metabolomic Profiling Reveals Potential New Early Diagnostic Biomarkers: observational clinical study","authors":"Claudia Febra, Joana Saraiva, Fátima Vaz, Joao Macedo, Hamza Mohammad Al-Hroub, Mohammad H Semreen, Rui Maio, Vitor Gil, Nelson Soares, Deborah Penque","doi":"10.21203/rs.3.rs-3507783/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-3507783/v1","url":null,"abstract":"Abstract Background:Venous thromboembolism(VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is still based on complex imaging exams due to the lack of biomarkers. Moreover, studies assessing the diagnostic capacity of novel metabolomics biomarkers in VTE are scarce. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile from plasma and red blood cells (RBCs). Methods: This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis (DVT) or pulmonary embolism (PE) admitted to the emergency room (ER). After gold standard imaging exams, we analysed the plasma and RBCs from 50 acute VTE and 12 nonacute VTE patients. We performed a metabolomics study and used mixed-effects modelling to compare the differences in metabolites. Results:The plasma metabolome had a suboptimal capability for differentiating between the presence or absence of acute VTE, with 23 significantly different molecules, but with ‘good’ performance for the best ROC curves. The metabolic pathway of D-glutamine and D-glutamate had the strongest impact on the acute VTE phenotype ( p = 0.001, false discovery rate = 0.06). RBCs revealed a consistent metabolomic signature of acute VTE. Among the 23 differentially abundant metabolites, we found 3 high-performance ROC curves with an area under the curve (AUC) higher than 0.9, including adenosine 3',5'-diphosphate (0.983), glutathione (0.923), and adenine (0.91). The metabolic set most impacting the differences observed was purine metabolism ( p = 0.000354, false discovery rate = 0.68). Conclusions:Our findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.","PeriodicalId":500086,"journal":{"name":"Research Square (Research Square)","volume":"85 18","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134900724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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