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Dewatering of Scenedesmus obliquus Cultivation Substrate with Microfiltration: Potential and Challenges for Water Reuse and Effective Harvesting 利用微滤技术对双孢蘑菇栽培基质进行脱水:水回用和有效收集的潜力与挑战
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-07-01 DOI: 10.1016/j.eng.2023.07.010

In the microalgae harvesting process, which includes a step for dewatering the algal suspension, directly reusing extracted water in situ would decrease the freshwater footprint of cultivation systems. Among various algae harvesting techniques, membrane-based filtration has shown numerous advantages. This study evaluated the reuse of permeate streams derived from Scenedesmus obliquus (S. obliquus) biomass filtration under bench-scale and pilot-scale conditions. In particular, this study identified a series of challenges and mechanisms that influence the water reuse potential and the robustness of the membrane harvesting system. In a preliminary phase of this investigation, the health status of the initial biomass was found to have important implications for the harvesting performance and quality of the permeate stream to be reused; healthy biomass ensured better dewatering performance (i.e., higher water fluxes) and higher quality of the permeate water streams. A series of bench-scale filtration experiments with different combinations of cross-flow velocity and pressure values were performed to identify the operative conditions that would maximize water productivity. The selected conditions, 2.4 m·s−1 and 1.4 bar (1 bar = 105 Pa), respectively, were then applied to drive pilot-scale microfiltration tests to reuse the collected permeate as a new cultivation medium for S. obliquus growth in a pilot-scale photobioreactor. The investigation revealed key differences between the behavior of the membrane systems at the two scales (bench and pilot). It indicated the potential for beneficial reuse of the permeate stream as the pilot-scale experiments ensured high harvesting performance and growth rates of biomass in permeate water that were highly similar to those recorded in the ideal cultivation medium. Finally, different nutrient reintegration protocols were investigated, revealing that both macro- and micro-nutrient levels are critical for the success of the reuse approach.

在微藻类收获过程中,有一个步骤是对藻类悬浮液进行脱水,直接就地再利用提取的水可减少培养系统的淡水足迹。在各种藻类收获技术中,膜过滤已显示出诸多优势。本研究评估了在工作台规模和中试规模条件下,对从双孢藻类(S. obliquus)生物过滤中提取的渗透水流进行再利用的情况。特别是,这项研究确定了影响水回用潜力和膜收集系统稳健性的一系列挑战和机制。在调查的初步阶段,发现初始生物质的健康状况对收集性能和待回用渗透水流的质量有重要影响;健康的生物质可确保更好的脱水性能(即更高的水通量)和更高的渗透水流质量。对不同的横流速度和压力值组合进行了一系列台式过滤实验,以确定能最大限度提高水生产率的操作条件。选定的条件分别为 2.4 米-秒-1 和 1.4 巴(1 巴 = 105 帕),然后将其用于驱动中试规模的微过滤试验,以便在中试规模的光生物反应器中将收集到的渗透水作为新的栽培介质重新利用,促进斜管藻的生长。这项研究揭示了两种规模(台式和中试)的膜系统行为之间的主要差异。中试规模的实验确保了渗透水中生物量的高采集性能和生长率,与理想培养基中记录的生物量生长率高度相似,这表明渗透水具有有益再利用的潜力。最后,对不同的养分再整合方案进行了研究,结果表明,宏观和微观养分水平对于再利用方法的成功至关重要。
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引用次数: 0
Neg-Entropy Mechanism as a Target for Natural Medicines 作为天然药物靶点的负熵机制
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-07-01 DOI: 10.1016/j.eng.2024.05.007
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引用次数: 0
European Union Issues World’s First Comprehensive Regulations for Artificial Intelligence 欧盟发布全球首个人工智能综合法规
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-07-01 DOI: 10.1016/j.eng.2024.06.006
Chris Palmer
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引用次数: 0
The Triple Combination of Meropenem, Avibactam, and a Metallo-β-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different β-Lactamase Producers 美罗培南、阿维巴坦和一种金属β-内酰胺酶抑制剂的三重组合优化了对不同β-内酰胺酶生产者的抗菌覆盖率
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-07-01 DOI: 10.1016/j.eng.2024.02.010

This work explores the potential of a triple combination of meropenem (MEM), a novel metallo-β-lactamase (MBL) inhibitor (indole-2-carboxylate 58 (InC58)), and a serine-β-lactamase (SBL) inhibitor (avibactam (AVI)) for broad-spectrum activity against carbapenemase-producing bacteria. A diverse panel comprising MBL- and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution method. The frequency of resistance (FoR) to MEM combined with InC58 was investigated. Mutants were sequenced and tested for cross resistance, fitness, and the stability of the resistance phenotype. Compared with the double combinations of MEM plus an SBL or MBL inhibitor, the triple combination extended the spectrum of activity to most of the isolates bearing SBLs (oxacillinase-48 (OXA-48) and Klebsiella pneumoniae carbapenemase-2 (KPC-2)) and MBLs (New Delhi metallo-β-lactamases (NDMs)), although it was not effective against Verona integron-encoded metallo-β-lactamase (VIM)-carrying Pseudomonas aeruginosa (P. aeruginosa) and OXA-23-carrying Acinetobacter baumannii (A. baumannii). The FoR to MEM plus InC58 ranged from 2.22 × 10−7 to 1.13 × 10−6. The resistance correlated with mutations to ompC and comR, affecting porin C and copper permeability, respectively. The mutants manifested a fitness cost, a decreased level of resistance during passage without antibiotic pressure, and cross resistance to another carbapenem (imipenem) and a β-lactamase inhibitor (taniborbactam). In conclusion, compared with the dual combinations, the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemase-producing bacteria, revealing a new strategy to combat β-lactamase-mediated antimicrobial resistance.

本研究探讨了美罗培南(MEM)、新型金属-β-内酰胺酶(MBL)抑制剂(吲哚-2-羧酸 58(InC58))和丝氨酸-β-内酰胺酶(SBL)抑制剂(阿维巴坦(AVI))三联疗法对产碳青霉烯酶细菌的广谱活性潜力。使用琼脂稀释法对由产生 MBL 和 SBL 的菌株组成的不同菌株组进行了三重组合药敏试验。研究了 MEM 与 InC58 组合的耐药性频率(FoR)。对突变体进行了测序,并测试了交叉抗性、适应性和抗性表型的稳定性。与 MEM 加 SBL 或 MBL 抑制剂的双重组合相比,三重组合扩大了对大多数带有 SBL(奥沙西林酶-48 (OXA-48) 和肺炎克雷伯菌碳青霉烯酶-2 (KPC-2))和 MBL(新德里金属-β-内酰胺酶 (NDM))的分离菌的活性范围、尽管它对携带维罗纳整合子编码金属-β-内酰胺酶(VIM)的铜绿假单胞菌(P.铜绿假单胞菌(P. aeruginosa)和携带 OXA-23 的鲍曼不动杆菌(A. baumannii)。对 MEM 加 InC58 的 FoR 从 2.22 × 10-7 到 1.13 × 10-6。耐药性与 ompC 和 comR 的突变有关,它们分别影响孔蛋白 C 和铜的渗透性。突变体在无抗生素压力的情况下表现出适应性代价、抗性水平下降以及对另一种碳青霉烯类(亚胺培南)和一种β-内酰胺酶抑制剂(他尼巴坦)的交叉抗性。总之,与双重组合相比,MEM 与 InC58 和 AVI 的三重组合对不同产碳青霉烯酶细菌具有更广泛的活性谱,揭示了一种对抗 β-内酰胺酶介导的抗菌药耐药性的新策略。
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引用次数: 0
A Deep-Learning and Transfer-Learning Hybrid Aerosol Retrieval Algorithm for FY4-AGRI: Development and Verification over Asia 用于 FY4-AGRI 的深度学习与迁移学习混合气溶胶检索算法:开发与亚洲验证
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-07-01 DOI: 10.1016/j.eng.2023.09.023

The Advanced Geosynchronous Radiation Imager (AGRI) is a mission-critical instrument for the Fengyun series of satellites. AGRI acquires full-disk images every 15 min and views East Asia every 5 min through 14 spectral bands, enabling the detection of highly variable aerosol optical depth (AOD). Quantitative retrieval of AOD has hitherto been challenging, especially over land. In this study, an AOD retrieval algorithm is proposed that combines deep learning and transfer learning. The algorithm uses core concepts from both the Dark Target (DT) and Deep Blue (DB) algorithms to select features for the machine-learning (ML) algorithm, allowing for AOD retrieval at 550 nm over both dark and bright surfaces. The algorithm consists of two steps: ① A baseline deep neural network (DNN) with skip connections is developed using 10 min Advanced Himawari Imager (AHI) AODs as the target variable, and ② sunphotometer AODs from 89 ground-based stations are used to fine-tune the DNN parameters. Out-of-station validation shows that the retrieved AOD attains high accuracy, characterized by a coefficient of determination (R2) of 0.70, a mean bias error (MBE) of 0.03, and a percentage of data within the expected error (EE) of 70.7%. A sensitivity study reveals that the top-of-atmosphere reflectance at 650 and 470 nm, as well as the surface reflectance at 650 nm, are the two largest sources of uncertainty impacting the retrieval. In a case study of monitoring an extreme aerosol event, the AGRI AOD is found to be able to capture the detailed temporal evolution of the event. This work demonstrates the superiority of the transfer-learning technique in satellite AOD retrievals and the applicability of the retrieved AGRI AOD in monitoring extreme pollution events.

先进地球同步辐射成像仪(AGRI)是风云系列卫星的关键任务仪器。AGRI 每 15 分钟获取一次全盘图像,每 5 分钟通过 14 个光谱波段观测东亚地区,从而能够探测高度可变的气溶胶光学深度(AOD)。迄今为止,气溶胶光学深度的定量检索一直具有挑战性,尤其是在陆地上。本研究提出了一种结合深度学习和迁移学习的 AOD 检索算法。该算法采用了暗目标(DT)和深蓝(DB)算法的核心概念,为机器学习(ML)算法选择特征,可在 550 nm 波长范围内对暗表面和亮表面进行 AOD 检索。该算法包括两个步骤:使用 10 分钟先进向日葵成像仪 AOD 作为目标变量,开发了一个具有跳接连接的基线深度神经网络(DNN);②使用 89 个地面站的太阳光度计 AOD 对 DNN 参数进行微调。站外验证表明,检索到的 AOD 具有很高的准确性,其特征是判定系数 (R2) 为 0.70,平均偏差误差 (MBE) 为 0.03,预期误差 (EE) 范围内的数据百分比为 70.7%。敏感性研究表明,650 和 470 纳米波长的大气顶部反射率以及 650 纳米波长的地表反射率是影响检索的两个最大的不确定性来源。在监测极端气溶胶事件的案例研究中,发现 AGRI AOD 能够捕捉到事件的详细时间演变过程。这项工作证明了转移学习技术在卫星 AOD 检索中的优越性,以及 AGRI AOD 在监测极端污染事件中的适用性。
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引用次数: 0
Highly Aromatic Norditerpenoid Heterodimers and Monomers from Trigonostemon fragilis 高芳香北二萜异二聚体及单体
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-07-01 DOI: 10.1016/j.eng.2023.09.015

Four new norditerpenoid heterodimers with different dimerization patterns—namely, trigofragiloids A–C (denoted as compounds 1–3) and (+)- and (−)-trigofragiloid D (compound 4)—and three new phenanthrenone norditerpenoids—namely, trigofragiloids E–G (compounds 5–7)—were isolated from Trigonostemon fragilis. Compounds 1 and 2 feature a novel heterodimeric carbon skeleton formed by the conjugation of a tetra-norditerpenoid and an ennea-norditerpenoid; they have been identified as class 2 atropisomers by means of quantum chemical calculations. Compound 3 is an unprecedented phenylpropanoid–norditerpenoid adduct with a new dimerization pattern. Compounds (+)- and (−)-4 are the first example of S-shaped 1,4-dioxane-fused norditerpenoid dimers. Inspired by the structure elucidation of compound 4, two co-occurring analogues, actephilol A and epiactephilol A, were structurally revised as a pair of geometrical isomers and were identified as two pairs of enantiomers, (+)- and (−)-8 and (+)- and (−)-9, respectively. Their structures were characterized using a combined method. Notably, compound 7 exhibits remarkable adenosine triphosphate-citrate lyase (ACLY) inhibition with a half-maximal inhibition concentration (IC50) value of (0.46 ± 0.11) μmol∙L−1, as active as the positive control BMS-303141, and a molecular docking study offers deep insight into the interaction between compound 7 and ACLY.

从香三角茎中分离到4个新的二聚体,分别为三甘油三酯A-C(标记为化合物1-3)、(+)-和(−)-三甘油三酯D(标记为化合物4)和3个新的菲蒽酮类三甘油三酯E-G(标记为化合物5-7)。化合物1和2具有由四-去二萜和烯-去二萜偶联形成的新型异二聚体碳骨架;通过量子化学计算,它们被鉴定为2类atropisomer。化合物3是一种前所未有的苯基丙烷-北二萜加合物,具有新的二聚化模式。化合物(+)-和(−)-4是s形1,4-二恶烷融合的北二萜二聚体的第一个例子。受化合物4结构解析的启发,两个共发生的类似物乙酰氨基酚A和乙酰氨基酚A在结构上被修正为一对几何异构体,并被鉴定为两对对映体,分别为(+)-和(−)-8和(+)-和(−)-9。用组合方法对它们的结构进行了表征。值得注意的是,化合物7对三磷酸腺苷-柠檬酸裂解酶(ACLY)具有显著的抑制作用,其半最大抑制浓度(IC50)值为(0.46±0.11)μmol∙L−1,与阳性对照BMS-303141的活性相当。通过分子对接研究,化合物7与ACLY的相互作用有了深入的了解。
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引用次数: 0
An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China 中国开发的抗菌新药临床管线的最新情况
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-07-01 DOI: 10.1016/j.eng.2024.02.009

Antibacterial resistance is a global health threat that requires further concrete action on the part of all countries. In this context, one of the biggest concerns is whether enough new antibacterial drugs are being discovered and developed. Although several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently, none provides comprehensive information on original antibacterial drugs at clinical stages in China. In this review, we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since 2019. Information was obtained by consulting official websites, searching commercial databases, retrieving literature, asking personnel from institutions or companies, and other means, and a considerable part of the data covered here has not been included in other reviews. As of June 30, 2023, a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and updated. Among them, two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration (NMPA) in China in 2019 and 2021, respectively, and 18 antibacterial agents are in clinical development, with one under regulatory evaluation, five in phase-3, six in phase-2, and six in phase-1. Most of the clinical candidates are new analogs or mono-components of traditional antibacterial pharmacophore types, including two dual-acting hybrid antibiotics and a recombinant antibacterial protein. Overall, despite there being 17 antibacterial clinical candidates, our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in China. Hopefully, Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development (R&D) of original antibacterial drugs.

抗菌药耐药性是一个全球性的健康威胁,需要所有国家采取进一步的具体行动。在这种情况下,人们最关心的问题之一就是是否有足够的新抗菌药物被发现和开发出来。尽管近期发表了几篇高质量的全球抗菌药物临床研究综述,但没有一篇综述全面介绍了中国处于临床阶段的原创抗菌药物。在本综述中,我们总结了自 2019 年以来中国批准上市和临床评价中的新型抗菌药物的最新进展。相关信息通过查询官方网站、检索商业数据库、检索文献、询问机构或企业人员等方式获得,其中相当一部分数据未被其他综述收录。截至 2023 年 6 月 30 日,共确定并更新了 17 家中国制药企业或开发商的 20 个抗菌药项目。其中,2个属于传统抗生素类的抗菌新药分别于2019年和2021年获得中国国家医药产品管理局批准,18个抗菌药处于临床开发阶段,其中1个正在进行监管评价,5个处于3期,6个处于2期,6个处于1期。大多数临床候选药物都是传统抗菌药药源类型的新类似物或单一成分,包括两种双效混合抗生素和一种重组抗菌蛋白。总体而言,尽管有 17 个抗菌药临床候选药物,但我们的分析表明,中国处于临床开发阶段的临床差异化抗菌药仍然相对较少。希望中国的制药企业和机构在未来的原创抗菌药物研发(R&D)中能够开发出更多具有创新性和临床差异化的候选药物,并具有良好的市场潜力。
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引用次数: 0
Corrigendum to “Bidirectional Causality Between Immunoglobulin G N-Glycosylation and Metabolic Traits: A Mendelian Randomization Study” [Engineering 26 (2023) 74–88] 免疫球蛋白 G N-糖基化与代谢特征之间的双向因果关系:孟德尔随机化研究" [Engineering 26 (2023) 74-88] 更正
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-07-01 DOI: 10.1016/j.eng.2024.05.011
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引用次数: 0
Natural Products Improve Organ Microcirculation Dysfunction Following Ischemia/Reperfusion- and Lipopolysaccharide-Induced Disturbances: Mechanistic and Therapeutic Views 天然产品可改善缺血/再灌注和脂多糖引起的器官微循环障碍:机制和治疗观点
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-07-01 DOI: 10.1016/j.eng.2023.11.016

Microcirculatory disturbances are complex processes caused by many factors, including abnormal vasomotor responses, decreased blood flow velocity, vascular endothelial cell injury, altered leukocyte and endothelial cell interactions, plasma albumin leakage, microvascular hemorrhage, and thrombosis. These disturbances involve multiple mechanisms and interactions among mechanisms that can include energy metabolism, the mitochondrial respiratory chain, oxidative stress, inflammatory factors, adhesion molecules, the cytoskeleton, vascular endothelial cells, caveolae, cell junctions, the vascular basement membrane, neutrophils, monocytes, and platelets. In clinical practice, aside from drugs that target abnormal vasomotor responses and platelet adhesion, there continues to be a lack of multi-target drugs that can regulate the complex mechanistic links and interactions underlying microcirculatory disturbances. Natural products have demonstrated obvious positive therapeutic effects in treating ischemia/reperfusion (I/R)- and lipopolysaccharide (LPS)-induced microcirculatory disturbances. In recent years, numerous research papers on the improvement of microcirculatory function by natural products have been published in international journals. In 2008 and 2017, the first listed author of this review was invited to publish reviews in the journal of Pharmacology & Therapeutics on the improvement of microcirculatory disturbances and organ injury induced by I/R using Salvia miltiorrhiza ingredients and other natural components of compounded Chinese medicine, respectively. This review systematically summarizes the effects, targets of action, and mechanisms of natural products regarding improving I/R- and LPS-induced microcirculatory disturbances and tissue injury. Based on this summary, scientific proposals are suggested for the discovery of new drugs to improve microcirculatory disturbances in disease.

微循环障碍是由多种因素引起的复杂过程,包括血管运动反应异常、血流速度下降、血管内皮细胞损伤、白细胞和内皮细胞相互作用改变、血浆白蛋白渗漏、微血管出血和血栓形成。这些紊乱涉及多种机制和机制间的相互作用,其中包括能量代谢、线粒体呼吸链、氧化应激、炎症因子、粘附分子、细胞骨架、血管内皮细胞、洞穴、细胞连接、血管基底膜、中性粒细胞、单核细胞和血小板。在临床实践中,除了针对异常血管运动反应和血小板粘附的药物外,仍然缺乏能够调节微循环障碍背后复杂机制联系和相互作用的多靶点药物。天然产物在治疗缺血/再灌注(I/R)和脂多糖(LPS)诱导的微循环障碍方面具有明显的积极疗效。近年来,国际期刊上发表了大量关于天然产物改善微循环功能的研究论文。2008年和2017年,本综述的第一作者应邀分别在《Pharmacology & Therapeutics》杂志上发表了关于丹参成分和其他复方中药天然成分改善I/R诱导的微循环障碍和器官损伤的综述。这篇综述系统地总结了天然产物在改善 I/R 和 LPS 引起的微循环障碍和组织损伤方面的作用、作用靶点和作用机制。在总结的基础上,为发现改善疾病微循环障碍的新药提出了科学建议。
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引用次数: 0
Planetary Homeostasis of Reactive Nitrogen Through Anaerobic Ammonium Oxidation 通过厌氧氨氧化实现活性氮的行星平衡
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-07-01 DOI: 10.1016/j.eng.2023.09.013

The availability of nitrogen (N) is crucial for both the productivity of terrestrial and aquatic ecosystems globally. However, the overuse of artificial fertilizers and the energy required to fix nitrogen have pushed the global nitrogen cycle (N-cycle) past its safe operating limits, leading to severe nitrogen pollution and the production of significant amounts of greenhouse gas nitrous oxide (N2O). The anaerobic ammonium oxidation (anammox) mechanism can counteract the release of ammonium and N2O in many oxygen-limited situations, assisting in the restoration of the homeostasis of the Earth’s N biogeochemistry. In this work, we looked into the characteristics of the anammox hotspots’ distribution across various types of ecosystems worldwide. Anammox hotspots are present at diverse oxic–anoxic interfaces in terrestrial systems, and they are most prevalent at the oxic–anoxic transition zone in aquatic ecosystems. Based on the discovery of an anammox hotspot capable of oxidizing ammonium anoxically into N2 without N2O by-product, we then designed an innovative concept and technical routes of nature-based anammox hotspot geoengineering for climate change, biodiversity loss, and efficient utilization of water resources. After 15 years of actual use, anammox hotspot geoengineering has proven to be effective in ensuring clean drinking water, regulating the climate, fostering plant and animal diversity, and enhancing long-term environmental quality. The sustainable biogeoengineering of anammox could be a workable natural remedy to resolve the conflicts between environmental pollution and food security connected to N management.

氮(N)的供应对全球陆地和水生生态系统的生产力至关重要。然而,人工化肥的过度使用和固氮所需的能量已使全球氮循环(N-cycle)超过其安全运行极限,导致严重的氮污染和大量温室气体一氧化二氮(N2O)的产生。厌氧氨氧化(anammox)机制可以在许多氧气有限的情况下抵消氨和氧化亚氮的释放,帮助恢复地球氮的生物地球化学平衡。在这项工作中,我们研究了anammox热点在全球各类生态系统中的分布特征。anammox热点存在于陆地系统的各种缺氧-缺氧界面,在水生生态系统的缺氧-缺氧过渡带最为普遍。在发现氨氧化热点能够将铵缺氧氧化成 N2 而不产生 N2O 副产物的基础上,我们设计了基于自然的氨氧化热点地球工程的创新理念和技术路线,以应对气候变化、生物多样性丧失和水资源的高效利用。经过 15 年的实际应用,anammox 热点地球工程在确保清洁饮用水、调节气候、促进动植物多样性和提高长期环境质量方面被证明是有效的。氨氧化物的可持续生物地球工程可以成为一种可行的自然疗法,解决与氮管理相关的环境污染和粮食安全之间的矛盾。
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引用次数: 0
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Engineering
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