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Carboxyl Ester Lipase Protects Against Metabolic Dysfunction-Associated Steatohepatitis by Binding to Fatty Acid Synthase 羧基酯脂肪酶通过与脂肪酸合成酶结合防止代谢功能障碍相关性脂肪性肝炎
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-10-01 DOI: 10.1016/j.eng.2024.04.018
Carboxyl ester lipase (CEL), a pivotal enzyme involved in lipid metabolism, is recurrently mutated in obese mice. Here, we aimed to elucidate the functional significance, molecular mechanism, and therapeutic potential of CEL in metabolic dysfunction-associated steatohepatitis (MASH). Hepatocyte-specific carboxyl ester lipase gene (Cel) knockout (CelΔHEP) and wildtype (WT) littermates were fed with choline-deficient high-fat diet (CD-HFD) for 16 weeks, or methionine- and choline-deficient diet (MCD) for three weeks to induce MASH. Liquid chromatography–mass spectrometry and co-immunoprecipitation were employed to identify the downstream targets of CEL. CD-HFD/MCD-fed WT mice received intravenous injections of CEL-adeno-associated viral, serotype 8 (AAV8) to induce specific overexpression of CEL in the liver. We observed a decrease in CEL protein levels in MASH induced by CD-HFD or MCD in mice. CelΔHEP mice fed with CD-HFD or MCD exhibited pronounced hepatic steatosis, inflammation, lipid peroxidation, and liver injury compared to WT littermates, accompanied by increased hepatic nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) activation. Consistently, Cel knockdown in mouse primary hepatocytes and AML12 cells aggravated lipid accumulation and inflammation, whereas CEL overexpression exerted the opposite effect. Mechanistically, CEL directly bound to fatty acid synthase (FASN), resulting in reduced FASN SUMOylation, which in turn promoted FASN degradation through the proteasome pathway. Furthermore, inhibition of FASN ameliorated hepatocyte lipid accumulation and inflammation induced by Cel knockdown in vivo and in vitro. Hepatocyte-specific CEL overexpression using AAV8-Cel significantly mitigated steatohepatitis in mice fed with CD-HFD or MCD. CEL protects against steatohepatitis development by directly interacting with FASN and suppressing its expression for de novo lipogenesis. CEL overexpression confers a therapeutic benefit in steatohepatitis.
羧基酯脂肪酶(CEL)是一种参与脂质代谢的关键酶,在肥胖小鼠中反复发生突变。在此,我们旨在阐明 CEL 在代谢功能障碍相关性脂肪性肝炎(MASH)中的功能意义、分子机制和治疗潜力。用胆碱缺乏的高脂饮食(CD-HFD)或蛋氨酸和胆碱缺乏的饮食(MCD)喂养肝细胞特异性羧基酯脂肪酶基因(Cel)敲除(CelΔHEP)和野生型(WT)小鼠16周,以诱导MASH。研究人员采用液相色谱-质谱法和共免疫沉淀法来确定CEL的下游靶标。CD-HFD/MCD 喂养的 WT 小鼠静脉注射 CEL 腺相关病毒血清型 8(AAV8)以诱导 CEL 在肝脏中特异性过表达。我们观察到,在 CD-HFD 或 MCD 诱导的小鼠 MASH 中,CEL 蛋白水平有所下降。与 WT 小鼠相比,用 CD-HFD 或 MCD 喂养的 CelΔHEP 小鼠表现出明显的肝脏脂肪变性、炎症、脂质过氧化和肝损伤,同时伴有肝脏核因子卡巴轻链-活化 B 细胞增强子(NF-κB)激活增加。同样,在小鼠原代肝细胞和 AML12 细胞中敲除 Cel 会加剧脂质积累和炎症,而过表达 CEL 则会产生相反的效果。从机理上讲,CEL 直接与脂肪酸合成酶(FASN)结合,导致 FASN SUMOylation 减少,进而促进 FASN 通过蛋白酶体途径降解。此外,抑制 FASN 可改善 Cel 敲除在体内和体外诱导的肝细胞脂质积累和炎症。使用AAV8-Cel过表达肝细胞特异性CEL可显著减轻以CD-HFD或MCD喂养的小鼠的脂肪性肝炎。CEL 通过直接与 FASN 相互作用并抑制其表达以促进脂肪的新生,从而防止脂肪性肝炎的发生。CEL 的过表达对脂肪性肝炎有治疗作用。
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引用次数: 0
A High-Resolution Measurement Method for Inner and Outer 3D Surface Profiles of Laser Fusion Targets Using a Laser Differential Confocal–Atomic Force Probe Technique 利用激光差分共焦-原子力探针技术高分辨率测量激光融合靶内外三维表面轮廓的方法
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-10-01 DOI: 10.1016/j.eng.2024.05.016
The high-resolution and nondestructive co-reference measurement of the inner and outer three-dimensional (3D) surface profiles of laser fusion targets is difficult to achieve. In this study, we propose a laser differential confocal (LDC)–atomic force probe (AFP) method to measure the inner and outer 3D surface profiles of laser fusion targets at a high resolution. This method utilizes the LDC method to detect the deflection of the AFP and exploits the high spatial resolution of the AFP to enhance the spatial resolution of the outer profile measurement. Nondestructive and co-reference measurements of the inner profile of a target were achieved using the tomographic characteristics of the LDC method. Furthermore, by combining multiple repositionings of the target using a horizontal slewing shaft, the inner and outer 3D surface profiles of the target were obtained, along with a power spectrum assessment of the entire surface. The experimental results revealed that the respective axial and lateral resolutions of the outer profile measurement were 0.5 and 1.3 nm, while the respective axial and lateral resolutions of the inner profile measurement were 2.0 nm and approximately 400.0 nm. The repeatabilities of the root-mean-square deviation measurements for the outer and inner profiles of the target were 2.6 and 2.4 nm, respectively. We believe our study provides a promising method for the high-resolution and nondestructive co-reference measurement of the inner and outer 3D profiles of laser fusion targets.
激光聚变靶内外三维(3D)表面轮廓的高分辨率无损共参照测量难以实现。在本研究中,我们提出了一种激光差分共焦(LDC)-原子力探针(AFP)方法,用于高分辨率测量激光聚变靶内外三维表面轮廓。该方法利用 LDC 方法检测原子力探针的偏转,并利用原子力探针的高空间分辨率来提高外轮廓测量的空间分辨率。利用 LDC 方法的断层扫描特性,实现了对目标内部轮廓的无损和共参照测量。此外,通过使用水平回转轴对目标进行多次重新定位,获得了目标的内外三维表面轮廓以及整个表面的功率谱评估。实验结果表明,外轮廓测量的轴向和横向分辨率分别为 0.5 和 1.3 nm,而内轮廓测量的轴向和横向分辨率分别为 2.0 nm 和大约 400.0 nm。目标外轮廓和内轮廓测量的均方根偏差重复性分别为 2.6 和 2.4 nm。我们相信,我们的研究为高分辨率和无损共参照测量激光聚变目标的内外三维轮廓提供了一种可行的方法。
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引用次数: 0
An Intelligent Quality Control Method for Manufacturing Processes Based on a Human–Cyber–Physical Knowledge Graph 基于人-网络-物理知识图谱的制造过程智能质量控制方法
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-10-01 DOI: 10.1016/j.eng.2024.03.022
Shilong Wang , Jinhan Yang , Bo Yang , Dong Li , Ling Kang
Quality management is a constant and significant concern in enterprises. Effective determination of correct solutions for comprehensive problems helps avoid increased backtesting costs. This study proposes an intelligent quality control method for manufacturing processes based on a human–cyber–physical (HCP) knowledge graph, which is a systematic method that encompasses the following elements: data management and classification based on HCP ternary data, HCP ontology construction, knowledge extraction for constructing an HCP knowledge graph, and comprehensive application of quality control based on HCP knowledge. The proposed method implements case retrieval, automatic analysis, and assisted decision making based on an HCP knowledge graph, enabling quality monitoring, inspection, diagnosis, and maintenance strategies for quality control. In practical applications, the proposed modular and hierarchical HCP ontology exhibits significant superiority in terms of shareability and reusability of the acquired knowledge. Moreover, the HCP knowledge graph deeply integrates the provided HCP data and effectively supports comprehensive decision making. The proposed method was implemented in cases involving an automotive production line and a gear manufacturing process, and the effectiveness of the method was verified by the application system deployed. Furthermore, the proposed method can be extended to other manufacturing process quality control tasks.
质量管理是企业持续关注的重要问题。有效确定综合问题的正确解决方案有助于避免增加回测成本。本研究提出了一种基于人-机-物(HCP)知识图谱的制造过程智能质量控制方法,该方法是一种系统化的方法,包含以下要素:基于 HCP 三元数据的数据管理与分类、HCP 本体构建、构建 HCP 知识图谱的知识提取以及基于 HCP 知识的质量控制综合应用。所提出的方法实现了基于 HCP 知识图谱的病例检索、自动分析和辅助决策,实现了质量监控、检验、诊断和维护的质量控制策略。在实际应用中,所提出的模块化分层 HCP 本体在知识的可共享性和可重用性方面表现出明显的优势。此外,HCP 知识图谱还能深度整合所提供的 HCP 数据,有效支持综合决策。所提出的方法在涉及汽车生产线和齿轮制造过程的案例中得到了实施,所部署的应用系统也验证了该方法的有效性。此外,所提出的方法还可以扩展到其他制造过程质量控制任务中。
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引用次数: 0
Droplet-Based Microfluidics with Mass Spectrometry for Microproteomics 用于微蛋白质组学的液滴微流控质谱技术
IF 12.8 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-09-06 DOI: 10.1016/j.eng.2024.08.018
Hang Li, Yudan Ma, Rongxin Fu, Jiaxi Peng, Yanbing Zhai, Jinhua Li, Wei Xu, Siyi Hu, Hanbin Ma, Aaron R. Wheeler, Shuailong Zhang
Microproteomics, the profiling of protein expressions in small cell populations or individual cells, is essential for understanding complex biological systems. However, sample loss and insufficient sensitivity of analytical techniques pose severe challenges to this field. Microfluidics, particularly droplet-based microfluidics, provides an ideal approach by enabling miniaturized and integrated workflows to process samples and offers several advantages, including reduced sample loss, low reagent consumption, faster reaction times, and improved throughput. Droplet-based microfluidics manipulates droplets of fluids to function as discrete reaction units, enabling complex chemical reactions and biological workflows in a miniaturized setting. This article discusses a variety of on-chip functions of droplet-based microfluidics, including cell sorting, cell culture, and sample processing. We then highlight recent advances in the mass spectrometry (MS)-based analysis of single cells using droplet-based microfluidic platforms, including digital microfluidics (DMF). Finally, we review the integrated DMF–MS systems that enable automated and parallel proteomic profiling of single cells with high sensitivity and discuss the applications of the technology and its future perspectives.
微观蛋白质组学是对小细胞群或单个细胞中蛋白质表达情况的分析,对于了解复杂的生物系统至关重要。然而,样品丢失和分析技术灵敏度不足给这一领域带来了严峻挑战。微流控技术,尤其是基于液滴的微流控技术,提供了一种理想的方法,它实现了样品处理工作流程的微型化和集成化,并具有多种优势,包括减少样品损失、降低试剂消耗、加快反应时间和提高通量。基于液滴的微流控技术可将液滴作为离散反应单元进行操作,从而在微型化环境中实现复杂的化学反应和生物工作流程。本文讨论了液滴微流体技术的各种片上功能,包括细胞分拣、细胞培养和样品处理。然后,我们重点介绍了利用液滴微流控平台(包括数字微流控(DMF))进行基于质谱(MS)的单细胞分析的最新进展。最后,我们回顾了实现高灵敏度单细胞自动并行蛋白质组分析的 DMF-MS 集成系统,并讨论了该技术的应用及其未来前景。
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引用次数: 0
Improving Long-Term Functional Outcomes of Ischemic Stroke in the Reperfusion Era 在再灌注时代改善缺血性中风的长期功能预后
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-09-01 DOI: 10.1016/j.eng.2024.04.004
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引用次数: 0
Hypergraph Computation 超图计算
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-09-01 DOI: 10.1016/j.eng.2024.04.017

Practical real-world scenarios such as the Internet, social networks, and biological networks present the challenges of data scarcity and complex correlations, which limit the applications of artificial intelligence. The graph structure is a typical tool used to formulate such correlations, it is incapable of modeling high-order correlations among different objects in systems; thus, the graph structure cannot fully convey the intricate correlations among objects. Confronted with the aforementioned two challenges, hypergraph computation models high-order correlations among data, knowledge, and rules through hyperedges and leverages these high-order correlations to enhance the data. Additionally, hypergraph computation achieves collaborative computation using data and high-order correlations, thereby offering greater modeling flexibility. In particular, we introduce three types of hypergraph computation methods: ① hypergraph structure modeling, ② hypergraph semantic computing, and ③ efficient hypergraph computing. We then specify how to adopt hypergraph computation in practice by focusing on specific tasks such as three-dimensional (3D) object recognition, revealing that hypergraph computation can reduce the data requirement by 80% while achieving comparable performance or improve the performance by 52% given the same data, compared with a traditional data-based method. A comprehensive overview of the applications of hypergraph computation in diverse domains, such as intelligent medicine and computer vision, is also provided. Finally, we introduce an open-source deep learning library, DeepHypergraph (DHG), which can serve as a tool for the practical usage of hypergraph computation.

互联网、社交网络和生物网络等现实世界的实际场景面临着数据稀缺和复杂关联的挑战,这限制了人工智能的应用。图结构是表述这种相关性的典型工具,但它无法模拟系统中不同对象之间的高阶相关性,因此图结构无法完全表达对象之间错综复杂的相关性。面对上述两个挑战,超图计算通过超通道对数据、知识和规则之间的高阶相关性进行建模,并利用这些高阶相关性来增强数据。此外,超图计算还能利用数据和高阶相关性实现协同计算,从而提供更大的建模灵活性。我们特别介绍了三种超图计算方法:①超图结构建模;②超图语义计算;③高效超图计算。然后,我们以三维(3D)物体识别等特定任务为重点,具体说明了如何在实践中采用超图计算,并揭示了与传统的基于数据的方法相比,超图计算可以减少 80% 的数据需求,同时在相同数据条件下实现相当的性能或提高 52% 的性能。我们还全面概述了超图计算在智能医学和计算机视觉等不同领域的应用。最后,我们介绍了一个开源深度学习库--DeepHypergraph(DHG),它可以作为超图计算的实际应用工具。
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引用次数: 0
Biomimetic Erythrocyte-Like Particles from Microfluidic Electrospray for Tissue Engineering 用于组织工程的微流体电喷雾仿红细胞颗粒
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-09-01 DOI: 10.1016/j.eng.2023.08.022

Microparticles have demonstrated value for regenerative medicine. Attempts in this field tend to focus on the development of intelligent multifunctional microparticles for tissue regeneration. Here, inspired by erythrocytes-associated self-repairing process in damaged tissue, we present novel biomimetic erythrocyte-like microparticles (ELMPs). These ELMPs, which are composed of extracellular matrix-like hybrid hydrogels and the functional additives of black phosphorus, hemoglobin, and growth factors (GFs), are generated by using a microfluidic electrospray. As the resultant ELMPs have the capacity for oxygen delivery and near-infrared-responsive release of both GFs and oxygen, they would have excellent biocompatibility and multifunctional performance when serving as microscaffolds for cell adhesion, stimulating angiogenesis, and adjusting the release profile of cargoes. Based on these features, we demonstrate that the ELMPs can stably overlap to fill a wound and realize controllable cargo release to achieve the desired curative effect of tissue regeneration. Thus, we consider our biomimetic ELMPs with discoid morphology and cargo-delivery capacity to be ideal for tissue engineering.

微粒已被证明具有再生医学的价值。这一领域的尝试往往集中在开发用于组织再生的智能多功能微粒上。受红细胞在受损组织中自我修复过程的启发,我们在此提出了新型仿生红细胞样微颗粒(ELMPs)。这些 ELMPs 由细胞外基质类混合水凝胶以及黑磷、血红蛋白和生长因子(GFs)等功能添加剂组成,通过微流体电喷雾技术生成。由于生成的 ELMPs 具有氧气输送能力,并能近红外响应地释放 GFs 和氧气,因此在作为微支架用于细胞粘附、刺激血管生成和调整货物释放轮廓时,它们将具有出色的生物相容性和多功能性能。基于这些特点,我们证明了 ELMPs 可以稳定地重叠填充伤口,并实现可控的货物释放,从而达到理想的组织再生治疗效果。因此,我们认为具有盘状形态和货物释放能力的生物仿生 ELMPs 是组织工程的理想选择。
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引用次数: 0
Magnetic Interactions with Strain Gradient in Ultrathin Pr0.67Sr0.33MnO3 Films 超薄 Pr0.67Sr0.33MnO3 薄膜中的磁相互作用与应变梯度
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-09-01 DOI: 10.1016/j.eng.2024.04.014

Strain gradient is a normal phenomenon around a heterostructural interface in ultrathin film, and it is important to determine its effect on magnetic interactions to understand interfacial coupling. In this work, ultrathin Pr0.67Sr0.33MnO3 (PSMO) films on different substrates are studied. For PSMO film under different in-plane strain conditions, the saturated magnetization and Curie temperature can be qualitatively explained by double-exchange interaction and the Jahn–Teller distortion. However, the difference in the saturated magnetization with zero field cooling and 5 T field cooling is proportional to the strain gradient. Strain-gradient-induced structural disorder is proposed to enhance phonon–electron antiferromagnetic interactions and the corresponding antiferromagnetic-to-ferromagnetic phase transition via a strong magnetic field during the field cooling process. A non-monotonous structural transition of the MnO6 octahedral rotation can enlarge the strain gradient in PSMO film on a SrTiO3 substrate. This work demonstrates the existence of the flexomagnetic effect in ultrathin manganite film, which should be applicable to other complex oxide systems.

应变梯度是超薄薄膜异质结构界面周围的一种正常现象,确定其对磁相互作用的影响对于理解界面耦合非常重要。本文研究了不同基底上的超薄 Pr0.67Sr0.33MnO3 (PSMO) 薄膜。对于不同面内应变条件下的 PSMO 薄膜,其饱和磁化和居里温度可通过双交换相互作用和 Jahn-Teller 畸变得到定性解释。然而,零场冷却和 5 T 场冷却时饱和磁化率的差异与应变梯度成正比。应变梯度引起的结构紊乱被认为是为了增强声子-电子反铁磁相互作用,以及在场强冷却过程中通过强磁场实现相应的反铁磁到铁磁相变。MnO6 八面体旋转的非单调结构转变可以扩大 SrTiO3 衬底上 PSMO 薄膜的应变梯度。这项工作证明了超薄锰矿薄膜中存在柔磁效应,它应该适用于其他复杂的氧化物体系。
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引用次数: 0
Application of Ice Pigging in a Drinking Water Distribution System: Impacts on Pipes and Bulk Water Quality 冰清管在饮用水分配系统中的应用:对管道和散装水质的影响
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-09-01 DOI: 10.1016/j.eng.2023.09.016

Ice pigging is an emerging technique for pipe cleaning in drinking water distribution systems. However, substantial confusion and controversy exist on the potential impacts of ice pigging on bulk water quality. This study monitored the microstructural features and composition of sediments and microbial community structures in bulk water in eight multimaterial Chinese networks. Chloride concentration analysis demonstrated that separate cleaning of pipes with different materials in complex networks could mitigate the risk of losing ice pigs and degrading water quality. The microstructural and trace element characterization results showed that ice pigs would scarcely disturb the inner surfaces of long-used pipes. The bacterial richness and diversity of bulk water decreased significantly after ice pigging. Furthermore, correlations were established between pipe service age, temperature, and chloride and total iron concentrations, and the 15 most abundant taxa in bulk water, which could be used to guide practical ice pigging operations.

冰清管是一种新兴的饮用水分配系统管道清洗技术。然而,冰清管对散装水质的潜在影响存在着大量的困惑和争议。本研究监测了中国8个多物质网络中散装水中沉积物的微观结构特征、组成和微生物群落结构。氯化物浓度分析表明,在复杂的管网中,用不同的材料分别清洗管道,可以降低冰猪丢失和水质下降的风险。显微组织和微量元素表征结果表明,冰猪几乎不会干扰长期使用的管道的内表面。冰清管后散装水细菌丰富度和多样性显著降低。此外,还建立了管道使用年限、温度、总铁和氯化物浓度与散装水中15个最丰富的分类群之间的相关性,可用于指导实际冰清管作业。
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引用次数: 0
An Integrated Analysis on the Synergistic Reduction of Carbon and Pollution Emissions from China’s Iron and Steel Industry 中国钢铁工业碳减排与污染减排的综合分析
IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Pub Date : 2024-09-01 DOI: 10.1016/j.eng.2023.09.018

Decarbonization and decontamination of the iron and steel industry (ISI), which contributes up to 15% to anthropogenic CO2 emissions (or carbon emissions) and significant proportions of air and water pollutant emissions in China, are challenged by the huge demand for steel. Carbon and pollutants often share common emission sources, indicating that emission reduction could be achieved synergistically. Here, we explored the inherent potential of measures to adjust feedstock composition and technological structure and to control the size of the ISI to achieve carbon emission reduction (CER) and pollution emission reduction (PER). We investigated five typical pollutants in this study, namely, petroleum hydrocarbon pollutants and chemical oxygen demand in wastewater, particulate matter, SO2, and NOx in off gases, and examined synergies between CER and PER by employing cross elasticity for the period between 2022 and 2035. The results suggest that a reduction of 8.7%–11.7% in carbon emissions and 20%–31% in pollution emissions (except for particulate matter emissions) could be achieved by 2025 under a high steel scrap ratio (SSR) scenario. Here, the SSR and electric arc furnace (EAF) ratio serve critical roles in enhancing synergies between CER and PER (which vary with the type of pollutant). However, subject to a limited volume of steel scrap, a focused increase in the EAF ratio with neglection of the available supply of steel scrap to EAF facilities would lead to an increase carbon and pollution emissions. Although CER can be achieved through SSR and EAF ratio optimization, only when the crude steel production growth rate remains below 2.2% can these optimization measures maintain the emissions in 2030 at a similar level to that in 2021. Therefore, the synergistic effects between PER and CER should be considered when formulating a development route for the ISI in the future.

钢铁工业(ISI)的脱碳和去污占中国人为二氧化碳排放(或碳排放)的15%,占空气和水污染物排放的很大比例,钢铁工业的脱碳和去污受到巨大钢铁需求的挑战。碳和污染物往往具有共同的排放源,这表明可以协同减排。在此,我们探讨了调整原料组成和技术结构以及控制ISI规模以实现碳减排(CER)和污染减排(PER)的内在潜力。本研究选取了5种典型污染物,即废水中的石油烃污染物和化学需氧量、颗粒物、SO2和废气中的NOx,并采用交叉弹性方法研究了2022 - 2035年期间CER和PER之间的协同效应。结果表明,到2025年,在高废钢比情景下,中国的碳排放可减少8.7% ~ 11.7%,污染排放(不含颗粒物排放)可减少20% ~ 31%。在这里,SSR和电弧炉(EAF)比例在增强CER和PER之间的协同作用(随污染物类型而异)方面发挥着关键作用。然而,在废钢数量有限的情况下,集中提高电炉利用率而忽视废钢对电炉设施的可用供应,将导致碳排放和污染排放的增加。虽然通过SSR和EAF比例优化可以实现CER,但只有当粗钢产量增长率保持在2.2%以下时,这些优化措施才能使2030年的排放量保持在与2021年相似的水平。因此,在制定未来ISI的发展路线时,应考虑PER和CER之间的协同效应。
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引用次数: 0
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