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山奈酚作为新型ADAM10抑制剂治疗金黄色葡萄球菌感染 Article

王婷婷, 王建锋, 许湘竹, 蒋帆, 吕红发, 齐清辉, 张灿, 吕强华, 邓旭明

《工程（英文）》 2023年第28卷第9期页码 206-221 doi: 10.1016/j.eng.2023.03.006

摘要：去整合素和金属蛋白酶10（ADAM10）作为α-毒素（Hla）不可或缺的特异性细胞受体，可通过多种机制促进金葡菌感染。ADAM10在致病机制中发挥的关键作用使其成为基于HDT治疗金葡菌感染的有力靶点。本研究首次证明ADAM10在金葡菌诱导的坏死性调亡中也发挥重要作用，这一发现拓宽了人们对ADAM10在金葡菌感染中作用的认识。通过荧光底物分解试验，我们进一步筛选出了一种强效ADAM10抑制剂——山奈酚，该化合物可抑制Hla引起的屏障破坏和细胞坏死性调亡，有效保护小鼠免受金葡菌感染。

关键词：宿主靶向治疗山奈酚 ADAM10抑制剂金黄色葡萄球菌感染屏障破坏坏死性调亡

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抑制FLT3 ——急性髓系白血病分子靶向治疗的原型 Review

Meira Yisraeli Salman, Jacob M. Rowe, Nir Weigert

《工程（英文）》 2021年第7卷第10期页码 1354-1368 doi: 10.1016/j.eng.2021.05.020

摘要： MRD的疗效在过去10年迅速发展，其特异性从免疫分型的10^-3发展到聚合酶链反应（PCR）的10^-4（且仅对于部分AML患者有效），并最终在具有下一代测序（NGS）技术的灵敏度极高的细胞中发展至10^-5甚至10^-6。本文的重点是研究最为深入的AML靶向药物之一——FMS样酪氨酸激酶3（FLT3）抑制剂，它影响了AML的预后与治疗。作为已被批准的其他新兴靶向药物以及目前正在开发的靶向药物的原型，本文将选择性地对FLT3抑制剂展开详细讨论。

关键词：急性髓系白血病靶向治疗 FLT3抑制剂米哚妥林吉瑞替尼奎扎替尼索拉非尼

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尿激酶型纤溶酶原激活剂(uPA)系统在子宫内膜癌中的研究进展

毛晓丽,朱艳

《中国工程科学》 2006年第8卷第5期页码 98-102

摘要：

尿激酶型纤溶酶原激活系统是纤溶系统的重要组成部分，它通过水解细胞外间质，参与组织改造和细胞迁移，在肿瘤细胞的侵袭和转移中发挥作用；讨论了uPA系统的结构、作用机理及与子宫内膜癌的关系，旨在为子宫内膜癌的诊断和治疗提供新方法。

关键词：尿激酶型纤溶酶原激活剂(uPA) 尿激酶型纤溶酶原激活剂受体(uPAR) 尿激酶型纤溶酶原激活剂抑制剂(PAIs) 子宫内膜癌

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头孢他啶-阿维巴坦耐药革兰氏阴性菌的流行病学特征及耐药机制 Review

徐婷婷, 郭育奇, 姬扬, 王保红, 周凯

《工程（英文）》 2022年第11卷第4期页码 138-145 doi: 10.1016/j.eng.2020.11.004

摘要：头孢他啶-阿维巴坦（CAZ-AVI）是一种新型头孢菌素/β-内酰胺酶抑制剂，为临床治疗CRO感染提供了一项重要选择。据报道，CAZ-AVI 能够抑制Ambler A类、C类以及部分D类酶的活性。然而，这种药物在临床使用后不久，细菌的耐药性就已经出现，并且呈上升趋势。

关键词：头孢他啶-阿维巴坦耐药机制碳青霉烯耐药性 β-内酰胺/β-内酰胺酶抑制剂

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利用改性纳米二氧化硅在页岩表面构建层次结构疏水表面强化钻井工程中的井壁稳定性 Article

黄贤斌, 孙金声, 李贺, 王韧, 吕开河, 李海潮

《工程（英文）》 2022年第11卷第4期页码 101-110 doi: 10.1016/j.eng.2021.05.021

摘要：实验结果表明，HNS在抑制页岩膨胀和分散方面表现出良好的性能，优于常用的页岩抑制剂KCl和聚胺。与水相比，HNS可使膨润土试样的线性膨胀高度降低20%，对强水化页岩的回收率提高11.53 倍。机理研究表明，HNS良好的井壁强化性能可归因于三个方面：首先，带正电荷的HNS通过静电吸附中和部分黏土表面的负电荷，从而抑制渗透水化作用；其次，HNS在页岩表面吸附后可形成具有微纳米层次结构的“荷叶状”表面，显著增加页岩表面的水相接触角，大幅度降低了页岩表面自由能，从而抑制表面水化；再次，毛细作用的减弱和页岩孔隙的有效封堵减少了水的侵入，对井壁稳定有利。本文所述的方法对于抑制页岩的表面水化和渗透水化提供了一种新途径。

关键词：疏水纳米颗粒页岩抑制剂钻井液井壁稳定

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在临床批准的免疫抑制剂药物作用下胎猪肾脏在成熟猴体内的发育情况 Article

Tsuyoshi Takamura, Kenji Matsui, Naoto Matsumoto, Yatsumu Saito, Toshinari Fujimoto, Susumu Tajiri, Shuichiro Yamanaka, Kei Matsumoto, Akimitsu Kobayashi, Izumi Yamamoto, Hiroshi Sasaki, Haruyuki Hirayama, Hitomi Matsunari, Kazuaki Nakano, Hiroshi Nagashima, Akihiko Kiyoshi, Takao Kuroda, Makoto Inoue, Takeshi Miyawaki, Takashi Yokoo, Eiji Kobayashi

《工程（英文）》 2022年第10卷第3期页码 65-73 doi: 10.1016/j.eng.2022.02.001

摘要：

在从猪到非人灵长类动物的肾脏异种移植中，仅使用临床批准的免疫抑制药物来控制免疫反应是困难的。仅使用美国食品药品监督管理局批准的药物进行免疫抑制。将胎猪肾脏移植到食蟹猴的网膜和腹主动脉旁区域。随时间取样（每个实验取样两次），对移植组织的移植成活率和发育进行病理学检查。尽管对食蟹猴和流入胎猪肾脏的受体血管给予相同的免疫抑制方案，但胎猪的肾脏仍免于排斥。猪-猴肾脏异种移植中胎猪肾脏的免疫原性低于新生猪肾脏。

关键词：食蟹猴猪肾脏胎猪肾脏免疫抑制

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应对可转移多黏菌素耐药性——饲料添加剂来源的白屈菜红碱具有双重效应 Article

宋黄威, 王雪杨, 张慕琛, 邹之宇, 杨思源, 易甜, 王建峰, 刘德俊, 沈应博, 代重山, 刘志海, Timothy R. Walsh, 沈建忠, 吴聪明, 汪洋

《工程（英文）》 2024年第32卷第1期页码 163-173 doi: 10.1016/j.eng.2023.06.012

摘要：在体外抑菌试验能使多黏菌素对mcr-1阳性大肠杆菌的MIC降低16倍（由 2 至 0.125 mg∙L⁻¹），且在肠道感染模型中与对照组相比，能降低10机制研究发现，白屈菜红碱通过靶向细菌细胞膜上的磷脂成分，增大细胞膜的流动性，抑制了细菌呼吸作用，扰乱质子动势（proton motive force, PMF），产生活性氧（reactive oxygenspecies, ROS），造成细菌胞内ATP耗竭，下调了mcr-1及接合转移相关基因的转录水平，从而实现既能增强多黏菌素对抗耐药菌作用，又能抑制耐药质粒接合转移的双重作用。

关键词：白屈菜红碱抗生素佐剂接合转移抑制剂多黏菌素双重作用

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3D finite element method (FEM) simulation of groundwater flow during backward erosion piping

Kristine VANDENBOER,Vera van BEEK,Adam BEZUIJEN

《结构与土木工程前沿（英文）》 2014年第8卷第2期页码 160-166 doi: 10.1007/s11709-014-0257-7

摘要： Backward erosion piping is an important failure mechanism for cohesive water retaining structures which are founded on a sandy aquifer. At present, the prediction models for safety assessment are often based on 2D assumptions. In this work, a 3D numerical approach of the groundwater flow leading to the erosion mechanism of backward erosion piping is presented and discussed. Comparison of the 2D and 3D numerical results explicitly demonstrates the inherent 3D nature of the piping phenomenon. In addition, the influence of the seepage length is investigated and discussed for both piping initiation and piping progression. The results clearly indicate the superiority of the presented 3D numerical model compared to the established 2D approach. Moreover, the 3D numerical results enable a better understanding of the complex physical mechanism involved in backward erosion piping and thus can lead to a significant improvement in the safety assessment of water retaining structures.

关键词： backward erosion piping groundwater flow 3D finite element method (FEM)

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PM₁₀ emissions from industrial coal-fired chain-grate boilers

Xinghua Li, Junzan Han, Lei Duan

《环境科学与工程前沿（英文）》 2017年第11卷第6期 doi: 10.1007/s11783-017-0966-y

摘要： Industrial coal-fired boiler is an important air pollutant emission source in China. The chain-grate boiler is the most extensively used type of industrial coal-fired boiler. An electrical low-pressure impactor, and a Dekati Low Pressure Impactor were applied to determine mass and number size distributions of PM at the inlet and the outlet of the particulate emission control devices at six coal-fired chain-grate boilers. The mass size distribution of PM generated from coal-fired chain-grate boilers generally displays a bimodal distribution that contains a submicron mode and a coarse mode. The PM in the submicron mode for burning with raw coal contributes to 33%±10 % of PM emissions, much higher than those for pulverized boilers. And the PM in the submicron mode for burning with briquette contributes up to 86 % of PM emissions. Multiclones and scrubbers are not efficient for controlling PM emission. Their average collection efficiencies for sub-micron particle and super-micron particle are 34% and 78%, respectively. Operating conditions of industrial steam boilers have influence on PM generation. Peak of the submicron mode during normal operation period is larger than the start-up period.

关键词： coal-fired chain-grate boiler PM₁₀ size distribution particulate emission control devices size-dependent collection efficiency

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Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice

《医学前沿（英文）》页码 957-971 doi: 10.1007/s11684-023-0988-8

摘要： Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.

关键词： DNAH10 mice motile cilia mutation primary ciliary dyskinesia

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Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient

《医学前沿（英文）》 2022年第16卷第4期页码 596-609 doi: 10.1007/s11684-021-0868-z

摘要： Sialic acid binding Ig-like lectin 10 (Siglec10) is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells. Here, by analyzing public databases containing 64 517 patients of 33 cancer types, we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types. In particular, Siglec10 was upregulated in patients with kidney renal clear cell carcinoma (KIRC) and was inversely associated with the prognosis of the patients. In 131 KIRC patients of our settings, Siglec10 was elevated in the tumor tissues of 83 (63.4%) patients compared with that in their counterpart normal kidney tissues. Moreover, higher level of Siglec10 was associated with advanced disease (stages III and IV) and worse prognosis. Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells. In addition, luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1, which were identified by data mining. These results demonstrate that Siglec10 may have important oncogenic functions in KIRC, and represents a novel target for the development of immunotherapies.

关键词： innate immune checkpoint Siglec10 kidney renal clear cell carcinoma

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A simple, azulene-based colorimetric probe for the detection of nitrite in water

López-Alled, Adam C. Sedgwick, Jannis Wenk, Tony D. James, Simon E. Lewis

《化学科学与工程前沿（英文）》 2020年第14卷第1期页码 90-96 doi: 10.1007/s11705-019-1790-7

摘要： We describe the synthesis and evaluation of an azulene-based chemodosimeter for nitrite. The probe was found to undergo two distinct color changes upon introduction aqueous nitrite ion. A near-instant formation of a grey color provides a qualitative indication of the presence of nitrite, followed by the formation of a deep-yellow/orange color, the endpoint from which quantitative data can be derived. The azulene probe exhibits 1:1 stoichiometry of reaction with nitrite in water, and is selective for nitrite over other anions. The azulene probe was applied to determine nitrite content in cured meat, and compared with the British Standard testing procedure (Griess test). The value obtained from the azulene-based probe agreed closely with the standard test. Our procedure only requires the preparation of one standard solution, instead of the three required for the standard Griess test.

关键词： azulene nitrite diazoquinone

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Home location inference from sparse and noisy data: models and applications

Tian-ran HU,Jie-bo LUO,Henry KAUTZ,Adam SADILEK

《信息与电子工程前沿（英文）》 2016年第17卷第5期页码 389-402 doi: 10.1631/FITEE.1500385

摘要： Accurate home location is increasingly important for urban computing. Existing methods either rely on continuous (and expensive) Global Positioning System (GPS) data or suffer from poor accuracy. In particular, the sparse and noisy nature of social media data poses serious challenges in pinpointing where people live at scale. We revisit this research topic and infer home location within 100 m×100 m squares at 70% accuracy for 76% and 71% of active users in New York City and the Bay Area, respectively. To the best of our knowledge, this is the first time home location has been detected at such a fine granularity using sparse and noisy data. Since people spend a large portion of their time at home, our model enables novel applications. As an example, we focus on modeling people’s health at scale by linking their home locations with publicly available statistics, such as education disparity. Results in multiple geographic regions demonstrate both the effectiveness and added value of our home localization method and reveal insights that eluded earlier studies. In addition, we are able to discover the real buzz in the communities where people live.

关键词： Home location Mobility patterns Healthcare

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The most influential “Top 10 Events” in carbon neutrality and climate change in 2022

《能源前沿（英文）》 2023年第17卷第1期页码 1-4 doi: 10.1007/s11708-023-0869-5

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Effect of IL-10 on formation of foam cell induced by ox-LDL

WANG Fei, DAI Yalei, XU Ting, XU Bo, WANG Kaifeng

《医学前沿（英文）》 2008年第2卷第3期页码 298-302 doi: 10.1007/s11684-008-0057-3

摘要： Atherosclerosis is a chronic disease that causes various cardiovascular complications. It has been realized that cellular and humoral immunity plays crucial roles in atherogenic lesion formation. In this study the effects of lipopolysaccharide (LPS) and interleukin-10 (IL-10) on the formation of foam cells during the early stages of atherosclerosis have been investigated. Macrophage was induced by phorbol myristate acetate (PMA) treatment on THP-1 cells. The cells were further stimulated by ox-LDL, ox-LDL plus LPS, ox-LDL plus IL-10 and LPS. By using an oil red O staining technique, the formation of foam cells was evaluated by lipid granules formation in the cells. The ratio of foam cell formation was increased from (9.77 ± 1.70)% to (16.27 ± 2.27)% after 24 h stimulation with ox-LDL, and the increase was observed with incubating time. The foam cells were significantly increased in the presence of LPS in a dose-dependent manner. The maximum increase of about 40% was observed. However, the significant elevation by LPS was abrogated when IL-10 was added. These results indicated that IL-10 can effectively prevent the formation of foam cells induced by ox-LDL with or without LPS. This study demonstrates that ox-LDL can cause foam cell formation from macrophages . LPS can significantly accelerate this event. IL-10, an anti-inflammatory cytokine, can inhibit the effect of ox-LDL and LPS. These results indicate that inflammatory effects in blood vessels can speed up foam cell formation. The inhibitive effect of IL-10 is an important factor for delaying atherosclerosis processes.

关键词： inflammatory presence interleukin-10 dose-dependent ox-LDL