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iSKIN: Integrated application of machine learning and Mondrian conformal prediction to detect skin sensitizers in cosmetic raw materials iSKIN:综合应用机器学习和蒙德里安保形预测技术检测化妆品原料中的皮肤致敏物质
Pub Date : 2024-02-15 DOI: 10.1002/smm2.1278
Weikaixin Kong, Jie Zhu, Peipei Shan, Huiyan Ying, Tongyu Chen, Bowen Zhang, Chao Peng, Zihan Wang, Yifan Wang, Liting Huang, Suzhen Bi, Weining Ma, Zhuo Huang, Sujie Zhu, Xueyan Liu, Chun Li
Animal experiments traditionally identify sensitizers in cosmetic materials. However, with growing concerns over animal ethics and bans on such experiments globally, alternative methods like machine learning are gaining prominence for their efficiency and cost‐effectiveness. In this study, to develop a robust sensitizer detector model, we first constructed benchmark data sets using data from previous studies and a public database, then 589 sensitizers and 831 nonsensitizers were collected. In addition, a graph‐based autoencoder and Mondrian conformal prediction (MCP) were combined to build a robust sensitizer detector, iSKIN. In the independent test set, the Matthews correlation coefficient (MCC) and the area under the receiver operating characteristic curve (ROCAUC) values of the iSKIN model without MCP were 0.472 and 0.804, respectively, which are higher than those of the three baseline models. When setting the significance level in MCP at 0.7, the MCC and ROCAUC values of iSKIN could achieve 0.753 and 0.927, respectively. Regrouping experiments proved that the MCP method is robust in the improvement of model performance. Through key structure analysis, seven key substructures in sensitizers were identified to guide cosmetic material design. Notably, long chains with halogen atoms and phenyl groups with two chlorine atoms at ortho‐positions were potential sensitizers. Finally, a user‐friendly web tool (http://www.iskin.work/) of the iSKIN model was deployed to be used by other researchers. In summary, the proposed iSKIN model has achieved state‐of‐the‐art performance so far, which can contribute to the safety evaluation of cosmetic raw materials and provide a reference for the chemical structure design of these materials.
传统上,通过动物实验来识别化妆品材料中的致敏物质。然而,随着人们对动物伦理的日益关注以及全球对此类实验的禁止,机器学习等替代方法因其高效性和成本效益而日益受到重视。在本研究中,为了开发出一种稳健的敏化物检测模型,我们首先利用以往研究的数据和公共数据库构建了基准数据集,然后收集了 589 种敏化物和 831 种非敏化物。此外,我们还将基于图的自动编码器和蒙德里安保形预测(MCP)结合起来,建立了鲁棒的敏化剂检测器 iSKIN。在独立测试集中,无 MCP 的 iSKIN 模型的马修斯相关系数(MCC)和接收者工作特征曲线下面积(ROCAUC)值分别为 0.472 和 0.804,均高于三个基线模型。当 MCP 的显著性水平设定为 0.7 时,iSKIN 模型的 MCC 和 ROCAUC 值分别达到 0.753 和 0.927。重新分组实验证明,MCP 方法在改善模型性能方面是稳健的。通过关键结构分析,确定了敏化剂中的七个关键子结构,为化妆品材料设计提供了指导。值得注意的是,含有卤素原子的长链和在正交位置含有两个氯原子的苯基是潜在的敏化剂。最后,iSKIN 模型的用户友好型网络工具(http://www.iskin.work/)已部署完毕,可供其他研究人员使用。总之,所提出的 iSKIN 模型达到了目前最先进的性能,可为化妆品原料的安全性评价做出贡献,并为这些原料的化学结构设计提供参考。
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引用次数: 0
iSKIN: Integrated application of machine learning and Mondrian conformal prediction to detect skin sensitizers in cosmetic raw materials iSKIN:综合应用机器学习和蒙德里安保形预测技术检测化妆品原料中的皮肤致敏物质
Pub Date : 2024-02-15 DOI: 10.1002/smm2.1278
Weikaixin Kong, Jie Zhu, Peipei Shan, Huiyan Ying, Tongyu Chen, Bowen Zhang, Chao Peng, Zihan Wang, Yifan Wang, Liting Huang, Suzhen Bi, Weining Ma, Zhuo Huang, Sujie Zhu, Xueyan Liu, Chun Li
Animal experiments traditionally identify sensitizers in cosmetic materials. However, with growing concerns over animal ethics and bans on such experiments globally, alternative methods like machine learning are gaining prominence for their efficiency and cost‐effectiveness. In this study, to develop a robust sensitizer detector model, we first constructed benchmark data sets using data from previous studies and a public database, then 589 sensitizers and 831 nonsensitizers were collected. In addition, a graph‐based autoencoder and Mondrian conformal prediction (MCP) were combined to build a robust sensitizer detector, iSKIN. In the independent test set, the Matthews correlation coefficient (MCC) and the area under the receiver operating characteristic curve (ROCAUC) values of the iSKIN model without MCP were 0.472 and 0.804, respectively, which are higher than those of the three baseline models. When setting the significance level in MCP at 0.7, the MCC and ROCAUC values of iSKIN could achieve 0.753 and 0.927, respectively. Regrouping experiments proved that the MCP method is robust in the improvement of model performance. Through key structure analysis, seven key substructures in sensitizers were identified to guide cosmetic material design. Notably, long chains with halogen atoms and phenyl groups with two chlorine atoms at ortho‐positions were potential sensitizers. Finally, a user‐friendly web tool (http://www.iskin.work/) of the iSKIN model was deployed to be used by other researchers. In summary, the proposed iSKIN model has achieved state‐of‐the‐art performance so far, which can contribute to the safety evaluation of cosmetic raw materials and provide a reference for the chemical structure design of these materials.
传统上,通过动物实验来识别化妆品材料中的致敏物质。然而,随着人们对动物伦理的日益关注以及全球对此类实验的禁止,机器学习等替代方法因其高效性和成本效益而日益受到重视。在本研究中,为了开发出一种稳健的敏化物检测模型,我们首先利用以往研究的数据和公共数据库构建了基准数据集,然后收集了 589 种敏化物和 831 种非敏化物。此外,我们还将基于图的自动编码器和蒙德里安保形预测(MCP)结合起来,建立了鲁棒的敏化剂检测器 iSKIN。在独立测试集中,无 MCP 的 iSKIN 模型的马修斯相关系数(MCC)和接收者工作特征曲线下面积(ROCAUC)值分别为 0.472 和 0.804,均高于三个基线模型。当 MCP 的显著性水平设定为 0.7 时,iSKIN 模型的 MCC 和 ROCAUC 值分别达到 0.753 和 0.927。重新分组实验证明,MCP 方法在改善模型性能方面是稳健的。通过关键结构分析,确定了敏化剂中的七个关键子结构,为化妆品材料设计提供了指导。值得注意的是,含有卤素原子的长链和在正交位置含有两个氯原子的苯基是潜在的敏化剂。最后,iSKIN 模型的用户友好型网络工具(http://www.iskin.work/)已部署完毕,可供其他研究人员使用。总之,所提出的 iSKIN 模型达到了目前最先进的性能,可为化妆品原料的安全性评价做出贡献,并为这些原料的化学结构设计提供参考。
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引用次数: 0
Constructing mechanically robust, efficient self‐healing, high‐energy, and recyclable energetic composites by hybrid dynamic lock strategy 通过混合动态锁定策略构建机械坚固、高效自愈合、高能量和可回收的高能量复合材料
Pub Date : 2024-01-31 DOI: 10.1002/smm2.1277
Zhe Sun, Yuhang Cheng, Borao Wan, Xiaoming Jin, Tianfu Zhang, Hongyi Zhu, Qi Xue, Lei Xiao, Guigao Liu, Wei Jiang, Guangpu Zhang
It is still a huge challenge to introduce effective crack‐healing ability into energetic composites with a high oxidizer content. In this article, a poly(urea‐urethane) energetic elastomer was prepared by the polycondensation reaction of glycidyl azido polymer (GAP), isophorone diisocyanate (IPDI), and 2‐aminophenyl disulfide (2‐APD). In the poly(urea‐urethane) elastomer structure, the hybrid dynamic lock, including multilevel H‐bonds and disulfide bonds, not only provides abundant dynamic interactions and promotes chain diffusion, but also enhances physical crosslinking density. Such a unique design fabricated the energetic elastomer with robust tensile strength (0.72 MPa), high stretchability (1631%), and outstanding toughness (8.95 MJ/m3) in the field of energetic polymers. Meanwhile, this energetic elastomer exhibited high self‐healing efficiency (98.4% at 60 °C) and heat release (Q = 1750.46 J/g). Experimental and theoretical results adequately explain the self‐healing mechanism, particularly the role of azido units. The high‐solid content (80 wt%) energetic composites based on the energetic elastomer presented outstanding micro‐defect self‐healing (97.8%) and recycling without loss of mechanical performance. The development of smart energetic composites with excellent self‐healing and recyclable ability provides a meaningful way for a wide range of applications in the field of energetic materials.
在氧化剂含量较高的高能复合材料中引入有效的裂纹愈合能力仍然是一个巨大的挑战。本文通过缩水甘油叠氮聚合物(GAP)、异佛尔酮二异氰酸酯(IPDI)和 2-氨基苯基二硫化物(2-APD)的缩聚反应,制备了一种聚脲-聚氨酯高能弹性体。在聚(脲-尿烷)弹性体结构中,包括多级 H 键和二硫键在内的混合动力锁不仅提供了丰富的动力相互作用,促进了链的扩散,还提高了物理交联密度。这种独特的设计制造出的高能弹性体具有强大的拉伸强度(0.72 兆帕)、高拉伸性(1631%)和出色的韧性(8.95 兆焦耳/立方米),在高能聚合物领域独树一帜。同时,这种高能弹性体还具有很高的自愈效率(60 °C时为98.4%)和热释放率(Q = 1750.46 J/g)。实验和理论结果充分解释了自愈机理,尤其是叠氮单元的作用。基于高能弹性体的高固含量(80 wt%)高能复合材料具有出色的微缺陷自愈合能力(97.8%),可回收再利用,且无机械性能损失。具有优异自愈合和可回收能力的智能高能复合材料的开发为高能材料领域的广泛应用提供了有意义的途径。
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引用次数: 0
Eco‐friendly materials for next‐generation vaccination: From concept to clinical reality 用于下一代疫苗接种的环保材料:从概念到临床现实
Pub Date : 2024-01-31 DOI: 10.1002/smm2.1274
Neha Kaushik, Paritosh Patel, Ravi Gupta, Apurva Jaiswal, Manorma Negi, Shweta B Borkar, Yogendra Kumar Mishra, June Hyun Kim, Eun Ha Choi, N. Kaushik
The vaccine is a premier healthcare intervention strategy in the battle against infectious infections. However, the development and production of vaccines present challenges in terms of complexity, cost, and time consumption. Alternative methodologies, such as nonthermal plasma and plant‐based technologies, have emerged as potential alternatives for conventional vaccine manufacturing processes. While plasma‐based approaches offer a rapid and efficient pathogen inactivation method devoid of harsh reagents, plant‐based techniques present a more economically viable and scalable avenue for vaccine production. The imperative urges these approaches to address pressing global health challenges posed by emerging and recurring infectious diseases, surpassing the limitations of traditional vaccine fabrication methods. The primary goal of this review is to provide a comprehensive overview of the current research landscape, covering conceptualization, production, and potential advantages of plasma‐based and plant‐based vaccines. Furthermore, exploring the obstacles and opportunities intrinsic to these strategies is undertaken, elucidating their potential impact on vaccination strategies. This systematic presentation specifies a detailed outline of recent vaccine research and developments, emphasizing the possibility of advanced green approaches to produce effective and secure vaccination programs.
疫苗是抗击传染性感染的首要医疗干预策略。然而,疫苗的开发和生产在复杂性、成本和时间消耗方面都存在挑战。非热等离子体和植物技术等替代方法已成为传统疫苗生产工艺的潜在替代方法。基于等离子体的方法提供了一种快速高效的病原体灭活方法,无需使用刺激性试剂,而基于植物的技术则为疫苗生产提供了一种更经济可行且可扩展的途径。当务之急是采用这些方法来应对新发和复发传染病带来的紧迫的全球健康挑战,超越传统疫苗制造方法的局限性。本综述的主要目的是全面概述当前的研究状况,包括基于血浆和植物的疫苗的概念化、生产和潜在优势。此外,还探讨了这些策略的内在障碍和机遇,阐明了它们对疫苗接种策略的潜在影响。本系统性报告详细概述了近期的疫苗研究和发展,强调了先进的绿色方法在制定有效、安全的疫苗接种计划方面的可能性。
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引用次数: 0
Metal‐organic framework‐based nanofibrous film for two different modes of triboelectric nanogenerators 用于两种不同模式三电纳米发电机的基于金属有机框架的纳米纤维膜
Pub Date : 2024-01-25 DOI: 10.1002/smm2.1270
R. Tabassian, Araz Rajabi-Abhari, Manmatha Mahato, H. Yoo, Hong Yeon Yoon, Jeong Young Park, Il‐Kwon Oh
Metal‐organic frameworks (MOFs) are nanomaterials with engineered chemical structures, offering remarkable properties. However, their limited film‐formation capability hinders their integration into triboelectric nanogenerators (TENGs). This study proposes a simple yet effective solution to overcome this challenge by employing electrospinning techniques to integrate the zeolitic imidazolate framework (ZIF‐8) into an easy‐to‐use nanofibrous mat. ZIF‐8 has high surface potential, a unique cubical structure, and an easy fabrication process that makes it an ideal material for TENGs. By incorporating ZIF‐8 into the electrospinning solution, significant improvements are achieved in the electropositivity of the resulting nanofibers. It leads to notable changes in the shape, morphology, and roughness of electrospun fibers, consequently enhancing the overall performance of the TENG. The results indicate that utilizing the ZIF‐based electrospun mat as a tribo‐positive material can increase transferred charges between electrodes by more than 100%. Utilizing the MOF‐based nanofibrous mat, this study also introduces a novel rotary TENG that works based on a mode of TENG operation called rolling mode. The reliable charge generation by the proposed rolling system reveals that this mode of TENG operation could be a superb alternative for traditional TENG modes, like contact/separation or sliding, which cause high levels of mechanical stress due to harsh physical impact or friction.
金属有机框架(MOFs)是一种具有工程化学结构的纳米材料,具有卓越的性能。然而,其有限的成膜能力阻碍了它们与三电纳米发电机(TENGs)的集成。本研究提出了一种简单而有效的解决方案来克服这一挑战,即采用电纺丝技术将沸石咪唑酸框架(ZIF-8)整合到易于使用的纳米纤维垫中。ZIF-8 具有高表面电位、独特的立方体结构和简便的制造工艺,使其成为 TENG 的理想材料。在电纺丝溶液中加入 ZIF-8,可显著提高纳米纤维的电位。它使电纺纤维的形状、形态和粗糙度发生了显著变化,从而提高了 TENG 的整体性能。研究结果表明,利用基于 ZIF 的电纺毡作为三正极材料,可使电极之间的电荷转移增加 100%以上。利用基于 MOF 的纳米纤维垫,本研究还介绍了一种新型旋转式 TENG,该 TENG 的工作模式称为滚动模式。拟议的滚动系统能可靠地产生电荷,这表明这种 TENG 运行模式是接触/分离或滑动等传统 TENG 模式的绝佳替代方案,因为传统 TENG 模式会因剧烈的物理冲击或摩擦而产生高水平的机械应力。
{"title":"Metal‐organic framework‐based nanofibrous film for two different modes of triboelectric nanogenerators","authors":"R. Tabassian, Araz Rajabi-Abhari, Manmatha Mahato, H. Yoo, Hong Yeon Yoon, Jeong Young Park, Il‐Kwon Oh","doi":"10.1002/smm2.1270","DOIUrl":"https://doi.org/10.1002/smm2.1270","url":null,"abstract":"Metal‐organic frameworks (MOFs) are nanomaterials with engineered chemical structures, offering remarkable properties. However, their limited film‐formation capability hinders their integration into triboelectric nanogenerators (TENGs). This study proposes a simple yet effective solution to overcome this challenge by employing electrospinning techniques to integrate the zeolitic imidazolate framework (ZIF‐8) into an easy‐to‐use nanofibrous mat. ZIF‐8 has high surface potential, a unique cubical structure, and an easy fabrication process that makes it an ideal material for TENGs. By incorporating ZIF‐8 into the electrospinning solution, significant improvements are achieved in the electropositivity of the resulting nanofibers. It leads to notable changes in the shape, morphology, and roughness of electrospun fibers, consequently enhancing the overall performance of the TENG. The results indicate that utilizing the ZIF‐based electrospun mat as a tribo‐positive material can increase transferred charges between electrodes by more than 100%. Utilizing the MOF‐based nanofibrous mat, this study also introduces a novel rotary TENG that works based on a mode of TENG operation called rolling mode. The reliable charge generation by the proposed rolling system reveals that this mode of TENG operation could be a superb alternative for traditional TENG modes, like contact/separation or sliding, which cause high levels of mechanical stress due to harsh physical impact or friction.","PeriodicalId":21794,"journal":{"name":"SmartMat","volume":"102 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139596616","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
Injectable microcarrier‐hydrogel composite for dental stem cell delivery and tissue regeneration 用于牙科干细胞输送和组织再生的可注射微载体-水凝胶复合材料
Pub Date : 2024-01-22 DOI: 10.1002/smm2.1268
Yu Jie Soh, Ruby Yu‐Tong Lin, Gopu Sriram, Wei Seong Toh, Victoria Soo Hoon Yu, Nileshkumar Dubey
Conventional methods of stem cell therapy for tissue regeneration often face challenges, such as poor cell viability and integration posttransplantation. To address this, we proposed transplanting cells within synthetic microenvironments that maintain viability, cell phenotype, support extracellular matrix (ECM) secretion, and promote differentiation to enhance the regeneration of damaged host tissue. This hypothesis was tested in dental tissue regeneration using dental pulp stem cell‐laden microcarriers (MCs) mixed in a gelatin methacrylate (GelMA) hydrogel as a delivery system. The combination of MCs and GelMA exhibited similar physical properties and favorable biological properties compared to GelMA alone. Specifically, cell‐laden MC mixed into GelMA enhanced cell proliferation and ECM secretion and maintained a normal phenotype. Notably, MC‐modified GelMA amplified odontogenic differentiation, mineralization, and vascular endothelial growth factor release. Moreover, the storage of MC‐modified GelMA showed no detrimental effects on its injection force, cell viability, and mineralization potential, which demonstrates that the composite hydrogel is a promising injectable vehicle for therapeutic stem cell delivery. This strategy may be broadly applied to various tissues and organ systems, in which the provision and instruction of a cell population to participate in regeneration may be clinically useful.
干细胞治疗组织再生的传统方法往往面临挑战,如细胞活力差和移植后整合。为解决这一问题,我们提出在合成微环境中移植细胞,以保持细胞活力、细胞表型、支持细胞外基质(ECM)分泌并促进分化,从而增强受损宿主组织的再生能力。在牙科组织再生过程中,使用牙髓干细胞微载体(MCs)混合甲基丙烯酸明胶(GelMA)水凝胶作为传输系统,对这一假设进行了测试。与单独的 GelMA 相比,MCs 和 GelMA 的组合具有相似的物理特性和良好的生物特性。具体来说,混入 GelMA 中的细胞负载 MC 可增强细胞增殖和 ECM 分泌,并保持正常的表型。值得注意的是,MC 改性 GelMA 能促进牙体分化、矿化和血管内皮生长因子的释放。此外,储存 MC 改性 GelMA 对其注射力、细胞存活率和矿化潜能均无不利影响,这表明复合水凝胶是一种很有前景的治疗性干细胞注射载体。这种策略可广泛应用于各种组织和器官系统,提供和指导细胞群参与再生可能对临床有用。
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引用次数: 0
Flexible organic integrated circuits free of parasitic capacitance fabricated through a simple dual self‐alignment method 通过简单的双自对准法制造出无寄生电容的柔性有机集成电路
Pub Date : 2024-01-22 DOI: 10.1002/smm2.1273
Baichuan Jiang, Xiao Han, Yu Che, Wenbin Li, Hong-wei Zheng, Jun Li, Cailing Ou, Nannan Dou, Zixiao Han, Tingyu Ji, Chuanhui Liu, Zhiyuan Zhao, Yunlong Guo, Yunqi Liu, Lei Zhang
In integrated circuits (ICs), the parasitic capacitance is one of the crucial factors that degrade the circuit dynamic performance; for instance, it reduces the operating frequency of the circuit. Eliminating the parasitic capacitance in organic transistors is notoriously challenging due to the inherent tradeoff between manufacturing costs and interlayer alignment accuracy. Here, we overcome such a limitation using a cost‐effective method for fabricating organic thin‐film transistors and rectifying diodes without redundant electrode overlaps. This is achieved by placing all electrodes horizontally and introducing sub‐100 nm gaps for separation. A representative small‐scale IC consisting of five‐stage ring oscillators based on the obtained nonparasitic transistors and diodes is fabricated on flexible substrates, which performs reliably at a low driving voltage of 1 V. Notably, the oscillator exhibits signal propagation delays of 5.8 μs per stage at a supply voltage of 20 V when utilizing pentacene as the active layer. Since parasitic capacitance has been a common challenge for all types of thin‐film transistors, our approach may pave the way toward the realization of flexible and large‐area ICs based on other emerging and highly performing semiconductors.
在集成电路(IC)中,寄生电容是降低电路动态性能的关键因素之一,例如,它会降低电路的工作频率。在有机晶体管中消除寄生电容是一项众所周知的挑战,因为制造成本和层间对准精度之间存在固有的权衡。在此,我们采用一种经济高效的方法来制造无多余电极重叠的有机薄膜晶体管和整流二极管,从而克服了这一限制。这是通过水平放置所有电极并引入 100 纳米以下的间隙来实现的。基于所获得的非寄生晶体管和二极管,在柔性衬底上制造出了一个具有代表性的由五级环形振荡器组成的小型集成电路,该集成电路在 1 V 的低驱动电压下也能可靠地工作。值得注意的是,当使用五碳烯作为有源层时,振荡器在 20 V 电源电压下每级的信号传播延迟为 5.8 μs。由于寄生电容一直是所有类型薄膜晶体管面临的共同挑战,我们的方法可能会为实现基于其他新兴高性能半导体的灵活大面积集成电路铺平道路。
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引用次数: 0
Tumor cell dissociation‐enhanced intravesical chemotherapy of orthotopic bladder cancer 肿瘤细胞解离增强型膀胱癌膀胱内化疗
Pub Date : 2024-01-22 DOI: 10.1002/smm2.1276
Zhaoyu Ma, Zhiduo Sun, Zhichao Ye, Kai Cai, Wenbin Zhong, Weiguang Yuan, Weiyun Zhang, Jin Zhang, Kai Zhang, Huageng Liang, Heyou Han, Yanli Zhao
Frequent intravesical chemotherapy is still the adopted clinical option after bladder cancer surgery with low adhesion, poor selectivity, low permeability, and drug resistance. Herein, we develop an ingenious bladder cancer dissociation method to enhance intravesical chemotherapy and tumor self‐exclusion with urine. Ethylene diamine tetraacetic acid (EDTA), a common Ca2+ chelator, is loaded with the typical clinical bladder instillation drug doxorubicin (Dox) in chitosan‐modified hollow gold nanorods and subsequently coated with cancer cell membranes. After bladder perfusion, the nanoplatform exhibits high affinity toward bladder tumors under homologous targeting, assisting in long‐term retention. Under NIR‐II laser irradiation, the photothermal effect accelerates the unloading of cargo, and the released EDTA then disrupts intratumoral junctions by depriving and chelating Ca2+ from the intercellular calcium‐dependent connexin. The consequential intertumoral dissociation gives access to the deeper penetration of Dox and allows the exclusion of the shed small tumor masses from the body with the urine. This distinctive tumor dissociation concept holds great promise for modern clinical intravesical chemotherapy and perhaps for other gastrointestinal malignancies.
频繁的膀胱内化疗仍是膀胱癌术后采用的临床方案,但存在粘附性低、选择性差、渗透性低和耐药性等问题。在此,我们开发了一种巧妙的膀胱癌解离方法,以加强膀胱内化疗和肿瘤与尿液的自我排异。在壳聚糖改性的空心金纳米棒中装入临床上常用的膀胱灌注药物多柔比星(Dox),并在其上包覆癌细胞膜。膀胱灌注后,该纳米平台在同源靶向作用下对膀胱肿瘤具有高亲和力,有助于长期保留。在近红外-II 激光照射下,光热效应加速了货物的卸载,释放出的乙二胺四乙酸通过剥夺和螯合细胞间钙依赖性连接蛋白中的 Ca2+,破坏瘤内连接。随之而来的瘤间解离使 Dox 能够深入渗透,并使脱落的小肿瘤随尿液排出体外。这种独特的肿瘤解离概念为现代临床膀胱内化疗带来了巨大的希望,或许也适用于其他胃肠道恶性肿瘤。
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引用次数: 0
Anticoagulant therapy without bleeding: A novel molybdenum‐based nanodots alleviate lethal coagulation in bacterial sepsis by inhibiting ROS‐facilitated caspase‐11 activation 抗凝治疗不出血:新型钼基纳米点通过抑制 ROS 促成的 caspase-11 激活缓解细菌性败血症中的致命凝血作用
Pub Date : 2024-01-19 DOI: 10.1002/smm2.1264
Chuang Yuan, Qicai Xiao, Qiaohui Chen, Qiong Huang, K. Ai, Xinyu Yang
Sepsis is a leading cause of death worldwide. This syndrome is commonly accompanied by overactivation of coagulation, excessive reactive oxygen species (ROS), and inflammatory cytokine storm. Notably, disseminated intravascular coagulation (DIC) accounts for around 40% of sepsis‐associated deaths. However, anticoagulant therapy is still difficult for sepsis treatment because of the lethal bleeding side effects. Although the relationship between ROS and inflammatory cytokine storm has been described clearly, the pathogenic role of ROS in DIC, however, is still unclear, which renders novel therapeutic approaches hard to achieve bedside for inhibiting DIC. Herein, our new finding reveals that ROS greatly facilitates the entry of lipopolysaccharide (LPS) into the macrophage cytoplasm, which subsequently activates the caspase‐11/gasdermin D pathway, and finally induces DIC through phosphatidylserine exposure. Based on this finding, novel gallic acid‐modified Mo‐based polyoxometalate dots (M‐dots) with outstanding antioxidant activity are developed to provide ideal and efficient inhibition of DIC. As expected, M‐dots are capable of markedly inhibiting sepsis‐caused coagulation, organ injury, and death in sepsis. This therapeutic strategy, blocking the upstream pathway of coagulation rather than coagulation itself, can avoid the side effects of extensive bleeding caused by conventional anticoagulation therapy, and will provide a new avenue for the efficient treatment of sepsis.
败血症是全球死亡的主要原因。这种综合征通常伴有凝血过度激活、活性氧(ROS)过多和炎症细胞因子风暴。值得注意的是,弥散性血管内凝血(DIC)约占败血症相关死亡病例的 40%。然而,由于致命的出血副作用,抗凝疗法仍难以用于败血症治疗。尽管 ROS 与炎性细胞因子风暴之间的关系已被清楚描述,但 ROS 在 DIC 中的致病作用仍不明确,这使得抑制 DIC 的新型治疗方法难以在床边实现。在此,我们的新发现揭示了 ROS 可极大地促进脂多糖(LPS)进入巨噬细胞胞质,进而激活 Caspase-11/gasdermin D 通路,最后通过磷脂酰丝氨酸暴露诱导 DIC。基于这一发现,新型没食子酸改性钼基多氧代金属酸盐点(M-点)应运而生,它具有出色的抗氧化活性,能理想、高效地抑制 DIC。正如预期的那样,M-点能够显著抑制败血症引起的凝血、器官损伤和死亡。这种阻断凝血上游途径而非凝血本身的治疗策略,可以避免传统抗凝疗法造成的大出血副作用,为脓毒症的高效治疗提供了一条新途径。
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引用次数: 0
Knee function assessment of anterior cruciate ligament injury with a Kirigami buckling‐resistant stretchable sensor 利用 Kirigami 抗扣压可拉伸传感器评估前十字韧带损伤的膝关节功能
Pub Date : 2024-01-17 DOI: 10.1002/smm2.1271
Xiaopeng Yang, Menglun Zhang, Pengfei Niu, Wenlan Guo, Chen Sun, Wei Pang, Guoqing Cui, Qiang Liu
Continuous and quantitative monitoring of knee joint function has clinical value in rehabilitation assessment and the timing of return to play for anterior cruciate ligament injury patients. However, the existing approaches, including clinical examination, arthrometry and inertial solutions, can only be used for qualitative, off‐line and low‐quality evaluations, respectively. Burgeoning Kirigami stretchable sensors could be a disruptive candidate solution, but they usually suffer from structural buckling issues when used for large strain applications, such as knee joint motion capture where the buckling degrades sensor reliability and repeatability. Here, we propose a buckling‐resistant stretchable and wearable sensor for knee joint motion capture. It enables continuous and precise motion signal capture of the knee joint and provides high wearing comfort and reliability. Clinical tests were conducted on 30 patients in the field, tracking data provided by the sensor from their initial hospitalization to later surgery. And the full rehabilitation of one subject was recorded and analyzed. The test results show that our sensor can dynamically assess knee function in real time and recommend the best timing for return to play, which paves the way for personalized and telerehabilitation.
对膝关节功能进行连续和定量监测,对于前交叉韧带损伤患者的康复评估和重返赛场的时机选择具有临床价值。然而,包括临床检查、关节测量和惯性解决方案在内的现有方法只能分别用于定性、离线和低质量评估。新兴的叽里呱啦可拉伸传感器可能是一种颠覆性的候选解决方案,但它们在用于大应变应用时通常会出现结构屈曲问题,例如膝关节运动捕捉,屈曲会降低传感器的可靠性和可重复性。在这里,我们提出了一种用于膝关节运动捕捉的抗屈曲可拉伸可穿戴传感器。它能连续、精确地捕捉膝关节的运动信号,并提供较高的佩戴舒适度和可靠性。我们在现场对 30 名患者进行了临床测试,跟踪了传感器提供的从最初住院到后来手术的数据。此外,还记录并分析了一名受试者的整个康复过程。测试结果表明,我们的传感器可以实时动态评估膝关节功能,并推荐恢复比赛的最佳时机,这为个性化和远程康复铺平了道路。
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