Mesoporous silica nanoparticles (MSNs) have emerged as promising drug carriers that can facilitate targeted anticancer drug delivery, but efficiency studies relying on active targeting mechanisms remain elusive. This study implements in vitro 3D cocultures, so-called microtissues, to model a physiologically relevant tumor microenvironment (TME) to examine the impact of surface-modified MSNs without targeting ligands on the internalization, cargo delivery, and cargo release in tumor cells and cancer-associated fibroblasts. Among these, acetylated MSNs most effectively localized in tumor cells in a 3D setting containing collagen, while other MSNs did so to a lesser degree, most likely due to remaining trapped in the extracellular matrix of the TME. Confocal imaging of hydrophobic model drug-loaded MSNs demonstrated effective cargo release predominantly in tumor cells, both in 2D and 3D cocultures. MSN-mediated delivery of an anticancer drug in the microtissues exhibited a significant reduction in tumor organoid size and enhanced the tumor-specific cytotoxic effects of a γ-secretase inhibitor, compared to the highly hydrophobic drug in free form. This inherent targeting potential suggests reduced off-target effects and increased drug efficacy, showcasing the promise of surface modification of MSNs as a means of direct cell-specific targeting and delivery for precise and successful targeted drug delivery.
{"title":"Surface Modification of Mesoporous Silica Nanoparticles as a Means to Introduce Inherent Cancer-Targeting Ability in a 3D Tumor Microenvironment","authors":"Neeraj Prabhakar, Erica Långbacka, Ezgi Özliseli, Jesse Mattsson, Alaa Mahran, Ilida Suleymanova, Cecilia Sahlgren, Jessica M. Rosenholm, Malin Åkerfelt, Matthias Nees","doi":"10.1002/smsc.202400084","DOIUrl":"https://doi.org/10.1002/smsc.202400084","url":null,"abstract":"Mesoporous silica nanoparticles (MSNs) have emerged as promising drug carriers that can facilitate targeted anticancer drug delivery, but efficiency studies relying on active targeting mechanisms remain elusive. This study implements in vitro 3D cocultures, so-called microtissues, to model a physiologically relevant tumor microenvironment (TME) to examine the impact of surface-modified MSNs without targeting ligands on the internalization, cargo delivery, and cargo release in tumor cells and cancer-associated fibroblasts. Among these, acetylated MSNs most effectively localized in tumor cells in a 3D setting containing collagen, while other MSNs did so to a lesser degree, most likely due to remaining trapped in the extracellular matrix of the TME. Confocal imaging of hydrophobic model drug-loaded MSNs demonstrated effective cargo release predominantly in tumor cells, both in 2D and 3D cocultures. MSN-mediated delivery of an anticancer drug in the microtissues exhibited a significant reduction in tumor organoid size and enhanced the tumor-specific cytotoxic effects of a γ-secretase inhibitor, compared to the highly hydrophobic drug in free form. This inherent targeting potential suggests reduced off-target effects and increased drug efficacy, showcasing the promise of surface modification of MSNs as a means of direct cell-specific targeting and delivery for precise and successful targeted drug delivery.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141612596","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}
Yun Seong Byeon, Wontae Lee, Sangbin Park, Dongil Kim, Jaewoo Jung, Min-Sik Park, Won-Sub Yoon
This review explores the challenges and advancements in the development of high-energy lithium-ion batteries (LIBs), particularly focusing on the electrochemical and structural stability of Ni-rich cathode materials. Despite their potential to increase the energy density of LIBs, these cathode materials encounter issues such as irreversible phase transitions and structural degradation during cycling, which ultimately affect their electrochemical performance. Elemental doping/substitution has emerged as promising strategies to address these challenges. However, the precise mechanisms underlying their performance enhancement remain unclear. The objective is to elucidate the complex reaction mechanisms triggered by doping and substitution in Ni-rich cathode materials by employing in situ operando analyses to uncover their effects on electrochemical behavior and structural integrity during cycling. This comprehensive investigation aims to clarify the roles of elemental dopants or substituents in the crystal structures of Ni-rich cathode materials, thereby offering valuable insights for the structural engineering of cathode materials in high-energy LIBs. By elucidating these intricate mechanisms, this review provides a practical roadmap for future research and significantly contributes to LIB technology by guiding material design and optimization strategies in the development of advanced LIBs.
{"title":"Comprehensive Understanding of Elemental Doping and Substitution of Ni-Rich Cathode Materials for Lithium-Ion Batteries via In Situ Operando Analyses","authors":"Yun Seong Byeon, Wontae Lee, Sangbin Park, Dongil Kim, Jaewoo Jung, Min-Sik Park, Won-Sub Yoon","doi":"10.1002/smsc.202400165","DOIUrl":"https://doi.org/10.1002/smsc.202400165","url":null,"abstract":"This review explores the challenges and advancements in the development of high-energy lithium-ion batteries (LIBs), particularly focusing on the electrochemical and structural stability of Ni-rich cathode materials. Despite their potential to increase the energy density of LIBs, these cathode materials encounter issues such as irreversible phase transitions and structural degradation during cycling, which ultimately affect their electrochemical performance. Elemental doping/substitution has emerged as promising strategies to address these challenges. However, the precise mechanisms underlying their performance enhancement remain unclear. The objective is to elucidate the complex reaction mechanisms triggered by doping and substitution in Ni-rich cathode materials by employing in situ operando analyses to uncover their effects on electrochemical behavior and structural integrity during cycling. This comprehensive investigation aims to clarify the roles of elemental dopants or substituents in the crystal structures of Ni-rich cathode materials, thereby offering valuable insights for the structural engineering of cathode materials in high-energy LIBs. By elucidating these intricate mechanisms, this review provides a practical roadmap for future research and significantly contributes to LIB technology by guiding material design and optimization strategies in the development of advanced LIBs.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141572416","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}
Aims: Heart failure (HF) is associated with profound changes in cardiac metabolism. At present, there is still a lack of relevant research to explore the key microbiome and their metabolites affecting the progression of HF. Herein, the interaction of gut microbiota and circulating free fatty acid (FFA) in HF patients and mice is investigated. Methods and Results: In HF patients, by applying metagenomics analysis and targeted FFA metabolomics, enriched abundance of Clostridium sporogenes (C.sp) in early and late stage of HF patients, which negatively correlated to saturated free fatty acid (SFA) levels, is identified. KEGG analysis further indicates microbiota gene enrichment in FFA degradation in early HF, and decreased gene expression in FFA synthesis in late HF. In HF mice (C57BL/6J) induced by isoproterenol (ISO), impaired intestinal permeability is observed, and decreased fecal C.sp and increased SFA are further validated. At last, by supplementing C.sp to ISO-induced HF mice, the cardiac function, fibrosis, and myocardial size are partially rescued, together with decreased circulating SFA levels. Conclusions: Clostridium abundance is increased in HF, compensating cardiac function deterioration via downregulation of circulating SFA levels. The results demonstrate that the gut microbiota–SFA axis plays an important role in HF protection, which may provide a strategic advantage for the probiotic therapy development in HF.
{"title":"Gut Microbiota Regulate Saturated Free Fatty Acid Metabolism in Heart Failure","authors":"Gulinigaer Tuerhongjiang, Manyun Guo, Xiangrui Qiao, Junhui Liu, Wen Xi, Yuanyuan Wei, Peining Liu, Bowen Lou, Chen Wang, Lizhe Sun, Xiao Yuan, Hui Liu, Ying Xiong, Yunlong Ma, Hongbing Li, Bo Zhou, Lijuan Li, Zuyi Yuan, Yue Wu, Jianqing She","doi":"10.1002/smsc.202300337","DOIUrl":"https://doi.org/10.1002/smsc.202300337","url":null,"abstract":"Aims: Heart failure (HF) is associated with profound changes in cardiac metabolism. At present, there is still a lack of relevant research to explore the key microbiome and their metabolites affecting the progression of HF. Herein, the interaction of gut microbiota and circulating free fatty acid (FFA) in HF patients and mice is investigated. Methods and Results: In HF patients, by applying metagenomics analysis and targeted FFA metabolomics, enriched abundance of <i>Clostridium sporogenes</i> (<i>C.sp</i>) in early and late stage of HF patients, which negatively correlated to saturated free fatty acid (SFA) levels, is identified. KEGG analysis further indicates microbiota gene enrichment in FFA degradation in early HF, and decreased gene expression in FFA synthesis in late HF. In HF mice (C57BL/6J) induced by isoproterenol (ISO), impaired intestinal permeability is observed, and decreased fecal <i>C.sp</i> and increased SFA are further validated. At last, by supplementing <i>C.sp</i> to ISO-induced HF mice, the cardiac function, fibrosis, and myocardial size are partially rescued, together with decreased circulating SFA levels. Conclusions: <i>Clostridium</i> abundance is increased in HF, compensating cardiac function deterioration via downregulation of circulating SFA levels. The results demonstrate that the gut microbiota–SFA axis plays an important role in HF protection, which may provide a strategic advantage for the probiotic therapy development in HF.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141572415","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}
Fabiana Giglio, Carmen Scieuzo, Sofia Ouazri, Valentina Pucciarelli, Dolores Ianniciello, Sophia Letcher, Rosanna Salvia, Ambrogio Laginestra, David L. Kaplan, Patrizia Falabella
The increasing global population and demand for meat have led to the need to find sustainable and viable alternatives to traditional production methods. One potential solution is cultivated meat (CM), which involves producing meat in vitro from animal stem cells to generate products with nutritional and sensory properties similar to conventional livestock-derived meat. This article examines current approaches to CM production and investigates how using insect cells could enhance the process. Cell sources are a critical issue in CM production, alongside advances in culture media, bioreactors for scalability, and scaffold development. Insect cells, compared to commonly used mammalian cells, may offer advantages in overcoming technological challenges that hinder cell culture development and expansion. The objective of this review is to emphasize how insects, as a cell source for CM production, could offer a more sustainable option. A crucial aspect for achieving this goal is a comprehensive understanding of the physiology of muscle and fat cells. In this work, the characteristics of insect and mammalian cells are compared, focusing particularly on muscle and fat cell development, regulatory pathways, hormonal regulation, and tissue composition. Insect cells are a promising source for CM, offering a sustainable and environmentally friendly alternative.
{"title":"A Glance into the Near Future: Cultivated Meat from Mammalian and Insect Cells","authors":"Fabiana Giglio, Carmen Scieuzo, Sofia Ouazri, Valentina Pucciarelli, Dolores Ianniciello, Sophia Letcher, Rosanna Salvia, Ambrogio Laginestra, David L. Kaplan, Patrizia Falabella","doi":"10.1002/smsc.202400122","DOIUrl":"https://doi.org/10.1002/smsc.202400122","url":null,"abstract":"The increasing global population and demand for meat have led to the need to find sustainable and viable alternatives to traditional production methods. One potential solution is cultivated meat (CM), which involves producing meat in vitro from animal stem cells to generate products with nutritional and sensory properties similar to conventional livestock-derived meat. This article examines current approaches to CM production and investigates how using insect cells could enhance the process. Cell sources are a critical issue in CM production, alongside advances in culture media, bioreactors for scalability, and scaffold development. Insect cells, compared to commonly used mammalian cells, may offer advantages in overcoming technological challenges that hinder cell culture development and expansion. The objective of this review is to emphasize how insects, as a cell source for CM production, could offer a more sustainable option. A crucial aspect for achieving this goal is a comprehensive understanding of the physiology of muscle and fat cells. In this work, the characteristics of insect and mammalian cells are compared, focusing particularly on muscle and fat cell development, regulatory pathways, hormonal regulation, and tissue composition. Insect cells are a promising source for CM, offering a sustainable and environmentally friendly alternative.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141577694","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}
The development of inorganic electrides offers new possibilities for studying topological states due to the nonnuclear-binding properties displayed by interstitial electrons. Herein, a sandwich electride 2[CaCl]+:2e− is designed, featuring a tetragonal lattice structure, including two atomic lattice layers and one interstitial electron layer. The interstitial electrons form nonsymmorphic-symmetry-protected Dirac points (DPs) at the X and M points, which are robust against the spin–orbit coupling effect. DPs exhibit an approximately elliptical shape, characterized by a relatively high anisotropy, resulting from the interplay between the electron and atomic layers. In addition, 2[CaCl]+:2e− possesses a lower work function (WF) (3.43 eV), endowing it with robust electron-supplying characteristics. Due to the low WF and interstitial electrons, 2[CaCl]+:2e− loaded Ru shows outstanding catalytic performance for N2 cleavage. A potential research platform for exploring the formation of topological states and promoting nitrogen cracking in electrides is provided.
由于间隙电子具有非核结合特性，无机电化物的发展为研究拓扑状态提供了新的可能性。在这里，我们设计了一种夹层电化物 2[CaCl]+:2e-，它具有四方晶格结构，包括两个原子晶格层和一个间隙电子层。间隙电子在 X 点和 M 点形成非非晶态对称保护的狄拉克点（DP），对自旋轨道耦合效应有很强的抵抗力。DPs呈现近似椭圆的形状，其特点是各向异性相对较高，这是电子层和原子层之间相互作用的结果。此外，2[CaCl]+:2e- 具有较低的功函数（WF）（3.43 eV），使其具有强大的电子供应特性。由于低功函数和间隙电子，2[CaCl]+:2e-负载的 Ru 在 N2 裂解过程中表现出卓越的催化性能。这为探索拓扑态的形成和促进电氧化物中的氮裂解提供了一个潜在的研究平台。
{"title":"Zero-Dimensional Interstitial Electron-Induced Spin–Orbit Coupling Dirac States in Sandwich Electride","authors":"Weizhen Meng, Jiayu Jiang, Yalong Jiao, Fengxian Ma, Ying Yang, Zhenxiang Cheng, Xiaotian Wang","doi":"10.1002/smsc.202400131","DOIUrl":"https://doi.org/10.1002/smsc.202400131","url":null,"abstract":"The development of inorganic electrides offers new possibilities for studying topological states due to the nonnuclear-binding properties displayed by interstitial electrons. Herein, a sandwich electride 2[CaCl]<sup>+</sup>:2e<sup>−</sup> is designed, featuring a tetragonal lattice structure, including two atomic lattice layers and one interstitial electron layer. The interstitial electrons form nonsymmorphic-symmetry-protected Dirac points (DPs) at the X and M points, which are robust against the spin–orbit coupling effect. DPs exhibit an approximately elliptical shape, characterized by a relatively high anisotropy, resulting from the interplay between the electron and atomic layers. In addition, 2[CaCl]<sup>+</sup>:2e<sup>−</sup> possesses a lower work function (WF) (3.43 eV), endowing it with robust electron-supplying characteristics. Due to the low WF and interstitial electrons, 2[CaCl]<sup>+</sup>:2e<sup>−</sup> loaded Ru shows outstanding catalytic performance for N<sub>2</sub> cleavage. A potential research platform for exploring the formation of topological states and promoting nitrogen cracking in electrides is provided.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141547914","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}
P. Monalisha, Maria Ameziane, Irena Spasojevic, Eva Pellicer, Rhodri Mansell, Enric Menéndez, Sebastiaan van Dijken, Jordi Sort
With the advent of Big Data, traditional digital computing is struggling to cope with intricate tasks related to data classification or pattern recognition. To mitigate this limitation, software-based neural networks are implemented, but they are run in conventional computers whose operation principle (with separate memory and data-processing units) is highly inefficient compared to the human brain. Brain-inspired in-memory computing is achieved through a wide variety of methods, for example, artificial synapses, spiking neural networks, or reservoir computing. However, most of these methods use materials (e.g., memristor arrays, spintronics, phase change memories) operated with electric currents, resulting in significant Joule heating effect. Tuning magnetic properties by voltage-driven ion motion (i.e., magnetoionics) has recently emerged as an alternative energy-efficient approach to emulate functionalities of biological synapses: potentiation/depression, multilevel storage, or transitions from short-term to long-term plasticity. In this perspective, the use of magnetoionics in neuromorphic applications is critically reviewed, with emphasis on modulating synaptic weight through: 1) control of magnetization by voltage-induced ion retrieval/insertion; and 2) control of magnetic stripe domains and skyrmions in gated magnetic thin films adjacent to solid-state ionic supercapacitors. The potential prospects in this emerging research area together with a forward-looking discussion on future opportunities are provided.
{"title":"Magnetoionics for Synaptic Devices and Neuromorphic Computing: Recent Advances, Challenges, and Future Perspectives","authors":"P. Monalisha, Maria Ameziane, Irena Spasojevic, Eva Pellicer, Rhodri Mansell, Enric Menéndez, Sebastiaan van Dijken, Jordi Sort","doi":"10.1002/smsc.202400133","DOIUrl":"https://doi.org/10.1002/smsc.202400133","url":null,"abstract":"With the advent of Big Data, traditional digital computing is struggling to cope with intricate tasks related to data classification or pattern recognition. To mitigate this limitation, software-based neural networks are implemented, but they are run in conventional computers whose operation principle (with separate memory and data-processing units) is highly inefficient compared to the human brain. Brain-inspired in-memory computing is achieved through a wide variety of methods, for example, artificial synapses, spiking neural networks, or reservoir computing. However, most of these methods use materials (e.g., memristor arrays, spintronics, phase change memories) operated with electric currents, resulting in significant Joule heating effect. Tuning magnetic properties by voltage-driven ion motion (i.e., magnetoionics) has recently emerged as an alternative energy-efficient approach to emulate functionalities of biological synapses: potentiation/depression, multilevel storage, or transitions from short-term to long-term plasticity. In this perspective, the use of magnetoionics in neuromorphic applications is critically reviewed, with emphasis on modulating synaptic weight through: 1) control of magnetization by voltage-induced ion retrieval/insertion; and 2) control of magnetic stripe domains and skyrmions in gated magnetic thin films adjacent to solid-state ionic supercapacitors. The potential prospects in this emerging research area together with a forward-looking discussion on future opportunities are provided.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141547913","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}
Xiao-Dong Zhang, Hui-Juan Yu, Shao-Qi Guan, Yu-Lin Lu, Yu Zhang, Yin-Hui Huang, Ya-Ping Wang, Chen-Hui Liu, Zhong-Min Cao, Yu-Han Qin, Mei Pan, Jun Shen, Cheng-Yong Su
To solve the oxygen dependence problem of photodynamic therapy (PDT), it is critical to explore photosensitizers that do not rely on O2 molecule to generate reactive oxygen species (ROS). Herein, a stable cationic metal-organic cage [Pd6(RuLoz3)8](BF4)28 (MOC-88) that possesses high +28 charges is designed. The cage-confined positive microenvironment enables efficient generation of hydroxyl radicals and improved yield of the singlet oxygen under one-/two-photon excitation, showing excellent performance to concurrently enhance Type-II and O2-independent-Type-I PDT. Moreover, the effective ROS production and robust lipid peroxidation trigger a series of signaling pathways (inflammasome, cyclic guanosine monophosphate–adenosine monophosphate synthase stimulator of interferon genes, and NF-κB) to evoke PANoptosis and ferroptosis in tumor cells, enabling MOC-88 to simultaneously cause the loss of cell membrane integrity, release a series of inflammatory cytokines and damage-associated molecular patterns, stimulate the maturation and antigen presentation ability of dendritic cells, and ultimately activate T-cell-dependent adaptive immunity in vivo to inhibit tumor growth.
为解决光动力疗法（PDT）的氧依赖性问题，探索不依赖氧气分子产生活性氧（ROS）的光敏剂至关重要。本文设计了一种具有高 +28 电荷的稳定阳离子金属有机笼 [Pd6(RuLoz3)8](BF4)28（MOC-88）。笼状封闭的正性微环境能在单/双光子激发下高效产生羟自由基并提高单线态氧的产量，在同时增强 II 型和不依赖于 O2 的 I 型 PDT 方面表现出卓越的性能。此外，有效的 ROS 生成和强大的脂质过氧化还能触发一系列信号通路（炎性体、环磷酸鸟苷-单磷酸腺苷合成酶、干扰素基因刺激器和 NF-κB），从而唤起肿瘤细胞的泛凋亡和铁凋亡、MOC-88 可同时导致细胞膜完整性丧失，释放一系列炎性细胞因子和损伤相关分子模式，刺激树突状细胞的成熟和抗原递呈能力，最终激活体内依赖 T 细胞的适应性免疫，从而抑制肿瘤生长。
{"title":"A Highly Charged Positive Cage Causes Simultaneous Enhancement of Type-II and O2-Independent-Type-I Photodynamic Therapy via One-/Two-Photon Stimulation and Tumor Immunotherapy via PANoptosis and Ferroptosis","authors":"Xiao-Dong Zhang, Hui-Juan Yu, Shao-Qi Guan, Yu-Lin Lu, Yu Zhang, Yin-Hui Huang, Ya-Ping Wang, Chen-Hui Liu, Zhong-Min Cao, Yu-Han Qin, Mei Pan, Jun Shen, Cheng-Yong Su","doi":"10.1002/smsc.202400220","DOIUrl":"https://doi.org/10.1002/smsc.202400220","url":null,"abstract":"To solve the oxygen dependence problem of photodynamic therapy (PDT), it is critical to explore photosensitizers that do not rely on O<sub>2</sub> molecule to generate reactive oxygen species (ROS). Herein, a stable cationic metal-organic cage [Pd<sub>6</sub>(RuL<sup>oz</sup><sub>3</sub>)<sub>8</sub>](BF<sub>4</sub>)<sub>28</sub> (MOC-88) that possesses high +28 charges is designed. The cage-confined positive microenvironment enables efficient generation of hydroxyl radicals and improved yield of the singlet oxygen under one-/two-photon excitation, showing excellent performance to concurrently enhance Type-II and O<sub>2</sub>-independent-Type-I PDT. Moreover, the effective ROS production and robust lipid peroxidation trigger a series of signaling pathways (inflammasome, cyclic guanosine monophosphate–adenosine monophosphate synthase stimulator of interferon genes, and NF-κB) to evoke PANoptosis and ferroptosis in tumor cells, enabling MOC-88 to simultaneously cause the loss of cell membrane integrity, release a series of inflammatory cytokines and damage-associated molecular patterns, stimulate the maturation and antigen presentation ability of dendritic cells, and ultimately activate T-cell-dependent adaptive immunity in vivo to inhibit tumor growth.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141547912","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}
Polar liquid crystals possess 3D orientational order coupled with unidirectional electric polarity, yielding fluid ferroelectrics. Such polar phases are generated by rod-like molecules with large electric dipole moments. 2,5-Disubstituted 1,3-dioxane is commonly employed as a polar motif in said systems, and herein it is shown to suffer from thermal instability as a consequence of equatorial-trans to axial-trans isomerism at elevated temperatures. Isosteric building blocks are utilized as potential replacements for the 1,3-dioxane unit, and in doing so new examples of fluid ferroelectric systems are obtained. For binary mixtures of certain composition, the emergence of a new fluid antiferroelectric phase, a finding not observed for either of the parent molecules, is observed. This study also reveals a critical tipping point for the emergence of polar order in otherwise apolar systems. These results hint at the possibility for uncovering new highly ordered polar liquid-crystalline phases and delineate distinct transition mechanisms in orientational and polar ordering.
{"title":"Emergent Antiferroelectric Ordering and the Coupling of Liquid Crystalline and Polar Order","authors":"Jordan Hobbs, Calum J. Gibb, Richard J. Mandle","doi":"10.1002/smsc.202400189","DOIUrl":"https://doi.org/10.1002/smsc.202400189","url":null,"abstract":"Polar liquid crystals possess 3D orientational order coupled with unidirectional electric polarity, yielding fluid ferroelectrics. Such polar phases are generated by rod-like molecules with large electric dipole moments. 2,5-Disubstituted 1,3-dioxane is commonly employed as a polar motif in said systems, and herein it is shown to suffer from thermal instability as a consequence of equatorial-trans to axial-trans isomerism at elevated temperatures. Isosteric building blocks are utilized as potential replacements for the 1,3-dioxane unit, and in doing so new examples of fluid ferroelectric systems are obtained. For binary mixtures of certain composition, the emergence of a new fluid antiferroelectric phase, a finding not observed for either of the parent molecules, is observed. This study also reveals a critical tipping point for the emergence of polar order in otherwise apolar systems. These results hint at the possibility for uncovering new highly ordered polar liquid-crystalline phases and delineate distinct transition mechanisms in orientational and polar ordering.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141547988","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}
Disuse osteoporosis (OP) is a state of bone loss due to lack of mechanical stimuli, probably induced by prolonged bed rest, neurological diseases, as well as microgravity. Currently the precise treatment strategies of disuse OP remain largely unexplored. Piezo1, a mechanosensitive calcium (Ca2+) ion channel, is a key force sensor mediating mechanotransduction and it is demonstrated to regulate bone homeostasis and osteogenesis in response to mechanical forces. Using structure-based drug design, a novel small-molecule Piezo1 agonist, MCB-22-174, which can effectively activate Piezo1 and initiate Ca2+ influx, is developed and is more potent than the canonical Piezo1 agonist, Yoda1. Moreover, MCB-22-174 is found as a safe Piezo1 agonist without any signs of serious toxicity. Mechanistically, Piezo1 activation promotes the proliferation of bone marrow mesenchymal stem cells by activating the Ca2+-related extracellular signal-related kinases and calcium–calmodulin (CaM)-dependent protein kinase II (CaMKII) pathway. Importantly, MCB-22-174 could effectively promote osteogenesis and attenuate disuse OP in vivo. Overall, the findings provide a promising therapeutic strategy for disuse OP by chemical activation of Piezo1.
{"title":"A Novel Piezo1 Agonist Promoting Mesenchymal Stem Cell Proliferation and Osteogenesis to Attenuate Disuse Osteoporosis","authors":"Ruihan Hao, Hairong Tang, Chunyong Ding, Bhavana Rajbanshi, Yuhang Liu, Ding Ma, Zhouyi Duan, Yuxin Qi, Liming Dai, Bingjun Zhang, Ao Zhang, Xiaoling Zhang","doi":"10.1002/smsc.202400061","DOIUrl":"https://doi.org/10.1002/smsc.202400061","url":null,"abstract":"Disuse osteoporosis (OP) is a state of bone loss due to lack of mechanical stimuli, probably induced by prolonged bed rest, neurological diseases, as well as microgravity. Currently the precise treatment strategies of disuse OP remain largely unexplored. Piezo1, a mechanosensitive calcium (Ca<sup>2+</sup>) ion channel, is a key force sensor mediating mechanotransduction and it is demonstrated to regulate bone homeostasis and osteogenesis in response to mechanical forces. Using structure-based drug design, a novel small-molecule Piezo1 agonist, MCB-22-174, which can effectively activate Piezo1 and initiate Ca<sup>2+</sup> influx, is developed and is more potent than the canonical Piezo1 agonist, Yoda1. Moreover, MCB-22-174 is found as a safe Piezo1 agonist without any signs of serious toxicity. Mechanistically, Piezo1 activation promotes the proliferation of bone marrow mesenchymal stem cells by activating the Ca<sup>2+</sup>-related extracellular signal-related kinases and calcium–calmodulin (CaM)-dependent protein kinase II (CaMKII) pathway. Importantly, MCB-22-174 could effectively promote osteogenesis and attenuate disuse OP in vivo. Overall, the findings provide a promising therapeutic strategy for disuse OP by chemical activation of Piezo1.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141527483","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}
Tactile sensing plays a vital role in human somatosensory perception as it provides essential touch information necessary for interacting with the environment and accomplishing daily tasks. The progress in textile electronics has opened up opportunities for developing intelligent wearable devices that enable somatosensory perception and interaction. Herein, a skin-inspired all-textile pressure sensor (ATP) is presented that emulates the sensing and interaction functions of human skin, offering wearability, comfort, and breathability. The ATP demonstrates impressive features, including ultrahigh sensitivity (1.46 × 106 kPa−1), fast response time (1 ms), excellent stability and durability (over 2000 compression-release cycles), a low detection limit of 10 Pa, and remarkable breathability (93.2%). The multipixel array of ATPs has been proven to facilitate static and dynamic mapping of spatial pressure, as well as pressure trajectory monitoring functions. Moreover, by integrating ATP with oscillation circuits, external force stimuli can be directly encoded into digital frequency pulses that resemble human physiological signals. The frequency of output pulses increases with the applied pressure. Consequently, an ATP-based artificial sensory system is constructed for intelligent tactile perception. This work provides a simple and versatile strategy for practical applications of wearable electronics in the fields of robotics, sports science, and human–machine interfaces technologies.
触觉传感在人类体感知觉中发挥着至关重要的作用，因为它提供了与环境互动和完成日常任务所必需的基本触觉信息。纺织电子技术的进步为开发可实现体感感知和互动的智能可穿戴设备带来了机遇。本文介绍了一种受皮肤启发的全纺织压力传感器（ATP），它能模拟人体皮肤的传感和交互功能，具有可穿戴性、舒适性和透气性。ATP 具有令人印象深刻的特点，包括超高灵敏度（1.46 × 106 kPa-1）、快速响应时间（1 毫秒）、出色的稳定性和耐用性（超过 2000 次压缩-释放循环）、10 Pa 的低检测限以及出色的透气性（93.2%）。事实证明，多像素 ATP 阵列有助于空间压力的静态和动态映射，以及压力轨迹监测功能。此外，通过将 ATP 与振荡电路集成，可将外力刺激直接编码为类似人体生理信号的数字频率脉冲。输出脉冲的频率随施加压力的增加而增加。因此，我们构建了一个基于 ATP 的人工感觉系统，用于智能触觉感知。这项工作为可穿戴电子设备在机器人学、运动科学和人机界面技术领域的实际应用提供了一种简单而通用的策略。
{"title":"Body-Integrated Ultrasensitive All-Textile Pressure Sensors for Skin-Inspired Artificial Sensory Systems","authors":"Bingjun Wang, Yuanhong Shi, Haotian Li, Qilin Hua, Keyu Ji, Zilong Dong, Zhaowei Cui, Tianci Huang, Zhongming Chen, Ruilai Wei, Weiguo Hu, Guozhen Shen","doi":"10.1002/smsc.202400026","DOIUrl":"https://doi.org/10.1002/smsc.202400026","url":null,"abstract":"Tactile sensing plays a vital role in human somatosensory perception as it provides essential touch information necessary for interacting with the environment and accomplishing daily tasks. The progress in textile electronics has opened up opportunities for developing intelligent wearable devices that enable somatosensory perception and interaction. Herein, a skin-inspired all-textile pressure sensor (ATP) is presented that emulates the sensing and interaction functions of human skin, offering wearability, comfort, and breathability. The ATP demonstrates impressive features, including ultrahigh sensitivity (1.46 × 10<sup>6</sup> kPa<sup>−1</sup>), fast response time (1 ms), excellent stability and durability (over 2000 compression-release cycles), a low detection limit of 10 Pa, and remarkable breathability (93.2%). The multipixel array of ATPs has been proven to facilitate static and dynamic mapping of spatial pressure, as well as pressure trajectory monitoring functions. Moreover, by integrating ATP with oscillation circuits, external force stimuli can be directly encoded into digital frequency pulses that resemble human physiological signals. The frequency of output pulses increases with the applied pressure. Consequently, an ATP-based artificial sensory system is constructed for intelligent tactile perception. This work provides a simple and versatile strategy for practical applications of wearable electronics in the fields of robotics, sports science, and human–machine interfaces technologies.","PeriodicalId":29791,"journal":{"name":"Small Science","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141527482","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}
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