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Albubody: an engineered scFv variant platform for site-specific drug conjugation and enhanced tumor efficacy
No full textAntibody-drug conjugates (ADCs) represent a promising approach for targeted cancer therapy. Although single-chain variable fragments (scFvs) hold potential as drug carriers, their application in ADCs has been limited. This study introduces Albubody, an engineered scFv fused with an albumin-binding domain (ABD), as a potential ADC scaffold designed to interact with serum albumin in vivo. The human epidermal growth factor receptor 2 (HER2)-targeting Albubody, derived from trastuzumab, is constructed, followed by computational analysis to identify optimal conjugation sites for the cytotoxic drug monomethyl auristatin E (MMAE). The incorporation of the non-natural amino acid p-azido-phenylalanine (pAzF) enables site-specific conjugation using strain-promoted azide-alkyne cycloaddition (SPAAC) chemistry, resulting in the formation of the Albubody-drug conjugate (4D5Albu-MMAE). 4D5Albu-MMAE retained HER2 binding affinity, indicating that site-specific conjugation did not compromise antigen recognition. HER2-specific in vitro cytotoxicity, cellular internalization, and efficient spheroid penetration were also confirmed. Compared to the conventional scFv-drug conjugate (4D5scFv-MMAE), 4D5Albu-MMAE exhibited prolonged systemic exposure and superior antitumor efficacy in HER2-positive xenograft models. This study highlights the potential of Albubody as an effective ADC platform and emphasizes the importance of site-specific conjugation in optimizing therapeutic outcomes for cancer treatment. © 2025 Elsevier B.V., All rights reserved.FALSEsciescopu
A complex hydride-based electrolyte additive for rechargeable Li−S batteries
No full textLithium−sulfur (Li−S) batteries are considered promising next-generation energy storage systems due to their high energy density, low-cost S cathodes, and potential for sustainable large-scale applications. However, they face significant challenges, including the lithium polysulfides (LiPS) shuttle effect associated with the S cathodes and interfacial reactions at the Li metal anodes, which occur concurrently and hinder their stable operation. To address these simultaneous issues at both the cathode and anode, we propose the use of complex hydrides as an electrolyte additive. Closo-type complex hydride Li(CB11H12) dissociates in the electrolyte to form mobile lithium cations and rigid polyanionic complex anions [CB11H12]−, which form Li+−solvent coordination by its weak coordinating ability. The weakened solvation free energy and the reducing ability of this modified electrolyte suppress LiPS dissolution at the S cathode as well as facilitates stable lithium anode reaction, enhancing the cycling stability and coulombic efficiency of Li−S batteries. The findings of this study underscore the importance of designing electrolyte structures using various complex hydrides and highlight their potential to address the limitations of Li−S batteries, paving the way for future advancements in this field. © 2025 Elsevier B.V., All rights reserved.TRUEscopu
Understanding the degradation mechanisms of Ba-based double perovskite electrodes for solid oxide electrochemical cells
No full textTo shed light on the degradation mechanisms, this study investigated the electrochemical characteristics and phase stability of PrBaFe2O5+ω (PBF) a representative double perovskite material, under atmospheric conditions. A ceramic manufacturing process was applied to fabricate dense bulk electrode for analyzing the surface exchange reaction comprehensively. Furthermore, a defect concentration analysis was performed, which offered insights into the double perovskite material properties and affirmed the accuracy of the analysis system by comparing the surface exchange coefficients utilizing the fabricated dense bulk electrode. When surface exchange reactions were measured in an atmosphere containing CO2 and moisture, significant degradation was observed. Our findings indicated that the deterioration in surface exchange reactions of the double perovskite electrode was primarily due to the hydroxide formation in the atmosphere, leading to phase decomposition. © 2025 Elsevier B.V.FALSEsciescopu
In Vitro Homotypic ER Membrane Fusion Assay Using Isolated Yeast Microsomes
No full textCell-free in vitro assays offer several advantages for elucidating molecular mechanisms underlying various biological processes. Here, we describe a simple and quantitative in vitro assay using isolated yeast microsomes to measure homotypic ER membrane fusion. In this assay, membrane fusion between ER microsomes is monitored by reconstitution of luciferase activity from split luciferase fragments. Our findings reveal that homotypic ER membrane fusion requires not only Sey1p, the yeast atlstin, but also ER-resident SNAREs, such as Sec22p and Sec20p, in Saccharomyces cerevisiae. © 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.FALSEscopu
An integrated transcriptomic approach for identifying enhancers in limb motor pools
No full textMotor neurons (MNs), which control body movement, consist of distinct motor pools, that target specific muscles. The precise delineation of these motor pools necessitates an understanding of their specialized gene expression profiles. By integrating single-cell transcriptomics and epigenomics, using scATAC-seq, scRNA-seq and histone modification datasets, we identified cis-regulatory elements (CREs) specific to five MN-lineage clusters, which exhibit distinct gene ontology terms, transcription factor (TF) binding motifs, and disease-associated traits across them. Notably, LIM-homeodomain (LIM-HD) TF motifs and their footprints were differentially enriched in corresponding individual motor column CREs, including a combined Isl1 and Lhx3 motif consistent with their known role in MN identity specification. Within the genomic locus of Etv4, a gene essential for limb motor pools, we identified three enhancer candidates among CREs enriched in LMC neurons. Functional assays demonstrated that these enhancers exhibited robust and specific activity in ETV4-expressing motor pools when electroporated into chicken neural tubes. This study demonstrates that an integrated in silico analysis of epigenetic and transcriptomic data at the single-cell level can predict putative CREs governing the identity of distinct MN subgroups, providing insights into motor pool diversification and gene regulation.TRUEsciescopu
Scale-Free and Phase-Agnostic Detection of Interturn Short-Circuit Faults in Permanent Magnet Synchronous Motors
No full textThis study presents a scale-free and phase-agnostic method for detecting interturn short-circuit faults (ISCFs) in the stator windings of permanent magnet synchronous motors (PMSMs). The proposed method integrates denoising and feature extraction with a crest-factor-based health indicator. A wavelet-based denoising method with average peak extraction is devised to enhance the sensitivity to fault-induced current deviations while suppressing external noise. The crest factor is modified to enable phase-agnostic detection across stator windings. To eliminate scale dependency associated with motor capacity, the modified crest factor is further calibrated using baseline data obtained under healthy conditions. The resulting health indicator, namely max-min crest factor, enables consistent and reliable ISCF detection without requiring motor-specific parameters or prior knowledge of the faulty phase. The effectiveness of the proposed method is validated through multiple case studies, including 1) numerical simulations, 2) laboratory-scale testbed experiments on small-capacity PMSMs (100 W and 1 kW), and 3) full-scale testing on an 82.5 kW PMSM under realistic operating conditions. The experimental results demonstrate that the method reliably detects ISCFs regardless of fault location or motor scale.TRUEsciescopu
Characterization of charge state distributions in Near-Infrared Laser-Driven tin plasmas for efficient EUV generation
No full textIn this paper, the charge state distributions of extreme ultraviolet (EUV) light source plasmas produced by near-infrared-wavelength lasers are systematically characterized. The spatiotemporal properties of laser-irradiated planar tin targets are examined using radiation-hydrodynamic simulations and non-local thermodynamic equilibrium calculations. Focusing on the distributions of Sn11+–Sn14+ ions, which are primarily responsible for “in-band” EUV emissions, a mean charge state of 12.5 is identified as the optimal ionization level for efficient EUV generation. This prediction is consistent with the experimental observation by Behnke et al. (2021) of short-wavelength spectra in the 7–10 nm range, where the contributions of the Sn11+–Sn14+ ions are well identified. Simulations further reveal that spatially and temporally uniform pulses more efficiently achieve the optimal mean charge state, producing up to 45 % more Sn11+–Sn14+ ions than Gaussian pulses of the same energy. These findings provide foundational insights for advancing laser-driven EUV light sources for industrial applications. © 2025 Elsevier B.V., All rights reserved.TRUEsciescopu
Development of a Robotic Navigation Scheme for Magnetic Nanoparticles
No full textThe future paradigm for targeted drug delivery lies in minimally invasive surgery. In this context, mobile micro/nanorobots hold great promise for targeted medical applications due to their advantages in accessing deep tissue regions and offering precise controllability. These micro/nanorobots are primarily powered by external sources such as optical, magnetic, acoustic, and electronic fields. Among these, magnetic fields stand out as the most prominent power source due to their safety and deep tissue penetration capabilities. Specifically, two types of magnetic actuation are employed: force-based and torque-based.
Both methods face common challenges, including the absence of training tools and real-time imaging modalities. The lack of a dedicated training platform presents a significant hurdle in transferring targeted drug delivery systems from engineers to medical practitioners. Furthermore, real-time imaging for micro/nanorobots requires at least micrometer-level spatial resolution to detect the micro/nanoscale and frame rates of tens per second to track their motion within blood vessels. Despite significant advancements in imaging modalities such as ultrasound, magnetic resonance imaging (MRI), photoacoustic imaging, fluorescence imaging, and magnetic particle imaging, achieving both spatial and temporal resolution remains a challenge.
In force-based actuation, the propulsion velocity of micro/nanorobots is negligible compared to blood flow, making it difficult to achieve meaningful locomotion within blood vessels. Torque-based actuation, on the other hand, often relies on rolling close to boundaries to generate locomotion. While the mechanisms of two-dimensional locomotion have been extensively studied in various environments, such as uneven surfaces and confined regions, three-dimensional locomotion of rolling micro/nanorobots has yet to be demonstrated. This limitation represents a major bottleneck in the practical application of micro/nanorobots. In this dissertation, we address these challenges by: 1) introducing a virtual reality platform, 2) developing an offline programming guidance scheme, 3) investigating the aggregation phenomena and effects, 4) proposing an aggregation model-based offline programming guidance scheme, and 5) analyzing inclined locomotion and swarm strategies.
To address the absence of training tools, we propose a virtual reality platform for magnetic targeting delivery. Training tools are widely utilized in biomedical engineering. For instance, in minimally invasive surgical devices such as the Da Vinci Robot, virtual reality platforms have been extensively adopted. These tools not only provide an immersive, three-dimensional experience that replicates real surgical settings but also significantly reduce surgical failures and side effects. Inspired by the Da Vinci Robot, we developed a virtual reality platform using a realistic blood vessel model, mathematically modeled magnetic forces, and computational fluid dynamics (CFD) simulations. Additionally, we integrated a haptic feedback algorithm to enhance and accelerate user training and manipulation efficiency. The effectiveness of this haptic feedback algorithm was evaluated through user studies, confirming that our self-developed virtual platform is well-suited for training users.
Second, to address the lack of real-time imaging modalities, we propose an alternative solution: an offline programming guidance scheme. Offline programming involves generating robot programs in computer software using 3D CAD data. Once the program is created and verified in the software, it is downloaded to the physical robot. For example, in welding applications, the CAD file of a welding cell is imported into offline programming software, where the desired torch path is planned. After completion, the trajectory is downloaded to the robot controller in the physical world. Inspired by this concept, we developed an offline programming guidance scheme for micro/nanorobots, leveraging its ability to operate without the need for real-time imaging modalities.
To ensure the software closely aligns with physical conditions, we calibrated our self-developed simulator against real-world parameters, including magnetic fields, fluidic flow, particle properties, and vessel geometry. In this system, users control micro/nanorobots within the simulator, and their commands are subsequently implemented in the physical environment. We demonstrated that this system operates effectively in a two-dimensional environment, providing a robust solution to the imaging challenges in micro/nanorobot applications.
Third, we investigate the aggregation phenomena during magnetic drug targeting. While some researchers have reported aggregation between micro/nanorobots in static environments, the use of micro/nanorobots is predominantly focused on dynamic environments such as blood flow. In these dynamic conditions, aggregation behavior changes significantly and has a profound impact on targeting efficiency. In this study, we examined the mechanisms governing interactions between micro/nanorobots in dynamic environments and identified the key influencing parameters.
Additionally, we developed a simulation platform to evaluate these control parameters. Using this platform, we assessed both targeting efficiency and the degree of aggregation under specific conditions. Targeting efficiency is crucial for maximizing drug delivery effectiveness. On the other hand, the degree of aggregation must be carefully modulated; excessive aggregation can obstruct blood vessels, making precise control critical. This platform provides a means to determine optimal control parameters that ensure high targeting efficiency while maintaining an appropriate degree of aggregation, serving as a valuable tool prior to conducting in-vivo experiments.
Fourth, we developed an aggregation model-based offline programming system. This model estimates the degree of aggregation during magnetic drug targeting, enabling precise calibration of the offline programming software with real-world conditions. By integrating the aggregation model, we observed significant improvements in targeting performance. Furthermore, we demonstrated the proposed concept using a three-dimensional rat brain vascular model with blood. Our system operated effectively in this complex environment, showcasing its strong potential for practical applications in targeted drug delivery.
Fifth, we investigated the three-dimensional locomotion mechanisms of microrollers and proposed swarm strategies to enhance their performance. We evaluated two different sizes of microrollers on inclined surfaces. Interestingly, the inclined motion was influenced not only by gravitational effects but also by hydrodynamic wall interactions. Our observations revealed that the texture of inclined surfaces significantly impacts locomotion. Specifically, on even surfaces, the size of the microroller does not affect inclined performance. However, on uneven surfaces, larger microrollers demonstrate superior locomotion capabilities. Despite these locomotion improvement, certain cases revealed limitations where individual microrollers failed to climb inclined walls.
To address these challenges, we proposed swarm strategies and demonstrated that these strategies significantly enhance inclined locomotion. This finding highlights the potential of microrollers swarm to overcome limitations in three-dimensional environments.|미래 지향적 약물 전달 패러다임은 최소 침습 수술에 있습니다. 이 맥락에서 이동식 마이크로/나노로봇은 깊은 조직 영역에 접근하고 정확하게 제어할 수 있는 장점을 바탕으로 표적 의료 응용에서 큰 잠재력을 가지고 있습니다. 이러한 마이크로/나노로봇은 주로 광학, 자기장, 음향, 전자기장과 같은 외부 에너지원으로 구동됩니다. 이 중 자기장은 안전성과 깊은 조직 침투 능력으로 가장 두드러지는 에너지원입니다. 자기장을 이용한 구동 방식은 크게 힘 기반과 토크 기반의 두 가지로 나뉩니다.
두 방법 모두 공통적인 문제점에 직면하고 있습니다. 첫째, 훈련 도구의 부재는 표적 약물 전달 시스템이 엔지니어에서 의학 실무자로 이전되는 과정에서 큰 장벽으로 작용합니다. 둘째, 실시간 이미징 기술의 부재는 마이크로/나노로봇을 혈관 내에서 추적하기 위해서는 최소 마이크로미터 수준의 공간 해상도와 초당 수십 프레임의 시간 해상도가 필요합니다. 초음파, 자기공명영상(MRI), 광음향 영상, 형광 영상, 자기 입자 영상과 같은 다양한 이미징 기술이 발전했지만, 이러한 공간적 및 시간적 해상도를 동시에 달성하는 것은 여전히 도전 과제로 남아 있습니다.
힘 기반 구동의 경우, 마이크로/나노로봇의 추진 속도가 혈류에 비해 미미하여 혈관 내에서 의미 있는 이동을 달성하기 어렵습니다. 반면, 토크 기반 구동은 주로 경계면을 따라 구르는 방식을 통해 이동을 생성합니다. 다양한 환경에서 2차원 이동 메커니즘은 광범위하게 연구되었지만, 마이크로/나노로봇의 3차원 이동은 아직 입증되지 않았습니다. 이 한계는 마이크로/나노로봇의 실질적인 응용을 가로막는 주요 병목 현상입니다.
본 논문에서는 이러한 문제를 해결하기 위해 다음과 같은 연구를 수행했습니다:
가상 현실 플랫폼 도입,
오프라인 프로그래밍 가이던스 스킴 개발,
응집 현상 및 그 효과 연구,
응집 모델 기반 오프라인 프로그래밍 가이던스 스킴 제안,
경사 이동 분석 및 스웜 전략 제안.
1. 가상 현실 플랫폼 도입
훈련 도구 부재 문제를 해결하기 위해, 자기장 기반 약물 전달을 위한 가상 현실(VR) 플랫폼을 제안했습니다. 훈련 도구는 의공학 분야에서 널리 사용되고 있으며, 대표적으로 다빈치 로봇 시스템은 VR 플랫폼을 활용해 최소 침습 수술을 위한 훈련 환경을 제공합니다. 이러한 플랫폼은 실제 수술 환경을 3차원으로 몰입감 있게 재현하여 실패율과 부작용을 크게 줄이는 데 기여합니다.
이와 같은 접근법에서 영감을 받아, 우리는 현실적인 혈관 모델, 자기장 수학적 모델링, 전산유체역학(CFD) 시뮬레이션을 통합한 가상 현실 플랫폼을 개발했습니다. 또한 햅틱 피드백 알고리즘을 추가해 사용자 훈련 효율성과 조작 정확도를 높였습니다. 사용자 연구를 통해 이 플랫폼의 효과를 검증했으며, 이를 통해 개발된 VR 플랫폼이 훈련 도구로서 적합함을 확인했습니다.
2. 오프라인 프로그래밍 가이던스 스킴
실시간 이미징 기술의 부재 문제를 해결하기 위해 오프라인 프로그래밍 가이던스 스킴을 제안했습니다. 오프라인 프로그래밍은 3D CAD 데이터를 기반으로 컴퓨터 소프트웨어에서 로봇 프로그램을 생성 및 검증한 후, 물리적 로봇에 적용하는 방식입니다. 예를 들어, 용접 응용에서는 용접 셀의 CAD 파일을 소프트웨어에 가져와 용접 경로를 계획하고 이를 물리적 로봇에 적용합니다.
이 개념에서 착안해, 우리는 마이크로/나노로봇을 위한 오프라인 프로그래밍 가이던스 스킴을 개발했습니다. 정확한 제어를 위해 자기장, 유체 흐름, 입자 특성, 혈관 기하학과 같은 물리적 조건을 기반으로 시뮬레이터를 보정했습니다. 사용자는 시뮬레이터 내에서 마이크로/나노로봇을 제어하고, 이 명령은 물리적 환경에 구현됩니다. 본 시스템은 2차원 환경에서 효과적으로 작동하며, 실시간 이미징의 대안으로서 강력한 솔루션을 제공합니다.
3. 자기장 기반 응집 현상 연구
마그네틱 약물 전달 중 발생하는 응집 현상을 연구했습니다. 기존 연구는 정적 환경에서의 응집 현상에 초점을 맞추었지만, 마이크로/나노로봇은 주로 동적 환경(예: 혈류)에서 사용됩니다. 이러한 동적 조건에서는 응집 행동이 크게 달라지며, 표적 효율성에 중요한 영향을 미칩니다.
우리는 동적 환경에서 마이크로/나노로봇 간 상호작용을 연구하고 영향을 미치는 핵심 변수를 규명했습니다. 또한 제어 매개변수를 평가할 수 있는 시뮬레이션 플랫폼을 개발해, 표적 효율성과 응집 정도를 최적화했습니다. 과도한 응집은 혈관 폐색을 유발할 수 있으므로, 이를 정밀하게 제어하는 것이 중요합니다.
4. 응집 모델 기반 오프라인 프로그래밍 시스템
응집 모델을 기반으로 한 오프라인 프로그래밍 시스템을 개발했습니다. 이 모델은 자기장 기반 약물 전달 중 발생하는 응집 정도를 예측하며, 오프라인 프로그래밍 소프트웨어를 물리적 환경에 정밀하게 맞출 수 있도록 지원합니다.
쥐의 뇌 혈관 모델을 사용해 제안된 개념을 검증했으며, 복잡한 3차원 환경에서 시스템이 효과적으로 작동함을 입증했습니다. 이를 통해 마이크로/나노로봇의 약물 전달 성능이 크게 개선되었습니다.
5. 경사 이동 메커니즘 및 스웜 전략
3차원 환경에서의 이동 메커니즘을 연구하고 이를 개선하기 위해 스웜 전략을 제안했습니다. 우리는 서로 다른 크기의 마이크로롤러를 경사면에서 평가했으며, 이동 성능이 중력 효과와 유체역학적 벽 상호작용에 의해 크게 영향을 받는다는 것을 확인했습니다. 특히, 경사면의 표면 질감이 이동에 중요한 역할을 했습니다.
평평한 표면에서는 마이크로롤러의 크기가 성능에 미치는 영향이 적었으나, 울퉁불퉁한 표면에서는 더 큰 마이크로롤러가 우수한 이동 성능을 보였습니다. 그러나 일부 상황에서는 단일 마이크로롤러가 경사면을 오르는 데 실패하는 한계가 있었습니다. 이를 극복하기 위해 스웜 전략을 도입했으며, 이 전략을 통해 경사 이동 성능이 크게 개선됨을 입증했습니다.Docto
Role of hot phonons and layer geometry in spintronic terahertz emission
No full textWe compare terahertz (THz) emission from bilayer and trilayer spintronic structures optimized for femtosecond laser excitation. The trilayer shows approximately twice the THz amplitude of the bilayer, owing to constructive spin-to-charge conversion at both interfaces. However, saturation behavior emerges in the trilayer due to hot phonon effects. Time-domain analysis of the extracted charge currents reveals distinct ultrafast spin transport dynamics. These results highlight the role of multilayer design and phonon interactions in enhancing the performance of spintronic THz emitters.TRUEsciescopu
Programable Prodrug Nanomodulator Targets Tumor Redox Homeostasis Imbalance to Amplify Disulfidptosis and Immunogenic Pyroptosis for Breast Tumor Immunotherapy
No full textDespite the great potential of photodynamic therapy (PDT), its success remains compromised by the abnormal redox homeostasis of tumor cells, which supports survival, growth, and resistance to oxidative therapeutic interventions by neutralizing reactive oxygen species (ROS). To overcome this barrier, a multifunctional prodrug nanomodulator (Pro@FLNC) is designed to induce disulfidptosis and immunogenic pyroptosis to trigger an antitumor immune response. Pro@FLNC features a prodrug core–shell structure where ursolic acid (UA) and Chlorin e6 (Ce6) are conjugated via a GSH-responsive linker and encapsulated in a DSPE-PEG-FA lipid shell for enhanced stability, biocompatibility, and tumor-specific targeting. Within the tumor microenvironment (TME), Pro@FLNC depletes intracellular GSH, disrupts redox homeostasis, and releases Ce6 and UA, triggering oxidative stress and mitochondrial dysfunction. These mechanisms amplify ROS production, promote lipid peroxidation, and initiate disulfidptosis, evidenced by increased SLC7A11 expression and F-actin collapse. Elevated ROS levels and metabolic imbalance-triggered disulfidptosis further activate immunogenic pyroptosis, releasing damage-associated molecular patterns (DAMPs) that stimulate dendritic cell maturation and cytotoxic T-cell activation. Together, Pro@FLNC reshapes the TME, reduces immunosuppressive cells, and promotes CD8+ T-cell infiltration, effectively suppressing primary tumors and metastases. This programmed prodrug nanomodulator offers a promising strategy to enhance PDT and immunotherapy for advanced breast cancer. © 2025 Wiley-VCH GmbH.FALSEsciescopu