Publications by authors named "ZhongZe Gu"

The regular workshops held by the Center for Alternatives to Animal Testing (CAAT) on biology-inspired microphysiological systems (MPS) taking place every four years, have become a reliable measure to assess fundamental scientific, industrial and regulatory trends for translational science in the MPS-field from a bird's eye view. The 2023 workshop participants at that time concluded that the technology as used within academia has matured significantly, underlined by the broad use of MPS and the steadily increasing number of high quality research publications - yet, broad industry adoption of MPS has been slow, despite strong interest. Academic research using MPS primarily aims to accurately recapitulate human biology in MPS-based organ models in areas where traditional models have been lacking key elements of human physiology, thereby enabling breakthrough discoveries for life sciences.

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Article Synopsis
  • Two-photon lithography (TPL) allows for the creation of highly detailed 3D structures with precision at the sub-micrometer level, but integrating new functionalities into these structures presents challenges with existing methods.
  • A novel "post-doping" approach is introduced, which involves infusing functional materials into the porous structures after they are printed, alleviating issues like material compatibility and nanoparticle agglomeration associated with traditional pre-doping techniques.
  • The study demonstrates this method by successfully impregnating various functional liquids into TPL-printed microstructures, showcasing the potential for versatile applications in fields such as bionics, electronics, and cell biology due to the customizable and localized properties achieved.
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Extracellular vesicles (EVs) offer promising noninvasive alternatives for convenient and noninvasive prostate cancer (PCa) diagnosis, but inefficient EV enrichment and cargo extraction hinder discovery and validation for their clinical applications. Here, we present an integrated pipeline based on functionalized magnetic beads to streamline and enhance the efficiency of urinary EV miRNA analysis. EVs are first enriched on amphiphilic magnetic beads through chemical affinity, followed by EV lysis and the isolation of miRNAs through solid phase extraction.

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Three-dimensional (3D) organotypic skin in vitro has attracted increasing attention for drug development, cosmetics evaluation, and even clinical applications. However, the severe contraction of these models restricts their application, especially in the analyses based on barrier functions such as percutaneous penetration. For the full-thickness skin equivalents, the mechanical properties of the dermis scaffold plays an important role in the contraction resistance.

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Exploring spatiotemporal patterns of high-dimensional electroencephalography (EEG) time series generated from complex brain system is crucial for deciphering aging and cognitive functioning. Analyzing high-dimensional EEG series poses challenges, particularly when employing distance-based methods for spatiotemporal dynamics. Therefore, we proposed an innovative methodology for multi-channel EEG data, termed as Spatiotemporal Information-based Similarity (STIBS) analysis.

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Exposure to micro- and nanoplastics (MNPs) has been implicated in potential cardiotoxicity. However, in vitro models based on cardiomyocyte cell lines lack crucial cardiac characteristics, while interspecies differences in animal models compromise the reliability of the conclusions. In addition, current research has predominantly focused on single-time point exposures to MNPs, neglecting comparative analyses of cardiac injury across early and late stages.

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Biological evaluation of biomedical materials faces constraints imposed by the limitations of traditional in vitro and animal experiments. Currently, miniaturized and biomimetic microfluidic technologies and organ-on-chip systems have garnered widespread attention in the field of drug development. However, their exploration in the context of biomedical material evaluation and medical device development remains relatively limited.

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Primary liver cancer (PLC) is a primary cause of cancer-related death worldwide, and novel treatments are needed due to the limited options available for treatment and tumor heterogeneity. 66 surgically removed PLC samples were cultured using the self-developed 2:2 method, and the final success rate for organoid culture was 40.9%.

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The advancement of electronic devices necessitates the development of three-dimensional (3D) high-precision conductive microstructures, which have extensive applications in bio-electronic interfaces, soft robots, and electronic skins. Two-photon polymerization (TPP) based 3D printing is a critical technique that offers unparalleled fabrication resolution in 3D space for intricate conductive structures. While substantial progress has been made in this field, this review summarizes recent advances in the 3D printing of conductive microstructures via TPP, mainly focusing on the essential criteria of photoresist resins suitable for TPP.

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Cellular forces play a crucial role in numerous biological processes, including tissue development, morphogenesis, and disease progression. However, existing methods for detecting cellular forces, such as traction force microscopy and atomic force microscopy, often face limitations in terms of high throughput, real-time monitoring, and applicability to complex biological systems. In this study, we utilized a novel Photonic Crystal Cellular Force Microscopy (PCCFM) system to visualize and quantify dynamic cellular forces.

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Brain organoids are widely used to model brain development and diseases. However, a major challenge in their application is the insufficient supply of oxygen and nutrients to the core region, restricting the size and maturation of the organoids. In order to vascularize brain organoids and enhance the nutritional supply to their core areas, two-photon polymerization (TPP) 3D printing is employed to fabricate high-resolution meshed vessels in this study.

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Increasing efforts have been made to develop proteins in circulating extracellular vesicles (EVs) as potential disease markers. It is in particular intriguing to measure post-translational modifications (PTMs) such as phosphorylation, preserved and stable in EVs. To facilitate the quantitative measurement of EV protein phosphorylation for potential clinical use, a label-free (LF) multiple reaction monitoring (MRM) strategy is introduced by utilizing a synthetic phosphopeptide set (phos-iRT) as the internal standards and a local normalization method.

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All-terrain microrobots possess significant potential in modern medical applications due to their superior maneuverability in complex terrains and confined spaces. However, conventional microrobots often struggle with adaptability and operational difficulties in variable environments. This study introduces a magnetic torque-driven all-terrain multiped microrobot (MTMR) to address these challenges.

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Inspired by the unidirectional liquid spreading on Nepenthes peristome, Araucaria leaf, butterfly wings, etc., various microfluidic devices have been developed for water collection, irrigation, physical/chemical reaction, and oil-water separation. Despite extensive progress, most natural and artificial structures fail to enhance the Laplace pressure difference or capillary force, thus suffering from a low unidirectional capillary height (<30 mm).

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Living organisms in nature possess diverse and vibrant structural colors generated from their intrinsic surface micro/nanostructures. These intricate micro/nanostructures can be harnessed to develop a new generation of colorful materials for various fields such as photonics, information storage, display, and sensing. Recent advancements in the fabrication of photonic crystals have enabled the preparation of structurally colored materials with customized geometries using 3D printing technologies.

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Psoriasis is an intractable immune-mediated disorder that disrupts the skin barrier. While studies have dissected the mechanism by which immune cells directly regulate epidermal cell proliferation, the involvement of dermal fibroblasts in the progression of psoriasis remains unclear. Here, we identified that signals from dendritic cells (DCs) that migrate to the dermal-epidermal junction region enhance dermal stiffness by increasing extracellular matrix (ECM) expression, which further promotes basal epidermal cell hyperproliferation.

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Exploring the spatiotemporal dynamic patterns of multi-channel electroencephalography (EEG) is crucial for interpreting dementia and related cognitive decline. Spatiotemporal patterns of EEG can be described through microstate analysis, which provides a discrete approximation of the continuous electric field patterns generated by the brain cortex. Here, we propose a novel microstate spatiotemporal dynamic indicator, termed the microstate sequence non-randomness index (MSNRI).

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Patient-derived organoids have proven to be a highly relevant model for evaluating of disease mechanisms and drug efficacies, as they closely recapitulate in vivo physiology. Colorectal cancer organoids, specifically, exhibit a diverse range of morphologies, which have been analyzed with image-based profiling. However, the relationship between morphological subtypes and functional parameters of the organoids remains underexplored.

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Vascularized organoid-on-a-chip (VOoC) models achieve substance exchange in deep layers of organoids and provide a more physiologically relevant system in vitro. Common designs for VOoC primarily involve two categories: self-assembly of endothelial cells (ECs) to form microvessels and pre-patterned vessel lumens, both of which include the hydrogel region for EC growth and allow for controlled fluid perfusion on the chip. Characterizing the vasculature of VOoC often relies on high-resolution microscopic imaging.

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Cell types with different morphology, and function collaborate to maintain organ function. As such, analyzing proteomic differences and connections between different types of cells forms the foundation for establishing functional connectomes and developing in vitro organoid simulation experiments. However, the efficiency of cell type isolation from organs is limited by time, equipment, and cost.

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Oral squamous cell carcinoma (OSCC) has become a global health problem due to its increasing incidence and high mortality rate. Early intervention through monitoring of the diagnostic biomarker levels during OSCC treatment is critical. Extracellular vesicles (EVs) are emerging surrogates in intercellular communication through transporting biomolecule cargo and have recently been identified as a potential source of biomarkers such as phosphoproteins for many diseases.

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Rapid and accurate identification and effective non-drug intervention are the worldwide challenges in the field of depression. Electroencephalogram (EEG) signals contain rich quantitative markers of depression, but whole-brain EEG signals acquisition process is too complicated to be applied on a large-scale population. Based on the wearable frontal lobe EEG monitoring device developed by the authors' laboratory, this study discussed the application of wearable EEG signal in depression recognition and intervention.

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Current techniques for visualizing and quantifying cellular forces have limitations in live cell imaging, throughput, and multi-scale analysis, which impede progress in cell force research and its practical applications. We developed a photonic crystal cellular force microscopy (PCCFM) to image vertical cell forces over a wide field of view (1.3 mm ⨯ 1.

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Photonic crystal hydrogels (PCHs), with smart stimulus-responsive abilities, have been widely exploited as colorimetric sensors for years. However, the current fabrication technologies are mostly applicable to produce PCHs with simple geometries at the sub-millimeter scale, limiting the introduction of structural design into PCH sensors as well as the accompanied advanced applications. This paper reports the microfabrication of three-dimensional (3D) PCHs with the help of supramolecular agarose PCH as a sacrificial scaffold by two-photon lithography (TPL).

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