Switchable and conspicuous retroreflective sensors inspired by the wing scale of an emerald swallowtail.

Butterfly wings possess distinct micro/nanostructures that contribute to their vibrant coloration, light-trapping capabilities, and sensitivity to various stimuli. These complex features have inspired the creation of diverse devices and systems, such as sensors, photovoltaics, photocatalysis, and robotics. Specifically, the wing scales of the Emerald Swallowtail (Papilio palinurus) display iridescent, polarization-sensitive, and retroreflective colors due to their hierarchical structures. However, current technologies fail to mimic these natural designs fully, limiting their practical application in everyday life. In this study, we introduce a groundbreaking method for fabricating artificial wing scales that emulate the biological structure's functionality with a much simpler geometry. By integrating self-graded lossy media into metallic micro-concavity arrays, we achieve pronounced iridescent effects in both coaxial and non-coaxial arrangements, while preserving retroreflective properties. In particular, the simplified design allows for switchable color patterns based on the viewing angle. Demonstrating the concept, we successfully employ these conspicuous retroreflectors in hydrogen gas detection and the bi-directional/switchable recognition of patterned signals.

Microfluidic model for in vitro acute Toxoplasma gondii infection and transendothelial migration.

The protozoan parasite Toxoplasma gondii (T. gondii) causes one of the most common human zoonotic diseases and infects approximately one-third of the global population. T. gondii infects nearly every cell type and causes severe symptoms in susceptible populations. In previous laboratory animal studies, T. gondii movement and transmission were not analyzed in real time. In a three-dimensional (3D) microfluidic assay, we successfully supported the complex lytic cycle of T. gondii in situ by generating a stable microvasculature. The physiology of the T. gondii-infected microvasculature was monitored in order to investigate the growth, paracellular and transcellular migration, and transmission of T. gondii, as well as the efficacy of T. gondii drugs.

Patient Safety Silence and Safety Nursing Activities: Mediating Effects of Moral Sensitivity.

Among the factors that threaten patient safety and quality of care due to the diversification and complication of hospital environments, nurses play a pivotal role regarding patient safety in the clinical setting. This study investigates the mediating effects of moral sensitivity on the relationship between nurses' patient safety silence and safety nursing activities and contributes to developing strategies. Nurses (n = 120) employed for at least one year in two university hospitals in Korea between 1 September and 30 October 2020 participated in the study. Data were analyzed using t-test, Pearson's correlation coefficients, and multiple regression using the SPSS/WIN 22.0 program. Additionally, the mediating effects were analyzed using Baron and Kenny's method and bootstrapping. Safety nursing activities were significantly negatively correlated with patient safety silence and significantly positively correlated with moral sensitivity. Patient safety silence was significantly negatively correlated with moral sensitivity. Moral sensitivity partially mediated the relationship between patient safety silence and safety nursing activities. There is a need to develop and implement individualized ethical programs that enhance moral sensitivity in nurses to promote patient safety nursing activities.

Medial Temporal Atrophy Alone is Insufficient to Predict Underlying Alzheimer's Disease Pathology.

BACKGROUND: The medial temporal region is the earliest affected structure in patients with Alzheimer's disease (AD), and its atrophy is known as the hallmark of AD. This study aimed to investigate the value of medial temporal atrophy (MTA) for detecting 18F-florbetaben positron emission tomography (PET)-proven AD pathology. METHODS: We retrospectively enrolled 265 subjects complaining of cognitive decline at a dementia outpatient clinic from March 2015 to December 2017. All subjects underwent brain magnetic resonance imaging, 18F-fluorodeoxyglucose PET, and 18F-florbetaben PET at baseline. We performed multivariable logistic regression analyses on variables including age, sex, years of education, white matter hyperintensities, apolipoprotein E (APOE) genotype, and memory composite scores in various combinations to investigate whether MTA was indicative of underlying AD pathology. RESULTS: Our sample population of 265 patients comprised 121 with AD-related cognitive impairment, 42 with Lewy bodies-related cognitive impairment, 32 with vascular cognitive impairment, and 70 with other or undetermined pathologies. In the multivariable logistic regression analyses, MTA was not an independent predictor of underlying AD pathology (P>0.200). The predictive power of underlying AD-related cognitive impairment significantly increased when multiple variables including APOE genotype and memory composite scores were considered together (area under the curve >0.750). CONCLUSION: Our results suggest that MTA alone may be insufficient to accurately predict the presence of AD pathology. It is necessary to comprehensively consider various other factors such as APOE genotype and a detailed memory function to determine whether the patient is at high risk of AD.

The Effects of Nurses' Knowledge of Withdrawal of Life-Sustaining Treatment, Death Anxiety, Perceptions of Hospice on Their Attitudes toward Withdrawal of Life-Sustaining Treatment.

PURPOSE: This descriptive study investigated the effects of nurses' knowledge of withdrawal of life-sustaining treatment, death anxiety, and perceptions of hospice care on their attitudes toward withdrawal of life-sustaining treatment. METHODS: Data were collected from 262 nurses at tertiary hospitals, general hospitals, or primary hospitals in Busan, Korea, and statistically analyzed using the t-test, analysis of variance, the Scheffé test, Pearson correlation coefficients, and hierarchical regression analysis. RESULTS: The participants' scores were 3.68±0.45 (out of 5) for attitudes toward withdrawal of life-sustaining treatment, 0.65±0.15 (out of 1) for knowledge of withdrawal of life-sustaining treatment, 2.61±0.26 (out of 4) for death anxiety, and 4.06±0.43 (out of 5) for perceptions of hospice care. Furthermore, knowledge of withdrawal of life-sustaining treatment and perceptions of hospice care showed positive correlations with attitudes toward withdrawal of life-sustaining treatment, while death anxiety showed a negative correlation. The most significant factors influencing attitudes toward withdrawal of life-sustaining treatment were perceptions of hospice care, followed by having experienced caring for patients who withdrew life-sustaining treatment, death anxiety, having a spouse, and ethical values, and the overall explanatory power was 43.0%. CONCLUSION: This study showed that perceptions of hospice were an important factor influencing nurses' attitudes toward withdrawal of life-sustaining treatment. Therefore, it is necessary to develop and validate educational intervention programs that can improve perceptions of hospice care.

Cancer-derived exosomes trigger endothelial to mesenchymal transition followed by the induction of cancer-associated fibroblasts.

Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor growth, but very little has been known about its characteristics and origin. Recently, cancer-derived exosome has been suggested to transdifferentiate CAFs, by a new mechanism of endothelial to mesenchymal transition (EndMT), initiating angiogenic processes and triggering metastatic evolution. However, an enabling tool in vitro is yet to be developed to investigate complicated procedures of the EndMT and the transdifferentiation under reconstituted tumor microenvironment. Here we proposed an in vitro microfluidic model which enables to monitor a synergetic effect of complex tumor microenvironment in situ, including extracellular matrix (ECM), interstitial flow and environmental exosomes. The number of CAFs differentiated from human umbilical vein endothelial cells (HUVECs) increased with melanoma-derived exosomes, presenting apparent morphological and molecular changes with pronounced motility. Mesenchymal stem cell (MSC)-derived exosomes were found to suppress EndMT, induce angiogenesis and maintain vascular homeostasis, while cancer-derived exosomes promoted EndMT. Capabilities of the new microfluidic model exist in precise regulation of the complex tumor microenvironment and therefore successful reconstitution of 3D microvasculature niches, enabling in situ investigation of EndMT procedure between various cell types. STATEMENT OF SIGNIFICANCE: This study presents an in vitro 3D EndMT model to understand the progress of the CAF generation by recapitulating the 3D tumor microenvironment in a microfluidic device. Both cancer-derived exosomes and interstitial fluid flow synergetically played a pivotal role in the EndMT and consequent formation of CAFs through a collagen-based ECM. Our approach also enabled the demonstration of a homeostatic capability of MSC-derived exosomes, ultimately leading to the recovery of CAFs back to endothelial cells. The in vitro 3D EndMT model can serve as a powerful tool to validate exosomal components that could be further developed to anti-cancer drugs.

Does Late Levodopa Administration Delay the Development of Dyskinesia in Patients with De Novo Parkinson's Disease?

BACKGROUND: It remains controversial whether late levodopa administration is a reasonable approach to reducing the risk of levodopa-induced dyskinesia in Parkinson's disease. OBJECTIVE: This study aimed to investigate the effects of levodopa sparing on the development of levodopa-induced dyskinesia. METHODS: We retrospectively reviewed medical records for patients with de novo Parkinson's disease who visited the Yonsei Parkinson Center between April 2009 and June 2015 and received at least 2 years of treatment. Among 657 patients with drug-naïve Parkinson's disease who met the study criteria, 90 were initially treated with dopamine agonists (levodopa-sparing group; levodopa supplementation after 2.15 years). Another 90 patients who were initially treated with levodopa (levodopa group) were matched to the 90 patients for age, sex, follow-up duration, Parkinson's disease duration, Unified Parkinson's Disease Rating Scale Part III scores, and baseline dopamine transporter availability in the posterior putamen. The effects of levodopa sparing on dyskinesia development were assessed with Kaplan-Meier estimates and a stratified Cox regression model adjusted for age of onset, sex, dopamine transporter availability, and daily levodopa dose per weight. RESULTS: The levodopa-sparing group had a comparable age of onset (54.80 ± 7.36 years) to the levodopa group (56.53 ± 6.16 years). The Kaplan-Meier analysis revealed that the risk of levodopa-induced dyskinesia after treatment initiation was similar between the groups. Once the levodopa-sparing group started levodopa supplementation, they had a higher risk of developing levodopa-induced dyskinesia. However, a stratified Cox regression model indicated that hazard ratios for levodopa sparing to levodopa-induced dyskinesia development were 0.138 (95% confidence interval 0.024-0.785) after treatment initiation and 0.438 (95% confidence interval 0.105-1.832) after levodopa initiation. CONCLUSION: Late levodopa administration was associated with a low risk of dyskinesia after adjusting for confounding effects and may be a reasonable strategy for prolonging the levodopa-induced dyskinesia-free period in Parkinson's disease.

Fabrication of type I collagen microcarrier using a microfluidic 3D T-junction device and its application for the quantitative analysis of cell-ECM interactions.

We presented a new quantitative analysis for cell and extracellular matrix (ECM) interactions, using cell-coated ECM hydrogel microbeads (hydrobeads) made of type I collagen. The hydrobeads can carry cells as three-dimensional spheroidal forms with an ECM inside, facilitating a direct interaction between the cells and ECM. The cells on hydrobeads do not have a hypoxic core, which opens the possibility for using as a cell microcarrier for bottom-up tissue reconstitution. This technique can utilize various types of cells, even MDA-MB-231 cells, which have weak cell-cell interactions and do not form spheroids in conventional spheroid culture methods. Morphological indices of the cell-coated hydrobead visually present cell-ECM interactions in a quantitative manner.

Intrinsic FGF2 and FGF5 promotes angiogenesis of human aortic endothelial cells in 3D microfluidic angiogenesis system.

The human body contains different endothelial cell types and differences in their angiogenic potential are poorly understood. We compared the functional angiogenic ability of human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs) using a three-dimensional (3D) microfluidic cell culture system. HAECs and HUVECs exhibited similar cellular characteristics in a 2D culture system; however, in the 3D microfluidic angiogenesis system, HAECs exhibited stronger angiogenic potential than HUVECs. Interestingly, the expression level of fibroblast growth factor (FGF)2 and FGF5 under vascular endothelial growth factor (VEGF)-A stimulation was significantly higher in HAECs than in HUVECs. Moreover, small interfering RNA-mediated knockdown of FGF2 and FGF5 more significantly attenuated vascular sprouting induced from HAECs than HUVECs. Our results suggest that HAECs have greater angiogenic potential through FGF2 and FGF5 upregulation and could be a compatible endothelial cell type to achieve robust angiogenesis.

Constructive remodeling of a synthetic endothelial extracellular matrix.

The construction of well-controllable in vitro models of physiological and pathological vascular endothelium remains a fundamental challenge in tissue engineering and drug development. Here, we present an approach for forming a synthetic endothelial extracellular matrix (ECM) that closely resembles that of the native structure by locally depositing basement membrane materials onto type 1 collagen nanofibers only in a region adjacent to the endothelial cell (EC) monolayer. Culturing the EC monolayer on this synthetic endothelial ECM remarkably enhanced its physiological properties, reducing its vascular permeability, and promoting a stabilized, quiescent phenotype. We demonstrated that the EC monolayer on the synthetic endothelial ECM neither creates non-physiological barriers to cell-cell or cell-ECM interactions, nor hinders molecular diffusion of growth factors and other molecules. The synthetic endothelial ECM and vascular endothelium on it may help us enter in a new phase of research in which various models of the biological barrier behavior can be tested experimentally.

Smooth muscle progenitor cells from peripheral blood promote the neovascularization of endothelial colony-forming cells.

Proangiogenic cell therapy using autologous progenitors is a promising strategy for treating ischemic disease. Considering that neovascularization is a harmonized cellular process that involves both endothelial cells and vascular smooth muscle cells, peripheral blood-originating endothelial colony-forming cells (ECFCs) and smooth muscle progenitor cells (SMPCs), which are similar to mature endothelial cells and vascular smooth muscle cells, could be attractive cellular candidates to achieve therapeutic neovascularization. We successfully induced populations of two different vascular progenitor cells (ECFCs and SMPCs) from adult peripheral blood. Both progenitor cell types expressed endothelial-specific or smooth muscle-specific genes and markers, respectively. In a protein array focused on angiogenic cytokines, SMPCs demonstrated significantly higher expression of bFGF, EGF, TIMP2, ENA78, and TIMP1 compared to ECFCs. Conditioned medium from SMPCs and co-culture with SMPCs revealed that SMPCs promoted cell proliferation, migration, and the in vitro angiogenesis of ECFCs. Finally, co-transplantation of ECFCs and SMPCs induced robust in vivo neovascularization, as well as improved blood perfusion and tissue repair, in a mouse ischemic hindlimb model. Taken together, we have provided the first evidence of a cell therapy strategy for therapeutic neovascularization using two different types of autologous progenitors (ECFCs and SMPCs) derived from adult peripheral blood.

Extracellular matrix heterogeneity regulates three-dimensional morphologies of breast adenocarcinoma cell invasion.

Plasticity and reciprocity of breast cancer cells to various extracellular matrice (ECMs) are three-dimensionally analyzed in quantitative way in a novel and powerful microfluidic in vitro platform. This successfully demonstrates the metastatic potential of cancer cells and their effective strategies of ECM proteolytic remodeling and morphological change, while interacting with other cells and invading into heterogeneous ECMs.

A versatile assay for monitoring in vivo-like transendothelial migration of neutrophils.

Spatiotemporal analysis of the inflammatory response has been limited by the difficulties of in vivo imaging and reconstitution of inflammation in vitro. Here, we present a novel method for establishing in vivo-like inflammatory models in a microfluidic device and quantitatively measuring the three-dimensional transmigration of neutrophils during the inflammatory process. This enabled us to concurrently characterize transendothelial migration behaviors of neutrophils under the influence of various inflammatory stimuli.