Asymptomatic patients with very severe aortic stenosis were randomly assigned to either early valve-replacement surgery or conservative care. At a median of 6 years of follow-up, the composite of ...operative mortality or death from cardiovascular causes occurred less frequently in the early-surgery group.
Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for ...brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases.
The fabrication of functional tissues is essential for clinical applications such as disease treatment and drug discovery. Recent studies have revealed that the mechanical environments of tissues, ...determined by geometric cell patterns, material composition, or mechanical properties, play critical roles in ensuring proper tissue function. Here, we propose an acoustophoretic technique using surface acoustic waves to fabricate therapeutic vascular tissue containing a three-dimensional collateral distribution of vessels. Co-aligned human umbilical vein endothelial cells and human adipose stem cells that are arranged in a biodegradable catechol-conjugated hyaluronic acid hydrogel exhibit enhanced cell-cell contacts, gene expression, and secretion of angiogenic and anti-inflammatory paracrine factors. The therapeutic effects of the fabricated vessel constructs are demonstrated in experiments using an ischemia mouse model by exhibiting the remarkable recovery of damaged tissue. Our study can be referenced to fabricate various types of artificial tissues that mimic the original functions as well as structures.
Nature has developed materials that are integrated and effective at controlling their properties of adhesiveness and cohesiveness; the chemistry of these materials has been optimized during ...evolution. For example, a catechol moiety found in the adhesive proteins of marine mussels regulates its properties between adhesion and cohesion, rapidly adapting to environmental conditions. However, in synthetic materials chemistry, introduced chemical moieties are usually monofunctional, either being adhesive or cohesive; typically, this is not effective compared to natural materials. Herein, it is demonstrated that hyaluronic acid‐catechol (HA‐catechol) conjugates can exhibit either adhesiveness, functionalizing the surface of materials, or cohesiveness, building 3D hydrogels. Up to now, catechol‐conjugated polymers have shown to be useful in one of these two functions. The usefulness of the polymer in stem cell engineering is demonstrated. A platform for neural stem cell culture may be prepared, utilizing the adhesive property of HA‐catechol, and hydrogels are fabricated to encapsulate the neural stem cells, utilizing the cohesive property of the HA conjugate. Moreover, the HA‐catechol hydrogels are highly neural stem cell compatible, showing better viability compared to existing methods based on HA hydrogels.
Hyaluronic acid catechol conjugate is able to change between adhesiveness and cohesiveness in a smart way. This is demonstrated to be useful for human neural stem cell culture, which cannot be stably cultured on typical polystyrene culture plates.
Phase-coherent transfer of optical frequencies over a long distance is required for diverse photonic applications, including optical clock dissemination and physical constants measurement. Several ...demonstrations were made successfully over fiber networks, but not much work has been done yet through the open air where atmospheric turbulence prevails. Here, we use an 18 km outdoor link to transmit multiple optical carriers extracted directly from a frequency comb of a 4.2 THz spectral width. In stabilization to a high-finesse cavity with a 1.5 Hz linewidth, the comb-rooted optical carriers are simultaneously transferred with collective suppression of atmospheric phase noise to -80 dBc Hz
. Microwaves are also delivered by pairing two separate optical carriers bound with inter-comb-mode coherence, for example a 10 GHz signal with phase noise of -105 dBc Hz
at 1 Hz offset. Lastly, an add-on demonstration is given for multi-channel coherent optical communications with the potential of multi-Tbps data transmission in free space.
This study aimed to investigate the difference in people's perceived crowding and risk perception during leisure activities using the criteria of spatial proximity during the COVID-19 pandemic. ...COVID-19 is a viral respiratory tract disease that poses an increasing risk of infection through person-to-person transmission in a confined space or close proximity to an infected person. It is thus crucial to maintain a sufficiently safe distance from others during leisure activities. In this study, measures concerning leisure activity spaces and the current status of leisure activities were investigated. Data were gathered from a total of 1078 participants via an online survey conducted from 26 to 29 October 2020. Frequency analysis was performed to investigate the sample characteristics and exploratory factor analysis was performed to analyze the validity of the measurement tools. Results revealed that people's perceived crowding of leisure activity spaces directly influenced their participation in leisure activities. Regarding age, those in their 20s were more aware of congestion and their risk perception was higher than those in their 40s and 50s. It was found that people perceived cultural and artistic activities to be dangerous as they often take place as part of tourism and leisure activities and amidst crowds. However, their high-risk perception indirectly influenced their participation patterns, making it difficult to enjoy leisure activities. To lower the risk perception of leisure activity spaces, it was necessary to secure more safe distancing than current regulations require. Future research must conduct a longitudinal investigation by objectively stratifying the degree of perceived crowding.
Dynamic manipulation of supramolecular self‐assembled structures is achieved irreversibly or under non‐physiological conditions, thereby limiting their biomedical, environmental, and catalysis ...applicability. In this study, microgels composed of azobenzene derivatives stacked via π–cation and π–π interactions are developed that are electrostatically stabilized with Arg–Gly–Asp (RGD)‐bearing anionic polymers. Lateral swelling of RGD‐bearing microgels occurs via cis‐azobenzene formation mediated by near‐infrared‐light‐upconverted ultraviolet light, which disrupts intermolecular interactions on the visible‐light‐absorbing upconversion‐nanoparticle‐coated materials. Real‐time imaging and molecular dynamics simulations demonstrate the deswelling of RGD‐bearing microgels via visible‐light‐mediated trans‐azobenzene formation. Near‐infrared light can induce in situ swelling of RGD‐bearing microgels to increase RGD availability and trigger release of loaded interleukin‐4, which facilitates the adhesion structure assembly linked with pro‐regenerative polarization of host macrophages. In contrast, visible light can induce deswelling of RGD‐bearing microgels to decrease RGD availability that suppresses macrophage adhesion that yields pro‐inflammatory polarization. These microgels exhibit high stability and non‐toxicity. Versatile use of ligands and protein delivery can offer cytocompatible and photoswitchable manipulability of diverse host cells.
Remote control of microgels via tissue‐penetrative light is demonstrated. Near‐infrared‐light‐upconverted ultraviolet light stimulates in situ swelling of RGD‐bearing microgels that increases RGD availability, thereby facilitating macrophage adhesion linked with pro‐regenerative polarization. Visible light induces the deswelling of RGD‐bearing microgels that decreases RGD availability that suppresses macrophage adhesion that yields pro‐inflammatory polarization.
The construction of carbon-coated heterostructures of bimetallic sulfide is an effective technique to improve the electrochemical activity of anode materials in lithium-ion batteries. In this work, ...the carbon-coated heterostructured ZnS-FeS2 is prepared by a two-step hydrothermal method. The crystallinity and nature of carbon-coating are confirmed by the investigation of XRD and Raman spectroscopy techniques. The nanoparticle morphology of ZnS and plate-like morphology of FeS2 is established by TEM images. The chemical composition of heterostructure ZnS-FeS2@C is discovered by an XPS study. The CV results have disclosed the charge storage mechanism, which depends on the capacitive and diffusion process. The BET surface area (37.95 m2g−1) and lower Rct value (137 Ω) of ZnS-FeS2@C are beneficial to attain higher lithium-ion storage performance. It delivered a discharge capacity of 821 mAh g−1 in the 500th continuous cycle @ A g−1, with a coulombic efficiency of around 100%, which is higher than the ZnS-FeS2 heterostructure (512 mAh g−1). The proposed strategy can improve the electrochemical performance and stability of lithium-ion batteries, and can be helpful in finding highly effective anode materials for energy storage devices.
Tissue engineering of skeletal muscle has been proposed as a potential regenerative treatment for extensive muscle damage. In this regard, the highly organized structure of skeletal muscles makes the ...alignment of cells especially indispensable in muscle tissue engineering. However, achieving the desired alignment continues to prove challenging, particularly in 3D engineered tissue constructs. In this study, a biomimetic approach for the generation of functional skeletal muscle fascicle‐like tissues by recapitulating 3D muscle‐like cellular and extracellular organization, is demonstrated. Anisotropic 3D alignment of muscle extracellular matrix (MEM) nanofibrils capable of providing a pro‐myogenic microenvironment by regulating the kinetics of fibrillogenesis in a stretchable elastomeric chip, is achieved. Reprogrammed muscle progenitor cells develop myofibers along the aligned MEM nanofibrils in a 3D configuration, culminating in the structural and functional maturation of skeletal muscle. The resultant 3D muscle fascicle‐like constructs support de novo muscle regeneration and induce functional restoration of injured muscles in animal models inflicted with volumetric muscle loss and congenital muscular dystrophy. This study not only highlights the fundamental roles of the muscle–mimetic structural guidance cues for 3D muscle tissue engineering, but also unveils the clinical potential of artificial muscle constructs in regenerative medicine.
The highly organized structure of skeletal muscle is recapitulated by anisotropic 3D alignment of muscle extracellular matrix (MEM) nanofibrils by regulating the kinetics of fibrillogenesis in a stretchable elastomeric chip. Reprogrammed muscle progenitor cells develop myofibers along the aligned MEM nanofibrils, culminating in the structural and functional maturation of skeletal muscle for treating volumetric muscle loss and dystrophic muscle disorders.
Targeted protein degradation allows targeting undruggable proteins for therapeutic applications as well as eliminating proteins of interest for research purposes. While several degraders that harness ...the proteasome or the lysosome have been developed, a technology that simultaneously degrades targets and accelerates cellular autophagic flux is still missing. In this study, we develop a general chemical tool and platform technology termed AUTOphagy-TArgeting Chimera (AUTOTAC), which employs bifunctional molecules composed of target-binding ligands linked to autophagy-targeting ligands. AUTOTACs bind the ZZ domain of the otherwise dormant autophagy receptor p62/Sequestosome-1/SQSTM1, which is activated into oligomeric bodies in complex with targets for their sequestration and degradation. We use AUTOTACs to degrade various oncoproteins and degradation-resistant aggregates in neurodegeneration at nanomolar DC
values in vitro and in vivo. AUTOTAC provides a platform for selective proteolysis in basic research and drug development.
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