Indoor-Light-Activated Blue TiO2-Molecule-WO3 Visible Photocatalyst for Antibacterial Performance against Escherichia coli.

Currently used visible light catalysts either operate with high-power light sources or require prolonged periods of time for catalytic reactions. This presents a limitation regarding facile application in indoor environments and spaces frequented by the public. Furthermore, this gives rise to elevated power consumption. Here, we enhance photocatalytic performance with blue TiO2 and WO3 complexes covalently coupled through an organic molecule, 3-mercaptopropionic acid, under indoor light. Antibacterial experiments against 108 CFU/mL Escherichia coli (E. coli) suspensions were conducted under indoor light exposure conditions. They showed a sterilization effect of almost 90% within 70 min and nearly 100% after 110 min. The complex generates reactive oxygen species (ROS), such as •OH and O2•-, under natural air conditions. We also showed that h+ and •OH are important for sterilizing E. coli using common scavengers. This research highlights the potential of these complexes to generate ROS, effectively playing a crucial role in antibacterial effects under indoor light.

Neuropathogenesis-on-chips for neurodegenerative diseases.

Developing diagnostics and treatments for neurodegenerative diseases (NDs) is challenging due to multifactorial pathogenesis that progresses gradually. Advanced in vitro systems that recapitulate patient-like pathophysiology are emerging as alternatives to conventional animal-based models. In this review, we explore the interconnected pathogenic features of different types of ND, discuss the general strategy to modelling NDs using a microfluidic chip, and introduce the organoid-on-a-chip as the next advanced relevant model. Lastly, we overview how these models are being applied in academic and industrial drug development. The integration of microfluidic chips, stem cells, and biotechnological devices promises to provide valuable insights for biomedical research and developing diagnostic and therapeutic solutions for NDs.

Implementation of the neuro-glia-vascular unit through co-culture of adult neural stem cells and vascular cells and transcriptomic analysis of diverse Aß assembly types.

BACKGROUND: The blood-brain barrier (BBB) is a specialized layer between blood vessels and tissue in the brain, which is comprised of a neuro-glia-vascular (NGV) unit, thus play a vital role in various brain diseases. NEW METHOD: We developed the in vitro NGV units by co-culturing brain microvascular endothelial cells (BMECs; bEnd.3) and primary neural stem cells extracted from subventricular zone of adult mice. This approach was designed to mimic the RNA profile conditions found in the microvessels of a mouse brain and confirmed through various comparative transcriptome analyses. RESULTS: Optimal NGV unit development was achieved by adjusting cell density-dependent co-culture ratios. Specifically, the morphogenic development and neuronal association of astrocyte endfeet were well observed in the contact region with BMECs in the NGV unit. Through transcriptome analysis, we compared co-cultured bEnd.3/NSCs with monocultured bEnd.3 or NSCs and additionally compared them with previously reported mouse brain vascular tissue to show that this NGV unit model is a suitable in vitro model for neurological disease such as Alzheimer's disease (AD). COMPARISON WITH EXISTING METHOD(S): This in vitro NGV unit was formed from neural stem cells and vascular cells in the brain of adult mice, not embryos. It is very useful for studying brain disease mechanisms by identifying proteins and genes associated with diseases progress. CONCLUSIONS: We suggest that this simple in vitro NGV model is appropriate to investigate the relationship between BBB changes and pathological factors in the fields of neurovascular biology and cerebrovascular diseases including AD.

Probing Interfacial Charge Transfer between Amyloid-ß and Graphene during Amyloid Fibrillization Using Raman Spectroscopy.

Charge transfer plays a key role in the structural transformation of amyloid-ß proteins (Aßs), as it fibrillizes from small monomers to intermediate oligomers and to ordered fibrils. While the protein fibrillization states have been identified using cryo-electron microscopy, X-ray diffraction, Raman, infrared, terahertz spectroscopies, etc., there is little known about the electronic states during the fibrilization of Aß protein. Here, we probe the charge transfer of Aß42 proteins at different aggregation stages adsorbed on monolayer graphene (Gr) and molybdenum disulfide (MoS2) using Raman spectroscopy. Monomers, oligomers, and fibrils prepared in buffer solutions were deposited and dried separately on Gr and MoS2 where well-established characteristic Raman modes (G, 2D for Gr and E2g, A1g for MoS2) were monitored. The shifts in Raman parameters showed that the small Aß monomers withdraw electrons, whereas fibrils donate electrons to Gr and MoS2. Oligomers undergo transient charge states near the neutrality point. This is explained in terms of modulated carrier concentration in Gr and MoS2. This finding provides insight into the electronic properties of Aßs that could be essential to identifying the onset of toxic fibril forms and developing a straightforward, label-free diagnosis using Gr and MoS2.

3D printed multi-growth factor delivery patches fabricated using dual-crosslinked decellularized extracellular matrix-based hybrid inks to promote cerebral angiogenesis.

Generally, brain angiogenesis is a tightly regulated process, which scarcely occurred in the absence of specific pathological conditions. Delivery of exogenous angiogenic factors enables the induction of desired angiogenesis by stimulating neovasculature formation. However, effective strategies of mimicking the angiogenesis process with exogenous factors have not yet been fully explored. Herein, we develop a 3D printed spatiotemporally compartmentalized cerebral angiogenesis inducing (SCAI) hydrogel patch, releasing dual angiogenic growth factors (GFs), using extracellular matrix-based hybrid inks. We introduce a new hybrid biomaterial-based ink for printing patches through dual crosslinking mechanisms: Chemical crosslinking with aza-Michael addition reaction with combining methacrylated hyaluronic acid (HAMA) and vascular-tissue-derived decellularized extracellular matrix (VdECM), and thermal crosslinking of VdECM. 3D printing technology, a useful approach with fabrication versatility with customizable systems and multiple biomaterials, is adopted to print three-layered hydrogel patch with spatially separated dual GFs as outer- and inner-layers that provide tunable release profiles of multiple GFs and fabrication versatility. Consequently, these layers of the patch spatiotemporally separated with dual GFs induce excellent neovascularization in the brain area, monitored by label-free photoacoustic microscopy in vivo. The developed multi-GFs releasing patch may offer a promising therapeutic approach of spatiotemporal drugs releasing such as cerebral ischemia, ischemic heart diseases, diabetes, and even use as vaccines. STATEMENT OF SIGNIFICANCE: Effective strategies of mimicking the angiogenesis process with exogenous factors have not yet been fully explored. In this study, we develop a 3D printed spatiotemporally compartmentalized cerebral angiogenesis inducing (SCAI) hydrogel patch, releasing dual angiogenic growth factors (GFs) using extracellular matrix-based hybrid inks. We introduce a new hybrid biomaterial-based ink through dual crosslinking mechanisms: Chemical crosslinking with aza-Michael addition, and thermal crosslinking. 3D printing technology is adopted to print three-layered hydrogel patch with spatially separated dual GFs as outer- and inner-layers that provide tunable release profiles of multiple GFs and fabrication versatility. Consequently, these layers of the patch spatiotemporally separated with dual GFs induce excellent neovascularization in the brain area, monitored by photoacoustic microscopy in vivo.

Subwavelength Terahertz Resonance Imaging (STRING) for Molecular Fingerprinting.

Subwavelength terahertz (THz) imaging methods are highly desirable for biochemical sensing as well as materials sciences, yet sensitive spectral fingerprinting is still challenging in the frequency domain due to weak light-matter interactions. Here, we demonstrate subwavelength THz resonance imaging (STRING) that overcomes this limitation to achieve ultrasensitive molecular fingerprinting. STRING combines individual ring-shaped coaxial single resonators with near-field spectroscopy, yielding considerable sensitivity gains from both local field enhancement and the near-field effect. As an initial demonstration, we obtained spectral fingerprints from isomers of α-lactose and maltose monohydrates, achieving sensitivity that was enhanced by up to 10 orders of magnitude compared to far-field THz measurements with pelletized samples. Our results show that the STRING platform could enable the development of THz spectroscopy as a practical and sensitive tool for the fingerprinting and spectral imaging of molecules and nanoparticles.

Human mini-blood-brain barrier models for biomedical neuroscience research: a review.

The human blood-brain barrier (BBB) is a unique multicellular structure that is in critical demand for fundamental neuroscience studies and therapeutic evaluation. Despite substantial achievements in creating in vitro human BBB platforms, challenges in generating specifics of physiopathological relevance are viewed as impediments to the establishment of in vitro models. In this review, we provide insight into the development and deployment of in vitro BBB models that allow investigation of the physiology and pathology of neurological therapeutic avenues. First, we highlight the critical components, including cell sources, biomaterial glue collections, and engineering techniques to reconstruct a miniaturized human BBB. Second, we describe recent breakthroughs in human mini-BBBs for investigating biological mechanisms in neurology. Finally, we discuss the application of human mini-BBBs to medical approaches. This review provides strategies for understanding neurological diseases, a validation model for drug discovery, and a potential approach for generating personalized medicine.

Identifying Fibrillization State of Aß Protein via Near-Field THz Conductance Measurement.

Progressive Alzheimer's disease is correlated with the oligomerization and fibrillization of the amyloid beta (Aß) protein. We identify the fibrillization stage of the Aß protein through label-free near-field THz conductance measurements in a buffer solution. Frequency-dependent conductance was obtained by measuring the differential transmittance of the time-domain spectroscopy in the THz range with a molar concentration of monomer, oligomer, and fibrillar forms of the Aß protein. Conductance at the lower frequency limit was observed to be high in monomers, reduced in oligomers, and dropped to an insulating state in fibrils and increased proportionally with the Aß protein concentration. The monotonic decrease in the conductance at low frequency was dominated by a simple Drude component in the monomer with concentration and nonlinear conductance behaviors in the oligomer and fibril. By extracting the structural localization parameter, a dimensionless constant, with the modified Drude-Smith model, we defined a dementia quotient (DQ) value (0 < De < 1) as a discrete metric for a various Aß proteins at a low concentration of 0.1 µmol/L; DQ = 1.0 ± 0.002 (fibril by full localization, mainly by Smith component), DQ = 0.64 ± 0.013 (oligomer by intermixed localization), and DQ = 0.0 ± 0.000 (monomer by Drude component). DQ values were discretely preserved independent of the molar concentration or buffer variation. This provides plenty of room for the label-free diagnosis of Alzheimer's disease using the near-field THz conductance measurement.

Supramolecular Peptide Hydrogel-Based Soft Neural Interface Augments Brain Signals through a Three-Dimensional Electrical Network.

Recording neural activity from the living brain is of great interest in neuroscience for interpreting cognitive processing or neurological disorders. Despite recent advances in neural technologies, development of a soft neural interface that integrates with neural tissues, increases recording sensitivity, and prevents signal dissipation still remains a major challenge. Here, we introduce a biocompatible, conductive, and biostable neural interface, a supramolecular ß-peptide-based hydrogel that allows signal amplification via tight neural/hydrogel contact without neuroinflammation. The non-biodegradable ß-peptide forms a multihierarchical structure with conductive nanomaterial, creating a three-dimensional electrical network, which can augment brain signal efficiently. By achieving seamless integration in brain tissue with increased contact area and tight neural tissue coupling, the epidural and intracortical neural signals recorded with the hydrogel were augmented, especially in the high frequency range. Overall, our tissuelike chronic neural interface will facilitate a deeper understanding of brain oscillation in broad brain states and further lead to more efficient brain-computer interfaces.

Endothelial-specific Crif1 deletion induces BBB maturation and disruption via the alteration of actin dynamics by impaired mitochondrial respiration.

Cerebral endothelial cells (ECs) require junctional proteins to maintain blood-brain barrier (BBB) integrity, restricting toxic substances and controlling peripheral immune cells with a higher concentration of mitochondria than ECs of peripheral capillaries. The mechanism underlying BBB disruption by defective mitochondrial oxidative phosphorylation (OxPhos) is unclear in a mitochondria-related gene-targeted animal model. To assess the role of EC mitochondrial OxPhos function in the maintenance of the BBB, we developed an EC-specific CR6-interactin factor1 (Crif1) deletion mouse. We clearly observed defects in motor behavior, uncompacted myelin and leukocyte infiltration caused by BBB maturation and disruption in this mice. Furthermore, we investigated the alteration in the actin cytoskeleton, which interacts with junctional proteins to support BBB integrity. Loss of Crif1 led to reorganization of the actin cytoskeleton and a decrease in tight junction-associated protein expression through an ATP production defect in vitro and in vivo. Based on these results, we suggest that mitochondrial OxPhos is important for the maturation and maintenance of BBB integrity by supplying ATP to cerebral ECs.