Our research group grasps dentin caries treatment from both "induction of decalcified dentin remineralization" and "induction of reparative dentin formation in deep-seated caries." It studies dentin ...remineralization/regeneration from each approach to developing a functional restorative material, thereby providing the dentin-pulp complex with self-restoration capacity. The resin monomer CMET developed by our group is a highly functional monomer capable of remineralization induction, dentin regeneration, and anti-biofilm formation, exhibiting a promising material for functional material development. Based on these findings, new bioactive coating material and universal bonding agent have been developed. Further improvement of these materials will enable caries prevention and self-repair of infected and demineralized dentin in sealed restorations, which is the ideal caries treatment. This will ultimately change caries treatment from "cutting and restorative" to "self-restorative."
No design rules have yet been established for producing solid electrolytes with a lithium-ion conductivity high enough to replace liquid electrolytes and expand the performance and battery ...configuration limits of current lithium ion batteries. Taking advantage of the properties of high-entropy materials, we have designed a highly ion-conductive solid electrolyte by increasing the compositional complexity of a known lithium superionic conductor to eliminate ion migration barriers while maintaining the structural framework for superionic conduction. The synthesized phase with a compositional complexity showed an improved ion conductivity. We showed that the highly conductive solid electrolyte enables charge and discharge of a thick lithium-ion battery cathode at room temperature and thus has potential to change conventional battery configurations.
This study aimed to evaluate the in vitro effect of the novel bioactive adhesive monomer CMET, a calcium salt of 4-methacryloxyethyl trimellitate acid (4-MET), on human dental pulp stem cells ...(hDPSCs) and its capacity to induce tertiary dentin formation in a rat pulp injury model. Aqueous solutions of four tested materials 4-MET, CMET, Ca(OH)
, and mineral trioxide aggregate (MTA) were added to the culture medium upon confluence, and solvent (dH
O) was used as a control. Cell proliferation was assessed using the Cell Counting Kit-8 assay, and cell differentiation was evaluated by real-time quantitative reverse transcription-polymerase chain reaction. The mineralization-inducing capacity was evaluated using alizarin red S staining and an alkaline phosphatase activity assay. For an in vivo experiment, a mechanical pulp exposure model was prepared on Wistar rats; damaged pulp was capped with Ca(OH)
or CMET. Cavities were sealed with composite resin, and specimens were assessed after 14 and 28 days. The in vitro results showed that CMET exhibited the lowest cytotoxicity and highest odontogenic differentiation capacity among all tested materials. The favorable outcome on cell mineralization after treatment with CMET involved p38 and c-Jun N-terminal kinases signaling. The nuclear factor kappa B pathway was involved in the CMET-induced mRNA expression of odontogenic markers. Similar to Ca(OH)
, CMET produced a continuous hard tissue bridge at the pulp exposure site, but treatment with only CMET produced a regular dentinal tubule pattern. The findings suggest that (1) the evaluated novel bioactive adhesive monomer provides favorable biocompatibility and odontogenic induction capacity and that (2) CMET might be a very promising adjunctive for pulp-capping materials.
East and Southeast Asia (ESEA) are facing age-related eye health issues. Low-vision rehabilitation (LVR), which is a special rehabilitation service for individuals with vision impairment, is a ...promising solution for these health issues; however, poor accessibility to LVR services has been reported globally, including ESEA. Therefore, this scoping review aimed to summarize and understand the barriers to accessing LVR services in ESEA. In total, 20 articles were ultimately considered eligible for this scoping review after an electronic database search using MEDLINE (PubMed), Web of Science, Academic Search Ultimate (EBSCO), and Ichushi-Web (Japanese medical literature database), and an independent review by two reviewers. Twenty-one potential barrier factors were identified in the full-text review. Notably, age, education, economic status, "previous experience using eye care service", and "knowledge, information, and awareness" were the possible barrier factors that were examined for their association with LVR utilization, with supportive evidence in many eligible studies. We also identified research gaps relating to geographical and ethnic diversity, the scope of LVR services, and barriers among eligible articles. Therefore, by conducting further studies addressing the research gaps identified in this scoping review, these findings can be used to make LVR services more accessible to people in ESEA.
Alzheimer's disease (AD) is the most common reason for elderly dementia in the world. We proposed that memory loss in AD is related to destabilization of mushroom postsynaptic spines involved in ...long-term memory storage. We demonstrated previously that stromal interaction molecule 2 (STIM2)-regulated neuronal store-operated calcium entry (nSOC) in postsynaptic spines play a key role in stability of mushroom spines by maintaining activity of synaptic Ca(2+)/calmodulin kinase II (CaMKII). Furthermore, we demonstrated previously that the STIM2-nSOC-CaMKII pathway is downregulated in presenilin 1 M146V knock-in (PS1-M146V KI) mouse model of AD, leading to loss of hippocampal mushroom spines in this model. In the present study, we demonstrate that hippocampal mushroom postsynaptic spines are also lost in amyloid precursor protein knock-in (APPKI) mouse model of AD. We demonstrated that loss of mushroom spines occurs as a result of accumulation of extracellular β-amyloid 42 in APPKI culture media. Our results indicate that extracellular Aβ42 acts by overactivating mGluR5 receptor in APPKI neurons, leading to elevated Ca(2+) levels in endoplasmic reticulum, compensatory downregulation of STIM2 expression, impaired synaptic nSOC, and reduced CaMKII activity. Pharmacological inhibition of mGluR5 or overexpression of STIM2 rescued synaptic nSOC and prevented mushroom spine loss in APPKI hippocampal neurons. Our results indicate that downregulation of synaptic STIM2-nSOC-CaMKII pathway causes loss of mushroom synaptic spines in both presenilin and APPKI mouse models of AD. We propose that modulators/activators of this pathway may have a potential therapeutic value for treatment of memory loss in AD. Significance statement: A direct connection between amyloid-induced synaptic mushroom spine loss and neuronal store-operated calcium entry pathway is shown. These results provide strong support for the calcium hypothesis of neurodegeneration and further validate the synaptic store-operated calcium entry pathway as a potential therapeutic target for Alzheimer's disease.
Oxide‐ion conductors are gaining attention as future materials in energy applications, such as solid oxide fuel cells. Many Bi‐containing compounds exhibit high oxide‐ion conductivity via ...conventional vacancy mechanism. However, interstitial oxide‐ion conduction is rare in Bi‐containing materials. Herein, high oxide‐ion conductivity is reported through interstitial oxygen sites in Sillén oxychlorides, LaBi2−xTexO4+x/2Cl (Bi2LaO4Cl‐based oxychlorides). Oxide‐ion conductivity of LaBi1.9Te0.1O4.05Cl is 20 mS cm−1 at 702 °C, and higher than best oxide‐ion conductors as Bi2V0.9Cu0.1O5.35 below 201 °C. Despite of the presence of Bi and Te species, LaBi1.9Te0.1O4.05Cl shows extremely high chemical and electrical stability at 400 °C from oxygen partial pressure 10−25 to 0.2 atm and high chemical stability under CO2 flow, wet 5% H2 in N2 flow, and air with natural humidity. Neutron scattering length density analysis, DFT calculations, and ab initio molecular dynamics simulations indicate that the extremely high oxide‐ion conduction is attributed to cooperative diffusion through interstitial oxygen sites (interstitialcy diffusion mechanism) in triple fluorite‐like layers. The present findings demonstrate the ability of LaBi2−xTexO4+x/2Cl as superior oxide‐ion conductors, which can open new horizons for oxide‐ion conductors.
Oxide‐ion conductors are an exciting class of materials in various applications. In this article it is shown that LaBi1.9Te0.1O4.05Cl exhibits extremely high chemical and electrical stability from oxygen partial pressure 10−25 to 0.2 atm. Bulk conductivity of this material is higher than the best oxide‐ion conductors, which is attributed to cooperative diffusion through interstitial oxygen sites in triple fluorite‐like layers.
Patients with Alzheimer's disease (AD) suffer from spatial memory impairment and wandering behavior, but the brain circuit mechanisms causing such symptoms remain largely unclear. In healthy brains, ...spatially tuned hippocampal place cells and entorhinal grid cells exhibit distinct spike patterns in different environments, a circuit function called “remapping.” We tested remapping in amyloid precursor protein knockin (APP-KI) mice with impaired spatial memory. CA1 neurons, including place cells, showed disrupted remapping, although their spatial tuning was only mildly diminished. Medial entorhinal cortex (MEC) neurons severely lost their spatial tuning and grid cells were almost absent. Fast gamma oscillatory coupling between the MEC and CA1 was also impaired. Mild disruption of MEC grid cells emerged in younger APP-KI mice, although the spatial memory and CA1 remapping of the animals remained intact. These results point to remapping impairment in the hippocampus, possibly linked to grid cell disruption, as circuit mechanisms underlying spatial memory impairment in AD.
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•Remapping of place and grid cells was investigated in APP knockin mice•Place cells were mildly deteriorated but showed severely disrupted remapping•Grid cells were severely impaired, leaving few neurons with the ability to remap•Disruption of grid cells, but not place cells, emerged in younger APP knockin mice
Place cells in the hippocampus exhibit distinct spike patterns in different environments, a circuit function called remapping. Jun et al. show that remapping is disrupted in the APP knockin mouse model, suggesting that remapping impairment is a circuit mechanism underlying spatial memory impairment in Alzheimer's disease.
Optical clearing methods facilitate deep biological imaging by mitigating light scattering in situ. Multi-scale high-resolution imaging requires preservation of tissue integrity for accurate signal ...reconstruction. However, existing clearing reagents contain chemical components that could compromise tissue structure, preventing reproducible anatomical and fluorescence signal stability. We developed ScaleS, a sorbitol-based optical clearing method that provides stable tissue preservation for immunochemical labeling and three-dimensional (3D) signal rendering. ScaleS permitted optical reconstructions of aged and diseased brain in Alzheimer's disease models, including mapping of 3D networks of amyloid plaques, neurons and microglia, and multi-scale tracking of single plaques by successive fluorescence and electron microscopy. Human clinical samples from Alzheimer's disease patients analyzed via reversible optical re-sectioning illuminated plaque pathogenesis in the z axis. Comparative benchmarking of contemporary clearing agents showed superior signal and structure preservation by ScaleS. These findings suggest that ScaleS is a simple and reproducible method for accurate visualization of biological tissue.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Alzheimer's disease (AD) is the most common type of neurocognitive disorder. Although both amyloid β peptide deposition and neurofibrillary tangle formation in the AD brain have been established as ...pathological hallmarks of the disease, many other factors contribute in a complex manner to the pathogenesis of AD before clinical symptoms of the disease become apparent. Longitudinal pathophysiological processes cause patients’ brains to exist in a state of chronic neuroinflammation, with glial cells acting as key regulators of the neuroinflammatory state. However, the detailed molecular and cellular mechanisms of glial function underlying AD pathogenesis remain elusive. Furthermore, recent studies have shown that peripheral inflammatory conditions affect glial cells in the brain through a process of neuroimmune communication. Such disease complexities make it difficult for the pathogenesis of AD to be understood, and impede the development of effective therapeutic strategies to combat the disease. Relevant AD animal models are thus likely to serve as a key resource to overcome many of these issues. Furthermore, as the pathogenesis of AD might be linked to conditions both within the brain as well as peripherally, it might become necessary for AD to be studied as a whole‐body disorder. The present review aimed to summarize insights regarding current AD research, and share perspectives for understanding glial function in the context of the pathogenesis of AD.
This review aims to summarize insights concerning current AD research and share perspectives for understanding glial function in the context of the pathogenesis of AD.
Type I collagen (COL-1) is the prevailing component of the extracellular matrix in a number of tissues including skin, ligament, cartilage, bone, and dentin. It is the most widely used tissue-derived ...natural polymer. Currently, mammalian animals, including pig, cow, and rat, are the three major sources for purification of COL-1. To reduce the risk of zoonotic infectious diseases transmission, minimize the possibility of immunogenic reaction, and avoid problems related to religious issues, exploration of new sources (other than mammalian animals) for the purification of type I collagen is highly desirable. Hence, the purpose of the current study was to investigate the in vitro responses of MDPC-23 to type I collagen isolated from tilapia scale in terms of cellular proliferation, differentiation, and mineralization. The results suggested that tilapia scale collagen exhibited comparable biocompatibility to porcine skin collagen, indicating it might be a potential alternative to type I collagen from mammals in the application for tissue regeneration in oral-maxillofacial area.