Porous Carbon Interlayer Derived from Traditional Korean Paper for Li-S Batteries.

A carbonized interlayer effectively helps to improve the electrochemical performance of lithium-sulfur (Li-S) batteries. In this study, a simple and inexpensive carbon intermediate layer was fabricated using a traditional Korean paper called "hanji". This carbon interlayer has a fibrous porous structure, with a specific surface area of 91.82 m2 g-1 and a BJH adsorption average pore diameter of 26.63 nm. The prepared carbon interlayer was utilized as an intermediary layer in Li-S batteries to decrease the charge-transfer resistance and capture dissolved lithium polysulfides. The porous fiber-shaped carbon interlayer suppressed the migration of polysulfides produced during the electrochemical process. The carbon interlayer facilitates the adsorption of soluble lithium polysulfides, allowing for their re-utilization in subsequent cycles. Additionally, the carbon interlayer significantly reduces the polarization of the cell. This simple strategy results in a significant improvement in cycle performance. Consequently, the discharge capacity at 0.5 C after 150 cycles was confirmed to have improved by more than twofold, reaching 230 mAh g-1 for cells without the interlayer and 583 mAh g-1 for cells with the interlayer. This study demonstrates a simple method for improving the capacity of Li-S batteries by integrating a functional carbon interlayer.

Efficient generation of brain organoids using magnetized gold nanoparticles.

Brain organoids, which are three-dimensional cell culture models, have the ability to mimic certain structural and functional aspects of the human brain. However, creating these organoids can be a complicated and difficult process due to various technological hurdles. This study presents a method for effectively generating cerebral organoids from human induced pluripotent stem cells (hiPSCs) using electromagnetic gold nanoparticles (AuNPs). By exposing mature cerebral organoids to magnetized AuNPs, we were able to cultivate them in less than 3 weeks. The initial differentiation and neural induction of the neurosphere occurred within the first week, followed by maturation, including regional patterning and the formation of complex networks, during the subsequent 2 weeks under the influence of magnetized AuNPs. Furthermore, we observed a significant enhancement in neurogenic maturation in the brain organoids, as evidenced by increased histone acetylation in the presence of electromagnetic AuNPs. Consequently, electromagnetic AuNPs offer a promising in vitro system for efficiently generating more advanced human brain organoids that closely resemble the complexity of the human brain.

Transcriptional activation of endogenous Oct4 via the CRISPR/dCas9 activator ameliorates Hutchinson-Gilford progeria syndrome in mice.

Partial cellular reprogramming via transient expression of Oct4, Sox2, Klf4, and c-Myc induces rejuvenation and reduces aged-cell phenotypes. In this study, we found that transcriptional activation of the endogenous Oct4 gene by using the CRISPR/dCas9 activator system can efficiently ameliorate hallmarks of aging in a mouse model of Hutchinson-Gilford progeria syndrome (HGPS). We observed that the dCas9-Oct4 activator induced epigenetic remodeling, as evidenced by increased H3K9me3 and decreased H4K20me3 levels, without tumorization. Moreover, the progerin accumulation in HGPS aorta was significantly suppressed by the dCas9 activator-mediated Oct4 induction. Importantly, CRISPR/dCas9-activated Oct4 expression rescued the HGPS-associated vascular pathological features and lifespan shortening in the mouse model. These results suggest that partial rejuvenation via CRISPR/dCas9-mediated Oct4 activation can be used as a novel strategy in treating geriatric diseases.

Single-cell RNA-sequencing identifies disease-associated oligodendrocytes in male APP NL-G-F and 5XFAD mice.

Alzheimer's disease (AD) is associated with progressive neuronal degeneration as amyloid-beta (Aß) and tau proteins accumulate in the brain. Glial cells were recently reported to play an important role in the development of AD. However, little is known about the role of oligodendrocytes in AD pathogenesis. Here, we describe a disease-associated subpopulation of oligodendrocytes that is present during progression of AD-like pathology in the male AppNL-G-F and male 5xFAD AD mouse brains and in postmortem AD human brains using single-cell RNA sequencing analysis. Aberrant Erk1/2 signaling was found to be associated with the activation of disease-associated oligodendrocytes (DAOs) in male AppNL-G-F mouse brains. Notably, inhibition of Erk1/2 signaling in DAOs rescued impaired axonal myelination and ameliorated Aß-associated pathologies and cognitive decline in the male AppNL-G-F AD mouse model.

Safety, high-performing and effects of the N/P ratio of a solid lithium ion battery using PEGDME based polymer electrolytes.

In this study, we report on the electrochemical properties of a solid state lithium ion battery (LIB) using a poly (ethylene glycol) dimethyl ether (PEGDME)-based solid polymer electrolyte (P-SPE). The LIB is prepared using a LiFePO4 (LFP) cathode and graphite anode material with P-SPE, and the kinetic properties of the lithium ions in the P-SPE are investigated. The synthesized P-SPE is shown to be suitable solid polymer electrolyte candidate for LIB applications. LFP and graphite are selected as electrode materials to validate their effectiveness in different battery cells with respect to their high energy density and inherent safety. The five-layer stacked 5 × 6 cm2 pouch-type LIB demonstrates a high capacity of 90 mAh (0.6 mAh/cm2) or more in the initial cycle, and it shows cycle stability with a capacity decrease of 20% over 500 cycles. We test the manufactured pouch-type full cells under extreme conditions (e. g., cutting, crushing and exposure of the battery cell to the atmosphere). LIBs using the developed P-SPE are promising solid polymer electrolyte candidates for wearable LIB as well as high energy LIB applications.

APOE ε4-dependent effects on the early amyloid pathology in induced neurons of patients with Alzheimer's disease.

BACKGROUND: The ε4 allele of apolipoprotein E (APOE ε4) is the strongest known genetic risk factor for late-onset Alzheimer's disease (AD), associated with amyloid pathogenesis. However, it is not clear how APOE ε4 accelerates amyloid-beta (Aß) deposition during the seeding stage of amyloid development in AD patient neurons. METHODS: AD patient induced neurons (iNs) with an APOE ε4 inducible system were prepared from skin fibroblasts of AD patients. Transcriptome analysis was performed using RNA isolated from the AD patient iNs expressing APOE ε4 at amyloid-seeding and amyloid-aggregation stages. Knockdown of IGFBP3 was applied in the iNs to investigate the role of IGFBP3 in the APOE ε4-mediated amyloidosis. RESULTS: We optimized amyloid seeding stage in the iNs of AD patients that transiently expressed APOE ε4. Remarkably, we demonstrated that Aß  pathology was aggravated by the induction of APOE ε4 gene expression at the amyloid early-seeding stage in the iNs of AD patients. Moreover, transcriptome analysis in the early-seeding stage revealed that IGFBP3 was functionally important in the molecular pathology of APOE ε4-associated AD. CONCLUSIONS: Our findings suggest that the presence of APOE ε4 at the early Aß-seeding stage in patient iNs is critical for aggravation of sporadic AD pathology. These results provide insights into the importance of APOE ε4 expression for the progression and pathogenesis of sporadic AD.

CRISPR/dCas9-Dnmt3a-mediated targeted DNA methylation of APP rescues brain pathology in a mouse model of Alzheimer's disease.

BACKGROUND: Aberrant DNA methylation patterns have been observed in neurodegenerative diseases, including Alzheimer's disease (AD), and dynamic changes in DNA methylation are closely associated with the onset and progression of these diseases. Particularly, hypomethylation of the amyloid precursor protein gene (APP) has been reported in patients with AD. METHODS: In this study, we used catalytically inactivated Cas9 (dCas9) fused with Dnmt3a for targeted DNA methylation of APP, and showed that the CRISPR/dCas9-Dnmt3a-mediated DNA methylation system could efficiently induce targeted DNA methylation of APP both in vivo and in vitro. RESULTS: We hypothesized that the targeted methylation of the APP promoter might rescue AD-related neuronal cell death by reducing APP mRNA expression. The cultured APP-KI mouse primary neurons exhibited an altered DNA-methylation pattern on the APP promoter after dCas9-Dnmt3a treatment. Likewise, the APP mRNA level was significantly reduced in the dCas9-Dnmt3a-treated wild-type and APP-KI mouse primary neurons. We also observed decreased amyloid-beta (Aß) peptide level and Aß42/40 ratio in the dCas9-Dnmt3a-treated APP-KI mouse neurons compared to the control APP-KI mouse neurons. In addition, neuronal cell death was significantly decreased in the dCas9-Dnmt3a-treated APP-KI mouse neurons. Furthermore, the in vivo methylation of APP in the brain via dCas9-Dnmt3a treatment altered Aß plaques and attenuated cognitive and behavioral impairments in the APP-KI mouse model. CONCLUSIONS: These results suggest that the targeted methylation of APP via dCas9-Dnmt3a treatment can be a potential therapeutic strategy for AD.

Systematic and mechanistic analysis of AuNP-induced nanotoxicity for risk assessment of nanomedicine.

For decades, nanoparticles (NPs) have been widely implemented in various biomedical fields due to their unique optical, thermal, and tunable properties. Particularly, gold nanoparticles (AuNPs) have opened new frontiers in sensing, targeted drug delivery, imaging, and photodynamic therapy, showing promising results for the treatment of various intractable diseases that affect quality of life and longevity. Despite the tremendous achievements of AuNPs-based approaches in biomedical applications, few AuNP-based nanomedicines have been evaluated in clinical trials, which is likely due to a shortage of understanding of the biological and pathological effects of AuNPs. The biological fate of AuNPs is tightly related to a variety of physicochemical parameters including size, shape, chemical structure of ligands, charge, and protein corona, and therefore evaluating the effects of these parameters on specific biological interactions is a major ongoing challenge. Therefore, this review focuses on ongoing nanotoxicology studies that aim to characterize the effect of various AuNP characteristics on AuNP-induced toxicity. Specifically, we focus on understanding how each parameter alters the specific biological interactions of AuNPs via mechanistic analysis of nano-bio interactions. We also discuss different cellular functions affected by AuNP treatment (e.g., cell motility, ROS generation, interaction with DNA, and immune response) to understand their potential human health risks. The information discussed herein could contribute to the safe usage of nanomedicine by providing a basis for appropriate risk assessment and for the development of nano-QSAR models.

Dormant state of quiescent neural stem cells links Shank3 mutation to autism development.

Autism spectrum disorders (ASDs) are common neurodevelopmental disorders characterized by deficits in social interactions and communication, restricted interests, and repetitive behaviors. Despite extensive study, the molecular targets that control ASD development remain largely unclear. Here, we report that the dormancy of quiescent neural stem cells (qNSCs) is a therapeutic target for controlling the development of ASD phenotypes driven by Shank3 deficiency. Using single-cell RNA sequencing (scRNA-seq) and transposase accessible chromatin profiling (ATAC-seq), we find that abnormal epigenetic features including H3K4me3 accumulation due to up-regulation of Kmt2a levels lead to increased dormancy of qNSCs in the absence of Shank3. This result in decreased active neurogenesis in the Shank3 deficient mouse brain. Remarkably, pharmacological and molecular inhibition of qNSC dormancy restored adult neurogenesis and ameliorated the social deficits observed in Shank3-deficient mice. Moreover, we confirmed restored human qNSC activity rescues abnormal neurogenesis and autism-like phenotypes in SHANK3-targeted human NSCs. Taken together, our results offer a novel strategy to control qNSC activity as a potential therapeutic target for the development of autism.

Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI promotes neuronal rejuvenation in aged mice.

An increasing number of studies have indicated that alterations in gut microbiota affect brain function, including cognition and memory ability, via the gut-brain axis. In this study, we aimed to determine the protective effect of Bifidobacterium bifidum BGN4 (B. bifidum BGN4) and Bifidobacterium longum BORI (B. longum BORI) on age-related brain damage in mice. We found that administration of B. bifidum BGN4 and B. longum BORI effectively elevates brain-derived neurotrophic factor expression which was mediated by increased histone 3 lysine 9 trimethylation. Furthermore, administration of probiotic supplementation reversed the DNA damage and apoptotic response in aged mice and also improved the age-related cognitive and memory deficits of these mice. Taken together, the present study highlights the anti-aging effects of B. bifidum BGN4 and B. longum BORI in the aged brain and their beneficial effects for age-related brain disorders.

Activation of melatonin receptor 1 by CRISPR-Cas9 activator ameliorates cognitive deficits in an Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of neurotoxic beta-amyloid (Aß) in the brain. Melatonin receptors have been reported to associate with aging and AD, and their expression decreased with the progression of AD. As an alternative to AD treatment, overexpression of melatonin receptors may lead to melatonin-like effects to treat alleviate the symptoms of AD. Here, we successfully activated the type 1 melatonin receptor (Mt1) in vivo brain using a Cas9 activator as a novel AD therapeutic strategy. The Cas9 activator efficiently activated the endogenous Mt1 gene in the brain. Activation of Mt1 via Cas9 activators modulated anti-amyloidogenic and anti-inflammatory roles in 5xFAD AD mice brain. Moreover, activation of Mt1 with the CRISPR/Cas9 activator improved cognitive deficits in an AD model. These results demonstrated the therapeutic potential of melatonin receptor activation via CRISPR/Cas9 activator for AD.

In vivo therapeutic genome editing via CRISPR/Cas9 magnetoplexes for myocardial infarction.

CRISPR/Cas9-mediated gene-editing technology has gained attention as a new therapeutic method for intractable diseases. However, the use of CRISPR/Cas9 for cardiac conditions such as myocardial infarction remains challenging due to technical and biological barriers, particularly difficulties in delivering the system and targeting genes in the heart. In the present study, we demonstrated the in vivo efficacy of the CRISPR/Cas9 magnetoplexes system for therapeutic genome editing in myocardial infarction. First, we developed CRISPR/Cas9 magnetoplexes that magnetically guided CRISPR/Cas9 system to the heart for efficient in vivo therapeutic gene targeting during heart failures. We then demonstrated that the in vivo gene targeting of miR34a via these CRISPR/Cas9 magnetoplexes in a mouse model of myocardial infarction significantly improved cardiac repair and regeneration to facilitate improvements in cardiac function. These results indicated that CRISPR/Cas9 magnetoplexes represent an effective in vivo therapeutic gene-targeting platform in the myocardial infarction of heart, and that this strategy may be applicable for the treatment of a broad range of cardiac failures.

Transcriptional activation with Cas9 activator nanocomplexes rescues Alzheimer's disease pathology.

CRISPR/Cas9-mediated gene activation is a potential therapeutic strategy that does not induce double-strand break (DSB) DNA damage. However, in vivo gene activation via a Cas9 activator remains a challenge, currently limiting its therapeutic applications. We developed a Cas9 activator nanocomplex that efficiently activates an endogenous gene in the brain in vivo, suggesting its possible application in novel therapeutics. We demonstrated a potential treatment application of the Cas9 activator nanocomplex by activating Adam10 in the mouse brain without introducing insertions and deletions (inDels). Remarkably, in vivo activation of Adam10 with the Cas9 activator nanocomplex improved cognitive deficits in an Alzheimer's disease (AD) mouse model. These results demonstrate the therapeutic potential of Cas9 activator nanocomplexes for a wide range of neurological diseases.

Electromagnetized gold nanoparticles improve neurogenesis and cognition in the aged brain.

Adult neurogenesis is the lifelong process by which new neurons are generated in the dentate gyrus. However, adult neurogenesis capacity decreases with age, and this decrease is closely linked to cognitive and memory decline. Our study demonstrated that electromagnetized gold nanoparticles (AuNPs) promote adult hippocampal neurogenesis, thereby improving cognitive function and memory consolidation in aged mice. According to single-cell RNA sequencing data, the numbers of neural stem cells (NSCs) and neural progenitors were significantly increased by electromagnetized AuNPs. Additionally, electromagnetic stimulation resulted in specific activation of the histone acetyltransferase Kat2a, which led to histone H3K9 acetylation in adult NSCs. Moreover, in vivo electromagnetized AuNP stimulation efficiently increased hippocampal neurogenesis in aged and Hutchinson-Gilford progeria mouse brains, thereby alleviating the symptoms of aging. Therefore, our study provides a proof-of-concept for the in vivo stimulation of hippocampal neurogenesis using electromagnetized AuNPs as a promising therapeutic strategy for the treatment of age-related brain diseases.

Administration of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI Improves Cognitive and Memory Function in the Mouse Model of Alzheimer's Disease.

Recent evidence indicates that gut microbiota could interact with the central nervous system and affect brain function, including cognition and memory. In this study, we investigated whether Bifidobacterium bifidum BGN4 (B. bifidum BGN4) and Bifidobacterium longum BORI (B. longum BORI) alleviated the pathological features in a mouse model of Alzheimer's disease (AD). Administration of B. bifidum BGN4 and B. longum BORI effectively suppressed amyloidosis and apoptotic processes and improved synaptic plasticity by ameliorating the neuroinflammatory response and BDNF expression. Moreover, behavioral tests indicated that B. bifidum BGN4 and B. longum BORI attenuated the cognitive and memory disability of AD mice. Taken together, the present study highlights the therapeutic potential of B. bifidum BGN4 and B. longum BORI for suppressing the pathological features of AD.

Color of Copper/Copper Oxide.

Stochastic inhomogeneous oxidation is an inherent characteristic of copper (Cu), often hindering color tuning and bandgap engineering of oxides. Coherent control of the interface between metal and metal oxide remains unresolved. Coherent propagation of an oxidation front in single-crystal Cu thin film is demonstrated to achieve a full-color spectrum for Cu by precisely controlling its oxide-layer thickness. Grain-boundary-free and atomically flat films prepared by atomic-sputtering epitaxy allow tailoring of the oxide layer with an abrupt interface via heat treatment with a suppressed temperature gradient. Color tuning of nearly full-color red/green/blue indices is realized by precise control of the oxide-layer thickness; the samples cover ≈50.4% of the standard red/green/blue color space. The color of copper/copper oxide is realized by the reconstruction of the quantitative yield color from the oxide "pigment" (complex dielectric functions of Cu2 O) and light-layer interference (reflectance spectra obtained from the Fresnel equations) to produce structural color. Furthermore, laser-oxide lithography is demonstrated with micrometer-scale linewidth and depth through local phase transformation to oxides embedded in the metal, providing spacing necessary for semiconducting transport and optoelectronics functionality.

Efficiency of magnetic resonance imaging for diagnosing unstable ligament injuries around the thumb metacarpophalangeal joint: A comparison to arthroscopy.

PURPOSE: This study aimed to assess the accuracy of MRI in identifying ulnar collateral ligament (UCL), radial collateral ligament (RCL), and volar plate (VP) injuries of the metacarpophalangeal joint (MCPJ) of the thumb by comparing with diagnostic arthroscopy. METHODS: A total of 56 consecutive patients (56 thumbs) who underwent arthroscopy of MCPJ of thumb were enrolled. MRI findings reviewed by consensus reading of two blinded radiologists were compared with arthroscopic examination. Statistical data, including sensitivity, specificity, accuracy, were analyzed. Additionally, the performance characteristics between 3.0-tesla (39 thumbs) and 1.5-tesla (17 thumbs) MRI and acute (≤4 weeks after injury) and chronic (>4 weeks) injuries were compared. RESULTS: Of the 56 thumbs, 38 thumbs (67.9%) showed complete correspondence between MRI and arthroscopic findings. The sensitivity, specificity and accuracy of MRI for detecting UCL injuries were 78.8%, 87.0%, and 82.1%, respectively. The sensitivity, specificity and accuracy of MRI for detecting RCL injuries were 85.7%, 91.4%, and 85.7%, respectively. The sensitivity, specificity, and accuracy of MRI for detecting VP injuries were 89.5%, 89.2%, and 81.0%, respectively. 3.0-tesla MRI showed higher correspondence with arthroscopic observation (76.9%) than 1.5-tesla MRI (47.1%) (p = 0.028). For acute injuries, 78.4% showed complete correspondence between MRI and arthroscopic findings, whereas 47.4% with chronic injuries revealed complete agreement (p = 0.019). CONCLUSION: Overall, MRI is moderately effective in evaluating ligamentous lesions around MCPJ of thumb, but MRI is more sensitive in diagnosing acute injuries. Furthermore, 3.0-tesla MRI can provide results with better accuracy for diagnosing ligamentous lesions around MCPJ of thumb. However, the sensitivity and the specificity are not applicable to all ligament injuries, but only the severe one which would agree for surgical options.

Prognostic Factors Affecting Clinical Outcomes of Arthroscopic Assisted Reduction and Volar Plating through Preservation of Pronator Quadratus for Intra-Articular Distal Radius Fracture.

Background: This study aimed to evaluate the clinical and radiological outcomes following an arthroscopic-assisted reduction and volar plating (AR-VP) surgery through pronator quadratus (PQ) preservation for treating intra-articular distal radius fractures (IA-DRFs) and to assess prognostic factors that affect functional outcomes. Methods: Between March 2014 and February 2017, 54 patients who had intra-articular DRF and underwent AR-VP through the PQ preservation technique and completed 1-year follow-up were enrolled. Patients were divided into the satisfactory group (excellent and good results) and an unsatisfactory group (fair and poor results) based on the modified Mayo Wrist Scoring System (MMWS) scored at 1-year follow-up to determinate prognostic factors that affected clinical outcomes. Patients' demographics, clinical outcome measures (VAS, DASH, PRWE, etc.), and pre-and post-operative radiographic parameters were analyzed. Results: The outcomes according to MMWS were 10 excellent, 22 good, 14 fair, and 8 poor. A univariate analysis showed a significant difference between the groups (p < .05) for all radiographic parameters, sex, and the presence of an intra-articular comminution. In the multivariate analysis, female gender, presence of an intra-articular comminution, and difference of palmar articular tilt compared to uninjured wrist (> 20.1°) at trauma were considered as significant poor prognostic factors of functional outcome. Conclusions: AR-VP surgery through PQ preservation for intra-articular DRFs has reliable clinical and radiological outcomes. However, female gender, presence of an intra-articular comminution, and difference of palmar articular tilt compared to the uninjured wrist (> 20.1°) at initial injury were considered poor prognostic factors for AR-VP through PQ preservation for intra-articular DRF.

Epitranscriptomic N6-Methyladenosine Modification Is Required for Direct Lineage Reprogramming into Neurons.

N6-methyladenosine (m6A), a conserved epitranscriptomic modification of eukaryotic mRNA (mRNA), plays a critical role in a variety of biological processes. Here, we report that m6A modification plays a key role in governing direct lineage reprogramming into induced neuronal cells (iNs). We found that m6A modification is required for the remodeling of specific mRNAs required for the neuronal direct conversion. Inhibition of m6A methylation by Mettl3 knockdown decreased the efficiency of direct lineage reprogramming, whereas increased m6A methylation by Mettl3 overexpression increased the efficiency of iN generation. Moreover, we found that transcription factor Btg2 is a functional target of m6A modification for efficient iN generation. Taken together, our results suggest the importance of establishing epitranscriptomic remodeling for the cell fate conversion into iNs.

Rad50 mediates DNA demethylation to establish pluripotent reprogramming.

DNA demethylation is characterized by the loss of methyl groups from 5-methylcytosine, and this activity is involved in various biological processes in mammalian cell development and differentiation. In particular, dynamic DNA demethylation in the process of somatic cell reprogramming is required for successful iPSC generation. In the present study, we reported the role of Rad50 in the DNA demethylation process during somatic cell reprogramming. We found that Rad50 was highly expressed in pluripotent stem cells and that Rad50 regulated global DNA demethylation levels. Importantly, the overexpression of Rad50 resulted in the enhanced efficiency of iPSC generation via increased DNA demethylation, whereas Rad50 knockdown led to DNA hypermethylation, which suppressed somatic cell reprogramming into iPSCs. Moreover, we found that Rad50 associated with Tet1 to facilitate the DNA demethylation process in pluripotent reprogramming. Therefore, our findings highlight the novel role of Rad50 in the DNA demethylation process during somatic cell reprogramming.