Local Structures of Ex-Solved Nanoparticles Identified by Machine-Learned Potentials.

In this study, we identify the local structures of ex-solved nanoparticles using machine-learned potentials (MLPs). We develop a method for training machine-learned potentials by sampling local structures of heterointerface configurations as a training set with its efficacy tested on the Ni/MgO system, illustrating that the error in interface energy is only 0.004 eV/Å2. Using the developed scheme, we train an MLP for the Ni/La0.5Ca0.5TiO3 ex-solution system and identify the local structures for both exo- and endo-type particles. The established model aligns well with the experimental observations, accurately predicting a nucleation size of 0.45 nm. Lastly, the density functional theory calculations on the established atomistic model verify that the kinetic barrier for the dry reforming of methane are substantially reduced by 0.49 eV on the ex-solved catalysts compared to that on the impregnated catalysts. Our findings offer insights into the local structures, growth mechanisms, and underlying origin of the catalytic properties of ex-solved nanoparticles.

Bmp4-Msx1 signaling and Osr2 control tooth organogenesis through antagonistic regulation of secreted Wnt antagonists.

Mutations in MSX1 cause craniofacial developmental defects, including tooth agenesis, in humans and mice. Previous studies suggest that Msx1 activates Bmp4 expression in the developing tooth mesenchyme to drive early tooth organogenesis. Whereas Msx1-/- mice exhibit developmental arrest of all tooth germs at the bud stage, mice with neural crest-specific inactivation of Bmp4 (Bmp4ncko/ncko), which lack Bmp4 expression in the developing tooth mesenchyme, showed developmental arrest of only mandibular molars. We recently demonstrated that deletion of Osr2, which encodes a zinc finger transcription factor expressed in a lingual-to-buccal gradient in the developing tooth bud mesenchyme, rescued molar tooth morphogenesis in both Msx1-/- and Bmp4ncko/ncko mice. In this study, through RNA-seq analyses of the developing tooth mesenchyme in mutant and wildtype embryos, we found that Msx1 and Osr2 have opposite effects on expression of several secreted Wnt antagonists in the tooth bud mesenchyme. Remarkably, both Dkk2 and Sfrp2 exhibit Osr2-dependent preferential expression on the lingual side of the tooth bud mesenchyme and expression of both genes was up-regulated and expanded into the tooth bud mesenchyme in Msx1-/- and Bmp4ncko/ncko mutant embryos. We show that pharmacological activation of canonical Wnt signaling by either lithium chloride (LiCl) treatment or by inhibition of DKKs in utero was sufficient to rescue mandibular molar tooth morphogenesis in Bmp4ncko/ncko mice. Furthermore, whereas inhibition of DKKs or inactivation of Sfrp2 alone was insufficient to rescue tooth morphogenesis in Msx1-/- mice, pharmacological inhibition of DKKs in combination with genetic inactivation of Sfrp2 and Sfrp3 rescued maxillary molar morphogenesis in Msx1-/- mice. Together, these data reveal a novel mechanism that the Bmp4-Msx1 pathway and Osr2 control tooth organogenesis through antagonistic regulation of expression of secreted Wnt antagonists.

A Rare Nasopharyngeal Teratoma Arising From the Vomer.

Teratomas are rare germ cell neoplasms derived from the 3 germinal layers (ectoderm, mesoderm, and endoderm). Nasopharyngeal teratoma is a very rare teratoma arising anywhere from the oronasal cavity, regarded as an expanding, avity filling lesion, with a high mortality rate because of severe airway obstruction, especially in the neonatal period and make up only 2% of all teratomas. The authors present a case of an infant girl with a single, finger-like, hairy teratoma arising from the vomer and protruding from the mouth with bilateral complete cleft palate, cleft lip, and cleft alveolus. Complete intraoral resection of the teratoma and cleft lip repair was conducted simultaneously. Reconstruction of the cleft palate was performed at a later stage. Recurrence occurred 9 months after surgery and extended complete surgical excision was performed after recurrence, with no recurrence observed again to date. Histopathologic examination confirmed the diagnosis of congenital mature teratoma.

Hippo pathway/Yap regulates primary enamel knot and dental cusp patterning in tooth morphogenesis.

The shape of an individual tooth crown is primarily determined by the number and arrangement of its cusps, i.e., cusp patterning. Enamel knots that appear in the enamel organ during tooth morphogenesis have been suggested to play important roles in cusp patterning. Animal model studies have shown that the Hippo pathway effector Yap has a critical function in tooth morphogenesis. However, the role of the Hippo pathway/Yap in cusp patterning has not been well documented and its specific roles in tooth morphogenesis remain unclear. Here, we provide evidence that Yap is a key mediator in tooth cusp patterning. We demonstrate a correlation between Yap localization and cell proliferation in developing tooth germs. We also show that, between the cap stage and bell stage, Yap is crucial for the suppression of the primary enamel knot and for the patterning of secondary enamel knots, which are the future cusp regions. When Yap expression is stage-specifically knocked down during the cap stage, the activity of the primary enamel knot persists into the bell-stage tooth germ, leading to ectopic cusp formation. Our data reveal the importance of the Hippo pathway/Yap in enamel knots and in the proper patterning of tooth cusps.

Requirement of Runx3 in pulmonary vasculogenesis.

Runx3 is essential for normal vertebrate lung development and Runx3 knockout (KO) mice die within 24 h after birth because of various organ defects including defects in alveolar expansion. For proper early lung development, vasculogenesis and angiogenesis are necessary in humans. Previous studies have reported that various signaling molecules, such as CD31, VEGF and vWF, are closely related to lung vasculogenesis and angiogenesis. To confirm the relationship between Runx3-related lung defects and vasculogenesis, the localization of various blood vessel markers is examined in WT and Runx3 KO mouse lungs at PN1. Our results indicate that CD31, VEGF and vWF were dramatically up-regulated by a loss of Runx3 during lung development. Moreover, U0126, a MEK inhibitor, rescued the lung phenotype and vascularization by regulation of ERK signaling. Therefore, it was concluded that lung vasculogenesis and angiogenesis were induced in the Runx3 KO mouse, which shows lung defects, by increased CD31, VEGF and vWF.

Mll4 regulates tooth enamel development.

Amelogenesis, or enamel development, is a highly regulated process that leads to the formation of tooth enamel, which is critical for protecting teeth from decay and wear. Disruptions in the amelogenesis process can result in amelogenesis imperfecta, a group of genetic conditions characterized by inadequately formed enamel. This condition can include enamel hypoplasia, marked by thinning or underdevelopment of the enamel layer. Mutations in the MLL4 (KMT2D) gene, which encodes a histone H3-lysine 4-methyltransferase, are associated with Kabuki syndrome, a developmental disorder that can involve dental anomalies such as enamel hypoplasia. However, the specific role of MLL4 in amelogenesis and its underlying mechanisms remain poorly understood. To investigate the role of Mll4 in amelogenesis, we generated a conditional knockout mouse line with an ectoderm-specific deletion of Mll4 (Krt14-Cre;Mll4 fl/fl , or Mll4-cKO) and examined the gross, radiographic, histological, cellular, and molecular features in these mice. Micro-computed tomography and scanning electron microscopy analyses revealed that adult Mll4-cKO mice exhibited 100% penetrant amelogenesis imperfecta, characterized by hypoplastic and hypomineralized enamel, partially phenocopying human Kabuki syndrome. Additionally, Mll4-cKO neonates developed molar tooth germs with minor cusp shape alterations and mild delays in ameloblast differentiation at birth. RNA-seq analysis of the first molar tooth germ at birth revealed that approximately 33.7% of known amelogenesis-related genes were significantly downregulated in the Mll4-cKO teeth. Intersection with Mll4 CUT&RUN-seq results identified 8 overlapping genes directly targeted by Mll4. Re-analysis of a single-cell RNA-seq dataset in the developing mouse incisor teeth revealed distinct roles for these genes in Mll4-regulated differentiation across various cell subtypes within the dental epithelium. Among these genes, Satb1 and Sp6 are likely directly targeted by Mll4 during the differentiation of pre-ameloblasts into ameloblasts. Taken together, we propose that Mll4 plays a crucial role in amelogenesis by directly activating key genes involved in ameloblast differentiation.

Mll4 regulates postnatal palate growth and midpalatal suture development.

MLL4, also known as KMT2D, is a histone methyltransferase that acts as an important epigenetic regulator during various organogenesis programs. Mutations in the MLL4 gene are the major cause for Kabuki syndrome, a human developmental disorder that involves craniofacial birth defects, including anomalies in the palate. The purpose of this study was to investigate the role of Mll4 and the underlying mechanisms in the development and growth of the palate. We generated a novel conditional knockout (cKO) mouse model with tissue-specific deletion of Mll4 in the palatal mesenchyme. By using micro-computed tomography (CT), histology, cell mechanism assays, and gene expression analysis approaches, we examined the development and growth of the palate in the Mll4-cKO mice. Gross intra-oral examination at adult stages showed that Mll4-cKO mice had defects along the midline of the palate, which included disrupted rugae pattern and widened midpalatal suture. Micro-CT-based skeletal analysis in the adult mice revealed that the overall palate width was decreased in the Mll4-cKO mice. By using whole-mount and histological staining approaches at perinatal stages, we identified that the midline defects started to appear as early as 1 day prior to birth, manifesting initially as a widened midpalatal suture, accompanied by increased cell apoptosis in the suture mesenchyme cells. Genome-wide analysis of mRNA expression in the midpalatal suture tissue showed that Mll4 is essential for timely expression of major genes for cartilage development, such as Col2a1 and Acan, at birth. These results were validated through immunofluorescence staining, confirming that the expression of chondrogenic markers Sox9 and Col2a1 were markedly decreased, whereas that of the osteogenic marker Runx2 remained unchanged, in the midpalatal suture of the Mll4-cKO mice. Indeed, time-course histological analysis during postnatal palate growth revealed retardation in the development of the suture cartilage in the Mll4-cKO mice. In parallel, time-course micro-CT analysis during postnatal palatogenesis confirmed a transverse growth deficit in the palate of the Mll4-cKO mice. Taken together, our results show that Mll4 is essential for timely occurrence of key cellular and molecular events that lead to proper midpalatal suture development and palate growth.

Retinoic acid signaling and the initiation of mammary gland development.

Retinoic acid receptors (RARs), which are involved in retinoic acid signal transduction, are essential for maintaining the differentiated state of epithelial tissues. Mammary glands are skin appendages whose development is initiated through continuous cell-cell interactions between the ectoderm and the adjacent mesenchyme. Considerable progress has been made in elucidating the molecular basis of these interactions in mammary gland formation in mouse embryos, including the network of initiating signals comprising Fgfs, Wnts and Bmps involved in gland positioning and the transcription factors, Tbx3 and Lef1, essential for mammary gland development. Here, we provide evidence that retinoic acid signaling may also be involved in mammary gland development. We documented the expression of gene-encoding enzymes that produce retinoic acid (Raldh2) and enzymes that degrade it (Cyp26a1, Cyp26b1). We also analyzed the expression of RAR-ß, a direct transcriptional target of retinoic acid signaling. Raldh2 and RAR-ß were expressed in E10-E10.5 mouse embryos in somites adjacent to the flank region where mammary buds 2, 3 and 4 develop. These expression patterns overlapped with that of Fgf10, which is known to be required for mammary gland formation. RAR-ß was also expressed in the mammary mesenchyme in E12 mouse embryos; RAR-ß protein was expressed in the mammary epithelium and developing fat pad. Retinoic acid levels in organ cultures of E10.5 mouse embryo flanks were manipulated by adding either retinoic acid or citral, a retinoic acid synthesis inhibitor. Reduced retinoic acid synthesis altered the expression of genes involved in retinoic acid homeostasis and also demonstrated that retinoic acid signaling is required for Tbx3 expression, whereas high levels of retinoic acid signaling inhibited Bmp4 expression and repressed Wnt signaling. The results of the experiments using RNAi against Tbx3 and Wnt10b suggested feedback interactions that regulate retinoic acid homeostasis in mammary gland-forming regions. We produced a molecular model for mammary gland initiation that incorporated retinoic acid signaling.

Long-lifetime water-washable ceramic catalyst filter for air purification.

Particulate matter (PM) and volatile organic compounds (VOCs) are recognised as hazardous air pollutants threatening human health. Disposable filters are generally used for air purification despite frequent replacement and waste generation problems. However, the development of a novel regenerable and robust filter for long-term use is a huge challenge. Here, we report on a new class of facile water-washing regenerable ceramic catalyst filters (CCFs), developed to simultaneously remove PM (>95%) and VOCs (>82%) in single-pass and maximized space efficiency by coating the inner and outer filter channels with an inorganic membrane and a Cu2O/TiO2 photocatalyst, respectively. The CCFs reveal four-fold increase in the maximum dust loading capacity (approximately 20 g/L) in relation to conventional filters (5 g/L), and can be reused after ten regeneration capability with simple water washing retaining initial PM and VOC removal performances. Thus, the CCFs can be well-suited for indoor and outdoor air purification for 20 years, which shows a huge increase in lifetime compared to the 6-month lifespan of conventional filters. Finally, we believe that the development and implementation of CCFs for air purification can open new avenues for sustainable technology through renewability and zero-waste generation.

BMP4 signaling mediates Zeb family in developing mouse tooth.

Tooth morphogenesis is regulated by sequential and reciprocal interaction between oral epithelium and neural-crest-derived ectomesenchyme. The interaction is controlled by various signal molecules such as bone morphogenetic protein (BMP), Hedgehog, fibroblast growth factor (FGF), and Wnt. Zeb family is known as a transcription factor, which is essential for neural development and neural-crest-derived tissues, whereas the role of the Zeb family in tooth development remains unclear. Therefore, this study aimed to investigate the expression profiles of Zeb1 and Zeb2 during craniofacial development focusing on mesenchyme of palate, hair follicle, and tooth germ from E12.5 to E16.5. In addition, we examined the interaction between Zeb family and BMP4 during tooth development. Both Zeb1 and Zeb2 were expressed at mesenchyme of the palate, hair follicle, and tooth germ throughout the stages. In the case of tooth germ at the cap stage, the expression of Zeb1 and Zeb2 was lost in epithelium-separated dental mesenchyme. However, the expression of Zeb1 and Zeb2 in the dental mesenchyme was recovered by Bmp4 signaling via BMP4-soaked bead and tissue recombination. Our results suggest that Zeb1 and Zeb2, which were mediated by BMP4, play an important role in neural-crest-derived craniofacial organ morphogenesis, such as tooth development.

MiR-200b is involved in Tgf-ß signaling to regulate mammalian palate development.

Various cellular and molecular events are involved in palatogenesis, including apoptosis, epithelial-mesenchymal transition (EMT), cell proliferation, and cell migration. Smad2 and Snail, which are well-known key mediators of the transforming growth factor beta (Tgf-ß) pathway, play a crucial role in the regulation of palate development. Regulatory effects of microRNA 200b (miR-200b) on Smad2 and Snail in palatogenesis have not yet been elucidated. The aim of this study is to determine the relationship between palate development regulators miR-200b and Tgf-ß-mediated genes. Expression of miR-200b, E-cadherin, Smad2, and Snail was detected in the mesenchyme of the mouse palate, while miR-200b was expressed in the medial edge epithelium (MEE) and palatal mesenchyme. After the contact of palatal shelves, miR-200b was no longer expressed in the mesenchyme around the fusion region. The binding activity of miR-200b to both Smad2 and Snail was examined using a luciferase assay. MiR-200b directly targeted Smad2 and Snail at both cellular and molecular levels. The function of miR-200b was determined by overexpression via a lentiviral vector in the palatal shelves. Ectopic expression of miR-200b resulted in suppression of these Tgf-ß-mediated regulators and changes of apoptosis and cell proliferation in the palatal fusion region. These results suggest that miR-200b plays a crucial role in regulating the Smad2, Snail, and in apoptosis during palatogenesis by acting as a direct non-coding, influencing factor. Furthermore, the molecular interactions between miR-200b and Tgf-ß signaling are important for proper palatogenesis and especially for palate fusion. Elucidating the mechanism of palatogenesis may aid the design of effective gene-based therapies for the treatment of congenital cleft palate.

Parasitic leiomyoma in the trocar site after laparoscopic myomectomy: A case report.

BACKGROUND: Laparoscopic myomectomy is increasingly used for resecting gynecological tumors. Leiomyomas require morcellation for retrieval from the peritoneal cavity. However, morcellated fragments may implant on the peritoneal cavity during retrieval. These fragments may receive a new blood supply from an adjacent structure and develop into parasitic leiomyomas. Parasitic leiomyomas can occur spontaneously or iatrogenically; however, trocar-site implantation is an iatrogenic complication of laparoscopic uterine surgery. We describe a parasitic leiomyoma in the trocar-site after laparoscopic myomectomy with power morcellation. CASE SUMMARY: A 50-year-old woman presented with a palpable abdominal mass without significant medical history. The patient had no related symptoms, such as abdominal pain. Computed tomography findings revealed a well-defined contrast-enhancing mass measuring 2.2 cm, and located on the trocar site of the left abdominal wall. She had undergone laparoscopic removal of uterine fibroids with power morcellation six years ago. The differential diagnosis included endometriosis and neurogenic tumors, such as neurofibroma. The radiologic diagnosis was a desmoid tumor, and surgical excision of the mass on the abdominal wall was successfully performed. The patient recovered from the surgery without complications. Histopathological examination revealed that the specimen resected from the trocar site was a uterine leiomyoma. CONCLUSION: Clinicians should consider the risks and benefits of laparoscopic vs laparotomic myomectomy for gynecological tumors. Considerable caution must be exercised for morcellation to avoid excessive tissue fragmentation.

Carbon-free high-performance cathode for solid-state Li-O2 battery.

The development of a cathode for solid-state lithium-oxygen batteries has been hindered in practice by a low capacity and limited cycle life despite their potential for high energy density. Here, a previously unexplored strategy is proposed wherein the cathode delivers a specific capacity of 200 milliampere hour per gram over 665 discharge/charge cycles, while existing cathodes achieve only ~50 milliampere hour per gram and ~100 cycles. A highly conductive ruthenium-based composite is designed as a carbon-free cathode by first-principles calculations to avoid the degradation associated with carbonaceous materials, implying an improvement in stability during the electrochemical cycling. In addition, water vapor is added into the main oxygen gas as an additive to change the discharge product from growth-restricted lithium peroxide to easily grown lithium hydroxide, resulting in a notable increase in capacity. Thus, the proposed strategy is effective for developing reversible solid-state lithium-oxygen batteries with high energy density.

Shh signaling is essential for rugae morphogenesis in mice.

Palatal ridges, or rugae palatinae, are corrugated structures observed in the hard palate region. They are found in most mammalian species, but their number and arrangement are species-specific. Nine palatal rugae are found in the mouse secondary palate. Previous studies have shown that epithelial Shh signaling in the palatal ridge plays an important role during rugae development. Moreover, Wnt family members, including LEF1, play a functional role in orofacial morphogenesis. To explore the function of Shh during rugae development, we utilized the maternal transfer of 5E1 (anti-Shh antibody) to mouse embryos. 5E1 induced abnormal rugae patterning characterized by a spotted shape of palatal ridge rather than a stripe. The expression patterns of Shh and Shh-related genes, Sostdc1, Lef1 and Ptch1, were disrupted following 5E1 injection. Moreover, rugae-specific cell proliferation and inter-rugae-specific apoptosis were affected by inhibition of Shh signaling. We hypothesize that the altered gene expression patterns and the change in molecular events caused by the inhibition of Shh signaling may have induced abnormal rugae patterning. Furthermore, we propose a reaction-diffusion model generated by Wnt, Shh and Sostdc1 signaling. In this study, we show that Sostdc1, a secreted inhibitor of the Wnt pathway, is a downstream target of Shh and hypothesize that the interaction of Wnt, Shh and Sostdc1 is a pivotal mechanism controlling the spatial patterning of palatal rugae.

Retinoic acid modulates chondrogenesis in the developing mouse cranial base.

The retinoic acid (RA) signaling pathway is known to play important roles during craniofacial development and skeletogenesis. However, the specific mechanism involving RA in cranial base development has not yet been clearly described. This study investigated how RA modulates endochondral bone development of the cranial base by monitoring the RA receptor RARγ, BMP4, and markers of proliferation, programmed cell death, chondrogenesis, and osteogenesis. We first examined the dynamic morphological and molecular changes in the sphenooccipital synchondrosis-forming region in the mouse embryo cranial bases at E12-E16. In vitro organ cultures employing beads soaked in RA and retinoid-signaling inhibitor citral were compared. In the RA study, the sphenooccipital synchondrosis showed reduced cartilage matrix and lower BMP4 expression while hypertrophic chondrocytes were replaced with proliferating chondrocytes. Retardation of chondrocyte hypertrophy was exhibited in citral-treated specimens, while BMP4 expression was slightly increased and programmed cell death was induced within the sphenooccipital synchondrosis. Our results demonstrate that RA modulates chondrocytes to proliferate, differentiate, or undergo programmed cell death during endochondral bone formation in the developing cranial base.

Innovative digital tools for new trends in teaching and assessment methods in medical and dental education.

With the goal of providing optimal care to patients, student-centered active learning and the development of clinical competency have become vital components of the education of future physicians capable of sustainably coping with future challenges. However, the shape of future medicine is dramatically changing based on advances in information and communication technology, and the current classroom model seems to have difficulties in fully preparing students for the future of medicine. New trends in teaching and assessment methods include computer-aided instruction, virtual patients, augmented reality, human patient simulations, and virtual reality for the assessment of students' competency. The digital technologies introduced in medical and dental education include Google Forms to collect students' answers, YouTube livestreaming, google art & culture (an online art museum), and choose-your-own-adventure as a story-telling technique. Innovations in digital technology will lead the way toward a revolution in medical and dental education, allowing learning to be individualized, interactive, and efficient.

Lung tissue regeneration after induced injury in Runx3 KO mice.

Runx3 is essential for normal murine lung development, and Runx3 knockout (KO) mice, which die soon after birth, exhibit alveolar hyperplasia. Wound healing, tissue repair, and regeneration mechanisms are necessary in humans for proper early lung development. Previous studies have reported that various signaling molecules, such as pErk, Tgf-beta1, CCSP, pJnk, Smad3, and HSP70 are closely related to wound healing. In order to confirm the relationship between lung defects caused by the loss of function of Runx3 and wound healing, we have localized various wound-healing markers after laser irradiation in wild-type and in Runx3 KO mouse lungs at post-natal day 1. Our results indicate that pERK, Tgf-beta1, CCSP, pJnk, and HSP70 are dramatically down-regulated by loss of Runx3 during lung wound healing. However, Smad3 is up-regulated in the Runx3 KO laser-irradiated lung region. Therefore, the lung wound-healing mechanism is inhibited in the Runx3 KO mouse, which shows abnormal lung architecture, by reduced pErk, Tgf-beta1, CCSP, pJnk, and HSP70 and by induced Smad3.

Laparoscopic Gastrectomy Using Instruments with a Minimal Diameter for Early Gastric Cancer: A Feasible Alternative to Conventional Laparoscopic Gastrectomy for Experienced Surgeons.

Background: The application of laparoscopic surgery using instruments that are 3 mm or less in diameter for patients with early gastric cancer (EGC) has not yet been established. We aimed to evaluate the feasibility and safety of laparoscopic gastrectomy using instruments with minimal diameter. Methods: We retrospectively analyzed 41 patients who underwent laparoscopic subtotal gastrectomy with D1-positive lymph node dissection for EGC. Among them, 17 patients underwent laparoscopic gastrectomy using instruments with a minimal diameter (experimental group), while 24 patients underwent conventional laparoscopic gastrectomy (control group). In the experimental group, we used two 3-mm trocars, one 5-mm trocar, and the GelPOINT® Advanced Access Platform. We compared operative outcomes between the two groups and assessed the learning curve of laparoscopic gastrectomy using instruments with minimal diameter. Results: The operative outcomes were similar between the two groups. The preoperative-to-postoperative day 2 ratio of neutrophil count in the experimental group was significantly lower than in the control group (2.07 versus 2.65; P = .038). Morbidity was not observed in the experimental group and 3 patients experienced complications in the control group, although it was not significantly different (P = .252). The operation time according to the accumulation of cases was stable without any significant change in the experimental group. Conclusions: Laparoscopic gastrectomy using instruments with minimal diameter is technically feasible and safe for EGC and could also be a good alternative to conventional laparoscopic gastrectomy to minimize the impact of surgical invasiveness when performed by experienced surgeons.

High-Energy Density Li-O2 Battery with a Polymer Electrolyte-Coated CNT Electrode via the Layer-by-Layer Method.

Li-O2 batteries have attracted considerable attention for several decades due to their high theoretical energy density (>3400 Wh/kg). However, it has not been clearly demonstrated that their actual volumetric and gravimetric energy densities are higher than those of Li-ion batteries. In previous studies, a considerable quantity of electrolyte was usually employed in preparing Li-O2 cells. In general, the electrolyte was considerably heavier than the carbon materials in the cathode, rendering the practical energy density of the Li-O2 battery lower than that of the Li-ion battery. Therefore, air cathodes with significantly smaller electrolyte quantities need to be developed to achieve a high specific energy density in Li-O2 batteries. In this study, we propose a core-shell-structured cathode material with a gel-polymer electrolyte layer covering the carbon nanotubes (CNTs). The CNTs are synthesized using the floating catalyst chemical vapor deposition method. The polymeric layer corresponding to the shell is prepared by the layer-by-layer (LbL) coating method, utilizing Li-Nafion along with PDDA-Cl [poly(diallyldimethylammonium chloride)]. Several bilayers of Li-Nafion and PDDA, on the CNT surface, are successfully prepared and characterized via X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The porous structure of the CNTs is retained after the LbL process, as confirmed by the nitrogen adsorption-desorption profile and BJH pore-size distribution analysis. This porous structure can function as an oxygen channel for facilitating the transport of oxygen molecules for reacting with the Li ions on the cathode surface. These polymeric bilayers can provide an Li-ion pathway, after absorbing a small quantity of an ionic liquid electrolyte, 0.5 M LiTFSI EMI-TFSI [1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide]. Compared to a typical cathode, where only liquid electrolytes are employed, the total quantity of electrolyte in the cathode can be significantly reduced; thereby, the overall cell energy density can be increased. A Li-O2 battery with this core-shell-structured cathode exhibited a high energy density of approximately 390 Wh/kg, which was assessed by directly weighing all of the cell components together, including the gas diffusion layer, the interlayer [a separator containing a mixture of LiTFSI, 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (PYR-14), and PDDA-TFSI], the lithium anode, and the LbL-CNT cathode. The cycle life of the LbL-CNT-based cathode was found to be 31 cycles at a limited capacity of 500 mAh/gcarbon. Although this is not an excellent performance, it is almost 2 times better than that of a CNT cathode without a polymer coating.

Sodium selenite induces superoxide-mediated mitochondrial damage and subsequent autophagic cell death in malignant glioma cells.

Malignant gliomas are resistant to various proapoptotic therapies, such as radiotherapy and conventional chemotherapy. In this study, we show that selenite is preferentially cytotoxic to various human glioma cells over normal astrocytes via autophagic cell death. Overexpression of Akt, survivin, XIAP, Bcl-2, or Bcl-xL failed to block selenite-induced cell death, suggesting that selenite treatment may offer a potential therapeutic strategy against malignant gliomas with apoptotic defects. Before selenite-induced cell death in glioma cells, disruption of the mitochondrial cristae, loss of mitochondrial membrane potential, and subsequent entrapment of disorganized mitochondria within autophagosomes or autophagolysosomes along with degradation of mitochondrial proteins were noted, showing that selenite induces autophagy in which mitochondria serve as the main target. At the early phase of selenite treatment, high levels of superoxide anion were generated and overexpression of copper/zinc superoxide dismutase or manganese superoxide dismutase, but not catalase, significantly blocked selenite-induced mitochondrial damage and subsequent autophagic cell death. Furthermore, treatment with diquat, a superoxide generator, induced autophagic cell death in glioma cells. Taken together, our study clearly shows that superoxide anion generated by selenite triggers mitochondrial damage and subsequent mitophagy, leading to irreversible cell death in glioma cells.