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To evaluate the effectiveness of electroacupuncture treatment for primary dysmenorrhea (PD), a literature review of a randomized controlled trials (RCTs) was performed where electroacupuncture was used as a treatment intervention in patients diagnosed with PD. Relevant clinical studies (N = 226) were retrieved from multiple databases according to the study inclusion/exclusion criteria, and interventions and outcomes were analyzed. As a result of the review, there were 6 RCTs which met the criteria. In all 4 studies that measured pain indicators (visual analog scales), electroacupuncture showed significantly positive changes. In addition, positive changes were observed in most indicators (MMDQ, PGF2a, PGE2, 6-keto PGF1, TXB2, clinical efficacy score, uterine arterial blood flow parameters, and blood viscosity). 2 studies showed that electroacupuncture had a stronger therapeutic effect than NSAIDs. No major side effects were reported. Electroacupuncture may be an effective and safe treatment for PD however, further RCTs are required.

PDF file, 779K, Figure S1. Expressionofp-KIT,p-AKT,andp-ERK increased according to the increased SCF concentrationin two KIT-expressingcelllines. Figure S2. Expression of KIT, p-KIT, p-AKT, and p-ERK after SCF treatment in two tumor cell lines with KIT mutation. FigureS3.Quantification of Westernblotting results for Fig.1E. FigureS4. Membranous KITexpression of DLD-1 was determined by FACS. Figure S5. Mutant KIT is not degraded after SCF treatment. Figure S6. FACS analysis of p-AKT and p-ERK expressing colon cancer cells treated with SCF and PMA. Figure S7. FACS analysis of KIT expression in the DLD-1 cells transfectedwith wild-type (Rab11-WT) or dominant-negative mutant form of Rab11 (Rab11-S25N). Figure S8. Effects of imatinibon CRC cells expressing KIT. FigureS9. DLD-1 cell number and invasion were increased after SCF and PMA treatment. FigureS10. Expression of SCF mRNA expression in CRC cell lines. Figure S11.Colon cancers expressing WT-KIT constantly generated activated KIT-SCF signaling as a result of KIT recycling in a condition of endogenous PKC-delta activation.

PDF file, 160K, Supplementary Table 1. Primer and siRNA sequences Supplementary Table 2. Clinicopathological characteristics of 250 colorectal cancers according to KIT expression.

Purpose: Abnormal signaling through receptor tyrosine kinase (RTK) moieties is important in tumorigenesis and drug targeting of colorectal cancers. Wild-type KIT (WT-KIT), a RTK that is activated upon binding with stem cell factor (SCF), is highly expressed in some colon cancers; however, little is known about the functional role of SCF-dependent KIT activation in colon cancer pathogenesis. We aimed to elucidate the conditions and roles of WT-KIT activation in colon cancer tumorigenesis.Experimental Design: Colorectal cancers with KIT expression were characterized by immunoblotting and immunohistochemistry. The biologic alterations after KIT-SCF binding were analyzed with or without protein kinase C (PKC) activation.Results: We found that WT-KIT was expressed in a subset of colon cancer cell lines and was activated by SCF, leading to activation of downstream AKT and extracellular signal-regulated kinase (ERK) signaling pathways. We also showed that KIT expression gradually decreased, after prolonged SCF stimulation, due to lysosomal degradation. Degradation of WT-KIT after SCF binding was significantly rescued when PKC was activated. We also showed the involvement of activated PKC-δ in the recycling of WT-KIT. We further showed that a subset of colorectal cancers exhibit expressions of both WT-KIT and activated PKC-δ and that expression of KIT is correlated with poor patient survival (P = 0.004).Conclusions: Continuous downstream signal activation after KIT-SCF binding is accomplished through PKC-δ–mediated recycling of KIT. This sustained KIT activation may contribute to tumor progression in a subset of colon cancers with KIT expression and might provide the rationale for a therapeutic approach targeting KIT. Clin Cancer Res; 19(18); 4961–71. ©2013 AACR.

Although the neuroinvasiveness of SARS-CoV-2 has been extensively studied, the correlation between virus infectivity and brain maturation remained unclear. Here, using human-induced pluripotent stem cells-derived three-dimensional cerebral organoids (CBOs), we present the first quantitative data for long-term kinetics of SARS-CoV-2 propagation in brain for 20 days post-infection. We showed that mature brains are more susceptible to SARS-CoV-2 than immature counterparts, evident from increased viral replication rate and higher TUNEL + cells proportion. Transcriptome profiling identified enhancement of corticogenesis and gliogenesis and indicated enrichments in translation machinery- and lipid metabolism-associated genes in mature brain, suggesting the major factors conferring the robust infectivity of SARS-CoV-2. The role of cholesterol in promoting viral replication was confirmed by the reduced number of infected cells in lipid lowering-drugs condition. Together, this study highlights that permissiveness of the brains to SARS-CoV-2 is greatly enhanced with their maturation and suggests cholesterol as a new target for suppressing viral replication.

To evaluate the effectiveness of acupuncture treatment for shoulder impingement syndrome (SIS) a literature review was conducted of randomized controlled trials (RCTs) where acupuncture was used as an intervention for patients diagnosed with SIS. Relevant clinical studies (N = 181) were retrieved from several databases based on the inclusion/exclusion criteria, and the interventions and results were analyzed. Six RCTs were selected to review based on the inclusion and exclusion criteria. In all 6 studies, the acupuncture treatment group showed significant positive changes in indicators evaluating pain, disability, and quality of life. A significant decrease in the evaluation indicators (Shoulder Pain and Disability Index, numeric rating scale, Visual Analogue Scale, Constant Murley Shoulder Assessment Score, patient’s global assessment, and doctor’s global assessment) and a significant increase in the questionnaire scores (UCLA, AL-score, EuroQol 5 Dimension Self-Report Questionnaire, and disabilities of the arm, shoulder, and hand) were observed. In addition, 1 study showed similar improvements in pain and quality of life measures in the acupuncture group and corticosteroid injection group. No major side effects were reported. Acupuncture may be an effective and safe treatment for SIS however, further RCTs are required.

As living liver transplantation has become a standard treatment method with a high success rate, many studies have investigated the experiences of living liver donors; however, their results have not been integrated. This qualitative meta-synthesis aimed to explore the life experiences of living liver donors to provide an in-depth understanding of meaningful common experiences. A comprehensive search on qualitative studies published in English or Korean was conducted in October 2021. The PRISMA statement was used for reporting each phase of the literature search, and MAXQDA2020 software was used for data analysis. Data synthesis was conducted using the three-step thematic synthesis method suggested by Thomas and Harden. Ten articles met the inclusion criteria. The analysis revealed five main themes: "Becoming an earnest donor," "Transitioning from a potential donor to an actual donor," "Difficulties in returning to normal life," "Re-examining the meaning of donation," and "Wishes for prospective donors." The study emphasizes that living liver donors need medical attention and intervention from multilateral perspectives as well as the need for systematic change in the society to enhance support for donors. This review provides comprehensive insights on how individuals became the living liver donor and the important aspects of living donation and other considerations in an integrated manner. Transplant teams, including nurses and coordinators, should have a comprehensive understanding of physical, psychological, and social experiences of donors ranging from decision-making to post donation health management.

PARP inhibitors are the first clinically approved drugs that were developed based on synthetic lethality. PARP inhibitors have shown promising outcomes since their clinical applications and have recently been approved as maintenance treatment for cancer patients with BRCA mutations. PARP inhibitors also exhibit positive results even in patients without homologous recombination (HR) deficiency. Therapeutic effects were successfully achieved; however, the development of resistance was unavoidable. Approximately 40–70% of patients are likely to develop resistance. Here, we describe the mechanisms of action of PARP inhibitors, the causes of resistance, and the various efforts to overcome resistance. Particularly, we determined the survival probability of cancer patients according to the expression patterns of genes associated with HR restoration, which are critical for the development of PARP inhibitor resistance. Furthermore, we discuss the innovative attempts to degrade PARP proteins by chemically modifying PARP inhibitors. These efforts would enhance the efficacy of PARP inhibitors or expand the scope of their usage.

Background People with disabilities are vulnerable to chronic diseases such as hypertension. In South Korea, over half of the population living with a physical disability suffer from hypertension. Understanding the typology of hypertension self-management patterns will assist with behavioural interventions for people with physical disabilities. Thus, this study aims to identify the typology of hypertension self-management behavioural patterns, the factors associated with the latent classes, and to recognise potential at-risk populations by comparing potential health outcomes among hypertensive adults with physical disabilities. Methods Data of 1551 participants were extracted from the 2017 National Survey of Disabled Persons. Latent classes were analysed using five indicators of self-management: smoking, alcohol consumption, physical activity, diet, and weight control. Determinants of self-management patterns, such as general characteristics, health-related factors, and social relationships, were identified using multinomial logistic regression. Further, health measures, such as health profile, psychological health, and patient experience, were compared. Results The following three latent classes were identified: “high self-management” group (40.8%), “harmful habitual behaviour” group (20.6%), and “inactive behaviour” group (38.6%). Compared with the high self-management group, the predictors of belonging to the harmful habitual behaviour group were being male, young, and single. Being female, employed, severely disabled, dependent, and unsatisfied with friendships were predictors of the inactive behaviour group. Those in the inactive behaviour group had a poor health-related quality of life, poor subjective health, depression, and unmet medical needs. Conclusions This study provides evidence that there are mutually exclusive subgroups of patients with hypertension regarding self-management patterns, identifies an array of predictive factors in each latent class membership, and distinguishes a high-risk group by comparing the health measures among patients with hypertension with physical disabilities. Analysing subgroups may assist in identifying and meeting the diverse needs of self-management support in hypertensive patients with physical disabilities.

Fungal sexual reproduction requires complex cellular differentiation processes of hyphal cells. The plant pathogenic fungus Fusarium graminearum produces fruiting bodies called perithecia via sexual reproduction, and perithecia forcibly discharge ascospores into the air for disease initiation and propagation. Lipid metabolism and accumulation are closely related to perithecium formation, yet the molecular mechanisms that regulate these processes are largely unknown. Here, we report that a novel fungal specific bZIP transcription factor, F. graminearum perithecium overproducing 1 (Fpo1), plays a role as a global transcriptional repressor during perithecium production and maturation in F. graminearum. Deletion of FPO1 resulted in reduced vegetative growth, asexual sporulation and virulence and overproduced perithecium, which reached maturity earlier, compared with the wild type. Intriguingly, the hyphae of the fpo1 mutant accumulated excess lipids during perithecium production. Using a combination of molecular biological, transcriptomic and biochemical approaches, we demonstrate that repression of FPO1 after sexual induction leads to reprogramming of carbon metabolism, particularly fatty acid production, which affects sexual reproduction of this fungus. This is the first report of a perithecium-overproducing F. graminearum mutant, and the findings provide comprehensive insight into the role of modulation of carbon metabolism in the sexual reproduction of fungi.

Summary Objective To compare the skeletal and dentoalveolar changes produced by the Damon system's treatment philosophy to traditional orthodontic treatment techniques. Materials and Methods An electronic search in four major databases was completed: Cochrane, PubMed, EMBASE, and Google Beta Scholar on October 5th, 2018. Randomized controlled trials, prospective and retrospective controlled clinical trials were included in this systematic review. The quality assessment of individual studies was done using two different tools: The Cochrane Risk of Bias Assessment Tool (RTCs) and The Methodological Index for Non-Randomized Studies (MINORS) (non-RCTs). Results Seven studies were included for this qualitative analysis. Six studies compared the Damon system to various types of conventional (non self-ligating bracket) system as a comparison group. One study used a quad helix as a comparison for a few months before a full bonding appointment with conventional brackets. The majority of studies found an increase in maxillary inter-canine, inter-premolar, and intermolar distance after the treatment in both the Damon and comparison groups. Yet, all studies concluded that there is no significant difference in the final transverse dimension between the two groups. One study also found that the transverse expansion was achieved mainly by tipping movement of posterior dentition, and a decrease in the posterior buccal bone area was evident in both groups after treatment. Conclusion There is not enough evidence to support the claim that the Damon system allows additional arch expansion with better tipping control than with traditional techniques.

Molecular glue degraders, such as lenalidomide and pomalidomide, bind to cereblon (CRBN) E3 ligase and subsequently recruit neosubstrate proteins, Ikaros (IKZF1) and Aiolos (IKZF3), for the ubiquitination-proteasomal degradation process. In this study, we explored structure-activity relationship analysis for novel GSPT1 degraders utilizing a benzotriazinone scaffold previously discovered as a novel CRBN binder. In particular, we focused on the position of the ureido group on the benzotriazinone scaffold, substituent effect on the phenylureido group, and methyl substitution on the benzylic position of benzotriazinone. As a result, we identified 34f (TD-522), which exhibits strong anti-proliferative effects in both KG-1 (EC

Aberrant epigenetic alteration has been associated with development of various cancers, including breast cancer. Since epigenetic modifications such as DNA methylation and histone modification are reversible, epigenetic enzymes, including histone modifying enzymes and DNA methyltransferases, emerge as attractive targets for cancer therapy. Although epi-drugs targeting histone deacetylation or DNA methylation have received FDA approval for cancer therapy, a very modest anti-tumor activity has been observed with monotherapy in clinical studies of breast cancer. To improve efficacy of epi-drugs in breast cancer, combination of epi-drugs with other therapies currently has been investigated. Additionally, basic researches to elucidate molecular causes of cancer should be extensively and intensively conducted in order to find novel epigenetic druggable targets. In this chapter, we summarize how epigenetic regulation affects the development of breast cancer and how to control cancer phenotype by modulating abnormal epigenetic modifications, and then suggest future research directions in epigenetics for breast cancer treatment.

Aberrant epigenetic alteration has been associated with development of various cancers, including breast cancer. Since epigenetic modifications such as DNA methylation and histone modification are reversible, epigenetic enzymes, including histone modifying enzymes and DNA methyltransferases, emerge as attractive targets for cancer therapy. Although epi-drugs targeting histone deacetylation or DNA methylation have received FDA approval for cancer therapy, a very modest anti-tumor activity has been observed with monotherapy in clinical studies of breast cancer. To improve efficacy of epi-drugs in breast cancer, combination of epi-drugs with other therapies currently has been investigated. Additionally, basic researches to elucidate molecular causes of cancer should be extensively and intensively conducted in order to find novel epigenetic druggable targets. In this chapter, we summarize how epigenetic regulation affects the development of breast cancer and how to control cancer phenotype by modulating abnormal epigenetic modifications, and then suggest future research directions in epigenetics for breast cancer treatment.

Hypoxic signaling occurs under several physiological and pathological conditions, such as in solid tumors. Hypoxia inducible factor 1 (HIF-1) mediates many hypoxic responses, and regulates hundreds of genes involved in many biological processes including tumor angiogenesis, invasion, and metabolism. Although the components of hypoxia that initiate and maintain the hypoxic responses have been well-studied, epigenetic regulation of the hypoxic responses is poorly understood. Thus, it would be useful to summarize current status of the field and discuss future directions. In this review, we will focus on the current understandings of epigenetic regulation in hypoxic response and discuss currently available epigenetic drugs to treat hypoxia-driven or related diseases.

연구목적: 본 연구의 목적은 일반초등학교와 인근 특수학교 간의 사물놀이로 구성된 통합교류활동 프로그램이 비장애 초등학생의 정서지능, 장애수용태도에 미치는 영향과 초등 중도․중복 장애학생(청각장애와 지적장애)들에게 미치는 영향을 밝히는 것이다. 연구방법: 연구참여자는 C일반초등학교와 N특수학교의 3학년 학생이며, 실험집단으로 비장애학생 24명과 중도․중복장애학생 8명은 통합동아리 시간에 총 16회기의 ‘통합교류활동 프로그램’에 참여하였다. 비장애학생의 종속변인 양적자료는 독립표본 t검정을 하였고 중도․중복 장애학생의 사전사후 변화는 관찰, N특수학교 담당교사, 특수교육보조원, 공익근무요원과의 면담, 학기 말 성과보고서에서 수합된 질적 자료로 제시하였다. 연구결과: 실험집단 비장애 초등학생들의 정서지능 전체 점수와 하위영역 3가지 점수는 통제집단에 비해 유의하게 높게 나타났다. 비장애 초등학생의 장애수용태도 전체점수와 하위영역에서 실험집단이 통제집단에 비해 유의하게 높게 나타났다. 중도․중복 장애학생들은 통합교류활동 프로그램 참여의 양과 질 향상, 대인관계에서 상호작용의 증진, 개인적 정서적 안정감과 행복감의 표현이 나타났다. 결론: 이 연구는 ‘통합교류활동’을 초등 정규교육과정의 통합동아리 활동으로 실시하고 그 긍정적 효과를 보고하는 첫 연구로서 분리교육 환경의 특수학교 학생들에게 비장애학생들과의 통합경험 제공, 통합동아리 활동 참여 후의 초등학생들의 성장, 사물놀이 활동선정의 적절성, 특수학교의 발전 방향 등에 대한 논의와 연구의 의의 및 제한점이 제공되었다.

Summary Because glioblastoma (GBM) exhibits high heterogeneity, it is desirable to use patient-derived cells from the first stage of screening for GBM drug discovery. Here, we describe a protocol to culture patient-derived GBM cells on the extracellular matrix-coated plates to allow high-throughput screening. Further, we detail approaches to identify the mechanism of action (MOA) of the selected effective drug through proteomics. This protocol will be useful for researchers interested in drug screening and the MOA of drugs. For complete details on the use and execution of this protocol, please refer to Nam et al. (2021)., Graphical abstract, Highlights • Methods for patient-derived GBM cell culture • Automated high-throughput screening methods using chemical libraries • Quantitative mass spectrometry to elucidate mechanism of action of drugs • Methods to perform data analysis from mass spectrometry, Because glioblastoma (GBM) exhibits high heterogeneity, it is desirable to use patient-derived cells from the first stage of screening for GBM drug discovery. Here, we describe a protocol to culture patient-derived GBM cells on the extracellular matrix-coated plates to allow high-throughput screening. Further, we detail approaches to identify the mechanism of action (MOA) of the selected effective drug through proteomics. This protocol will be useful for researchers interested in drug screening and the MOA of drugs.

Uncontrolled autophagy has been associated with the development and progression of various cancers that are resistant to cancer therapy. Therefore, many efforts to modulate uncontrolled autophagy as a cancer treatment have been attempted, from basic science to clinical trials. However, it remains difficult to equally apply autophagy modulators to cancer therapy because autophagy is a double-edged sword in cancer: it can be tumor-suppressive or tumor-protective. Therefore, the precise mechanisms of autophagy modulators and their varied responsiveness to each cancer type should be addressed in detail. This study will describe the precise mechanisms of developing various autophagy modulators, their current therapeutic applications and future perspectives.

Summary Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with poor survival rate. Temozolomide (TMZ) is used as standard chemotherapy to treat GBM, but a large number of patients either respond poorly and/or develop resistance after long-term use, emphasizing the need to develop potent drugs with novel mechanisms of action. Here, using high-throughput compound screening (HTS), we found that azathioprine, an immunosuppressant, is a promising therapeutic agent to treat TMZ-resistant GBM. Through integrative genome-wide analysis and global proteomic analysis, we found that elevated lipid metabolism likely due to hyperactive EGFR/AKT/SREBP-1 signaling was inhibited by azathioprine. Azathioprine also promoted ER stress-induced apoptosis. Analysis of orthotopic xenograft models injected with patient-derived GBM cells revealed reduced tumor volume and increased apoptosis after azathioprine and TMZ co-treatment. These data indicate that azathioprine could be a powerful therapeutic option for TMZ-resistant GBM patients., Graphical abstract, Highlights • Azathioprine as a promising drug for temozolomide-resistant GBM treatment • Azathioprine inhibits aberrantly elevated lipid metabolism in GBM • Azathioprine promotes ER stress-induced apoptosis in GBM • Through orthotropic xenograft models, anti-GBM effect of azathioprine is confirmed, Biological Sciences; Cell Biology; Proteomics; Cancer Systems Biology; Cancer

Triple-negative breast cancer (TNBC) has an aggressive phenotype and poor prognosis due to the lack of specific targeted treatments. The development of an effective therapeutic strategy with a novel mechanism is essential for TNBC management. Olaparib, a PARP inhibitor, has been approved for the treatment of breast or ovarian cancer patients with breast cancer gene 1/2 (BRCA1/2) mutations. Here, we report the development of a small molecule targeting PARP1 based on the hydrophobic tagging (HyT) method. Targeted protein misfolding and consequent degradation are caused by HyT. Hydrophobic-tagged olaparib induces the proteasome-dependent degradation of PARP1 and shows enhanced antitumor effects compared to olaparib in TNBC cells. In addition, hydrophobic-tagged olaparib causes ER stress-related unfolded protein response (UPR), autophagy, and apoptosis. These results point towards encouraging prospects for chemically modifying approved drugs that not only exhibit superior effects compared to those of the original drugs by triggering novel mechanisms but also provide great feasibility in the translational scenario.

We report the first air-passivated ambipolar BP transistor formed by applying benzyl viologen, which serves as a surface charge transfer donor for BP flakes. The passivated BP devices exhibit excellent stability under both an ambient atmosphere and vacuum; their transistor performance is maintained semi-permanently. Unlike their intrinsic p-type properties, passivated BP devices present advantageous ambipolar properties with much higher electron mobility up to ∼83 cm(2) V(-1) s(-1) from 2-terminal measurement at 300 K, compared to other reported studies on n-type BP transistors. On the basis of the n-type doping effect that originated from benzyl viologen, we also systematically investigated the BP thickness dependence of our devices on electrical properties, in which we found the best electron transport performance to be attained when an ∼10 nm thick BP flake was used.

A biomimetic multifunctional nanocomposite was synthesized, in which a polydopamine (PDA) thin film was deposited on a layered double hydroxide (LDH) through an interlayer polymerization. Kinetic controlled polymerization of dopamine (DA) in a basic buffer solution under a nitrogen atmosphere provided a synthetic pathway for the nanostructured PDA/LDH composites without polymer agglomerates, allowing the crystallinity of the pristine LDH nanoparticles to be maintained. The contraction of the interlayer spacing for the (00l) reflection of PDA/LDH nanocomposites demonstrated intercalation of PDA into the LDH interlayer space. The catalytic activity of the PDA/LDH nanocomposites was evaluated by observing the reduction of p-nitrophenol in the presence of NaBH4, in which the PDA layer acts as a protection layer against surface contamination of the nanocomposites. Electrochemical capacitive performance was also observed due to the strong adhesion of PDA to the Ni foam electrode. The nanostructure of the PDA/LDH nanocomposites induced by interlayer polymerization drove the incorporative organic–inorganic functional materials with blocked surfaces and improved the electrochemical properties, providing a reliable synthetic pathway to prepare multifunctional nanohybrid materials.

Safety and security system have been internationally enhanced in a field of shipping logistics. Accordingly, techniques for safety and security have been studied steadily. The need of portable radiation detection device is increasing by the search of the container is enhanced. In this paper, we propose a study to improve the life of the system and the realization of portable radiation detection device based on Cortex-A9. Configuration of a portable radiation detection device is configured largely to an analog board and the digital platform and the sensor module. The power used in each stage of the analog board is varied. Uses a switching regulator to use various power supply thereby to generate an error result and cause the switching noise. It is proposed to reduce the power consumption reducing technique for the study.

The inflammatory response mediated by nuclear factor κB (NF-κB) signaling is essential for host defense against pathogens. Although the regulatory mechanism of NF-κB signaling has been well studied, the molecular basis for epigenetic regulation of the inflammatory response is poorly understood. Here we identify a new signaling axis of PKCα-LSD1-NF-κB, which is critical for activation and amplification of the inflammatory response. In response to excessive inflammatory stimuli, PKCα translocates to the nucleus and phosphorylates LSD1. LSD1 phosphorylation is required for p65 binding and facilitates p65 demethylation, leading to enhanced stability. In vivo genetic analysis using Lsd1SA/SA mice with ablation of LSD1 phosphorylation and chemical approaches in wild-type mice with inhibition of PKCα or LSD1 activity show attenuated sepsis-induced inflammatory lung injury and mortality. Together, we demonstrate that the PKCα-LSD1-NF-κB signaling cascade is crucial for epigenetic control of the inflammatory response, and targeting this signaling could be a powerful therapeutic strategy for systemic inflammatory diseases, including sepsis.

Lysine-specific demethylase 1 (LSD1) is a histone demethylase that participates in transcriptional repression or activation. Recent studies reported that LSD1 is involved in learning and memory. Although LSD1 phosphorylation by PKCα was implicated in circadian rhythmicity, the importance of LSD1 phosphorylation in learning and memory is unknown. In this study, we examined the roles of LSD1 in synaptic plasticity and memory using Lsd1SA/SA knock-in (KI) mice, in which a PKCα phosphorylation site is mutated. Interestingly, short-term and long-term contextual fear memory as well as spatial memory were impaired in Lsd1 KI mice. In addition, short-term synaptic plasticity, such as paired pulse ratio and post-tetanic potentiation was impaired, whereas long-term synaptic plasticity, including long-term potentiation and long-term depression, was normal. Moreover, the frequency of miniature excitatory postsynaptic current was significantly increased, suggesting presynaptic dysfunction in Lsd1 KI mice. Consistent with this, RNA-seq analysis using the hippocampus of Lsd1 KI mice showed significant alterations in the expressions of presynaptic function-related genes. Intriguingly, LSD1n-SA mutant showed diminished binding to histone deacetylase 1 (HDAC1) compared to LSD1n-WT in SH-SY5Y cells. These results suggest that LSD1 is involved in the regulation of presynaptic gene expression and subsequently regulates the hippocampus-dependent memory in phosphorylation-dependent manner.

Glaucoma is one of the leading causes of preventable blindness, affecting > 2 million people in the United States. Recently, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors were found to exert preventive effects against glaucoma. However, there is no evidence for the role of 11β-HSD1 inhibitors against glaucoma. Here, we developed a novel 11β-HSD1 inhibitor, (1R,2S,3S,5R,6S,7S)-6-(2-(6-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl)acetamido)-adamantane-2-carboxamide (KR-67607) and showed its protective effects against ischemia-reperfusion-induced eye injury. We demonstrate that KR-67607 effectively reduced cortisol levels in mouse eyes and maintained the trabecular meshwork (TM) structure in the presence of transient ischemic stress. Furthermore, KR-67607 reversed the elevation of intra-ocular pressure (IOP), suggesting that the TM structure maintained by KR-67607 prevented the excessive rise in IOP that exacerbates glaucoma. KR-67607 was shown to have a higher specificity for 11β-HSD1 than carbenoxolone (CBX) in vitro. Moreover, KR-67607 reduced apoptosis and the structural disruption of TM cells. Antioxidation was the major protective pathway of KR-67607 against chemically-induced ischemia-reperfusion in TM cells and the glucocorticoid receptor (GR) was closely associated with this pathway. When TM cells undergo ischemic stress, GR is activated and then translocates to the cell nucleus where it interferes with Nrf-2-mediated antioxidant gene expression. However, when KR-67607 inhibited GR translocation, Nrf-2 was able to induce antioxidant gene transcription, which consequently, enhanced the antioxidant capacity of the cells. In conclusion, our current work describes a novel selective 11β-HSD1 inhibitor for glaucoma treatment and provides evidence of its physiological role in anti-oxidative pathways in the TM.

The circadian clock is a self-sustaining oscillator that controls daily rhythms. For the proper circadian gene expression, dynamic changes in chromatin structure are important. Although chromatin modifiers have been shown to play a role in circadian gene expression, the in vivo role of circadian signal-modulated chromatin modifiers at an organism level remains to be elucidated. Here, we provide evidence that the lysine-specific demethylase 1 (LSD1) is phosphorylated by protein kinase Cα (PKCα) in a circadian manner and the phosphorylated LSD1 forms a complex with CLOCK:BMAL1 to facilitate E-box-mediated transcriptional activation. Knockin mice bearing phosphorylation-defective Lsd1(SA/SA) alleles exhibited altered circadian rhythms in locomotor behavior with attenuation of rhythmic expression of core clock genes and impaired phase resetting of circadian clock. These data demonstrate that LSD1 is a key component of the molecular circadian oscillator, which plays a pivotal role in rhythmicity and phase resetting of the circadian clock.

A polydopamine (PDA) thin film with a dense and conformal surface was prepared under optimized deposition conditions using O2 gas as an oxygen source. The PDA-based organic phototransistors exhibited high photosensitivity and photo-controlled switching properties under light illumination.

Safety and security system have been internationally enhanced in a field of shipping logistics. Accordingly, techniques for safety and security have been studied steadily. The need of portable radiation detection device is increasing by the search of the container is enhanced. In this paper, we propose to study on the application of the temperature compensation algorithm to the platform to improve the accuracy and the realization of portable radiation detection device based on Cortex-A9. Analog board deforms signal output from the sensor. And Cortex-A9 platform analyzes the signal received and displays the results. Additionally we use the temperature compensation algorithm and thereby we ca look the same results even if the temperature changes.

Autism spectrum disorders (ASDs) are a group of developmental disorders that cause variable and heterogeneous phenotypes across three behavioral domains such as atypical social behavior, disrupted communications, and highly restricted and repetitive behaviors. In addition to these core symptoms, other neurological abnormalities are associated with ASD, including intellectual disability (ID). However, the molecular etiology underlying these behavioral heterogeneities in ASD is unclear. Mutations in SHANK2 genes are associated with ASD and ID. Interestingly, two lines of Shank2 knockout mice (e6-7 KO and e7 KO) showed shared and distinct phenotypes. Here, we found that the expression levels of Gabra2, as well as of GABA receptor-mediated inhibitory neurotransmission, are reduced in Shank2 e6-7, but not in e7 KO mice compared with their own wild type littermates. Furthermore, treatment of Shank2 e6-7 KO mice with an allosteric modulator for the GABAA receptor reverses spatial memory deficits, indicating that reduced inhibitory neurotransmission may cause memory deficits in Shank2 e6-7 KO mice. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.

Interpenetration is known for the structures of many minerals and ice; most notably for ice, it exists in doubly interpenetrating (VI, VII, and VIII) and non-interpenetrating (Ih) forms with the latter being porous and having nearly half of the density of the former. In synthetic materials, specifically in metal–organic frameworks (MOFs), interpenetration is generally considered undesirable because it reduces porosity. However, on the contrary, many advantageous properties also arise when MOFs are interpenetrated, such as selective guest capture, stepwise gas adsorption, enhanced framework robustness, photoluminescence control, and guest-responsive porosity. Therefore, various strategies have been suggested to control interpenetration during synthesis. However, once these extended network materials are prepared as interpenetrating or non-interpenetrating structures, the degree of interpenetration generally remains unchanged, because numerous chemical bonds must be broken and subsequently reformed in a very concerted way during the process unlike some interlocked coordination compounds in solution (Figure 1a).

Polymerized melanin thin films were electrochemically synthesized in a 5,6-dihydroxyindole precursor solution on indium tin oxide (ITO) substrates using the cyclic voltammetry and constant potential methods. Tris(hydroxymethyl)aminomethane (THAM) and phosphate buffer solutions were applied to prepare the films that were well deposited to the ITO substrates. The films that were synthesized in the THAM buffer solution exhibited a faster growth rate and better adhesion to the ITO electrodes than the films in the phosphate buffer. The film thickness linearly increased at the growth rate of 0.8 nm/s as the deposition time and number of cycles increased. Two electrochemical conditions produced similar thicknesses as well as physical properties in each buffer solution. However, the constant potential method demonstrated that this provides the synthetic advantages of faster deposition and less consumption of electric charge compared to the cyclic voltammetry route.

This paper describes a facile strategy for fabricating arrays of two- and three-dimensional gold nanostructures using PDMS-infiltrated polystyrene (PS) colloidal crystals. PDMS molding of colloidal crystal, gold vapor deposition, and subsequent calcination of PS produced gold thin layers over hexagonal PDMS microwell arrays with hemispherical air-voids of approximately 140 nm on glass substrates. Vapor deposition of perfluoroalkylsilane thin layers improved the thermal stability of the colloidal template over 100 °C, providing a route to preparation of hollow architectures with gold thin layers supported by PDMS nanostructures. Surface modification of the PDMS using poly(allylamine hydrochloride) induced two-dimensional colloidal crystals of PS and PMMA spheres through electrostatic interactions. Particle aggregation of 13 nm gold nanoparticles in the PDMS microwells demonstrated a surface plasmon resonance band red-shifted to 810 nm, in comparison with that on the flat surface at 720 nm.

A dip-coating technique was used to deposit self-assembled monolayer arrays of PMMA colloidal particles with a diameter of 125 nm onto a silicon surface coated with (3-aminopropyl)-triethoxysilane (APTES), exploiting the electrostatic interaction between the negative particle and the positive substrate. The PMMA colloidal arrangement was controlled efficiently by the dipping time and temperature, concentration and pH of the colloidal solutions. A non-close-packed monolayer assembly was prepared without the need for pre-patterned templates. The deposition of platinum metal on the 2D PMMA arrays and subsequent thermal treatment produced ordered hemispherical Pt nanoshells, 74 nm in height, as soft-lithographic templates and biological sensor materials.

Monolayer assemblies of zeolite microcrystals, polymer nanobeads and caged proteins were successfully applied to a highly ordered MgAl-LDH monolayer by using the electrostatic attractions between the negatively charged particles and positively charged MgAl-LDH without chemical modifications. Ultrasonication leads to the monolayer assembly of ZSM-5 microcrystals with a maximum preferred contact over the MgAl-LDH monolayer, where the ZSM-5 microcrystals are oriented in the (0k0) crystallographic direction. PMMA and ferritin were also adsorbed on the monolayer LDH nanocrystal surface through self-assembly in solution. Homogeneous PMMA colloids-LDH composite layers on Si were successfully prepared, thanks to the improved interfacial compatibility between the immobilized LDH and polymer surface charges. Thermal treatment at 150 °C resulted in the formation of continuous polymer coatings over the LDH/Si monolayer. The mixing of colloidal solutions of LDH and PMMA led to the formation of bulk-type polymer-LDH composites after the melting of the polymer phase, where the polymer was homogeneously coated over the LDH crystals without the phase segregation of the LDH nanocrystals. The charged hydroxide layers of the LDH nanocrystals provided the multi-functional interface characteristics required to assemble the functional particles, resulting in the binary hybrid structures of inorganic-inorganic, polymer-inorganic or bio-inorganic composites. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)