Efficacy and safety of a fixed-dose combination of dapagliflozin and linagliptin (AJU-A51) in patients with type 2 diabetes mellitus: A multicentre, randomized, double-blind, parallel-group, placebo-controlled phase III study.

AIMS: To evaluate the efficacy and safety of add-on dapagliflozin in patients with type 2 diabetes mellitus (T2D) who had inadequate glycaemic control with metformin and linagliptin. MATERIALS AND METHODS: A total of 235 patients with inadequate response to metformin (≥1000 mg/day) plus linagliptin (5 mg/day) were randomized to receive either dapagliflozin/linagliptin fixed-dose combination (FDC [AJU-A51]) 10/5 mg/day (n = 117) or linagliptin 5 mg plus placebo (n = 118) for 24 weeks. After the main treatment period, patients who received linagliptin plus placebo were treated with AJU-A51 for an additional 28 weeks. Change in glycated haemoglobin (HbA1c) from baseline to Week 24 was the primary endpoint. RESULTS: AJU-A51 significantly reduced HbA1c levels (from 7.93% ± 0.82% to 7.11% ± 0.61%) compared with linagliptin plus placebo (from 7.80% ± 0.71% to 7.87% ± 0.94%), with a least squares mean difference of -0.88% (95% confidence interval -1.07 to -0.68; p < 0.0001) at 24 weeks. The AJU-A51 group had a significantly higher proportion of patients who achieved HbA1c <7.0% at Week 24 than the control group (44.8% vs. 18.6%; p < 0.001). The AJU-A51 group maintained glycaemic efficacy up to 52 weeks, whereas the control group showed a substantial reduction in HbA1c after switching to AJU-A51 in the extension study period. Both groups had similar incidence of treatment-emergent and serious adverse events, and no cases of symptomatic hypoglycaemia were reported. CONCLUSIONS: Dapagliflozin and linagliptin FDC (AJU-A51) showed potent glucose-lowering effects, with good tolerability, in patients with T2D who had poor glycaemic control on metformin and linagliptin (ClinicalTrials.gov [NCT06329674]).

Designing for community engagement: user-friendly refugee wellness center planning process and concept, a health design case study.

BACKGROUND: Refugee and immigrant populations have diverse cultural factors that affect their access to health care and must be considered when building a new clinical space. Health design thinking can help a clinical team evaluate and consolidate these factors while maintaining close contact with architects, patients' community leaders, and hospital or institutional leadership. A diverse group of clinicians, medical students, community leaders and architects planned a clinic devoted to refugee and immigrant health, a first-of-its-kind for South Philadelphia. METHODS: The planning process and concept design of this wellness center is presented as a design case study to demonstrate how principles and methods of human-centered design were used to create a community clinic. Design thinking begins with empathizing with the end users' experiences before moving to ideation and prototyping of a solution. These steps were accomplished through focus groups, a design workshop, and iterations of the center's plan. RESULTS: Focus groups were thematically analyzed and generated two themes of access and resources and seven subthemes that informed the design workshop. A final floor plan of the wellness center was selected, incorporating priorities of all stakeholders and addressing issues of disease prevention, social determinants of health, and lifestyle-related illness that were relevant to the patient population. CONCLUSIONS: Design thinking methods are useful for health care organizations that must adapt to the needs of diverse stakeholders and especially populations that are underserved or displaced. While much has been written on the theory and stages of design thinking, this study is novel in describing this methodology from the beginning to the end of the process of planning a clinical space with input from the patient population. This study thus serves as a proof of concept of the application of design thinking in planning clinical spaces.

A novel simulation module for segmental mandibulectomy and mandible reconstruction using 3D models.

INTRODUCTION: Mandibular resection and reconstruction are common but complex procedures in head and neck surgery. Resection with adequate margins is critical to the success of the procedure but technical training is restricted to real case experience. Here we describe our experience in the development and evaluation of a mandibular resection and reconstruction simulation module. METHODS: 3D printed (3DP) models of a mandible with a pathologic lesion were developed from imaging data from a patient with an ameloblastoma. During an educational conference, otolaryngology trainees participated in a simulation in which they reviewed a CT scan of the pathologic mandible and then planned their osteotomies before and after handling a 3DP model demonstrating the lesion. The adequacy of the osteotomy margins was assessed and components of the simulation were rated by participants with pre- and post-training surveys. RESULTS: 52 participants met criteria. After reviewing the CT scan, 34 participants (65.3 %) proposed osteotomies clear of the lesion. This proportion improved to 48 (92.3 %, p = 0.001) after handling the 3D model. Among those with initially adequate margins (n = 33), 45.5 % decreased their margins closer to the ideal, 27.2 % made no revision, 21.2 % widened their margins. 92 % of participants found the simulation beneficial for surgical planning and technical training. After the exercise, the majority of participants had increased confidence in conceptualizing the boundaries of the lesion (69.2 %) and their abilities to ablate (76.5 %). CONCLUSIONS: The structured mandibulectomy simulation using 3DP models was useful in the development of trainee experience in segmental mandible resection. LAY SUMMARY: This study presents the first mandibulectomy simulation module for trainees with the use of 3DP models. The use of a 3DP model was also shown to improve the quality of surgical training.

Slow-wave sleep and obstructive sleep apnea in patients with type 2 diabetes mellitus.

PURPOSE: This study aimed to analyze sleep architecture and obstructive sleep apnea (OSA) in patients with type 2 diabetes and clarify the association between sleep characteristics and glycemic control. METHODS: All participants underwent metabolism-related laboratory testing and a cross-sectional analysis of nocturnal polysomnography for sleep parameter analysis. Data were analyzed using the chi-squared test, a one-way analysis of variance, and Kruskal-Wallis test to compare the differences among three groups (type 2 diabetes, prediabetes, and control groups). The prevalence of OSA was evaluated using descriptive statistics and comparing the group divided into HbA1c quartiles. Univariate and multivariate linear regression analyses were used to determine factors associated with glycemic control. RESULTS: Of 75 study participants (age 57.3 ± 4.1 years, 32 men), there were 25 participants each in the type 2 diabetes, prediabetes, and control groups. Participants with type 2 diabetes had significantly decreased slow-wave sleep duration (77.9 ± 30.0 min, p = 0.026) and shortened rapid eye movement sleep latency (median 75 min, p = 0.018) compared with those in the prediabetes and control groups. Forty-five participants (60%) had OSA (apnea-hypopnea index ≥ 5/h), 18 of whom were in the type 2 diabetes group. The prevalence of OSA in this group was 72%. The prevalence of moderate-to-severe OSA was significantly higher in the type 2 diabetes group than in the control group (p = 0.025) and in groups with HbA1c levels of > 6.7% than in groups with HbA1c levels of < 5.3% (p = 0.007). Multiple regression analysis showed that dyslipidemia (ß = 0.179, p = 0.000) and slow-wave sleep duration (ß = - 0.113, p = 0.008) were independently associated with the HbA1c level. CONCLUSION: Our results suggest that increasing slow-wave sleep is positively associated with glycemic control.

Increased Pro-Inflammatory T Cells, Senescent T Cells, and Immune-Check Point Molecules in the Placentas of Patients With Gestational Diabetes Mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy. To define the altered pathway in GDM placenta, we investigated the transcriptomic profiles from human placenta between GDM and controls. METHODS: Clinical parameters and postpartum complications were reviewed in all participants. Differentially expressed canonical pathways were analyzed between the GDM and control groups based on transcriptomic analysis. CD4+ T, CD8+ T, and senescent T cell subsets were determined by flow cytometry based on staining for specific intracellular cytokines. RESULTS: Gene ontology analysis revealed that the placenta of GDM revealed upregulation of diverse mitochondria or DNA replication related pathways and downregulation of T-cell immunity related pathways. The maternal placenta of the GDM group had a higher proportion of CD4+ T and CD8+ T cells than the control group. Interestingly, senescent CD4+ T cells tended to increase and CD8+ T cells were significantly increased in GDM compared to controls, along with increased programmed cell death-1 (CD274+) expression. Programmed death-ligand 1 expression in syncytotrophoblasts was also significantly increased in patients with GDM. CONCLUSION: This study demonstrated increased proinflammatory T cells, senescent T cells and immune-check point molecules in GDM placentas, suggesting that changes in senescent T cells and immune-escape signaling might be related to the pathophysiology of GDM.

[The peak latency prolongation of the blink reflex in a patient with trigeminal neuralgia of Meckel's cave mass]. / A pislogási reflexcsúcs latenciájának megnyúlása egy Meckel-barlang-terime következtében kialakuló trigeminusneuralgia esetben.

The blink reflex test of the trigeminal nerve can provide valuable information about lesions site. However it may not find small compressive lesions. We observed peak latency prolongation of the blink reflex test in a patient with trigeminal neuralgia caused by a small Meckel's cave mass, in whom the onset latency was normal. Conclusion - We suggest peak latency of the blink reflex might be a valuable aid for discerning small mass in patients with trigeminal neuralgia. This is the first case report of compressive trigeminal neuralgia showing peak latency prolongation of the blink reflex test.

ARID1A and PGR proteins interact in the endometrium and reveal a positive correlation in endometriosis.

Endometriosis is a disorder in which endometrial cells normally limited to the lining of the uterus proliferate outside the uterine cavity and can cause pelvic pain and infertility. ARID1A levels are significantly reduced in the eutopic endometrium from women with endometriosis. Uterine specific Arid1a knock-out mice were infertile due to loss of epithelial progesterone receptor (PGR) signaling. However, the functional association of ARID1A and PGR in endometriosis has not been studied. We examined the expression patterns and co-localization of ARID1A and PGR in eutopic endometrium from women with and without endometriosis using immunostaining and Western blot analysis. ARID1A and PGR proteins co-localized in the epithelium during the proliferative and the early secretory phases. Our immunoprecipitation analysis and proximity ligation assay (PLA) revealed physical interaction between ARID1A and PGR-A but not PGR-B in the mouse and human endometrium. ARID1A levels positively correlated with PGR levels in the eutopic endometrium of women with endometriosis. Our results bring new perspectives on the molecular mechanisms involved in endometrial receptivity and progesterone resistance in endometriosis. The interrelationship between ARID1A and PGR may contribute to explaining the non-receptive endometrium in endometriosis-related infertility.

Mig-6 is essential for glucose homeostasis and thermogenesis in brown adipose tissue.

Brown adipose tissue (BAT) is an anti-obese and anti-diabetic tissue that stimulates energy expenditure in the form of adaptive thermogenesis through uncoupling protein 1 (UCP1). Mitogen-inducible gene-6 (Mig-6) is a negative regulator of epidermal growth factor receptor (EGFR) that interacts with many cellular partners and has multiple cellular functions. We have recently reported that Mig-6 is associated with diabetes and metabolic syndrome. However, its function in BAT is unknown. We generated a brown adipocyte-specific Mig-6 knock-in mouse (BKI) to examine the role of Mig-6 in BAT. Mig-6 BKI mice had improved glucose tolerance on a normal chow diet. Mig-6 BKI mice also revealed activated thermogenesis and the size of the BAT lipid droplets was reduced. Additionally, Mig-6 regulated cAMP-PKA signaling-induced UCP1 expression in brown adipocytes. Taken together, these results demonstrate that Mig-6 affects glucose tolerance and thermogenesis in BAT.

Heminiphilus faecis gen. nov., sp. nov., a member of the family Muribaculaceae, isolated from mouse faeces and emended description of the genus Muribaculum.

The novel strain AM35T was isolated from the faeces of C57BL/6 mice. These cells are strictly anaerobic, gram negative, oxidase negative, catalase positive, rod-shaped and non-motile. The strain produced creamy yellowish colonies on brain heart infusion (BHI) agar with hemin. Growth was investigated at 30-41 °C in the presence of 0.5-1.5% (w/v) NaCl at pH 6.5-8.5. Taxonomic analysis based on 16S rRNA gene sequencing revealed that strain AM35T is affiliated with the family Muribaculaceae and closely related to the genus Muribaculum. The genomic DNA G + C content of strain AM35T was 47.8 mol%. We detected the whole-cell sugars ribose and galactose; meso-2,6-diaminopimelic acid was absent. The major fatty acids (> 10%) were anteiso-C15:0 and iso-C15:0; the major polar lipid was phosphatidylethanolamine. The major respiratory quinones were MK-10 and MK-11. Based on our phylogenetic, phenotypic and chemotaxonomic analyses, strain AM35T represents a novel genus within the family Muribaculaceae, for which we propose the name Heminiphilus faecis gen. nov., sp. nov. The type strain of Heminiphilus faecis gen. nov., sp. nov. is AM35T (= KCTC 15907 T = DSM 110151 T).

Development of a novel denture care agent with highly active enzyme, arazyme.

BACKGROUND: The importance of efficient denture deposit removal and oral hygiene has been further underscored by the continuous increase of denture wearers. Denture hygiene management has also become an important aspect associated with denture-induced stomatitis. This study aims to evaluate the denture cleaning effect of arazyme, the metalloprotease produced from the Serratia proteamaculans HY-3. We performed growth inhibition tests against oral opportunistic pathogens to be used as a potential oral health care agent. METHODS: The proteolytic activities of arazyme was evaluated over broad ranges of temperature, pH, and denture components compared to those of subtilisin in commercially available denture cleansers. The washing effects of arazyme were also measured by using homogeneously soiled EMPA 105 cottons. To investigate the denture cleaning capability of arazyme, artificially contaminated dentures were treated with arazyme, subtilisin (Everlase 6.0T), and Polident®, respectively. The growth kinetics of Candida albicans, Enterococcus faecalis, Staphylococcus epidermis, and Streptococcus mutans were evaluated in the presence of different concentrations of arazyme to estimate the prevention effects of arazyme against major oral opportunistic pathogens. RESULTS: Arazyme showed strong proteolytic activities over wide temperature and pH ranges compared with the serine protease of the subtilisin family. Arazyme demonstrated efficient removal and decomposition of artificially contaminated dentures and showed explicit washing effects against soiled cottons. Moreover arazyme inhibited the growth of oral opportunistic pathogens, including C. albicans, E. faecalis, S. epidermis, and S. mutans, with more than 80% inhibition against C. albicans, the major cause of denture stomatitis, with 250 mg/mL arazyme. CONCLUSIONS: Arazyme shows promise as a biological oral health care agent with effective cleaning and antimicrobial activities and is a potential source for developing novel denture care agents.

Analysis of the effect of organic solvent-sheet interfacial interaction on the exfoliation of sulfur-doped reduced graphene oxide sheets in a solvent system using molecular dynamics simulations.

In this study, the effect of interfacial interaction between solvent and sheets on the exfoliation of sulfur-doped reduced graphene oxide (SrGO) sheets was studied, using molecular dynamics simulations. Four organic solvents of toluene, tetrahydrofuran, N-methyl-2-pyrrolidone, and sulfolane, were used in this simulation. An insertion simulation considering the size effect of insertion molecules was used to determine the insertion efficiency of the solvent molecules. The insertion efficiency of toluene was the best among the four solvents due to the influence of the effective thickness of the solvent. An exfoliation simulation considering electrostatic interaction was conducted to evaluate the exfoliation efficiency of the SrGO sheets. Unlike the insertion efficiency case, the sulfolane was found to have the best exfoliation efficiency among the four solvents, due to the strong electrostatic repulsion and weak attractive energy between the SrGO sheets. The exfoliation efficiency of the SrGO sheets was improved by increasing the sulfur content and the ratio of the thiol type to the total number of sulfur-doped groups. These results reveal that decreasing the attractive energy and increasing the electrostatic repulsion between the solvent and SrGO sheets are a useful way to improve the exfoliation efficiency of SrGO sheets.

3D printed temporal bone as a tool for otologic surgery simulation.

PURPOSE: In this face validity study, we discuss the fabrication and utility of an affordable, computed tomography (CT)-based, anatomy-accurate, 3-dimensional (3D) printed temporal bone models for junior otolaryngology resident training. MATERIALS AND METHODS: After IRB exemption, patient CT scans were anonymized and downloaded as Digital Imaging and Communications in Medicine (DICOM) files to prepare for conversion. These files were converted to stereolithography format for 3D printing. Important soft tissue structures were identified and labeled to be printed in a separate color than bone. Models were printed using a desktop 3D printer (Ultimaker 3 Extended, Ultimaker BV, Netherlands) and polylactic acid (PLA) filament. 10 junior residents with no previous drilling experience participated in the study. Each resident was asked to drill a simple mastoidectomy on both a cadaveric and 3D printed temporal bone. Following their experience, they were asked to complete a Likert questionnaire. RESULTS: The final result was an anatomically accurate (XYZ accuracy = 12.5, 12.5, 5 µm) 3D model of a temporal bone that was deemed to be appropriate in tactile feedback using the surgical drill. The total cost of the material required to fabricate the model was approximately $1.50. Participants found the 3D models overall to be similar to cadaveric temporal bones, particularly in overall value and safety. CONCLUSIONS: 3D printed temporal bone models can be used as an affordable and inexhaustible alternative, or supplement, to traditional cadaveric surgical simulation.

Aerodynamic size separation of glass fiber aerosols.

The objective of this study was to investigate the efficacy of an aerodynamic separation scheme for obtaining aerosols with nearly monodisperse fiber lengths as test samples for mechanistic toxicological evaluations. The approach involved the separation of aerosolized glass fibers using an Aerodynamic Aerosol Classifier (AAC) or a multi-cyclone sampling array, followed by the collection of separated samples on filter substrates, and the measurement of each sample fiber length distribution. A glass fiber aerosol with a narrow range of aerodynamic sizes was selected and sampled with the AAC or multi-cyclone sampling array in two separate setups. The fiber length and diameter were measured using a field emission scanning electron microscope. The glass fiber aerosol was separated in distinct groups of eight with the AAC and of four with the multi-cyclone sampling array. The geometric standard deviations of the fiber length distributions of the separated aerosols ranged from 1.49 to 1.69 for the AAC and from 1.6 to 1.8 for multi-cyclone sampling array. While the separation of glass fiber aerosols with an AAC is likely to produce two different length fiber groups and the length resolution may be acceptable, the overall mass throughput of these separation schemes is limited.

Relationship of the Built Environment on Nursing Communication Patterns in the Emergency Department: A Task Performance and Analysis Time Study.

INTRODUCTION: The physical layout of the emergency department affects the way in which patients and providers move within the space and can cause substantial changes in workflow and, therefore, affect communication patterns between providers. There is no 1 ED design that enables the best patient care, and quantitative studies looking at ED design are limited. The goal of this study was to examine how different ED designs, centralized and decentralized, are associated with communication patterns among health care professionals. METHODS: A task performance, direct observation time study was used. By developing a novel tablet-based digital mapping tool using a cloud-based mapping platform (ArcGIS), data on provider actions and interactions were collected and mapped to a precise location within the emergency department throughout an entire nursing shift. RESULTS: The difference in the duration of nurse-physician interactions between the 2 ED designs was statistically significant. Within the centralized design, nurse-physician interactions totaled 14 minutes and 38 seconds compared with 30 minutes and 11 seconds in the decentralized design (t = 2.31, P = 0.02). More conversations between nurses and physicians occurred inside the patient's room in the decentralized design. DISCUSSION: Our findings suggest that the ED design affects communication patterns among health care providers and that the design has the potential to affect the quality of patient care.

Analysis of the distribution of assimilation products and the characteristics of transcriptomes in rice by submergence during the ripening stage.

BACKGROUND: Research on the submergence stress of rice has concentrated on the quiescence strategy to survive in long-term flooding conditions based on Submergence-1A (SUB1A). In the case of the ripening period, it is important that submergence stress can affect the quality as well as the survival of rice. Therefore, it is essential to understand the changes in the distribution of assimilation products in grain and ripening characteristics in submergence stress conditions. However, such studies have been insufficient at the physiological and molecular biological levels. RESULTS: We confirmed that the distribution rate of assimilation products in grain was decreased by submergence treatment. These results were caused by an increase in the distribution rate of assimilation products to the stem according to escape strategy. To understand this phenomenon at the molecular level, we analyzed the relative expression levels of genes related to sucrose metabolism, and found that the sucrose phosphate synthase gene (OsSPS), which induces the accumulation of sucrose in tissues, was decreased in the seeds and leaves, but not in the stems. Furthermore, the sucrose transporter gene (OsSUT) related to sucrose transport decreased in the seeds and leaves, but increased in stems. We also analyzed the biological metabolic processes related to starch and sucrose synthesis, carbon fixation, and glycolysis using the KEGG mapper with selected differentially expressed genes (DEGs) in seeds, stems, and leaves caused by submergence treatment. We found that the expression of genes for each step related to starch and D-glucose synthesis was down-regulated in the seeds and leaves but up-regulated in the stem. CONCLUSION: The results of this study provide basic data for the development of varieties and corresponding technologies adapted to submergence conditions, through understanding the action network of the elements that change in the submergence condition, as well as information regarding useful DEGs.

Highly Sensitive Lab on a Chip (LOC) Immunoassay for Early Diagnosis of Respiratory Disease Caused by Respirable Crystalline Silica (RCS).

Respirable crystalline silica (RCS) produced in mining and construction industries can cause life-threatening diseases such as silicosis, lung cancer, and chronic obstructive pulmonary disease (COPD). These diseases could be more effectively treated and prevented if RCS-related biomarkers were identified and measured at an early stage of disease progression, which makes development of a point of care test (POCT) platform extremely desirable for early diagnosis. In this work, a new, highly sensitive lab on a chip (LOC) immunoassay has been designed, developed, and characterized for tumor necrosis factor α (TNF-α), a protein biomarker that causes lung inflammation due to RCS exposure. The designed LOC device is composed of four reservoirs for sample, enzyme conjugated detection antibody, wash buffer, and chemiluminescence substrate in liquid form, along with three spiral reaction chambers for test, positive control, and negative control. All reservoirs and spiral microchannels were connected in series and designed to perform sequential delivery of immunoassay reagents with minimal user intervention. The developed LOC measured TNF-α concentrations as low as 16 pg/mL in plasma from RCS-exposed rats and also had a limit of detection (LOD) of 0.5 pg/mL in spiked artificial serum. In addition, the analysis time was drastically reduced to about 30 min, as opposed to hours in conventional methods. Successful implementation of a highly sensitive, chemiluminescence-based immunoassay on a preloaded LOC with proper quality control, as reported in this work, can pave the way toward developing a new rapid POCT platform for in-field clinical diagnosis.

Expression of PIK3IP1 in the murine uterus during early pregnancy.

The ovarian steroid hormones, estrogen (E2) and progesterone (P4), are essential regulators of uterine functions necessary for development, embryo implantation, and normal pregnancy. ARID1A plays an important role in steroid hormone signaling in endometrial function and pregnancy. In previous studies, using high density DNA microarray analysis, we identified phosphatidylinositol-3-kinase interacting protein 1 (Pik3ip1) as one of the genes up-regulated by ARID1A. In the present study, we performed real-time qPCR and immunohistochemistry analysis to investigate the regulation of PIK3IP1 by ARID1A and determine expression patterns of PIK3IP1 in the uterus during early pregnancy. The expression of PIK3IP1 was strong at the uterine epithelial and stromal cells of the control mice. However, expression of PIK3IP1 was remarkably reduced in the Pgrcre/+Arid1af/f mice and progesterone receptor knock-out (PRKO) mice. During early pregnancy, PIK3IP1 expression was strong at day 2.5 of gestation (GD 2.5) and then slightly decreased at GD 3.5 at the epithelium and stroma. After implantation, PIK3IP1 expression was detected at the secondary decidualization zone. To determine the ovarian steroid hormone regulation of PIK3IP1, we examined the expression of PIK3IP1 in ovariectomized control, Pgrcre/+Arid1af/f, and PRKO mice treated with P4 or E2. P4 treatment increased the PIK3IP1 expression at the luminal and glandular epithelium of control mice. However, the PIK3IP1 induction was decreased in both the Pgrcre/+Arid1af/f and PRKO mice, compared to controls. Our results identified PIK3IP1 as a novel target of ARID1A and PGR in the murine uterus.

Synthesis of biologically-active reduced graphene oxide by using fucoidan as a multifunctional agent for combination cancer therapy.

A therapeutic reduced graphene oxide (RGO) is synthesized by using fucoidan (Fu) as the reducing and surface functionalizing agent. The synthesized Fu-RGO exhibits promising characteristics for therapeutic applications such as high dispersity in aqueous media, biocompatibility, selective cytotoxicity to cancer cells, high loading capacity of the anticancer drug, and photothermal conversion effect. Therefore, Fu-GO is successfully harnessed as a combinatorial cancer treatment platform through bio-functional (Fu), chemo (doxorubicin (Dox)) and photothermal (RGO with near-infrared irradiation) modalities.

Influences of carboxyl functionalization of intercalators on exfoliation of graphite oxide: a molecular dynamics simulation.

In this study, the influences of the carboxyl functionalization of intercalators on exfoliation of graphite oxide were analyzed using molecular dynamics (MD) simulations. Molecular models of four-layered graphene oxide (GO) sheets, four different solvents (ethanol, dimethylformamide, tetrahydrofuran, and N-methyl-2-pyrrolidone), and four different intercalators (anthracene, 2-anthracenecarboxylic acid, 2,3-anthracenedicarboxylic acid, and 2,6-anthracenedicarboxylic acid) were used in the MD simulations. A separation simulation of GO sheets was performed to determine the point at which the GO sheets begin to exfoliate. An insertion simulation was used to obtain the minimum kinetic energy required for exfoliation and to calculate GO-solvent and GO-intercalator interaction energies. As the simulation result, GO-solvent and GO-intercalator interactions affected the minimum kinetic energy required for exfoliation. Having more carboxyl functional groups on the anthracene improved both the GO-intercalator interaction and the efficiency of the intercalators during exfoliation. These results reveal that increasing the interaction energy between the GO sheets and the insertion molecules is an efficient way to improve the performance of the solvents and the intercalators for the exfoliation of GO sheets.

ARID1A Is Essential for Endometrial Function during Early Pregnancy.

AT-rich interactive domain 1A gene (ARID1A) loss is a frequent event in endometriosis-associated ovarian carcinomas. Endometriosis is a disease in which tissue that normally grows inside the uterus grows outside the uterus, and 50% of women with endometriosis are infertile. ARID1A protein levels were significantly lower in the eutopic endometrium of women with endometriosis compared to women without endometriosis. However, an understanding of the physiological effects of ARID1A loss remains quite poor, and the function of Arid1a in the female reproductive tract has remained elusive. In order to understand the role of Arid1a in the uterus, we have generated mice with conditional ablation of Arid1a in the PGR positive cells (Pgrcre/+Arid1af/f; Arid1ad/d). Ovarian function and uterine development of Arid1ad/d mice were normal. However, Arid1ad/d mice were sterile due to defective embryo implantation and decidualization. The epithelial proliferation was significantly increased in Arid1ad/d mice compared to control mice. Enhanced epithelial estrogen activity and reduced epithelial PGR expression, which impedes maturation of the receptive uterus, was observed in Arid1ad/d mice at the peri-implantation period. The microarray analysis revealed that ARID1A represses the genes related to cell cycle and DNA replication. We showed that ARID1A positively regulates Klf15 expression with PGR to inhibit epithelial proliferation at peri-implantation. Our results suggest that Arid1a has a critical role in modulating epithelial proliferation which is a critical requisite for fertility. This finding provides a new signaling pathway for steroid hormone regulation in female reproductive biology and furthers our understanding of the molecular mechanisms that underlie dysregulation of hormonal signaling in human reproductive disorders such as endometriosis.