Synergetic effects of concurrent chronic exposure to a mixture of OCPs and high-fat diets on type 2 diabetes and beneficial effects of caloric restriction in female zebrafish.

This study aimed to investigate the relationship among chronic exposure to a low concentration of organochlorine pesticides (OCPs), high-fat diet (HFD)-induced obesity, and caloric restriction in type 2 diabetes (T2D). Thus, female zebrafish were divided into four groups and treated for 12 weeks as follows: (i) negative control, (ii) HFD (obesity) control, (iii) obesity + a mixture of OCPs (OP), and (iv) obesity + a mixture of OCPs + caloric restriction (OPR). We then assessed T2D-related effects via hematological analysis, histopathology, mitochondrial evaluation, and multiomics analyses. The OP group showed a significant increase in glucose levels, whereas the OPR group maintained glucose at nonsignificant levels. Multiomics analyses revealed that the exacerbated metabolic effects in the OP group were associated with molecular alterations in oxidative stress, inflammation, nucleotide metabolism, and glucose/lipid homeostasis. These alterations were histologically verified by the increased numbers of hypertrophic adipocytes and inflammatory cells observed. Caloric restriction activated pathways related to antioxidant response, mitochondrial fatty acid oxidation, and energy metabolism in zebrafish, leading to preserved glucose homeostasis. In conclusion, this study identified molecular mechanisms underlying the synergistic effect of concurrent exposure to a mixture of OCPs and HFD as well as shed light on the beneficial effect of regular caloric restriction in T2D development.

Transcriptome-metabolome-wide association study (TMWAS) in rats revealed a potential carcinogenic effect of DEHP in thyroid associated with eicosanoids.

The incidence of thyroid cancer (TC) has increased considerably in the last few decades. Environmental factors, including plasticizers, are recognized as potential risks leading to thyroid cancer in humans. In this study, we used a transcriptome-metabolome-wide association study to find the unidentified carcinogenic mechanism of di-2-ethylhexyl phthalate (DEHP) in thyroid and biomarkers for non-invasive diagnosis. Rats were treated with different doses of DEHP (0, 0.3, 3, 30, 150 mg DEHP/kg bw/day) for 13 weeks. Then, the thyroids were processed for Ki67 staining and RNA-seq. Also, 17-h urine samples were collected for high-resolution metabolomics analysis. After a high dose of DEHP exposure, the terminal body weights and the thyroid and parathyroid glands weights were not altered. However, the liver weights and numbers of Ki67-positive cells were increased. Further, multivariate statistical analysis revealed that metabolic shifts were considerably altered above 30 mg DEHP/kg bw/day. In RNA-seq analysis, some cancer-related genes were altered, including 18 upregulated and 9 downregulated transcripts. These cancer transcripts and whole metabolome data were integrated to uncover thyroid cancer-related metabolic pathways, which revealed that cancer-related transcripts had a network structure linked to eicosanoids such as leukotriene D4 and prostaglandin. In brief, our study demonstrated that DEHP can induce thyroid hyperplasia through the eicosanoid-associated pathway, providing further insight into the mechanism of DEHP-associated thyroid cancer.

Ethyl Gallate Dual-Targeting PTPN6 and PPARγ Shows Anti-Diabetic and Anti-Obese Effects.

The emergence of the high correlation between type 2 diabetes and obesity with complicated conditions has led to the coinage of the term "diabesity". AMP-activated protein kinase (AMPK) activators and peroxisome proliferator-activated receptor (PPARγ) antagonists have shown therapeutic activity for diabesity, respectively. Hence, the discovery of compounds that activate AMPK as well as antagonize PPARγ may lead to the discovery of novel therapeutic agents for diabesity. In this study, the knockdown of PTPN6 activated AMPK and suppressed adipogenesis in 3T3-L1 cells. By screening a library of 1033 natural products against PTPN6, we found ethyl gallate to be the most selective inhibitor of PTPN6 (Ki = 3.4 µM). Subsequent assay identified ethyl gallate as the best PPARγ antagonist (IC50 = 5.4 µM) among the hit compounds inhibiting PTPN6. Ethyl gallate upregulated glucose uptake and downregulated adipogenesis in 3T3-L1 cells as anticipated. These results strongly suggest that ethyl gallate, which targets both PTPN6 and PPARγ, is a potent therapeutic candidate to combat diabesity.

A Novel NOX Inhibitor Treatment Attenuates Parkinson's Disease-Related Pathology in Mouse Models.

Parkinson's disease (PD) is a progressive neurodegenerative motor disorder without an available therapeutic to halt the formation of Lewy bodies for preventing dopaminergic neuronal loss in the nigrostriatal pathway. Since oxidative-stress-mediated damage has been commonly reported as one of the main pathological mechanisms in PD, we assessed the efficacy of a novel NOX inhibitor from AptaBio Therapeutics (C-6) in dopaminergic cells and PD mouse models. The compound reduced the cytotoxicity and enhanced the cell viability at various concentrations against MPP+ and α-synuclein preformed fibrils (PFFs). Further, the levels of ROS and protein aggregation were significantly reduced at the optimal concentration (1 µM). Using two different mouse models, we gavaged C-6 at two different doses to the PD sign-displaying transgenic mice for 2 weeks and stereotaxically PFF-injected mice for 5 weeks. Our results demonstrated that both C-6-treated mouse models showed alleviated motor deficits in pole test, hindlimb clasping, crossbeam, rotarod, grooming, and nesting analyses. We also confirmed that the compound treatment reduced the levels of protein aggregation, along with phosphorylated-α-synuclein, in the striatum and ventral midbrain and further dopaminergic neuronal loss. Taken together, our results strongly suggest that NOX inhibition can be a potential therapeutic target for PD.

Early Prediction of Sepsis Onset Using Neural Architecture Search Based on Genetic Algorithms.

Sepsis is a life-threatening condition with a high mortality rate. Early prediction and treatment are the most effective strategies for increasing survival rates. This paper proposes a neural architecture search (NAS) model to predict the onset of sepsis with a low computational cost and high search performance by applying a genetic algorithm (GA). The proposed model shares the weights of all possible connection nodes internally within the neural network. Externally, the search cost is reduced through the weight-sharing effect between the genotypes of the GA. A predictive analysis was performed using the Medical Information Mart for Intensive Care III (MIMIC-III), a medical time-series dataset, with the primary objective of predicting sepsis onset 3 h before occurrence. In addition, experiments were conducted under various prediction times (0-12 h) for comparison. The proposed model exhibited an area under the receiver operating characteristic curve (AUROC) score of 0.94 (95% CI: 0.92-0.96) for 3 h, which is 0.31-0.26 higher than the scores obtained using the Sequential Organ Failure Assessment (SOFA), quick SOFA (qSOFA), and Simplified Acute Physiology Score (SAPS) II scoring systems. Furthermore, the proposed model exhibited a 12% improvement in the AUROC value over a simple model based on the long short-term memory neural network. Additionally, it is not only optimally searchable for sepsis onset prediction, but also outperforms conventional models that use similar predictive purposes and datasets. Notably, it is sufficiently robust to shape changes in the input data and has less structural dependence.

Nepetin Acts as a Multi-Targeting Inhibitor of Protein Tyrosine Phosphatases Relevant to Insulin Resistance.

Protein tyrosine phosphatases (PTPs) are essential modulators of signal transduction pathways and has been implicated in many human diseases such as cancer, diabetes, obesity, autoimmune disorders, and neurological diseases, indicating that PTPs are next-generation drug targets. Since PTPN1, PTPN2, and PTPN11 have been reported to be negative regulators of insulin action, the identification of PTP inhibitors may be an effective strategy to develop therapeutic agents for the treatment of type 2 diabetes. In this study, we observed for the first time that nepetin inhibits the catalytic activity of PTPN1, PTPN2, and PTPN11 in vitro, indicating that nepetin acts as a multi-targeting inhibitor of PTPN1, PTPN2, and PTPN11. Furthermore, treatment of mature 3T3-L1 adipocytes with 20 µM nepetin stimulates glucose uptake through AMPK activation. Taken together, our findings provide evidence that nepetin, a multi-targeting inhibitor of PTPN1, PTPN2, and PTPN11, could be a promising therapeutic candidate for the treatment of type 2 diabetes.

Millimeter-Scale Continuous Film of MoS2 Synthesized Using a Mo, Na, and Seeding Promoter-Based Coating as a Solid Precursor.

While the chemical vapor deposition technique can be used to fabricate 2D materials in a larger area, materials like MoS2 have limited controllability due to their lack of self-controlling nature. This article presents a new technique for synthesizing a void-free millimeter-scale continuous monolayer MoS2 film through the diffusion of a well-controlled Mo, Na, and seeding promoter-based coating under a low-pressure N2 atmosphere. Compared to the conventional method, this technique provides precise control of solid precursors, where MoS2 grows next to the coating. At 800 °C, the synthesized MoS2 showed a uniform single-layer MoS2 film; however, a Na-free coating showed nanoscale voids and poor crystal quality, which are attributed to a higher edge-attachment barrier that slows down the MoS2 lateral growth. The synthesized MoS2 with Na-containing solution showed an intense PL peak with a 1.86 eV band gap. Even at the relatively low temperature of 700 °C, compared to the Na-excluded condition, MoS2 showed almost two times higher area coverage with a comparatively larger crystal size. This finding may assist in the future development of MoS2-based electronic and optoelectronic devices such as transistors and photodetectors.

Resilience in the Surgical Scheduling to Support Adaptive Scheduling System.

Operating Room (OR) managers frequently encounter uncertainties related to real-time scheduling, especially on the day of surgery. It is necessary to enable earlier identification of uncertainties occurring in the perioperative environment. This study aims to propose a framework for resilient surgical scheduling by identifying uncertainty factors affecting the real-time surgical scheduling through a mixed-methods study. We collected the pre- and post-surgical scheduling data for twenty days and a one-day observation data in a top-tier general university hospital in South Korea. Data were compared and analyzed for any changes related to the dimensions of uncertainty. The observations in situ of surgical scheduling were performed to confirm our findings from the quantitative data. Analysis was divided into two phases of fundamental uncertainties categorization (conceptual, technical and personal) and uncertainties leveling for effective decision-making strategies. Pre- and post-surgical scheduling data analysis showed that unconfirmed patient medical conditions and emergency cases are the main causes of frequent same-day surgery schedule changes, with derived factors that affect the scheduling pattern (time of surgery, overtime surgery, surgical procedure changes and surgery duration). The observation revealed how the OR manager controlled the unexpected events to prevent overtime surgeries. In conclusion, integrating resilience approach to identifying uncertainties and managing event changes can minimize potential risks that may compromise the surgical personnel and patients' safety, thereby promoting higher resilience in the current system. Furthermore, this strategy may improve coordination among personnel and increase surgical scheduling efficiency.

Discovery of metabolic alterations in the serum of patients infected with Plasmodium spp. by high-resolution metabolomics.

INTRODUCTION: Despite the advances in diagnosis and treatment, malaria has still not been eradicated. Metabolic interactions between the host and Plasmodium may present novel targets for malaria control, but such interactions are yet to be deciphered. An exploration of metabolic interactions between humans and two Plasmodium species by high-resolution metabolomics may provide fundamental insights that can aid the development of a new strategy for the control of malaria. OBJECTIVES: This study aimed at exploring the metabolic changes in the sera of patients infected with Plasmodium falciparum and Plasmodium vivax. METHODS: Uni- and multivariate metabolomic analyses were performed on the sera of four groups of patients, namely normal control (N, n = 100), P. falciparum-infected patients (PF, n = 21), P. vivax-infected patients (PV, n = 74), and non-malarial pyretic patients (Pyr, n = 25). RESULTS: Univariate and multivariate analyses of N, PF, and PV groups showed differential metabolic phenotypes and subsequent comparisons in pairs revealed significant features. Pathway enrichment test with significant features showed the affected pathways, namely glycolysis/gluconeogenesis for PF and retinol metabolism for PV. The metabolites belonging to the affected pathways included significantly low 2,3-diphosphoglycerate and glyceraldehyde-3-phosphate in the sera of PF. The sera of PV had significantly low levels of retinol but high levels of retinoic acid. CONCLUSION: Our study reveals metabolic alterations induced by Plasmodium spp. in human serum and would serve as a milestone in the development of novel anti-malarial strategies.

Effect of developmental exposure to bisphenol A on steroid hormone and vitamin D3 metabolism.

High exposure to bisphenol A (BPA) in children has been associated with the outcomes of several diseases, including those related to developmental problems. To elucidate the mechanism of BPA mediated developmental toxicity, plasma and urine from rats exposed to BPA was analyzed with high resolution metabolomics, beginning from post-natal day 9, for 91 days. Female and male rats were orally administered 5 different BPA doses to elucidate dose- and sex-specific BPA effects. Regarding dose-specific effects, multivariate statistical analysis showed that metabolic shifts were considerably altered between 5, 50 and 250 mg BPA/kg bw/day in treated rats. A nonmonotonicity and monotonicity between BPA dose and metabolic response were major trajectories, showing overall metabolic changes in plasma and urine, respectively. Metabolic perturbation in the steroid hormone biosynthesis pathway was significantly associated with dose- and sex-specific BPA effects. Intermediate metabolites in the rate-limiting step of steroid hormone biosynthesis down-regulated steroid hormones in the 250 mg treatment. Further, our study identified that BPA increased urinary excretion of vitamin D3 and decreased its concentration in blood, suggesting that perturbation of vitamin D3 metabolism may be mechanistically associated with neurodevelopmental disorders caused by BPA. Three metabolites showed a decrease in sex difference with high BPA dose because female rats were more affected than males, which can be related with early puberty onset in female. In brief, the results demonstrated that BPA induces dose- and sex-specific metabolic shifts and that perturbation of metabolism can explain developmental problems.

Validation of the Korean Stroop Test in Diagnosis of Minimal Hepatic Encephalopathy.

The burden of minimal hepatic encephalopathy (MHE) is significant, but no universal criteria for diagnosis have been established. We aimed to validate the Korean Stroop Test for MHE screening. Chronic hepatitis B-related liver cirrhosis patients were recruited prospectively from 13 centers. The Korean Stroop Test consisted of two Stroop-off states (color and word) and two Stroop-on states (inhibition and switching). Accuracy adjusted psychomotor speed (rate correct score) of these tests were analyzed. Sex- and age- adjusted rate correct scores of these tests were rated as the Korean Stroop Score (K-Stroop score). MHE was diagnosed when Portosystemic Encephalopathy Syndrome Test (PHES) scores were below -4. A total of 220 liver cirrhosis patients and 376 healthy controls were enrolled. Prevalence of MHE was 20.6% in cirrhosis patients. Rate correct scores and the K-Stroop score showed significant differences between healthy controls, cirrhosis patients without MHE, and cirrhosis patients with MHE. The rate correct score of the K-Stroop score was 0.74 (95% Confidence Interval: 0.66-0.83, P < 0.001). Female gender and the K-Stroop score were significant for MHE diagnosis. The Korean Stroop Test is simple and valid for screening of MHE.

A Systems Vaccinology Approach Reveals the Mechanisms of Immunogenic Responses to Hantavax Vaccination in Humans.

Hantavax is an inactivated vaccine for hemorrhagic fever with renal syndrome (HFRS). The immunogenic responses have not been elucidated yet. Here we conducted a cohort study in which 20 healthy subjects were administered four doses of Hantavax during 13-months period. Pre- and post- vaccinated peripheral blood mononuclear cells (PBMCs) and sera were analysed by transcriptomic and metabolomic profilings, respectively. Based on neutralizing antibody titers, subjects were subsequently classified into three groups; non responders (NRs), low responders (LRs) and high responders (HRs). Post vaccination differentially expressed genes (DEGs) associated with innate immunity and cytokine pathways were highly upregulated. DEG analysis revealed a significant induction of CD69 expression in the HRs. High resolution metabolomics (HRM) analysis showed that correlated to the antibody response, cholesteryl nitrolinoleate, octanoyl-carnitine, tyrosine, ubiquinone-9, and benzoate were significantly elevated in HRs, while chenodeoxycholic acid and methyl palmitate were upregulated in NRs and LRs, compared with HRs. Additionally, gene-metabolite interaction revealed upregulated gene-metabolite couplings in, folate biosynthesis, nicotinate and nicotinamide, arachidonic acid, thiamine and pyrimidine metabolism in a dose dependent manner in HR group. Collectively, our data provide new insight into the underlying mechanisms of the Hantavax-mediated immunogenicity in humans.

Selective growth of monolayer and bilayer graphene patterns by a rapid growth method.

The use of next-generation graphene requires the control of the number of deposition layers together with its fast synthesis for its use in advanced and miniaturized devices. Here, this article describes a novel technique for the selective growth of a continuous film of a graphene pattern (controlled monolayer/multilayer design) by the chemical vapor deposition (CVD) method on Cu foils modified by different plasma treatments. Ex situ Ar plasma treatment is the preferred treatment for monolayer graphene (I2D/IG = 1.81) synthesis. Bilayer graphene (I2D/IG = 1.05) growth was influenced by applying an additional oxygen plasma treatment, which led to different morphologies and control of the surface-active nature of Cu. The required design was achieved by a photolithography process. Graphene synthesis was performed by a short annealing process (60 s) followed by a single-step short burst of graphene growth (60 s). Relatively high density graphene nuclei with faster graphene growth resulted in monolayer graphene in the Ar plasma-treated area. Ex situ oxygen plasma treatment in selected areas was capable of controlling the amount of graphene nuclei formation, while the kink structure was capable of bolstering the adsorption of a relatively high amount of carbon adatoms, resulting in bilayer graphene.

Synthesis and Characterization of Graphene/ITO Nanoparticle Hybrid Transparent Conducting Electrode.

The combination of graphene with conductive nanoparticles, forming graphene-nanoparticle hybrid materials, offers a number of excellent properties for advanced engineering applications. A novel and simple method was developed to deposit 10 wt% tin-doped indium tin oxide (ITO) nanoparticles on graphene. The method involved a combination of a solution-based environmentally friendly electroless deposition approach and subsequent vacuum annealing. A stable organic-free solution of ITO was prepared from economical salts of In(NO3)3 ·H2O and SnCl4. The obtained ITO nanostructure exhibited a unique architecture, with uniformly dispersed 25-35 nm size ITO nanoparticles, containing only the crystallized In2O3 phase. The synthesized ITO nanoparticles-graphene hybrid exhibited very good and reproducible optical transparency in the visible range (more than 85%) and a 28.2% improvement in electrical conductivity relative to graphene synthesized by chemical vapor deposition. It was observed that the ITO nanoparticles affect the position of the Raman signal of graphene, in which the D, G, and 2D peaks were redshifted by 5.65, 5.69, and 9.74 cm-1, respectively, and the annealing conditions had no significant effect on the Raman signatures of graphene.

Multisensory Integration Strategy for Modality-Specific Loss of Inhibition Control in Older Adults.

Older adults are known to have lesser cognitive control capability and greater susceptibility to distraction than young adults. Previous studies have reported age-related problems in selective attention and inhibitory control, yielding mixed results depending on modality and context in which stimuli and tasks were presented. The purpose of the study was to empirically demonstrate a modality-specific loss of inhibitory control in processing audio-visual information with ageing. A group of 30 young adults (mean age = 25.23, Standar Desviation (SD) = 1.86) and 22 older adults (mean age = 55.91, SD = 4.92) performed the audio-visual contour identification task (AV-CIT). We compared performance of visual/auditory identification (Uni-V, Uni-A) with that of visual/auditory identification in the presence of distraction in counterpart modality (Multi-V, Multi-A). The findings showed a modality-specific effect on inhibitory control. Uni-V performance was significantly better than Multi-V, indicating that auditory distraction significantly hampered visual target identification. However, Multi-A performance was significantly enhanced compared to Uni-A, indicating that auditory target performance was significantly enhanced by visual distraction. Additional analysis showed an age-specific effect on enhancement between Uni-A and Multi-A depending on the level of visual inhibition. Together, our findings indicated that the loss of visual inhibitory control was beneficial for the auditory target identification presented in a multimodal context in older adults. A likely multisensory information processing strategy in the older adults was further discussed in relation to aged cognition.

Fabrication of highly conductive graphene/ITO transparent bi-film through CVD and organic additives-free sol-gel techniques.

Indium tin oxide (ITO) still remains as the main candidate for high-performance optoelectronic devices, but there is a vital requirement in the development of sol-gel based synthesizing techniques with regards to green environment and higher conductivity. Graphene/ITO transparent bi-film was synthesized by a two-step process: 10 wt. % tin-doped ITO thin films were produced by an environmentally friendly aqueous sol-gel spin coating technique with economical salts of In(NO3)3.H2O and SnCl4, without using organic additives, on surface free energy enhanced (from 53.826 to 97.698 mJm-2) glass substrate by oxygen plasma treatment, which facilitated void-free continuous ITO film due to high surface wetting. The chemical vapor deposited monolayer graphene was transferred onto the synthesized ITO to enhance its electrical properties and it was capable of reducing sheet resistance over 12% while preserving the bi-film surface smoother. The ITO films contain the In2O3 phase only and exhibit the polycrystalline nature of cubic structure with 14.35 ± 0.5 nm crystallite size. The graphene/ITO bi-film exhibits reproducible optical transparency with 88.66% transmittance at 550 nm wavelength, and electrical conductivity with sheet resistance of 117 Ω/sq which is much lower than that of individual sol-gel derived ITO film.

Multi-Sensory Integration Impairment in Patients with Minimal Hepatic Encephalopathy.

Paper-and-pencil-based psychometric tests are the gold standard for diagnosis of cognitive dysfunction in liver disease. However, they take time, can be affected by demographic factors, and lack ecological validity. This study explored multi-sensory integration ability to discriminate cognitive dysfunction in cirrhosis. Thirty-two healthy controls and 30 cirrhotic patients were recruited. The sensory integration test presents stimuli from two different modalities (e.g., image/sound) with a short time lag, and subjects judge which stimuli appeared first. Repetitive tests reveal the sensory integration capability. Performance in the sensory integration test, psychometric tests, and functional near-infrared spectroscopy for patients was compared to controls. Sensory integration capability, the perceptual threshold to discriminate the time gap between an image and sound stimulus, was significantly impaired in cirrhotic patients with minimal hepatic encephalopathy (MHE) compared to controls (p < 0.01) and non-MHE patients (p < 0.01). Sensory integration test showed good correlation with psychometric tests (NCT-A, r = 0.383, p = 0.002; NCT-B, r = 0.450, p < 0.01; DST-F, r = -0.322, p = 0.011; DST- B, r = -0.384, p = 0.002; ACPT, r = -0.467, p < 0.01). Psychometric tests were dependent on age and education level, while the sensory integration test was not affected. The sensory integration test, where a cut-off value for the perceptual threshold was 133.3ms, recognized MHE patients at 90% sensitivity and 86.5% specificity.

Virtual daily living test to screen for mild cognitive impairment using kinematic movement analysis.

Questionnaires or computer-based tests for assessing activities of daily living are well-known approaches to screen for mild cognitive impairment (MCI). However, questionnaires are subjective and computerized tests only collect simple performance data with conventional input devices such as a mouse and keyboard. This study explored the validity and discriminative power of a virtual daily living test as a new diagnostic approach to assess MCI. Twenty-two healthy controls and 20 patients with MCI were recruited. The virtual daily living test presents two complex daily living tasks in an immersive virtual reality environment. The tasks were conducted based on subject body movements and detailed behavioral data (i.e., kinematic measures) were collected. Performance in both the proposed virtual daily living test and conventional neuropsychological tests for patients with MCI was compared to healthy controls. Kinematic measures considered in this study, such as body movement trajectory, time to completion, and speed, classified patients with MCI from healthy controls, F(8, 33) = 5.648, p < 0.001, η2 = 0.578. When both hand and head speed were employed in conjunction with the immediate free-recall test, a conventional neuropsychological test, the discrimination power for screening MCI was significantly improved to 90% sensitivity and 95.5% specificity (cf. the immediate free-recall test alone has 80% sensitivity and 77.3% specificity). Inclusion of the kinematic measures in screening for MCI significantly improved the classification of patients with MCI compared to the healthy control group, Wilks' Lambda = 0.451, p < 0.001.

Crosstalk between signals initiated from TLR4 and cell surface BAFF results in synergistic induction of proinflammatory mediators in THP-1 cells.

Cellular response to stimulation is mediated by meshwork of signaling pathways that may share common signaling adaptors. Here, we present data demonstrating that signaling pathways initiated from the membrane-bound form of B-cell activating factor (BAFF) can crosstalk with lipopolysaccharide (LPS)-induced signaling for synergistic expression of proinflammatory mediators in the human macrophage-like cell line THP-1. Co-treatment of the cells with BAFF-specific monoclonal antibody and LPS resulted in enhanced mitogen-activated protein kinase (MAPK)/mitogen- and stress-activated protein kinase (MSK)-mediated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 subunit (Ser276), which then interacts with CREB binding protein (CBP) for subsequent acetylation. Simultaneously, the phosphorylation of cyclic AMP-response element binding protein (CREB) was enhanced through the combined action of phosphatidylinositol-3-kinase (PI3K)/AKT and MAPK/MSK pathways, and the resulting phospho-CREB interacted with the NF-κB/CBP complex. Transfection of CREB-specific siRNA inhibited the BAFF-mediated enhancing effect indicating that the formation of the CREB/NF-κB/CBP complex is required for the synergistic induction of the proinflammatory genes. These findings indicate that BAFF-mediated reverse signaling can modulate LPS-induced inflammatory activation through regulation of NF-κB and CREB activity and point out the necessity to re-evaluate the role of BAFF in diseases where its expression is high in macrophages.

Crystallographic Wet Chemical Etching of Semipolar GaN (11-22) Grown on m-Plane Sapphire Substrates.

This paper reports the etch rates and etched surface morphology of semipolar GaN using a potassium hydroxide (KOH) solution. Semipolar (11-22) GaN could be etched easily using a KOH solution and the etch rate was higher than that of Ga-polar c-plane GaN (0001). The etch rate was anisotropic and the highest etch rate was measured to be approximately 116 nm/min for the (1011) plane and 62 nm/min for the (11-20) plane GaN using a 4 M KOH solution at 100 °C, resulting in specific surface features, such as inclined trigonal cells.