Clinical significance of heat shock protein 90α expression as a biomarker of prognosis in patients with gastric cancer.

BACKGROUND: Heat shock protein 90 (HSP90) possesses two major isoforms - HSP90α and HSP90ß. They have essential roles in the protection against stressful conditions. They are also important for the re-establishment of cellular homeostasis. We investigated the clinical significance of HSP90α and HSP90ß expression in patients with gastric cancer (GC). METHODS: HSP90α and HSP90ß expression levels were examined immunohistochemically in surgical specimens obtained from 186 GC patients. The correlations between their expression levels and clinicopathological parameters including patient survival were analyzed. RESULTS: The frequencies of larger tumor size (maximum diameter ≥4 cm) and more prominent tumor invasion (≥pT3) in the high intensity HSP90α expression group were 73.4% and 68.8% higher, respectively, than those in the low intensity group (both P = 0.001). High HSP90α expression level was also significantly associated with lymphatic invasion, lymph node metastasis, and advanced stage (TNM stage ≥III) disease (P = 0.047, P = 0.046, and P = 0.004, respectively). Patients with high HSP90α expression levels demonstrated significantly worse survival than those with low HSP90α expression levels (P = 0.047). In contrast, survival did not differ significantly according to the intensity of HSP90ß expression. CONCLUSIONS: Our results showed that HSP90α overexpression might be associated with disease progression and poorer survival in patients with GC. Therefore, HSP90α could be used as possible biomarker for the prognosis of GC.

Salispheres from Different Major Salivary Glands for Glandular Regeneration.

Dysfunctional salivary glands (SGs) are a clinical challenge due to the lack of effective treatments. Cell therapy with stem/progenitor cells may improve this situation by providing promising therapeutic solutions. Therefore, exploring abundant cellular sources is important. Three major pairs of SGs are located in different anatomic regions: the parotid glands, the submandibular glands, and the sublingual glands. Although SG stem/progenitor cells can be isolated and cultivated from all major SGs as salispheres, the differences among SG origins remain unclear. In this study, salispheres were successfully isolated from all major SGs. The salispheres demonstrated unique cellular features that originated from their native tissues. The characteristic expression profiles and cellular features of SG stem cells were demonstrated in all salispheres. When they were transplanted into irradiated animals, the salispheres were all capable of improving the saliva secretion that was disrupted by irradiation. Typical histologic structures could be observed in most parts of the treated glands, and the fibrotic environments of irradiated submandibular glands were remodeled by all salispheres regardless of origins. This study characterized the cellular features and in vivo effects of salispheres that were derived from different anatomic origins. The results suggest the possibility of functional redundancy among distinct pairs of major SGs, which is useful for the design of cell therapy to treat dysfunctional glandular organs.

Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial.

BACKGROUND: Capecitabine plus oxaliplatin (XELOX) has shown modest activity and tolerable toxicity in a phase II trial for biliary tract cancers (BTCs). Meanwhile, gemcitabine plus oxaliplatin (GEMOX) has been the reference arm in recent phase II and III trials for BTCs. We aimed to investigate the efficacy of XELOX versus GEMOX as first-line therapy for advanced BCTs. PATIENTS AND METHODS: In this open-label, randomized, phase III, noninferiority trial, we randomly selected patients with metastatic BCTs to receive GEMOX (gemcitabine 1000 mg/m2 on days 1 and 8, and oxaliplatin 100 mg/m2 on day 1) or XELOX (capecitabine 1000 mg/m2, twice daily, on days 1-14 and oxaliplatin 130 mg/m2 on day 1) as first-line treatment, given every 3 weeks, totaling eight cycles. The primary end point was to prove the noninferiority of XELOX to GEMOX in terms of 6-month progression-free survival (PFS) rate. RESULTS: In total, 114 patients randomly received GEMOX and 108 randomly received XELOX. The median PFS was 5.3 months for the GEMOX group and 5.8 months for the XELOX group. The 6-month PFS rate was 44.5% for the GEMOX group and 46.7% for the XELOX group. The 95% confidence interval of the 6-month PFS rate difference between both groups was -12% to 16%, meeting the criteria for noninferiority of XELOX to GEMOX. There was no difference in objective response (P=0.171) and median overall survival (P=0.131) between both groups. The most common grade three to four adverse events were neutropenia and thrombocytopenia. No patient died of treatment-related causes. The XELOX group had significantly lower frequencies of hospital visits than the GEMOX group (P<0.001). CONCLUSION: XELOX showed significant noninferiority to GEMOX in terms of 6-month PFS rate. Thus, XELOX could be an alternative first-line treatment of BCTs. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (number NCT01470443).

A Compressed-Sensing Based Blind Deconvolution Method for Image Deblurring in Dental Cone-Beam Computed Tomography.

In cone-beam computed tomography (CBCT), reconstructed images are inherently degraded, restricting its image performance, due mainly to imperfections in the imaging process resulting from detector resolution, noise, X-ray tube's focal spot, and reconstruction procedure as well. Thus, the recovery of CBCT images from their degraded version is essential for improving image quality. In this study, we investigated a compressed-sensing (CS)-based blind deconvolution method to solve the blurring problem in CBCT where both the image to be recovered and the blur kernel (or point-spread function) of the imaging system are simultaneously recursively identified. We implemented the proposed algorithm and performed a systematic simulation and experiment to demonstrate the feasibility of using the algorithm for image deblurring in dental CBCT. In the experiment, we used a commercially available dental CBCT system that consisted of an X-ray tube, which was operated at 90 kVp and 5 mA, and a CMOS flat-panel detector with a 200-µm pixel size. The image characteristics were quantitatively investigated in terms of the image intensity, the root-mean-square error, the contrast-to-noise ratio, and the noise power spectrum. The results indicate that our proposed method effectively reduced the image blur in dental CBCT, excluding repetitious measurement of the system's blur kernel.

Importance of Timed and Detailed Evaluation of Kidney Transplantation Candidates.

Kidney transplant recipients are at increased risk of cardiovascular morbidity and malignant neoplasm, and meticulous evaluation of potential recipients is needed to minimize risks of complications after transplantation. The purpose of this study was to analyze the results of preoperative assessments and document the importance of timed and detailed examinations. METHODS: Medical records of patients evaluated as kidney transplant candidates from January 2015 to September 2017 were retrospectively collected and analyzed. RESULTS: Of the 216 patients evaluated during the study period, 135 (62.5%) were male, 112 (51.9%) had diabetes mellitus, 163 (75.5%) had hypertension, 31 (14.4%) had a cardiovascular event history, and 7 (3.2%) had previous history of malignant neoplasms. Mean (SD) patient age was 50.7 (10.8) years. All 216 recipient candidates underwent echocardiography. Mean (SD) ejection fraction was 57.8% (5.9%), and 48 candidates (22.2%) showed regional wall motional abnormality. Coronary angiography was performed on 81 candidates, and in 57 (70.4%) of these, coronary artery disease was detected. Malignant neoplasms were detected in 10 (4.6%) candidates. Kidney transplantation was performed on 55 candidates. One recipient died of Pneumocystis jirovecii pneumonia at 15 months after kidney transplant, but there was no death-censored graft failure, newly detected malignant neoplasm, or cardiovascular event over a mean (SD) follow-up duration of 15.5 (8.6) months. CONCLUSION: Evaluation of kidney transplant candidates resulted in diagnoses of malignant neoplasms in 4.6% of patients and coronary artery disease in 26.4% of patients. The results of this study demonstrate candidates for kidney transplant should undergo detailed preoperative evaluation.

Modification of Erythrocyte Membrane Fatty Acid Contents After Kidney Transplantation: A Prospective Study.

BACKGROUND: Modifications of erythrocyte membrane fatty acid (FA) contents may affect cellular function or transmembrane receptors. One cross-sectional study has shown that kidney transplant (KTP) recipients have lower erythrocyte membrane oleic acid content than dialysis patients do. Therefore, we prospectively tested whether erythrocyte membrane contents of FA including oleic acid change after KTP. METHODS: We recruited 23 KTP recipients (September 2011 through May 2014). Blood samples were obtained immediately before KTP and 6 months after. Erythrocyte membrane FA contents were measured by gas chromatography. RESULTS: Mean age of the enrolled KTP recipients was 45.3 ± 10.9 years, and men represented 66.7% of the cases. ABO-incompatible KTPs constituted 14.3% and cadaver donors 42.9% of the cases. Steroids, mycophenolate mofetil, and tacrolimus were used as immunosuppressive treatment. There was no significant difference in dietary consumption between time points before and 6 months after KTP. Total cholesterol and low-density lipoprotein cholesterol levels were significantly higher at 6 months after KTP as compared with baseline. Erythrocyte membrane contents of polyunsaturated FA, ω-3 FA, ω-6 FA, and the ω-3 index were significantly higher, but erythrocyte membrane contents of total saturated FAs, total monounsaturated FAs, including oleic acid, total trans-FA, palmitoleic acid, and the ω-6-to-ω-3 ratio were significantly lower at 6 months after KTP. CONCLUSIONS: Erythrocyte membrane FA contents significantly changed toward a more favorable cardiovascular profile after KTP. These changes in erythrocyte membrane FA contents may be related to improved renal function because of the absence of significant dietary changes.

Eliminating artifacts in single-grid phase-contrast x-ray imaging for improving image quality.

In this study, we propose a modification to a single-grid phase-contrast x-ray imaging (PCXI) system using a Fourier domain analysis technique to extract absorption, scattering, and differential phase-contrast images. The proposed modification is to rotate the x-ray grid in the image plane to achieve spectral separation between the desired information and the moiré artifact, which is introduced by the superposition of the periodic image of the grid shadow and the periodic sampling by the detector. In addition, we performed some system optimization by adjusting distances between source, object, grid, and detector to further improve image quality. This optimization aimed to increase the spectral spacing between the primary spectrum (lower frequency) and the harmonics of the spectrum (higher frequency) used to extract the various image contrasts. The table-top setup used in the experiment consisted of a focused-linear grid with a 200-lines/inch strip density, a microfocus x-ray tube with a 55-µm focal spot size, and a CMOS flat-panel detector with a 49.5-µm pixel size. The x-ray grid was rotated at 27.8° with respect to the detector and the sample was placed as close as possible to the x-ray tube. Our results indicated that the proposed method effectively eliminated the PCXI artifacts, thus improving image quality.

Evolution and persistence of resistance-associated substitutions of hepatitis C virus after direct-acting antiviral treatment failures.

Daclatasvir plus asunaprevir (DCV+ASV) treatment is an all-oral direct-acting antiviral (DAA) therapy for the genotype 1b HCV-infected patients. In this study, we investigated how resistance-associated substitutions (RASs) evolved after treatment failures and assessed the effect of those substitutions on viral fitness. Sequencing of NS5A and NS3 revealed typical RASs after treatment failures. Interestingly, the RASs of NS3 reverted to the wild-type amino acid within 1 year after treatment failures. However, the RASs of NS5A were stable and did not change. The effect of NS5A and NS3 RASs on viral RNA replication was assessed after mutagenic substitution in the genotype 1b HCV RNA. Among single substitutions, the effect of D168V was more substantial than the others and the effect of the triple mutant combination (D168V+L31V+Y93H) was the most severe. The RAS at NS5A Y93 affected both viral RNA replication and virus production. Finally, the effect of trans-complementation of NS5A was demonstrated in our co-transfection experiments and these results suggest that such a trans-complementation effect of NS5A may help maintain the NS5A RASs for a long time even after cessation of the DAA treatment. In conclusion, the results from this investigation would help understand the emergence and persistence of RASs.

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-glucoside potentiates self-renewal of human dental pulp stem cells via the AMPK/ERK/SIRT1 axis.

AIM: To evaluate the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (THSG) on cell proliferation and examine the mechanisms of THSG-enhanced proliferative potential in human dental pulp stem cells (hDPSC). METHODOLOGY: After treatment with THSG, hDPSC were collected. Cell viability was determined by MTS assay, while messenger RNA (mRNA) expressions of proliferation and stem cell markers were analyzed using real-time PCR. Flow cytometry was also conducted to analysis protein expression of stem cell markers. A colony-forming unit assay of hDPSC was carried out. Cellular telomerase activity was also identified using real-time PCR. In addition, proliferation-related proteins involved in the effects of THSG on hDPSC were analyzed by Western blotting. Data were analyzed using one-way analysis of variance and two-tailed Student's t-test. RESULTS: Cell viability, colony-forming rates and telomerase activities of hDPSCs were enhanced after THSG treatment. mRNA expressions of proliferation markers (including expressions of NAD+-dependent histone deacetylase sirtuin 1 (SIRT1), proliferating cell nuclear antigen (PCNA), cyclin D1 and ribonucleotide reductase subunit M2 (RRM2)) increased significantly after THSG treatment (P < 0.05). Treatment with THSG for 3 h significantly augmented SIRT1 protein expression (P < 0.05). Furthermore, activities of proliferation-related proteins (including AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK) had also significantly increased at 3 h (P < 0.05). After THSG treatment, increased gene and protein expressions of pluripotent-like stem cell markers (including NANOG, OCT4, and SOX2) were observed. CONCLUSIONS: 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-glucoside treatment enhanced the renewal ability and proliferative potential of hDPSCs via the AMPK/ERK/SIRT1 axis, which may provide a novel autogenic cell-based therapeutic strategy in regenerative dentistry.

Impact of controlled attenuation parameter on detecting fibrosis using liver stiffness measurement.

BACKGROUND: Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis. AIM: To determine how to use CAP in interpreting liver stiffness measurements. METHODS: This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP. RESULTS: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis. CONCLUSIONS: Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.

Accurate representation of interference colours (Michel-Lévy chart): from rendering to image colour correction.

Here a work flow towards an accurate representation of interference colours (Michel-Lévy chart) digitally captured on a polarised light microscope using dry and oil immersion objectives is presented. The work flow includes accurate rendering of interference colours considering the colour temperature of the light source of the microscope and chromatic adaptation to white points of RGB colour spaces as well as the colour correction of the camera using readily available colour targets. The quality of different colour correction profiles was tested independently on an IT8.7/1 target. The best performing profile was using the XYZ cLUT algorithm and it revealed a ΔE00 of 1.9 (6.4 no profile) at 5× and 1.1 (8.4 no profile) at 100× magnification, respectively. The overall performance of the workflow was tested by comparing rendered interference colours with colour-corrected images of a quartz wedge captured over a retardation range from 80-2500 nm at 5× magnification. Uncorrected images of the quartz wedge in sRGB colour space revealed a mean ΔE00 of 12.3, which could be reduced to a mean of 4.9 by applying a camera correction profile based on an IT8.7/1 target and the Matrix only algorithm (ΔE00 < 1.0 signifies colour differences imperceptible by the human eye). ΔE00 varied significantly over the retardation range of 80-2500 nm of the quartz wedge, but the reasons for this variation is not well understood and the quality of colour correction might be further improved in future by using custom made colour targets specifically designed for the analysis of high-order interference colours.

Survival benefit of liver resection for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma.

BACKGROUND: Although transarterial chemoembolization is recommended as the standard treatment for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma (BCLC-B HCC), other treatments including liver resection have been used. This study aimed to determine the survival benefit of treatment strategies including resection for BCLC-B HCC compared with non-surgical treatments. METHODS: The nationwide multicentre database of the Korean Liver Cancer Association was reviewed. Patients with BCLC-B HCC who underwent liver resection as a first or second treatment within 2 years of diagnosis and patients who received non-surgical treatment were selected randomly. Survival outcomes of propensity score-matched groups were compared. RESULTS: Among 887 randomly selected patients with BCLC-B HCC, 83 underwent liver resection as first or second treatment and 597 had non-surgical treatment. After propensity score matching, the two groups were well balanced (80 patients in each group). Overall median survival in the resection group was better than that for patients receiving non-surgical treatment (50·9 versus 22·1 months respectively; P < 0·001). The 1-, 2-, 3- and 5-year overall survival rates in the resection group were 90, 88, 75 and 63 per cent, compared with 79, 48, 35 and 22 per cent in the no-surgery group (P < 0·001). In multivariable analysis, non-surgical treatment only (hazard ratio (HR) 3·35, 95 per cent c.i. 2·16 to 5·19; P < 0·001), albumin level below 3·5 g/dl (HR 1·96, 1·22 to 3·15; P = 0·005) and largest tumour size greater than 5·0 cm (HR 1·81, 1·20 to 2·75; P = 0·005) were independent predictors of worse overall survival. CONCLUSION: Treatment strategies that include liver resection offer a survival benefit compared with non-surgical treatments for potentially resectable BCLC-B HCC.

Early complications after percutaneous radiofrequency ablation for hepatocellular carcinoma: an analysis of 1,843 ablations in 1,211 patients in a single centre: experience over 10 years.

AIM: To evaluate the incidence of adverse events and associated factors after radiofrequency ablation (RFA) in patients with hepatocellular carcinoma within 30 days. MATERIALS AND METHODS: The early complications that occurred within 30 days after RFA at a single institution from January 2000 to July 2010 were reviewed in order to evaluate the morbidity, mortality, and risk factors associated with the complications. In total, 1,211 patients (845 men, 70.5%) with a mean age of 68 years (range, 27-88 years) underwent 1,843 RFA procedures. RESULTS: The overall incidence rate of complications was 6.8% (125 cases). Major complications (n=36, 2%) included liver abscess (n=15, 0.8%), intraperitoneal bleeding (n=8, 0.4%), liver failure (n=5, 0.3%), variceal bleeding (n=3, 0.2%), haemothorax (n=2, 0.1%), cholecystitis (n=2, 0.1%), and bowel perforation (n=1, 0.1%). Among the minor complications (n=89, 4.8%), the most common was the post RFA syndrome accompanied by pain and fever (n=75, 4.1%). Other minor complications included significant pleural effusion (n=7, 0.4%), skin wound infection (n=4, 0.2%), and thermal injuries to the skin (n=3, 0.2%). Procedural infections significantly increased with tumour size (OR=1.379; 95% confidence interval [CI], 1.191-1.579; p<0.001), and multiple overlapping ablations (OR=1.118; 95% CI, 1.019-1.227, p=0.018). Thrombocytopenia (<50,000/µl), prothrombin time, and serum albumin level were significantly associated with post-RFA bleeding episodes (p=0.041, p=0.021, and p=0.003, respectively). The overall mortality rate was 0.3% (three cases of hepatic failure, two case of sepsis, and one case of renal failure). CONCLUSIONS: RFA is a safe and effective local treatment for hepatocellular carcinoma. Careful selection of patients and appropriate RFA planning could decrease procedural mortality and morbidity.

Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells.

OBJECTIVES: Eukaryotic translation initiation factor 3 (eIF3) is a multi-subunit complex that plays a critical role in translation initiation. Expression levels of eIF3 subunits are elevated or decreased in various cancers, suggesting a role for eIF3 in tumorigenesis. Recent studies have shown that the expression of the eIF3b subunit is elevated in bladder and prostate cancer, and eIF3b silencing inhibited glioblastoma growth and induced cellular apoptosis. In this study, we investigated the role of eIF3b in the survival of osteosarcoma cells. METHODS: To investigate the effect of eIF3b on cell viability and apoptosis in osteosarcoma cells, we first examined the silencing effect of eIF3b in U2OS cells. Cell viability and apoptosis were examined by the Cell Counting Kit-8 (CCK-8) assay and Western blot, respectively. We also performed gene profiling to identify genes affected by eIF3b silencing. Finally, the effect of eIF3b on cell viability and apoptosis was confirmed in multiple osteosarcoma cell lines. RESULTS: eIF3b silencing decreased cell viability and induced apoptosis in U2OS cells, and by using gene profiling we discovered that eIF3b silencing also resulted in the upregulation of tumour necrosis factor receptor superfamily member 21 (TNFRSF21). We found that TNFRSF21 overexpression induced cell death in U2OS cells, and we confirmed that eIF3b silencing completely suppressed cell growth in multiple osteosarcoma cell lines. However, eIF3b silencing failed to suppress cell growth completely in normal fibroblast cells. CONCLUSION: Our data led us to conclude that eIF3b may be required for osteosarcoma cell proliferation by regulating TNFRSF21 expression.Cite this article: Y. J. Choi, Y. S. Lee, H. W. Lee, D. M. Shim, S. W. Seo. Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells. Bone Joint Res 2017;6:186-193. DOI: 10.1302/2046-3758.63.BJR-2016-0151.R2.

The rectal mucosa and condomless receptive anal intercourse in HIV-negative MSM: implications for HIV transmission and prevention.

Most HIV transmissions among men who have sex with men (MSM), the group that accounted for 67% of new US infections in 2014, occur via exposure to the rectal mucosa. However, it is unclear how the act of condomless receptive anal intercourse (CRAI) may alter the mucosal immune environment in HIV-negative MSM. Here, we performed a comprehensive characterization of the rectal mucosal immune environment for the phenotype and production of pro-inflammatory cytokines by CD4 and CD8 T cells, global transcriptomic analyses, and the composition of microbiota in HIV-negative MSM. Our results show that compared with men who had never engaged in anal intercourse, the rectal mucosa of MSM engaging in CRAI has a distinct phenotype characterized by higher levels of Th17 cells, greater CD8+ T cell proliferation and production of pro-inflammatory cytokines, molecular signatures associated with mucosal injury and repair likely mediated by innate immune cells, and a microbiota enriched for the Prevotellaceae family. These data provide a high-resolution model of the immunological, molecular, and microbiological perturbations induced by CRAI, will have direct utility in understanding rectal HIV transmission among MSM, and will enhance the design of future biomedical prevention interventions, including candidate HIV vaccines.

Surface modulation and back reflection from foil targets irradiated by a Petawatt femtosecond laser pulse at oblique incidence.

A significant level of back reflected laser energy was measured during the interaction of ultra-short, high contrast PW laser pulses with solid targets at 30° incidence. 2D PIC simulations carried out for the experimental conditions show that at the laser-target interface a dynamic regular structure is generated during the interaction, which acts as a grating (quasi-grating) and reflects back a significant amount of incident laser energy. With increasing laser intensity above 1018 W/cm2 the back reflected fraction increases due to the growth of the surface modulation to larger amplitudes. Above 1020 W/cm2 this increase results in the partial destruction of the quasi-grating structure and, hence, in the saturation of the back reflection efficiency. The PIC simulation results are in good agreement with the experimental findings, and, additionally, demonstrate that in presence of a small amount of pre-plasma this regular structure will be smeared out and the back reflection reduced.

Blue Emitters Based on Aryl End-Capped Pyrene Groups for OLEDs.

We have synthesized four pyrene-derived blue emitting materials using Suzuki cross coupling reactions. All OLED devices using these materials as emitting materials showed efficient blue electroluminescence (EL). Particularly, a device using 1,1'-(9,9-dimethyl-9H-fluorene-2,7-diyl)bis-pyrene (1) showed best EL properties with the luminous efficiency of 4.32 cd/A, the power efficiency of 3.98 lm/W and the external quantum efficiency of 2.48% at 500 cd/m2.

Reactivation of Tert in the medial prefrontal cortex and hippocampus rescues aggression and depression of Tert(-/-) mice.

The role of telomerase reverse transcriptase (TERT) has been extensively investigated in the contexts of aging and cancer. Interestingly, Tert(-/-) mice exhibit additional but unexpected aggressive and depressive behaviors, implying the potential involvement of TERT function in mood control. Our conditional rescue experiments revealed that the depressive and aggressive behaviors of Tert(-/-) mice originate from Tert deficiency in two distinct brain structures. Reactivation of Tert in the hippocampus was sufficient to normalize the depressive but not the aggressive behaviors of Tert(-/-) mice. Conversely, re-expression of Tert in the medial prefrontal cortex (mPFC) reversed the aggressive but not the depressive behavior of Tert(-/-) mice. Mechanistically, decreased serotonergic signaling and increased nitric oxide (NO) transmission in the hippocampus transduced Tert deficiency into depression as evidenced by our observation that the infusion of a pharmacological agonist for serotonin receptor 1a (5-HTR1A) and a selective antagonist for neuronal NO synthase into the hippocampus successfully normalized the depressive behavior of Tert(-/-) mice. In addition, increased serotonergic transmission by the 5-HTR1A agonist in the mPFC was sufficient to rescue the aggressive behavior of Tert(-/-) mice. Thus, our studies revealed a novel function of TERT in the pathology of depression and aggression in a brain structure-specific manner, providing direct evidence for the contribution of TERT to emotional control.