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Macrophage migration is an essential step in host defense against infection and wound healing. Elevation of cAMP by inhibiting phosphodiesterase 4 (PDE4), enzymes that specifically degrade cAMP, is known to suppress various inflammatory responses in activated macrophages, but the role of PDE4 in macrophage migration is poorly understood. Here we show that the migration of Raw 264.7 macrophages stimulated with LPS was markedly and dose-dependently induced by the PDE4 inhibitor rolipram as assessed by scratch wound healing assay. Additionally, this response required the involvement of serum in the culture medium as serum starvation abrogated the effect. Further analysis revealed that rolipram and serum exhibited synergistic effect on the migration, and the influence of serum was independent of PDE4 mRNA expression in LPS-stimulated macrophages. Moreover, the enhanced migration by rolipram was mediated by activating cAMP/exchange proteins directly activated by cAMP (Epac) signaling, presumably via interaction with LPS/TLR4 signaling with the participation of unknown serum components. These results suggest that PDE4 inhibitors, together with serum components, may serve as positive regulators of macrophage recruitment for more efficient pathogen clearance and wound repair.

Background: Modification of human airway smooth muscle (ASM) function by proinflammatory cytokines has been regarded as a potential mechanism underlying bronchial hyperresponsiveness in asthma. Human ASM cells express intercellular adhesion molecule (ICAM)-1 in response to cytokines. Synthetic ligands for peroxisome proliferator-activated receptor (PPAR)γ reportedly possess anti-inflammatory and immunomodulatory properties. In this study, we examined whether ciglitazone, a synthetic PPARγ ligand, can modulate the basal and tumor necrosis factor (TNF)α-induced ICAM1 gene expression in human ASM cells. Methods: Human ASM cells were treated with TNFα. ICAM-1 expression was assessed by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. PPARγ activity was inhibited by target-specific small interfering (si) RNA targeting PPARγ and GW9662, a PPARγ antagonist. Activity of nuclear factor (NF)-κB was assessed by using immunoblot analysis, immune-confocal images, and electrophoretic mobility shift assay (EMSA). Results: By flow cytometry, ciglitazone alone had no effect on ICAM-1 expression in ASM cells, but inhibited ICAM-1 expression in response to TNFα (10 ng/ml) in a dose-dependent manner (1-10 μM). It also inhibited TNFα-induced ICAM1 gene expression by RT-PCR analysis. Knockdown of PPAR γ gene by target-specific siRNA targeting PPAR γ enhanced ICAM-1 expression and the inhibitory effect of ciglitazone on TNFα-induced ICAM-1 expression was reversed by PPARγ siRNA and GW9662. SN-50 (10 μg/ml), an inhibitor for nuclear translocation of NF-κB, inhibited TNFα-induced ICAM-1 expression. Ciglitazone did not prevent TNFα-induced degradation of the cytosolic inhibitor of NF-κB (IκB), but inhibited the nuclear translocation of p65 induced by TNFα and suppressed the NF-κB/DNA binding activity. Conclusion: These findings suggest that ciglitazone inhibits TNFα-induced ICAM1 gene expression in human ASM cells through the ligand-dependent PPARγ activation and NF-κB-dependent pathway.

We report the observation of an order of magnitude enhancement of the thermoelectric figure of merit (ZT = 0.36) in topological insulator Bi1.5Sb0.5Te1.7Se1.3 nanowires at 300 K as compared with the bulk specimen (ZT = 0.028). The enhancement was primarily due to an order of magnitude increase in the electrical conductivity of the surface-dominated transport and thermally activated charge carriers in the nanowires. Magnetoresistance analysis revealed the presence of Dirac electrons and determined that the Fermi level was near the conduction band edge. This may be the first thermoelectric measurement of samples with a chemical potential in the gap of a topological insulator without gate tuning, and provides an opportunity to study the contribution of surface states to the Seebeck coefficient and resistivity without concern for the complex effect of band bending.

Background: Despite the use of anatomic resection, the post-surgical recurrence rate remains high in early-stage non-small cell lung cancer (NSCLC). Chronic infl ammation plays a role in the mechanism that promotes tumor initiation. This study aimed to investigate the association between recurrence outcome and chronic infl ammation-related co-morbidities in early-stage resected NSCLC. Methods: A review of medical records for recurrence outcome and co-morbidities, in terms of chronic obstructive pulmonary disease (COPD), DM, asthma and cardiovascular diseases, was performed with 181 patients with stage I NSCLC that underwent anatomic resection. Results: Subjects with T descriptors as T2a disease (49.5 vs. 28.0%, p < 0.05) and the presence of COPD (42.4 vs. 20.7%, p < 0.01) had a higher risk of tumor recurrence. Univariate analysis for recurrence-free survival showed T descriptor as T2a (21.5 months vs. NR, p < 0.05) and the presence of COPD (20.5 months vs. NR, p < 0.01) as signifi cant factors predicting reduced survival. The presence of COPD (HR: 1.98; 95% CI, 1.29–.02, p < 0.01) and T descriptor as T2a (HR: 2.01; 95% CI, 1.04–3.91, p < 0.05) remain independent predictors of reduced recurrence-free survival in the Cox regression model. Patients with COPD were at higher risk of brain recurrence (OR: 7.88; 95% CI, 1.50–41.3, p < 0.01). In contrast, patients without COPD showed a tendency toward recurrence in bone and liver (OR: 4.13; 95% CI, 1.08–15.8, p = 0.05). Conclusion: Subjects with COPD and T2a disease had a higher risk of recurrence. The role of COPD as a recurrence promoter merits further prospective investigation.

OBJECTIVES: The diagnosis of peripheral pulmonary lesions (PPLs) often involves endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB), washing and brushing. Certain echoic features of PPL have been associated with biopsy yield. This study compared yields of TBB and bronchial washing (TBBW) with those of TBBW plus bronchial brushing and analysed the associations between clinical and echoic features and yield. METHODS: We performed a retrospective review of 271 patients undergoing TBB for PPL. TBBW was performed in 139 patients and 132 underwent TBBW plus brushing. RESULTS: The diagnostic yield of TBBW plus brushing was superior to that of TBBW (80.3 vs 66.2%, P< 0.01). In TBBW patients, lesions

Introduction Most studies related to healthcare-associated infection with Acinetobacter baumannii (HAIA) are on acutely ventilated patients. Little is known regarding the incidence and outcomes of HAIA in chronically ventilated patients. Methods A retrospective study of chronically ventilated patients covering the period May 2002 to May 2008 was conducted to determine the incidence of patients with HAIA. The Cox proportional hazard model was used to estimate differences in the 30-day mortality between those with and those without HAIA by case-control study after controlling for confounders. Results Of 240 patients who were chronically ventilated for 49,207 days, 78 (32.5%) acquired HAIA at a rate of 1.59/1,000 patient day. The central venous catheter-related bloodstream infections rate was 8.78 per 1,000 catheter days; the ventilator-associated pneumonia rate was 1.26 per 1,000 ventilator days; and the catheter-associated urinary tract infections rate was 0.17 per 1,000 catheter days. Fifty (64.1%) HAIA and 58 (64.4%) non-HAIA patients were treated well and survived without ICU admission. After univariate and multivariate analyses, prolonged ventilation days (odds ratio: 3.4; 95% confidence interval: 1.7-6.1; P = 0.01] and inappropriate empiric antibiotics within 48 hours (odds ratio: 7.9; 95% confidence interval: 3.9-9.8; P = 0.02) were independent factors that predicted the 30-day mortality of HAIA among chronically ventilated patients. Conclusions Although chronically ventilated patients with HAIA have longer ventilator days, higher antibiotics resistance, and high rate per 100 patients of ventilator-associated pneumonia, most patients are treated well. Compared with patients without HAIA, prolonged ventilation days and inappropriate empiric antibiotics within 48 hours are independent factors of the 30-day mortality.

Profiles of spectral lines due to the thermal motion of light-emitting particles are formulated based on the classical and the relativistic Doppler effects, respectively. For the classical case, the well-known Doppler-broadened line profile is reproduced. For the relativistic case, the line profile obtained is asymmetrically broadened with increasing temperature. However, the peak frequency remains unshifted, in contrast to blueshifted, as has been predicted in the current literature. Reasoning is given as to why the relativistic Doppler-broadened line profile currently accepted is probably invalid.

Bradykinin (BK), a G-protein-coupled-receptor (GPCR) agonist via the B2 receptor induces interleukin (IL)-6 expression in airway smooth muscle (ASM) cells by involving the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. In some cell species, GPCR agonists have been shown to activate the ERK 1/2 pathway via transactivation of epidermal growth factor (EGF) receptor (EGFR). In this study, we tested whether there is cross-talk between BK and EGF in the regulation of IL-6 gene expression in ASM cells.ASM cells were treated with BK, EGF, AG-1478 and genistein. IL-6 production was analyzed by enzyme-linked immunosorbent assay (ELISA). Immunoblot study was used for detection of ERK1/2 activation. Transactivation of EGFR phosphorylation was detected by immunoprecipitation.ELISA showed that EGF (10 ng/ml, 18 hr) increased IL-6 secretion (from 234 +/- 35 to 923 +/- 494 pg/ml, n = 5, p0.05), and significantly enhanced BK-induced IL-6 secretion (from 4383 +/- 296 to 8312 +/- 1267 pg/ml, n = 5, p0.05) in ASM. Moreover, AG-1478 (2 microM), reduced BK-induced IL-6 secretion by 28% and abrogated the synergic induction of IL-6 induced by BK plus EGF (from 8312 +/- 1267 to 3229 +/- 597 pg/ml, n = 5, p0.05). AG-1478 dual effects on IL-6 secretion induced by BK alone or BK plus EGF were also observed in cells treated with genistein, a tyrosine kinase inhibitor, and AG-825, an ErbB-2 inhibitor. Immunoblot analysis demonstrated that AG-1478 had no effect on ERK1/2 activation by BK (1 microM, 10 min). Immunoprecipitation studies showed that BK (1 muM for 2, 5 and 10 min) did not directly transactivate EGFR phosphorylation.These data show that BK and EGF act in concert to regulate the expression of IL-6 in ASM cells possibly via transcriptional mechanisms involving EGFR-associated key signaling molecules.

In this study, structurally uniform single crystalline PbTe nanowires (NWs) were synthesized using a stress-induced growth. Selected-area electron diffraction patterns show that the PbTe NWs were grown along the [100] direction. The electrical conductivity σ of a NW with 142 nm in diameter exhibited a semiconducting behavior at 50–300 K. An enhancement of electrical conductivity σ up to 2383 S m−1 at 300 K is much higher than σ [0.44–1526 S m−1, Chen et al., Appl. Phys. Lett. 103, p023115, (2013)] in previous studies. The room temperature magnetoresistance of the 142 nm NW was ∼0.8% at B = 2 T, which is considerably higher than that [0.2% at B = 2 T, Ovsyannikov et al., Sol. State Comm. 126, 373, (2003)] of the PbTe bulk reported.

In this study, a series of Bi1.5Sb0.5Te1.7Se1.3 (BSTS) flakes 80-nm to 140-μm in thickness was fabricated to investigate their metallic surface states. We report the observation of surface-dominated transport in these topological insulator BSTS nanoflakes. The achievement of surface-dominated transport can be attributed to high surface mobility (∼3000 cm2/V s) and low bulk mobility (12 cm2/V s). Up to 90% of the total conductance, the surface channel was estimated based on the thickness dependence of electrical conductance and the result of the Shubnikov-de Hass oscillations in a 200-nm BSTS. The nature of nontrivial Dirac surface states was also confirmed by the weak anti-localization effect.

We show that for Hamiltonian of the form, H=c(t)∂x∂x+V(x,t), the general potential V(x, t) for which Airy packets remain nonspreading under time evolution can only be of the form V(x,t)=p(t)x+q(t), where p(t) and q(t) are real functions. We derive rules for constructing nonspreading Airy packets from this general potential. We also consider normalizable packets obtained from Airy packet times a converging factor, such as eβx, with β> 0. We show that there is no potential which sustains nonspreading wave packets of this kind.