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In this study, we present morphology control investigations on zinc oxide (ZnO) nanorods synthesized by microwave heating of a mixture of zinc nitrate hexahydrate and hexamethylenetetramine (HMTA) precursors in deionized water (DI water). To study the morphology and structural variations of the obtained ZnO nanorods in different molar ratio of zinc nitrate hexahydrate to HMTA, X-ray diffraction (XRD), scanning electron microscopy (SEM) images, Raman scattering, and photoluminescence (PL) spectroscopy were measured. XRD and SEM images are utilized to examine the crystalline quality as well as the morphological properties of the ZnO nanorods. It is found that morphology control can be achieved by simply adjusting the reactant concentrations and the molar ratio of zinc nitrate hexahydrate to HMTA. Raman scattering and PL spectroscopy measurements were demonstrated to study the size- and shape-dependent optical response of the ZnO nanorods. The Raman scattering result shows that the intensity of LO mode at around 576 cm−1 decreases with the increase in the molar ratio of zinc nitrate hexahydrate to HMTA, indicating the reduction of defect concentrations in the synthesized ZnO nanorods. Room temperature PL spectrum of the synthesized ZnO nanorods reveals an ultraviolet (UV) emission peak and a broad visible emission. An enhancement of UV emission appears in the PL spectra as the molar ratio of zinc nitrate hexahydrate to HMTA increases, indicating that the defect concentration of the synthesized ZnO nanorods can be reduced by increasing the molar ratio.

Oct4, a member of the POU-domain transcription factor family, has been implicated in the cancer stem cell (CSC)-like properties of various cancers. However, the precise role of Oct4 in colorectal CSC initiation remains uncertain. Numerous studies have demonstrated a strong link between inflammation and tumorigenesis in colorectal cancers. In this study, we demonstrated that Oct4 overexpression enhances CSC-like properties of colorectal cancer cells (CRCs), including sphere formation, cell colony formation, cell migration, invasiveness, and drug resistance. In addition, putative CSC markers, stemness genes, drug-resistant genes, as well as interleukin (IL)-8 and IL-32 were upregulated. Microarray-based bioinformatics of CRCs showed higher expression levels of embryonic stem cell-specific genes in cells that overexpressed Oct4. Neutralization of either IL-8 or IL-32 with specific antibodies partially blocked the tumorigenic effects induced by either Oct4 overexpression or by the addition of conditioned media from Oct4-overexpressing CRCs. In addition, the presence of Oct4-overexpressing CRCs enhanced the tumorigenic potential of parental CRCs in vivo. In summary, these data suggest that IL-8 and IL-32 play a role in regulating the CSC-like properties that promote tumorigenesis of CRCs in both autocrine and paracrine manners.

The study aimed to evaluate whether the inflammatory marker "high-sensitivity C-reactive protein (hsCRP)" level was associated with impaired heart rate recovery at 1 min after exercise termination (HRR-1) in middle-aged patients with severe obstructive sleep apnea (OSA).Thirty middle-aged male patients (40-64 years old) with severe OSA (apnea-hypopnea index [AHI] ≥ 30 h(-1)) and 30 subjects without OSA (AHI5 h(-1)), matched with age and body mass index (BMI), were recruited. All subjects underwent an overnight polysomnography and completed a symptom-limited maximal exercise test. Cardiopulmonary parameters included peak oxygen consumption (VO(2peak)) and heart rate response during and immediately after exercise. Fasting blood samples were drawn for hsCRP analysis.Patients with severe OSA had significantly higher hsCRP levels (0.18 vs. 0.07 mg/dl, P0.01), lower reduced HRR-1, peak heart rate, and VO(2peak) values than those in the controls. The hsCRP levels significantly correlated with HRR-1 in the OSA group (r = -0.69, P0.01) after adjustment for VO(2peak) (r = -0.66, P0.01). Furthermore, stepwise multiple regression analysis showed that HRR-1 and AHI were significant predictors of hsCRP levels in all participants (adjusted R(2) = 0.53, P0.01).Blunted HRR was shown in middle-aged men with severe OSA, and it was associated with high hsCRP levels significantly.

Photoluminescence (PL) spectra of a quaternary alloy In 0.014 Al 0.105 Ga 0.881 N thin film grown by low pressure metalorganic chemical vapor deposition (MOCVD) are studied experimentally in the temperature range of 10–300 K. It is shown that the temperature dependence can be well studied by the Eliseev's model to characterize the scale of the exciton-localization effects for the exciton localization energy. Moreover, the Urbach energy was determined from an analysis of the low-energy side of the PL lineshape. From the temperature dependence of Urbach energy, the value of Urbach energy can be described by the Einstein oscillator model which takes into consideration the contributions from both the thermal and structural disorders.

Endothelin-1 (ET-1) has been demonstrated to induce insulin resistance (IR) and lipolysis, raising the possibility that ET-1 may also contribute to the elevated fatty acid levels in IR-associated comorbidities. We attempted to evaluate whether ET-1 also affects the long-chain fatty acid (LCFA) utilization in 3T3-L1 adipocytes. The effects of chronic ET-1 exposure on basal and insulin-stimulated LCFA uptake, and LCFA uptake kinetics were examined in 3T3-L1 adipocytes. Chronic exposure to ET-1 induced IR and suppressed basal and insulin-stimulated LCFA uptake. Given that insulin acutely stimulates LCFA uptake, there was dramatically similar trend of dose-response curves for ET-1-suppressed LCFA uptake, and also similar corresponding IC₅₀ values, between basal and insulin-stimulated states, reflecting that ET-1 predominantly suppresses basal LCFA uptake. Results of LCFA kinetics, western blots, and CD36 inhibition using sulfosuccinimidyl oleate (SSO) revealed that suppression of LCFA uptake by ET-1 is associated with downregulation of CD36. ET type A receptor (ET(A)R) antagonist BQ-610 reversed the IR induction and the ET-1-suppressed LCFA uptake. Exogenous replenishment of phosphatidylinositol (PI) 4, 5-bisphosphate (PIP₂) prevented IR induction, but not the suppression of LCFA uptake by ET-1. Pharmacological inhibition of the activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) completely blocked the ET-1-suppressed LCFA uptake. Serving as an inducer of IR, ET-1 also chronically suppresses LCFA uptake via PIP₂-independent and ERK-dependent pathway. The interplay between impaired glucose disposal and diminished LCFA utilization, induced by ET-1, could worsen the dysregulation of adipose metabolism and energy homeostasis in insulin-resistant states.

The precise pathogenesis of obesity remains controversial. In obesity, diminished adipose glucose utilization suggests that some other substrates may be responsible for the adipose triglyceride (TG) overaccumulation. Here we attempted to evaluate if long-chain fatty acid (LCFA) flux was modulated by a physiologically relevant condition of hyperinsulinemia in 3T3-L1 adipocytes and if the altered LCFA influx might eventually contribute to the TG overaccumulation in obesity. The effects of prolonged insulin exposure to adipocytes on basal, insulin-stimulated LCFA uptake as well as intracellular LCFA metabolism were measured. Prolonged insulin exposure was found to induce insulin resistance (IR) yet enhance basal and insulin-stimulated LCFA uptake in normoglycemic condition, and the addition of high glucose exacerbated these abnormalities of both glucose and LCFA influx. Along with the enhanced LCFA uptake was an increase in the rates of intracellular LCFA deposition and incorporation into TG; but a decrease was found in basal and insulin-suppressive LCFA oxidation, as well as in isoproterenol-induced fatty acid efflux. Inhibition of either phosphatidylinositol 3-kinase or mitogen-activated protein kinase (MAPK) pathway did not prevent the induction of IR, whereas the enhanced basal and insulin-stimulated LCFA uptake was abrogated by inhibition of MAPK pathway. In hyperinsulinemic insulin-resistant 3T3-L1 adipocytes, basal and insulin-stimulated LCFA uptake tends to increase via a MAPK-dependent mechanism. The increment of LCFA influx predominantly accounts for TG overaccumulation, but not for mitochondrial oxidation, and is prone to retain within adipocytes. These findings may interpret the plausible mechanism of pathogenesis for obesity in hyperinsulinemia-associated IR.

We have studied the enhancement of conversion efficiency in GaAs solar cells using silver nanoparticles with particle average sizes between 11.4 to 17.2 nm. The maximum enhancement of 20.2% in conversion efficiency is achieved for the GaAs solar cells where the Ag nanoparticles have been incorporated. The simulations according to Mie theory suggest that the increased radiative scattering and conversion efficiency is due to a combined effect of the surface plasmon resonance and the interband transition.

Prostate cancer (PCa) is the most common noncutaneous cancer in men worldwide. One of its major treatments is androgen deprivation therapy, but PCa frequently relapses as aggressive castration resistant local tumors and distal metastases. Hence, the development of novel agents or treatment modalities for advanced PCa is crucial. Many tumors, including PCa, first metastasize to regional lymph nodes via lymphatic vessels. Recent findings demonstrate that the bioactive lipid lysophosphatidic acid (LPA) promotes PCa progression by regulating vascular endothelial growth factor-C (VEGF-C), a critical mediator of tumor lymphangiogenesis and lymphatic metastasis. Many of the underlying molecular mechanisms of the LPA–VEGF-C axis have been described, revealing potential biomarkers and therapeutic targets that may aid in the diagnosis and treatment of advanced PCa. Herein, we review the literature that illustrates a functional role for LPA signaling in PCa progression. These discoveries may be especially applicable to anti-lymphangiogenic strategies for the prevention and therapy of metastatic PCa.

We report the characterization of nano-size zinc oxide (ZnO) powder synthesized via microwave-assisted heating of Zn(CH 3 COO) 2 ·2H 2 O and NaHCO 3 solution with deionized water (DI water) as the solvent. The as-synthesized ZnO powder was calcined at temperatures from 400 to 800 °C for 8 h. The X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) spectra revealed pure wurtzite structure for the ZnO nanopowder (NP) calcined at 800 °C. Scanning electron microscopy (SEM) images showed increasing size ZnO NP with uniform size distribution with increase in calcination temperature. Significant UV emission at about 373 nm has been observed in the photoluminescence (PL) spectra of the as-synthesized and calcined ZnO NP. Our results showed enhanced PL intensity with a reduced full-width at half-maximum (FWHM) for ZnO NP synthesized at higher calcination temperature.

The structural and optical properties of ZnO films deposited on Si substrate following rapid thermal annealing (RTA) have been investigated by X-ray diffraction (XRD), atomic force microscopy (AFM), and photoluminescence (PL) measurements. After RTA treatment, the XRD spectra have shown an effective relaxation of the residual compressive stress, an increase of the intensity and narrowing of the full-width at half-maximum (FWHM) of the (0 0 2) diffraction peak of the as-grown ZnO film. AFM images show roughening of the film surface due to increase of grain size after RTA. The PL spectrum reveals a significant improvement in the UV luminescence of ZnO films following RTA at 800 °C for 1 min.

To form a low noise figure and uniform shortpass band in optical fiber communications an improved automatic filtered power control (AFPC) pumping method is proposed here. A modulated single laser signal was entered in a closed feedback loop, in which the erbium-doped fiber amplifier (EDFA) was used as a part of the AFPC loop. Owing to the constant filtered signal and the quadrature phase shift delay inside the feedback loop, an optical pass band was uniformly formed. This EDFA attains high performance with a low noise figure simultaneously. The method was successfully applied to the fabrication of practical 12.0 m length of erbium-doped fiber pumped at 980 nm wavelength and 20 dBm power. Experiments prove that the signal gain of the loop remain flat in the range of 18.2 to 22.4 dB with a worst case error of ±0.5 dB and the noise figure was reduced by 2.2 dB at optimal, which correspond to a shortpass range of 40 nm band pass from 1525 nm to 1565 nm in wavelength. Of course, it should be possible to extent the system performance to all pumping configurations for semiconductor optical amplifiers. This provides the simplest and most economical way to transmit a well-defined band of modulated laser signal and to reject all other unwanted radiation.

OBJECTIVES: To compare a bioelectrical impedance analysis (BIA) prediction equation for estimating skeletal muscle mass (SM) with magnetic resonance imaging (MRI)-measured SM and to investigate the prevalence of sarcopenia in community-dwelling elderly people in Taiwan. DESIGN: Cross-sectional survey. SETTING: Communities in the district of Zhongzheng, Taipei. PARTICIPANTS: Forty-one volunteers (aged 22–90) for BIA equation validation; 302 individuals aged 65 and older and 200 adults aged 18 to 40 for the investigation of the prevalence of sarcopenia. MEASUREMENTS: Skeletal muscle mass was estimated using a BIA prediction equation and measured using MRI. RESULTS: No statistical difference between MRI-measured and BIA-derived SM was observed (difference of −0.44 ± 1.55 kg, P=.08). The prevalence of sarcopenia in was 18.6% in elderly women and 23.6% in elderly men. CONCLUSION: Estimation of SM using a BIA equation was validated in Taiwanese volunteers. It was confirmed that sarcopenia is an emerging health problem in the aging population in Taiwan.

This study was designed: (1) to test the reliability of surface electromyography (sEMG) recording of the diaphragm and external intercostals contractions response to cervical magnetic stimulation (CMS), (2) to examine the amount and the types of inspiratory muscle fatigue that developed after maximum voluntary ventilation (MVV) maneuvers.Ten male college students without physical disability (22.1±2.0 years old) participated in the study and each completed a control (quiet breathing) trial and a fatigue (MVV maneuvers) trial sequentially. In the quiet breathing trial, the subjects maintained quiet breathing for five minutes. The subjects performed five maximal static inspiratory efforts and received five CMS before and after the quiet breathing. In the MVV trial, subjects performed five maximal inspiratory efforts and received five CMS before, immediately after, and ten minutes after two sets of MVV maneuvers performed five minutes apart. Maximal inspiratory pressure (PImax), sEMG of diaphragm and external intercostals during maximal static inspiratory efforts and during CMS were recorded. In the quiet breathing trial, high intraclass correlation coefficients (ICC=0.95-0.99) were observed in all the variables. In the MVV trial, the PImax, the EMG amplitude and the median power frequency during maximal static inspiratory efforts significantly decreased in both the diaphragm and the external intercostals immediately after the MVV maneuvers Sensors 2008, 8 2175 (P < 0.05) and remained decreased in the diaphragm but not in the external intercostals after ten minutes of recovery. MVV maneuvers induced no EMG changes during CMS in either the diaphragm or the external intercostals (P > 0.05). It is concluded that the sEMG recordings of the diaphragm during maximal static inspiratory efforts and in response to CMS allow reproducible sequential assessment of diaphragm contractility. MVV maneuvers resulted in inspiratory muscles fatigue, possibly central fatigue.

Single crystals of 2H-MoSe 2 were investigated by the anisotropic photoconductivity (PC) measurements as a function of temperature in the range of 12–300 K. A significant shift towards lower energy has been observed in the PC spectra of the edge plane with respect to the van der Waals plane. The anisotropy in the indirect energy gap is being attributed to crystal anisotropy. The parameters that describe the temperature dependence of the anisotropic indirect energy gap are evaluated and discussed utilizing the Varshni and Manoogian–Woolley semi-empirical relationships. The Debye temperature of the sample has also been estimated by the fitted values.

The influence of rapid thermal annealing (RTA) on the optical and structural properties of ZnO thin films grown on Si substrate has been investigated by X-ray diffraction (XRD), photoluminescence (PL), and Raman scattering (RS) measurements. The relaxation of the residual stress by increasing the annealing temperature during the RTA process was observed by the measured shift of (002) XRD diffraction peak towards 34.40∘ and the shift of RS E 2 (high) mode closer to 437 cm−1. The process also resulted in a reduction of the measured full-width at half maximum (FWHM) of the PL emission line and that of the asymmetrical broadening of RS E 2 (high) mode. The observed changes have demonstrated that RTA is a viable technique for improving the crystalline quality of ZnO/Si films.

Wolfram syndrome 2 (WFS2) is a premature aging syndrome caused by an irreversible mitochondria-mediated disorder. Cisd2, which regulates mitochondrial electron transport, has been recently identified as the causative gene of WFS2. The mouse Cisd2 knockout (KO) (Cisd2(-/-)) recapitulates most of the clinical manifestations of WFS2, including growth retardation, osteopenia, and lordokyphosis. However, the precise mechanisms underlying osteopenia in WFS2 and Cisd2 KO mice remain unknown. In this study, we collected embryonic fibroblasts from Cisd2-deficient embryos and reprogrammed them into induced pluripotent stem cells (iPSCs) via retroviral transduction with Oct4/Sox2/Klf4/c-Myc. Cisd2-deficient mouse iPSCs (miPSCs) exhibited structural abnormalities in their mitochondria and an impaired proliferative capability. The global gene expression profiles of Cisd2(+/+), Cisd2(+/-), and Cisd2(-/-) miPSCs revealed that Cisd2 functions as a regulator of both mitochondrial electron transport and Wnt/β-catenin signaling, which is critical for cell proliferation and osteogenic differentiation. Notably, Cisd2(-/-) miPSCs exhibited impaired Wnt/β-catenin signaling, with the downregulation of downstream genes, such as Tcf1, Fosl1, and Jun and the osteogenic regulator Runx2. Several differentiation markers for tridermal lineages were globally impaired in Cisd2(-/-) miPSCs. Alizarin red S staining and flow cytometry analysis further revealed that Cisd2(-/-) miPSCs failed to undergo osteogenic differentiation. Taken together, our results, as determined using an miPSC-based platform, have demonstrated that Cisd2 regulates mitochondrial function, proliferation, intracellular Ca(2+) homeostasis, and Wnt pathway signaling. Cisd2 deficiency impairs the activation of Wnt/β-catenin signaling and thereby contributes to the pathogeneses of osteopenia and lordokyphosis in WFS2 patients.

Background Fabry disease (FD) causes progressive glycosphingolipid accumulation and damage in various organs, and several proinflammatory processes may be involved in this disease. Enzyme replacement therapy (ERT) can reduce the severity of Fabry cardiomyopathy (FC), but whether ERT could attenuate proinflammatory cytokines in FC remains unclear. In this study, we attempted to evaluate the efficacy of ERT on proinflammatory cytokines and vascular cell adhesion biomarkers. Methods We enrolled 25 patients with FC and administered ERT to them according to the present clinical guideline. We analyzed and compared echocardiographic and blood examination results between 25 patients with FD without left ventricular hypertrophy (LVH), 25 patients with FC with LVH who were receiving ERT, and 25 healthy age- and sex-matched controls. The parameters of cardiac function at baseline and 12 months after ERT were assessed through echocardiography, and the expression profiles of proinflammatory biomarkers were determined. Results Left ventricular mass (LVM), LVM index (LVMI), interventricular septal thickness at diastole, and serum levels of globotriaosylsphingosine (Gb3) were elevated in patients with FC. Meanwhile, several proinflammatory cytokines, including interleukin (IL)-6, IL-2, IL-1b, tumor necrosis factor-α, intercellular adhesion molecule, soluble vascular cell adhesion molecule, and monocyte chemoattractant protein-1 (MCP-1) were concomitantly increased. ERT significantly reduced these transthoracic echocardiographic parameters and lyso-Gb3 and proinflammatory cytokine levels. The changes in IL-6, MCP-1, and lyso-Gb3 levels were positively correlated with the change in LVMI. Conclusions Our study has revealed that proinflammatory biomarkers, particularly IL-6 and MCP-1, may represent effective biomarkers for evaluating ERT outcomes in patients with FC.

Objectives. Cardiac autonomic imbalance accompanies the progression of chronic heart failure (CHF). It is unclear whether exercise training could modulate autonomic control in CHF. This study aimed to review systematically the effects of exercise training on heart rate recovery (HRR) and heart rate variability (HRV) in patients with CHF.Methods. Literatures were systematically searched in electronic databases and relevant references. Only published randomized controlled trials (RCTs) focusing on exercise training for CHF were eligible for inclusion. Outcome measurements included HRR and HRV parameters.Results. Eight RCTs were eligible for inclusion and provided data on 280 participants (186 men). The participants were 52–70 years of age with New York Heart Association functional class II-III of CHF. Each study examined either aerobic or resistance exercise. Two trials addressed outcome of HRR and six HRV among these studies. Two RCTs showed that moderate aerobic exercise could improve HRR at 2 minutes after exercise training in CHF. Five of six RCTs demonstrated positive effects of exercise training on HRV which revealed the increments in high frequency (HF) and decrements in LF (low frequency)/HF ratio after training.Conclusion. Participation in an exercise training program has positive effects on cardiac autonomic balance in patients with CHF.

The purpose of “Evidence in Practice” is to illustrate how evidence is gathered and used to guide clinical decision making. This article is not a case report. The examination, evaluation, and intervention sections are purposely abbreviated. A 48-year-old man developed severe anterior chest pressure with pain radiating to the left arm in the morning and was sent to the emergency department. Both his serum creatinine phosphokinase and creatinine phosphokinase-MB band levels were elevated significantly, and an elevated plasma troponin I level (14.1 IU) also was noted. The electrocardiogram (ECG) confirmed the evolution of an extensive anteroseptal myocardial infarction (MI). He then was transferred to the intensive care unit where 100 mg of tissue plasminogen activator was administered, followed by a heparin drip; his chest pain subsided with only intermittent episodes thereafter. Monitoring with ECG revealed occasional episodes of ventricular tachycardia, and congestive heart failure was suspected. After medical treatment in the intensive care unit, the patient rarely experienced any chest pain and had a normal sinus rhythm. Three days later, cardiac catheterization was performed, which revealed a 90% occlusion of the left anterior descending artery at the second diagonal, a 50% occlusion of the mid-right coronary artery, a 50% occlusion of a diagonal artery of the circumflex artery, and left ventricular dysfunction (left ventricular ejection fraction of 40%). His New York Heart Association classification was functional class I. A percutaneous transluminal coronary angioplasty (PTCA) with the insertion of a stent in the occluded left anterior descending artery was successfully performed on the same day. Two days later, the patient was discharged with the following medications prescribed: calcium channel blockers (diltiazem, 60 mg 3 times a day), antiplatelet agents (aspirin, 100 mg every day), and nitrates (sublingual nitroglycerin as required). His cardiologist did not prescribe a beta-blocker because of concern about …

The absorption-edge anisotropy of 2H- MoSe2 was studied by photoconductivity (PC) measurements as a function of temperature in the range of 12–300 K. A significant shift towards lower energies has been observed in the PC spectra on the edge plane with respect to those corresponding to the van der Waals (VdW) plane. The parameters that describe the temperature dependence of the absorption edges are evaluated by the Bose–Einstein empirical expression. Effective phonon energy was estimated from the temperature dependence of the Urbach energy. The estimated effective phonon energy for the VdW and edge planes, respectively, can be correlated to the observed Raman active E 1g and A 1g modes.

Chemical vapor transport (CVT) process with bromine as a transporting agent has been utilized for growing large-size MoSe 2 single crystals by adding niobium dopant (nominal concentration ∼0.5%) during the growth process. The maximum-size crystals are about 10×10 mm 2 in surface area and 2 mm in thickness. The large edge plane facilitates an easier study of the influence of crystal anisotropy on the electrical and optical properties of the layered crystals. Anisotropy of the conductivity and indirect band gap parallel and perpendicular to the crystal c -axis due to the interlayer van der Waals interaction and red shift of the indirect and direct band gaps due to doping have been measured. It is found that the electrical and optical properties of niobium-doped MoSe 2 are almost similar to those of the pure MoSe 2 single crystal apart from a drastic reduction in the conductivity anisotropy and red shift of the band gap.

The renin-angiotensin system plays a critical role in the pathogenesis of obesity, obesity-associated hypertension, and insulin resistance. However, the biological actions of angiotensin II (AII) on insulin sensitivity remain controversial. Because angiotensinogen and AII receptors are expressed on adipose tissue, we investigated the effect of AII on the insulin sensitivity of isolated rat adipocytes. The results of a receptor binding assay showed the maximal AII binding capacity of adipocytes to be 8.3 ± 0.9 fmol/7 × 106 cells and the dissociation constant to be 2.72 ± 0.11 nm. Substantial expression of both type 1 and 2 AII (AT1 and AT2) receptors was detected by RT-PCR. AII had no effect on basal glucose uptake, but significantly potentiated insulin-stimulated glucose uptake; this effect was abolished by the AT1 antagonist, losartan. In addition, AII did not alter the insulin binding capacity of adipocytes, but increased insulin-stimulated tyrosine phosphorylation of the insulin receptor β-subunit, Akt phosphorylation, and translocation of glucose transporter 4 to the plasma membrane. AII potentiated insulin-stimulated glucose uptake through the AT1 receptor and by alteration of the intracellular signaling of insulin. Intraperitoneal injection of Sprague Dawley rats with AII increased insulin sensitivity in vivo. In conclusion, we have shown that AII enhances insulin sensitivity both in vitro and in vivo, suggesting that dysregula-tion of the insulin-sensitizing effect of AII may be involved in the development of insulin resistance.

Previous studies have paid much attention to the impact on functional impairment or quality of life from vertebral fractures secondary to osteoporosis, but little research has addressed the function of osteoporotic women without fractures. The purposes of this study were: (1) to describe spinal performance and functional impairment in postmenopausal women with osteoporosis and osteopenia without vertebral fracture, and (2) to investigate the relationship between them. Thirty postmenopausal women diagnosed as having osteoporosis or osteopenia were recruited who fulfilled the following criteria: (1) menopause for at least 6 months; (2) no vertebral fracture; (3) no medication that would interfere with calcium intake. Measurements included assessment of functional impairment and spinal performance including trunk extension/flexion isokinetic strength, spinal range of motion (ROM) and movement velocity in three planes (sagittal, frontal and transverse). The results showed that spinal ROM and velocity were significantly reduced in the osteoporosis group compared with the osteopenia group ( p0.05), but no significant difference in trunk strength was shown. Functional impairment level showed a slight difference between the two groups ( p = 0.042). There was a significant correlation between spinal ROM and motion velocity with bone mineral density; however, functional impairment correlated with motion velocity only in the transverse plane (trunk rotation) ( p0.05). Spinal strength did not show any correlation with other parameters. It was concluded that spinal motion performance declined and functional impairment increased in relation to the severity of bone mineral loss in postmenopausal women without vertebral fracture, but their physical performance was not correlated with functional impairments.

Background: Numerous studies have reported the relationship between sleep duration and obesity in elderly adults; however, little is known about the relationship of sleep duration and sarcopenia. Objective: We examined the relationship of sleep duration with obesity and sarcopenia in community-dwelling older adults. Methods: A total of 488 community-dwelling adults (224 men and 264 women) aged ≥65 years were included in the analysis. Self-reported sleep duration and anthropometric data were collected. Skeletal muscle mass was estimated using the predicted equation from a bioelectrical impedance analysis measurement. Obesity and sarcopenia were defined according to the body mass index and the skeletal muscle mass index, respectively. Results: The association between sleep duration and sarcopenia exhibited a U shape in older adults. Compared to adults with 6-8 h of sleep, adults with Conclusion: There were significant associations of sleep duration with either obesity or sarcopenia in community-dwelling older adults. Gender differences in these associations were also observed.

MicroRNA122 (miR122), a liver-specific microRNA, plays critical roles in homeostatic regulation and hepatic-specific differentiation. Induced pluripotent stem cells (iPSCs) have promising potential in regenerative medicine, but it remains unknown whether non-viral vector-mediated miR122 delivery can enhance the differentiation of iPSCs into hepatocyte-like cells (iPSC-Heps) and rescue thioacetamide-induced acute hepatic failure (AHF) in vivo. In this study, we demonstrated that embedment of miR122 complexed with polyurethane-graft-short-branch polyethylenimine copolymer (PU-PEI) in nanostructured amphiphatic carboxymethyl-hexanoyl chitosan (CHC) led to dramatically enhanced miR122 delivery into human dental pulp-derived iPSCs (DP-iPSCs) and facilitated these DP-iPSCs to differentiate into iPSC-Heps (miR122-iPSC-Heps) with mature hepatocyte functions. Microarray and bioinformatics analysis further indicated that CHC/PU-PEI-miR122 promoted the gene-signature pattern of DP-iPSCs to shift into a liver-specific pattern. Furthermore, intrahepatic delivery of miR122-iPSC-Heps, but not miR-Scr-iPSC-Heps, improved liver functions and rescued recipient survival, and CHC-mediated delivery showed a better efficacy than that using phosphate buffered saline as a delivery vehicle. In addition, these transplanted miR122-iPSC-Heps remained viable and could produce circulatory albumin for 4 months. Taken together, our findings demonstrate that non-viral delivery of miR122 shortens the time of iPSC differentiation into hepatocytes and the delivery of miR122-iPSC-Heps using CHC as a vehicle exhibited promising hepatoprotective efficacy in vivo. miR122-iPSC-Heps may represent a feasible cell source and provide an efficient and alternative strategy for hepatic regeneration in AHF. Refereed/Peer-reviewed

Osteoporosis is one of the most common skeletal disorders affecting postmenopausal women. The purpose of this study was to investigate whether a 24-week program of aerobic high-impact loading exercise was beneficial for enhancing physical fitness and bone mineral density (BMD) in osteopenic postmenopausal women. Forty-three postmenopausal women aged 48-65 years participated in this study. The BMD of the spine (L2-L4) and right femoral neck of each woman was below 1 SD of the mean of premenopausal women, as examined by dual X-ray absorptiometry. The assignment of subjects into exercise or control group was not randomized but based on each subject's anticipated compliance to the 6-month long exercise program. Twenty-two subjects joined the exercise group and attended the training programs and 21 served as the control group. Exercise programs included treadmill walking at an intensity above 70% of maximal oxygen consumption (VO2max) for 30 minutes, followed by 10 minutes of stepping exercise using a 20-cm-high bench. The program was conducted three times per week for 24 weeks. Physical fitness measurements included testing of flexibility, muscular strength and endurance, body composition, and cardiopulmonary fitness. The results showed that the quadriceps strength, muscular endurance, and VO2max in the exercise group had significant improvements, whereas no improvement was found in any of the physical fitness parameters in the control group. The BMD of the L2-L4 and the femoral neck in the exercise group increased 2.0% (P0.05) and 6.8% (P0.05) and those in the control group decreased 2.3% (P0.05) and 1.5% (P0.05), respectively. In conclusion, aerobics combined with high-impact exercise at a moderate intensity was effective in offsetting the decline in BMD in osteopenic postmenopausal women.

A 60-year-old woman presented with an enlarging goitre associated with a 9-month history of dysphagia, hoarseness, heat intolerance, palpitations and weight loss. Physical examination revealed an enlarged right thyroid gland, 8 cm × 4 cm, soft, with no associated cervical lymphadenopathy. Her pulse rate was 90 BPM, regular. She had no eye signs, tremor or sweaty palms. Thyroid function tests showed free thyroxine (fT4) of 7.75 pmol/L (normal: 12.00–22.00 pmol/L) and TSH < 0.005 mU/L (normal: 0.27–4.20 mU/L). A repeat sample to check triiodothyronine (T3) level showed elevated free T3 level at 7.71 pmol/L (normal: 3.1–6.8 pmol/L) confirming …

Background Allergic disorders have increased substantially in recent years. Asthma is characterized by airway damage and remodeling. Reprogramming induced pluripotent stem cells (iPSCs) from adult somatic cells transfected by Oct-4/Sox-2/Klf-4, but not c-Myc, has shown the potential of embryonic-like cells. These cells have potential for multilineage differentiation and provide a resource for stem cell-based utility. However, the therapeutic potential of iPSCs without c-Myc (iPSC-w/o-c-Myc) in allergic diseases and airway hyperresponsiveness has not been investigated. The aim of this study was to evaluate the therapeutic effect of iPSC-w/o-c-Myc transplantation in a murine asthma model. Methods BALB/c mice were sensitized with alum-adsorbed ovalbumin (OVA) and then challenged with aerosolized OVA. Phosphate-buffered saline or iPSC-w/o-c-Myc was then intravenously injected after inhalation. Serum allergen-specific antibody levels, airway hyperresponsiveness, cytokine levels in spleen cells and bronchoalveolar lavage fluid (BALF), and cellular distribution in BALF were then examined. Results Treatment with iPSC-w/o-c-Myc effectively suppressed both Th1 and Th2 antibody responses, which was characterized by reduction in serum allergen-specific IgE, IgG, IgG1, and IgG2a levels as well as in interleukin-5 and interferon-γ levels in BALF and in OVA-incubated splenocytes. Meanwhile, regulatory cytokine, interleukin-10, was enhanced. Transplantation of iPSC-w/o-c-Myc also significantly attenuated cellular infiltration in BALF and allergic airway hyperresponsiveness. However, no tumor formation was observed 6 months after transplantation. Conclusions Administration of iPSC-w/o-c-Myc not only inhibited Th1 inflammatory responses but also had therapeutic effects on systemic allergic responses and airway hyperresponsiveness. iPSC-w/o-c-Myc transplantation may be a potential modality for treating allergic reactions and bronchial asthma.

Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that binds to a family of G protein-coupled receptors (GPCRs), termed S1P1-S1P5. Our previous study has reported that S1P induces autophagy in human prostate cancer PC-3 cell. In addition, S1P-induced autophagy plays a prosurvival role in PC-3 cells. Accumulating evidence has shown that the autophagy responses triggered by ER stress signaling have cytoprotective effects. Thus, we attempted to investigate whether S1P-induced autophagy is a result of triggering ER stress in PC-3 cells. By monitoring XBP-1 mRNA splicing, a characteristic of ER stress, we demonstrate that S1P triggers ER stress in a concentration-dependent and time-dependent manner. Moreover, DiH S1P, a membrane-nonpermeable S1P analog without intracellular effects also enhances ER stress. Meanwhile, we also show that S1P5 is required for S1P-induced ER stress by using RNA interference experiments. Furthermore, signaling analyses revealed that PI3K, PLC, and ROS production were involved in S1P's effects on ER stress induction. On the other hand, knockdown of XBP-1 abolished S1P-induced autophagy. In summary, our results demonstrate for the first time that the extracellular S1P-triggered ER stress is responsible for autophagy induction in PC-3 cells.

Chronic lung diseases cause serious morbidity and mortality, and effective treatments are limited. Induced pluripotent stem cells (iPSCs) lacking the reprogramming factor c-Myc (3-gene iPSCs) can be used as ideal tools for cell-based therapy because of their low level of tumorigenicity. In this study, we investigated whether 3-gene iPSC transplantation could rescue bleomycin-induced pulmonary fibrosis. After the induction of pulmonary inflammation and fibrosis via intratracheal delivery of bleomycin sulfate, mice were i.v. injected with 3-gene iPSCs or conditioned medium (iPSC-CM) at 24 h after bleomycin treatment. Administration of either 3-gene iPSCs or iPSC-CM significantly attenuated collagen content and myeloperoxidase activity, diminished neutrophil accumulation, and rescued pulmonary function and recipient survival after bleomycin treatment. Notably, both treatments reduced the levels of inflammatory cytokines and chemokines, including interleukin 1 (IL-1), IL-2, IL-10, tumor necrosis factor-α, and monocyte chemotactic protein 1 yet increased the production of the antifibrotic chemokine interferon-γ-induced protein 10 (IP-10) in bleomycin-injured lungs. Furthermore, IP-10 neutralization via treatment with IP-10-neutralizing antibodies ameliorated the reparative effect of either 3-gene iPSCs or iPSC-CM on collagen content, neutrophil and monocyte accumulation, pulmonary fibrosis, and recipient survival. Intravenous delivery of 3-gene iPSCs/iPSC-CM alleviated the severity of histopathologic and physiologic impairment in bleomycin-induced lung fibrosis. The protective mechanism was partially mediated by the early moderation of inflammation, reduced levels of cytokines and chemokines that mediate inflammation and fibrosis, and an increased production of antifibrotic IP-10 in the injured lungs.

Induced pluripotent stem cells (iPSCs) are generated by reprogramming somatic cells to a pluripotent state by the introduction of specific factors. They can be generated from cells of different origins, such as fibroblasts, keratinocytes, hepatocytes, and blood. iPSCs are similar to embryonic stem cells (ESCs) in several aspects, such as morphology, expression of pluripotency markers, and the ability to develop teratoma that contains tissue from three germ layers. In addition, iPSCs can undergo tridermal differentiation, including hepatic specific lineages. Considering that iPSCs could be a source of hepatocyte regeneration, iPSC-based therapy has been widely implicated in the treatment of liver disease and hepatic regeneration. In the present review, we discuss the therapeutic potential of iPSCs in hepatic repair and focus on the clinical applications of iPSCs.

Communication between cells and extracellular environments is of interest because of its critical roles in cell development and differentiation. Particularly, this signal transduction is commonly believed to rely on the contact and binding of the participating molecules/proteins, suggesting that the binding distance needed is less than a few nanometers. However, it is difficult to precisely match the rapidly binding interaction which depends on the probability of molecular collision in living systems, raising a hypothesis that another mechanism exists, could promote this signal communication, and remains unknown. Here we report that a long-range signal delivery over 10-μm and 20-μm polydimethylsiloxane(PDMS) barriers can be observed in microfluidically tetracycline (Tet) inducible expression systems. Results show that a significant increment of the long-range induced green fluorescent protein in human embryonic kidney 293T (HEK 293T) cells by the stimulation of Tet is demonstrated, and that such a signal induction is not dominated by Tet diffusion and displays a specific bindingless property. In addition, our experimental results, combined with theoretical modeling, suggest that this communication exhibits a bump-shaped characteristic depending on barrier thickness, materially structural property, surface roughness, and agonist concentration. It strongly relies on the PDMS barrier to delivery signal; therefore, we call such a mechanism as “wired” cell communication instead of wireless. These results could ignite interests in the novel and “wired” cell communication, which we call it X-signal, and in the use of such systems for the study of cellular biology and development of new drug.

In patients with obstructive sleep apnea (OSA), intermittent apnea and hypopnea might cause different adaptations in inspiratory and peripheral muscles. In this study we aimed to determine the changes that occur in muscle activation characteristics during incremental exercise testing in patients with severe OSA. Surface electromyography of inspiratory muscles and knee extensors was performed.Eleven men with severe OSA and 11 matched controls were recruited. Changes in muscle activity were compared by determining root mean square (RMS) and median power frequency (MPF) values obtained at different exercise intensities.The ratios of RMS to oxygen consumption in inspiratory muscles and vastus lateralis increased significantly at peak workload in the control group (P0.05), but not in the OSA group.Patients with severe OSA demonstrated an inability to increase motor unit recruitment of inspiratory muscles and knee extensors during incremental exercise.