(2,3,7,8,38,41,45,47,58,59,70) and contraction (20,24,26,28,32 ] i responses to hypoxia in isolated PA (43). One possible explanation for these findings is that hypoxia caused release of Ca 2ϩ from SR in PASMC, leading to SR depletion, activation of store-operated Ca 2ϩ channels (SOCC), and capacitative Ca 2ϩ entry (CCE). Recently, we reported that several so-called "canonical transient receptor potential (TRPC)" proteins were expressed in smooth muscle of distal PA (60), which are thought to be the major vascular locus of HPV (49). These proteins are homologs of TRP and TRP-like proteins that make up Ca 2ϩ channels in Drosophila photoreceptors and are thought to compose mammalian SOCC, many forms of which may also be permeable to Na ϩ and other cations and therefore function as nonselective cation channels (NSCC) (34, 37, 51). Consistent with TRPC expression, we and others demonstrated the presence of CCE in distal PA (51, 60). More recently, we found that acute hypoxia increased [Ca 2ϩ ] i , Ca 2ϩ influx, and CCE in distal PASMC and that these effects were completely blocked by removal of extracellular Ca 2ϩ or SOCC/NSCC antagonists, but not nifedipine (61). These findings are consistent with recent observations from other laboratories (21,22,35) and suggest that HPV may require activation of SOCC in PASMC; however, it is well known that cell isolation and culture can alter cell phenotype. Moreover, changes in PASMC [Ca 2ϩ ] i do not necessarily translate to changes in pulmonary vascular resistance. In the present study, therefore, we assessed the contribution of SOCC and CCE to HPV in isolated lungs, where physiologically relevant pulmonary vasomotor responses can be measured directly. METHODS Isolated Lung PreparationOur protocol was approved by the Institutional Animal Care and Use Committee of the Johns Hopkins University. Male Wistar rats (200 -400 g) were anesthetized with pentobarbital sodium (65 mg/kg ip). A tracheostomy was performed, and the animal was ventilated with room air at a tidal volume of 10 ml/kg and a rate of 30 min Ϫ1(Harvard Rodent Ventilator model 883; Harvard Apparatus, Holliston, MA). A thoracotomy was performed, heparin (100 units) was injected into the right ventricular cavity, and the animal was exsanguinated from the femoral artery. The ventilating gas was changed to 16% O 2-5% CO2. Cannulae were inserted into the main PA and left atrium, which drained into a heated reservoir. The lungs were perfused with

No abstract

Recent advances have identified an important role of bone morphogenetic protein 4 (BMP4) in pulmonary vascular remodeling, yet the underlying mechanisms remain largely unexplored. We have previously found that Ca(2+) influx through store-operated calcium channels (SOCC), which are mainly thought to be composed of canonical transient receptor potential (TRPC) proteins, likely contribute to the pathogenic development of chronic hypoxic pulmonary hypertension. In this study, we investigated the effect of BMP4 on expression of TRPC and store-operated Ca(2+) entry (SOCE) in pulmonary arterial smooth muscle cells (PASMCs). Real-time quantitative PCR and Western blotting revealed that treatment with BMP4 (50 ng/ml, 60 h) increased TRPC1, TRPC4, and TRPC6 mRNA and protein expression in growth-arrested rat distal PASMCs. Moreover, in comparison to vehicle control, cells treated with BMP4 also exhibited enhanced SOCE, and elevated basal intracellular calcium concentration ([Ca(2+)](i)) as determined by fluorescent microscopy using the Ca(2+) indicator Fura-2 AM. Perfusing cells with Ca(2+)-free Krebs-Ringer bicarbonate solution (KRBS) or KRBS containing SOCC antagonists SKF-96365 or NiCl(2) attenuated the increases in basal [Ca(2+)](i) caused by BMP4. Specific knockdown of BMP4 by small interference RNA significantly decreased the mRNA and protein expression of TRPC1, TRPC4, and TRPC6 and reduced SOCE and basal [Ca(2+)](i) in serum-stimulated PASMCs. We conclude that BMP4 regulates calcium signaling in PASMCs likely via upregulation of TRPC expression, leading to enhanced SOCE and basal [Ca(2+)](i) in PASMCs, and by this mechanism contributes to pulmonary vascular remodeling during pulmonary arterial hypertension.

A novel spinel Co VO is studied as the Li-ion battery anode material and it is sandwiched with a 3D ultralight porous current collector (PCC) and amorphous carbon. Co VO demonstrates the high capacity and excellent cyclability because of the mixed lithium storage mechanisms. The 3D composite structure requires no binders and replaces the conventional current collector (Cu foil) with a 3D ultralight porous metal scaffold, yielding the high electrode-based capacity. Such a novel composite anode also enables the close adhesion of Co VO to the PCC scaffold. The resulting monolithic electrode has the rapid electron pathway and stable mechanical properties, which lead to the excellent rate capabilities and cycling properties. At a current density of 1 A g , the PCC and carbon sandwiched Co VO anode is able to deliver a stable reversible capacity of about 706.8 mAh g after 1000 cycles. Generally, this study not only develops a new Co VO anode with high capacity and good cyclability, but also demonstrates an alternative approach to improve the electrochemical properties of high capacity anode materials by using ultralight porous metallic current collector instead of heavy copper foil.

BackgroundGraves’ disease is the most common form of autoimmune thyroid disorder, characterized by hyperthyroidism due to circulating autoantibodies. To address the pathological features and establish a therapeutic approach of this disease, an animal model carrying the phenotype of Graves’ disease (GD) in concert with Graves’ Ophthalmopathy (GO) will be very important. However, there are no ideal animal models that are currently available. The aim of the present study is to establish an animal model of GD and GO disease, and its pathological features were further characterized.MethodsA recombinant plasmid pcDNA3.1- T289 was constructed by inserting the TSHR A-subunit gene into the expression vector pcDNA3.1, and genetic immunization was successfully performed by intramuscular injection of the plasmid pcDNA3.1-T289 on female 8-week-old BALB/c mice. Each injection was immediately followed by in vivo electroporation using ECM830 square wave electroporator. Morphological changes of the eyes were examined using 7.0T MRI scanner. Levels of serum T4 and TSHR antibodies (TRAb) were assessed by ELISA. The pathological changes of the thyroid and orbital tissues were examined by histological staining such as H&E staining and Alcian blue staining.ResultsMore than 90% of the immunized mice spontaneously developed goiter, and about 80% of the immunized mice manifested increased serum T4 and TRAb levels, combined with hypertrophy and hyperplasia of thyroid follicles. A significantly increased synthesis of hyaluronic acid was detected in in the immunized mice compared with the control groups.ConclusionWe have successfully established an animal model manifesting Graves’ hyperthyroidism and ophthalmopathy, which provides a useful tool for future study of the pathological features and the development of novel therapies of the diseases.

Positive feelings are an important health dimension for family caregivers of cancer patients. The aim of this study was to investigate whether Langerian mindfulness is a valid proactive method to increase the positive feelings of family caregivers for cancer patients. Participants were randomly assigned to either a mindfulness group or a mindlessness group and completed the Caregiver Reaction Assessment (CRA) as a measure of caregivers’ feelings before the intervention. Subsequently, both groups were given four sessions of mindfulness training using “innovation classification”. Finally, participants completed the Langer Mindfulness Scale (LMS) and the Positive Aspects of Caregiving (PAC) scale as post-intervention measures. The results revealed that participants in the mindfulness and mindlessness groups differed significantly in LMS and PAC scores, with the mindfulness group having higher levels of positive feelings than those in the mindlessness group. The results also indicated that mindfulness level significantly predicted positive feelings of caregivers. Thus mindful interventions may play a meaningful role in promoting family caregivers’ spirituality and faith, improving the willingness of sharing their thoughts, beliefs, and grief, which could be useful for increasing the positive feelings of caregivers.

The aim of the present study was to investigate the effects of () and () on rats subjected to 5 h of stress, induced by water-floating followed by treadmill exercise. Hypothalamus-pituitary-adrenal (HPA) activity and c-Fos and Fos-related antigen 2 (Fra-2) mRNA expression levels in the hypothalamus of the rats were evaluated. Rats were distributed into four groups: (n=12), (n=10), stress control (n=10) and quiet control (n=8). Following a training period of 6 consecutive days, the , and stress control groups underwent a 3-h water-floating session in the presence of feline predators immediately followed by 2 h treadmill running to induce psychological and physical stress. Following compound stress induction, the serum levels of corticosterone (CORT), adrenocorticotropic hormone and interleukin-1β and the mRNA expression levels of hypothalamic corticotropin-releasing hormone (CRH), neuropeptide-Y, c-Fos and Fra-2 were evaluated using enzyme-linked immunosorbent assay, radioimmunoassay and quantitative polymerase chain reaction, respectively. The results indicated that and markedly decreased the stress-induced elevation of CRH and peripheral CORT levels. The mRNA expression levels of c-Fos and Fra-2 in the hypothalamus were significantly increased after 5 h compound stress, and reduced levels of c-Fos expression were detected in rats treated with . Thus, and exert an anti-stress effect in rats subjected to stress by balancing the HPA axis, and possibly by reducing the expression of c-Fos in the hypothalamus.

Since the discovery of wireless telegraphy in 1897, wireless communication via electromagnetic (EM) signals has become a standard solution to address increasing demand for information transfer in modern society. With the rapid growth of EM wave manipulation technique, programmable metasurface (PM) has emerged as a new type of wireless transmitter by directly modulating digital information without complex microwave components, thus providing an alternative to simplify the conventional wireless communication system. However, the challenges of improving information security and spectrum utilization still exist. Here, a dual-band metasurface-assisted wireless communication scheme is introduced to provide additional physical channels for the enhancement of information security. The information is divided into several parts and transmitted through different physical channels to accomplish information encryption, greatly reducing the possibility of eavesdropping. As the proof of concept, a dual-channel and high-security wireless communication system based on a 1-bit PM is established to simultaneously transmit two different parts of a picture to two receivers. Experiments show that the transmitted picture can be successfully retrieved only if the received signals of different receivers are synthetized as predefined. The proposed scheme provides a new route of employing PM in information encryption and spectrum utilization of wireless communication.