Search

The roles of the Hippo‑Yes‑associated protein (YAP) pathway in lung injury and repair remain elusive. The present study examined the effects of systemic inhibition or stimulation of YAP activity on lung injury, repair and inflammation in a mouse model of lipopolysaccharide (LPS)‑induced lung injury. Mice were treated with or without YAP inhibitor, verteporfin, or with or without YAP stimulator, XMU‑MP‑1, and intraperitoneally injected with LPS (7.5 mg/kg). Lung injury and repair were evaluated by histological analysis and by testing for markers of lung injury. Lung inflammation was assessed by measuring tissue levels of inflammatory mediators. Lung injury was associated with a decreased, whereas lung repair was associated with an increased YAP activity evidenced by nuclear translocation. Lung injury was associated with a high level of lung inflammation and epithelial adherens junction disassembly, but not with cell proliferation or epithelial cell regeneration. The injury phase was defined as 0‑48 h post‑LPS injection, and the 48‑168 h time period was considered the repair phase. Inhibition of YAP activity at the injury phase, using verteporfin, exacerbated, whereas its stimulation, using XMU‑MP‑1, alleviated lung injury, lung inflammation and epithelial adherens junction disassembly. Inhibition or stimulation of YAP activity at the injury phase had no effects on cell proliferation or epithelial regeneration. By contrast, lung repair was associated with inflammation resolution, increased cell proliferation, epithelial regeneration and reassembly of epithelial adherens junctions. Inhibition of YAP activity at the repair phase delayed inflammation resolution, impeded lung recovery, inhibited cell proliferation and epithelial regeneration, and inhibited epithelial adherens junction reassembly. Stimulation of YAP activity at the repair phase reversed all these processes. The results of the current study demonstrated that the Hippo‑YAP activity serves a protective role against endotoxemic lung injury. The Hippo‑YAP activity alleviated lung inflammation and injury at the injury phase and promoted inflammation resolution and lung repair at the repair phase.

ObjectivePain assessment based on facial expressions is an essential issue in critically ill patients, but an automated assessment tool is still lacking. We conducted this prospective study to establish the deep learning-based pain classifier based on facial expressions.MethodsWe enrolled critically ill patients during 2020–2021 at a tertiary hospital in central Taiwan and recorded video clips with labeled pain scores based on facial expressions, such as relaxed (0), tense (1), and grimacing (2). We established both image- and video-based pain classifiers through using convolutional neural network (CNN) models, such as Resnet34, VGG16, and InceptionV1 and bidirectional long short-term memory networks (BiLSTM). The performance of classifiers in the test dataset was determined by accuracy, sensitivity, and F1-score.ResultsA total of 63 participants with 746 video clips were eligible for analysis. The accuracy of using Resnet34 in the polychromous image-based classifier for pain scores 0, 1, 2 was merely 0.5589, and the accuracy of dichotomous pain classifiers between 0 vs. 1/2 and 0 vs. 2 were 0.7668 and 0.8593, respectively. Similar accuracy of image-based pain classifier was found using VGG16 and InceptionV1. The accuracy of the video-based pain classifier to classify 0 vs. 1/2 and 0 vs. 2 was approximately 0.81 and 0.88, respectively. We further tested the performance of established classifiers without reference, mimicking clinical scenarios with a new patient, and found the performance remained high.ConclusionsThe present study demonstrates the practical application of deep learning-based automated pain assessment in critically ill patients, and more studies are warranted to validate our findings.

Mechanisms underlying the association between asthma and obesity remain poorly understood. Obesity appears to be a risk factor for asthma, and obese asthmatics fare poorly compared to lean asthmatics.To explore the possibility that reduced regulatory T cell (Treg) number and function contribute to the obesity-asthma association. We concentrated on obese females with childhood-onset asthma, since Treg may be involved in this phenotype.We recruited 64 women (ages 18-50) into four groups: lean (BMI 18-25 kg/mObese asthmatics had worse lung function, asthma control, and quality of life compared to lean asthmatics. Compared to lean or obese control groups, the number of Treg cells in the obese asthmatics was approximately 1.58- or 1.73-fold higher. The ability of Treg cells from obese-asthmatics to suppress Tresp cell proliferation was reduced.Obese, atopic women with childhood diagnosed asthma demonstrate increased Treg cell number and mildly decreased Treg cell function. Our data do not support the view that reduced Treg cell number contributes to this obese-asthma phenotype.

Background and objective Pulmonary Hypertension (pH) is a chronic progressive disease. Endothelial cells (EC) play a central and critical role in the initiation and progression of pH. The NF-κB family (NF-κB1 (p50/p105), NF-κB2 (p52/p100), RelA (p65), RelB, and C-Rel) regulates a wide array of genes involved in inflammatory responses, cell proliferation, and survival. The involvement of specific NF-κB family members in the pathogenesis of hypoxia-induced pH remains to be determined. The objective of this study was to assess the specific role of individual NF-κB family members in mediating endothelial cell responses to hypoxia and its downstream effect on smooth muscle cell proliferation. Methods and results NF-κB family members’ expression were selectively reduced by siRNA in human pulmonary microvascular endothelial cells. Cells were then exposed to hypoxia (1%) for 24 h. Endothelin1, ICAM1 gene expression and Stat1 and Stat3 phosphorylation were assessed. Smooth muscle cells (SMC) proliferation was assessed by culturing them with EC conditioned media. Reduction of either NF-κB2 or RelA in EC, led to a significant decrease in Endothelin1 and ICAM1 gene expression. C-Rel knockdown resulted in a significant increase in phosphorylated STAT1; both C-Rel and RelA knockdown significantly decreased phosphorylated STAT3 in EC. There was a significant reduction in SMC proliferation, and AKT/ERK phosphorylation in SMC, when cultured in RelA knockdown, EC conditioned media. Conclusion RelA in EC plays crucial role in hypoxia induced vascular remodeling and development of pH. Targeting RelA in EC alleviates SMC proliferation as well as inflammation related processes.

Ground penetrating radar (GPR) is a non-destructive detection technology. With the development of radar technology, new requirements are placed on the performance of GPR. By analyzing the shortcomings of traditional GPR that can only transmit specific pulses, a pulse-controllable GPR transmitter scheme based on JESD204B communication protocol is proposed and a prototype is produced. The performance of GPR is improved from two aspects: detection scene and detection accuracy. The feasibility of the design is proved by experiments.

Clinical ladder (CL)-3 nurses should have both an ability to integrate the clinical information of critically ill patients and to carry out the administrative work of the intensive care unit. However, in our unit, only 15.3% of nurses hold CL-3 certification, which is much lower than the hospital average of 23.1%. Thus, we initiated a project to raise this percentage in our unit. An analysis in January 2016 showed that the main obstacles to obtaining CL-3 certification in our unit were inability to write case reports, inadequate in-service education, and a lack of certified educators.The purpose of this project was to increase the number of CL-3-certified nurses in our intensive care unit.The resolution included holding courses on case report writing, briefings, and oral presentation techniques; assigning a preceptor to make nursing staff assignments; encouraging nurses to participate in the clinical nursing preceptor education training camp; and conducting practice tests using a multiple assessment tool.After implementation of this project, the percentage of unit nurses who had passed CL-3 increased to 39.0%.This project not only allowed our fellow nurses to share in the joy of clinical ladder advancement but also improved the atmosphere in the unit by encouraging self-development. This project helped stimulate professional growth among our staff and improved the quality of clinical care.提升某內科加護病房護理人員N3能力進階比率.N3護理人員具備重症整合性之照護能力，堪能勝任加護病房護理業務，但是本院某加護病房N3以上能力進階僅佔15.3%，低於全院N3以上能力進階比率23.1%，故引發專案動機。2016年1月經現況分析原因，包括：個案報告寫作能力不足、在職教育主講能力不足、未取得教師認證。.本專案目的在提升某內科加護病房護理人員N3能力進階比率。.安排個案報告寫作訓練、安排指導員輔導、教導簡報製作技巧、演練口頭報告、安排參加教師訓練營、演練使用多元化評估工具。.專案推動後單位N3能力進階比率提升至39.0%。.同儕間互相分享能力進階順利晉級的喜悅，亦鼓舞單位各層級的能力進階風氣，且提升護理專業成長與助益臨床照護品質。.

Blood pressure regulation is known to be maintained by a neuro-endocrine circuit, but whether immune cells contribute to blood pressure homeostasis has not been determined. We previously showed that CD4+ T lymphocytes that express choline acetyltransferase (ChAT), which catalyzes the synthesis of the vasorelaxant acetylcholine, relay neural signals. Here we show that these CD4+CD44hiCD62Llo T helper cells by gene expression are a distinct T-cell population defined by ChAT (CD4 TChAT). Mice lacking ChAT expression in CD4+ cells have elevated arterial blood pressure, compared to littermate controls. Jurkat T cells overexpressing ChAT (JTChAT) decreased blood pressure when infused into mice. Co-incubation of JTChAT and endothelial cells increased endothelial cell levels of phosphorylated endothelial nitric oxide synthase, and of nitrates and nitrites in conditioned media, indicating increased release of the potent vasorelaxant nitric oxide. The isolation and characterization of CD4 TChAT cells will enable analysis of the role of these cells in hypotension and hypertension, and may suggest novel therapeutic strategies by targeting cell-mediated vasorelaxation.

The interaction between nanomaterials and biological macromolecules (including protein) is the important basis of biological safety assessments of nanomaterials. In this paper, the fluorescence spectroscopy, synchronous fluorescence spectroscopy and circular dichroism spectroscopy) were used to analyze the interaction between four water-soluble carboxyl carbon nanotubes (long-SWCNTs-COOH, short-SWCNTs-COOH, DWCNTs-COOH and MWCNTs-COOH) and human serum albumin. Results showed that the four water-soluble carboxylated carbon nanotubes could quench the intrinsic fluorescence of human serum albumin at different extents. Under the same concentration, the quenching ability of four carboxylated carbon nanotubes were in the order of DWCNTs-COOHMWCNTs-COOHlong-SWCNTs-COOHshort-SWCNTs-COOH. The synchronous fluorescence spectroscopy of human serum albumin in the absence and presence of four carbon nanotubes indicated that the binding location of MWCNTs-COOH was close to tryptophan (Trp) residue and DWCNTs-COOH was close to the tyrosine (Tyr) residues while those of long-SWCNT-COOH and short-SWCNT-COOH have no significant difference to two amino acid residues. The four water-soluble carboxyl carbon nanotubes could cause slight changes of the CD spectra of human serum albumin as well as the α-helix and β-sheet contents of human serum albumin. The above results indicate the fluorescence quenching effect of carbon nanotubes on human serum albumin was related to their structural properties. During the binding process, the human serum albumin conformation remained unchanged, and there were slight changes as to its secondary structure, but there is no obvious dose-response relationship could be observed. The mechanism was also discussed.

Objectives The purpose of this study was to further clarify the role and underlying mechanism of miR-324-5p in gastric cancer. Methods The expressions of miR-324-5p and TSPAN8 as determined by qRT-PCR or Western blot were compared between the gastric cancer tissues and normal tissues. Human gastric cancer cell line SGC-7901 was cultured and transfected with miR-324-5p mimic/inhibitor or pcDNA-TSPAN8. The cell survival was assessed by the cell viability and apoptosis. Luciferase reporter gene assays were performed to explore the interaction between miR-324-5p and TSPAN8 in SGC-7901 cells. Key findings MiR-324-5p was decreased in human gastric carcinoma tissues (n = 33), but TSPAN8 protein expression was increased in the gastric carcinoma tissues (n = 33). Moreover, miR-324-5p inhibited the viability and induced the apoptosis of gastric cancer cells in vitro. TSPAN8 is a functional target of miR-324-5p in gastric cancer. MiR-324-5p was further confirmed to reduce gastric cancer cell viability and induce apoptosis via downregulating TSPAN8 in SGC-7901 cells in vitro. Additionally, miR-324-5p overexpression markedly inhibited the tumorigenesis of gastric cancer cells in vivo, as shown by the smaller tumour volume compared with the control. Conclusions This study suggested a novel, probable mechanism of miR-324-5p in gastric cancer context and revealed that miR-324-5p inhibited gastric cancer cell survival by targeting TSPAN8.

Obstructive sleep apnea (OSA) is highly prevalent in the USA and is recognized as an independent risk factor for atherosclerotic cardiovascular disease. Identification of atherosclerosis risk factor attributable to OSA may provide opportunity to develop preventive measures for cardiovascular risk reduction. Chronic intermittent hypoxia (CIH) is a prominent feature of OSA pathophysiology and may be a major mechanism linking OSA to arteriosclerosis. Animal studies demonstrated that CIH exposure facilitated high-cholesterol diet (HCD)-induced atherosclerosis, accelerated the progression of existing atherosclerosis, and induced atherosclerotic lesions in the absence of other atherosclerosis risk factors, demonstrating that CIH is an independent causal factor of atherosclerosis. Comparative studies revealed major differences between CIH-induced and the classic HCD-induced atherosclerosis. Systemically, CIH was a much weaker inducer of atherosclerosis. CIH and HCD differentially activated inflammatory pathways. Histologically, CIH-induced atherosclerotic plaques had no clear necrotic core, contained a large number of CD31+ endothelial cells, and had mainly elastin deposition, whereas HCD-induced plaques had typical necrotic cores and fibrous caps, contained few endothelial cells, and had mainly collagen deposition. Metabolically, CIH caused mild, but HCD caused more severe dyslipidemia. Mechanistically, CIH did not, but HCD did, cause macrophage foam cell formation. NF-κB p50 gene deletion augmented CIH-induced, but not HCD-induced atherosclerosis. These differences reflect the intrinsic differences between the two types of atherosclerosis in terms of pathological nature and underlying mechanisms and support the notion that CIH-induced atherosclerosis is a new paradigm that differs from the classic HCD-induced atherosclerosis.

Objective— Disruption of endothelial barrier integrity is a characteristic of many inflammatory conditions. However, the origin and function of endothelial cells (ECs) restoring endothelial barrier function remain unknown. This study defined the roles of resident ECs (RECs) and bone marrow–derived endothelial progenitor cells (BMDEPCs) in endothelial barrier restoration after endotoxemic lung injury. Approach and Results— We generated mice that enable to quantify proliferating RECs or BMDEPCs and also to study the causal link between REC or BMDEPC proliferation and endothelial barrier restoration. Using these mouse models, we showed that endothelial barrier restoration was associated with increased REC and BMDEPC proliferation. RECs and BMDEPCs participate in barrier repair. Immunofluorescence staining demonstrated that RECs proliferate in situ on endothelial layer and that BMDEPCs are engrafted into endothelial layer of lung microvessels at the active barrier repair phase. In lungs, 8 weeks after lipopolysaccharide-induced injury, the number of REC-derived ECs (CD45 − /CD31 + /BrdU + /rtTA + ) or BMDEPC-derived ECs (CD45 − /CD31 + /eNOS + /GFP + ) increased by 22- or 121-fold, respectively. The suppression of REC or BMDEPC proliferation by blocking REC or BMDEPC intrinsic nuclear factor-κB at the barrier repair phase was associated with an augmented endothelial permeability and impeded endothelial barrier recovery. RECs and BMDEPCs contributed differently to endothelial barrier repair. In lungs, 8 weeks after lipopolysaccharide-induced injury, REC-derived ECs constituted 22%, but BMDEPC-derived ECs constituted only 3.7% of the total new ECs. Conclusions— REC is a major and BMDEPC is a complementary source of new ECs in endothelial barrier restoration. RECs and BMDEPCs play important roles in endothelial barrier restoration after inflammatory lung injury.

Recurrent chromosome 20q gain is implicated in progressive cancer behaviors and has been associated with clinical outcomes in multiple types of cancer; however, its prognostic significance in hepatocellular carcinoma (HCC) and the involved genes remain unclear. Array comparative genomic hybridization and expression arrays were used to detect copy number alterations (CNAs) and expression levels, respectively. The associations between CNAs in 20q and outcomes were analyzed on 66 patients, for which the follow-up period was 2.6–73.3 months. One hundred seventeen tumors were further investigated to identify target genes in the potentially outcome-related CNAs. Regional or whole 20q gain was detected in 24 (36.4 %) of the 66 HCC cases. The most recurrent gains were 20q11.21–12, 20q12–13.12, 20q13.12–13.33 and 20q13.33. Of the CNAs, 20q13.12–13.33 gain was significantly associated with reduced extrohepatic metastasis-free and overall survival, as well as with elevated postoperative AFP level, tumor vascular invasion and advanced tumor stage. Multivariate Cox analysis identified 20q13.12–13.33 gain as an independent prognostic marker for metastasis (HR 3.73, 95 % CI 1.08–12.87) and death (HR 3.00, 95 % CI 1.26–7.13). A panel of 19 genes in 20q13.12–13.33 was significantly overexpressed in HCCs with gain compared to HCCs without. High expression (greater than median) for 5 of the 19 genes, DDX27, B4GALT5, RNF114, ZFP64 and PFDN4, correlated significantly with vascular invasion, and high RNF114 expression also with advanced tumor stage. Gain at 20q13.12–13.33 is a prognostic marker of metastasis and death, and DDX27, B4GALT5, RNF114, ZFP64, and PFDN4 are probable target genes which may be involved together in the unfavorable outcomes of HCC patients.

A broadband circularly polarized (CP) antenna with simple structure and wide angular coverage is proposed. The interlaced coplanar dipole is excited by a coaxial cable to achieve the CP wave. To obtain a high gain and low backward radiation, a rectangular cavity-backed reflector is used. An initial design at around 6.0 GHz is presented to show the performance of this configuration. An impedance bandwidth and axial ratio bandwidth of about 35.6 and 33.5% can be achieved at this frequency. Also, a stable gain of about 10 ± 0.5 dBi and a wide axial ratio beamwidth of about 200° over the frequency of interest are obtained. Then, a parametric analysis is conducted to estimate the significance of the design parameters that affect the antenna's performance. Finally, a prototype at 11.0 GHz is fabricated to validate the design. The measured results are in good agreement with the simulated ones, which shows that the design can be easily applied to other frequency and that the design may be a good candidate for the CP antenna family. © 2015 Wiley Periodicals, Inc. Microwave Opt Technol Lett 57:377–381, 2015

A broadband antenna based on magnetoelectric dipole is proposed. The proposed antenna is composed of a bowtie-shaped electric dipole and an elliptical ring antenna that works as a magnetic dipole. For a broadband performance, a microstrip-to-coplanar stripline transition balun is used to excite the antenna. All of them are printed on the same plane perpendicular to the ground. To validate the design, prototypes of the proposed antenna have been fabricated and measured. The measurement results show that the antenna has a wide impedance bandwidth of 66.7% (2.45–4.90 GHz) for voltage standing wave ratio (VSWR) less than 2 and a gain of 6.0–7.3 dBi over the operating frequency band. Meanwhile a high front-to back ratio better than 16 dB over the operating frequency is achieved. The agreements between the simulation and measurement results indicate that the proposed antenna is suitable for wireless communication systems and phased array systems. © 2014 Wiley Periodicals, Inc. Int J RF and Microwave CAE 25:213–218, 2015.

Background and Purpose Ulinastatin (UTI), a serine protease inhibitor, was recently found to have an anti-inflammatory action. However, the mechanisms mediating this anti-inflammatory effect are not well understood. This study tested the hypothesis that UTI suppresses allergic inflammation by inducing the expression of haem oxygenase 1 (HO1). Experimental Approach Control mice and mice sensitized (on days 1, 9 and 14) and challenged (on days 21 to 27) with ovalbumin (OVA) were treated with UTI. The effects of UTI on basal expression of HO1 and that induced by OVA challenge were examined. The involvement of UTI-induced HO1 expression in anti-inflammatory and antioxidant effects of UTI was also evaluated. Key Results UTI markedly increased basal HO1 protein expression in lungs of control mice in a time- and dose-dependent manner, and augmented HO1 protein expression induced by OVA. The up-regulation of HO1 mediated by UTI in sensitized and OVA-challenged mice was associated with reduced airway inflammation, alleviated tissue injury, reduced oxidant stress and enhanced antioxidant enzyme activities. Inhibition of HO1 activity using HO1 inhibitor, zinc protoporphyrin, attenuated inhibitory effects of UTI on inflammation and oxidant stress, and its stimulant effects on antioxidant enzyme activities. Mechanistic analysis showed that UTI increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), stimulated Nrf2 DNA binding activity and concomitantly up-regulated HO1 mRNA expression. Conclusions and Implications UTI is a potent and naturally occurring inducer of HO1 expression. HO1 up-regulation contributes significantly to the anti-inflammatory and organ-protective effects of UTI, which has important research and therapeutic implications.

A novel broadband high gain vertical planar printed antenna is presented. The proposed antenna is composed of a bowtie-shaped electric dipole, a loop antenna that works as a magnetic dipole, a microstrip-to-coplanar stripline transition balun, and the H-shaped resonator (HSR) structures that are used for gain enhancement, all of which are printed in the same plane perpendicular to the ground. Prototypes of the HSR-loaded antenna and the unloaded one were fabricated and measured. Analyses and comparisons of the proposed antenna are made. The HSR-loaded antenna has a wide impedance bandwidth of 51.9%, ranging from 2.31 GHz to 3.93 GHz and a stable gain of about 7.4-9.7 dBi over the whole operating band. Compared with the unloaded structure, a gain increment of about 0.5-6.0 dB over the whole band is obtained. The good electrical performances make the antenna suitable for the wireless communication systems and phased arrays.

At present, China is establishing eco-compensation mechanism on the basis of key ecological function zones and ecological factors, but trans-provincial eco-compensation mechanism (especially in river basin) is making slow progress due to its complicated stakeholders involvement. The promulgation of relevant papers, such as Planning on National Main Functional Zones and National Key Ecological Function Zones, provide important basis and new thoughts for implementing eco-compensation mechanism in China. In this paper, we take trans-provincial key ecological function zone as breakthrough point to study trans-provincial river basin eco-compensation mechanism, and take the source area of Dongjiang River in Jiangxi province and Guangdong province as an example to put forward some ideas for trans-provincial river basin eco-compensation mechanism designing based on the key ecological function zones. Taking the study of key ecological function zone as the platform, we propose a framework of river basin eco-compensation plan, which includes particular design in the following aspects: the funding needs, funding sources, financial operation mechanism, monitoring and evaluation, organizational management and compensation security system. Designing River basin eco-compensation mechanism in source areas while based on key ecological function zone, which will increase the scientific nature and rationality of policy making, is more in line with ideas and concepts of payment for ecosystem services (PES) and it will effectively promote scientific and rational development and implementation of river basin eco-compensation. However there are still many inevitable problems in the following aspects: river basin eco-compensation monitoring and evaluation, management of river basin eco-compensation and measures to ensure the long-term effect of river basin eco-compensation policy. With the in-depth understanding of eco-compensation study and practice in China, these problems should be constantly improved and Chinas eco-compensation mechanism will become increasingly complete and rigorous in the future.

Being located in the northwest of Beijing, Guanting Reservoir has been an important source to supply water for life, production and landscape; however, with the increasing urbanization and population agglomeration in the upstream since 1980s, the resource and environment of Guanting Reservoir Basin was also undertaken an increasingly pressure accordingly with water quantity dropped and quality deteriorated, so Guanting Reservoir was ruled out of the drinking water supply system of Beijing since 1997. As a series of ecological protection and management project have been implemented with the 21st century coming, Guanting Reservoir restored its water-supply function for agriculture, ecology and industry in 2003, and restored its function as drinking water source in 2007, so it became an emergency water-supply source of Beijing again. The environmental protection status and economic development model of Guanting Reservoir Basin plays an essential role for water security of Beijing. In this paper, taken Guanting Reservoir Basin as the study case, the land use data of different periods since 1980s have been extracted from remote sensing images of the study area to analyze the land use changes. Based on the land use data, Costanza ecosystem service value formula and correction parameter suitable for China situations, the basin ecosystem service value is calculated to analyze the changes in leading ecosystem function of Guanting Reservoir Basin in different periods. In combination with the social and economic statistical data, the driving factors are discussed for changes in the leading function, and the approaches are put forward to enhance the upstream ecosystem function, so as to guarantee the sustainable economic and social development in the Basin. It is indicated from the research results that: (1) the driving forces for the changes in dominate ecosystem functions of Guanting Reservoir Basin mainly result from policy factor, population factor and economic factor; (2) the ecosystem services of Guanting Reservoir Basin are presented as asymmetric spatial characteristic; and (3) the eco-compensation mechanism is an important means to balance the asymmetry of ecosystem services between the upstream and downstream of Guanting Reservoir Basin and enhance the upstream capacity for provision of ecosystem services. The quantitative eco-compensation mechanism is the key point of follow-up research to enhance ecosystem services; the scenario analysis will have a prospective potential to propose some policy suggestions with more operability.

A novel ultrawideband bandpass filter with one notch-band, high selectivity, and wide stopband is investigated in this article. The basic filter is composed of two microstrip-slot transitions with novel annular stubs, which are used to obtain the required bandwidth with high selectivity. And, a cross-coupling between the feed lines (input and output) is introduced to broaden the stopband. In addition, a short-circuited stepped-impedance resonator is used to obtain one notch-band. The simulated and experimental performances are presented in this work where good agreement is obtained. © 2013 Wiley Periodicals, Inc. Microwave Opt Technol Lett 55:2624–2628, 2013

Background: The mechanisms of fat mass (FM) loss in cystic fibrosis (CF) are poorly understood but could represent complex pathways involving dysregulation of appetite-modulating peptides and an amplified inflammatory response. Nesfatin-1 is a newly described peptide that decreases food intake and FM but has not been studied in CF. Objectives: We hypothesized that changes in the appetite-suppressing hormone nesfatin-1 would be physiological, and levels would be lower in advanced CF patients with lower FM compared to those with milder disease and healthy controls. We determined the levels of the cytokines TNF-α, IL-1β, and IL-6 as they have been associated with weight loss in disease states. Methods: Fifty-four adult CF subjects, i.e. 17 with severe, 22 with moderate, and 15 with mild disease, as well as 18 controls were recruited. PFT and body composition analysis (via bioelectrical impedance) were performed. Nesfatin-1 and cytokine levels were determined by ELISA. Results: Contrary to our proposed hypothesis, nesfatin-1 levels were highest in CF patients with severe disease and the lowest FM. A significant negative correlation between nesfatin-1 levels and FM was found only in the severe CF group (r = -0.7, p = 0.003). In forward stepwise regression analysis, only FM was significantly associated with nesfatin-1 levels. Levels of TNF-α and IL-6 were elevated in the severe CF group, but there was no association with either FM or nesfatin-1. Conclusion: In advanced CF and low FM, nesfatin-1 plasma levels are significantly increased and inversely correlated with the FM. Our results further suggest that nesfatin-1 exerts its effects independently of TNF-α or IL-6.

Blood pressure regulation is known to be maintained by a neuro-endocrine circuit, but whether immune cells contribute to blood pressure homeostasis has not been defined. We previously described that CD4+ T lymphocytes that express choline acetyltransferase (ChAT), which catalyzes the synthesis of the vasorelaxant acetylcholine, relay neural signals1. Here we show that these CD4+ CD44high CD62Llow T helper cells by gene expression are a distinct T cell population defined by ChAT (CD4 TChAT). Mice lacking ChAT expression in CD4+ cells have elevated arterial blood pressure and echocardiographic assessment consistent with increased vascular resistance as compared to littermate controls. Jurkat T cells overexpressing ChAT (JTChAT) decreased blood pressure when infused into mice. Co-incubation of JTChAT increased endothelial cell levels of phosphorylated eNOS, and of nitrates and nitrites in conditioned media, indicating increased release of the potent vasodilator nitric oxide. The isolation and characterization of CD4 TChAT cells will enable analysis of the role of these cells in hypotension and hypertension, and may suggest novel therapeutic strategies by targeting cell-mediated vasorelaxation.

The emulsion polymerization of methyl methacrylate (MMA) with butyl acrylate (BA) using aqueous polyurethane dispersion as seed was undertaken to prepare acrylic-polyurethane (PUA) hybrid emulsions with high solid content. The concentrations of the anionic groups were varied by adding different amount of dimethylolpropionic acid (DMPA). The emulsions with a similar bimodal particle size distribution (PSD) were obtained. The viscosity of the emulsions is about 350 mPa.s while the solid content is about 55%.

Current animal models of chronic intermittent hypoxia (CIH)-induced atherosclerosis have limitations. Mechanisms of CIH-induced atherosclerosis are poorly understood. This study tested new mouse models of CIH-induced atherosclerosis and defined the role of NF-κB p50 in CIH-induced atherosclerosis. Mice deficient in apolipoprotein E (ApoE-KO) or in both ApoE and p50 genes (ApoE-p50-DKO) were exposed to sham or CIH. Atherosclerotic lesions on aortic preparations were analyzed. CIH exposure caused atherosclerosis in ApoE-KO mice fed a normal chow diet and with no preexisting atherosclerotic condition in an exposure time-dependent manner. CIH caused more pronounced atherosclerotic lesions in ApoE-p50-DKO mice on a normal chow diet without preexisting atherosclerosis. ApoE-KO and ApoE-p50-DKO mice exposed to CIH for 30 and 9 weeks, respectively, displayed similar areas of atherosclerotic lesions on cross sections of aortic root. P50 gene deletion in ApoE-p50-DKO mice significantly augmented CIH-induced serum levels of tumor necrosis factor-α and IL-6, aortic tumor necrosis factor-α, and inducible nitric oxide synthase expression and aortic infiltration of Mac3-positive macrophages. CIH caused a greater elevation in serum cholesterol level in ApoE-p50-DKO than in ApoE-KO mice. CIH down-regulated hepatic low-density lipoprotein receptor and HMG-CoA reductase expression in ApoE-p50-DKO but not in ApoE-KO mice. We found two new mouse models that are useful for studying mechanisms and pathways of CIH-induced atherosclerosis. We showed that NF-κB p50 protects against CIH-induced atherosclerosis by inhibiting vascular inflammation and hypercholesterolemia.

This study develops an integrated causal path analysis, based on both category-based affect theory and the technology acceptance model (TAM), to identify the antecedents of consumers' attitudes toward self-service technologies. Using online stock trading systems as an example (N = 267), this study employs structural equation modeling to confirm the research structure. The results reveal that consumers' attitudes toward self-service technologies depend on their attitude toward technologies and attitude toward self-services, in support of category-based affect theory. Further, computer self-efficacy and network information literacy positively influence attitude toward technologies, and both perceived ease of use and perceived usefulness positively influence attitude toward self-service technologies, which were proposed in the two theories, were also found. Therefore, this study suggests that integrated attitude model of the category-based affect and TAM can be applied to properly explain the attitude formin...

Investigations on conformal phased array pattern synthesis using a novel hybrid evolutionary algorithm are presented. First, in order to overcome the drawbacks of the standard genetic algorithm (GA) and the particle swarm optimization (PSO), an improved genetic algorithm (IGA) and an improved particle swarm optimization (IPSO) algorithm are proposed by introducing novel mechanisms. Then, inspired by the idea of grafting in botany, a hybrid algorithm called HIGAPSO is proposed, which combines IGA and IPSO to take advantages of both methods. After that, a spherical array antenna using wide-band stacked patch antenna elements is selected as a synthesis example to illustrate the power of HIGAPSO in solving realistic optimization problems. Finally, HIGAPSO is used to optimize the amplitude of the element current excitation of the spherical conformal array. Experimental results show that the hybrid algorithm is superior to GAs and PSOs when applied to both the classical test function and the practical problem of conformal antenna array synthesis.

Endothelium has long been considered both a source and a target of systemic inflammation. However, to what extent endothelial activation contributes to systemic inflammation remains unclear. This study addresses the relative contribution of endothelial activation to systemic inflammation and multiple organ dysfunction and injury (MOD/I) in an E. coli peritonitis model of sepsis. We prevented endothelial activation using transgenic (TG) mice that conditionally overexpress a mutant I-kappaBalpha, a NF-kappaB inhibitor, selectively on endothelium. TG mice and their transgene negative littermates (WT) were injected with saline or E. coli (10(8) CFU per mouse). At 7 h after E. coli infection, markers of systemic inflammation, endothelial activation, and MOD/I were assessed. WT-E. coli mice showed significantly increased serum levels of TNF-alpha, IL-1beta, IFN-gamma, IL-6, KC, and MCP-1; tissue levels of TNF-alpha, IL-6, KC, MCP-1, ICAM-1, and VCAM-1; endothelial leakage index in heart, lungs, liver, and kidney; significantly increased serum levels of AST, ALT, BUN, and creatinine; and increased mortality. Blockade of NF-kappaB-mediated endothelial activation in TG mice had no effects on serum levels of TNF-alpha, IL-1beta, IFN-gamma, IL-6, KC, and MCP-1 (markers of systemic inflammation), and tissue levels of TNF-alpha, IL-6, KC, and MCP-1, but significantly reduced tissue levels of ICAM-1 and VCAM-1 (markers of endothelial inflammation and activation) in those four organs. TG-E. coli mice displayed reversed endothelial leakage index; reduced serum levels of AST, ALT, BUN, and creatinine; and improved survival. Our data demonstrate that endothelial NF-kappaB-driven inflammatory response contributes minimally to systemic inflammation, but plays a pivotal role in septic MOD/I, suggesting that endothelium is mainly a target rather than a source of systemic inflammation.

Aiming at increasing the radiation bandwidth and reducing the antenna size, this article designs the stacked patch antenna and forms the spherical antenna array by virtue of fractal geometry. To minimize the sidelobe level and improve the convergence speed, a hybrid genetic algorithm integrating the main features of genetic algorithm (GA) and particle swarm optimization (PSO) called HGAPSO is adopted. Furthermore, a modified Bernstein polynomial is exploited to reduce the number of optimization variables as well as to obtain a smooth unimodal amplitude distribution. Compared with the uniformly excited conformal antenna array, the maximum relative sidelobe can be reduced by more than 10 dB. © 2009 Wiley Periodicals, Inc. Microwave Opt Technol Lett 51: 1487–1491, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.24348

The cDNA library of an ovary from Small Tail Han sheep before estrus was constructed by switching mechanism at 5 end of RNA transcript (SMART) approach. This library had a plaque liter of 1 × 109 pfu mL−1 and a 96% recombinant ratio of which the fragment length of inserted average cDNA sequences was 1.0 kb. Based on bioinformatics analysis of the sequences, we obtained 338 expressed sequence tags (ESTs) from 380 cDNA clones which indicated 191 contigs. These contigs consist of 89 unmatched ESTs, 9 homologous known genes in sheep, and 93 homologous sequences in species of mouse, bovine, and human beings, including 19 sequences expressed in the ovary or follicle and 14 unknown sequences. Several candidate genes associated with sheep reproduction trait such as epidermal growth factor (EGF), estrogen receptor (ESR), Inhibin, follicle stimulating hormone receptor (FSHR), prostaglandin (PG), and transforming growth factor-β (TGF-β) were identified and the homologous were cloned from this library, which will contribute to compile expression profiles and find the major genes of prolificacy of Small Tail Han sheep.

Impedance-Matching technique is in common use for antennas to broaden their bandwidth. Its application in hightemperature superconducting microstrip antennas is studied theoretically in this paper. It is found that employing an impedance-matching network directly to HTS microstrip antennas to broaden their bandwidth is of little significance.

Objectives a) To determine whether decreased sarcoplasmic calcium release channel (CRC) activity is a mechanism by which myocardial contractility is reduced in endotoxemia; b) to determine whether nitric oxide modulates CRC activity in endotoxemia; and c) to examine two nitric oxide signaling pathways in relation to CRC function in endotoxemia. Design Randomized, prospective using a rat model of endotoxemia. Setting : Research laboratory. Subjects Sprague-Dawley rats. Interventions Endotoxemia was induced by lipopolysaccharide administration. The effects of nitric oxide were studied using the highly selective inducible nitric oxide synthase inhibitor N-(3-(aminomethyl)benzyl)acetamidine dihydrochloride (1400W) and the specific guanylyl cyclase inhibitor 1-H (1, 2, 4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Measurements and main results We assessed myocardial contractility, myocardial nitric oxide content, and guanosine-3',5' (cyclic) phosphate (cGMP) content. We determined CRC activity by calcium release and ryanodine binding assays. We followed these variables at four time points through the course of endotoxemia. We found that myocardial contractility and CRC activity were decreased in late but not in early endotoxemia. Furthermore, inducible nitric oxide synthase inhibition with 1400W restored contractility and CRC activity in late endotoxemia but paradoxically worsened these variables in early endotoxemia. Through the use of the guanylyl cyclase inhibitor ODQ, we demonstrate that nitric oxide acts through cGMP-mediated mechanisms in early and late endotoxemia. We investigated cGMP-independent pathways by assessing the oxidative status of the CRC. We found that in late endotoxemia, nitric oxide decreased the number of free thiols, demonstrating that nitric oxide also acts through cGMP-independent pathways. Conclusions Nitric oxide has a dual effect on the CRC in endotoxemia. At low concentrations, as measured in early endotoxemia, nitric oxide stabilizes the CRC through cGMP-mediated mechanisms. In late endotoxemia, high nitric oxide concentrations decrease channel activity through both cGMP-dependent and cGMP-independent mechanisms.

The study uses Johnson and Johnson's Learning Together approach as a strategy for teaching third-grade learners' information literacy. The study explored the perceptions and attitudes as well as the interactive processes, behavior and patterns of K3 children learning information technology via a cooperative approach. Data collection included a survey, the instructors' observations and reflective journals as well as interviews with the students. The findings of the study are summarized in the following four areas. First, generally speaking, the study showed the positive value of a cooperative approach when effectively integrated into computer curriculums. Second, the study found that group interaction was more procedure-related, including topic choice, duty assignation, content selection, and computer operation. Third, it was found that most learners mastered computer skills, but approached their knowledge-building project with less of a sense of synthesis and integration. Finally, the study found four different forms of interactions (Individual, Authoritative, Argumentative and Consolidated) emerging during the earlier stages of learning with group cohesion increasing at later stages. It can be concluded that learners' attitudes and interactive quality in their group learning is promoted to varying degrees, and most learners are capable of mastering computer skills. However, given the time limitation of four months and that it was the instructors' and learners' first attempt at cooperative learning, there was still much to learn for mastery of the course and much to be desired in scaffolding learners' for highly effective cooperative learning. The paper concludes with some recommendations for the future design of an information technology curriculum for cooperative learning.

The study investigates the value and effectiveness of online workshops as a tool for creating professional learning communities. The pattern of interaction, mentoring quality and attitude of teacher toward participation in a Web-based Teacher's Professional Development Platform were addressed. One hundred and twenty eight participants were co-mentored by three senior elementary mathematics teachers to meet a professional development requirement. Data collection involved content analysis and supplemental surveys. The content analyzed included the participants' message posts, the quality of the dialogue and the quality of mentoring by assistants. A survey was administered to elucidate participants' attitudes towards and perceptions of the Web as a tool for professional development. The study revealed that most participants claimed to have benefited emotionally and intellectually from using telecommunications networks for professional development and support. Positive learning effects on members were satisfactory, yet their participation was not highly interactive or as reflective as the authors would have wished. Closely examining the messages posted by participants revealed that the categories general introduction and organization were most, with the fewest associated queries and responses. The assistants' mentoring strategies mainly included feedback/praise, directing, modeling, questioning, cognitive elaboration and efforts to explore accounted for less than 10% altogether. That is, the assistants focused more on social and organizational functions, and less on intellectual function. The study was significant in that the computer-mediated workshop nurtured the teachers' professional growth, but their participation was neither highly interactive nor and, even though there much anecdotal evidence supported the claim that members enjoyed and valued the online workshops. The paper concludes by offering some recommendations concerning the future design of technology in professional learning.

Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression is an important mechanism underlying ischemia-reperfusion (I/R) induced neutrophil activation and tissue injury in other organs. However, I/R of the lungs has not been shown to upregulate ICAM-1 expression. We determined the time course profile of lung I/R-induced ICAM-1 expression and assessed the role of ICAM-1 in mediating neutrophil sequestration, transmigration, and I/R injury in the isolated blood-perfused rat lungs. I/R had a biphasic effect on ICAM-1 expression, an early downregulation and a late-phase upregulation. Superoxide dismutase and neutrophil depletion prevented the early ICAM-1 downregulation. The late-phase ICAM-1 upregulation coincided with the I/R-induced increase in pulmonary microvascular leakage index. ICAM-1 monoclonal antibody (MAb) reversed the I/R-induced increase in pulmonary microvascular leakage index, with control antibody being ineffective. Neither I/R nor ICAM-1 MAb affected lung MPO activity and circulating neutrophil count. Lung I/R significantly increased bronchoalveolar lavage fluid neutrophil count and the GSSG-to-(GSSG+GSH) ratio. ICAM-1 MAb blocked the I/R-induced increase in GSSG-to-(GSSG+GSH) ratio but had no effect on bronchoalveolar lavage fluid neutrophil count. Our results demonstrated that lung I/R up- and downregulates ICAM-1 expression depending on the duration of reperfusion. ICAM-1 upregulation is an important mechanism of I/R-induced pulmonary endothelial injury.

Objectives: To determine the time course for myocardial production of nitric oxide, peroxynitrite, and glutathione, to determine the activities of the myocardial antioxidant enzymes glutathione peroxidase, superoxide dismutase, and glutathione reductase throughout endotoxemia and into recovery, and to correlate the levels of these variables to left ventricular contractility in endotoxemia. Design: Rats were treated with lipopolysaccharide. Endotoxemic hearts were examined at baseline, 4, 16, 24, and 48 hrs after lipopolysaccharide. Saline time-control groups were treated identically. Setting: A pulmonary research laboratory of a university teaching hospital. Measurements and Main Results: Lipopolysaccharide administration resulted in decreased contractility at 16 hrs as assessed by the isolated papillary muscle technique. Contractility recovered by 24 hrs. Myocardial glutathione content initially increased, but it was decreased from baseline by 16 hrs, as was glutathione peroxidase activity. Both superoxide dismutase and glutathione reductase activities were increased early (4 hrs) and remained elevated throughout the course of the experiment. Myocardial nitric oxide content (assessed by the chemiluminescence technique) was increased by 4 hrs and was markedly elevated by 16 hrs. Nitric oxide levels remained elevated despite recovery of contractility at 24 hrs. Similarly, peroxynitrite (assessed by measurement of 3-nitrotyrosine by high-pressure liquid chromatography) was elevated at 16 hrs and remained elevated despite normalization of contractility at 24 and 48 hrs. Conclusions: Myocardial dysfunction in endotoxemia correlates mainly with decreased glutathione content and glutathione peroxidase activity rather than nitric oxide or peroxynitrite formation. These data indicate that lipopolysaccharide-induced myocardial dysfunction is not solely caused by elevated myocardial nitric oxide levels but rather caused by the sum of complex interactions between various oxygen- and nitrogen-derived radicals.

Background: Recruitment of bone marrow derived endothelial progenitor cells (BMDEPCs) alleviates multiple organ injury (MOI) and improves outcomes. However, mechanisms mediating BMDEPC recruitment following septic MOI remain largely unknown. This study characterized the kinetics of BMDEPC recruitment and proliferation and defined the role of NF-k Bi n regulating BMDEPC recruitment and proliferation. Methods and Main Findings: Chimeric mice with an intact or disrupted NF-kB p50 gene and BMDEPC-restricted expression of green fluorescent protein were created and injected with LPS (2 mg/kg, i.p.). BMDEPC recruitment and proliferation in multiple organs were quantified. BMDEPC recruitment and proliferation are highly organ-dependent. Lungs had the highest number of BMDEPC recruitment, whereas heart, liver and kidney had only a small fraction of the number of BMDEPCs in lungs. Number of proliferating BMDEPCs was several-fold higher in lungs than in other 3 organs. Kinetically, BMDEPC recruitment into different organs showed different time course profiles. NF-kB plays obligatory roles in mediating BMDEPC recruitment and proliferation. Universal deletion of NF-kB p50 gene inhibited LPS-induced BMDEPC recruitment and proliferation by 95% and 69% in heart. However, the contribution of NF-kB to these regulations varies significantly between organs. In liver, universal p50 gene deletion reduced LPS-induced BMDEPC recruitment and proliferation only by 49% and 35%. NF-kB activities in different tissue compartments play distinct roles. Selective p50 gene deletion either in stromal/ parenchymal cells or in BM/blood cells inhibited BMDEPC recruitment by a similar extent. However, selective p50 gene deletion in BM/blood cells inhibited, but in stromal/parenchymal cells augmented BMDEPC proliferation. Conclusions: BMDEPC recruitment and proliferation display different kinetics in different organs following endotoxemic MOI. NF-kB plays obligatory and organ-dependent roles in regulating BMDEPC recruitment and proliferation. NF-kB activities in different tissue compartments play distinct roles in regulating BMDEPC proliferation.

Endothelial barrier disruption is a hallmark of multiple organ injury (MOI). However, mechanisms governing the restoration of endothelial barrier function are poorly understood. Here, we uncovered an NF-κB-to-AP-1 switch that regulates the transition from barrier injury to repair following endotoxemic MOI. Endothelial NF-κB mediates barrier repair by inhibiting endothelial cell (EC) apoptosis. Blockade of endothelial NF-κB pathway activated the activator protein (AP)-1 pathway (NF-κB-to-AP-1 switch), which compensated for the anti-apoptotic and barrier-repair functions of NF-κB. The NF-κB-to-AP-1 switch occurred at 24 hours (injury to repair transition phase), but not at 48 hours (repair phase) post-LPS, and required an inflammatory signal within the endothelium. In the absence of an inflammatory signal, the NF-κB-to-AP-1 switch failed, resulting in enhanced EC apoptosis, augmented endothelial permeability, and impeded transition from barrier injury to recovery. The NF-κB-to-AP-1 switch is a protective mechanism to ensure timely transition from endothelial barrier injury to repair, accelerating barrier restoration following MOI.

The pathophysiology of septic shock is characterized by the induction of multiple proinflammatory genes and their products. Transcription factors play key roles in the transcription of these genes. Transcription factors may play important roles in the pathophysiology of septic shock. However, little information is available regarding the in vivo transcription factor activities during sepsis. We have studied the in vivo effects of LPS on the DNA binding activities of transcription factors Sp1 (promoter selective transcription factor), AP-2 (activating protein-2), AP-1 (activating protein-1), NF-κB (nuclear factor kappa B), and CREB (cAMP response element binding protein). We found that LPS up-regulated the DNA binding activity of inducible transcription factors AP-1, NF-κB, and CREB in a time-dependent manner, but down-regulated the DNA binding activity of constitutive transcription factors Sp1 and AP-2. Thus, LPS regulates the inducible and constitutive transcription factors differentially under in vivo conditions.

National Heart and Lung Institute, Imperial College School of Medicine, London SW3 6LY1 We studied the e•ects of ovalbumin (OA) sensitization and challenge on inducible nitric oxidesynthase (iNOS) gene and protein expression in Brown-Norway rats in vivo.2 By use of Northern analysis, a 4.4-kb iNOS mRNA transcript was weakly observed in control ratlung but there was a 3 fold increase in lungs sensitized to OA alone (P50.05). In sensitized rats, fourhours after exposure to OA aerosol, there was a 6 fold increase in iNOS mRNA transcript (P50.05),which returned to baseline at 24 h.3 Immunostaining with an anti-mouse iNOS antibody revealed some patchy staining of airwayepithelium in nai¨ve rats. There were no changes in sensitized rats exposed to saline, but sensitized andOA-exposed rats showed increased expression in iNOS staining in macrophages.4 Electrophoretic mobility shift assays of lung nuclear extracts showed a marked increase in nuclearfactor-kB (NF-kB)-binding activity at 2 h after allergen exposure with return to baseline at 6, 12 and24 h.5 We concluded that there is increased iNOS gene and protein expression associated with increasedNF-kB DNA-binding in lungs of sensitized and challenged rats. The increase in iNOS expression mayunderlie the increase in exhaled NO found after allergen challenge and may contribute to thedevelopment of allergen-induced airway hyperresponsiveness.Keywords: Nitric oxide; ovalbumin; inducible nitric oxide synthase; nuclear factor-kB; bronchial hyperresponsiveness

Objectives: The role of nitric oxide in mediating the early phase of hypotension and cardiovascular hyporeactivity in sepsis, and the cellular sources of inducible nitric oxide synthase expression under in vivo conditions, remain unclear. The objective of this study was to elucidate the time course and cellular location of inducible nitric oxide synthase messenger RNA (mRNA) expression in rats treated with lipopolysaccharide in vivo. Design: Prospective, placebo-controlled, laboratory study. Setting: Experimental laboratory of a postgraduate medical research institution. Subjects: Normal, anesthetized rats. Interventions: Animals were treated with lipopolysaccharide (15 mg/kg ip), saline (1 mL/kg ip), or lipopolysaccharide plus dexamethasone (3 mg/kg ip, 50 mins before lipopolysaccharide administration) in vivo 4 hrs before the removal of tissues. Measurements and Main Results: Total RNA and mRNA were extracted. Total RNA was used for reverse transcription polymerase chain reaction. Poly-(A) + mRNA was isolated for Northern blot analysis. Cryostat sections of heart and lung were prepared for in situ hybridization to elucidate the cellular location of the inducible nitric oxide synthase gene. Hearts, lungs, aortae, and pulmonary arteries from lipopolysaccharide-treated animals expressed inducible nitric oxide synthase mRNA, which was markedly inhibited by pretreatment with dexamethasone (except in aorta). The threshold time point for inducible nitric oxide synthase mRNA induction was between 20 and 40 mins after lipopolysaccharide administration. The quantity of mRNA increased progressively thereafter, reaching a plateau between 4 and 8 hrs and decreasing markedly by 24 hrs. These findings are consistent with the time course of lipopolysaccharide-induced hypotension and cardiovascular hyporeactivity in animal models of septic shock and in man. Inducible nitric oxide synthase mRNA was mainly detected in vascular and airway smooth muscle cells, cardiac myocytes, pneumocytes, and infiltrated inflammatory cells, but was also identified in airway epithelial and vascular endothelial cells. Vascular smooth muscle represented the predominant cell type expressing inducible nitric oxide synthase under these conditions. Conclusions: These results provide further molecular evidence for the involvement of nitric oxide in the early phase of hypotension and cardiovascular hyporeactivity seen in septic shock. They also suggest that nitric oxide derived from vascular smooth muscle cells may contribute significantly to this hypotension and cardiovascular reactivity.

The excretion of manure-borne steroid hormones, including estrogens and androgens in Liaoning, Jilin and Heilongjiang province was estimated in this study on the basis of statistical data and by using the referenced estimation method in developed countries. In addition, the potential ecological risk of manure-borne steroid estrogens to local surface water systems from applying animal manure was preliminarily assessed. As a result of the rapid development of animal production, the excretions of manure-borne steroid hormones increased in all the three northeast provinces. In 2008, the emissions of total manure-borne estrogens and androgens increased by 2 272.7, 1 951.1 and 1 634.8 kg compared to those in 1998 in Liaoning, Jilin and Heilongjiang provinces, respectively. Especially, the growth rates in the three capital cities of Shenyang, Changchun and Harbin were the fastest among their own provinces. The largest emissions of manure-borne steroid hormones, as well as the highest concentration of predicted estradiol equivalency (EEQs) in the surface water system were found in Liaoning province. According to the lowest observable effect concentration for 17beta-estradiol (10 ng x L(-1)) recommended by the Environmental Agency of United Kingdom, 17.1 ng x L(-1) of EEQs level in Liaoning province might have become a potential risk to local surface water systems.

Background Hypoxic pulmonary arterial hypertension (PAH) is a disabling disease with limited treatment options. Hypoxic pulmonary vascular remodeling is a major cause of hypoxic PAH. Pharmacological agents that can inhibit the remodeling process may have great therapeutic value. Objective To examine the effect of intermedin (IMD), a new calcitonin gene-related peptide family of peptide, on hypoxic pulmonary vascular remodeling. Methods Rats were exposed to normoxia or hypoxia (∼10% O 2 ), or exposed to hypoxia and treated with IMD, administered by an implanted mini-osmotic pump (6.5 μg/rat/day), for 4 weeks. The effects of IMD infusion on the development of hypoxic PAH and right ventricle (RV) hypertrophy, on pulmonary vascular remodeling, on pulmonary artery smooth muscle cell (PASMC) proliferation and apoptosis, and on the activations of l -arginine nitric oxide (NO) pathway and endoplasmic reticulum stress apoptotic pathway were examined. Results Rats exposed to hypoxia developed PAH and RV hypertrophy. IMD treatment alleviated PAH and prevented RV hypertrophy. IMD inhibited hypoxic pulmonary vascular remodeling as indicated by reduced wall thickness and increased lumen diameter of pulmonary arterioles, and decreased muscularization of distal pulmonary vasculature in hypoxia-exposed rats. IMD treatment inhibited PASMC proliferation and promoted PASMC apoptosis. IMD treatment increased tissue level of constitutive NO synthase activity and tissue NO content in lungs, and enhanced l -arginine uptake into pulmonary vascular tissues. IMD treatment increased cellular levels of glucose-regulated protein (GRP) 78 and GRP94, two major markers of endoplasmic reticulum (ER) stress, and increased caspase-12 expression, the ER stress-specific caspase, in lungs and cultured PASMCs. Conclusions These results demonstrate that IMD treatment attenuates hypoxic pulmonary vascular remodeling, and thereby hypoxic PAH mainly by inhibiting PASMC proliferation. Promotion of PASMC apoptosis may also contribute to the inhibitory effect of IMD. Activations l -arginine–NO pathway and of ER stress-specific apoptosis pathway could be the mechanisms mediating the anti-proliferative and pro-apoptotic effects of IMD.

Endotoxin and cytokines have been reported to have both stimulatory and inhibitory effects on endothelial cell-derived nitric oxide release. The discrepancy may be explained by differential regulation of the endothelial and inducible type of nitric oxide synthase gene expression. This study aimed to investigate the differential effect of lipopolysaccharide treatment in vivo on the three isoforms (endothelial, brain-type, and inducible) of nitric oxide synthase gene expression in the rat.Prospective, controlled, animal trial.Experimental laboratory of a postgraduate medical research institution.Normal, anesthetized rats.Animals were treated with lipopolysaccharide (15 mg/kg iP), saline (1 mL/kg ip), or lipopolysaccharide plus dexamethasone (3 mg/kg ip, 50 mins before lipopolysaccharide administration) in vivo 4 hrs before experimentation.The expression of endothelial, brain-type, and inducible nitric oxide synthase mRNAs was quantified by Northern blot analysis using bovine, rat, and mouse cDNA probes, respectively. An endothelial nitric oxide synthase mRNA was detected at 4.3 kilobase in the heart, lung, and aorta, and a 10-kilobase brain-type nitric oxide synthase mRNA was detected in the brain. The endothelial and brain-type signals were strong in tissues from animals treated with saline, but were reduced by three- to four-fold in tissues from lipopolysaccharide-treated rats as estimated by optical density ratio. The 4.4-kilobase inducible nitric oxide synthase mRNA detected using the murine cDNA probe was absent or negligible in the heart, lung, and brain from saline-treated rats, but was markedly increased in the same tissues from lipopolysaccharide-treated animals. Dexamethasone significantly inhibited lipopolysaccharide-induced inducible nitric oxide synthase mRNA expression, but had no effect on the down-regulation of endothelial and brain nitric oxide synthase mRNAs.Rats treated with lipopolysaccharide in vivo display down-regulation of endothelial nitric oxide mRNA in the heart, lung, and aorta, and brain-type nitric oxide synthase mRNA in the brain There was a parallel up-regulation of inducible nitric oxide synthase mRNA in all tissues except in the aorta. Dexamethasone prevents the induction of inducible nitric oxide synthase mRNA. but has no effect on the down-regulation of endothelial and brain-type nitric oxide synthase mRNAs induced by lipopolysaccharide. Thus, endotoxin regulates constitutive and inducible nitric oxide synthase mRNA differentially.

1. Prostaglandins are important regulatory mediators of cardiovascular and pulmonary functions which may become disordered in patients with sepsis. The mechanisms controlling their synthesis and release under these circumstances remain unclear. Cyclo-oxygenase (COX, prostaglandin G/H synthase) is a key enzyme in prostaglandin synthesis and has two isoforms (COX-1 and COX-2). COX-1 is constitutively expressed and is probably responsible for prostaglandin release under physiological conditions, whereas COX-2 is expressed at high levels upon induction. 2. We investigated the effect of lipopolysaccharide treatment in vivo on differential COX-1 and COX-2 mRNA expression in the rat. 3. The 2.8 kb COX-1 message was detected in all lungs and seven hearts of eight control rats. In lipopolysaccharide-treated animals, COX-1 expression was reduced by approximately 5-fold in lungs and 2-fold in hearts as quantified by densitometry. In parallel, a marked upregulation of COX-2 mRNA expression was observed. The 4.4 kb COX-2 transcript was absent or expressed at low level in control lungs and hearts, but was increased by approximately 7- and 12-fold in lipopolysaccharide-treated lungs and hearts respectively. Neither the down-regulation of COX-1 nor the upregulation of COX-2 mRNA induced by lipopolysaccharide was significantly affected by pretreatment with dexamethasone in lung and heart, although expression of inducible nitric oxide synthase, induced by lipopolysaccharide, was markedly inhibited in the same tissues. 4. The down-regulation of COX-1 and upregulation of COX-2 may contribute to the multi-organ failure seen in sepsis.

Objectives Patients with obstructive sleep apnea have an impaired endothelium-dependent vasodilator response. The mechanisms underlying this impairment remain unclear. We tested the hypothesis that chronic intermittent hypoxia (CIH) impairs endothelium-dependent vasodilatation by NF-κB-mediated down-regulation of endothelial nitric oxide synthase (eNOS) expression. Methods Wild type (WT) mice and mice deficient in NF-κB p50 or TNF-α gene were exposed to sham or CIH. Aortic NF-κB activity and aortic expression of TNF-α were determined. Aortic and mesenteric artery levels of eNOS expression were examined and their correlation to endothelium-dependent vasodilator response in vitro and vasodepressor response in vivo were analyzed. Results WT mice exposed to CIH for five to eight weeks showed significantly reduced eNOS protein expression in aortas and mesenteric arteries, associated with significantly blunted vasodilator and vasodepressor responses to acetylcholine, but not to sodium nitroprusside. CIH activated NF-κB, which preceded TNF-α up-regulation and eNOS down-regulation. NF-κB p50 gene deletion blocked NF-κB activation, inhibited TNF-α expression, prevented eNOS down-regulation and reversed the impaired endothelium-dependent vasodepressor response induced by CIH. TNF-α knockout prevented CIH-induced eNOS down-regulation and restored the endothelium-dependent vasodepressor response. Conclusions CIH exposure impairs endothelium-dependent vasodilator mechanism by stimulating NF-κB-mediated TNF-α generation, which in turn, down-regulates eNOS expression, resulting in an impaired endothelium-dependent vasodilatation.

Background: Males have a higher prevalence of hepatocellular carcinoma (HCC) than females in general, but the reasons for the sex disparity are still obscure. DNA copy number alteration (CNA) is a major feature of solid tumors including HCC, but whether CNA plays a role in sex-related differences in HCC development has never been evaluated. Methods: High-resolution array comparative genomic hybridization (CGH) was used to examine 17 female and 46 male HCC patients with chronic hepatitis B virus (HBV) infection in Shanghai, China. Two-tailed Fisher’s exact or χ2 tests was used to compare CNAs between females and males. Results: The overall frequencies and patterns of CNAs in female and male cases were similar. However, female HCC tumors presented more copy number gains compared to those in males on 1q21.3-q22 (76.5% vs. 37.0%, P = 0.009), 11q11 (35.3% vs. 0.0%, P = 0.0002) and 19q13.31-q13.32 (23.5% vs. 0.0%, P = 0.004), and loss on 16p11.2 (35.3% vs. 6.5%, P = 0.009). Relative to females, male cases had greater copy number loss on 11q11 (63.0% vs. 17.6%, P = 0.002). Further analyses showed that 11q11 gain correlated with 19q13.31-q13.32 gain (P = 0.042), 11q11 loss (P = 0.011) and 16p11.2 loss (P = 0.033), while 1q21.3-q22 gain correlated with 19q13.31-q13.32 gain (P = 0.046). Conclusions: These findings suggest that CNAs may play a role in sex-related differences in HBVassociated HCC development.

Current animal models of chronic intermittent hypoxia (CIH)-induced atherosclerosis have limitations. Mechanisms of CIH-induced atherosclerosis are poorly understood. This study tested new mouse models of CIH-induced atherosclerosis and defined the role of NF-κB p50 in CIH-induced atherosclerosis. Mice deficient in apolipoprotein E (ApoE-KO) or in both ApoE and p50 genes (ApoE-p50-DKO) were exposed to sham or CIH. Atherosclerotic lesions on aortic preparations were analyzed. CIH exposure caused atherosclerosis in ApoE-KO mice fed a normal chow diet and with no preexisting atherosclerotic condition in an exposure time-dependent manner. CIH caused more pronounced atherosclerotic lesions in ApoE-p50-DKO mice on a normal chow diet without preexisting atherosclerosis. ApoE-KO and ApoE-p50-DKO mice exposed to CIH for 30 and 9 weeks, respectively, displayed similar areas of atherosclerotic lesions on cross sections of aortic root. P50 gene deletion in ApoE-p50-DKO mice significantly augmented CIH-induced serum levels of tumor necrosis factor-α and IL-6, aortic tumor necrosis factor-α, and inducible nitric oxide synthase expression and aortic infiltration of Mac3-positive macrophages. CIH caused a greater elevation in serum cholesterol level in ApoE-p50-DKO than in ApoE-KO mice. CIH down-regulated hepatic low-density lipoprotein receptor and HMG-CoA reductase expression in ApoE-p50-DKO but not in ApoE-KO mice. We found two new mouse models that are useful for studying mechanisms and pathways of CIH-induced atherosclerosis. We showed that NF-κB p50 protects against CIH-induced atherosclerosis by inhibiting vascular inflammation and hypercholesterolemia.