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Sex differences in the long-term prognosis of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients undergoing alcohol septal ablation (ASA) remain unclear, especially in the Chinese Han population.This cohort study included 320 HOCM Chinese Han patients who underwent ASA because of symptomatic left ventricular outflow tract (LVOT) obstruction. Patients were grouped according to sex: females (mean±standard deviation age [SD] 50.7±6.8 years) and males (mean±SD age 52.6±7.3 years). Individuals were followed over the long term.Pre-procedure, women had more symptoms (New York Heart Association [NYHA] class III-IV 67.3% vs 56.3%, p=0.03), more atrial fibrillation (23.5% vs 14.6%, p=0.047) than men. Transient complete atrioventricular block after ASA was more common in woman than in men (34.0 vs 23.4%; p=0.048). Residual LVOT gradient, post-procedural residual left ventricular wall thickness, NYHA functional class, and adverse arrhythmic events were comparable between the two groups. The 10-year survival rate (77% vs 89%, p=0.037) and the annual adverse arrhythmic event rate (1.3% vs 0.4%, p0.01) following ASA were significantly worse in women compared with men. Kaplan-Meier analysis showed a significantly lower survival in women compared with men (p=0.023). In multivariable modelling, female sex remained independently associated with higher all-cause mortality (hazard ratio, 1.12; 95% confidence interval, 1.08-1.27; p=0.03) when adjusted for age, NYHA class III-IV symptoms, and other cardiovascular comorbidities.Female patients with HOCM undergoing ASA tended to have more severe symptoms and adverse arrhythmic events. The 10-year survival rate after ASA was significantly worse in women compared with men with HOCM. Sex may need to be considered as an important factor in the clinical management of patients with symptomatic HOCM.

The dramatic changes in Land-Use and Land-Cover (LULC) in urbanizing areas have led to problems such as urban flooding and water pollution. Green Stormwater Infrastructure (GSI) has become a new approach to mitigate these problems. The comprehensive assessment of GSI strategies and their combinations is the foundation for decision making regarding GSI implementation. Using the rapidly developing Western New City of Zhuhai in China as an example, this study applies Storm Water Management Model (SWMM) to evaluate Single and Combined GSI strategies. Four indicators—runoff volume control, peak flow reduction, pollutant removal, and economic cost—are selected to conduct a Multi-Criteria Decision Analysis with the use of Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS). The performance evaluation of Single and Combined GSIs suggests that: (i) there may exist linear or nonlinear relation between the efficiency of a Single GSI and the size of its implementation. (ii) the optimal LULC-cost effective range may be identified for certain GSI, and (iii) Distributed-Centralized Combined GSIs are superior to other strategies in regard to reduction of runoff, TSS and peak flow. The TOPSIS assessment indicates that the cost weight ( w c ) has significant impact on the multi-criteria decision-making, and all strategies may be classified into three categories: effectiveness, cost, and stability. The results of TOPSIS show that the Distributed-Centralized Combined GSIs (scenarios S3, S5) are the best options if w c is not an important factor, while the Centralized Single GSI (S6) is the best option if w c becomes more important. Furthermore, this study can provide the well-informed alternative stormwater management plans and GSI decisions for local planners and water resource managers in the rapidly urbanizing sponge cities.

Some symbiotic microbes are restricted to specialized host cells called bacteriocytes. However, the molecular and cellular mechanisms underlying the development of bacteriocytes are largely obscure. We find that maternally inherited bacteriocytes proliferate in adult females but degenerate in adult males of the whitefly Bemisia tabaci. Single-cell transcriptomics and immunohistochemistry reveal that cell division only occurs in the bacteriocytes of adult females, whereas autophagy and apoptosis are induced in the bacteriocytes of adult males. A transcription factor, Adf-1, enriched in bacteriocytes, is highly expressed in female bacteriocytes relative to male bacteriocytes. Silencing Adf-1 reduces the bacteriocyte number and Portiera titer and activates autophagy and apoptosis in females. The differential dynamics of both cell division and death in bacteriocytes and distinct expression of Adf-1 in bacteriocytes between whitefly sexes underlie the sexual differentiation of bacteriocyte development. Our study reveals that insect sex affects the development of bacteriocytes by cellular and molecular remodeling.

Global warming conditions and the impending energy crisis have gained attention of the research community worldwide. Urban researchers have been increasingly focused on energy-efficient cities from varying perspectives to gain insight and improve efficiency contributions in overall design components. Micro-level studies with families or individuals as research units have yielded abundant accomplishments, yet top urban macro-level factors with the highest energy consumption impact have not been identified. Direct CO 2 Emissions (DCE) of urban residents in 286 cities at the prefectural level and above in China are first estimated in this study. The relationship between DCE and urban macro-level factors including climatic, socio-economic and urban form with partial correlation analyses is then investigated. Findings and suggestions include: (1) Climatic metrics exert significant impact on residential Central Heating DCE and Electricity DCE with cities in different Building Climate Divisions exhibiting DCE variations. (2) Metrics measuring economic development levels exhibit the most significant positive impact on Electricity DCE, Gas DCE, Transportation DCE and total DCE per capita; however, total DCE per GDP decreases as economic development level rises. (3) Urban form metrics significantly impact Electricity DCE with greater effects on Transportation DCE, thus indicating the need for further research on urban form metrics.

Sap-sucking insects are important pests in agriculture and good models to study insect biology. The role of ecdysone pathway genes in the life history of this group of insects is largely unknown likely due to a lack of efficient gene silencing methods allowing functional genetic analyses. Here, we developed a new and high throughput method to silence whitefly genes using a leaf-mediated dsRNA feeding method. We have applied this method to explore the roles of genes within the molting hormone-ecdysone synthesis and signaling pathway for the survival, reproduction and development of whiteflies. Silencing of genes in the ecdysone pathway had a limited effect on the survival and fecundity of adult whiteflies. However, gene silencing reduced survival and delayed development of the whitefly during nymphal stages. These data suggest that the silencing method developed here provides a useful tool for functional gene discovery studies of sap-sucking insects, and further indicate the potential of regulating the ecdysone pathway in whitefly control.

Objective To evaluate the safety and feasibility of percutaneous coronary intervention and antiplatelet therapy in patients who have undergone endovascular graft exclusion. Methods From January 2005 to July 2007, percutaneous transluminal intervention (PCI) was performed in 13 patients who had undergone endovascular graft exclusion for the treatment of either acute or chronic Stanford B aortic dissection. Anticoagulant and antiplatelet treatments were administered according to the standard protocol. Patients were followed up for a mean period of 11months. Clinical characteristics, false lumen thrombosis and angiographic data were collected. Results PCI was technically successful in all 13 patients and no severe complications, including death, paraplegia or renal failure occurred during hospitalization. Complete false lumen thrombosis was observed in all patients within 6months. There were no major complications such as death, dissection rupture, or aneurysm development during the follow-up period. Conclusion Our data suggested that PCI and standard antiplatelet therapy are feasible and safe in patients who have undergone endovascular stent graft exclusion for Stanford B aortic dissection.

The whitefly Bemisia tabaci has risen to international prominence since the 1980s due to the rapid spread around the globe by the two species B and Q within this species complex. The invasion of B has often been associated with the displacement of indigenous whiteflies. As the genetic structure of B. tabaci is diverse, more case studies of the competitive relationships between B and indigenous species of the whitefly species complex will help to understand further the mechanisms underlying the invasion of B. We examined the competitive interactions between B and ZHJ2, a widely distributed indigenous whitefly in Asia, on host plants with differential levels of suitability to the two species in the laboratory, and also tested the effect of insecticide application on the competitive relationships. Three species of plants were tested including cotton, a plant showing similar levels of suitability to both species, squash, a plant showing higher suitability to B than to ZHJ2, and kidney bean, a plant showing higher suitability to ZHJ2 than to B. In the case of no insecticide application, B displaced ZHJ2 on cotton, squash, and kidney bean by the 6th, 3rd and 10th generation, respectively. With the application of imidacloprid, the displacement of ZHJ2 by B on cotton occurred by the 5th generation. As the displacement progressed, the proportion of B females increased, and the proportion of ZHJ2 females decreased on cotton and squash. In contrast, on kidney bean the proportion of B females remained unchanged while that of ZHJ2 increased. These results show the strong capacity of the invasive B to displace ZHJ2, and indicate that host plants with differential levels of suitability to the two species may affect the speed but not the trend of displacement and insecticide application may accelerate the process of displacement.

The bio-effects of cellular repressor of E1A-stimulated genes (CREG) have been proposed to depend on its N-glycosylation and binding to mannose-6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R). The present study aimed to investigate the detailed mode and specific sites for their binding and the functional relevance of this binding in the phenotypic modulation of vascular smooth muscle cells (SMCs). Wild-type and glycosylation mutant human CREG (wtCREG and mCREG) proteins were expressed and isolated from HEK293 cells. CREG knocked-down SMCs were used to evaluate their biological activity. Both wtCREG and mCREG arrest cell cycle progression of CREG knocked-down SMCs when added to the culture medium. In vitro binding assay revealed that CREG bound to M6P/IGF2R extracellular domains 7-10 and 11-13 in a glycosylation-dependent and -independent manner, respectively. Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody suggest that the binding to domains 11-13, as well as to 7-10, is adequate for CREG to modulate SMC proliferation. These data suggest that soluble CREG protein can exert its biological function via glycosylation-independent binding to the extracellular domains 11-13 of cell surface M6P/IGF2R, and thereby provide novel insights into CREG modulation of SMC phenotypic switching from contractile to proliferative.

For the purpose of developing flexible organic photovoltaic devices, we have fabricated two flexible devices using 5-formyl-2,2′:5′,2″:5″,2‴-quaterthiophene (4T-CHO), 5-formyl-2,2′:5′, 2″:5″,2‴:5‴,2⁗-quinquethiophene (5T-CHO) and 3,4,9,10-perylenetertracarboxylic dianhydride (PTCDA). The PET-ITO/4T-CHO/PTCDA/Al device has an open circuit voltage (Voc) of 1.56 V, photoelectric conversion efficiency of 0.77%. The PET-ITO/5T-CHO/PTCDA/Al device has a Voc of 1.70 V, photoelectric conversion efficiency of 0.84%. The two flexible devices have high Voc (1.56 and 1.70 V). It is possible that intermolecular hydrogen bonding between –CHO group of nT-CHO and carboxylic dianhydride of PTCDA contributes to enhancing the efficiency by promoting interfacial electron transfer and eliminating the subconducting band trap sites.

For the purpose of developing organic photovoltaic devices with good performance characteristics, we have fabricated two devices using 4T-CHO, 5T-CHO and PTCDA. The ITO/4T-CHO/PTCDA/Al device has a V oc of 2.45 V and photoelectric conversion efficiency of 2.76%. The ITO/5T-CHO/PTCDA/Al device has a V oc of 2.1 3V and photoelectric conversion efficiency of 2.90%. The two devices have higher V oc (2.45 and 2.13 V). It is possible that intermolecular hydrogen bonding between CHO group of n T-CHO and carboxylic dianhydride of PTCDA contribute to enhance the efficiency by promoting interfacial electron transfer and eliminating the subconducting band trap sites.

The presence of the blood-brain barrier complicates drug delivery in the development of therapeutic agents for the treatment of glioblastoma multiforme (GBM). The use of local gene transfer in the brain has the potential to overcome this delivery barrier by allowing the expression of therapeutic agents directly at the tumor site. In this study, we describe the development of a recombinant adeno-associated (rAAV) serotype 8 vector that encodes an optimized soluble inhibitor, termed sVEGFR1/R2, of vascular endothelial growth factor (VEGF). VEGF is an angiogenic factor highly up-regulated in GBM tumor tissue and correlates with disease progression. In subcutaneous models of GBM, VEGF inhibition following rAAV-mediated gene transfer significantly reduces overall tumor volume and increases median survival time following a single administration of vector. Using orthotopic brain tumor models of GBM, we find that direct intracranial administration of the rAAV-sVEGFR1/R2 vector to the tumor site demonstrates anti-tumor efficacy at doses that are not efficacious following systemic delivery of the vector. We propose that rAAV-mediated gene transfer of a potent soluble VEGF inhibitor in the CNS represents an effective antiangiogenic treatment strategy for GBM.

The toroviruses, Berne virus (BEV) and Breda virus (BRV), are recognized pathogens of horses and cattle, respectively. Torovirus-like particles (TVLPs) that are immunologically related to BRV have been reported as etiological agents of gastroenteritis in humans. Of the toroviruses, only BEV has been shown to replicate in cell culture. Hence, these agents can be routinely detected only by electron microscopy (EM), although serological testing has been used as well. Our studies have provided supporting evidence that the TVLPs detected in the stool specimens of pediatric patients with gastroenteritis are human toroviruses. By EM, these particles are morphologically similar to BEV and BRV. Thin-section electron microscopy revealed that TVLPs contain toroidal-shaped nucleocapsids. Viruses purified from human fecal specimens agglutinate rabbit erythrocytes. BRV antiserum as well as convalescent sera from patients with gastroenteritis whose stools contain TVLPs were shown to contain antibodies that react with purified TVLPs as demonstrated by hemagglutination inhibition, immunoelectron microscopy, and immunoblotting. RNA extracted from partially purified TVLP preparations is amplifiable by RT-PCR using primers bracketing a 219-base region at the 3′ end of the Berne virus genome. Sequence analysis of amplicons from five isolates showed a high degree of identity with the corresponding BEV sequence.

Glioblastoma Multiforme (GBM) is the most common primary brain tumor leading to more than 12,000 deaths per year in the US. Radiation and chemotherapy has achieved limited success in the treatment of GBM and gene therapy may be a promising new strategy. We have investigated the gene transfer efficiencies of AAV serotypes –2, -5 and –6 encoding GFP in the murine CNS. AAV vectors derived from serotype 6 using the strong constitutive CAG promoter provide the optimum transduction efficiency in both the absence (normal brain) and presence of tumor (murine 4C8 glioma and human U87 glioma) in the murine brain. Following this work, the therapeutic potential of recombinant AAV-6 gene delivery of soluble forms of the human vascular endothelial growth factor receptors (sVEGFR) for blocking glioma growth in vivo following local (intra-tumoral) and systemic administration was investigated. Initially, soluble forms of VEGFR1 (domains 1-7) and VEGFR2 (domains 1-7) were constructed by fusion to an Fc segment of human IgG1, however, both receptors showed minimal efficacy in inhibiting subcutaneous C6 (rat glioma) and U87 glioma tumors following expression in vivo. To address this lack of efficacy, a chimeric soluble VEGF receptor was constructed, comprising of domains from VEGFR1 and VEGFR2 linked to IgG1 Fc, termed sVEGFR1/2. Assays in vitro and in CAM demonstrated that the sVEGFR1/2 molecule has VEGF binding affinities comparable to that of VEGFR1 coupled with the favorable bioavailability of the sVEGFR2 receptor. Furthermore, the sVEGFR1/2 molecule completely prevented tumor progression >80 days post-tumor implantation in comparison to the control group in a murine sub-cutaneous U87 human glioma model and demonstrated similar efficacy in the C6 model. The potency of a recombinant AAV-6 vector encoding the sVEGFR1/2 transgene to treat orthotopic murine 4C8 glial tumors in BFD2F1 immuno-competent mice was then examined. Animals received AAV-VEGFR1/2 delivered intra-tumorally by stereotaxic injection into pre-established (7-day) 4C8 tumors. Thirty days post-tumor implantation, animals treated with AAV6-VEGFR1/2 vector showed > 80% decrease in tumor growth in comparison to control animals as assessed by MRI. Survival was also significantly extended by treatment with the soluble chimeric VEGF receptor expressed from the AAV-6 vector. In addition, the efficacy of systemic sVEGFR1/2 expression following AAV mediated gene transfer to the liver on orthotopic 4C8 tumor growth was compared to local delivery to determine the impact of the blood brain barrier of the efficacy of the transgene. This work suggests that local delivery of a potent anti-VEGF agent by AAV-6 mediated gene transfer may be a novel and effective strategy for blocking the growth of human glioma tumors in vivo and may present a niche in which local gene therapy has advantage over systemic protein therapies.

The metastatic spread of tumor cells represents a critical point in tumor progression. The presence of metastases in regional lymph nodes is a strong indicator of poor patient survival in many types of cancer. Production of the lymphangiogenic factor, vascular endothelial growth factor C (VEGF-C), has been detected in tumors and the significance of VEGF-C mediated lymphangiogenesis for tumors has been demonstrated. VEGF-C stimulates tumor lymphangiogenesis and metastasis to regional lymph nodes by binding to VEGF receptor 3 (VEGFR3). A number of studies have demonstrated that blocking VEGFR3 signaling suppresses tumor lymphangiogenesis and lymph node metastasis. In this study, we investigated whether AAV-mediated gene delivery of a soluble VEGFR3 fusion protein, sVEGFR3-Fc, inhibits development of lymph node metastases in prostate (PC-3mlg2) and melanoma (A375mln1) tumor models. Tumor cell lines were established from lymph node metastases of mice bearing PC-3 and A375 subcutaneous tumors, respectively. These tumor cell lines were transduced with the luciferase gene enabling the detection of lymphatic and systemic metastases by luminescence imaging. A single injection of AAV-sVEGFR3-Fc inhibited tumor cell metastasis to the regional lymph nodes. The inhibition was approximately 70% in PC-3mlg2 and A375mln1 models, as evident by the reduced number of tumor-bearing lymph nodes when compared with the animals injected with an AAV null vector. We are currently performing dose response studies in both tumor models to determine the optimum VEGFR3 serum levels required for efficient block of lymphogenic metastasis.