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Shengjue Xiao,1,* Zhenwei Wang,1,* Ronghua Zuo,2,* Yufei Zhou,3 Yiqing Yang,1 Tian Chen,1 Naifeng Liu1 1Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Naifeng Liu, Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, People’s Republic of China, Tel +86 025 8327 2002, Email liunf@seu.edu.cnObjective: Our research was designed to investigate the relationship between systemic immune inflammation (SII) index and all-cause, cardiovascular disease (CVD), and cancer-related mortality in patients with CVD.Methods: We used the National Health and Nutrition Examination Survey data from 1999 to 2018 to conduct this study. The association between SII index and all-cause, CVD, and cancer-related mortality in patients with CVD was examined using restricted cubic splines (RCS), Cox proportional hazard models, and subgroup analysis, respectively. CVD was defined as a composite of five outcomes of CVD, including coronary heart disease (CHD), congestive heart failure (CHF), angina pectoris, myocardial infarction, and stroke. Additionally, the link between SII index and all-cause, CVD, and cancer-related mortality in patients with a composite of five outcomes of CVD was also explored.Results: In total, 5329 participants were included. The RCS also showed a U-curve correlation between SII index and the all-cause, CVD, and cancer-related mortality in patients with CVD. As compared with the individuals with lowest quartile of SII index, h

Zhao Li,1 Yiqing Yang,1 Liqiang Zheng,2 Guozhe Sun,1 Xiaofan Guo,1 Yingxian Sun1 1Department of Cardiology, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2Department of Clinical Epidemiology, Library, Department of Health Policy and Hospital Management, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of ChinaCorrespondence: Yiqing Yang; Yingxian Sun Tel +86 24 83282688Fax +86 24 83282346Email yangyiqing0725@163.com; yingxiansun123@163.comObjective: To develop and validate a new prediction model for the general population based on a large panel of both traditional and novel factors in cardiovascular disease (CVD).Design and Setting: We used a prospective cohort in the Northeast China Rural Cardiovascular Health Study (NCRCHS).Participants: A total of 11,956 participants aged ≥ 35 years were recruited between 2012 and 2013, using a multistage, randomly stratified, cluster-sampling scheme. In 2015 and 2017, the participants were invited to join the follow-up study for incident cardiovascular events. The loss to follow-up number was 351. At the study’s end, we obtained the CVD outcome events for 10,349 participants.Primary and Secondary Outcome Measures: The prediction model was developed using demographic factors, blood biochemical indicators, electrocardiographic (ECG) characteristics, and echocardiography indicators collected at baseline (Model 1). Framingham-related variables, namely age, sex, smoking, total and high-density lipoprotein cholesterol and diabetes status were used to construct the traditional model (Model 2).Results: For the observed population (n = 10,349), the median follow-up time was 4.66 years. The total incidence of CVD was 1.1%/year, including stroke (n = 342) and coronary heart disease (n = 175). The results of Model 1 indicated that in addition to the traditional risk factors, QT interval (p < 0.001), aortic root diameter (p < 0.001), and ventricu

Assembly interface of aircraft vertical tail is a large thin-wall structure and made from titanium alloys, which causes easily machining vibration, deformation and undercutting in finish machining due to its low stiffness, low thermal conductivity, and high chemical activity. To address these problems, a novel eddy current damper for assembly interfaces machining (ECD-AIM) is proposed to suppress multimodal vibration in the machining of the assembly interfaces. Within the context, the mathematical model of damping performance of the damper is established based on the principle of electromagnetic induction, based on which a novel design of the damper is proposed, and optimized by considering the relationship between damping performance and the key components of the damper. Then, the dynamics model of the suppression system of the assembly interface machining is established, where the relationship between vibration velocity and damping performance of the damper is obtained by using numerical analysis and finite element simulation. Finally, the damping performance of the damper is validated in terms of the three configurations (no applied ECD-AIM, a single ECD-AIM, and dual ECD-AIMs) via a set of dynamic tests (impact tests and harmonic tests) and cutting tests. The test results demonstrate that the configuration of dual ECD-AIMs can guarantee stability and reliability of assembly interface machining. The proposed damper can provide a feasible solution for vibration suppression in a limited workspace., QC 20200421

Zhongyuan Tang, Weiwei Feng, Yiqing Yang, Qun Wang Department of Obstetrics & Gynecology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Weiwei FengDepartment of Obstetrics & Gynecology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, People’s Republic of ChinaTel +86 21 64370045Email fww12066@rjh.com.cnBackground: Ovarian cancer is the third leading cause of death among gynecological cancers in women in China. Chemotherapy is an important method for comprehensive treatment of ovarian cancer, but the curative effect is poor.Purpose: In this study, gemcitabine (GEM) -loaded RGD modified liposomes (LPs) were developed by the emulsification-solvent evaporation method and evaluated for their antitumor activity in vitro and in vivo.Methods: The physicochemical properties of LPs such as particle size, zeta potential and in vitro drug release were investigated. We also demonstrated the effect of RGD-GEM-PEG LPs in ovarian cancer.Results: RGD-PEG3500-DSPE GEM LPs had a uniform spherical morphology. The mean particle size and polydispersity index were determined to be 106.7 nm and 0.13 respectively. The ER% and DL% of the formulation were 79.6±3.1% and 6.1±1.4% respectively. Compared with the free drug, RGD modified GEM LPs had sustained-release properties in vitro. In vivo, compared with the DiD-RGD-PEG3500-DSPE GEM LPs group, free DiD-GEM and DiD-GEM LPs had no obvious fluorescence intensity in tumor of mice at all times, indicating that ordinary liposomes and drugs had no tumor targeting function. RGD-PEG3500-DSPE GEM LPs showed a superior antiproliferative effect on SKOV3 cells and had a better antitumor effect in vivo than non-modified LPs.Conclusion: These results indicated that RGD-PEG3500-DSPE GEM LPs were a promising candidate for antitumor drug delivery.Keywords: RGD, gemcitabine

Cerebral cavernous malformations (CCMs) are a cause of stroke and seizure for which no effective medical therapies yet exist. CCMs arise from the loss of an adaptor complex that negatively regulates MEKK3-KLF2/4 signalling in brain endothelial cells, but upstream activators of this disease pathway have yet to be identified. Here we identify endothelial Toll-like receptor 4 (TLR4) and the gut microbiome as critical stimulants of CCM formation. Activation of TLR4 by Gram-negative bacteria or lipopolysaccharide accelerates CCM formation, and genetic or pharmacologic blockade of TLR4 signalling prevents CCM formation in mice. Polymorphisms that increase expression of the TLR4 gene or the gene encoding its co-receptor CD14 are associated with higher CCM lesion burden in humans. Germ-free mice are protected from CCM formation, and a single course of antibiotics permanently alters CCM susceptibility in mice. These studies identify unexpected roles for the microbiome and innate immune signalling in the pathogenesis of a cerebrovascular disease, as well as strategies for its treatment.

The emergence of smartwatches poses new challenges to information security. Although there are mature touch-based authentication methods for smartphones, the effectiveness of using these methods on smartwatches is still unclear. We conducted a user study (n=16) to evaluate how authentication methods (PIN and Pattern), UIs (Square and Circular), and display sizes (38mm and 42mm) affect authentication accuracy, speed, and security. Circular UIs are tailored to smartwatches with fewer UI elements. Results show that 1) PIN is more accurate and secure than Pattern; 2) Pattern is much faster than PIN; 3) Square UIs are more secure but less accurate than Circular UIs; 4) display size does not affect accuracy or speed, but security; 5) Square PIN is the most secure method of all. The study also reveals a security concern that participants' favorite method is not the best in any of the measures. We finally discuss implications for future touch-based smartwatch authentication design.

Mammals transport blood through a high-pressure, closed vascular network and lymph through a low-pressure, open vascular network. These vascular networks connect at the lymphovenous (LV) junction, where lymph drains into blood and an LV valve (LVV) prevents backflow of blood into lymphatic vessels. Here we describe an essential role for platelets in preventing blood from entering the lymphatic system at the LV junction. Loss of CLEC2, a receptor that activates platelets in response to lymphatic endothelial cells, resulted in backfilling of the lymphatic network with blood from the thoracic duct (TD) in both neonatal and mature mice. Fibrin-containing platelet thrombi were observed at the LVV and in the terminal TD in wild-type mice, but not Clec2-deficient mice. Analysis of mice lacking LVVs or lymphatic valves revealed that platelet-mediated thrombus formation limits LV backflow under conditions of impaired valve function. Examination of mice lacking integrin-mediated platelet aggregation indicated that platelet aggregation stabilizes thrombi that form in the lymphatic vascular environment to prevent retrograde blood flow. Collectively, these studies unveil a newly recognized form of hemostasis that functions with the LVV to safeguard the lymphatic vascular network throughout life.

Congenital long QT syndrome (LQTS) is a hereditary disorder that leads to sudden cardiac death secondary to fatal cardiac arrhythmias. Although many genes for LQTS have been described, the etiology remains unknown in 30%-40% of cases. In the present study, a large Chinese family (four generations, 49 individuals) with autosomal-dominant LQTS was clinically evaluated. Genome-wide linkage analysis was performed by using polymorphic microsatellite markers to map the genetic locus, and positional candidate genes were screened by sequencing for mutations. The expression pattern and functional characteristics of the mutated protein were investigated by western blotting and patch-clamp electrophysiology. The genetic locus of the LQTS-associated gene was mapped to chromosome 11q23.3-24.3. A heterozygous mutation (Kir3.4-Gly387Arg) was identified in the G protein-coupled, inwardly rectifying potassium channel subunit Kir3.4, encoded by the KCNJ5 gene. The Kir3.4-Gly387Arg mutation was present in all nine affected family members and absent in 528 ethnically matched controls. Western blotting of human cardiac tissue demonstrated significant Kir3.4 expression levels in the cardiac ventricles. Heterologous expression studies with Kir3.4-Gly387Arg revealed a loss-of-function electrophysiological phenotype resulting from reduced plasma membrane expression. Our findings suggest a role for Kir3.4 in the etiology of LQTS.

The inward rectifier K(+) channel Kir2.1 mediates the potassium I(K1) current in the heart. It is encoded by KCNJ2 gene that has been linked to Andersen's syndrome. Recently, strong evidences showed that Kir2.1 channels were associated with mouse atrial fibrillation (AF), therefore we hypothesized that KCNJ2 was associated with familial AF. Thirty Chinese AF kindreds were evaluated for mutations in KCNJ2 gene. A valine-to-isoleucine mutation at position 93 (V93I) of Kir2.1 was found in all affected members in one kindred. This valine and its flanking sequence is highly conserved in Kir2.1 proteins among different species. Functional analysis of the V93I mutant demonstrated a gain-of-function consequence on the Kir2.1 current. This effect is opposed to the loss-of-function effect of previously reported mutations in Andersen's syndrome. Kir2.1 V93I mutation may play a role in initiating and/or maintaining AF by increasing the activity of the inward rectifier K(+) channel.

Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice. We first reported an S140G mutation of KCNQ1, an alpha subunit of potassium channels, in one Chinese kindred with AF. However, the molecular defects and cellular mechanisms in most patients with AF remain to be identified. We evaluated 28 unrelated Chinese kindreds with AF and sequenced eight genes of potassium channels (KCNQ1, HERG, KCNE1, KCNE2, KCNE3, KCNE4, KCNE5, and KCNJ2). An arginine-to-cysteine mutation at position 27 (R27C) of KCNE2, the beta subunit of the KCNQ1-KCNE2 channel responsible for a background potassium current, was found in 2 of the 28 probands. The mutation was present in all affected members in the two kindreds and was absent in 462 healthy unrelated Chinese subjects. Similar to KCNQ1 S140G, the mutation had a gain-of-function effect on the KCNQ1-KCNE2 channel; unlike long QT syndrome-associated KCNE2 mutations, it did not alter HERG-KCNE2 current. The mutation did not alter the functions of the HCN channel family either. Thus, KCNE2 R27C is a gain-of-function mutation associated with the initiation and/or maintenance of AF.

This study utilizes the venture capital industry in the West as a base to examine the characteristics of China's venture capital industry. Based on questionnaire and interview survey, I find reasonably consistent views around the world on the relative importance of various venture capitalist roles. However, the findings present that how those roles are implemented, how investor/investee relationship is developed, and how VCs is managing their firms, largely vary in different regions, and shaped by many influences, such as historical reasons, culture and cognitive differences, government systems, and institutional environment. It seems that a model stated in western literatures is not valid in China. Further, the study suggests that venture capital industry is vital for the innovation and industrialization of Chinese economy, and several recommendations for both government on macro intervention and VC firms on upgrading of professional are presented.

This study utilizes the venture capital industry in the West as a base to examine the characteristics of China's venture capital industry. Based on questionnaire and interview survey, I find reasonably consistent views around the world on the relative importance of various venture capitalist roles. However, the findings present that how those roles are implemented, how investor/investee relationship is developed, and how VCs is managing their firms, largely vary in different regions, and shaped by many influences, such as historical reasons, culture and cognitive differences, government systems, and institutional environment. It seems that a model stated in western literatures is not valid in China. Further, the study suggests that venture capital industry is vital for the innovation and industrialization of Chinese economy, and several recommendations for both government on macro intervention and VC firms on upgrading of professional are presented.

This study utilizes the venture capital industry in the West as a base to examine the characteristics of China's venture capital industry. Based on questionnaire and interview survey, I find reasonably consistent views around the world on the relative importance of various venture capitalist roles. However, the findings present that how those roles are implemented, how investor/investee relationship is developed, and how VCs is managing their firms, largely vary in different regions, and shaped by many influences, such as historical reasons, culture and cognitive differences, government systems, and institutional environment. It seems that a model stated in western literatures is not valid in China. Further, the study suggests that venture capital industry is vital for the innovation and industrialization of Chinese economy, and several recommendations for both government on macro intervention and VC firms on upgrading of professional are presented.

This study utilizes the venture capital industry in the West as a base to examine the characteristics of China's venture capital industry. Based on questionnaire and interview survey, I find reasonably consistent views around the world on the relative importance of various venture capitalist roles. However, the findings present that how those roles are implemented, how investor/investee relationship is developed, and how VCs is managing their firms, largely vary in different regions, and shaped by many influences, such as historical reasons, culture and cognitive differences, government systems, and institutional environment. It seems that a model stated in western literatures is not valid in China. Further, the study suggests that venture capital industry is vital for the innovation and industrialization of Chinese economy, and several recommendations for both government on macro intervention and VC firms on upgrading of professional are presented.