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International audience; Arabidopsis histone deacetylase HDA19 is required for gene expression programs of a largespectrum of plant developmental and stress-responsive pathways. How this enzyme sensescellular environment to control its activity remains unclear. In this work, we show that HDA19is post-translationally modified by S-nitrosylation at 4 Cysteine (Cys) residues. HDA19 S-nitrosylation depends on the cellular nitric oxide (NO) level which is enhanced under oxidativestress. We find that HDA19 is required for cellular redox homeostasis and plant tolerance tooxidative stress which in turn stimulates its nuclear enrichment, S-nitrosylation and epigeneticfunctions including binding to genomic targets, histone deacetylation, and gene repression. TheCys137 of the protein is involved in basal and stress-induced S-nitrosylation and is required forHDA19 functions in developmental, stress-responsive, and epigenetic controls. Together, theseresults indicate that S-nitrosylation regulates HDA19 activity and is a mechanism of redox-sensing for chromatin regulation of plant tolerance to stress.

Background. It is known to all the doctors and patients that both the morality and incidence rate of chronic heart failure (CHF) are quite high among various heart diseases. Traditional Chinese medicine (TCM) comprehensive intervention becomes a rising prospective therapy for patients with CHF. Considering the efficacy of TCM, the study aims to test the safety as well as the validity of TCM comprehensive intervention in patients who are struggling with CHF. Methods. The study is an essentially randomized, single-central, placebo-controlled, double-blinded crossover trial. Eighty-two eligible subjects aged 18–75 years with CHF are supposed to be recruited. According to the subject plan, all the patients will be divided into group A and B. The patients in group A will receive oral Qishen Taohong granules (QTGs) combined with TCM external treatment and standard Western medicine for four weeks. After that, a 2-week washout would be proceeded; this group will be reallocated to another four weeks with oral placebo granules combined with TCM external treatment and standard Western medicine. In contrast, group B will perform the opposite protocol. The primary outcome conforms to the classification from the New York Heart Association (NYHA). Meanwhile, the secondary outcomes are echocardiogram, N-terminal pro-B-type natriuretic peptide (NT-proBNP), Chronic Heart Failure Quality of Life Scale of Integrated Chinese and Western Medicine (CHFQLS), TCM syndrome, symptom, sign, six-minute walk test (6MWT), Pittsburgh Sleep Quality Index (PSQI), Montreal cognitive assessment (MoCA), major adverse cardiovascular events (MACEs), and metabolomics. Discussion. Based on conventional treatments, TCM comprehensive intervention may further improve the patients’ cardiac function and then enhance their quality of life. The results will provide high-quality evidence of TCM comprehensive intervention in treating CHF.

BACKGROUND Acute myocardial infarction (AMI) is characterized by chest pain as well as cardiac troponin I (cTnI) and electrocardiography (ECG) changes. Recently, clinical researchers have used the term “MINOCA” to indicate myocardial infarction with nonobstructive coronary arteries. To the best of our knowledge, no report has documented MINOCA in a young patient after choledocholithiasis by endoscopic retrograde cholangiopancreatography (ERCP). CASE SUMMARY An 18-year-old Chinese man presented to the cardiac intensive care unit with chest pain radiating to the left shoulder for 1 h after choledocholithiasis by ERCP and the following treatment. ECG showed a sinus rhythm with ST-segment elevation in the II, III, and aVF leads compared with the baseline. Laboratory data revealed cTnI levels of 67.55 ng/mL and 80 ng/mL at the peak (relative index below 0.034 ng/mL) and creatine kinase-MB levels of 56 U/L and 543 U/L at the peak (relative index below 24 U/L). AMI was suspected, and coronary angiography was performed the second day. The results revealed a smooth angiographic appearance of all arteries. The patient had been diagnosed with gallstones and cholecystitis for four years but had not accepted treatment. He had abdominal pain and bloating a week previously and underwent ERCP and subsequent treatments on the second day of admission; 1.4 cm × 1.6 cm of stones were removed from his common bile duct during surgery. The results of his laboratory tests at admission revealed abnormal alanine aminotransferase, aspartate aminotransferase, glutamyl transpeptidase, total bile acid, total bilirubin, direct bilirubin, and indirect bilirubin levels. His temperature, heart rate, blood pressure, and body mass index were normal. His echocardiographic examination revealed no obvious abnormalities in the structure and movement of the ventricular wall and an estimated left ventricular ejection fraction of 57% after the heart attack. His cholesterol and triglycerides were within normal ranges, and his low-density lipoprotein cholesterol was 2.23 mmol/L (normal range 2.03-3.34 mmol). Further testing after AMI revealed nothing remarkable in his erythrocyte sedimentation rate, thyroid function, and tumour markers. CONCLUSION We ultimately made a diagnosis of MINOCA caused by coronary artery spasm, which seemed to be the most suitable diagnosis of this young patient. We are concerned that the heart attack may have been induced by the ERCP rather than occurred coincidentally afterward, so we should investigate the timing of the event further. Additional studies are needed to unravel the underlying pathophysiology.

Atrial fibrillation (AF) is the common arrhythmias. Myocardial fibrosis (MF) is closely related to atrial remodeling and leads to AF. MF is the main cause of cardiovascular diseases and a pathological basis of AF. Thus, the underlying mechanism in MF and AF development should be fully elucidated for AF therapeutic innovation. Autophagy is a highly conserved lysosomal degradation pathway, and the relationship between autophagy and MF has been previously shown. Moreover, research reported that quercetin (Que) could ameliorate MF. The current study aimed to explore the mechanism of Que in MF. The results in this study showed that in clinical AF patients and in aged rats, miR-223-3p was high-expressed, while FOXO3 and autophagy pathway related proteins, such as ATG7, p62/SQSTM1 and the ratio of LC3B-II/LC3B-I were significantly inhibited. In vivo and in vitro studies, we found that Que can effectively inhibit the expression of miR-223-3p in AF model cells and rats myocardial tissues, and meanwhile enhance the expression of FOXO3 and activate the autophagy pathway, and significantly inhibit myocardial fibrosis, and improve myocardial remodeling in atrial fibrillation. All in all, in this study, we found that Que prevents isoprenaline-induced MF by increasing autophagy via regulating miR-223-3p/FOXO3.

Objective: Myocardial ischemia/reperfusion (I/R) injury is one of the causes of most cardiomyocyte injuries and deaths. Berberine (BBR) has been suggested a potential to exert protective effects against myocardial I/R injury. This systematic review aims to determine the intrinsic mechanisms of BBR's protective effects in myocardial I/R injury.Methods: Seven databases were searched for studies performed from inception to July 2020. Methodological quality was assessed by SYRCLE's-RoB tool.Results: Ten studies including a total of 270 animals were included in this study. The methodology quality scores of the included studies ranged from 5 to 7 points. The meta-analysis we conducted demonstrated that BBR significantly reduced myocardial infarct size and the incidence of ventricular arrhythmia, compared to control groups (P < 0.00001). Cardiac function of animals in the BBR treatment group was also markedly increased (P < 0.00001). The index of myocardial apoptosis and the levels of biomarkers of myocardial infarction (LDH and CK) were also decreased in the BBR treatment groups compared to the control groups (P < 0.00001).Conclusions: The pre-clinical evidence, according to our study, showed that BBR is a promising therapeutic agent for myocardial I/R injury. However, this conclusion should be further investigated in clinical studies.

Jumonji C (JmjC) domain proteins are histone lysine demethylases that require ferrous iron and alpha-ketoglutarate (or α-KG) as cofactors in the oxidative demethylation reaction. In plants, α-KG is produced by isocitrate dehydrogenases (ICDHs) in different metabolic pathways. It remains unclear whether fluctuation of α-KG levels affects JmjC demethylase activity and epigenetic regulation of plant gene expression. In this work, we studied the impact of loss of function of the cytosolic ICDH (cICDH) gene on the function of histone demethylases in Arabidopsis thaliana. Loss of cICDH resulted in increases of overall histone H3 lysine 4 trimethylation (H3K4me3) and enhanced mutation defects of the H3K4me3 demethylase gene JMJ14. Genetic analysis suggested that the cICDH mutation may affect the activity of other demethylases, including JMJ15 and JMJ18 that function redundantly with JMJ14 in the plant thermosensory response. Furthermore, we show that mutation of JMJ14 affected both the gene activation and repression programs of the plant thermosensory response and that JMJ14 and JMJ15 repressed a set of genes that are likely to play negative roles in the process. The results provide evidence that histone H3K4 demethylases are involved in the plant response to elevated ambient temperature.

Summary: Zika virus (ZIKV) can cause microcephaly in the fetus. However, its effects on body growth and the development of children with postnatal ZIKV infection are largely unknown. To examine this, we intraperitoneally challenged mouse pups with ZIKV. Infection causes an irreversible growth delay and deficits in spatial learning and memory, with growth-relevant hormones significantly reduced during infection. These effects are associated with ZIKV RNA expression in the hypothalamus, blood, and brain but not in the pituitary and thyroid. Infection is also associated with hypothalamic inflammation, and ZIKV antigen is detectable in neuroendocrine cells producing thyrotropin-releasing hormone. Moreover, early administration of growth hormone could significantly improve growth delay. Our results demonstrate that ZIKV can infect the hypothalamus, causing multi-hormone deficiencies and delayed growth and development in a mouse model. Therefore, prospective multidisciplinary follow-up of ZIKV-infected children may be necessary to understand potential effects of this virus on childhood development. : Wu et al. find that ZIKV infection in mouse pups causes hypothalamic damage and dysfunction of the hypothalamic-pituitary axis, featuring multi-hormone deficiencies and resulting in irreversible growth delay and memory impairment during adulthood. Early administration of the relevant hormones could partially improve the long-term sequelae in the neuroendocrine system. Keywords: Zika virus, hypothalamus, multi-hormone deficiencies, growth delay, memory impairment, TSH-producing endocrine cells

Backgroud Xuezhitong (XZT) is an extract of Allium macrostemon Bunge that has lipid-lowering properties. Objective To evaluate the effects of XZT on lipids in subjects with hypertriglyceridemia (HTG) without severe dyslipidaemia. Methods A total of 358 subjects with HTG were enrolled and randomly assigned to receive XZT (2700 mg daily), xuezhikang (XZK) (1200 mg daily) or placebo. The primary endpoint was the reduction or percent reduction in the TG level over 12 weeks of treatment. Results At the 12-week follow-up, a reduction in the TG level from baseline was observed in both groups, but the XZT and XZK groups demonstrated a significantly greater reduction than the placebo group (30.77%, 24.02% vs 11.59%, P P P Conclusions XZT significantly reduced TG levels and was well tolerated. Longer-term studies in more diverse patient populations are needed to corroborate these findings. Clinical Trial Registration www.chictr.org.cn Identifier: ChiCTR1900025854.

A chemical study of the ethyl acetate (EtOAc) extract from the deep-sea-derived fungus Penicillium thomii YPGA3 led to the isolation of a new austalide meroterpenoid (1) and seven known analogues (28), two new labdane-type diterpenoids (9 and 10) and a known derivative (11). The structures of new compounds 1, 9, and 10 were determined by comprehensive analyses via nuclear magnetic resonance (NMR) and mass spectroscopy (MS) data. The absolute configurations of 1, 9, and 10 were determined by comparisons of experimental electronic circular dichroism (ECD) with the calculated ECD spectra. Compound 1 represented the third example of austalides bearing a hydroxyl group at C-5 instead of the conserved methoxy in other known analogues. To our knowledge, diterpenoids belonging to the labdane-type were discovered from species of Penicillium for the first time. Compound 1 showed cytotoxicity toward MDA-MB-468 cells with an IC50 value of 38.9 M. Compounds 2 and 11 exhibited inhibition against &alpha, glucosidase with IC50 values of 910 and 525 M, respectively, being more active than the positive control acarbose (1.33 mM).

Objective. The study aimed to evaluate the efficacy and safety of Bushenjiangya-optimized (BSJYO) granule on left ventricular diastolic dysfunction (LVDD) in hypertensive (HTN) patients. Methods. 120 patients diagnosed with HTN plus LVDD were randomly assigned to the BSJYO granule group and placebo group, and all patients received basal western medicine (WM) treatment. After eight weeks of treatment, we evaluated echocardiography, traditional Chinese medicine (TCM) syndromes, 24-hour ambulatory blood pressure, liver and kidney functions, and adverse events. Major adverse cardiovascular events (MACEs) were collected at 6-month follow-up. Results. Compared with pretreatment, E/Ea (Doppler-derived index of filling pressure and worsening LVDD) significantly decreased significantly after 8 weeks of treatment in the BSJYO granule plus basal WM group (10.52 ± 1.87 vs. 9.49 ± 1.49, P<0.01), alongside reductions in significantly effective response (SER), effective response (ER), and total effective response (TER = SER + ER) in TCM symptom scores (21.59% vs. 71.70%, P<0.01). There were no differences between treatment groups in kidney and liver function, early adverse events, or MACE. Conclusion. BSJYO granule plus basal WM is an effective and safe therapy for HTN patients with LVDD.

Background: Whether Traditional Chinese training (TCT) is effective in Cardiovascular diseases (CVDs) patients remains to need further evidence. We conducted a meta-analysis to examine the effects of TCT on exercise capacity and quality of life in CVDs patients. Methods and Results: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and WeiPu databases (from inception to December 2019) were searched for relevant articles. Interventions considered were TCTs with or without comparisons (Western Routine Medicine Treatment or usual care). Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I2 test. 21 randomized controlled trials (RCTs) (n=1517) met the inclusion criteria. The six-minute walk test of patients performing TCT improved by 73.78 m (95% CI 32.57-114.99, P=0.0004; I2=99%, P

Dengue virus (DENV) infection has become a severe public health problem worldwide. However, there is no specific antiviral drug available yet. In this study, we found that DENV serotype 2 (DENV2) infection enhanced the expression of β3 integrin on human umbilical vein endothelial cells (HUVECs) and that DENV2 antigens co-localized with β3 integrin. DENV2 envelope protein (E) directly interacted with β3 integrin, and their interacting sites were located at domain III of E protein (EDIII). Several synthetic peptides were designed based on the amino acid sequence of EDIII, and peptides P4 and P7 could inhibit DENV2 entry into HUVECs in a dose-dependent manner. The inhibitory concentration (IC50) of the two peptides was 19.08 ± 2.52 μM for P4 and 12.86 ± 5.96 μM for P7. Moreover, P7 containing an FG-loop, but not P4, could also inhibit DENV1 entry into HUVECs. Our results suggest a novel mechanism in which interaction between β3 integrin and EDIII is involved in DENV entry. The findings on the inhibitory effect of the peptides on viral entry have significance for anti-DENV drug design.

Recently, Manual control of lighting system is still the main force in most huge events and situations, which contribute serious waste of electricity. For the tobacco distribution center, there are special lighting management methods, such as setting a uniform time to open and close the lighting equipment in the joint workshop. Although a certain amount of electric energy can be saved by this means, it cannot meet the actual demand. In the essay, according to the actual situation of tobacco distribution center joint workshop, the OPTICS Algorithm is improved to conduct cluster analysis on the location data of personnel in the workshop, finding out the illume area where the personnel are relatively densely distributed. Besides, it can also calculate the number of lamps that need to be turned on under the condition of meeting the specified illumination. The experimental results demonstrate that the energy saving effect is particularly obvious when the people are widely distributed in the lighting places.

To exam the effect and safety of conventional acupuncture (CA) on cardiac arrhythmia. Nine medical databases were searched until February 2016 for randomized controlled trials. Heterogeneity was measured by Cochran Q test. Meta-analysis was conducted if I2 was less than 85% and the characteristics of included trials were similar. Nine qualified studies involving 638 patients were included. Only 1 study had definitely low risk of bias, while 7 trials were rated as unclear and 1 as high. Meta-analysis of CA alone did not have a significant benefit on response rate compared to amiodarone in patients with atrial fibrillation (Af) and atrial flutter (AF) [relative risk (RR): 1.09; 95% confidence interval (CI): 0.79–1.49; P=0.61; I2=61%, P=0.11]. However, 1 study with higher methodological quality detected a lower recurrence rate of Af in CA alone as compared with sham acupuncture plus no treatment, and benefits on ventricular rate and time of conversion to normal sinus rhythm were found in CA alone group by 1 study, as well as the response rate in CA plus deslanoside group by another study. Meta-analysis of CA plus anti-arrhythmia drug (AAD) was associated with a significant benefit on the response rate when compared with AAD alone in ventricular premature beat (VPB) patients (RR, 1.19, 95% CI: 1.05–1.34; P=0.005; I2=13%, P=0.32), and an improvement in quality-of-life score (QOLS) of VPB also showed in 1 individual study. Besides, a lower heart rate was detected in the CA alone group by 1 individual study when compared with no treatment in sinus tachycardia patients (MD–21.84 [–27.21,–16.47]) and lower adverse events of CA alone were reported than amiodarone. CA may be a useful and safe alternative or additive approach to AADs for cardiac arrhythmia, especially in VPB and Af patients, which mainly based on a pooled estimate and result from 1 study with higher methodological quality. However, we could not reach a robust conclusion due to low quality of overall evidence.

Japanese encephalitis virus (JEV) is a pathogenic cause of Japanese Encephalitis (JE), which is a zoonotic disease transmitted by mosquitoes and amplified by pigs. Infection of JEV may lead to severe neurological sequelae, even death in humans and reproductive disorders in pigs. Vaccination is the only way to control JEV infection in humans. For pigs play important role in the JEV transmission cycle, developing a new veterinary vaccine is considered as a useful strategy for cutting off the transmission route of JEV. We have previously reported that DNA vaccine pCAG-JME, expressing prM-E proteins of JEV, is effective in mice through intramuscular injection (IM). However, the poor immunogenicity, due to low expression of immunogen, is the major obstacle for the development of DNA vaccine in large animals. In the present study, therefore, we immunized mice and pigs with pCAG-JME intramuscularly accompanied with electroporation (EP) stimulation, the attractive gene delivery approach. As compared with IM, EP-mediated vaccination markedly increased the expression of immunogen in the injection site and induced a dose- and time-dependent immune response. 100% survival rate was observed in groups vaccinated with doses ranged from 10 to 100μg, indicating that 10μg of DNA with EP for individual was enough for inducing effective protection in mice. Surprisingly, survival rate and end-point titers of anti-JEV antibodies were higher in mice even at lower dose of DNA (5μg) than that in mice inoculated 100μg through IM. Notably, the prM-E antigens also induced high antibody response in pig, while the neutralizing antibody titer achieved 1:320. Our results suggested that EP-mediated DNA immunization might act as an effective strategy against JEV, at least in pig, and that EP has a potential application prospect in DNA vaccination.

International audience; Elevated ambient temperatures affect plant growth and substantially impact biomass and crop yield. Recent results have indicated that chromatin remodelling is critical in plant thermal responses but how histone modification dynamics affects plant thermal response has not been clearly demonstarted. Here we show that Arabidopsis histone deacetylase genes HDA9, HDA15 and HDA19 play distinct roles in plant response to elevated ambient temperature. hda9 and hda19 mutants showed a warm-temperature-insensitive phenotype at 27°C, whereas hda15 plants displayed a constitutive warm-temperature-induced phenotype at 20°C and an enhanced thermal response at 27°C. The hda19 mutation led to upregulation of genes mostly related to stress response at both 20 and 27°C. The hda15 mutation resulted in upregulation of many warm temperature responsive as well as metabolic genes at 20 and 27°C, while hda9 led to differential expression of a large number of genes at 20°C and impaired induction of warm-temperature-responsive genes at 27°C. HDA15 is associated with thermosensory mark genes at 20°C and that the association is decreased after shifting to 27°C, indicating that HDA15 is a direct repressor of plant thermal-responsive genes at normal temperature. In addition, as hda9, the hda15 mutation also led to upregulation of many metabolic genes and accumulation of primary metabolites. Furthermore, we show that HDA15 interacts with the transcription factor HFR1 (long Hypocotyl in Far Red1) to cooperatively repress warm-temperature response. Our study demonstrates that the histone deacetylases target to different sets of genes and play distinct roles in plant response to elevated ambient temperature.

Testicular invasion and persistence are features of Zika virus (ZIKV), but their mechanisms are still unknown. Here, we showed that S100A4+ macrophages, a myeloid macrophage subpopulation with susceptibility to ZIKV infection, facilitated ZIKV invasion and persistence in the seminiferous tubules. In ZIKV-infected mice, S100A4+ macrophages were specifically recruited into the interstitial space of testes and differentiated into interferon-γ-expressing M1 macrophages. With interferon-γ mediation, S100A4+ macrophages down-regulated Claudin-1 expression and induced its redistribution from the cytosol to nucleus, thus increasing the permeability of the blood-testis barrier which facilitated S100A4+ macrophages invasion into the seminiferous tubules. Intraluminal S100A4+ macrophages were segregated from CD8+ T cells and consequently helped ZIKV evade cellular immunity. As a result, ZIKV continued to replicate in intraluminal S100A4+ macrophages even when the spermatogenic cells disappeared. Deficiencies in S100A4 or interferon-γ signaling both reduced ZIKV infection in the seminiferous tubules. These results demonstrated crucial roles of S100A4+ macrophages in ZIKV infection in testes., Author summary Zika virus (ZIKV), a flavivirus usually transmitted by mosquito bites, was recently reported to establish long-term infection in testes and consequently to transmit sexually from male to female. To uncover the underlying mechanisms, we characterized the gene expression profile of ZIKV-infected mouse testes and selected S100A4+ macrophages as crucial factors for long-term ZIKV infection in testes. S100A4+ macrophages originate from bone marrow and are susceptible to ZIKV infection. Using ZIKV susceptible mice, we found that ZIKV infection attracted S100A4+ macrophages to accumulate in the testes and differentiate into interferon-γ-expressing cells. In further experiments, we introduced S100A4+ macrophages-depleted mice and interferon-I/II signaling deficient mice. We demonstrated that interferon-γ secreted by S100A4+ macrophages induced the tight junction protein Claudin-1 to translocate from the plasma membrane into nuclei, thus increasing the permeability of the blood-testis barrier, an indispensable structure surrounding the seminiferous tubules and protecting spermatogenic cells inside from viral infection and immune attack. Taken together, we proposed a mechanism for the long-term ZIKV infection, in which S100A4+ macrophages not only function as Trojan horses to bring ZIKV into the seminiferous tubules, but also serve as a solid shelter for ZIKV replication even when spermatogenic cells have been largely destroyed by ZIKV infection.

Introduction Heart failure with reduced ejection fraction (HFrEF) is defined as the clinical diagnosis of heart failure (HF) and ejection fraction (EF) ≤40%, which is a severe public healthcare issue and brings a heavy social and economic burden for patients with HFrEF. Chinese herbal medicine (CHM) has a long history in treating HF. Questions concerning the efficacy and acceptability of CHM-related interventions in adult patients with HFrEF led us to use the method of systematic review and network meta-analysis to integrate direct and indirect evidence to create hierarchies for all CHM. Methods and analysis Nine medical databases, including PubMed, EMBASE (OVID), the Cochrane Library, Google Scholar, Web of Science, CNKI, VIP, Wanfang Database and CBM will be searched from the date of database inception to June 2015 (updated to March 2017) without language and publication status restriction. Completely randomised controlled trials (RCTs) comparing CHM or CHM plus routine treatment with CHM, CHM plus routine treatment, routine treatment, no treatment or placebo for adults with HFrEF will be examined. Our primary outcomes will include all-cause mortality, HF-related death, all-cause rehospitalisation, HF-related rehospitalisation and acceptability (discontinuation due to any adverse events during treatment). Secondary outcomes will include response rate, mean value or mean difference from baseline of surrogate indexes. We will perform the Bayesian network meta-analyses (NMA) for the most frequently reported primary or secondary outcome and the acceptability outcome, if available. Meta-regression, subgroup analyses and sensitivity analyses will be conducted based on prespecified effect modifiers to assess the robustness of the findings. Dissemination The results of this NMA will provide useful information about the effectiveness and acceptability of CHM in adults with HFrEF, which will also have implications for clinical practice and further research. Findings will be disseminated through peer-reviewed journal publication and conference presentations. PROSPERO registration number CRD42016053854.

Objective. To examine the effects and safety of oral compound Chinese medicine (CCM) plus routine western medicine (RWM) in in-stent restenosis (ISR). Methods. Various electronic databases (CBM, CNKI, VIP, Wanfang, PubMed, EMBASE, and Cochrane Library) were searched until April 2017. The quality of the included studies was evaluated, and meta-analyses were performed using RevMan5.3 and STATA 12.0 software. Moreover, funnel plot and Egger’s publication bias plots were analysed to identify publication bias and adverse reactions were reported. A sensitive analysis was carried out according to the quality score. Results. In all, 40 RCTs involving 4536 patients were selected for this review. The pooled estimates of three studies showed that the benefit to the number of ISRs (NoR) was more substantial for CCM plus RWM than for RWM alone (RR 0.24, 95% CI 0.10 to 0.57, P=0.001;I2=0%, P=0.81). The rate of ISR was significantly lower for CCM plus RWM than for the same RWM alone (RR 0.44, 95% CI 0.37 to 0.53, P<0.00001; I2=0%, P=0.95). CCM plus RWM benefitted the rate of ISR when a CM placebo plus RWM was used as the control intervention (RR 0.34, 95% CI 0.20 to 0.57, P<0.0001; I2=0%, P=0.95). The difference of adverse reactions was not significant. For secondary outcomes, the CCM plus RWM group did not reduce the rates of revascularization and cardiac death, but it did reduce the rate of recurrent angina over the results observed in the RWM alone group. In addition, funnel plot and Egger’s publication bias plot indicated that there was publication bias. The association between the use of CCM plus RWM and RWM alone remained significant after the sensitivity analysis excluding studies with low quality score (quality score ⩽ 4) with a pooled RR of 0.41 (95% CI, 0.34–0.50). Conclusion. Oral CCM plus RWM clearly benefitted patients with percutaneous coronary intervention (PCI) because it prevented and treated ISR better than was observed for either RWM alone or a CM placebo plus RWM.

Introduction. A concealed pulmonary vein (PV) bigeminy (cPVB) may be found in some patients with atrial fibrillation (AF) during sinus rhythm (SR). The aim of this study was to investigate whether the presence of cPVB during SR is associated with a higher PV firing. Methods and Results. Seven hundred seventy-six PVs (excluding 5 right middle PVs and 8 left common trunks) were mapped in 198 patients with paroxysmal AF (PAF) who underwent circumferential PV isolation. cPVB with a mean coupling interval of 136 ± 16 ms during SR was observed prior to ablation in 22 (11%) patients. Focal firing was provoked prior to ablation in 144 (19%) PVs. The incidence of focal firing was greater in PVs exhibiting cPVB compared with PVs without cPVB (89% vs. 16%; P<0.001). Also, the number of radiofrequency applications required for isolation was greater in ipsilateral PVs, exhibiting cPVB compared with ipsilateral PVs without cPVB (21.6 ± 6.8 vs. 18.2 ± 5.6; P=0.024). During a follow-up of 32 ± 20 months, the single ablation success rate was 82%. Compared with patients without cPVB, patients with cPVB were associated with higher recurrence rate of AF (27% vs. 17%; p=0.032). Conclusion. cPVB during SR was observed prior to index ablation in 11% of PAF patients. Such a potential itself may be a PV firing in a concealed manner, which does not reactivate LA. The PV exhibiting cPVB required a greater number of radiofrequency applications for isolation. Compared to patients without cPVB, the recurrence rate of AF in patients with cPVB was greater.

AbsatrctZika virus (ZIKV) has caused major concern globally due to its rapid dissemination and close association with microcephaly in children and Gullian-Barr syndrome in adults. In this study, we identified a patient returned from Cambodia who experienced high fever, chill and myalgia. Lab tests discovered sign of severe liver injury including significantly elevated serum transaminases’ level, decreased serum albumin level, and markedly increased levels of lactic dehydrogenase, alpha-hydroxybutyric dehydrogenase and creatine kinase in serum. Moreover, severe thrombocytopenia and altered blood levels of fibrinogen and fibrinogen degradation product were also observed, indicating the existence of clotting disorders. A ZIKV strain clustered into the Asian lineage was isolated from the patient’s serum. When inoculated into suckling mice, this virus significantly retarded mouse body-weight gain and caused 70% mortality. Our results demonstrate a close association between ZIKV and severe liver injury and coagulation disorders and suggest that clinicians should be aware of compatible symptoms in patients and manage them accordingly.

Dengue virus (DENV), the causative agent of dengue fever (DF), is one of the most important mosquito-borne viruses that can infect humans. Although much effort has been made on prevention and control of dengue, there are currently no anti-viral drugs or worldwide approved vaccines yet. In this study, we immunized six-week-old Balb/c mice with DNA vaccine candidates E and NS1-2a of DENV serotype 2 or the combination of them (E+NS1-2a) via an electroporation (EP)-assisted intramuscular gene delivery system and evaluated the immune response and protection. The highest specific antibody titres and cytokine levels secreted by splenocytes as well as the highest survival rate were observed in the E+NS1-2a group, followed by E group and NS1-2a group. Our data suggested that the combination of E and NS1-2a delivered by EP may be a superior preventive strategy against DENV.

This paper describes the evolution of the microstructure and conductivity of electroless copper deposition on a glass substrate for applications in electronics manufacture. The glass was activated using a (3-aminopropyl)trimethoxysilane pre-treatment followed by a Pd/Sn catalyst. Surface morphology of the deposited copper films was characterized using a dual beam focused ion beam field emission scanning electron microscope, and together with atomic force microscopy, showed clearly that the roughness and grain size tended to increase with the plating time. Film thickness measurements showed a high initial deposition rate, which slowed to a constant level as the thickness increased above 100 nm. This corresponded with the resistivity of the films which decreased rapidly as the thickness increased from 20 to 100 nm, but then remained largely stable at a level approximately twice that of bulk copper.

PurposeThe purpose of this paper is to highlight a novel manufacturing process for a biochip with a multi‐electrode array (MEA) that is specifically designed for use in characterising cardio‐active substances and to demonstrate a novel proposed solution prototype that has been constructed to meet the needs of end‐users.Design/methodology/approachPractical problems encountered with conventional MEA biochips are described and a novel biochip design to tackle these problems is presented. The manufacturing approach used to produce the prototypes of that design is described and depicted.FindingsThe novel prototype MEA biochips were successfully manufactured using conventional electronics manufacturing approaches. Prototypes demonstrated limited successes in the early stages of testing. Further revisions of the feature geometry are required to implement an alternative MEA biochip that is suitably reliable.Research limitations/implicationsBasic photolithography techniques have been used to construct a base substrate for proof‐of‐principle studies. Increased sophistication in manufacturing stages is required in future iterations of the proposed concept.Originality/valueThis paper introduces a problem encountered by MEA system adopters that requires a suitable solution. The scale up of an electronics manufacturing process‐based solution to the problems described holds much promise for the screening of new chemical entities.

Eu3+-doped trigonal LaAlO3 and orthorhombic GdAlO3 phosphors have been successfully synthesized by sol-gel method. The crystallization processes of the phosphors have been characterized by X-ray diffraction (XRD) and thermogravimetry-differential scanning calorimetry (TG-DSC). The optical properties of these phosphors were investigated using the photoluminescence (PL) and photoluminescence excitation (PLE) spectra. The influences of the different structures and bonding of the hosts on the luminescence performance of Eu3+ ion-doped LaAlO3 and GdAlO3 were investigated in detail based on chemical bond theory. Under appropriate UV-radiation, the reddish orange light emitted from GdAlO3:Eu3+ was brighter than that from LaAlO3:Eu3+. Such a brightly luminescent phosphor could be considered as an ideal optical material for the development of new optical display systems. (C) 2011 Elsevier Ltd. All rights reserved.

In view of the low precision and poor interaction in current traditional indoor navigation system of digital map, this paper puts forward an indoor guide strategy, which combines WiFi positioning technology with mobile AR technology. At the same time, the traditional natural feature extraction algorithm is improved by combining FASE with SURF. FAST-SURF can meet the requirement of robustness and real-time performance. A new mobile AR indoor guide system is designed and implemented in the digital museum based on the Android platform. Experiments show that the system has better practicability and broad application prospects with high precision of positioning and matching, good real-time performance and high precision of positioning navigation.

The high volume production of substrates able to support high density interconnection is becoming increasingly difficult as the pitch of devices continues to decrease. An important issue is the alignment of microvias and pads which is made particularly challenging by the dimensional instability of traditional organic substrates. In this work, glass has been investigated as an alternative substrate material. Glass offers potential advantages including: electrical insulation, dimensional stability, thermal expansion similar to Si and optical transparency. This paper examines manufacturing processes for the preparation of substrates built up from 50 to 100 ?m thick glass sheets. Excimer laser machining was used to form microvias and tracks in the glass which were metallised using electroless plating methods. Using a photoresist layer during the laser machining process helped to reduce debris on the glass surface and could be used to direct the subsequent deposition of electroless copper or nickel such that circuit patterns could be created. Lamination of the thin glass sheets was investigated using direct glass to glass bonding and through the use of an intermediate layer. A method for the combination of these techniques to create multilayer substrates is proposed.

This paper describes the characterization of electroless copper deposition on glass substrates with respect to surface morphology and adhesion. Silanisation of the glass surfaces with (3-aminopropyl)-trimethoxysilane (APTS) was used to provide a surface-coupled layer of functional molecules to assist in the improvement of adhesion of a Pd/Sn catalyst and the subsequent copper deposition. Surface morphology of the deposited films was characterized by field emission scanning electron microscopy (SEM) and together with atomic force microscopy (AFM), showed that the roughness and grain size tended to increase with the plating time. Tape peel testing was used to assess the adhesion of the coatings. All the deposits prepared with an electroless bath temperature of 40degC with a thickness up to 150 nm were found to adhere well to the glass substrate. Copper films were peeled off easily with increased thickness. This paper focuses on the development of thin copper films (Lt 200 nm thick) and considers the early stages of deposition in order to investigate further the role of the catalyst on adhesion.

This paper reports the effect of a Pd/Sn catalyst treatment process on the adhesion of electroless copper deposited onto a glass substrate. Adhesion of the copper varied with catalyst treatment time: short or extended catalyst immersion times led to lower adhesion. In this work silanisation of the glass surface with (3-aminopropyl)-trimethoxysilane was used to provide a layer of functional molecules to assist the adhesion of the Pd/Sn catalyst. Surface analysis of the catalyzed glass was carried out by X-ray Photoelectron Spectroscopy (XPS) and together with Time-of-Flight Secondary Ion Mass Spectrometry, showed that the Pd/Sn structures changed with increasing immersion time in the catalyst bath. The Pd XPS core level peaks indicated that Pd(0) became more significant in the catalyst layer than Pd(II) with increasing immersion time. Tape peel testing was used to assess the adhesion of the coatings: thin layers adhered well to the glass, but for layers thicker than 160 nm tape tests removed large areas. The failure surfaces of copper layers peeled off the glass were also examined by XPS which indicated that the failure occurred between the copper and catalyst.

Glass is a potential substrate material for the manufacture of substrates for high density electrical and optical interconnect. However, in order to realize such substrates, metallization is required to form conductive tracks and pads. In this work, electroless copper was used due to its relatively low cost, fast speed and potential for high volume production. Silanisation of the glass surfaces with (3-aminopropyl) trimethoxysilane (APTS) was used to provide a surface-coupled layer of functional molecules to assist in the adhesion of Pd/Sn catalyst and the subsequent copper deposition. The composition and microstructure of the modified glass surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Tape peel testing was used to qualitatively assess the adhesion of the copper to the smooth glass surface. For layers less than 150 nm thick, adhesion was good, but thicker coatings tended to peel away easily. Preliminary analysis of the peeled surfaces indicated that failure occurred at the interface between the copper and the catalyst. As an alternative approach for improving adhesion, laser machining was used to roughen the glass and direct the deposition of electroless copper, such that circuit patterns with good adhesion were formed.

PurposeTo present the aims and preliminary findings of a research project to investigate the manufacture of multilayer glass substrates built up from thin glass sheets.Design/methodology/approachThe approaches that may be taken to create glass substrates and the challenges involved are described. Excimer laser machining was used for the formation of microvias and other features in individual glass sheets. In addition, methods for the electroless copper metallisation of the smooth glass surfaces were studied. Finally, a technique for the lamination of the glass layers using low temperature, pressure assisted bonding was investigated.FindingsMicrovias with 100 μm diameter entry holes were successfully machined in 100 μm thick glass sheets and process windows were identified to reduce debris and hole taper. Using appropriate pre‐treatment steps, electroless copper coatings could be deposited uniformly over the smooth glass surface, however, further improvements in adhesion were found to be necessary. The direct lamination of glass layers was found to be possible using pressure and temperature applied over long periods of time. Improvements to the lamination process were made to reduce the initiation of cracks which were assessed using fatigue testing.Research limitations/implicationsThe feasibility of the individual steps in the fabrication of glass substrates has been demonstrated. Further work is necessary to control the processes in order to limit microcrack formation, improve copper coating adhesion and ensure uniform lamination of multiple glass layers.Originality/valueThe use of glass materials could enable the manufacture of substrates for high density electrical interconnect with integrated optical waveguides.

A variety of microstructured YF3:Eu3+ with different morphologies have been successfully synthesized using a simple inorganic salt as the only structure-directing agent in the hydrothermal system. The cations of Al3+, Li+, Mg2+, Na+, K+ and Ba2+ were found to determine the size and morphology of the as-prepared microstructured YF3. The prepared samples were systematically characterized by powder X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), photoluminescence (PL) and photoluminescent excitation spectra (PLE). Detailed proofs indicated that the process of growing different morphologies of YF3:Eu3+ microparticles were dominated by different growth mechanisms. Furthermore, photoluminescent properties were also investigated.

Uniform and well-crystallized NaLa(MoO4)2 microspheres were prepared by a facile one-step hydrothermal synthesis without involving any surfactants or templates. The as-obtained products were systematically characterized by powder X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), photoluminescence (PL), and photoluminescent excitation spectra (PLE). The influence of the starting pH value on the phase and morphology of NaLa(MoO4)2 microspheres was discussed. Furthermore, the formation mechanism of the microspheres was dominated by the consequence of a fast crystallization, dissolution and recrystallization. Finally, the luminescent properties of Eu3+ and Dy3+ ion activated NaLa(MoO4)2 microspheres were investigated. The results demonstrated that NaLa(MoO4)2:Ln3+ (Ln = Eu, Dy) microspheres exhibited good luminescent properties and might have potential applications in lighting technology.

This paper describes the different catalytic surfaces of Pd/Sn formed before electroless copper deposition onto a glass substrate. In this study, silanization of the glass surfaces with (3-aminopropyl) trimethoxysilane was used to provide a surface-coupled layer of functional molecules to assist in the adsorption of Pd/Sn catalyst and the subsequent copper deposition. The composition and microstructure of the modified glass surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry. These showed that catalytic Pd/Sn structures on the surface changed with increasing immersion time in the catalyst bath. The core-level XPS spectrum of Pd indicated that metallic Pd(0) became more significant in the catalyst layer than Pd(II) with the increasing immersion time. A model of the adsorption process is proposed to explain these changes. It was observed that too high a quantity of Pd(0) does not always improve the adhesion of the Cu deposits in the electroless process.