Impacts of Non-alcoholic Fatty Liver Disease on Acute Coronary Syndrome: Evidence and Controversies.

PURPOSE OF REVIEW: Acute coronary syndrome (ACS) and non-alcoholic fatty liver disease (NAFLD) are two clinically common disease entities that share numerous risk factors. This review aimed to discuss the impacts of NAFLD on ACS. RECENT FINDINGS: In an era of improved control of traditional risk factors, the substantial burden of cardiometabolic abnormalities has caused widespread concern. NAFLD is considered the hepatic component of metabolic syndrome, which can exert an impact on human health beyond the liver. Accumulating studies have demonstrated that NAFLD is closely related to cardiovascular disease, especially coronary artery disease. Interestingly, although recent data have suggested an association between NAFLD and the incidence and outcomes of ACS, the results are not consistent. In this review, we comprehensively summarized evidence and controversies regarding whether NAFLD is a contributor to either the development of ACS or worse outcomes in patients with ACS. The potential pathophysiological and molecular mechanisms involved in the impacts of NAFLD on ACS were also elucidated.

ALDH2 Gene rs671 Polymorphism May Decrease the Risk of Essential Hypertension.

Aldehyde dehydrogenase-2 (ALDH2) rs671 G>A polymorphism can influence the activity of ALDH2 and may be associated with the risk of essential hypertension (EH). Although many previous studies have explored such a relationship, the conclusion is still controversial.The PubMed, Embase, and China National Knowledge Infrastructure databases were searched on the ALDH2 gene and EH. We used the Newcastle-Ottawa Scale to evaluate the quality of the study. Then we calculated the strength of relationship between ALDH2 rs671 mutation and EH by utilizing odds ratios and 95% confidence intervals. Besides, subgroup analysis and sensitivity analysis were performed and the publication bias was assessed.There were 12 studies containing 8153 cases and 10,162 controls. Our meta-analysis showed significant association between ALDH2 rs671 polymorphism and EH in four genetic models (the allele model, the homozygote model, the heterozygote model, and the dominant model), whereas it did not indicate this connection in the recessive model. However, a trend of decreased risk still could be seen. Furthermore, we also found an obvious association between rs671 mutation and the risk of EH in the male group than in the female group in all five genetic models.We concluded that ALDH2 rs671 G>A polymorphism may decrease the risk of EH. Furthermore, susceptibility to EH reduced in males but not in females. As a variant in ALDH2, rs671 G>A could be an attractive candidate for genetic therapy of EH. In addition, more case-control studies should be conducted to strengthen our conclusion and evaluate the gene-gene and gene-environment interactions between the ALDH2 gene and EH.

Association Between MTHFR C677T Polymorphism and Congenital Heart Disease.

Many published studies have evaluated the association between the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) polymorphism and the risk of congenital heart disease (CHD); however, the specific conclusion is still controversial.To get a more accurate conclusion, we used a meta-analysis to evaluate the association between the MTHFR gene C677T polymorphism and the risk of CHD.Based on the design-based search strategy, a comprehensive literature search was conducted on PubMed, OVID, Cochrane Library, Embase, Wanfang, CNKI, and Web of Science. We selected the Newcastle-Ottawa Scale (NOS) to assess the quality of the included studies. We performed a heterogeneity test on the results of the study and calculated the combined odds ratios (ORs) and its corresponding 95% confidence intervals (95% CIs) under a random- or fixed-effect model. Subgroup analyses were conducted by ethnicity, source of controls, sample size, and genotyping method. Sensitivity analysis was used to insure authenticity of this meta-analysis result. Egger's test and Begg's funnel plot were performed to detect publication bias.Eventually, our meta-analysis included 15 eligible studies. We observed a significant correlation between the MTHFR C677T polymorphism and the development of CHD in the recessive model (OR: 1.35, 95% CI: 1.06-1.71, P = 0.006) for the overall population. In subgroups stratified by ethnicity and source of controls, subgroup analyses indicated similar associations in Asians and hospital-based groups, but not for Caucasians and population-based groups. Egger's test and Begg's funnel plot demonstrated no significant publication bias in our study.Our analysis identified that MTHFR C677T allele is a risk genetic for CHD development, especially in Asians compared with Caucasians.

Role of Endothelial Nitric Oxide Synthase Polymorphisms in Atrial Fibrillation: A PRISMA-Compliant Meta-Analysis.

BACKGROUND Research interest in endothelial nitric oxide synthase(eNOS) polymorphisms and atrial fibrillation (AF) has grown in last recent years, but the results of individual studies are inconsistent due to their small sample sizes. MATERIAL AND METHODS We searched databases for eligible studies on eNOS and AF, extracted the relevant data, and rigorously screened them according to inclusion and exclusion criteria. Then, we evaluated the study quality according to the Newcastle-Ottawa scale score, and we pooled the odds ratios (ORs) and 95% confidence intervals (CIs) by using a random-effects model or fixed-effects model based on inter-study heterogeneity. In addition, we performed subgroup analysis and sensitivity analysis and assessed publication bias. RESULTS According to the inclusion and exclusion criteria, we finally found 8 studies in this search. The recessive (OR=0.81; 95% CI=0.67 to 0.97; p=0.988; I²=0.0%) model showed that the eNOS 786T/C polymorphism was relevant to AF. We also found that the eNOS 786T/C polymorphism decreases the risk of AF, especially in white people (OR=0.81; 95% CI=0.67 to 0.97; P=0.023 for recessive model) and in the control population (OR=0.79; 95% CI=0.65 to 0.97; P=0.022 for recessive model). We found no obvious publication bias. CONCLUSIONS The eNOS gene loci 786T/C polymorphism is relevant to the risk of AF. Our results suggest that the 786T/C polymorphism significantly decreases AF risks in white people and control populations. Larger studies are required for further evaluation.

Growth of Rhodes grass and leaching of ions from seawater neutralized bauxite residues after amendment with gypsum and organic wastes.

A 32-week leaching column study was carried out in the greenhouse to investigate the effects of incorporation of gypsum, cattle manure, biosolids, gypsum plus cattle manure and gypsum plus biosolids into the topsoil layer (0-10 cm) on growth of Rhodes grass, and on root distribution and chemical and microbial properties in the topsoil and subsoil (10-30 cm) layers of seawater neutralized bauxite residues. The columns were leached for a period of 8 weeks prior to sowing Rhodes grass and during that time the bulk of the salts accumulated during seawater neutralization were leached out. The main cation leached was Na+ and the main balancing anions were Cl- and SO42-. During this period the pH of leachates rose from 7 to 8 up to 9-10. At the end of the study, exchangeable Na and pH were lowered in the surface horizon by all treatments with a combination of gypsum plus organic amendments having the greatest effect. The latter treatments also caused a significant decrease in pH, extractable Al and exchangeable Na in the subsoil. Rhodes grass dry matter production followed the order Control < gypsum < cattle manure = gypsum plus cattle manure < biosolids = gypsum plus biosolids. Growth of roots into the subsoil layer was inhibited in the Control and gypsum treatments but when organic amendments were applied, 50% or more of root dry matter was recovered in the subsoil layer. It was concluded that incorporating a combination of gypsum and organic matter into the surface soil is an effective strategy for revegetation of bauxite residue.

Tumor Necrosis Factor-α Gene Polymorphism (G-308A) and Dilated Cardiomyopathy.

The issue that genetic polymorphism of tumor necrosis factor-α (TNF-α) is associated with dilated cardiomyopathy (DCM) is debatable. We sought to investigate the potential role of TNF-α gene polymorphism (G-308A) in the susceptibility to dilated cardiomyopathy.We retrieved PubMed, EMBASE, and CNKI to collect all articles which reported on the association between TNF-α G-308A polymorphism and dilated cardiomyopathy. Two authors used the Newcastle-Ottawa Scale (NOS) checklist to assess the quality of the included studies. The odds ratio (OR) with 95% confidence intervals (CI) were pooled in a specific genetic model to assess the association and Stata version 14.0 software was used.A total of 9 studies with 1338 patients and 1677 controls were included in this study. The results from this meta-analysis indicated that TNF-α G-308A polymorphism significantly increased the risk of dilated cardiomyopathy in heterozygous comparison (GA versus GG: OR = 1.87; 95%CI = 1.03-3.40; P < 0.05). The increased risk of DCM was also found in Asian populations using a dominant model and heterozygous comparison (GA+AA versus GG: OR = 2.00, 95%CI = 1.02-3.92, P < 0.05; GA versus GG: OR = 1.94, 95%CI = 1.23-3.06, P < 0.05).The current meta-analysis revealed that TNF-α gene polymorphism (G-308A) may be associated with the susceptibility to DCM.

Suppressing PKC-dependent membrane P2X3 receptor upregulation in dorsal root ganglia mediated electroacupuncture analgesia in rat painful diabetic neuropathy.

Painful diabetic neuropathy (PDN) is a common and troublesome diabetes complication. Protein kinase C (PKC)-mediated dorsal root ganglia (DRG) P2X3 receptor upregulation is one important mechanism underlying PDN. Accumulating evidence demonstrated that electroacupuncture (EA) at low frequency could effectively attenuate neuropathic pain. Our previous study showed that 2-Hz EA could relieve pain well in PDN. The study aimed to investigate whether 2-Hz EA relieves pain in PDN through suppressing PKC-mediated DRG P2X3 receptor upregulation. A 7-week feeding of high-fat and high-sugar diet plus a single injection of streptozotocin (STZ) in a dose of 35 mg/kg after a 5-week feeding of the diet successfully induced type 2 PDN in rats as revealed by the elevated body weight, fasting blood glucose, fasting insulin and insulin resistance, and the reduced paw withdrawal threshold (PWT), as well as the destructive ultrastructural change of sciatic nerve. DRG plasma membrane P2X3 receptor level and DRG PKC expression were elevated. Two-hertz EA failed to improve peripheral neuropathy; however, it reduced PWT, DRG plasma membrane P2X3 receptor level, and DRG PKC expression in PDN rats. Intraperitoneal administration of P2X3 receptor agonist αß-meATP or PKC activator phorbol 12-myristate 13-acetate (PMA) blocked 2-Hz EA analgesia. Furthermore, PMA administration increased DRG plasma membrane P2X3 receptor level in PDN rats subject to 2-Hz EA treatment. These findings together indicated that the analgesic effect of EA in PDN is mediated by suppressing PKC-dependent membrane P2X3 upregulation in DRG. EA at low frequency is a valuable approach for PDN control.

Properties of seawater neutralized bauxite residues and changes in chemical, physical and microbial properties induced by additions of gypsum and organic matter.

Seawater neutralization is a technique that can be used to treat bauxite residue prior to its storage but, as yet, no attempts have been made to revegetate it. Seawater neutralized bauxite residue was found to have a pH1:5 of 9.3 and to be highly saline (EC1.5 16.5 dS m-1). After leaching pH1:5 rose to 9.7 and the residue was still highly sodic (ESP = 64-69%). Addition of 1% gypsum, prior to leaching, arrested this increase in pH while with 5% gypsum addition the pH1:5 was lowered to 8.9. Addition of 5% gypsum also reduced ESP to 38% and increased watercress germination in the residue from 58% in control treatments to 88%. The major ions in leachates were Na+ and Cl- and gypsum application increased the quantities of Na+, Ca2+ and SO42- leached. Addition of 6% biosolids or 6% poultry manure added exchangeable cations to the mud and lowered ESP by 5-11%.The EC was 2.8-3.7 (mean 3.1) times higher and pH 0.2-0.7 (mean 0.43) units lower in saturation paste compared with 1:5 soil:water extracts. Addition of amendments had only small effects on physical properties. While organic C content was increased more by biosolids than poultry manure addition the reverse was the case for soluble organic C, microbial biomass C and basal respiration. It was concluded that although seawater neutralization initially lowers the pH of bauxite residues it is unlikely to increase the ease with which they can be revegetated.

GATA-4 induces changes in electrophysiological properties of rat mesenchymal stem cells.

BACKGROUND: Transplanted mesenchymal stem cells (MSC) can differentiate into cardiac cells that have the potential to contribute to heart repair following ischemic injury. Overexpression of GATA-4 can significantly increase differentiation of MSC into cardiomyocytes (CM). However, the specific impact of GATA-4 overexpression on the electrophysiological properties of MSC-derived CM has not been well documented. METHODS: Adult rat bone marrow MSC were retrovirally transduced with GATA-4 (MSC(GATA-4)) and GFP (MSC(Null)) and subsequently co-cultured with neonatal rat ventricular cardiomyocytes (CM). Electrophysiological properties and mRNA levels of ion channels were assessed in MSC using patch-clamp technology and real-time PCR. RESULTS: MSC(GATA-4) exhibited higher levels of the TTX-sensitive Na(+) current (INa.TTX), L-type calcium current (ICa.L), transient outward K(+) current (Ito), delayed rectifier K(+) current (IKDR) and inwardly rectifying K(+) current (IK1) channel activities reflective of electrophysiological characteristics of CM. Real-time PCR analyses showed that MSC(GATA-4) exhibited upregulated mRNA levels of Kv1.2, Kv2.1, SCN2a1, CCHL2a, KV1.4 and Kir1.1 channels versus MSC(Null). Interestingly, MSC(GATA-4) treated with IGF-1 neutralizing antibodies resulted in a significant decrease in Kir1.1, Kv2.1, KV1.4, CCHL2a and SCN2a1 channel mRNA expression. Similarly, MSC(GATA-4) treated with VEGF neutralizing antibodies also resulted in an attenuated expression of Kv2.1, Kv1.2, Kv1.4, Kir1.1, CCHL2a and SCN2a1 channel mRNAs. CONCLUSIONS: GATA-4 overexpression increases Ito, IKDR, IK1, INa.TTX and ICa.L currents in MSC. Cytokine (VGEF and IGF-1) release from GATA-4 overexpressing MSC can partially account for the upregulated ion channel mRNA expression. GENERAL SIGNIFICANCE: Our results highlight the ability of GATA4 to boost the cardiac electrophysiological potential of MSC.

KCNN3 SNP rs13376333 on Chromosome 1q21 Confers Increased Risk of Atrial Fibrillation.

To investigate the relationship between KCNN3 SNP (single-nucleotide polymorphism) rs13376333 and risk of atrial fibrillation (AF) and to provide evidence for prevention and treatment for AF.The PubMed, Embase, OVID, Cochrane library, CNKI, and Wan Fang databases were searched to identify studies on the relationship between KCNN3 SNP rs13376333 polymorphism and atrial fibrillation. Two authors performed independent article reviews and study quality assessment using the Newcastle-Ottawa Scale (NOS) checklist.Seven studies involving 24,339 individuals were included in the meta-analysis. The overall combined OR of rs13376333 polymorphism was observed for both lone AF (OR: 1.58 [95%CI: 1.37 to 1.82]; P < 0.001; I(2) = 47.0%) and total AF (OR: 1.33 [95%CI: 1.14 to 1.54]; P < 0.001; I(2) = 0). Further, when stratified by ethnicity, control sources, sample sizes, and genotyping method, similar results were observed in both subgroups. Sensitivity analysis revealed that the source of control was the source of the heterogeneity for lone AF. Omission of any single study had little effect on the combined risk estimate. No evidence of publication bias was found.This meta-analysis suggests that KCNN3 SNP rs13376333 polymorphism significantly increases the risk of lone AF and total AF, which suggests the rs13376333 polymorphism of the KCNN3 gene may play an important role in the pathogenesis of AF.

GATA-4 protects against hypoxia-induced cardiomyocyte injury: effects on mitochondrial membrane potential.

Our previous studies have suggested that GATA-4 increases the differentiation of bone-marrow-derived mesenchymal stem cells (MSCs) into cardiac phenotypes. This study further investigated whether GATA-4 enhances MSC-mediated cardioprotection following hypoxia. MSCs were harvested from rat bone marrow and transduced with GATA-4 (MSC(GATA-4)). To mimic ischemic injury, cultured cardiomyocytes (CMs) isolated from neonatal rat ventricles were exposed to hypoxia or were pretreated with concentrated conditioned medium (CdM) from MSC(GATA-4) or transduced control MSC (MSC(Null)) for 16 h before exposure to hypoxic culture conditions (low glucose and low oxygen). Myocyte damage was estimated by annexin-V-PE and TUNEL technique and by lactate dehydrogenase (LDH) release. Cell survival was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium (MTT) uptake. Mitochondrial membrane potential was determined using confocal microscopy. ELISA studies indicated that insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) were significantly increased in MSC(GATA-4) compared with MSC(Null). Hypoxia-induced apoptosis/cell death was significantly reduced when CMs were co-cultured with MSC(GATA-4) in a dual-chamber system. Cell protection mediated by MSC(GATA-4) was mimicked by treating CMs with CdM from MSC(GATA-4) and abrogated with IGF-1- and VEGF-neutralizing antibodies. MSC(GATA-4) protects CMs under hypoxic conditions. The release of IGF-1 and VEGF from MSC(GATA-4) is likely to be responsible for protection of CMs.

Safety and Efficacy of Vitamin K Antagonists vs. Novel Oral Anticoagulants in Patients With Left Ventricular Thrombus: A Meta-Analysis.

Aims: A meta-analysis was conducted to evaluate the safety and efficacy of novel oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in patients with left ventricular thrombus (LVT). Methods and Results: We searched PubMed, Web of Science, and Cochrane Library for cohort studies comparing the use of VKAs vs. NOACs for the treatment of LVT from the earliest date available to September 30, 2020. The predetermined efficacy and safety outcomes included thromboembolic events, resolution of LVT, clinically significant bleedings, and all-cause death. Fixed-effects model was used to estimate the pooled effects. Publication bias analyses and sensitivity analyses were conducted to check the robustness of results. A total of 6 studies enrolling 837 patients (mean age 60.2 ± 1.6 years; 77.2% were male) were included. We found no significant differences in thromboembolic events [relative risk (RR) 1.69, 95% confidence interval (CI) 0.94-3.06, P 0.08, I2 12.7%], the rate of resolution of thrombus (RR 1.08, 95% CI 0.96-1.21, P 0.21, I2 4.8%), and clinically significant bleedings (RR 0.70, 95% CI 0.37-1.32, P 0.27, I2 0%) between the VKAs and NOACs group. Additionally, no significant difference in all-cause mortality was found between the two groups (RR 1.24, 95% CI 0.79-1.96, P 0.35, I2 0.0%). Sensitivity analyses, using the "1-study removed" method, detected no significant differences. Conclusion: NOACs and VKAs have similar efficacy and safety in treating LVT, prompting the inference that NOACs are the possible alternatives of VKAs in LVT therapy.

hAECs and their exosomes improve cardiac function after acute myocardial infarction in rats.

BACKGROUND: Human amniotic epithelial cells (hAECs) are seed cells used to treat acute myocardial infarction (AMI), but their mechanism remains unclear. METHODS: We cultured hAECs and extracted exosomes from culture supernatants. Next, we established a stable AMI model in rats and treated them with hAECs, exosomes, or PBS. We assess cardiac function after treatment by echocardiography. Additionally, heart tissues were collected and analyzed by Masson's trichrome staining. We conducted the tube formation and apoptosis assays to explore the potential mechanisms. RESULTS: Cardiac function was improved, and tissue fibrosis was decreased following implantation of hAECs and their exosomes. Echocardiography showed that the EF and FS were lower in the control group than in the hAEC and exosome groups, and that the LVEDD and LVESD were higher in the control group (P<0.05). Masson's trichrome staining showed that the fibrotic area was larger in the control group. Tube formation was more efficient in the hAEC and exosome groups (P<0.0001). Additionally, the apoptosis rates of myocardial cells in the hAEC and exosome groups were significantly decreased (P<0.0001). CONCLUSIONS: hAECs and their exosomes improved the cardiac function of rats after AMI by promoting angiogenesis and reducing the apoptosis of cardiac myocytes.

New regulatory mechanisms for the intracellular localization and trafficking of influenza A virus NS1 protein revealed by comparative analysis of A/PR/8/34 and A/Sydney/5/97.

During influenza A virus infection, the NS1 protein is engaged in different functions in different intracellular compartments. In this study, we showed that the NS1 of A/PR/8/34 localized in different positions from that of A/Sydney/5/97 when transiently expressed in Madin-Darby canine kidney cells. Residue 221 of NS1 was identified to be a new key residue involved in the C-terminal nuclear localization signal (NLS) and nucleolar localization signal (NoLS) of NS1 from A/Sydney/5/97. Analysis of chimeric NS1 and further mutants showed that residues responsible for the binding between NS1 and the cleavage and polyadenylation specificity factor (CPSF) are correlated with the intracellular localization of transiently expressed NS1 proteins. Fluorescence loss in photobleaching imaging revealed that the NS1 protein with both functional NLSs and nuclear export signal (NES) was able to shuttle between the nucleus and cytoplasm. Drug inhibition experiments and fluorescence resonance energy transfer analysis suggested that NS1 was exported out of the cell nuclei via a Crm1-independent pathway. Moreover, it is likely that another cytoplasmic localization-related sequence exists in the NS1 protein other than the leucine-rich NES. These findings provide new insights into the mechanism of intracellular localization and trafficking of influenza A virus NS1 protein, which is important for understanding its function.

Characterization of a monomeric heat-labile classical alkaline phosphatase from Anabaena sp. PCC7120.

Alkaline phosphatases (APs), known inducible enzymes of the Pho regulon and poorly characterized in cyanobacteria, hydrolyze phosphomonoesters to produce inorganic phosphate (P(i)) during P(i) starvation. In this study, two predicted alkaline phosphatase genes in the genome of Anabaena sp. PCC 7120, all2843 and alr5291, were apparently induced during P(i) starvation. Sequence analysis showed that alr5291 encodes a protein that is an atypical alkaline phosphatase like other cyanobacteria PhoAs, but the protein encoded by all2843 is very similar to the classical PhoAs, such as Escherichia coli alkaline phosphatase (EAP). To date, there have been no reports about classical phoA in cyanobacterial genomes. The alkaline phosphatase AP(A), coded by all2843, is characterized as a metalloenzyme containing Mg2+ and Zn2+ with molar ratio of 1 : 2. Site-directed mutagenesis analysis indicated that, though the active center of AP(A) is highly conserved in comparison with EAP, differences do exist between AP(A) and EAP in metal ion coordination. Besides, biochemical analysis revealed that AP(A) is a monomeric protein and inactivated rapidly at 50 degrees C. These results suggest that AP(A) is the first monomeric heat-labile classical PhoA found in cyanobacteria.

Imaging and characterizing influenza A virus mRNA transport in living cells.

The mechanisms of influenza A virus mRNA intracellular transport are still not clearly understood. Here, we visualized the distribution and transport of influenza A virus mRNA in living cells using molecular beacon (MB) technology. Confocal-FRAP measurements determined that the transport of influenza A virus intronless mRNA, in both nucleus and cytoplasm, was energy dependent, being similar to that of Poly(A)(+) RNA. Drug inhibition studies in living cells revealed that the export of influenza A virus mRNA is independent of the CRM1 pathway, while the function of RNA polymerase II (RNAP-II) may be needed. In addition, viral NS1 protein and cellular TAP protein were found associated with influenza A virus mRNA in the cell nucleus. These findings characterize influenza A virus mRNA transport in living cells and suggest that influenza A virus mRNA may be exported from the nucleus by the cellular TAP/p15 pathway with NS1 protein and RNAP-II participation.

Biochemical characterization and mutational improvement of a thermophilic esterase from Sulfolobus solfataricus P2.

A thermophilic esterase, SsoPEst, from Sulfolobus solfataricus P2 was cloned and expressed in E. coli AD494 (DE3). Gene sequencing indicated the encoded 353 amino acids had less than 32% identity with reported esterases. The recombinant enzyme hydrolyzed p-nitrophenyl esters but not tributyrin or tricaprylin, exhibiting the highest specific activity (1.1 U/mg) with p-nitrophenyl caprylate. The enzyme was optimally active at pH 5.5 and 80 degrees C. It retained 50% activity after 1 h incubation at 80 degrees C. Activity was significantly inhibited by PMSF. Five SsoPEst mutants were generated by site-directed mutagenesis. One mutant had a higher specific activity of 2.8 U/mg at 37 degrees C and 14 U/mg at 80 degrees C than the wild-type enzyme which exhibited 0.7 U/mg at 37 degrees C and 3.8 U/mg at 80 degrees C against p-nitrophenyl butyrate.

Seeding-induced self-assembling protein nanowires dramatically increase the sensitivity of immunoassays.

Aiming to build a supersensitive and easily operable immunoassay, bifunctional protein nanowires were generated by seeding-induced self-assembling of the yeast amyloid protein Sup35p that genetically fused with protein G and an enzyme (methyl-parathion hydrolase, MPH), respectively. The protein nanowires possessed a high ratio of enzyme molecules to protein G, allowing a dramatic increase of the enzymatic signal when protein G was bound to an antibody target. As a result, a 100-fold enhancement of the sensitivity was obtained when applied in the detection of the Yersinia pestis F1 antigen.

Correlation of left atrial strain with left ventricular end-diastolic pressure in patients with normal left ventricular ejection fraction.

Left ventricular diastolic dysfunction (LVDD) remains challenging to be assessed by echocardiography. We sought to explore the relationship between left atrial strain and left ventricular (LV) diastolic function in patients with normal left ventricular ejection fraction (LVEF) by invasive left-heart catheterization. 55 consecutive individuals with LVEF > 50% underwent LV catheterization. Standard transthoracic echocardiography was performed during 12 h before or after the procedure. Left atrial (LA) strain were obtained by speckle tracking echocardiography. When LVEF ≥ 50%, the group with elevated left ventricular end-diastolic pressure (LVEDP) (n = 35) showed decreased left atrial reservoir strain (LASr) (35.2 ± 7.7% vs 21.3 ± 7.2%, p < 0.001), left atrial conduit strain (LASct) (17.6 ± 6.3% vs 11.9 ± 4.1%, p < 0.001), left atrial contraction strain (LAScd) (16.6 ± 7.2% vs 9.5 ± 5.0%, p < 0.001) and increased E/e' ration(8.9 ± 2.6 vs 10.1 ± 3.5, p = 0.17). LVEDP negatively correlated with LASr (R = 0.662, p < 0.001), LASct (R = 0.575, p < 0.001) and LAScd (R = 0.456, p < 0.001), but not with E/e'. LASr, LASct and LAScd were all independent predictors of elevated LVEDP (p < 0.05), with a higher C-statistic for the model including LASr (0.95, 0.86 and 0.93 respectively). The area under the curve (AUC) for LASr is 0.914 (cutoff value is 26.7%, sensitivity is 90%, specificity is 82.9%). In patients with normal LV ejection fraction, left atrial strain presented good correlation with LVEDP, and LASr was superior to LASct and LAScd to predict LVEDP. LA strain demonstrated better agreement with the invasive reference than E/e'.

Rs10757274 gene polymorphisms in coronary artery disease: A systematic review and a meta-analysis.

BACKGROUND: It has been reported the rs10757274 SNP (present on locus 9p21 in the gene for CDKN2BAS1) might be associated with susceptibility to coronary artery disease (CAD). Owing to mixed and inconclusive results, we conducted a meta-analysis to investigate the association between rs10757274 polymorphism and the risk of CAD. OBJECTIVES: The present study aimed to investigate the relationship between rs10757274 polymorphism and the risk of CAD. METHODS: All studies of the rs10757274 SNP with CAD that were published between 2007 and 2018 were retrieved from the PubMed database. Meta-analysis was performed with Stata 14.0 software. The effect size of the rs10757274 SNP with CAD risk was assessed based on the odds ratios (ORs) with calculation of 95% confidence interval (CI). RESULTS: Eleven studies including 52,209 subjects (cases: 7990, controls: 44,219) were included in the final data combination. Pooled overall analyses showed that rs10757274 (allele model: P < .001; dominant model: P < .001; recessive model: P < .001; Heterozygote codominant: P = .002; Homozygote codominant: P < .001) polymorphisms were significantly associated with the likelihood of CAD. Significant heterogeneity between individual studies appears in all 5 models. Further subgroup analyses revealed that rs10757274 polymorphisms were all significantly correlated with the likelihood of CAD and no heterogeneity were observed in West Asians. CONCLUSIONS: Our findings indicated that rs10757274 polymorphisms may serve as genetic biomarkers of CAD, especially in West Asians.