Association between Blood Lead Levels and Silent Myocardial Infarction in the General Population.

Background: Although the link between lead exposure and patterns of cardiovascular disease (CVD) has been reported, its association with silent myocardial infarction (SMI) remains unexplored. We aimed to assess the association between blood lead levels (BLLs) and SMI risk. Methods: We included 7283 (mean age 56.1 ± 2.52 years, 52.5% women) participants free of CVD from the Third National Health and Nutrition Examination Survey. BLL was measured using graphite-furnace atomic absorption spectrophotometry. SMI was defined as ECG evidence of myocardial infarction (MI) without history of MI. The association between SMI and BLLs was examined using multivariable logistic regression. Results: SMI was detected in 120 participants with an unweighted prevalence of 1.65%. Higher BLL correlated with higher SMI prevalence across BLL tertiles. In multivariable-adjusted models, participants in the third BLL tertile had more than double the odds of SMI (OR: 3.42, 95%CI: 1.76-6.63) compared to the first tertile. Each 1 µg/dL increase in BLL was linked to a 9% increase in SMI risk. This association was consistent across age, sex, and race subgroups. Conclusions: Higher BLLs are associated with higher odds of SMI in the general population. These results underscore the significance of the ongoing efforts to mitigate lead exposure and implement screening strategies for SMI in high-risk populations.

Racial differences in prevalence and impact of electrocardiographic subclinical myocardial injury risk factors.

BACKGROUND: We explored whether the reported racial differences in subclinical myocardial injury (SCMI) are due to variations in the prevalence or differential impact of the SCMI risk factors. METHODS: This analysis included 3074 Whites, 1337 Blacks, and 1441 Mexican Americans from the Third National Health and Nutrition Examination Survey who were free of cardiovascular disease. SCMI was defined from standard electrocardiograms as a cardiac infarction/injury score ≥ 10 points. Multivariable logistic regression analysis was used to assess the association of SCMI with its risk factors stratified by race. Multiplicative interaction between each risk factor and race was also examined. RESULTS: Overall prevalence of SCMI was 20.3%, with Mexican Americans exhibiting a lower prevalence than Whites and Blacks (16.5%, 20.4%, and 20.7%, respectively). Whites had more prevalence of dyslipidemia and smoking. Mexican Americans had more diabetes, while Blacks had more hypertension, obesity, and left ventricular hypertrophy. Significant risk factors for SCMI were older age, lower income (<20 K), smoking, diabetes, and no regular exercise. The association of SCMI with age was more pronounced in Mexican Americans (p-value for interaction 0.03), whereas the associations of SCMI with smoking, no-regular exercise, and diabetes were stronger in Whites (p-value for interaction 0.04, 0.001, 0.007, respectively). CONCLUSIONS: Heterogeneity in the racial differences in the prevalence of SCMI risk factors exists, but they do not explain racial differences in SCMI. The stronger associations of smoking, diabetes, and no regular exercise with SCMI partially explain the higher prevalence of SCMI in Whites.

Comprehensive studies for evaluating promising properties of Cu/graphene/fly ash nanocomposites.

Copper (Cu)'s electrical conductivity makes it attractive for industrial usage. Due to its inferior mechanical characteristics, thermal expansion, and wear resistance, its applications are limited. This manuscript solves these issues while retaining its major feature, excellent electrical conductivity. In this regard, different quantities of graphene (Gr) and fly ash (FA) nanoparticles were combined with Cu in a planetary ball mill at 440 rpm for 20 h using powder metallurgy (PM). The microstructure of the generated powders was characterized using X-ray diffraction technique and transmission electron microscopy. The powders underwent compression and were then subjected to firing at three distinct temperature levels, reaching a maximum of 850 °C. In addition, an analysis was conducted on the microstructure, mechanical properties, wear resistance, thermal expansion behaviour, and electrical conductivity of the sintered samples. Based on the findings, the inclusion of a hybrid of Gr and FA ceramics effectively led to a reduction in particle sizes. The bulk density slightly decreases with the addition of hybrid ceramic while increasing with the rise in sintering temperature. The hybrid composited Cu/0.8 vol.% Gr/8 vol.% FA recorded an increase in the microhardness, ultimate stress, and Young's modulus of 25, 20, and 50%, respectively, relative to the Cu matrix. Furthermore, the wear rate and coefficient of thermal expansion for the same sample decreased by 67 and 30%, respectively. Finally, increasing the sintering temperature showed a clear improvement in the mechanical, electrical, and corrosion properties. Based on the results obtained, it can be concluded that the prepared hybrid nanocomposites can be used in power generation, power transmission, electronic circuits, and other applications.

Joint Association of Albuminuria and Left Ventricular Hypertrophy With Incident Heart Failure in Adults at High Risk With Hypertension: A Systolic Blood Pressure Intervention Trial Substudy.

Albuminuria and left ventricular hypertrophy (LVH) are independent predictors of heart failure (HF); however, to the best of our knowledge, their combined effect on the risk of HF has not yet been explored. Therefore, we examined the joint associations of albuminuria and electrocardiographic-LVH with incident acute decompensated HF (ADHF), and whether albuminuria/LVH combinations modified the effects of blood pressure control strategy in reducing the risk of ADHF. A total of 8,511 participants from the Systolic Blood Pressure Intervention Trial (SPRINT) were included. Electrocardiographic-LVH was present if any of the following criteria were present: Cornell voltage, Cornell voltage product, or Sokolow-Lyon. Albuminuria was defined as urine albumin/creatinine ratio ≥30 mg/g. ADHF was defined as hospitalization or emergency department visit for ADHF. Cox proportional hazard models were used to examine the association of neither LVH nor albuminuria (reference), either LVH or albuminuria, and both (LVH + albuminuria) with incident ADHF. Over a median follow-up of 3.2 years, 182 cases of ADHF occurred. In adjusted models, concomitant albuminuria and LVH were associated with greater risk of ADHF than either albuminuria or LVH in isolation (hazard ratio [95% confidence interval]: 4.95 [3.22 to 7.62], 2.04 [1.39 to 3.00], and 1.47 [0.93 to 2.32], respectively, additive interaction p = 0.01). The effect of intensive blood pressure in reducing ADHF was attenuated in participants with coexisting albuminuria and LVH without any interaction between treatment group assignment and albuminuria/LVH categories (interaction p = 0.26). In conclusion, albuminuria and LVH are additive predictors of ADHF. The effect of intensive blood pressure control in reducing ADHF risk did not vary significantly across albuminuria/LVH combinations.

[Diffusion tensor field estimation based on 3D U-Net and diffusion tensor imaging model constraint].

OBJECTIVE: To propose a diffusion tensor field estimation network based on 3D U-Net and diffusion tensor imaging (DTI) model constraint (3D DTI-Unet) to accurately estimate DTI quantification parameters from a small number of diffusion-weighted (DW) images with a low signal-to-noise ratio. METHODS: The input of 3D DTI-Unet was noisy diffusion magnetic resonance imaging (dMRI) data containing one non-DW image and 6 DW images with different diffusion coding directions. The noise-reduced non-DW image and accurate diffusion tensor field were predicted through 3D U-Net. The dMRI data were reconstructed using the DTI model and compared with the true value of dMRI data to optimize the network and ensure the consistency of the dMRI data with the physical model of the diffusion tensor field. We compared 3D DTI-Unet with two DW image denoising algorithms (MP-PCA and GL-HOSVD) to verify the effect of the proposed method. RESULTS: The proposed method was better than MP-PCA and GL-HOSVD in terms of quantitative results and visual evaluation of DW images, diffusion tensor field and DTI quantification parameters. CONCLUSION: The proposed method can obtain accurate DTI quantification parameters from one non-DW image and 6 DW images to reduce image acquisition time and improve the reliability of quantitative diagnosis.

Joint Association of Albuminuria and Left Ventricular Hypertrophy with Incident Heart Failure in High-Risk Adults with Hypertension: a SPRINT substudy.

Background: Albuminuria and left ventricular hypertrophy (LVH) are independent predictors of heart failure (HF), however their combined effect on risk of HF has not been explored previously. Objectives: To examine the joint associations of albuminuria and electrocardiographic (ECG) LVH with incident acute decompensated HF (ADHF), and whether albuminuria/LVH combinations modified the effects of blood pressure control strategy in reducing the risk of ADHF. Methods: 8,511 participants from the SPRINT (Systolic Blood Pressure Intervention Trial) were included. ECG-LVH was present if any of the following criteria: Cornell voltage, Cornell voltage product, or Sokolow Lyon were present. Albuminuria was defined as urine albumin-creatinine ratio (UACR) ≥30 mg/g. ADHF was defined as hospitalization or emergency visit for ADHF. Cox proportional hazard models were used to examine the association of neither LVH, nor albuminuria (reference), either LVH or albuminuria, and both (LVH + albuminuria) with incident ADHF. Results: Over a median follow-up of 3.2 years, 182 cases of ADHF occurred. In adjusted models, concomitant albuminuria and LVH were associated with higher risk of ADHF than either albuminuria or LVH in isolation (HR (95% CI): 4.95 (3.22-7.62), 2.04 (1.39-3.00), and 1.47 (0.93-2.32), respectively (additive interaction p=0.01). The effect of intensive blood pressure in decreasing ADHF attenuated among participants with co-existing albuminuria and LVH without any interaction between treatment group assignment and albuminuria/LVH categories (interaction p-value= 0.26). Conclusions: Albuminuria and LVH are additive predictors of ADHF. The effect of intensive blood pressure control in decreasing ADHF risk did not vary significantly across albuminuria/LVH combinations.

Relationship between premature ventricular complexes and stroke mortality in the general population.

OBJECTIVES: Predictors for increased stroke mortality identify those who may need closer monitoring and better hospital care. While the link between premature ventricular complexes (PVCs) and incident ischemic stroke has been reported, studies on the association with fatal stroke are non-existent. MATERIALS AND METHODS: We examined the association of PVCs with stroke mortality in 8047 participants (56.5 ± 0.39 years, 53% women, 80.9% Non-Hispanic Whites) without prior history of stroke from the Third National Health and Nutrition Examination Survey. National Death Index was used to identify the date and cause of death. PVCs were detected from 12­lead standard electrocardiograms. Cox proportional hazard analysis was used to examine the association between any PVC with stroke mortality. RESULTS: Approximately 2.1% (n = 134) participants had PVCs at baseline. Over a median follow-up of 22 years, 337 fatal strokes occurred. More strokes occurred in participants with baseline PVCs compared to those without (unadjusted cumulative incidence of stroke 9.5% vs. 2.5% respectively, p-value 0.001). In a multivariable-adjusted model, the presence of PVC was associated with an increased risk of stroke mortality (HR (95%CI): 2.50 (1.15-5.43). This association was stronger in participants with coronary heart disease (CHD) than those without it (HR (95%CI): 5.98 (2.2-16.2) vs. 1.97 (0.75-5.1) respectively; interaction-p = 0.008). CONCLUSIONS: PVCs are associated with an increased risk of stroke mortality, especially among individuals with CHD. Whether improved hospital care or modifying PVCs could change outcomes should be examined in prospective studies.

[Analysis of the level of T lymphocyte subsets and the relationship with the prognosis of pulmonary fibrosis in patients with paraquat poisoning].

Objective: To analyze the levels of T lymphocyte subsets (CD3, CD4, CD8 and CD4/CD8) in patients with paraquat poisoning, and to explore the relationship between the changes of T lymphocyte subsets and the prognosis of pulmonary fibrosis. Methods: In October 2019, a total of 47 patients with oral 20% paraquat low water solvent poisoning in Guangzhou 12th people's Hospital from June 2018 to June 2019 were selected as the research objects. Patients were divided into early death group (16 cases died within 2 weeks) and non early death group (31 cases survived more than 2 weeks) . The non early death group was divided into pulmonary fibrosis group (23 cases) and normal lung group (8 cases) . 20 healthy people in the same period were randomly selected as the control group. The neutrophils (N) , C reaction protein (CRP) , alanine aminotransferase (ALT) , creatinine (Cr) , amylase (aAMY) , creatine kinase isoenzyme (CKMB) , pH, HCO(3)(-), blood oxygen saturation (SO(2)) and lactic acid (Lac) of patients poisoned within 3 d were examined every day. Independent sample t-test was used for inter group comparison, and paired sample t-test was used for intra group comparison. Results: Compared with non early death group, the levels of N, CRP, ALT, Cr, aAMY, CKMB and Lac in early death group increased (P<0.05) , while pH and HCO(3)(-) decreased (P<0.05) . Compared with the control group, the levels of CD3, CD4 and CD4/CD8 were decreased on the first day in the early death group and non early death group (P<0.05) , and the levels of CD3, CD4 and CD4/CD8 were decreased on the 15th day in the pulmonary fibrosis group (P<0.05) . Compared with the normal lung group, the levels of CD3, CD4 and CD4/CD8 in the pulmonary fibrosis group decreased on the 15th day (P<0.05) . Conclusion: The persistent low cellular immune function in patients with paraquat poisoning is related to the progress of pulmonary fibrosis, which is an important factor affecting the prognosis of patients with pulmonary fibrosis.

Electrocardiographic myocardial injury and stroke mortality in the general population.

BACKGROUND: Recent evidence suggests a link between myocardial infarction and stroke risk, but it is unclear whether such risk exists with electrocardiographic myocardial injury in otherwise healthy individuals. Therefore, we explored the association of myocardial injury with stroke mortality in participants free of cardiovascular disease. METHODS: This analysis included 6017 participants (58.4 ± 13.4 years, 54.1% women, 50.3% white) from the Third National Health and Nutrition Examination Survey. Cardiac infarction/injury score (CIIS), a weighted scoring system composed of several electrocardiographic waveform components related to myocardial injury and ischemia, was used to define myocardial injury. Stroke mortality was ascertained using the National Death Index during follow-up. Multivariable adjusted Cox proportional hazard analysis was used to examine the association between baseline myocardial injury and risk of stroke mortality. RESULTS: Over a median follow-up of 14 years, 152 stroke deaths occurred. Stroke mortality was more common in those with than those without myocardial injury (3.8% vs. 2.1%, respectively; p = 0.0003). In a model adjusted for potential confounders, the myocardial injury was associated with a 44% increased risk of stroke mortality (HR (95%CI):1.44(1.02-2.03)). In a similar model, each 1 CIIS score point increase was associated with a 2% increase in the risk of stroke mortality (HR (95%CI):1.02 (1.00-1.04), p = 0.01). CONCLUSIONS: Electrocardiographic myocardial injury in cardiovascular disease-free adults is associated with an increased risk of stroke mortality suggesting a potential link between asymptomatic myocardial injury and risk of cardiac thromboembolism. Whether screening and management of myocardial injury would reduce such risk requires further investigation.

[Investigation of acute poisoning event caused by carbofuran].

Objective: To analyze the epidemiological characteristics and response process of an acute poisoning event caused by carbofuran in buttered tea and provide scientific evidence for the investigation of similar events in the future. Methods: Field epidemiological survey, animal experiments and laboratory tests were conducted for an acute poisoning event occurred in Suopo township of Danba county of Sichuan province in 2018. Descriptive epidemiological method was used to analyze the epidemiological characteristics of the acute poisoning event. Results: A total of 26 poisoning cases occurred in 3 villages. The total attack rate was 41.27%. No death cases were reported. The 26 cases occurred in a few minutes after drinking buttered tea, the main symptoms were vomit, dizziness, miosis and nausea. A dog showed the same symptoms after drinking a sample of buttered tea. Carbofuran was detected in buttered tea, vomitus and zanba samples. Conclusions: The acute poisoning was caused by carbofuran in buttered tea, the transmission mode was point source spread. Effective epidemiological investigation and simple animal experiment can provide evidence for the rapid sample detection and clinical treatment of cases in emergency response. Timely case treatment and strict poisoning source control are the key measures to reduce casualty and prevent the spread of poisoning.

Superior robustness of ExEm-spFRET to IIem-spFRET method in live-cell FRET measurement.

We recently developed two quantitative fluorescence resonance energy transfer (FRET) measurement methods based on spectral unmixing of emission spectra (IIem-spFRET) and excitation-emission spectra (ExEm-spFRET), respectively. We here evaluated robustness of the two methods by implementing them on a self-assembled quantitative FRET measurement system using the cells expressing different constructs. For the cells with larger signal-to-noise (S/N) ratio (>9), the two methods obtained consistent FRET efficiency (E) values and total concentration ratio (RC) values of acceptor to donor for all constructs; for the cells with 3 < S/N < 9, IIem-spFRET obtained bigger RC values than the expected value for VCV construct; for the cells with S/N < 3, although IIem-spFRET method obtained inaccurate E and RC values for VCV construct, the two methods also obtained consistent E and RC values for all other constructs. Collectively, both ExEm-spFRET and IIem-spFRET methods are very applicable for live-cell FRET measurement, and ExEm-spFRET has superior robustness especially for the cells with low S/N ratio. LAY DESCRIPTION: Fluorescent proteins (FPs)-based fluorescence resonance energy transfer (FRET) has been widely used as a powerful technique to study protein-protein interaction and stoichiometry of macromolecular complexes in living cells. There are two key issues for quantitative FRET measurement especially in living cells: donor emission crosstalk (donor fluorescence is collected in acceptor detection channel) and acceptor excitation crosstalk (acceptor is excited directly under donor excitation) due to the spectral overlap of FPs. Two-wavelengths excitation-based spectral linear unmixing of emission spectra can resolve donor emission crosstalk due to the obvious difference in emission spectra between donor and acceptor, but additional reference is necessary for the correction of acceptor excitation crosstalk. Spectral unmixing of excitation-emission spectra has inherent ability to resolve donor emission crosstalk and acceptor excitation crosstalk simultaneously without additional reference. We recently developed two quantitative FRET measurement methods based on spectral unmixing of emission spectra (IIem-spFRET) and excitation-emission spectra (ExEm-spFRET), respectively. We here evaluate robustness of the two methods by implementing them on a self-assembled quantitative FRET measurement system using the same cells expressing different constructs under different signal-to-noise (S/N) ratios. For the cells with S/N > 9, the two methods obtained consistent FRET efficiency (E) values and total concentration ratio (RC) values of acceptor to donor for all constructs; for the cells with 3 < S/N < 9, IIem-spFRET obtained bigger RC values than the expected value for VCV construct; for the cells with S/N < 3, although IIem-spFRET method obtained inaccurate E and RC values for VCV construct, the two methods also obtained consistent E and RC values for all other constructs. Collectively, our experimental results demonstrate that both ExEm-spFRET and IIem-spFRET methods are very applicable for live-cell FRET measurement, and ExEm-spFRET has superior robustness especially for the cells high E and low S/N ratio.

Supplementation with Oligonol, Prevents Weight Gain and Improves Lipid Profile in Overweight and Obese Saudi Females.

BACKGROUND: Obesity is a global health problem, increasing susceptibility to Type 2 Diabetes (T2DM) and Cardiovascular Disease (CVD). Varieties of products have been proposed for treatment with varying degrees of success. Recent studies, suggested Oligonol; an optimized phenolic product mixture from Lychee Fruit Polyphenols (LFP); as such treatment in Japanese population. OBJECTIVES: We aimed to investigate the effect of oligonol on weight, insulin resistance by (HOMA-IR), lipids profile, leptin, Adiponectin, and resistin in healthy overweight and obese Saudi females. SUBJECTS AND METHODS: 60 Saudi healthy overweight and obese females were enrolled in a double blind case/control study to take either Oligonol or placebo for 12 weeks without dietary or lifestyle re-strictions. Weight, height, Waist Circumference (WC), hip circumference (HC), and blood pressure were measured, and fasting blood samples of participants were taken before, and at the end of study. Total cholesterol, HDL-cholesterol, triglycerides, glucose, insulin, leptin, adiponectin, and resistin were meas-ured. LDL- cholesterol, HOMA-IR were calculated by equation. RESULTS: 47 subjects completed the study, 25 in placebo group, and 22 in Oligonol group. No ill effects were noted in any participant. Oligonol reduced means of serum triglycerides (P=0.008), and resistin (P=0.045) significantly. In addition, no weight gain was noted in oligonol group, unlike placebo group which exhibited significant increase in mean weight (P= 0.036), WC (P=0.027), HC (P= 0.047), and leptin (P <0.001). CONCLUSION: Oligonol could be suggested as future hypolipidemic and weight controlling agent for overweight and obese Saudi females.

Clinical efficacy of sequential therapy with voriconazole on COPD patients in acute phase with pulmonary aspergillosis and effects on cytokines and pulmonary functions.

OBJECTIVE: To explore the clinical efficacy of sequential therapy with voriconazole on chronic obstructive pulmonary disease (COPD) patients in acute phase with pulmonary aspergillosis and its effects on cytokines and pulmonary functions. PATIENTS AND METHODS: A total of 110 COPD patients in acute phase with pulmonary aspergillosis who were admitted to the hospital between February 2015 and November 2016 were enrolled. We divided them randomly into two groups, i.e., the control group (n = 55) and the treatment group (n = 55). Patients in the control group took itraconazole capsules orally (200 mg/time, twice per day for three days followed by once per day). Patients in treatment group underwent sequential treatment with voriconazole through intravenous infusion at a dose of 5 mg/kg/time twice a day for 3 days followed by a dose of 4 mg/kg/time, twice a day for 8 days. Then, patients took voriconazole orally at a dose of 150 mL/time, twice a day for 6 days. Patients in two groups received the treatment for a total of 14 days. After treatment, we evaluated the levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-8. The total lung capacity (TLC), diffusing capacity of the lung for carbon monoxide (DLco), and arterial oxygen saturation (SaO2), were measured as well. RESULTS: The total effectiveness rates of the treatment group and the control group were 83.63% and 61.82%. The differences had statistical significance (p < 0.01). After treatment, the incidence of chest pain, cough, sputum-coughing, hemoptysis, cyanosis, and dyspnea in the treatment group was significantly fewer than that in the control group (p < 0.05). TCL, DLco, and SaO2 in the two groups were significantly ameliorated by treatment (p < 0.05). The amelioration in the treatment group was more prominent than that in the control group (p < 0.05). The levels of TNF-α, IL-8, and IL-6 in the two groups were decreased dramatically by the treatments. The decrease in the treatment group was significantly lower than those in the control group (p < 0.05). Occurrence of adverse reactions in treatment group and control group were 8.33% and 6.25%, respectively; (p > 0.05). CONCLUSIONS: Sequential therapy with voriconazole exhibits promising clinical efficacy in COPD patients in acute phase with pulmonary aspergillosis. The treatment ameliorated the clinical symptoms and vital signs of patients significantly. It also improved the pulmonary functions and inhibited the inflammatory responses of patients with evident clinical efficacy.

Association between phosphodiesterase type 5 inhibitors use and risk of melanoma: a meta-analysis.

This meta-analysis aimed to clarify the actual association between the phosphodiesterase type 5 inhibitors (PDE5-Is) use and the risk of melanoma in erectile dysfunction (ED) patients. A systematic literature search was conducted in online databases in October, 2016 to identify studies focusing on the association between PDE5-Is use and the risk of melanoma. Summarized multivariate adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to assess the strength of associations. A total of six clinical trials containing more than one million participants were included. ED patients  using PDE5-Is shared a significant high risk of melanoma (RR=1.12, 95% CI=1.03-1.21, p=0.006). Positive associations were observed in all kinds of prescriptions: single prescription (RR=1.20, 95% CI=1.06-1.35, p=0.003), medium number of prescription (RR=1.15, 95% CI=1.01-1.30, p=0.03), and high number of prescription (RR=1.18, 95% CI=1.05-1.34, P=0.006). Additionally, PDE5-Is were also found to be significantly associated with increased risk of basal cell carcinoma (RR=1.14, 95% CI=1.09-1.19, p<0.00001). Our study indicates that PDE5-Is use could significantly increase the risk of melanoma and basal cell carcinoma. However, the risk of melanoma did not rise significantly with the increased number of prescriptions. Consequently, owing to the lack of information about other potential synergistic factors, it is difficult for us to make a solid conclusion that application of PDE5-Is is the direct cause of increased risk of melanoma. Their relationship needs to be validated by further evidences.

Simultaneous measurement of quantum yield ratio and absorption ratio between acceptor and donor by linearly unmixing excitation-emission spectra.

Quantum yield ratio (QA /QD ) and absorption ratio (KA /KD ) in all excitation wavelengths used between acceptor and donor are indispensable to quantitative fluorescence resonance energy transfer (FRET) measurement based on linearly unmixing excitation-emission spectra (ExEm-spFRET). We here describe an approach to simultaneously measure QA /QD and KA /KD values by linearly unmixing the excitation-emission spectra of at least two different donor-acceptor tandem constructs with unknown FRET efficiency. To measure the QA /QD and KA /KD values of Venus (V) to Cerulean (C), we used a wide-field fluorescence microscope to image living HepG2 cells separately expressing each of four different C-V tandem constructs at different emission wavelengths with 435 nm and 470 nm excitation respectively to obtain the corresponding excitation-emission spectrum (SDA ). Every SDA was linearly unmixed into the contributions (weights) of three excitation-emission spectra of donor (WD ) and acceptor (WA ) as well as donor-acceptor sensitisation (WS ). Plot of WS /WD versus WA /WD for the four C-V plasmids from at least 40 cells indicated a linear relationship with 1.865 of absolute intercept (QA /QD ) and 0.273 of the reciprocal of slope (KA /KD ), which was validated by quantitative FRET measurements adopting 1.865 of QA /QD and 0.273 of KA /KD for C32V, C5V, CVC and VCV constructs respectively in living HepG2 cells.

[Value of anti-Müllerian hormone in predicting pregnant outcomes of polycystic ovary syndrome patients undergone assisted reproductive technology].

Objective: Explore the value of anti-Müllerian hormone (AMH) in predicting pregnant outcomes of polycystic ovary syndrome (PCOS) patients undergone assisted reproductive technology. Methods: The study totally recruited 1 697 patients who underwent the first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle in Sun Yat-sen Memorial Hospital from the January 2014 to December 2015. The patients were divided into two groups based on the age<35 (n=758) and ≥35 years old (n=939) , compare the basic data and pregnant outcomes of controlled ovarian hyerstimulation. Spearman correlation method was conducted to analyze the relations between AMH and clinical outcomes. The logistic regression method and partial correlation analysis were used to judge the main factors which determine pregnancy outcomes by controlled the confounding factors. The receiver operating characteristic curve (ROC) was used to evaluate the predictive sensitivity and specificity of AMH. Results: In the group of PCOS patient younger than 35 years, AMH were correlated with the number of antral follicles (r=0.388) and retrieved oocytes (r=0.235) . When the effect of total dosage and starting dosage of gonadotropin were controlled, AMH was still significantly associated with the number of retrieved oocytes (P<0.05) . AMH had no predictive value for the clinical pregnancy of PCOS patient younger than 35 years (area under ROC curve=0.481, P=0.768) . In the group of PCOS patient≥35 years old, AMH were correlated with the number of antral follicles (r=0.450) , retrieved oocytes (r=0.399) , available embryo (r=0.336) and high quality embryo (r=0.235) . When the effect of total dosage and starting dosage of gonadotropin were controlled, the correlations were still significant between those indexes (all P<0.05) . AMH had no predictive value for the clinical pregnancy of PCOS patient ≥35 years old (area under ROC curve=0.535, P=0.560) . However, the clinical pregnancy rate of the group of PCOS patient ≥35 years old was slightly higher than the control group (P=0.062) . Conclusions: AMH has no predictive value for the pregnancy outcome of PCOS patient. The pregnancy rate of PCOS patient ≥35 years old is slightly higher than the younger group, because the PCOS patient may have better ovarian reserve.

Multichannel wide-field microscopic FRET imaging based on simultaneous spectral unmixing of excitation and emission spectra.

Simultaneous spectral unmixing of excitation and emission spectra (ExEm unmixing) has inherent ability resolving spectral crosstalks, two key issues of quantitative fluorescence resonance energy transfer (FRET) measurement, of both the excitation and emission spectra between donor and acceptor without additional corrections. We here set up a filter-based multichannel wide-field microscope for ExEm unmixing-based FRET imaging (m-ExEm-spFRET) containing a constant system correction factor (fsc ) for a stable system. We performed m-ExEm-spFRET with four- and two-wavelength excitation respectively on our system to quantitatively image single living cells expressing FRET tandem constructs, and obtained accurate FRET efficiency (E) and concentration ratio of acceptor to donor (RC ). We also performed m-ExEm-spFRET imaging for single living cells coexpressing CFP-Bax and YFP-Bax, and found that the E values were about 0 for control cells and about 28% for staurosporin-treated cells when RC were larger than 1, indicating that staurosporin induced significant oligomerisation.

Phosphate steering by Flap Endonuclease 1 promotes 5'-flap specificity and incision to prevent genome instability.

DNA replication and repair enzyme Flap Endonuclease 1 (FEN1) is vital for genome integrity, and FEN1 mutations arise in multiple cancers. FEN1 precisely cleaves single-stranded (ss) 5'-flaps one nucleotide into duplex (ds) DNA. Yet, how FEN1 selects for but does not incise the ss 5'-flap was enigmatic. Here we combine crystallographic, biochemical and genetic analyses to show that two dsDNA binding sites set the 5'polarity and to reveal unexpected control of the DNA phosphodiester backbone by electrostatic interactions. Via 'phosphate steering', basic residues energetically steer an inverted ss 5'-flap through a gateway over FEN1's active site and shift dsDNA for catalysis. Mutations of these residues cause an 18,000-fold reduction in catalytic rate in vitro and large-scale trinucleotide (GAA)n repeat expansions in vivo, implying failed phosphate-steering promotes an unanticipated lagging-strand template-switch mechanism during replication. Thus, phosphate steering is an unappreciated FEN1 function that enforces 5'-flap specificity and catalysis, preventing genomic instability.

Corrigendum: Phosphate steering by Flap Endonuclease 1 promotes 5'-flap specificity and incision to prevent genome instability.

[This corrects the article DOI: 10.1038/ncomms15855.].