Analyte-triggered in situ "off-on" of Tyndall effect for smartphone-based quantitative nanosensing of Ag+ ions.

This work describes two new colorimetric methods for smartphone-based point-of-care nanosensing of toxic Ag+ ions. They were based on the analyte-triggered in situ "off-on" of Tyndall effect (TE) of non-plasmonic colloid or plasmonic metal nanoprobes. The first TE-inspired assay (TEA) focused on the initial analytical application of precipitation reactions where a non-plasmonic AgCl colloid could be formed once mixing the analyte with a NaCl solution. Such AgCl colloid displayed strong visual TE signals after their irradiation by a laser pointer pen, which unexpectedly achieved a detection limit of ~ 400 nM. The second TEA was further designed to reduce the limit down to ~ 78 nM using the analyte's oxidizability towards 3,3',5,5'-tetramethylbenzidine molecules. The redox reaction could create positively charged products that could make negatively charged plasmonic gold nanoparticles aggregate through electrostatic interactions to remarkably amplify their TE responses. Both limits were lower than the minimum allowable Ag+ level (~ 460 nM) in drinking water issued by the World Health Organization. The satisfactory recovery results for detecting Ag+ ions in river, pond, tap, and drinking water additionally demonstrated good selectivity, accuracy and practicality of the proposed methods for potential point-of-need uses in environmental analysis, public health, water safety, etc.

Abnormal inter-ventricular diastolic mechanical delay in patients with ST-segment elevation myocardial infarction.

BACKGROUND: This study aimed to investigate the ventricular mechanical relaxation pattern and its clinical influence in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Echocardiography was performed to measure mitral and tricuspid diastolic opening times. Left ventricular diastolic mechanical delay (LVMDd) was defined as diastolic filling of the right ventricle earlier than that of the left ventricle, and right ventricular diastolic mechanical delay (RVMDd) was defined as the right ventricular diastolic filling later than left ventricular filling. RESULTS: Among 152 patients with STEMI, 100 (65.8%) had LVMDd, and 47 (30.9%) had RVMDd. In-hospital complications were significantly increased in patients with RVMDd (61.6% vs. 41.0%, P = 0.017). Those with RVMDd exhibited significantly lower left ventricular global longitudinal strain (11.7 ± 4.1% vs. 13.2 ± 4.0%, P = 0.035), global work index (913.8 ± 365.9 vs. 1098.9 ± 358.8 mmHg%, P = 0.005) and global constructive work (1218.6 ± 392.8 vs. 1393.7 ± 432.7 mmHg%, P = 0.021). Mitral deceleration time significantly decreased (127.4 ± 33.5 vs. 145.6 ± 41.7 ms, P = 0.012), and the ratio of early mitral inflow to early mitral annular velocity (E/E') significantly increased [13.0(11.0-20.0) vs. 11.9(9.3-14.3), P = 0.006] in the RVMDd group. Logistic regression analysis showed that age (odds ratio [OR]:0.920; P = 0.001), brain natriuretic peptide level (OR: 1.1002; P = 0.036) and mitral E/E' (OR: 1.187; P = 0.003) were independently associated with RVMDd. CONCLUSIONS: Delayed right ventricular filling is related to more severe left ventricular systolic and diastolic dysfunction in STEMI patients. More attention should be paid to patients with RVMDd to prevent adverse events during hospitalization.

Usefulness of echocardiographic myocardial work in evaluating the microvascular perfusion in STEMI patients after revascularization.

BACKGROUND: Left ventricular myocardial work (MW) assessed by echocardiography has recently been introduced as a new index of global and regional myocardial performance. The presence of microvascular obstruction after revascularization in ST-segment elevation myocardial infarction (STEMI) patients predicts poor clinical outcomes. This study aimed to explore the usefulness of MW in identifying impaired microvascular perfusion (MVP) in the patients with STEMI after revascularization. METHODS: One hundred and sixty STEMI patients who underwent myocardial contrast echocardiography (MCE) within 48 h after percutaneous coronary intervention (PCI) were included. Patients were divided into normal MVP and impaired MVP groups according to the myocardial perfusion score. The clinical data, coronary angiography results and echocardiographic data including Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were collected. RESULTS: Impaired MVP was found in 60% of patients. Compared with the normal MVP group, GWI (909.2 ± 287.6 mmHg% vs. 1191.2 ± 378.2 mmHg%), GCW (1198.3 ± 339.6 mmHg% vs. 1525.9 ± 420.5 mmHg%), GWE (82.7 ± 7.8% vs. 86.8 ± 5.6%) and GLS (- 11.0 ± 3.4% vs. - 14.4 ± 3.8%) were significantly reduced in the impaired MVP group. Whereas there was no statistically significant difference in left ventricular ejection fraction (LVEF) and GWW, multivariate logistic regression analysis showed that peak troponin I (OR 1.017, 95% CI 1.006-1.029; P = 0.004), final TIMI flow ≤ 2 (OR 16.366, 95% CI 1.998-134.06; P = 0.009), left ventricular end-diastolic volume index (LVEDVi) (OR 1.139 95% CI 1.048-1.239; P = 0.002), and GWI (OR 0.997 95% CI 0.994-1.000; P = 0.029) were independently associated with impaired MVP. GWI showed a good sensitivity (86.8%) but low specificity (53.7%) in identifying impaired MVP (AUC 0.712, 95% CI 0.620-0.804; P < 0.001). Combination with GWI can improve the diagnostic value of TNI or LVEVi for impaired MVP. CONCLUSION: Impaired MVP is relatively common in STEMI patients after revascularization and independently associated with left ventricular GWI assessed by echocardiography. GWI confer incremental value to MVP assessment in STEMI patients.

Coronary microcirculation dysfunction evaluated by myocardial contrast echocardiography predicts poor prognosis in patients with ST-segment elevation myocardial infarction after percutaneous coronary intervention.

BACKGROUND: The mortality rate of acute ST-segment elevation myocardial infarction (STEMI) remains substantial, despite advances in treatment strategies. Coronary microcirculation dysfunction (CMD) persists after percutaneous coronary intervention (PCI) in a substantial proportion of STEMI patients. The association between CMD assessed using myocardial contrast echocardiography (MCE) and prognosis requires further elucidation. This study aimed to evaluate the impact of CMD after successful PCI on the prognosis of patients with STEMI. METHODS: We enrolled 167 patients with STEMI after PCI who underwent MCE during hospitalization between January 2018 and March 2022. Patients were classified into the CMD and non-CMD groups according to the results of MCE. The clinical data and MCE results of both groups were analyzed. Follow-up was conducted for major adverse cardiac events. RESULTS: MCE detected CMD in 105 patients (62.9%). The CMD group contained fewer hypertensive patients (55.2% versus 74.2%, P = 0.015). Patients with CMD exhibited significantly higher levels of plasma troponin I (TnI) [73.2 (23.0-124.0) versus 28.9 (12.7-80.2) ng/mL, P = 0.004], higher levels of plasma B-type natriuretic peptide [255 (99-641) versus 193 (59-389) pg/mL, P = 0.004], poorer Killip classification (P = 0.038), and different culprit vessels (P < 0.001) compared to the non-CMD group. Patients with CMD exhibited lower left ventricular ejection fraction [50 (43-58) versus 61 (54-67) %, P < 0.001], poorer wall motion score index values (1.68 ± 0.4 versus 1.31 ± 0.26, P < 0.001) and poorer left ventricular global longitudinal strain [-11.2 (-8.7 to -14.1) versus -13.9 (-11.0 to -17.2) %, P < 0.001] compared to the non-CMD group. Patients underwent follow-up for 13 (7-20) months. After adjusting for hypertension, peak TnI level, culprit vessel, and Killip classification, CMD was an independent predictor of total major adverse cardiac events at 13 months' follow-up [adjusted odds ratio (OR), 2.457; 95% confidence interval (CI), 1.042-5.790; P = 0.040], and patients with CMD had a higher risk of hospitalization for heart failure (adjusted OR, 5.184; 95% CI, 1.044-25.747; P = 0.044) and repeat myocardial infarction (adjusted OR, 2.896; 95% CI, 1.109-7.565; P = 0.030). CONCLUSIONS: MCE is a safe and effective method for detecting CMD in patients with STEMI. CMD detected by MCE after successful PCI in patients with STEMI is a common occurrence, which is associated with a significantly worse prognosis, especially hospitalization for heart failure and repeat myocardial infarction.

Echocardiographic left ventricular hypertrophy and geometry in Chinese chronic hemodialysis patients: the prevalence and determinants.

BACKGROUND: To investigate the prevalence of left ventricular hypertrophy (LVH) and explore left ventricular geometry in maintenance hemodialysis (MHD) patients, and to explore the risk factors of LVH which is an important predictor of cardiovascular events. METHODS: The subjects were patients who are on MHD for more than 3 months in Peking University People's Hospital from March 2015 to February 2017. Demographic and clinical data were retrospectively collected. Left ventricular mass was measured by echocardiography. LVH is defined by Left ventricular mass index (LVMI) > 115 g/m2 for men and > 95 g/m2 in women. LVMI and relative wall thickness were used to determine left ventricular geometry. Logistic regression was used to analyze the risk factors of LVH. RESULTS: Altogether, 131 patients including 77 males were enrolled. The median age was 60 (47, 69) years, with a median dialysis vintage of 48 (18, 104) months. There were 80 patients with LVH, the prevalence rate was 61.1%, and 66.3% of them were moderate to severe LVH. We found that (1) most of the patients were concentric hypertrophy; (2) one-third of the patients were concentric remodeling; (3) only 4 cases with normal geometry. The pre-dialysis serum sodium level and time average pre-dialysis systolic blood pressure (SBP) were independent risk factors of LVH. CONCLUSION: LVH is prevalent in MHD patients. Concentric hypertrophy and concentric remodeling are the most common geometric patterns. Attention should be paid to long-term pre-dialysis SBP management and pre-dialysis sodium control as they might be potentially modifiable risk factors for LVH.

Left ventricular function and coronary microcirculation in patients with mild reduced ejection fraction after STEMI.

BACKGROUND: The characteristics of heart failure (HF) with mildly reduced ejection fraction (EF) (HFmrEF) overlap with those of HF with reduced EF (HFrEF) and HF with preserved EF (HFpEF) and need to be further explored. This study aimed to evaluate left ventricular (LV) function and coronary microcirculation in patients with mildly reduced ejection fraction after acute ST-segment elevation myocardial infarction (STEMI). METHODS: We enrolled 119 patients with STEMI who had undergone speckle tracking imaging and myocardial contrast echocardiography during hospitalization from June 2016 to June 2021. They were classified into normal, HFmrEF, and HFrEF groups according to their left ventricular EF (LVEF): ≥ 50%, 40-50%, and ≤ 40%, respectively. The data of the HFmrEF group were analyzed and compared with those of the normal and HFrEF groups. RESULTS: HFmrEF was observed in 32 patients (26.9%), HFrEF in 17 (14.3%), and normal LVEF in 70 patients (58.8%). The mean global longitudinal strain (GLS) of all patients was - 11.9 ± 3.8%. The GLS of HFmrEF patients was not significantly different from that of the HFrEF group (- 9.9 ± 2.5% and - 8.0 ± 2.3%, respectively, P = 0.052), but they were both lower than that of the normal group (- 13.8% ± 3.5%, P < 0.001). The HFmrEF group exhibited significantly poorer myocardial perfusion index (1.24 ± 0.33) than the normal group (1.08 ± 0.14, P = 0.005) but displayed no significant difference from the HFrEF group (1.18 ± 0.19, P = 0.486). Moreover, a significant difference in the incidence of regional wall motion (WM) abnormalities in the three groups was observed (P = 0.009), and the WM score index of patients with HFmrEF was 1.76 ± 0.30, similar to that of patients with HFrEF (1.81 ± 0.43, P = 0.618), but poorer than that in the normal group (1.33 ± 0.25, P < 0.001). CONCLUSIONS: GLS is a more sensitive tool than LVEF for detecting LV systolic dysfunction. The LV systolic function, coronary microcirculation, and WM in patients with HFmrEF was poorer than that of patients with normal LVEF, but comparable to that in patients with HFrEF. Patients with HFmrEF after STEMI require more attention and appropriate management.

Transforming glucose into fluorescent graphene quantum dots via microwave radiation for sensitive detection of Al3+ ions based on aggregation-induced enhanced emission.

This paper initially describes a nanosensor for fluorescence detection of Al3+ ions by using graphene quantum dots (GQDs) that are synthesized via microwave-assisted single-step ring-closure condensation of glucose molecules. The one-pot synthesis strategy based on the microwave radiation could be finished in several minutes and no post-modification of the GQDs was required. In particular, the GQD nanoprobes showed a sensitive and specific fluorescence enhancement response to Al3+. The involved mechanism might be the Al3+-mediated aggregation of the GQDs leading to aggregation-induced enhanced emission (AIEE). Under optimal conditions, this new fluorescent nanosensor was able to quantitatively detect Al3+ in a linear concentration range of 0.4-500 µM. The limit of detection was estimated to be ∼59.8 nM according to the 3σ rule, which made it be among the most sensitive systems currently available for sensing the target ion. Moreover, satisfactory recovery results (ranging from 96.8 to 109.7%) of analyzing a set of real water examples additionally validated its accuracy for practical applications. Considering its simplicity, high sensitivity and specificity, low cost, and good reliability, the developed fluorescent nanosensing system for Al3+ holds great promise for broad uses in water safety, environmental monitoring, and waste management.

Fluorescent kinetics combined with fourth-order calibration for the determination of diclofenac sodium in environmental water.

A method that combines five-way fluorescence kinetics with fourth-order calibration for interference-free quantification of diclofenac sodium in river water was proposed and tested. Traditional fluorescence methods may not be suitable for such measurements since the fluorescence properties of the analyte are highly dependent on both pH and irradiation time in situ. In the method considered here, a five-way emission-excitation-time-pH data array was obtained from the samples by introducing the pH level and irradiation time as two extra modes. Then the data array was resolved by three fourth-order calibration algorithms: alternating fitting weighted residue quinquelinear decomposition (AFWRQQLD), five-way parallel factor analysis (five-PARAFAC), and alternating quinquelinear decomposition (AQQLD). The average recoveries and detection limits calculated for diclofenac sodium in a set of analyte-spiked river water samples using AFWRQQLD, five-PARAFAC, and AQQLD were 97.2 ± 3.2% and 1.9 ng mL-1, 96.8 ± 3.0% and 4.0 ng mL-1, and 92.6 ± 2.7% and 2.5 ng mL-1, respectively. A study of other figures of merit, statistical analysis, an elliptical joint confidence region test, and a t-test were additionally carried out to validate the analytical performance of the proposed method in detail. The results demonstrated that this new method required only two steps (fluorescence measurement and algorithm analysis) to determine the analyte concentration. It could therefore provide the basis for developing novel reliable and sensitive approaches for the accurate detection of pharmaceutical pollutants with unstable fluorescence properties in real complex matrices such as environmental water samples. Graphical Abstract ᅟ.

[Protein interacting with kinase Cα mediates the down-regulation of myocardial norepinephrine transporter expression in mice with adriamycin-induced congestive heart failure].

OBJECTIVE: To investigate the interaction between myocardial norepinephrine (NET) and protein interacting with kinase Cα (PICK1), and examine the myocardial expression pattern of NET and PICK1 in mice with adriamycin-induced congestive heart failure. METHODS: (1) Cellular experiments: 293T cells were transfected with NET, GFP-PICK1, NET+GFP-PICK1 or NET+GFP-PICK1(KD-AA), respectively. Immunofluorescence staining was performed 48 h after the transfection. (2) Animal experiments: 40 male C57BL/6J mice were divided into control group and adriamycin group (intraperitoneal injection of 2 mg/kg adriamycin with a cumulative amount of 22 mg/kg). The myocardial mRNA and protein expression level of NET, PICK1 and adrenergic receptor (ß1-AR) were detected by real-time PCR and Western blot after 10 weeks. RESULTS: (1) PICK1 mediates the intracellular trafficking of NET. (2) Compared to controls, cardiac mRNA expression of NET remained unchanged, but PICK1 and ß1-AR mRNA level were significantly reduced in the heart failure mice. (3) Myocardial NET protein expression level was significantly reduced, whereas tyrosine hydroxylase (TH) protein expression was significantly upregulated in heart failure mice. (4) The myocardial density of sympathetic nerve fibers remained unchanged in heart failure mice. CONCLUSIONS: Cardiac expression of NET and PICK1 are down-regulated in heart failure mice. Reduced PICK1-mediated intracellular trafficking of NET may be involved in the impairment of NET function in this congestive heart failure mice model.

Variables associated with pulmonary hypertension screened by echocardiography in chronic myeloid leukemia patients on dasatinib therapy.

Background: Pulmonary hypertension (PH) is a rare but life-threatening adverse event (AE) of dasatinib, but the associated variables are not clear. This study aimed to explore the variables associated with PH by echocardiography in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving dasatinib therapy. Methods: Echocardiography was performed to estimate the probability of PH and pulmonary artery systolic pressure (PASP). Binary logistic analysis and Fine-Gray hazard model were used to identify the variables associated with PH by using cross-sectional and longitudinal data. Results: Among the 243 patients in the cross-sectional dataset, with a median dasatinib therapy duration of 27 months, 30 (12.3%) were classified as having a high probability of PH. Increasing age (OR = 1.7, p = 0.002; OR = 1.5, p = 0.003) and pericardial effusion (OR = 4.3, p = 0.004; OR = 3.2, p = 0.014) were significantly associated with a high probability of PH and PASP ≥ 40 mmHg, respectively. Among the 161 patients in the longitudinal dataset, the 3-year cumulative incidences of a high probability of PH and PASP ≥ 40 mmHg were 9.3% and 22.1%, respectively. Pericardial effusion (HR = 3.8, p = 0.005) and cardiopulmonary comorbidities (HR = 3.2, p = 0.021) were significantly associated with a high probability of PH; increasing age (HR = 1.5, p < 0.001) and dasatinib as ≥ 3rd-line therapy (p = 0.032; 2nd-line vs. 1st-line, HR = 2.0, p = 0.200; ≥ 3rd-line vs. 1st-line, HR = 3.4, p = 0.047) were significantly associated with PASP ≥ 40 mmHg. Conclusion: Increasing age, pericardial effusion, cardiopulmonary comorbidities, and dasatinib as ≥ 3rd-line TKI therapy were associated with PH in the patients with CML-CP on dasatinib therapy.

Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes.

Protein interacting with c kinase 1 (PICK1) regulates the trafficking of receptors and ion-channels such as AMPA receptors. Traditionally, the PICK1 PDZ domain is regarded as an adaptor capable of binding to receptors trafficked by PICK1, and the lipid-binding BAR domain functions to tether PICK1 directly to membranes. Here, we show that the PICK1 PDZ domain can directly interact with lipid membranes. The PDZ domain and lipid membrane interaction is mediated by both a polybasic amino-acid cluster and a conserved 'Cys-Pro-Cys' motif located away from the peptide ligand-binding groove. Disruption of the PDZ and lipid membrane interaction totally abolished synaptic targeting of PICK1. Although mutation of the CPC motif did not affect the interaction between PICK1 and AMPA receptors, the mutant PICK1 was unable to cluster the GluR2 subunit of the receptor. In neurons, PICK1 containing the same mutation displayed dramatically compromised capacity in the trafficking of AMPA receptors. Taken together, our findings not only uncovered the novel lipid membrane-binding property of the PICK1 PDZ domain, but also provided direct evidence supporting the functional relevance of the PDZ-lipid interaction.

Ultrasensitive visual detection of Hg2+ ions via the Tyndall effect of gold nanoparticles.

This work reports a new methodology for naked-eye nanosensing of Hg2+ where the Tyndall effect of gold nanoparticles (GNPs) acts as a light scattering signalling readout. Its utility is demonstrated with ultrasensitive detection of the target with a limit down to 0.13 nM (∼5461-fold sensitivity improvement over conventional GNP-based methods with surface plasmon resonance signalling).

A Comparative Study of Systolic and Diastolic Mechanical Synchrony in Canine, Primate, and Healthy and Failing Human Hearts.

Aim: Mechanical dyssynchrony (MD) is associated with heart failure (HF) and may be prognostically important in cardiac resynchronization therapy (CRT). Yet, little is known about its patterns in healthy or diseased hearts. We here investigate and compare systolic and diastolic MD in both right (RV) and left ventricles (LV) of canine, primate and healthy and failing human hearts. Methods and Results: RV and LV mechanical function were examined by pulse-wave Doppler in 15 beagle dogs, 59 rhesus monkeys, 100 healthy human subjects and 39 heart failure (HF) patients. This measured RV and LV pre-ejection periods (RVPEP and LVPEP) and diastolic opening times (Q-TVE and Q-MVE). The occurrence of right (RVMDs) and left ventricular systolic mechanical delay (LVMDs) was assessed by comparing RVPEP and LVPEP values. That of right (RVMDd) and left ventricular diastolic mechanical delay (LVMDd) was assessed from the corresponding diastolic opening times (Q-TVE and Q-MVE). These situations were quantified by values of interventricular systolic (IVMDs) and diastolic mechanical delays (IVMDd), represented as positive if the relevant RV mechanical events preceded those in the LV. Healthy hearts in all species examined showed greater LV than RV delay times and therefore positive IVMDs and IVMDd. In contrast a greater proportion of the HF patients showed both markedly increased IVMDs and negative IVMDd, with diastolic mechanical asynchrony negatively correlated with LVEF. Conclusion: The present IVMDs and IVMDd findings have potential clinical implications particularly for personalized setting of parameter values in CRT in individual patients to achieve effective treatment of HF.

Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depression.

Cerebellar long-term depression (LTD) is a major form of synaptic plasticity that is thought to be critical for certain types of motor learning. Phosphorylation of the AMPA receptor subunit GluR2 on serine-880 as well as interaction of GluR2 with PICK1 have been suggested to contribute to the endocytic removal of postsynaptic AMPA receptors during LTD. Here, we show that targeted mutation of PICK1, the GluR2 C-terminal PDZ ligand, or the GluR2 PKC phosphorylation site eliminates cerebellar LTD in mice. LTD can be rescued in cerebellar cultures from mice lacking PICK1 by transfection of wild-type PICK1 but not by a PDZ mutant or a BAR domain mutant deficient in lipid binding, indicating the importance of these domains in PICK1 function. These results demonstrate that PICK1-GluR2 PDZ-based interactions and GluR2 phosphorylation are required for LTD expression in the cerebellum.

oxHDL decreases the expression of CD36 on human macrophages through PPARgamma and p38 MAP kinase dependent mechanisms.

CD36, belongs to class B scavenger receptor family, is a macrophage receptor for oxidized low-density lipoprotein (oxLDL) and has been proven to play a critical role in atherosclerotic foam cell formation. In addition, CD36 expression is regulated by many factors including oxLDL and HDL. A recent study suggests that CD36 can also bind with oxidized high-density lipoprotein (oxHDL). However, the direct role of oxHDL in atherosclerosis is still not clear and it is not known whether oxHDL has any influence on the expression of CD36 in macrophages. Here, we performed experiments to investigate the effect of oxHDL on the expression of CD36 on human peripheral blood monocytes-macrophages and the possible mechanisms. Our results suggest that the uptake of oxHDL by CD36 on macrophages accelerates foam cell formation. In addition, oxHDL can down-regulate both the mRNA and surface protein expression of CD36 on human peripheral macrophages in vitro. oxHDL increased the mRNA expression and protein phosphorylation of peroxisome proliferators-activated receptor-gamma (PPARgamma). Using different mitogen-activated protein kinase (MAPK) inhibitors, we demonstrated that oxHDL regulated CD36 and PPARgamma expression in a p38-MAP kinase dependent mechanism.

[Simvastatin suppress lipopolysaccharides induced upregulation of lipoprotein associated phospholipase A(2) expression in macrophages via inactivation of p38MAPK pathway].

OBJECTIVE: To investigate the effects of simvastatin on lipopolysaccharides (LPS) induced upregulation of Lp-PLA(2) in human peripheral blood monocytes-macrophages and the related mechanisms. METHODS: Peripheral blood monocytes of healthy volunteer were isolated and incubated for 2-3 days. Monocytes were incubated with various concentrations of LPS for 6 h or with 1 µg/ml of LPS for different times in LPS group. In simvastatin group and MAPK inhibitors groups, cells were pre-treated with simvastatin (10(-2) - 10(-7) mmol/L) or various MAPK inhibitors (10 µmol/L SB203580, 20 µmol/L U0126, and 20 µmol/L SP600125) before LPS co-incubation. Lp-PLA(2) activity was measured by chronometry, Lp-PLA(2) mRNA expression was detected by RT-PCR. Protein expressions of Lp-PLA(2) and p38MAPK and phosphorylated p38MAPK were examined by Western blot. RESULTS: (1) LPS significantly upregulated Lp-PLA(2) mRNA and protein expression, as well as the enzyme activity in a time and concentration dependent manner, which could be significantly attenuated by simvastatin in a time and concentration dependent manner. (2) Simvastatin significantly reduced LPS-induced p38MAPK phosphorylation. The p38 MAPK inhibitor SB203580, but not MEK1/2 inhibitor U0126 and JNK inhibitor SP600125, completely prevented LPS-mediated up-regulation of Lp-PLA(2) at protein level. CONCLUSION: This study demonstrated that LPS significantly upregulated Lp-PLA(2) mRNA and protein expression, as well as the enzyme activity in a time and concentration dependent manner via Rho-p38MAPK pathway, which could be significantly suppressed by simvastatin.

Low Transvalvular Flow Rate Predicts Mortality in Patients With Low-Gradient Aortic Stenosis Following Aortic Valve Intervention.

OBJECTIVES: This study aimed to assess the value of low transvalvular flow rate (FR) for the prediction of mortality compared with low stroke volume index (SVi) in patients with low-gradient (mean gradient: <40 mm Hg), low aortic valve area (<1 cm2) aortic stenosis (AS) following aortic valve intervention. BACKGROUND: Transaortic FR defined as stroke volume/left ventricular ejection time is also a marker of flow; however, no data exist comparing the relative prognostic value of these 2 transvalvular flow markers in patients with low-gradient AS who had undergone valve intervention. METHODS: We retrospectively followed prospectively assessed consecutive patients with low-gradient, low aortic valve area AS who underwent aortic valve intervention between 2010 and 2014 for all-cause mortality. RESULTS: Of the 218 patients with mean age 75 ± 12 years, 102 (46.8%) had low stroke volume index (SVi) (<35 ml/m2), 95 (43.6%) had low FR (<200 ml/s), and 58 (26.6%) had low left ventricular ejection fraction <50%. The concordance between FR and SVi was 78.8% (p < 0.005). Over a median follow-up of 46.8 ± 21 months, 52 (23.9%) deaths occurred. Patients with low FR had significantly worse outcome compared with those with normal FR (p < 0.005). In patients with low SVi, a low FR conferred a worse outcome than a normal FR (p = 0.005), but FR status did not discriminate outcome in patients with normal SVi. By contrast, SVi did not discriminate survival either in patients with normal or low FR. Low FR was an independent predictor of mortality (p = 0.013) after adjusting for age, clinical prognostic factors, European System for Cardiac Operative Risk Evaluation II, dimensionless velocity index, left ventricular mass index, left ventricular ejection fraction, heart rate, time, type of aortic valve intervention, and SVi (p = 0.59). CONCLUSIONS: In patients with low-gradient, low valve area aortic stenosis undergoing aortic valve intervention, low FR, not low SVi, was an independent predictor of medium-term mortality.

Lipid binding regulates synaptic targeting of PICK1, AMPA receptor trafficking, and synaptic plasticity.

The targeting and surface expression of membrane proteins are critical to their functions. In neurons, synaptic targeting and surface expression of AMPA-type glutamate receptors were found to be critical for synaptic plasticity such as long-term potentiation and long-term depression (LTD). PICK1 (protein interacting with C kinase 1) is a cytosolic protein that interacts with many membrane proteins, including AMPA receptors via its PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain. Its interactions with membrane proteins regulate their subcellular targeting and surface expression. However, the mechanism by which PICK1 regulates protein trafficking has not been fully elucidated. Here, we show that PICK1 directly binds to lipids, mainly phosphoinositides, via its BAR (Bin/amphiphysin/Rvs) domain. Lipid binding of the PICK1 BAR domain is positively regulated by its PDZ domain and negatively regulated by its C-terminal acidic domain. Mutation of critical residues of the PICK1 BAR domain eliminates its lipid-binding capability. Lipid binding of PICK1 controls the subcellular localization of the protein, because BAR domain mutant of PICK1 has diminished synaptic targeting compared with wild-type PICK1. In addition, the BAR domain mutant of PICK1 does not cluster AMPA receptors. Moreover, wild-type PICK1 enhances synaptic targeting of AMPA receptors, whereas the BAR domain mutant of PICK1 fails to do so. The BAR domain mutant of PICK1 loses its ability to regulate surface expression of the AMPA receptors and impairs expression of LTD in hippocampal neurons. Together, our findings indicate that the lipid binding of the PICK1 BAR domain is important for its synaptic targeting, AMPA receptor trafficking, and synaptic plasticity.

[Identification of rhizoma atractylodes based on FTIR spectra and radial basis function network].

In order to recognize the atractylodes macrocephala Koidz. (rhizoma atractylodes) and its confusable varieties, three kinds of models of radial basis function network(RBF), nonlinear-linear, linear-linear, and nonlinear-nonlinear model, were used combined with their Fourier transform infrared spectra (FTIR). Rhizoma atractylodes models were collected by Fourier transform infrared spectra, 36 samples were gathered as a training target, and 27 samples as a test set, then their supervision training was performed using three models each. When the summation of error square of the training target was selected as 0. 01, the correct rate for recognition of Fourier transform infrared spectra using each RBF was 100% for the training set, but was different for the test set, which depended on the number of mode in hidden layer, S1. It was found that with the increase of S1, the correct rate would decrease oppositely. This may be caused by the high degree of the nonlinearity of the networks, so that the models of networks were not fit for the training of this kind of sample set. When using linear-linear model of RBF, the correct rate varied with S1 to some extent, but was generally about 85%. Recognizing ability obtained using nonlinear-linear model of RBF was the best. Its correct rate of recognition was >97%. When S1 =3, and so this method can be used to recognize atractylodes macrocephala Koidz. (rhizoma atractylodes) and its confusable varieties simply, rapidlly and accurately.