Multimode Stimuli-Responsive Room-Temperature Phosphorescence Achieved by Doping Butterfly-like Fluorogens into Crystalline Small-Molecular Hosts.

Materials with stimuli-responsive purely organic room-temperature phosphorescence (RTP) exempt from exquisite molecular design and complex preparation are highly desirable but still relatively rare. Moreover, most of them work in a single switching mode. Herein, we employ a versatile host-guest-doped strategy to facilely construct efficient RTP systems with multimode stimuli-responsiveness without ingenious molecular design. By conveniently doping butterfly-like guests, namely, N,N'-diphenyl-dihydrodibenzo[a,c]phenazines (DPACs), featured with vibration-induced emission into the small-molecular hosts via various methods, RTP systems with finely tunable photophysical properties are readily obtained. Through systematic mechanistic studies and with the aid of a series of control experiments, we unveil the critical role of the host crystallinity in achieving efficient RTP. By virtue of the inherent environmental sensitivity of both RTP and fluorescence of the DPACs, our systems exhibit multiple-stimuli-responsiveness with the luminescence not only switching between the fluorescence and phosphorescence but also continuously changing in the fluorescence color. Advanced dynamic anticounterfeiting and multilevel information encryption is thereby realized.

Melanoma differentiation-associated protein 5 prevents cardiac hypertrophy via apoptosis signal-regulating kinase 1-c-Jun N-terminal kinase/p38 signaling.

Pathological cardiac hypertrophy (CH) is driven by maladaptive changes in myocardial cells in response to pressure overload or other stimuli. CH has been identified as a significant risk factor for the development of various cardiovascular diseases, ultimately resulting in heart failure. Melanoma differentiation-associated protein 5 (MDA5), encoded by interferon-induced with helicase C domain 1 (IFIH1), is a cytoplasmic sensor that primarily functions as a detector of double-stranded ribonucleic acid (dsRNA) viruses in innate immune responses; however, its role in CH pathogenesis remains unclear. Thus, the aim of this study was to examine the relationship between MDA5 and CH using cellular and animal models generated by stimulating neonatal rat cardiomyocytes with phenylephrine and by performing transverse aortic constriction on mice, respectively. MDA5 expression was upregulated in all models. MDA5 deficiency exacerbated myocardial pachynsis, fibrosis, and inflammation in vivo, whereas its overexpression hindered CH development in vitro. In terms of the underlying molecular mechanism, MDA5 inhibited CH development by promoting apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, thereby suppressing c-Jun N-terminal kinase/p38 signaling pathway activation. Rescue experiments using an ASK1 activation inhibitor confirmed that ASK1 phosphorylation was essential for MDA5-mediated cell death. Thus, MDA5 protects against CH and is a potential therapeutic target.

Modulating the Luminescence, Photosensitizing Properties, and Mitochondria-Targeting Ability of D-π-A-Structured Dihydrodibenzo[a,c]phenazines.

Herein, pyridinium and 4-vinylpyridinium groups are introduced into the VIE-active N,N'-disubstituted-dihydrodibenzo[a,c]phenazines (DPAC) framework to afford a series of D-π-A-structured dihydrodibenzo[a,c]phenazines in consideration of the aggregation-benefited performance of the DPAC module and the potential mitochondria-targeting capability of the resultant pyridinium-decorated DPACs (DPAC-PyPF6 and DPAC-D-PyPF6). To modulate the properties and elucidate the structure-property relationship, the corresponding pyridinyl/4-vinylpyridinyl-substituted DPACs, i.e., DPAC-Py and DPAC-D-Py, are designed and studied as controls. It is found that the strong intramolecular charge transfer (ICT) effect enables the effective separation of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of DPAC-PyPF6 and DPAC-D-PyPF6, which is conducive to the generation of ROS. By adjusting the electron-accepting group and the π-bridge, the excitation, absorption, luminescence, photosensitizing properties as well as the mitochondria-targeting ability can be finely tuned. Both DPAC-PyPF6 and DPAC-D-PyPF6 display large Stokes shifts (70-222 nm), solvent-dependent absorptions and emissions, aggregation-induced emission (AIE), red fluorescence in the aggregated state (λem = 600-650 nm), aggregation-promoted photosensitizing ability with the relative singlet-oxygen quantum yields higher than 1.10, and a mitochondria-targeting ability with the Pearson coefficients larger than 0.85. DPAC-D-PyPF6 shows absorption maximum at a longer wavelength, slightly redder fluorescence and better photosensitivity as compared to DPAC-PyPF6, which consequently leads to the higher photocytotoxicity under the irradiation of white light as a result of the larger π-conjugation.

MiR-134-5p Regulates Myocardial Apoptosis and Angiogenesis by Directly Targeting KDM2A After Myocardial Infarction.

MiR-134-5p was found to have potential diagnostic value for myocardial infarction (MI), but its biological role in MI has not been reported. In this study, MI mouse model was established. Quantitative real-time PCR (qRT-PCR) and western blot were used to measure the expression of miR-134-5p, lysine demethylase 2A (KDM2A), and vascular endothelial growth factor (VEGF). Dual-Luciferase reporter (DLR) assay was used to explore the relationship between miR-134-5p and KDM2A. The influence of miR-134-5p on cardiomyocytes apoptosis was detected using methyl thiazolyl tetrazolium (MTT) assay. The results revealed that miR-134-5p was highly expressed in infarction tissues of MI mice. Knockdown of miR-134-5p inhibited hypoxia/reoxygenation (H/R) -induced cardiomyocyte apoptosis. In addition, KDM2A was the target gene of miR-134-5p and negatively regulated by miR-134-5p. The promotion effect on the protein level of KDM2A and VEGF induced by miR-134-5p inhibitor can be reversed by shKDM2A in cardiomyocytes. Further, silencing of miR-134-5p promoted myocardial angiogenesis and inhibited myocardial apoptosis via upregulating KDM2A in MI mice. Taken together, our research revealed that knockdown of miR-134-5p increased KDM2A expression, thereby suppressing myocardial apoptosis and promoting myocardial angiogenesis.

Analyzing Complexity and Fractality of Glucose Dynamics in a Pregnant Woman with Type 2 Diabetes under Treatment.

Currently, the rapid development of continuous glucose monitoring (CGM) device brings new insights into the treatment of diabetic patients including those during pregnancy. Complexity and fractality have recently under fast development for extracting information embodied in glucose dynamics measured using CGM. Although scientists have investigated the difference of complexity in glucose dynamics between diabetes and non-diabetes in order to discover better approaches for diabetes care, no one has analyzed the complexity and fractality of glucose dynamics during the process of adopting CGM to successfully treat pregnant women with type 2 diabetes. Thus, we analyzed the complexity and fractality using power spectral density (PSD), multi-scale sample entropy (MSE) and multifractal detrended fluctuation analysis (MF-DFA) in a clinical case. Our results show that (i) there exists multifractal behavior in blood glucose dynamics; (ii) the alpha stable distribution fits to the glucose increment data better than the Gaussian distribution; and (iii) the "global" complexity indicated by multiscale entropy, spectrum exponent and Hurst exponent increase and the "local" complexity indicated by multifractal spectrum decrease after the successful therapy. Our results offer findings that may bring value to health care providers for managing glucose levels of pregnant women with type 2 diabetes as well as provide scientists a reference on applying complexity and fractality in the clinical practice of treating diabetes.

Dioscin Attenuates Myocardial Damages in Diabetic Rats maybe by Regulating NO-sGC-cGMP-PKG Pathway.

PURPOSE: The objective of this research was to explore the effect of dioscin on myocardium in streptozotocin (STZ)-induced diabetic rats and the underlying mechanisms. METHODS: Diabetic rat model was established by a single intravenous injection of streptozocin (STZ). The rats were divided into 5 groups: control group, control+dioscin group, model group (diabetes), DDL group (diabetic rats treated with 100 µg/kg/day dioscin) and DDH group (diabetic rats treated with 200 µg/kg/day dioscin). Each group was continuously intervened for 6 weeks. Hemodynamic parameters were detected and pathological alterations of myocardium were observed by hematoxylin-eosin (HE) staining. Inflammatory response and related proteins in the NO-sGC-cGMP-PKG pathway were detected by western blot. RESULTS: Dioscin treatment can increase ejection fraction (EF) and decrease left ventricular end-diastolic pressure (LVEDP) as well as time constant of left ventricular pressure decay (Tau) parameters in diabetic rats, suggesting the improvement of left ventricular function. By histopathology observation, we found that dioscin treatment can also improve myocardial histological lesions caused by diabetes. In addition, the levels of inflammatory cytokines TGF-ß1, TNF-α and IL-1ß of the model group were remarkably higher than those in the control group (p<0.01), while after being treated with dioscin these cytokines were obviously decreased (p<0.05). The levels of PDE-5, PKG and p-VASP in the diabetic rats were significantly declined after being treated by dioscin in a dose-dependent manner (p<0.05). CONCLUSION: Dioscin may prevent the myocardial injury in diabetic rats by up-regulating NO-sGC-cGMP-PKG pathway.

An Improved Method of Handling Missing Values in the Analysis of Sample Entropy for Continuous Monitoring of Physiological Signals.

Medical devices generate huge amounts of continuous time series data. However, missing values commonly found in these data can prevent us from directly using analytic methods such as sample entropy to reveal the information contained in these data. To minimize the influence of missing points on the calculation of sample entropy, we propose a new method to handle missing values in continuous time series data. We use both experimental and simulated datasets to compare the performance (in percentage error) of our proposed method with three currently used methods: skipping the missing values, linear interpolation, and bootstrapping. Unlike the methods that involve modifying the input data, our method modifies the calculation process. This keeps the data unchanged which is less intrusive to the structure of the data. The results demonstrate that our method has a consistent lower average percentage error than other three commonly used methods in multiple common physiological signals. For missing values in common physiological signal type, different data size and generating mechanism, our method can more accurately extract the information contained in continuously monitored data than traditional methods. So it may serve as an effective tool for handling missing values and may have broad utility in analyzing sample entropy for common physiological signals. This could help develop new tools for disease diagnosis and evaluation of treatment effects.

Demonstrating the Potential of Using Transcutaneous Oxygen and Carbon Dioxide Tensions to Assess the Risk of Pressure Injuries.

Pressure injuries have a high incidence in elderly and critically ill patients, and can endanger lives in severe cases. The key to reducing the incidence of pressure injuries is to find an objective, noninvasive, automatic and consistent scientific method for assessing pressure injuries. To serve this need, we conducted a clinical study to investigate the potential of using transcutaneous oxygen tension (TcPO2) and transcutaneous carbon dioxide tension (TcPCO2) for assessing pressure injuries. From the results of the study we found that first, the values of TcPO2 and TcPCO2 are sensitive to the change of pressure imposed on the measured region and to the risk status of a pressure injury when a pressure is imposed. Second, the magnitude of change in TcPO2 and TcPCO2 is higher in patients with a high risk of a pressure injury compared with those who have a low risk. Third, TcPO2 and TcPCO2 are both significantly correlated with the Braden score, the widely used score for assessing the risk of a pressure injury. Therefore, TcPO2 and TcPCO2 have a potential to be an effective and convenient scientific tool for assessing the risk of pressure injuries.

ANSYS-MATLAB co-simulation of mucus flow distribution and clearance effectiveness of a new simulated cough device.

Coughing is an irritable reaction that protects the respiratory system from infection and improves mucus clearance. However, for the patients who cannot cough autonomously, an assisted cough device is essential for mucus clearance. Considering the low efficiency of current assisted cough devices, a new simulated cough device based on the pneumatic system is proposed in this paper. Given the uncertainty of airflow rates necessary to clear mucus from airways, the computational fluid dynamics Eulerian wall film model and cough efficiency (CE) were used in this study to simulate the cough process and evaluate cough effectiveness. The Ansys-Matlab co-simulation model was set up and verified through experimental studies using Newtonian fluids. Next, model simulations were performed using non-Newtonian fluids, and peak cough flow (PCF) and PCF duration time were analyzed to determine their influence on mucus clearance. CE growth rate (λ) was calculated to reflect the CE variation trend. From the numerical simulation results, we find that CE rises as PCF increases while the growth rate trends to slow as PCF increases; when PCF changes from 60 to 360 L/min, CE changes from 3.2% to 51.5% which is approximately 16 times the initial value. Meanwhile, keeping a long PCF duration time could greatly improve CE under the same cough expired volume and PCF. The results indicated that increasing the PCF and PCF duration time can improve the efficiency of mucus clearance. This paper provides a new approach and a research direction for control strategy in simulated cough devices for airway mucus clearance.

CGManalyzer: an R package for analyzing continuous glucose monitoring studies.

Summary: The R package CGManalyzer contains functions for analyzing data from a continuous glucose monitoring (CGM) study. It covers a wide and comprehensive range of data analysis methods including reading a series of datasets, obtaining summary statistics of glucose levels, plotting data, transforming the time stamp format, fixing missing values, evaluating the mean of daily difference and continuous overlapping net glycemic action, calculating multiscale sample entropy, conducting pairwise comparison, displaying results using various plots including a new type of plot called an antenna plot, etc. This package has been developed from our work in directly analyzing data from various CGM devices such as the FreeStyle Libre, Glutalor, Dexcom and Medtronic CGM. Thus, this package should greatly facilitate the analysis of various CGM studies. Availability and implementation: The package for Windows is available from CRAN: http://cran.r-project.org/mirrors.html. The source file CGManalyzer_1.0.tar.gz is available in the Supplementary Material and at the website of Zhang's lab https://quantitativelab.fhs.umac.mo/analytic-tool/. Contact: douglaszhang@umac.mo. Supplementary information: Supplementary data are available at Bioinformatics online.

Detection of sputum by interpreting the time-frequency distribution of respiratory sound signal using image processing techniques.

Motivation: Sputum in the trachea is hard to expectorate and detect directly for the patients who are unconscious, especially those in Intensive Care Unit. Medical staff should always check the condition of sputum in the trachea. This is time-consuming and the necessary skills are difficult to acquire. Currently, there are few automatic approaches to serve as alternatives to this manual approach. Results: We develop an automatic approach to diagnose the condition of the sputum. Our approach utilizes a system involving a medical device and quantitative analytic methods. In this approach, the time-frequency distribution of respiratory sound signals, determined from the spectrum, is treated as an image. The sputum detection is performed by interpreting the patterns in the image through the procedure of preprocessing and feature extraction. In this study, 272 respiratory sound samples (145 sputum sound and 127 non-sputum sound samples) are collected from 12 patients. We apply the method of leave-one out cross-validation to the 12 patients to assess the performance of our approach. That is, out of the 12 patients, 11 are randomly selected and their sound samples are used to predict the sound samples in the remaining one patient. The results show that our automatic approach can classify the sputum condition at an accuracy rate of 83.5%. Availability and implementation: The matlab codes and examples of datasets explored in this work are available at Bioinformatics online. Contact: yesoyou@gmail.com or douglaszhang@umac.mo. Supplementary information: Supplementary data are available at Bioinformatics online.

miR-155 Promotes ox-LDL-Induced Autophagy in Human Umbilical Vein Endothelial Cells.

As an evolutionarily conserved metabolic process, autophagy is involved in the process of atherosclerosis (AS). MicroRNA-155 (miR-155), a multifunctional miRNA, plays an important role in many physiological and pathological conditions, including AS and autophagy. However, the effect of miR-155 on the regulation of autophagy in endothelial cells has not been reported to date. Therefore, the objective of our study was to investigate the role of miR-155 in autophagy induced by oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells (HUVECs). Our results demonstrated that ox-LDL induced autophagy in HUVECs and increased the expression of miR-155 significantly. Overexpression of miR-155 improved autophagic activity, whereas low expression of miR-155 inhibited autophagic activity. Therefore, the data demonstrated that miR-155 has a modulating effect on the autophagy of vascular endothelial cells.

[Determination of N-isopropylaniline in workplace air by high-performance liquid chromatography].

OBJECTIVE: To establish the method of high-performance liquid chromatography (HPLC) for the determination of N-isopropylaniline in workplace air. METHODS: N-isopropylaniline in the air was collected by silicone tube, and was then dissolved by acetonitrile and determined by HPLC-UV detector. RESULTS: There was a linear relationship within the range of 0.0-100.0 µg/ml with the method, and the regression equation was y=22 863x+10 665(r=0.999 9); the detection limit was 0.005 µg/ml, and the minimum detectable concentration was 1.7x10(-3) mg/m3 (3.0 L sampling volume); the average recoveries of standard addition were 96.2%-101.3%. The within-run precision was 2.31%-2.99%, and the between-run precision was 3.21%-4.55%. The average desorption efficiency was 97.6%, the breakthrough volume was more than 8.12 mg, the sampling efficiency waE 100%, and the samples could be stored for at least 7 days at room temperature. CONCLUSION: The indicators ol the method all meet the requirements of GBZ/T 210.4-2008 (Determination methods of air chemicals in workplace), and can be used for the determination of N-isopropylaniline in workplace air.

[Gas chromatography for determination of N-butylbenzene in workplace atmosphere].

OBJECTIVE: To establish a method for the determination of N-butylbenzene in the workplace atmosphere by gas chromatography. METHODS: N-butylbenzene in the workplace atmosphere was collected by activated charcoal tube, desorbed using carbon disulfide, and determined by capillary column gas chromatography. RESULTS: The method showed a linear relationship within the range of 0∼100 µg/ml. The regression equation was y = 0.870x-0.014, with the correlation coefficient r being 0.999 9. The limit of detection was 0.32 µg/ml. The minimum detectable concentration was 0.21 mg/m³ (with sampled air volume of 1.5 L). The average spike recovery rate was 97.8%∼102.6%. The within-run precision was 3.06% and the between-run precision was 3.64%. The rate of average desorption was 99.6%. The breakthrough volume was 6.34 mg. The sampling efficiency was 100%. The samples could be stored for at least 7 days at room temperature. CONCLUSION: All parameters of the method meet the requirements of GBZ/T 210.4-2008 "Guide for establishing occupational health standards-Part 4 Determination methods of air chemicals in workplace" and can be applied for the determination of N-butylbenzene in workplace atmosphere.

displayHTS: a R package for displaying data and results from high-throughput screening experiments.

The R package displayHTS implements recently developed methods and figures for displaying data and hit selection results in high-throughput screening (HTS) experiments. It generates not only certain useful distinctive graphics such as the plate-well series plot, plate image and dual-flashlight plot but also other commonly used figures such as volcano plot and plate correlation plot. These figures are critical for visualizing the data and displaying important features of HTS data and hit selection results.

Tris(1,10-phenanthroline-5,6-dione-κN,N')zinc bis-(perchlorate) acetonitrile monosolvate.

In the title compound, [Zn(C(12)H(6)N(2)O(2))(3)](ClO(4))(2)·CH(3)CN, the Zn(II) atom is coordinated by six N atoms from three chelating 1,10-phenanthroline-5,6-dione ligands in a distorted octa-hedral environment. In the crystal, inter-molecular C-H⋯O hydrogen bonds and O⋯π and N⋯π inter-actions [O⋯centroid distances = 2.907 (5) and 2.843 (7) Å; N⋯centroid distance = 2.861 (10) Å] link the complex cations, perchlorate anions and acetonitrile solvent mol-ecules into a three-dimensional network.

Bounds on the number of hidden neurons in three-layer binary neural networks.

This paper investigates an important problem concerning the complexity of three-layer binary neural networks (BNNs) with one hidden layer. The neuron in the studied BNNs employs a hard limiter activation function with only integer weights and an integer threshold. The studies are focused on implementations of arbitrary Boolean functions which map from [0, 1]n into [0, 1]. A deterministic algorithm called set covering algorithm (SCA) is proposed for the construction of a three-layer BNN to implement an arbitrary Boolean function. The SCA is based on a unit sphere covering (USC) of the Hamming space (HS) which is chosen in advance. It is proved that for the implementation of an arbitrary Boolean function of n-variables (n > or = 3) by using SCA, [3L/2] hidden neurons are necessary and sufficient, where L is the number of unit spheres contained in the chosen USC of the n-dimensional HS. It is shown that by using SCA, the number of hidden neurons required is much less than that by using a two-parallel hyperplane method. In order to indicate the potential ability of three-layer BNNs, a lower bound on the required number of hidden neurons which is derived by using the method of estimating the Vapnik-Chervonenkis (VC) dimension is also given.