Experimental and Computational Approach to Studying Supramolecular Structures in Propanol and Its Halogen Derivatives.

A series of four alcohols, n-propanol and its halogen (Cl, Br, and I) derivatives, were selected to study the effects of variation in polarity and halogen-driven interactions on the hydrogen bonding pattern and supramolecular structure by means of experimental and theoretical methods. It was demonstrated on both grounds that the average strength of H-bonds remains the same but dissociation enthalpy, the size of molecular nanoassemblies, as well as long-range correlations between dipoles vary with the molecular weight of halogen atom. Further molecular dynamics simulations indicated that it is connected to the variation in the molecular order introduced by specific halogen-based hydrogen bonds and halogen-halogen interactions. Our results also provided important experimental evidence supporting the assumption of the transient chain model on the molecular origin of the structural process in self-assembling alcohols.

Predicting the Density-Scaling Exponent of a Glass-Forming Liquid from Complex Dielectric Permittivity Measurements.

One of the challenging problems related to the liquid-glass transition phenomenon is establishing a link between the character of intermolecular interactions and the behavior of molecular dynamics. Introducing the density scaling concept, according to which dynamic quantities, e.g., viscosity or structural relaxation time (τ_{α}) measured at different thermodynamic conditions are expressed as a single universal curve if plotted against ρ^{γ}/T, led to significant progress in solving this problem since the scaling exponent γ defines the steepness of the repulsive part of the intermolecular potential. Herein, we found that relaxation dynamics of van der Waals and H-bonding glass formers, for which the Kirkwood factor (g_{K}) is an isomorph-invariant quantity, satisfy an alternative scaling, logτ_{α} vs T(Δϵ_{s}T)^{-γ}. As a result, the exponent γ is determined from the temperature and pressure evolutions of τ_{α} and dielectric relaxation strength Δϵ-both obtained in a single dielectric experiment, which makes the γ coefficient to be accessed in the future for an extensive database of glass-forming liquids.

Self-Assembled Nanostructures in Aprotic Ionic Liquids Facilitate Charge Transport at Elevated Pressure.

Ionic liquids (ILs), revealing a tendency to form self-assembled nanostructures, have emerged as promising materials in various applications, especially in energy storage and conversion. Despite multiple reports discussing the effect of structural factors and external thermodynamic variables on ion organization in a liquid state, little is known about the charge-transport mechanism through the self-assembled nanostructures and how it changes at elevated pressure. To address these issues, we chose three amphiphilic ionic liquids containing the same tetra(alkyl)phosphonium cation and anions differing in size and shape, i.e., thiocyanate [SCN]-, dicyanamide [DCA]-, and tricyanomethanide [TCM]-. From ambient pressure dielectric and mechanical experiments, we found that charge transport of all three examined ILs is viscosity-controlled at high temperatures. On the other hand, ion diffusion is much faster than structural dynamics in a nanostructured supercooled liquid (at T < 210 ± 3 K), which constitutes the first example of conductivity independent from viscosity in neat aprotic ILs. High-pressure measurements and MD simulations reveal that the created nanostructures depend on the anion size and can be modified by compression. For small anions, increasing pressure shapes immobile alkyl chains into lamellar-type phases, leading to increased anisotropic diffusivity of anions through channels. Bulky anions drive the formation of interconnected phases with continuous 3D curvature, which render ion transport independent of pressure. This work offers insight into the design of high-density electrolytes with percolating conductive phases providing efficient ion flow.

Tailoring Phosphonium Ionic Liquids for a Liquid-Liquid Phase Transition.

The existence of more than one liquid state in a single-component system remains the most intriguing physical phenomenon. Herein, we explore the effect of cation self-assembly on ion dynamics in the vicinity of liquid-liquid and liquid-glass transition of tetraalkyl phosphonium ([Pmmm,n]+, m = 4, 6; n = 2-14) ionic liquids. We found that nonpolar local domains formed by 14-carbon alkyl chains are crucial in obtaining two supercooled states of different dynamics within a single ionic liquid. Although the nano-ordering, confirmed by Raman spectroscopy, still occurs for shorter alkyl chains (m = 6, n < 14), it does not bring calorimetric evidence of LLT. Instead, it results in peculiar behavior of ion dynamics near the liquid-glass transition and 20-times smaller size of the dynamic heterogeneity compared to imidazolium ionic liquids. These results represent a crucial step toward understanding the nature of the LLT phenomenon and offer insight into the design of efficient electrolytes based on ionic liquids revealing self-assembly behavior.

Detection of hypermethylated BCAT1 and IKZF1 DNA in blood and tissues of colorectal, breast and prostate cancer patients.

BACKGROUND: Detection of circulating cell-free DNA (ccfDNA) methylated in BCAT1 and IKZF1 is sensitive for detection of colorectal cancer (CRC), but it is not known if these biomarkers are present in other common adenocarcinomas. OBJECTIVE: Compare methylation levels of BCAT1 and IKZF1 in tissue and plasma from breast, prostate, and colorectal cancer patients. METHODS: Blood was collected from 290 CRC, 32 breast and 101 prostate cancer patients, and 606 cancer-free controls. Tumor and matched normal tissues were collected at surgery: 26 breast, 9 prostate and 15 CRC. DNA methylation in BCAT1 and IKZF1 was measured in blood and tissues. RESULTS: Either biomarker was detected in blood from 175/290 (60.3%) of CRC patients. The detection rate was higher than that measured in controls (48/606 (8.1%), OR = 18.2, 95%CI: 11.1-29.0). The test positivity rates in breast and prostate cancer patients were 9.4% (3/32) and 6.9% (7/101), respectively, and not significantly different to that measured in gender-matched controls (8.0% (33/382) females (OR = 0.84, 95%CI: 0.23-3.1) and 7.6% (26/318) males (OR = 0.86, 95%CI: 0.65-2.1). In tumor and non-neoplastic tissues, 93.5% (14/15) of CRC tumors were methylated in BCAT1 and/or IKZF1 (p< 0.004). Only 11.5% (3/26) and 44.4% (4/9) (p= 0.083) of breast and prostate tumors were hypermethylated in these two genes. CONCLUSIONS: Detection of circulating DNA methylated in BCAT1 and IKZF1 is sensitive and specific for CRC but not breast or prostate cancer.

Pressure-induced liquid-liquid transition in a family of ionic materials.

Liquid-liquid transition (LLT) between two disordered phases of single-component material remains one of the most intriguing physical phenomena. Here, we report a first-order LLT in a series of ionic liquids containing trihexyl(tetradecyl)phosphonium cation [P666,14]+ and anions of different sizes and shapes, providing an insight into the structure-property relationships governing LLT. In addition to calorimetric proof of LLT, we report that ion dynamics exhibit anomalous behavior during the LLT, i.e., the conductivity relaxation times (τσ) are dramatically elongated, and their distribution becomes broader. This peculiar behavior is induced by isobaric cooling and isothermal compression, with the τσ(TLL,PLL) constant for a given system. The latter observation proves that LLT, in analogy to liquid-glass transition, has an isochronal character. Finally, the magnitude of discontinuity in a specific volume at LLT was estimated using the Clausius-Clapeyron equation.

Complex Reorientation Dynamics of Sizable Glass-Formers with Polar Rotors Revealed by Dielectric Spectroscopy.

We present the results of dielectric measurements for three sizable glass-formers with identical nonpolar cores linked to various dipole-labeled rotors that shed new light on the picture of reorientation of anisotropic systems with significant moment of inertia revealed by broadband dielectric spectroscopy. The dynamics of sizable glass-formers formed by partially rigid molecular cores linked to small polar rotors in many respects differs from that of typical glass-formers. For instance, the extraordinarily large prefactors (τ0 > 10-12 s) in the Vogel-Fulcher-Tammann equation were found. The rich and highly diverse relaxation pattern was governed by the location of a dipole, its ability to rotate freely, and the degree of coupling to the motion of the entire sizable system.

Astaxanthin Alleviates Ochratoxin A-Induced Cecum Injury and Inflammation in Mice by Regulating the Diversity of Cecal Microbiota and TLR4/MyD88/NF-κB Signaling Pathway.

Ochratoxin A (OTA) is a common environmental pollutant found in a variety of foods and grains, and excessive OTA consumption causes serious global health effects on animals and humans. Astaxanthin (AST) is a natural carotenoid that has anti-inflammatory, antiapoptotic, immunomodulatory, antitumor, antidiabetes, and other biological activities. The present study is aimed at investigating the effects of AST on OTA-induced cecum injury and its mechanism of action. Eighty C57 mice were randomly divided into four groups, including the control group, OTA group (5 mg/kg body weight), AST group (100 mg/kg body weight), and AST intervention group (100 mg/kg body weight AST+5 mg/kg body weight OTA). It was found that AST decreased the endotoxin content, effectively prevented the shortening of mouse cecum villi, and increased the expression levels of tight junction (TJ) proteins, consisting of occludin, claudin-1, and zonula occludens-1 (ZO-1). AST increased the number of goblet cells, the contents of mucin-2 (MUC2), and defensins (Defa5 and ß-pD2) significantly, while the expression of mucin-1 (MUC1) decreased significantly. The 16S rRNA sequencing showed that AST affected the richness and diversity of cecum flora, decreased the proportion of lactobacillus, and also decreased the contents of short-chain fatty acids (SCFAs) (acetate and butyrate). In addition, AST significantly decreased the expression of TLR4, MyD88, and p-p65, while increasing the expression of p65. Meanwhile, the expression of inflammatory factors including TNF-α and INF-γ decreased, while the expression of IL-10 increased. In conclusion, AST reduced OTA-induced cecum injury by regulating the cecum barrier function and TLR4/MyD88/NF-κB signaling pathway.

Thorough studies of tricyanomethanide-based ionic liquids - the influence of alkyl chain length of the cation.

The glassy, supercooled, and normal liquid states of the 1-alkyl-3-methylimidazolium tricyanomethanide series [CnC1im][TCM] (n = 2, 4, 6, 8, and 16) were investigated by dielectric and mechanical (rheological) experiments supplemented by X-ray diffraction. The conductivity relaxation was found to be accompanied by a pronounced secondary relaxation. However, based on ambient and high-pressure results as well as the coupling model, we assumed that the latter one can not be classified as Johari-Goldstein relaxation. Moreover, the studies on the nanoscale organization of ionic liquids indicated that 1-alkyl-3-methylimidazolium tricyanomethanide ILs begin to form nanoscale aggregates when the alkyl chain of the cation has six carbon atoms.

The correlation between novel peripheral blood cell ratios and 90-day mortality in patients with acute ischemic stroke.

BACKGROUND: We aimed to investigate the correlation between the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR), platelet-to-white blood cell ratio (PWR) and 90-day mortality in patients with acute ischemic stroke (AIS). METHODS: We retrospectively included 633 patients with AIS from January 2017 to May 2018. The correlation between each indicator and the degree of neurologic deficit was assessed. Kaplan-Meier survival curves based on blood cell ratios were used to analyze the 90-day survival rate of patients with AIS. RESULTS: A total of 663 patients with AIS were enrolled, of which 24 (3.6%) experienced recurrence and 13 (2.0%) died. NLR>3.23 (odds ratio; OR = 2.236; 95% confidence interval [CI], 1.472-3.397; P<0.001), PNR<31.14 (OR = 0.471; 95% CI, 0.297-0.749; P = 0.001), and PWR<20.62 (OR = 0.498; 95% CI, 0.309-0.800; P = 0.004) were associated with an unfavorable 90-day prognosis. NLR>3.23, PWR<20.62, and PNR<31.14 were associated with an increased risk of 90-day mortality. CONCLUSION: PNR, PWR, and NLR were associated with the 90-day mortality of patients with AIS. Patients with high NLRs or low PWRs and PNRs may have a greater risk of mortality than other patients. These clinical indicators may help clinicians judge unfavorable prognosis early and implement the appropriate interventions.

Astaxanthin Protects Ochratoxin A-Induced Oxidative Stress and Apoptosis in the Heart via the Nrf2 Pathway.

This study assessed the protective mechanism of astaxanthin (ASX) against ochratoxin A- (OTA-) induced cardiac injury in mice. Four groups of mice were established: control group (0.1 mL olive oil + 0.1 mL NaHCO2), OTA group (0.1 mL OTA 5 mg/kg body weight), ASX group (0.1 mL ASX 100 mg/kg body weight), and ASX + OTA group (0.1 mL ASX 100 mg/kg body weight, 2 h later, 0.1 mL OTA 5 mg/kg body weight). The test period lasted for 27 days (7 days of dosing, 2 days of rest). Electrocardiogram, body weight, heart weight, tissue pathology, oxidative markers (malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH)), biochemical markers (creatine kinase (CK), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH)), electron microscopy, TUNEL, and Western blot tests were used to examine the effects of OTA on myocardial injury and ASX detoxification. The results showed that OTA exposure significantly decreased both body weight and heart weight. OTA induced a decrease in heart rate in mice and decreased tissue concentrations of SOD, CAT, and GSH, while increasing serum concentrations of cardiac enzymes (CK, CK-MB, and LDH) and tissue MDA. ASX improved heart rate, cardiac enzymes, and antioxidant levels in mice. The results of tissue pathology and TUNEL assay showed that ASX protects against OTA-induced myocardial injury. In addition, Western blot results showed that the OTA group upregulated Keap1, Bax, Caspase3, and Caspase9, while it downregulated Nrf2, HO-1, and Bcl-2 protein expression. ASX played a protective role by changing the expression of Keap1, Nrf2, HO-1, Bax, Bcl-2, Caspase3, and Caspase9 proteins. These results indicate that the protective mechanism of ASX on the myocardium works through the Keap1-Nrf2 signaling pathway and mitochondria-mediated apoptosis pathway. This study provides a molecular rationale for the mechanism underlying OTA-induced myocardial injury and the protective effect of ASX on the myocardium.

Pro-angiogenic activity of Tongnao decoction on HUVECs in vitro and zebrafish in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongnao Decoction (TND) is a Chinese decoction approved and used in Jiangsu Province Hospital for the treatment of ischemic stroke. It shows conclusive efficiency in the improvement of neurologic impairment and activities of daily living of the patients. AIM OF THE STUDY: Recently, angiogenesis has been recognized as a potential therapeutic strategy for treating cerebral ischemia. This study was aimed to provide comprehensive evidence for the pro-angiogenic effect of TND and characterize the underlying mechanism. MATERIALS AND METHODS: We firstly established the chemical fingerprinting of TND. Then, the in vitro pro-angiogenic activities of TND were tested on human umbilical vein endothelial cells (HUVECs) through cell viability, wound healing and tube formation assays. The in vivo pro-angiogenic effects were evaluated on transgenic zebrafish embryos [Tg (fli-1: EGFP)] through the formation of intersegmental vessels (ISVs), subintestinal vessels (SIVs) and central arteries (CtAs). Lastly, the potential mechanisms of TND were analyzed by a blocking assay with eight pathways-specific kinase inhibitors. RESULTS: TND promoted the proliferation, migration and tube formation of HUVECs. TND also rescued the impairment of ISVs, SIVs and CtAs caused by VRI in a dose-dependent manner in zebrafish embryos. TND could activate vascular endothelial growth factor receptor-2 (VEGFR-2), phosphoinositide 3-kinase (PI3K) - protein kinase B (Akt) and Raf - mitogen-activated protein kinase1/2 (MEK1/2) - extracellular regulated kinase 1/2 (ERK1/2) signaling pathways. CONCLUSION: Our study firstly demonstrated the pro-angiogenic activities of TND. Our work provided evidences for the clinical usage of TND in restoring neurovascular function through promoting angiogenesis in the ischemic cerebral microvascular.

Astaxanthin Protects OTA-Induced Lung Injury in Mice through the Nrf2/NF-κB Pathway.

The aim of this research was to evaluate the potential protective mechanism of astaxanthin (ASTA) against oxidative damage and inflammation caused by ochratoxin (OTA) in mouse lung. We divided mice into a control group (CG), an OTA group (PG), an astaxanthin group (AG), and an OTA+ASTA group (JG). Oxidative indices (malondialdehyde (MDA), total superoxide dismutase (T-SOD), and reduced glutathione (GSH)) and inflammatory markers (interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α)) were assayed in the lung, and the lung-weight-to-body-weight ratio was calculated. Apoptosis was detected in pathological sections by the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Oxidative damage and inflammation were detected in the lung of mice after exposure to OTA. Besides, Nrf2- and NF-κB-pathway-associated proteins were detected by Western blot. In contrast with OTA, ASTA significantly raised the expression of Nrf2, HO-1, and MnSOD, while the expression of other proteins (Keap1, TLR4, and NF-κB) was significantly decreased. These results indicate that ASTA exerted protective effects against OTA-induced oxidative damage and inflammation in the lung by regulating the Nrf2 and NF-κB pathways.

Fault Diagnosis from Raw Sensor Data Using Deep Neural Networks Considering Temporal Coherence.

Intelligent condition monitoring and fault diagnosis by analyzing the sensor data can assure the safety of machinery. Conventional fault diagnosis and classification methods usually implement pretreatments to decrease noise and extract some time domain or frequency domain features from raw time series sensor data. Then, some classifiers are utilized to make diagnosis. However, these conventional fault diagnosis approaches suffer from the expertise of feature selection and they do not consider the temporal coherence of time series data. This paper proposes a fault diagnosis model based on Deep Neural Networks (DNN). The model can directly recognize raw time series sensor data without feature selection and signal processing. It also takes advantage of the temporal coherence of the data. Firstly, raw time series training data collected by sensors are used to train the DNN until the cost function of DNN gets the minimal value; Secondly, test data are used to test the classification accuracy of the DNN on local time series data. Finally, fault diagnosis considering temporal coherence with former time series data is implemented. Experimental results show that the classification accuracy of bearing faults can get 100%. The proposed fault diagnosis approach is effective in recognizing the type of bearing faults.