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Negative feelings caused by external stress can continually agonize adrenergic receptors via promoting catecholamine secretion, causing cardiovascular disease. This study examines the mechanism by which persistent β-adrenergic receptor agonism induces myocardial injury. A rat model of cardiac injury was herein established using isoproterenol (5 mg/kg, continuous intraperitoneal injection for 3 days), and multiomics technology combined with metabolomics and proteomics was used to explore the mechanism by which persistent β-adrenergic receptor agonism induces myocardial injury. The mechanism underlying this phenomenon was further verified at the cellular level. Isoproterenol-induced persistent β-adrenergic receptor agonism promoted the release of reactive oxygen species, and P53, S100-A9, and complement 3 were shown to be involved in complement system activation pathways. Our data have demonstrated that isoproterenol could trigger ROS/P53/S100-A9 positive feedback to aggravate myocardial damage associated with complement activation.

Unstable angina (UA) is a coronary disease with a high mortality and morbidity worldwide. The present study aimed to use non-invasive techniques to identify urine biomarkers in patients with UA, so as to provide more information for the early diagnosis and treatment of the disease. Based on metabolomics, urine samples from 28 patients with UA and 28 healthy controls (HCs) were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A total of 16 significant biomarkers that could distinguish between patients with UA and HCs, including D-glucuronic acid, creatinine, succinic acid and N-acetylneuraminic acid, were identified. The major metabolic pathways associated with UA were subsequently analyzed by non-targeted metabolomics. The results demonstrated that amino acid and energy metabolism, fatty acid metabolism, purine metabolism and steroid hormone biosynthetic metabolism may serve important roles in UA. The results of the current study may provide a theoretical basis for the early diagnosis of UA and novel treatment strategies for clinicians. The trial was registered with the Chinese Clinical Trial Registration Center (registration no. ChiCTR-ROC-17013957) at Tianjin University of Traditional Chinese Medicine.

Background As a recognized risk factor for cardiovascular disease (CVD), hyperlipidemia (HLP) has developed into a high incidence disease that seriously threatens human health. Finding a new target for effective treatment of HLP will be a powerful way to reduce the incidence of CVD. The purpose of this study was to find potential biomarkers in urine of HLP patients and analyze their metabolic pathways to study the pathogenesis of HLP. Methods An UPLC-Q-TOF/MS technology was used to detect the metabolites in urine of 60 HLP patients and 60 normal controls. Based on PLS-DA pattern recognition, potential biomarkers related to HLP were screened out. Results 22 potential biomarkers related to HLP were identified, which involved amino acid metabolism, fatty acid metabolism, nucleotide metabolism, steroid hormone metabolism and intestinal flora metabolism, and their possible pathogenesis was found to be related to inflammatory reaction and oxidative stress. Conclusion The non-targeted metabolomic method based on UPLC-Q-TOF/MS technology can effectively identify potential biomarkers in the urine of HLP patients and explore the possible pathogenesis. Our research will lay a foundation for finding new targets for the treatment of HLP and provide a basis for clinical research on the treatment of HLP.

Currently, research on cardiac injury by aconitine focuses on its effect to directly interfere with the function of cardiac ion channels. Further, abnormal lipid metabolism could cause cardiac injury via inflammatory signaling pathway. In our preliminary study, we discovered that aconitine could alter the metabolism processes of various substances, including palmitic acid. Inspired by these studies, we investigated how elevation of palmitic acid by aconitine causes cardiac injury. Aconitine induced cardiac injury in rats (0.32 mg/kg, d = 7), and the cardiac injury was confirmed by electrocardiogram and serum biochemical study. The proteomic and metabolomic results showed that the palmitic acid level increases in heart tissue, and the NOD-like receptor (NLR) signaling pathway showed a strong effect of cardiac injury. The palmitic acid results in cell viability decline and activates NLR signaling in vitro. The shRNA-mediated knockdown of NLRP3 and NOD1/2 attenuates palmitic acid-induced inhibitory effect on cells and inhibited activation of the NLR signaling pathway. Collectively, this study reveals that aconitine provoked palmitic acid elevation could aggravate cardiac injury via the NLR signaling pathway. This study suggests that drug triggered disorder of the metabolism process could evoke cardiac injury and could propose a new strategy to study drug cardiac injury.

The particle phase state is a key factor for determining gas particle partitioning, particle reactive gas uptake, and multiphase chemical reactions, with associated links to secondary aerosol formation. In this study, the particle phase state was investigated by measuring particle rebound fraction f in the highly polluted atmosphere of Beijing, China. The particle phase state was sensitive to ambient relative humidity (RH). The particles changed from rebounding to adhering when the RH increased above 60%, suggesting a transition from the semisolid to liquid state. This transition RH was below the deliquescence RH of both (NH4)2SO4 and NH4NO3. Submicrometer particles were in the liquid state during heavy haze episodes. This might be because the elevated RH and inorganic fraction in particles resulted in an increase in aerosol liquid water content. The transition to a liquid phase state, marking the beginning of the haze episode, might kick off a positive feedback loop. The liquid particles might readily ta...

Background Coronary heart disease (CHD) is the leading cause of death worldwide, and its pathogenesis has attracted much attention. Metabolomics serves as an important tool for diagnosing diseases and exploring their pathogenesis in recent years. In this study, CHD patients were studied by comparing them with normal subjects to elucidate biomarkers that are linearly correlated with the severity of coronary stenosis. Methods An ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to analyze the urine metabolites of CHD patients and normal subjects. A total of 131 subjects included 27 patients who presented with 50–69% coronary stenosis, 22 with 70–89% stenosis, 29 with 90–99% stenosis, 24 with 100% stenosis, and 29 normal subjects. Results A total of 14 potential biomarkers associated with CHD were identified, and among them 4 biomarkers were linearly correlated with the severity of coronary stenosis in CHD patients. The metabolic pathways involved were amino acid metabolism, fatty acid metabolism, energy metabolism, and other pathways. Conclusion This study identified the biomarkers and metabolic pathways that may be involved in the occurrence and development of CHD, laying a theoretical foundation for better diagnosis and treatment of CHD in the future.

Ginkgo tea is a kind of health food produced from Ginkgo biloba leaves. The market of Ginkgo tea encountered many difficulties because of its bad palatability and vague function statement. In this study, two kinds of glycosidase were used to improve the flavor of Ginkgo tea, and three kinds of bioactivities were selected to investigate the health care function of the tea infusion. The aroma components extracted by headspace absorb (HSA) method during the making of Ginkgo tea were analyzed by GC-MS. The flavonoids and ginkgolides released into the tea infusion were studied by HPLC. A combination of &beta, glucosidase (&beta, G) and &alpha, rhamnosidase (&alpha, R) was applied during the making of the tea. The contents of characteristic aroma components and the release of total flavonoids and ginkgolides were increased significantly by adding &beta, G and &alpha, R. The composition of flavone glycosides was changed greatly. The free radical scavenging, inhibition of inflammatory cell activation, and tumor cytotoxicity activities of the tea were demonstrably improved. According to the release of active components, Ginkgo tea can be brewed repeatedly for at least three times. The enzymes used here show potential application prospects in the making of Ginkgo tea or tea drink to get higher contents of flavonoids, ginkgolides, and aroma components.

Hydrolytic activity for chlorogenic acid (CGA) has been recognized as an important side activity of some types of ferulic acid esterases. The purpose of this work was to enhance the efficient expression of ferulic acid esterase (FAE) and to explore its application in the processing of sunflower seed. Two novel FAEs from Aspergillus aculeatus (AaSD14) were expressed in genetically engineered E. coli BL21 (DE3), and their properties, including temperature, pH, metal ions and substrate specificity, were characterized after purification. Competitive CGA hydrolysis activity was observed in these recombined ferulic acid esterases (reFAEs) with reFAE1 of 246.37 U/g and reFAE2 of 340.95 U/g, which were 56.6 and 78.4 times higher than that of the wild strain (4.35 U/g), respectively. Meanwhile, the fermentation cycle was greatly shortened to 2.0 d. These reFAEs were recognized as type C FAE through substrate specificity assays. Treatment of sunflower seed protein (SSP) using reFAE2 resulted in a remarkable color change, from green to milk-white, confirming the activity of CGA biodegradation. Therefore, it shows certain potential in the processing of sunflower seed and other related foodstuffs.

Formaldehyde (HCHO) is one of the most important intermediate products of atmospheric photochemical reactions and is also a radical source that promotes ozone formation. Given its high solubility, HCHO is likely to exist in particulate form. In this work, gaseous HCHO (HCHOg) and particulate HCHO (HCHOp) were separated and collected by a rotating wet annular denude (RWAD) and an aerosol growth chamber–coil aerosol cooler (AC). The collected HCHO from the RWAD and AC are measured by two online Hantzsch method-based formaldehyde analyzers. The comprehensive campaign was held in the Yangtze River Delta of China from 15 May to 18 June 2018, which is during the harvest season. Several biomass burning events were identified by using acetonitrile as a tracer. During the period influenced by biomass burning, the mixing ratios of HCHOg and HCHOp were respectively 122% and 231% higher than those during other time periods. The enhancement ratio of HCHOg to acetonitrile obtained from this work generally agrees with those from the existing literature. Biomass burning contributed 14.8% to HCHOg, but the abundant freshly discharged precursors it emitted greatly promoted the secondary production of HCHOg. We suggest that the high concentration of HCHOp during the biomass burning period was from uptake of HCHOg by aerosols during their transportation; the liquid state particles are conducive to HCHOg uptake. High relative humidity, a low particle rebound fraction f, as well as low temperatures may result in higher uptake coefficient values.

Lithium ion (Li-ion) batteries work as the basic energy storage components in modern railway systems, hence estimating and improving battery efficiency is a critical issue in optimizing the energy usage strategy. However, it is difficult to estimate the efficiency of lithium ion batteries accurately since it varies continuously under working conditions and is unmeasurable via experiments. This paper offers a learning-based simulation method that employs experimental data to estimate the continuous-time energy efficiency and coulombic efficiency of lithium ion batteries, taking lithium titanate batteries as an example. The state of charge (SOC) regions and discharge current rates are considered as the main variables that may affect the efficiencies. Over eight million empirical datasets are collected during a series of experiments performed to investigate the efficiency variation. A back propagation (BP) neural network efficiency estimation and simulation model is proposed to estimate the continuous-time energy efficiency and coulombic efficiency. The empirical data collected in the experiments are used to train the BP network model, which reveals a test error of 10−4. With the input of continuous SOC regions and discharge currents, continuous-time efficiency can be estimated by the trained BP network model. The estimated and simulated result is proven to be consistent with the experimental results.

Gout Party is a Chinese medicine prescription composed of Aconiti Lateralis Radix Praeparaia, Aconiti Radix Cocta, Cremastrae Pseudobulbus Pleiones Pseudobulbus, Smilacis Glabrae Rhizoma, Rehmanniae Radix, and Glycyrrhizae Radix et Rhizoma, which can relieve joint pain caused by gouty arthritis (GA) and rheumatoid, and has a therapeutic effect on acute gouty arthritis (AGA). However, little information is available on the molecular biological basis and therapeutic mechanism of Gout Party for the treatment of AGA. AGA model was established by injecting sodium urate, and colchicine served as a positive control drug. We established a metabolomic method based on ultra-high-performance liquid chromatography&ndash, tandem quadrupole/time-of-flight mass spectrometry (UHPLC&ndash, Q&ndash, TOF/MS) to analyze the plasma samples of model group rats and blank group rats. Multiple statistical analyses, including principal component analysis (PCA) and partial least square discrimination analysis (PLS-DA), were used to examine metabolite profile changes in plasma samples. Finally, we identified 2&ndash, ketobutyric acid, 3&ndash, hexenedioic acid, but&ndash, 2&ndash, enoic acid, and so on, 22 endogenous metabolites associated with AGA. After successful molding, we found that 2&ndash, enoic acid, argininic acid, galactonic acid, lactic acid, equol 4&prime, &ndash, O&ndash, glucuronide, deoxycholic acid glycine conjugate, glycocholic acid, sphinganine 1&ndash, phosphate, LPE (0:0/20:3), LPE (0:0/16:0), LPC (15:0) decreased significantly (p &lt, 0.05 or p &lt, 0.01), alanine, erythrulose, 3&ndash, dehydrocarnitine, m&ndash, methylhippuric acid, 3&ndash, hydroxyoctanoic acid, p&ndash, cresol sulfate, estriol 3&ndash, sulfate 16&ndash, glucuronide, 10&ndash, hydroxy&ndash, 9&ndash, (phosphonooxy)octadecenoate, docosahexaenoic acid increased significantly (p &lt, 0.01). After Gout Party treatment, 14 biomarkers had a tendency to normal conditions. These above biomarkers were mainly involved in fatty acid metabolism, bile acid metabolism, amino acid metabolism, and energy metabolism pathways. These results suggested that Gout Party exerted therapeutic effects of treating AGA by improving energy metabolism disorder and amino acid metabolism dysfunction, and attenuating fatty acid metabolism abnormal and inflammation. The results of this experiment provided a reference for revealing the metabolic mechanism produced by Gout Party in the treatment of AGA, but the subsequent studies need to be further improved and supported by relevant cell experiments and clinical experiments.

Ethnopharmacological evidence The Dan-Lou tablet (DLT), a well-known Chinese prescription, has definitive clinical efficacy in the treatment of precordial discomfort and pain caused by coronary heart disease (CHD). However, the pharmacological mechanism of DLT in the treatment of CHD has not been clearly elucidated and needs to be further explored. Aim of the study We aimed to identify relevant biological pathways by assessing changes in biomarkers in response to DLT intervention in CHD to reveal the potential biological mechanism of DLT treatment for CHD. Materials and methods The major chemical components in DLT were qualitatively analyzed using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and a model of CHD in rats was subsequently established with a high-fat diet and left anterior coronary artery ligation (LADCA) followed by DLT intervention. Next, the metabolic profile of rat serum samples was analyzed using nontargeted metabolomics, wherein changes in the metabolites in serum samples before and after DLT administration were measured by PLS-DA, and two pathways of DLT treatment for CHD were predicted. Finally, predicted metabolomic pathways were verified by detecting and analyzing tissues from the rat model, revealing the mechanism of DLT in the treatment of CHD. Results Forty-five major chemical components were identified by the chemical characterization of DLT. In terms of metabolism, 17 biomarkers of CHD in rats were identified. Among these biomarkers, linoleic acid, γ-linolenic acid and lysophosphatidylcholines (LPCs) were found to play an important role in energy metabolism and glycerophospholipid metabolism. Protein analysis revealed that EGFR phosphorylation was inhibited in CHD rats after DLT treatment, which lowered the expression of TNF-α, IL-6 and MMP9, decreased the expression levels of ox-LDL and MDA, and increased the expression of SOD. Conclusion The mechanism of DLT in the treatment of CHD involves inhibiting the expression of EGFR and the activation of the MAPK signaling pathway by regulating glycerophospholipid metabolism (LPCs) and energy metabolism (linoleic acid and γ-linolenic acid). Therefore, inflammation-related (TNF-α, IL-6, MMP9) and oxidative stress-related (ox-LDL, MDA, SOD) indicators are affected, leading to the regulation of the oxidative stress state and anti-inflammatory effects.