Search

The circadian clock is the biochemical oscillator with a near 24-h period that is responsible for generating the circadian rhythms in peripheral organs including the lung. Mounting evidence suggests that circadian clock disruption during chronic lung diseases plays an essential role in augmented oxidative stress, inflammatory response, metabolic imbalances, hypoxia/hyperoxia, mucus secretion, dysregulated autophagy, and alters pulmonary function. Here, we review circadian clock disruption and discuss candidate clock genes that are altered at the transcriptional or translational level in chronic pulmonary diseases. This review aims to provide the current knowledge and understanding of the circadian molecular clock disruption in chronic pulmonary diseases which will further advance the development of novel clock-based therapeutics in the future. Circadian clock disruption in the lung is associated with chronic pulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), cystic fibrosis (CF), pulmonary arterial hypertension (PAH), and lung cancer. Cumulative evidence from preclinical models demonstrates the promising role of the circadian clock in modulating immune response and other associated phenotypes observed in chronic pulmonary diseases. Understanding the core molecular mechanisms contributing to circadian clock disruption in chronic lung diseases will help advance the development of novel clock-based therapeutics in the future. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cigarette smoke (CS) exposure induces mitochondrial dysregulation and abnormal mitophagy. • We employed mitoQC reporter mice, a mitochondrial reporter strain as mitophagy marker using GFP+/mCherry+. • Mitochondrial complexes and function related genes were inhibited with alterations in complexes I and III were observed. • Mitochondrial dynamic markers, mitochondrial fusion/fission, and mitochondrial translocate/transfer markers were altered. • Thus, mitoQC reporter mouse model can be employed to assess the dysregulated mitochondrial complexes and dynamics. Cigarette smoke (CS) is known to cause impaired mitophagy and mitochondrial dysregulation in the pathogenesis of chronic obstructive pulmonary disease (COPD)/emphysema. Mitochondrial complexes and dynamics are affected by acute CS exposure in lung epithelium and mouse lung. We hypothesize that chronic CS exposure (4 months) will induce lung mitochondrial dysregulation and abnormal mitophagy. In this study, we employed the mitoQC reporter mice, a mitochondrial reporter strain, which can reflect the mitophagy based on the fluorescence-tagged mitochondria. Chronic CS exposure induced lung inflammatory cell infiltration, airspace enlargement, and lung cellular senescence. We showed the higher occurrence of mitophagy (GFP/mCherry) in the lung cells by CS exposure, associated with more mitochondrial fluorescence signals (GFP+/mCherry+). After chronic CS exposure, the mitochondrial complexes and function related genes were inhibited, while protein levels of complexes I and III slightly changed. Additionally, chronic CS exposure down-regulated most of the mitochondrial dynamic markers at gene expression level, included mitochondrial fusion/fission and mitochondrial translocate/transfer markers. For the markers related to mitophagy, Pink1 and Parkin, decreased gene and protein levels of Parkin, and decreased gene expression of Pink1, were identified in the CS exposure group. Hence, CS-induced mitophagy is mediated by Pink1-Parkin independent mechanism. Thus, we have shown that the chronic CS epxosure dysregulated mitochondrial complexes and dynamics and induced mitophagy, using the state-of-the art mitoQC reporter mouse model. Our results suggested that dysregulated mitochondrial function and dynamics are associated with CS-induced lung injury and phenotypic development of chronic lung diseases, such as COPD/ emphysema. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The viscosities of the middle-lower crust of the Longmenshan Thrust Belt (LTB), China, are studied. • Rheological properties are not the main controlling factor on fault activity of the LTB. • The lower fault activity along the southern LTB may be due to a greater number of structures. Abstract Seven continuous GPS stations are located on the hanging wall of the Longmenshan Thrust Belt, and post-seismic deformation data of the 2013 Lushan earthquake have been recorded for nearly four years following the earthquake. We transform the data from a global reference frame to the South China Block reference frame, and then, the secular motion and post-seismic deformation of the Wenchuan earthquake are excluded using an exponential fit model. Based on our results, the viscosities of the low velocity zone at a depth of ∼25 km and of the middle and lower crust around the Longmenshan Thrust Belt are obtained as 2.75 × 10 17 P a · s and 2.56 × 10 18 P a · s , respectively. The post-seismic rebound, which was observed near the Lushan epicenter, may represent the occurrence of overslip during the earthquake. The more complex structural style may have produced weaker fault activity along the southern segment of the Longmenshan Thrust Belt than along its middle and northern segments. [ABSTRACT FROM AUTHOR]

Abstract: In order to investigate the effect and mechanism of action of rosuvastatin on atherosclerotic lesion in a Wistar rat model, 16 Wistar rats were fed a cholesterol-rich, vitamin D3 overload diet and underwent balloon injury of the aorta. One day prior to injury, half of the rats began rosuvastatin treatment (5mg/kg/d) via oral gavage. Eight control rats received a basal diet and sham operation. After 14 weeks of treatment, the animals were sacrificed. Blood was collected to measure lipid and angiotensin II (Ang II) levels and morphologic analysis was performed on the aorta. Scavenger receptor-class B type I (SR-BI), Ang II type-1 (AT1) receptor and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK1/2) protein and mRNA levels were measured via Western blot and real time reverse transcriptase polymerase chain reaction, respectively. Spearman's rank correlation was utilized to examine the relationships between SR-BI and Ang II or AT1 receptor expression. The atherosclerosis model group demonstrated an increase in plasma lipid levels and aortic plaque formation. After 14 weeks of treatment with rosuvastatin, there was a significant decrease in plasma lipid and Ang II levels accompanied by an improvement in aortic lesions. Rosuvastatin increased the expression of SR-BI but significantly inhibited the expression of AT1 receptor and p-ERK1/2. SR-BI protein expression was inversely correlated with both the level of Ang II and expression of the AT1 receptor. In conclusion, rosuvastatin attenuates atherosclerosis in the Wistar rat model, and its anti-atherosclerotic activity may be through upregulation of SR-BI expression and inhibition of p-ERK1/2 levels and AT1 receptor expression. [Copyright &y& Elsevier]

The pathological cardiac functions of ankyrin repeat domain 1 (ANKRD1) in left ventricle can directly aggravate cardiac hypertrophy (CH) and fibrosis through the activation of extracellular signal-regulated kinase (ERK)/ transcription factor GATA binding protein 4 (GATA4) pathway, and subsequently contribute to heart failure (HF). Baoyuan Decoction (BYD), which is a famous classic Chinese medicinal formulation, has shown impressive cardioprotective effects clinically and experimentally. However, the knowledge is still limited in its underlying mechanisms against HF. To explore whether BYD plays a protective role against HF by attenuating CH via the ANKRD1-ERK/GATA4 pathway. In vivo , HF rat models were prepared using left anterior descending coronary artery (LADCA) ligation. Rats in the BYD group were administered a dosage of 2.57 g/kg of BYD for 28 days, while in the positive control group rats were given 4.67 mg/kg of Fosinopril. In vitro , a hypertrophic model was constructed by stimulating H9C2 cells with 1 uM Ang II. An ANKRD1-overexpressing cell model was established through transient transfection of ANKRD1 plasmid into H9C2 cells. Subsequently, BYD intervention was performed on the cell models to further elucidate its effects and underlying mechanism. In vivo results showed that BYD significantly improved cardiac function and inhibited pathological hypertrophy and fibrosis in a rat model of HF post-acute myocardial infarction (AMI). Noticeably, label-free proteomic analysis demonstrated that BYD could reverse the CH-related biological turbulences, mainly through ANKRD1-ERK/GATA4 pathway. Further in vitro results validated that the hypertrophy was attenuated by BYD through suppression of AT1R, ANKRD1, Calpain1, p-ERK1/2 and p-GATA4. The results of in vitro model indicated that BYD could reverse the outcome of transfected over-expression of ANKRD1, including down-regulated expressions of ANKRD1, p-ERK1/2 and p-GATA4. BYD ameliorates CH and improves HF through the ANKRD1-ERK/GATA4 pathway, providing a novel therapeutic option for the treatment of HF. [Display omitted] [ABSTRACT FROM AUTHOR]

In this paper, we apply the method of Granger causality which is more accurate than classical correlation analysis method to determine whether the main air pollutants — Nitrogen oxides (NO x ), SO2 (Sulfur Dioxide), CO (carbon monoxide), TSP (total suspended particulates), PM10 (particulate matter smaller than 10 microns) and the mortality of respiratory diseases of the residents in Beijing have causal relationship. After ensuring NO x , SO2 and CO as the responsible substances, we use the time series method to construct the autoregressive integrated moving average model (ARIMA) of the pollutants, so that we could predict the amount of the pollutants from 2005 to 2008. Then we use the predicted value of pollutants as the input of the neural network model and obtain the output as the change of the death rate of respiratory diseases from 2005 to 2008. In the end, reducing the amount of pollutants by 10% and inputting the data in the neural network model, we make the prediction to evaluate the level of the pollutants and concluded that NO x is the most important pollutant to control. [Copyright &y& Elsevier]

It is well-known that fish have the ability to adapt to complex water flow environments. However, most research on bionic robotic fishes has focused on static water conditions. There remains a lot of room on the control of robotic fish in water flow. While static flow serves as the fundamental element of water flow, this paper seeks to address the issue of target point approaching control for bionic robotic fish in static water environments. Recognizing the challenges posed by the proportional–integral–derivative (PID) control and model predictive control (MPC) methods encountering the complex non-linear system, this study proposes a hybrid control approach that based on model predictive decision-making strategy. The proposed hybrid control method is effective in guiding robotic fish towards target points in both static water and static flow environments and achieving rapid system convergence under the premise of significantly reducing the calculation error. This work provides a potential reference for the control of bionic robotic fish in static flow. [Display omitted] • Complete the target point approaching task of bionic robot fish in different water fields, including static water and static flow. • A dynamic model of a single joint robot fish considering the influence of the flow. • A hybrid controller combining PID controller and model predictive controller. • Comparative target point approaching experiments on PID control, MPC control and hybrid control. [ABSTRACT FROM AUTHOR]

Glycyrrhetinic acid (GA) shows great efficiency against non-small cell lung cancer (NSCLC), but the detailed mechanism is unclear, which has limited its clinical application. Herein, we investigated the potential targets of GA against NSCLC by activity-based protein profiling (ABPP) technology and the combination of histopathology and proteomics validation. In vitro and in vivo results indicated GA significantly inhibited NSCLC via promotion of peroxiredoxin-6 (Prdx6) and caspase-3 (Casp3)-mediated mitochondrial apoptosis. This original finding will provide theoretical and data support to improve the treatment of NSCLC with the application of GA. [Display omitted] • First-time integrated analysis profiling of non-small cell lung cancer (NSCLC) and Glycyrrhetinic acid (GA) treatment by integrating activity-based protein profiling (ABPP) technology, histopathology and proteomics validation both in vitro and in vivo. • Identification of GA promoted ROS accumulation and inhibited proliferation of NSCLC cells. • Identification of Casp3 and Prdx6 were direct target proteins of GA in the treatment of NSCLC cells. [ABSTRACT FROM AUTHOR]

With social and economic development and improvement of science and technology, tunnel boring machines, raise boring machines, reaming machines and road headers have been unprecedentedly applied to underground engineering construction. Mechanical rock breakage experiments became an indispensable mean for mechanical excavation of underground engineering. It can also guide the design and operation of excavation machines. This paper introduces the new mechanical rock breakage experimental platform developed by Beijing University of Technology. The design and manufacture of this platform considered the influence of high in situ stress, cutter head rotation and rock breakage by multi-cutters at the same time on the rock breakage process. Different tools, such as rolling cutters, scraper, ripper, and pick, for different excavation machines can be tested in the platform. It can also take into account the different rock mass structure in the sample box. Different construction conditions with different cutting tools can be realistically modeled. The experimental platform consists of a mechanical system, a hydraulic system, an automatic control system and a data acquisition system. After installation of the designed experimental platform, several tests with different construction conditions were conducted. The experimental results showed that the platform reached its design requirements. [ABSTRACT FROM AUTHOR]