Gadd45a deletion aggravates hematopoietic stem cell dysfunction in ATM-deficient mice

Ataxia telangiectasia mutated (ATM) kinase plays an essential role in the maintenance of genomic stability. ATM-deficient (ATM(−/−)) mice exhibit hematopoietic stem cell (HSC) dysfunction and a high incidence of lymphoma. Gadd45a controls cell cycle arrest, apoptosis and DNA repair, and is involved in the ATM-p53 mediated DNA damage response. However, the role of Gadd45a in regulating the functionality of ATM(−/−) HSCs is unknown. Here we report that Gadd45a deletion did not rescue the defects of T-cells and B-cells development in ATM(−/−) mice. Instead, ATM and Gadd45a double knockout (ATM(−/−) Gadd45a(−/−)) HSCs exhibited an aggravated defect in long-term self-renewal capacity compared to ATM(−/−) HSCs in HSC transplantation experiments. Further experiments revealed that the aggravated defect of ATM(−/−) Gadd45a(−/−) HSCs was due to a reduction of cell proliferation, associated with an accumulation of DNA damage and subsequent activation of DNA damage response including an up-regulation of p53-p21 signaling pathway. Additionally, ATM(−/−) Gadd45a(−/−) mice showed an increased incidence of hematopoietic malignancies, as well as an increased rate of metastasis than ATM(−/−) mice. In conclusion, Gadd45a deletion aggravated the DNA damage accumulation, which subsequently resulted in a further impaired self-renewal capacity and an increased malignant transformation in ATM(−/−) HSCs

A New Switched State Jump Observer for Traffic Density Estimation in Expressways Based on Hybrid-Dynamic-Traffic-Network-Model

When faced with problems such as traffic state estimation, state prediction, and congestion identification for the expressway network, a novel switched observer design strategy with jump states is required to reconstruct the traffic scene more realistically. In this study, the expressway network is firstly modeled as the special discrete switched system, which is called the piecewise affine system model, a partition of state subspace is introduced, and the convex polytopes are utilized to describe the combination modes of cells. Secondly, based on the hybrid dynamic traffic network model, the corresponding switched observer (including state jumps) is designed. Furthermore, by applying multiple Lyapunov functions and S-procedure theory, the observer design problem can be converted into the existence issue of the solutions to the linear matrix inequality. As a result, a set of gain matrices can be obtained. The estimated states start to jump when the mode changes occur, and the updated value of the estimated state mainly depends on the estimated and the measured values at the previous time. Lastly, the designed state jump observer is applied to the Beijing Jingkai expressway, and the superiority and the feasibility are demonstrated in the application results

Drug Target Prediction Based on the Herbs Components: The Study on the Multitargets Pharmacological Mechanism of Qishenkeli Acting on the Coronary Heart Disease

In this paper, we present a case study of Qishenkeli (QSKL) to research TCM's underlying molecular mechanism, based on drug target prediction and analyses of TCM chemical components and following experimental validation. First, after determining the compositive compounds of QSKL, we use drugCIPHER-CS to predict their potential drug targets. These potential targets are significantly enriched with known cardiovascular disease-related drug targets. Then we find these potential drug targets are significantly enriched in the biological processes of neuroactive ligand-receptor interaction, aminoacyl-tRNA biosynthesis, calcium signaling pathway, glycine, serine and threonine metabolism, and renin-angiotensin system (RAAS), and so on. Then, animal model of coronary heart disease (CHD) induced by left anterior descending coronary artery ligation is applied to validate predicted pathway. RAAS pathway is selected as an example, and the results show that QSKL has effect on both rennin and angiotensin II receptor (AT1R), which eventually down regulates the angiotensin II (AngII). Bioinformatics combing with experiment verification can provide a credible and objective method to understand the complicated multitargets mechanism for Chinese herbal formula

A brief discussion on the interference and elimination of rainfall to the water pipe inclinometer at Fengning station

Observation data of DSQ water pipe inclinometer and meteorology at Fengning seismic station from 2021 to 2023 were selected. Correlation analysis and convolution filter analysis were performed on rainfall and observation data, and convolution filter method and regression analysis were used to eliminate the lag effect of rainfall, and the relationship between rainfall and water pipe stress variables was judged. The results show that the trend change of the Fengning DSQ water pipe inclinometer was related to rainfall, and the daily variation of the observed data had a good linear relationship with the rainfall accumulation value, but did not obviously correlate with the instantaneous rainfall, and the response time had a lag of 1 day. Convolution filtering can better eliminate the step change caused by rainfall, but it failed to completely eliminate the southward inclination of NS and eastward inclination of EW after the rainfall of the water pipe meter from June to September 2021. Other factors may also affect the inclination of NS to S and EW to E of the water pipe meter

Formamide deionized accelerates the somatic embryogenesis of Cunninghamia lanceolata

Aim of the study: To improve the efficiency of the somatic embryogenesis (SE) in Cunninghamia lanceolata. Area of the study: The study was conducted at Nanjing Forestry University (Nanjing, China). Material and methods: Immature cones of C. lanceolata, genotype 01A1 which was planted in Yangkou State-owned Forest Farm (Fujian, China), were used to induced callus. These calli were used to induce SE, concentration gradients of 0 g/L, 0.01134 g/L, 0.1134 g/L, 1.1134 g/L and 11.34 g/L of FD was added, to explore the optimal concentration for promoting SE of C. lanceolata. Main results: Low concentration of FD promoted the maturation of somatic embryos, while high concentration of FD lead to browning of embryogenic callus. The seedling rate and rooting number of seedlings induced by different concentrations of FD were significantly different. Research highlights: This study may aid in the rapid maturation of C. lanceolata somatic embryos and is useful for accelerated C. lanceolata breeding. Keywords: C. lanceolata; Formamide Deionized; Somatic embryogenesis; Seedling rate. Abbreviations used: FD (Formamide Deionized), FD0 (the concentration of 0 g/L FD), FD0.01134 (the concentration of 0.01134 g/L FD), FD0.1134 (the concentration of 0.1134 g/L FD), FD1.134 (the concentration of 1.134 g/L FD), FD11.34 (the concentration of 11.34 g/L FD)