Interactive Effects of Enalapril Administration and Novel HIIT Wheel-Bed Training in Aged Rats

Introduction: Growing research suggests that aerobic high-intensity interval training (HIIT) improves cardiovascular function and physical performance compared with moderate intensity continuous training (MICT). However relatively few animal models of HIIT are available to inform about the benefits of this exercise—particularly among older animals. In addition, there is little evidence for how HIIT training interacts with adjuvant pharmacological therapies known to enhance the impact of MCIT in older individuals such as Angiotensin Converting Enzyme (ACE) Inhibitors.Purpose: The aim of the present study was to establish a HIIT protocol in aged rats based on forced running wheel-bed, and to subsequently (1) establish the feasibility of the HIIT protocol in a proof-of-concept study evaluating interactions between HIIT and (2) the result of combining HIIT + ACE inhibitor treatment using the ACE inhibitor enalapril.Methods: Two groups of rats were used in this study. The feasibility of using wheel-bed for HIIT training was tested in group one (15- and 30-month-old male rats). In the second group, 37 24-month-old Fisher 344 x Brown Norway male rats were randomly divided into four subgroups: control, enalapril, HIIT training group, and HIIT training combined with enalapril administration. The training and administration lasted for 4 weeks. After the intervention, locomotor activity, exercise tolerance, and grip strength were tested.Results: Our feasibility study suggested that middle-aged and aged rats were able to successfully complete the HIIT training. In our intervention study, HIIT training alone, regardless of adjuvant enalapril intervention, did raise treadmill exercise tolerance vs. the sedentary condition. Measures of healthspan were not negatively impacted by HIIT training.Conclusion: The novel HIIT protocol based on forced running wheel-bed was successfully employed in aged rats. We conclude that future studies should compare the results and of multi-modal intervention strategies which include both HIIT and MICT in combination with adjuvant therapies such as enalapril to improve exercise tolerance and other global indices of healthspan

Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia

BackgroundAKT3 appears to play a role in lung cancer. However, its role in ventilator-associated pneumonia is still unclear. Therefore, this study aimed to investigate the role of AKT3 in macrophages during ventilator-associated pneumonia.MethodsThe mRNA level of AKT3, Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), The data is analyzed using the Xiantao academic analysis tool. Additionally, the roles of AKT3 in ventilator-associated pneumonia (VAP) were investigated through in vivo experiments.ResultsAKT3 was differentially expressed in various normal and tumor tissues. Functional enrichment analysis indicated the immunomodulatory function and inflammatory response of AKT3 in lung cancer. Depletion of macrophages protected against lung epithelial cells and significantly decreased MMP9, MMP19, FTH, and FTL expression levels and increased GPX4 expression levels, while partially reversing the changes in macrophage. Mechanistically, macrophage depletion attenuates ferroptosis of lung epithelial cells by modulating AKT3 following VAP.ConclusionCollectively, this study suggests the need for further validation of the immunoregulatory function of AKT3 in lung cancer. Additionally, macrophage depletion mitigates lung injury by modulating the AKT3/GPX4 pathway in the context of VAP

Medicarpin induces G1 arrest and mitochondria-mediated intrinsic apoptotic pathway in bladder cancer cells

Bladder cancer (BC) is the tenth most commonly diagnosed cancer. High recurrence, chemoresistance, and low response rate hinder the effective treatment of BC. Hence, a novel therapeutic strategy in the clinical management of BC is urgently needed. Medicarpin (MED), an isoflavone from Dalbergia odorifera, can promote bone mass gain and kill tumor cells, but its anti-BC effect remains obscure. This study revealed that MED effectively inhibited the proliferation and arrested the cell cycle at the G1 phase of BC cell lines T24 and EJ-1 in vitro. In addition, MED could significantly suppress the tumor growth of BC cells in vivo. Mechanically, MED induced cell apoptosis by upregulating pro-apoptotic proteins BAK1, Bcl2-L-11, and caspase-3. Our data suggest that MED suppresses BC cell growth in vitro and in vivo via regulating mitochondria-mediated intrinsic apoptotic pathways, which can serve as a promising candidate for BC therapy

Surface subsidence monitoring with an improved distributed scatterer interferometric SAR time series method in a filling mining area

Statistically homogeneous pixel (SHP) selection and DS phase optimization are two critical steps in the distributed scatterer interferometric SAR (DS-InSAR) time series method. In this paper, a new algorithm named dynamic hypothesis test of confidence interval (D-HTCI) is proposed, which reduces the wrong selection rate of SHP and increases the number of SHP selections. Using adaptive spatial nonlocal filtering method for DS phase optimization, the phase standard deviation (PSD) and the sum of phase differences (SPD) show that compared with the traditional covariance matrix decomposition method, the optimization quality is improved by 2.1 and 1.8 times, respectively. Combining 24 scenes Sentinel-1A data from September 17, 2017 to July 14, 2018, the method is applied to monitor surface subsidence of the Daizhuang filling mining area (Jining, Shandong, China). The results show that the proposed method has mm-level accuracy for monitoring of surface subsidence in a filling mining area

Impaired intracellular calcium homeostasis enhances protein O-GlcNAcylation and promotes vascular calcification and stiffness in diabetes

Vascular calcification is accelerated in patients with diabetes mellitus and increases risk of cardiovascular events and mortality. Vascular smooth muscle cells (VSMC) play a key role in regulating vascular tone and contribute significantly to the development of diabetic vasculopathy. In this study, the function of stromal interaction molecule 1 (STIM1), an important regulator for intracellular calcium homeostasis, in diabetic vascular calcification was investigated, and the underlying molecular mechanisms were uncovered.A SMC-specific STIM1 deletion mouse model (STIM1Δ/Δ) was generated by breeding the STIM1 floxed mice (STIM1f/f) with SM22α-Cre transgenic mice. Using aortic arteries from the STIM1Δ/Δ mice and their STIM1f/f littermates, we found that SMC-specific STIM1 deletion induced calcification of aortic arteries cultured in osteogenic media ex vivo. Furthermore, STIM1 deficiency promoted osteogenic differentiation and calcification of VSMC from the STIM1Δ/Δ mice. In the low-dose streptozotocin (STZ)-induced mouse model of diabetes, SMC-specific STIM1 deletion markedly enhanced STZ-induced vascular calcification and stiffness in the STIM1Δ/Δ mice. The diabetic mice with SMC-specific STIM1 ablation also exhibited increased aortic expression of the key osteogenic transcription factor, Runx2, and protein O-GlcNAcylation, an important post-translational modulation that we have reported to promote vascular calcification and stiffness in diabetes. Consistently, elevation of O-GlcNAcylation was demonstrated in aortic arteries and VSMC from the STIM1Δ/Δ mice. Inhibition of O-GlcNAcylation with a pharmacological inhibitor abolished STIM1 deficiency-induced VSMC calcification, supporting a critical role of O-GlcNAcylation in mediating STIM1 deficiency-induced VSMC calcification. Mechanistically, we identified that STIM1 deficiency resulted in impaired calcium homeostasis, which activated calcium signaling and increased endoplasmic reticulum (ER) stress in VSMC, while inhibition of ER stress attenuated STIM1-induced elevation of protein O-GlcNAcylation.In conclusion, the study has demonstrated a causative role of SMC-expressed STIM1 in regulating vascular calcification and stiffness in diabetes. We have further identified a novel mechanisms underlying STIM1 deficiency-induced impairment of calcium homeostasis and ER stress in upregulation of protein O-GlcNAcylation in VSMC, which promotes VSMC osteogenic differentiation and calcification in diabetes

Calculation of Volume Fractions of In Situ TiB and Residual Stress Distributions in Functionally Graded Composite of Ti–TiB–TiB2

Ti matrix composite with a polylaminate structure was successfully fabricated via spark plasma sintering (SPS) process. A temperature gradient field (TGF) was obtained during the sintering to form functionally graded material (FGM) in a vacuum under 40 MPa for 5 min. The actual volume fractions of TiB in the matrix were calculated based on the X-ray diffraction pattern. The target volume fractions of TiB were 0%, 20%, 40%, 60%, 80% and 100%. The calculated TiB volume fractions were slightly higher than the target volume fractions in layers 2–4 and lower than the target volume fractions in layers 5–6 and the deviations in layers 4 and 5 were less than 5% of the target volume. Based on the elastic axial symmetry model, the residual stress distributions in the Ti matrix composite with a polylaminate structure were simulated, indicating a relatively low thermal residual stress in the FGM

A Deep Learning Application for Deformation Prediction from Ground-Based InSAR

Ground-based synthetic aperture radar interferometry (GB-InSAR) has the characteristics of high precision, high temporal resolution, and high spatial resolution, and is widely used in highwall deformation monitoring. The traditional GB-InSAR real-time processing method is to process the whole data set or group in time sequence. This type of method takes up a lot of computer memory, has low efficiency, cannot meet the timeliness of slope monitoring, and cannot perform deformation prediction and disaster warning forecasting. In response to this problem, this paper proposes a GB-InSAR time series processing method based on the LSTM (long short-term memory) model. First, according to the early monitoring data of GBSAR equipment, the time series InSAR method (PS-InSAR, SBAS, etc.) is used to obtain the initial deformation information. According to the deformation calculated in the previous stage and the atmospheric environmental parameters monitored, the LSTM model is used to predict the deformation and atmospheric delay at the next time. The phase is removed from the interference phase, and finally the residual phase is unwrapped using the spatial domain unwrapping algorithm to solve the residual deformation. The predicted deformation and the residual deformation are added to obtain the deformation amount at the current moment. This method only needs to process the difference map at the current moment, which greatly saves time series processing time and can realize the prediction of deformation variables. The reliability of the proposed method is verified by ground-based SAR monitoring data of the Guangyuan landslide in Sichuan Province

Investigation on Mining Subsidence Based on Multi-Temporal InSAR and Time-Series Analysis of the Small Baseline Subset—Case Study of Working Faces 22201-1/2 in Bu’ertai Mine, Shendong Coalfield, China

High-intensity coal mining (large mining height, shallow mining depth, and rapid advancing) frequently causes large-scale ground damage within a short period of time. Understanding mining subsidence under high-intensity mining can provide a basis for mining-induced damage assessment, land remediation in a subsidence area, and ecological reconstruction in vulnerable ecological regions in Western China. In this study, the mining subsidence status of Shendong Coalfield was investigated and analyzed using two-pass differential interferometric synthetic aperture radar (DInSAR) technology based on high-resolution synthetic aperture radar data (RADARSAT-2 precise orbit, multilook fine, 5 m) collected from 20 January 2012 to June 2013. Surface damages in Shendong Coalfield over a period of 504 days under open-pit mining and underground mining were observed. Ground deformation of the high-intensity mining working faces 22201-1/2 in Bu’ertai Mine, Shendong Coalfield was monitored using small baseline subset (SBAS) InSAR technology. (1) DInSAR detected and located 85 ground deformation areas (including ground deformations associated with past-mining activity). The extent of subsidence in Shendong Coalfield presented a progressive increase at an average monthly rate of 13.09 km2 from the initial 54.98 km2 to 225.20 km2, approximately, which accounted for 7% of the total area of Shendong Coalfield; (2) SBAS-InSAR reported that the maximum cumulative subsidence area reached 5.58 km2 above the working faces 22201-1/2. The advance speed of ground destruction (7.9 m/day) was nearly equal to that of underground mining (8.1 m/day)