Influence of trimetazidine on myocardial injury in mice with diabetic cardiomyopathy.

INTRODUCTION: The prevalence of diabetes mellitus is increasing year by year globally, and diabetic cardiomyopathy (DCM), as the most common complication of type 2 diabetes mellitus, seriously affects the prognosis of patients. Trimetazidine (TMZ), as a drug affecting myocardial energy metabolism, mainly reduces the oxidation rate of ß-oxidation by inhibiting 3-ketoacyl-CoA thiolase (3-KAT), a key enzyme in ß-oxidation of free fatty acid (FFA), so that the energy metabolism substrate of cardiomyocytes preferentially selects glucose rather than fatty acids, increases the content of intracellular adenosine triphosphate (ATP), enhances the contractile function of cardiomyocytes, and improves the state of cellular ischemia and hypoxia. Previous studies have shown that TMZ is closely related to the activation and induction of apoptosis of the MAPK pathway and AMPK pathway, and plays a role in the treatment of diabetic cardiomyopathy, but the specific mechanism is still unclear. OBJECTIVE: This study aims to investigate the impact of TMZ on myocardial damage in mice exhibiting diabetic cardiomyopathy (DCM), and to furnish a laboratory foundation for the clinical treatment of diabetic cardiomyopathy. METHOD: Male db/db mice (6 weeks old, n = 21) and male wild-type (wt) (6 weeks old, n = 20) mice were selected for the study. The wt mice were randomly assigned to the wt group (n = 10) and wt + TMZ group (n = 10), while the remaining db/db mice were randomly allocated to the db/db group (n = 11) and db/db + TMZ group (n = 10). Following 8 weeks of feeding, the wt + TMZ group and db/db + TMZ group received TMZ via gavage, whereas the remaining groups were administered physiological saline. Periodic measurements of blood glucose, blood lipids, and myocardial enzymes were conducted in mice, with samples obtained after the 12th week for subsequent biochemical analysis, myocardial pathology assessment, immunohistochemistry, western blot analysis, and TUNEL staining (TdT-mediated dUTP Nick-End Labeling). RESULT: GLU, TC, TG, LDL-C, and CK-MB levels were significantly higher in db/db mice compared to wt mice (GLU: M ± SD wt 5.94 ± 0.37, db/db 17.63 ± 0.89, p < 0.05, ES = 0.991; TC: M ± SD wt 3.01 ± 0.32, db/db 6.97 ± 0.36, p < 0.05, ES = 0.972; TG: M ± SD wt 0.58 ± 0.2, db/db 1.75 ± 0.14, p < 0.05, ES = 0.920; LDL-C: M ± SD wt 1.59 ± 0.12, db/db 3.87 ± 0.14, p < 0.05, ES = 0.989; CK-MB: M ± SD wt 0.12 ± 0.01, db/db 0.31 ± 0.04, p < 0.05, ES = 0.928). HDL-C levels were significantly lower in db/db mice (M ± SD wt 1.89 ± 0.08, db/db 0.64 ± 0.09, p < 0.05, ES = 0.963). Histopathological analysis confirmed myocardial damage in db/db mice. Treatment with TMZ reduced GLU, TC, TG, LDL-C, and CK-MB levels (p < 0.05, ES > 0.9) and increased HDL-C levels compared to untreated db/db mice. Additionally, TMZ treatment significantly decreased myocardial cell apoptosis (p < 0.05, ES = 0.980). These results demonstrate the efficacy of TMZ in reversing myocardial injury in DCM mice. CONCLUSION: TMZ can mitigate myocardial damage in db/db mice by downregulating the expression of caspase-12, a protein associated with the endoplasmic reticulum stress (ERS) cell apoptosis pathway, consequently diminishing cell apoptosis. This underscores the protective efficacy of TMZ against myocardial damage in mice afflicted with DCM.

A dynamic model of coalbed methane emission from boreholes in front of excavation working face: numerical model and its application.

China's current energy consumption is primarily fueled by coal, increasing coal mining with growing energy demand. Coal and gas outburst accidents are common problems in coal mining, and prediction methods are fundamental for preventing such accidents. The gas emission characteristics of boreholes are a combination of comprehensive coal properties and coal seam gas occurrence status; thus, the accurate prediction of gas emissions from boreholes is crucial for preventing such hazards. This paper presents a method for measuring the gas flow rate in continuous boreholes, which is used to predict outburst danger in front of the working face. The model was compared with field measurement data and found suitable for research. The effects of different initial gas pressures, different borehole radius, and different burial depths on gas emissions from boreholes were studied. The results showed that (1) initial gas pressure is the main influencing factor of gas gushing. The amount of gas emission during drilling and the attenuation of gas pressure are more sensitive to pressure. An increase in gas pressure considerably increases the amount of gas gushing out of drilling holes. (2) The increase in the drilling radius increases the generation of coal cuttings, the area of the drilling hole wall, and the degree of damage to the drilling hole wall. Consequently, the amount of gas gushing out of the drilling hole increases. (3) In situ stress occurs mainly because of the increase in gas pressure with an increase in burial depth and the increase in gas desorption caused by the increase in damage to the borehole wall. This study provides a new outburst prediction method, which involves identifying outburst hazards through the gas gushing out of the borehole. The results are expected to aid the control of underground coal and gas outbursts and ensure the safe production of coal mines.

Sodium glucose cotransporter-2-inhibitor dapagliflozin improves nonalcoholic fatty liver disease by ameliorating dipeptidyl-peptidase-4 protein expression in diabetic mice.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. It can progress from simple steatosis to nonalcoholic steatohepatitis and may even develop into liver fibrosis, hepatocirrhosis, or hepatocellular carcinoma, but there is no effective treatment. MATERIAL AND METHODS: Wild-type (wt) and diabetic (db/db) mouse NAFLD-induced models were used to investigate the hepatoprotective effects and potential mechanisms of dapagliflozin (a new oral hypoglycaemic drug) on type 2 diabetes mellitus (T2DM) complicated with NAFLD, and to establish wt and db/db mouse NAFLD-induced and dapagliflozin treatment models. RESULTS: Dapagliflozin reduces blood glucose, glycosylated haemoglobin, blood lipids, and serum transaminase levels in db/db mice and improves T2DM-related liver injury accompanied by NAFLD; the mechanism may be related to the decrease in dipeptidyl-peptidase-4 (DPP4) protein expression and improvement in liver enzymes. Further mechanism-related studies by our team revealed that dapagliflozin can also downregulate the expression of DPP4 proteins in the liver and reduce serum soluble DPP4 enzyme levels, thereby improving the hepatic steatosis and insulin resistance of NAFLD. CONCLUSION: Dapagliflozin may be an effective drug for the treatment of T2DM-induced NAFLD and NAFLD, providing a reliable laboratory basis and new treatment methods for the clinical treatment of NAFLD.

Blasting dust diffuse characteristics of spiral tunnel and dust distribution model: similar experiment and numerical modeling.

The special linear shape of spiral tunnel changes the air flow structure during tunnel construction and changes the diffuse and distribution of blasting dust. Mastering the blasting dust distribution and diffuse mechanisms can provide theoretical basis for ventilation layout and dust removal measures during spiral tunnel construction. To study the influence of spiral shape on dust diffusion and concentration distribution after tunnel blasting, a similar scale model of 1:20 and full-scale numerical model of spiral tunnel during construction were established. The similarity criterion and the similarity ratio of each physical quantity are derived from the dust motion equation. The dust distribution and diffuse characteristics in the spiral tunnel under different dust release quantity and release velocity were studied by model experiment. The dust distribution and diffuse characteristics in spiral tunnel with different curvature radius were studied by numerical simulation. The dust distribution model is refined based on the research results. The dust distribution model divides the tunnel into heavily polluted area and slightly polluted area, and the influence characteristics of the curvature radius on the dust export area are found. The layout of ventilation systems can be optimized according to the volume of heavily polluted areas. The heavily polluted area should be as small as possible; the dust in the heavily polluted area should be discharged to the slightly polluted area in an orderly manner to avoid the accumulation of dust. Dust removal measures can also be arranged according to the dust export location to improve dust removal efficiency.

Crack Evolution and Failure Modes of Shale Containing a Pre-Existing Fissure under Compression.

To investigate the crack evolution of Longmaxi shales with a single prefabricated fissure, a CCD (charge coupled device) camera and AE (acoustic emission) monitoring equipment were employed. On the basis of real-time CCD photographs and AE events, a real-time crack evolution process in fissured shale specimens under uniaxial compression was investigated. The crack initiation angle and extension angle were calculated, the relationship between the crack initiation stress, strength, and crack angle was compared, and the proportion of tensile and shear cracks at different stages of the whole compression process was briefly analyzed. The results demonstrate that, with the increase in fissure angle (α), the weakening ability of the prefabricated fissure to uniaxial compressive strength and crack initiation stress was reduced. The initial cracks and secondary cracks always appeared at the tip of the pre-existing fissure in the form of tensile cracks for α = 30-90°. The crack initiation angle and expansion angle increased first and then decreased rapidly with α increasing. Furthermore, the ultimate failure modes were mixed tensile and shear failure when α = 0-90°. The crack evolution of the fissured shale was progressive, but the final failure of the fissured specimen occurred rapidly. Furthermore, the appearance of the cracks, stress drops, and AE counts had good consistency in time.

Microscopic investigations on the healing and softening of damaged salt by uniaxial deformation from CT, SEM and NMR: effect of fluids (brine and oil).

Nowadays, a salt cavern, used as underground energy storage (e.g. natural gas, crude oil, hydrogen), is becoming more and more popular in China due to its many advantages, such as low permeability (≤10-21 m2), good water-soluble mining and the damage-healing characteristic of salt rocks. It not only solves the problem of energy resource supply-demand imbalance in China, but also provides a better, more secure and cost-effective way to store energy compared to aboveground energy storage systems. As for salt cavern storage, permeability is our primary concern in engineering, which is mainly influenced by damage and healing. In this work, some damaged salt specimens were prepared by uniaxial compression tests (the loading rate was 0.033 mm s-1). Then those specimens were immersed in either a saturated brine solution or oil at 50 °C for a few days. Microscopic investigations were carried out by X-ray Computed Tomography (CT), Scanning Electron Microscope (SEM) and Nuclear Magnetic Resonance (NMR) to investigate the change of salt microstructures after healing. Possible micro-healing mechanisms were discussed. It was found that fluids played an important role in the healing process of damaged salt. Healing effectiveness of micro-pores and -cracks with the brine solution was higher than that with oil mainly because of crystal recrystallization. The surface of the grains was smooth and had no visible microcracks after healing in brine, while there were many pits and micro-tunnels with oil. Oil could hinder the healing process by impeding the diffusion effect and restraining grain recrystallization. Meanwhile, intragranular and intergranular water could also work as a lubricant resulting in softening which made salt rock more deformable. NMR results confirmed that damaged salt had a better recovery with brine, displaying lower porosity and lower permeability compared to that with oil. This work provides preliminary microscopic investigations on the healing of damaged salt in order to reveal the salt healing mechanism.