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Doxorubicin (DOX) is restricted due to its severe cardiotoxicity. There is still a lack of viable and effective drugs to prevent or treat DOX-induced cardiotoxicity(DIC). Vericiguat is widely used to treat heart failure with reduced ejection fraction. However, it is not clear whether vericiguat can improve DIC. In the present study, we constructed a DIC model using mice and neonatal rat cardiomyocytes and found that vericiguat ameliorated DOX-induced cardiac insufficiency in mice, restored DOX-induced mitochondrial dysfunction in neonatal rat cardiomyocytes, and inhibited the expression of inflammatory factors. Further studies showed that vericiguat improved mitochondrial dysfunction and reduced mtDNA leakage into the cytoplasm by up-regulating PRKG1, which activated PINK1 and then inhibited the STING/IRF3 pathway to alleviate DIC. These findings demonstrate for the first time that vericiguat has therapeutic potential for the treatment of DIC. The model illustrated that DOX inhibited PRKG1, PINK1 and PARKIN expression in the heart and activated STING/INF3 signaling pathway, leading to myocardial inflammation and cardiac dysfunction. Vericiguat alleviated myocardial inflammation and cardiac dysfunction by activating PRKG1, promoting PINK1 and PARKIN expression, inhibiting STING/INF3 signaling pathway, and improving mitochondrial function [Display omitted]. [ABSTRACT FROM AUTHOR]

• An annular nozzle model with bi-directional coupling of transient processes was developed. • Comparative analysis of powder convergence characteristics by means of high-speed camera and simulation. • The heat of Fe-based powders under different parameters was studied using simulations and experimental methods. Extreme high-speed laser cladding technology (EHLA) is widely employed in critical parts manufacturing and repairing due to its high efficiency. The appearance and quality of the cladding layer are directly influenced by the powder flow characteristics and the interaction between powder trajectory and laser beam. In order to elaborate Fe-based powder flow characteristics of the EHLA process, this study established a powder flow model with a ring-shaped nozzle using a transient process bidirectional coupling. The accuracy of the powder flow model was verified using a high-speed camera. The results demonstrated that the error between the simulation results and the real-time images was within 10 %, confirming the validity of the powder flow model. The temperature profiles of laser-powder coupled model indicated that the optimal melting effect of Fe-based powder was achieved at a laser power of 1500 W. Moreover, the maximum elevation angle of the powder flow was mainly influenced by the carrier gas and protective gas flow rate. The experimental and simulation results showed that the optimal process was a protective gas flow rate of 40 L/min and a carrier gas flow rate of 7 L/min. [ABSTRACT FROM AUTHOR]

Understanding the molecular structural evolution mechanism during coal pyrolysis can help better regulate coal conversions for developing clean coal technology. This study investigated changes in functional groups and polycyclic aromatic hydrocarbons (PAHs) during pyrolysis of a perhydrous bituminous coal at temperature of 75–600 °C. Results indicated that aliphatic, C–O, C=O, OH, aromatic C=C, and aromatic C–H groups declined in relative abundance below 300 °C. These declines were attributed to cracking of hydrogen bonds and devolatilization. Meanwhile, the alkyl side chains of alkylated PAHs, i.e., alkyl-naphthalenes and alkyl-phenanthrenes, were continuously detached. Pyrolysis at 300–450 °C was characterized by elevated aromaticity, reflected by increments in the relative abundances of aromatic C–H, aromatic carbon, pyridine nitrogen, and protonated carbon. PAH evolutions at this stage exhibited relative increases of 4-–6-ring PAHs with relative decreases of 2-–3-ring PAHs. Pyrolysis at 450–600 °C was characterized by an increment of aromatic C=C and significant increases in relative abundances of 4-–6-ring PAHs in emitted particulate and gaseous phases. The elevation of pyrolysis temperature transformed coal macromolecules into more compact structure. The molecular structural units of chars were formulated as C 245 H 227 N 3 O 14 S, C 239 H 193 N 3 O 8 S, C 228 H 152 N 2 O 3 S, and C 221 H 113 NO 3 S for coal and chars produced at 300, 500, and 600 °C, respectively. Changes in three-dimensional molecular structural units reflected step-by-step intense deformation and condensed process. • The evolution behaviors of various functional groups varied at different temperature stages. • Hydrogen bond crackings, devolatilization, and dealkylation reactions occurred below 300 °C. • Aromatic and protonated carbons increased above 300 °C due to aromaticity elevation. • Changes in PAH compositions recorded dealkylation, polymerization and condensation reactions. • Molecular formulas varied from C 245 H 227 N 3 O 14 S for coal to C 221 H 113 NO 3 S for 600 °C char. [ABSTRACT FROM AUTHOR]

[Display omitted] • Changes in n -alkane, terpane, and sterane indices show the combined effects of maturation and depositional environment. • Pr/Ph, Pr/ n -C 17 , and Ph/ n -C 18 ratios record the influence of depositional environment. • Epimerization reactions of hopanes and steranes are affected by thermal maturity and origin. • Degree of demethylation consistently depends on rank but is higher in Da Baoding coals compared to Huainan coals. • Individual PACs indices show variable trends with maturity and are sensitive to organofacies. Biomarkers in coal can evolve dramatically in terms of their concentration and distribution during coalification, limiting their use in source allocation of coal-derived pollution. Here we analyzed a broad range of aliphatics (i.e., 26 n -alkanes, 6 isoprenoids, 32 terpanes, 19 steranes) and 77 polycyclic aromatic compounds (PACs) in the Permo-Carboniferous and Late Triassic coals from the Chinese Huainan and Da Baoding coalfields, respectively. These coals, classifying as high volatile bituminous B to low volatile bituminous with vitrinite reflectance (R r) values ranging from 0.71 to 1.74 %, show variable organic geochemical features owing to the combined effects of thermal maturity and organofacies. Changes in the n -alkanes and isoprenoids indicate the loss of aliphatic fractions associated with maturation owing to cracking of the long-chain alkanes. The stratigraphic changes in the pristane to phytane ratios (Pr/Ph), Pr/ n -C 17 , and Ph/ n -C 18 reflect a control exerted by the depositional environment in the Huainan coals. In addition, principal component analysis (PCA) recognizes the Pr/ n -C 17 , Ph/ n -C 18 , carbon preference index (CPI), and odd-to-even predominance 2 (OEP 2) as organofacies sensitive indices. Intercomparison of the PAC distributions suggest different maturation pathways for the coals from the Huainan and Da Baoding coalfields. The demethylation processes related to coalification preferentially occur on the polymethyl substitutes that occur to a greater degree in the Da Baoding coals than in the Huainan coals. Nine PAC indices display distinctive patterns when plotting against R r. The DMP-2 vs DBT:DBF cross-plot explicitly separates the Huainan and Da Baoding coals into three distinctive zones representing different depositional environments and sources of organic matter. Moreover, PCA explicitly discriminate the maturation sensitive indices (i.e., MNR, DNR-1, TrMN-1, TrMN, TeMN, MPR, and MPI-1) from organofacies sensitive indices (i.e., DMP-2 and DBT:DBF). [ABSTRACT FROM AUTHOR]