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Myocardial infarction (MI) results in high mortality. The size of fibrotic scar tissue following MI is an independent predictor of MI outcomes. Thioredoxin-interacting protein (TXNIP) is involved in various fibrotic diseases. Its role in post-MI cardiac fibrosis, however, remains poorly understood. In the present study, we investigate the biological role of TXNIP in post-MI cardiac fibrosis and the underlying mechanism using mouse MI models of the wild-type (WT), Txnip-knockout (Txnip-KO) type and Txnip-knock-in (Txnip-KI) type. After MI, the animals present with significantly upregulated TXNIP levels, and their fibrotic areas are remarkably expanded with noticeably impaired cardiac function. These changes are further aggravated under Txnip-KI conditions but are ameliorated in Txnip-KO animals. MI also leads to increased protein levels of the fibrosis indices Collagen I, Collagen III, actin alpha 2 (ACTA2), and connective tissue growth factor (CTGF). The Txnip-KI group exhibits the highest levels of these proteins, while the lowest levels are observed in the Txnip-KO mice. Furthermore, Txnip-KI significantly upregulates the levels of transforming growth factor (TGF)B1, p-Smad3, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), Cleaved Caspase-1, and interleukin (IL)1B after MI, but these effects are markedly offset by Txnip-KO. In addition, after MI, the Smad7 level significantly decreases, particularly in the Txnip-KI mice. TXNIP may aggravate the progression of post-MI fibrosis and cardiac dysfunction by activating the NLRP3 inflammasome, followed by IL1B generation and then the enhancement of the TGFB1/Smad3 pathway. As such, TXNIP might serve as a novel potential therapeutic target for the treatment of post-MI cardiac fibrosis.

Thioredoxin interacting protein (TXNIP) is a potential drug target for type 2 diabetes mellitus (T2DM) treatment. A series of quinazoline derivatives were designed, synthesised, and evaluated to inhibit TXNIP expression and protect from palmitate (PA)-induced β cell injury. In vitro cell viability assay showed that compounds D-2 and C-1 could effectively protect β cell from PA-induced apoptosis, and subsequent results showed that these two compounds decreased TXNIP expression by accelerating its protein degradation. Mechanistically, compounds D-2 and C-1 reduced intracellular reactive oxygen species (ROS) production and modulated TXNIP-NLRP3 inflammasome signalling, and thus alleviating oxidative stress injury and inflammatory response under PA insult. Besides, these two compounds were predicted to possess better drug-likeness properties using SwissADME. The present study showed that compounds D-2 and C-1, especially compound D-2, were potent pancreatic β cell protective agents to inhibit TXNIP expression and might serve as promising lead candidates for the treatment of T2DM. [ABSTRACT FROM AUTHOR]

Abnormal metabolism has become a potential target for highly malignant and invasive triple-negative breast cancer (TNBC) due to its relatively low response to traditional therapeutics. The existing metabolic interventions demonstrated unsatisfactory therapeutic outcomes and potential systemic toxicity, resulting from the metabolic instability and limited targeting ability of inhibitors as well as complex tumor microenvironment. To address these limitations, here we developed a robust pyroelectric BaTiO3@Au core—shell nanostructure (BTO@Au) to selectively and persistently block energy generation of tumor cells. Stimulated by near-infrared (NIR) laser, the Au shell could generate heat to activate the BaTiO3 core to produce reactive oxygen species (ROS) regardless of the constrained microenvironment, thus prominently inhibits mitochondrial oxidative phosphorylation (OXPHOS) and reduces ATP production to induce TNBC cell apoptosis. The therapeutic effects have been well demonstrated in vitro and in vivo, paving a new way for the development of metabolic interventions. [ABSTRACT FROM AUTHOR]

The catalytic conversion of CO or CO/CO2 mixtures to higher alcohols (HAs) using hydrogenation reactions remains challenging in C1 chemistry and also one of the most promising reactions for the utilization of non-petroleum resources. Here, the experiment and characterization tests of CuCoMn/Al2O3 show that copper is much more dispersed on γ-Al2O3 than cobalt, and the interaction between cobalt and Mn metals is stronger. And, mixed cobalt–manganese oxides are formed in the calcined catalyst, promoting the formation of higher alcohols. Under the optimum conditions, the catalyst demonstrated a total alcohol selectivity of 44.6%, and the fraction of higher alcohols reached up to 85.3% among the total alcohol products, which is superior to the classical modified CuCo-based catalysts. And in the gas mixture reaction with a CO : CO2 ratio of 8 : 2, the conversion rate of the catalyst to CO and CO2 reached 34.8% and 27.3%, respectively, and the selectivity (C1+ slate 1-alcohol) was 53.2%. [ABSTRACT FROM AUTHOR]

Hydrological forecasting in semi-arid and semi-arid areas is always the focus problem for hydrologists, and the watershed hydrological model is an effective tool for simulating and forecasting hydrological processes. The double excess watershed model (DEWM) was proposed by the Chinese hydrologists in Shanxi Province and was widely used in local reservoirs. Practical application of reservoirs for many years shows that there exist certain problems in the structure of model. Therefore, we modify the structure from three aspects: 1.Employ new infiltration formulas, 2.Simplify filling container structure and proposes a curve of the underground infiltration capacity, 3.Modify the evaporation simulation. Floods of Zhangfeng reservoir are used to verify the applicability of the modified model (MDEWM). Use the SCE algorithm to calibrate the model parameters, and compare the flow processes of calibration period and validation period with the measured values respectively. The flood peak pass rate are 83.3% and 91.7% in calibration period, and peak current are 50% and 100% in validation period of MDEWM, which results are better than DEWM or equal to it. The research of this article can provide a certain theoretical significance and practical value for flood forecasting, reservoir scheduling and water management in semi-arid and semi-humid areas. [ABSTRACT FROM AUTHOR]

A new algorithm, parameter adaptive DE mixed algorithm, is presented based on the standard differential evolution algorithm. In the process of adjusting the scaling factor and the crossover factor, the comparison judgment of individual fitness is added into the algorithm to improve the convergence speed of the algorithm. At the same time, after the differential evolution algorithm reaches the iterative number, the optimal solution of the differential evolution algorithm is used as the starting point of the trust region reflection to perform secondary optimization andform a mixed differential evolution algorithm finally. Six standard test functions were adopted to test the performance of the parameter adaptive DE mixed algorithm. The test result shows that the new algorithm can greatly improve the convergence of the algorithm. In order to verify the solution quality of the parameter adaptive DE mixed algorithm, 18 historical floods of Zhangfeng Reservoir were taken as study case in this paper, by using this new algorithm and the commonly used SCE-UA algorithm in hydrological model parameters optimization to calibrate the parameters of hydrological model. The results show that the pass rate of the flood peak is 83.3%, and the pass rate of the peak time is 91.7% during the calibrated period, the pass rate of the flood peak and peak time are 66.7% and 83.3% during the tested period by the new algorithm. Compared with the SCE-UA algorithm, the proposed parameter adaptive DE mixed algorithm can more effectively approximate the measured flow process, it indicatesit is feasible that the algorithm can be applied to the parameters calibration of the hydrological model. [ABSTRACT FROM AUTHOR]