Discovery of novel NLRP3 inhibitors based on machine learning and physical methods.

The NLRP3 inflammasome plays a crucial role in inflammatory responses, particularly in alcohol-related liver disease (ALD). Given that NLRP3 has emerged as a potential therapeutic target for ALD, the development of effective inhibitors is of great importance. In this study, we trained 11 regression models, and the results showed that LightGBM, Random Forest, and XGBoost performed the best, achieving R² values of 0.774, 0.755, and 0.719, respectively. Using machine learning models and physical methods, we screened more than 11.5 million compounds from Asinex, Princeton, UkrOrgSynthesis, Chemdiv, Chembridge, Alinda, Enamine, and Lifechemicals, which led to the identification of 26 potential NLRP3 inhibitors. Furthermore, molecular dynamics simulations and MMGBSA binding energy calculations confirmed the stability of the interactions between NLRP3 and three key molecules: 19,655,631 (source Chembridge), 38,214,692 (source Chembridge), and Z1180203703 (source Enamine). Additionally, ADMET analysis revealed their favorable pharmacokinetic properties. This study provides insights and candidate molecules for discovering NLRP3 inhibitors, potentially applicable in treating related diseases.

Precast Assembled Road Paving Technology: Progress and Prospects.

This article presents a systematic review of the most cutting-edge research on precast pavement technology for the first time. Firstly, precast pavement is divided into two categories, precast cement concrete pavement and precast carpeted flexible pavement, according to the application of precast technology in pavement engineering. Subsequently, the structural characteristics, advantages, and disadvantages of various precast pavement systems are compared and analyzed; technical problems in precast pavement systems are explained; and future development directions are identified. In addition, the text specifically mentions the great contribution of precast carpeted flexible pavement technology in reducing the harmful effects of asphalt fumes on humans and the environment. This work will promote the application of prefabrication in road engineering and provide suggestions and references for subsequent research.

Effect of Industrial Solid Waste as Fillers on the Rheology and Surface Free Energy of Asphalt Mastic.

The continuous growth of industrial solid waste production has generated many environmental problems. We evaluated the potential of industrial solid waste as a substitute filler in asphalt mastic, with the aim of increasing the use of sustainable road construction materials. In this study, X-ray fluorescence spectroscopy (XRF) and scanning electron microscopy (SEM) were used to characterize the oxide composition and micromorphology of limestone (LS), red mud (RM), steel slag (SS), and ground granulated blast-furnace slag (GGBFS). Four asphalt mastics containing LS, RM, SS, and GGBFS with a filler-to-binder weight ratio of one were prepared. An evaluation of the rheology and wetting of the solid-waste-filler asphalt mastic was conducted using a frequency sweep, temperature sweep, linear amplitude sweep (LAS), multiple stress creep and recovery (MSCR), and surface free energy (SFE) methods. The results showed that SS increased the complex modulus, elastic component of the asphalt mastic and decreased the nonrecoverable creep compliance at stress levels of 0.1 and 3.2 kPa, which improved the rutting resistance of the asphalt mastic and reduced deformation under high-temperature conditions. The RM and GGBFS increased the fatigue performance of the asphalt mastic under strain loading, enhanced its fatigue life, and maintained good performance under long-term loading. The dispersive component of the SFE parameter of the solid-waste-filler asphalt mastic was larger than the polar component for the largest share of the surface energy composition. The SFE of the asphalt mastic prepared from the industrial solid-waste filler was reduced; however, the difference was insignificant compared to the limestone asphalt mastic. Solid-waste-filler asphalt mastic has performance characteristics, and its actual application can be based on different performance characteristics to select an appropriate solid-waste filler. The results of this study provide new technological solutions for solving the utilization rate of solid waste materials and sustainable road construction in the future.

Effects of Wnt/ß-catenin signaling on bisphenol A exposure in male mouse reproductive cells.

Bisphenol A (BPA) is a chemical used in numerous consumer products that is able to interfere with the mammalian endocrine system. The aim of the present study was to investigate the effects of BPA on male mouse reproductive cells following prenatal to postnatal exposure. In addition, the influence of BPA was detected on the expression levels of ß­catenin and dickkopf WNT signaling pathway inhibitor 1 (DKK­1) during the differentiation of spermatogenic cells in the mouse testes. ß­catenin and DKK­1 are two important proteins of the Wnt/ß­catenin signaling pathway. On gestational day 1, pregnant ICR mice were randomly divided into four groups: A dimethyl sulfoxide group, and three groups treated with various concentrations of BPA (0.5, 10, and 50 µg/kg). BPA was administered from gestational day 1 to weaning on postnatal day (PND) 42. The number of murine pups and the male:female ratio was recorded for each group. On PND 42, the male pups were sacrificed and their wet weights and testicular coefficients were measured. Immunohistochemical and western blot analyses were used to detect the protein expression of ß­catenin and DKK­1 in the testicular tissue samples of the six­week­old male mice. The results indicated that the number of murine pups, as well as the testicular viscera coefficient of the male mice, significantly decreased in the BPA­treated groups, as compared with the control group (P<0.05, P<0.01); however, no significant difference was observed in the male/female ratio in the BPA­treated groups, as compared with the control group (P>0.05). The results from the immunohistochemical and western blot analyses indicated that the protein expression of ß­catenin and DKK­1 were significantly increased in the BPA­treated groups, as compared with the control group, and the distribution of spermospore and Leydig cells also increased in the testes. These results suggest that high expression levels of ß­catenin and DKK­1 may participate in BPA­induced pathogenesis in male mouse reproductive cells.