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Hepatocellular carcinoma (HCC) is a highly detrimental cancer type and has limited therapeutic options, posing significant threats to human health. The development of HCC has been associated with a disorder in bile acid (BA) metabolism. In this study, we employed an integrative approach, combining various datasets and omics analyses, to comprehensively characterize the tumor microenvironment in HCC based on genes related to BA metabolism. Our analysis resulted in the classification of HCC samples into four subtypes (C1, C2a, C2b, and C3). Notably, subtype C2a, characterized by the highest bile acid metabolism score (BAMS), exhibited the highest survival probability. This subtype also demonstrated increased immune cell infiltration, lower cell cycle scores, reduced AFP levels, and a lower risk of metastasis compared to subtypes C1 and C3. Subtype C1 displayed poorer survival probability and elevated cell cycle scores. Importantly, the identified subtypes based on BAMS showed potential relevance to the gene expression of drug targets in currently approved drugs and those under clinical research. Genes encoding VEGFR (FLT4 and KDR) and MET were elevated in C2, while genes such as TGFBR1, TGFB1, ADORA3, SRC, BRAF, RET, FLT3, KIT, PDGFRA, and PDGFRB were elevated in C1. Additionally, FGFR2 and FGFR3, along with immune target genes including PDCD1 and CTLA4, were higher in C3. This suggests that subtypes C1, C2, and C3 might represent distinct potential candidates for TGFB1 inhibitors, VEGFR inhibitors, and immune checkpoint blockade treatments, respectively. Significantly, both bulk and single-cell transcriptome analyses unveiled a negative correlation between BA metabolism and cell cycle-related pathways. In vitro experiments further confirmed that the treatment of HCC cell lines with BA receptor agonist ursodeoxycholic acid led to the downregulation of the expression of cell cycle-related genes. Our findings suggest a plausible involvement of BA metabolism in liver carcinogenesis, potentially mediated through the regulation of tumor cell cycles and the immune microenvironment. This preliminary understanding lays the groundwork for future investigations to validate and elucidate the specific mechanisms underlying this potential association. Furthermore, this study provides a novel foundation for future precise molecular typing and the design of systemic clinical trials for HCC therapy. [ABSTRACT FROM AUTHOR]

Accurately and conveniently acquiring the tensile fracture strength of rocks at different temperatures is vital no matter for the security or economical design of deep underground engineering projects. Extensive testing in the laboratory, assisted with fitting approaches, is the main method to obtain the high-temperature tensile fracture strength in the available literature. However, the high-temperature destruction test is difficult to conduct and requires numerous time and resources. In this work, considering the main physical mechanisms such as phase transition and thermal damage that affect the tensile fracture strength of rocks at high temperatures, theoretical models for predicting their temperature-dependent tensile fracture strength (TDTFS) are established based on the Force-Heat Equivalence Energy Density Principle. The presented models achieve great prediction on the different variation trends of tensile strength below and above the phase transition temperature, as well as the corresponding sudden change of strength. For rocks without phase transition, the presented model only needs some physical parameters tested at room temperature can get a good prediction capacity on the TDTFS. Moreover, a new theoretical characterization model of the equivalent thermal damage parameter was presented and take a comparison with the previous model. Finally, the potential applications and limitations of the TDTFS model are further discussed. The application threshold of the presented TDTFS models is relatively low, and they may therefore be suitable as a method for providing a rapid and preliminary evaluation of strength at a large temperature range for rock engineering. [ABSTRACT FROM AUTHOR]

Ammonia decomposition to produce hydrogen is an important part of the "ammonia-hydrogen" storage and transportation industry. Due to the limited efficiency of the catalytic decomposition of ammonia, the decomposition gas often contains undecomposed ammonia, so "ammonia-hydrogen" separation is an essential step. Introducing supersonic separation technology to the field of "ammonia-hydrogen" separation, a supersonic condensation model considering the non-equilibrium condensation of ammonia with surge waves was developed, and the condensation flow characteristics of ammonia in Laval nozzles were investigated, and the effects of outlet pressure on the supersonic flow and condensation characteristics of ammonia were explored. The results show that ammonia flows in the Laval nozzles and expands at high velocity, reaching a critical state of condensation after the throat, and nucleates and condenses extensively within a very short distance, and the droplet radius and liquid phase mass fraction continue to increase. After the shock wave occurs, the subcooling rapidly drops to a negative value and the condensed droplets begin to evaporate in large quantities. There is a low temperature zone between between the knots of the surge string. The droplet radius will slightly increase when the subcooling is greater than 0 K, but it will then evaporate rapidly. As the pressure ratio (ratio of outlet back pressure to inlet static pressure) increases from 0.18 to 0.62, the mass fraction of the liquid phase at the Laval nozzle outlet decreases from 0.064 to 0, and the Laval nozzle liquefaction efficiency continues to decrease until it loses its liquefaction capacity completely. [ABSTRACT FROM AUTHOR]