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BACKGROUND: Nuclear protein transport is essential in guiding the traffic of important proteins and RNAs between the nucleus and cytoplasm. Export of proteins from the nucleus is mostly regulated by Exportin 1 (XPO1). In cancer, XPO1 is almost universally hyperactive and can promote the export of important tumor suppressors to the cytoplasm. Currently, there are no studies evaluating XPO1 amplifications and mutations in NSCLC and the impact on outcomes. METHODS: Tumor samples were analyzed using next-generation sequencing (NGS) (NextSeq, 592 Genes), immunohistochemistry (IHC), and whole transcriptome sequencing (WTS, NovaSeq) (Caris Life Sciences, Phoenix, AZ). Survival was extracted from insurance claims data and calculated from time of tissue collection to last contact using Kaplan-Meier estimate. RESULTS: Among 18,218 NSCLC tumors sequenced, 26 harbored XPO1 mutations and 24 had amplifications. XPO1 mutant tumors were more likely to have high TMB (79% vs. 52%, p = 0.007) and less likely to have high PD-L1 (32% vs. 68%, p = 0.03). KRAS co-mutations were seen in 19% (n = 5) and EGFR co-mutations were rare (n = 2). Among the 17,449 NSCLC tumors with clinical data, there were 24 XPO1 mutant. Comparison of survival between XPO1 mutant and WT showed a negative association with a hazard ratio (HR) of 1.932 (95% CI: 1.144-3.264 p = 0.012). XPO1 amplification was not associated with survival. CONCLUSIONS: XPO1 pathogenic mutations were associated with a poor survival in NSCLC. Although XPO1 mutations are rare in NSCLC, further studies to assess its associations with treatment responses are warranted.

This study focused on the characterization of emulsions and microparticles encapsulating Chavir essential oil (EO) by application of modified whey protein concentrate–maltodextrin (WPC-MD). Different physical, chemical, morphological, thermal, and antioxidant properties and release behavior of spray-dried microparticles were assessed. Antioxidant, solubility, emulsifying, and foaming activities of modified WPC were increased compared to those of primary material. The results indicated that the particle size distribution varied depending on the type of carriers used, with the smallest particles formed by hydrolyzed WPC (HWPC). Binary blends of modified WPC-MD led to improved particle sizes. The spray-drying yield ranged from 64.1% to 85.0%, with higher yields observed for blends of MD with sonicated WPC (UWPC). Microparticles prepared from primary WPC showed irregular and wrinkled surfaces with indentations and pores, indicating a less uniform morphology. The UWPC as a wall material led to microparticles with increased small cracks and holes on their surface. However, HWPC negatively affected the integrity of the microparticles, resulting in broken particles with irregular shapes and surface cracks, indicating poor microcapsule formation. Encapsulating EO using WPC-MD increased the thermal stability of EO significantly, enhancing the degradation temperature of EO by 2 to 2.5-fold. The application of primary WPC (alone or in combination with MD) as wall materials produced particles with the lowest antioxidant properties because the EO cannot migrate to the surface of the particles. Enzymatic hydrolysis of WPC negatively impacted microparticle integrity, potentially increasing EO release. These findings underscore the crucial role of wall materials in shaping the physical, morphological, thermal, antioxidant, and release properties of spray-dried microparticles, offering valuable insights for microencapsulation techniques.

The composite strata structure is a common geological formation in western China. The study of the failure characteristics of the composite structure is of great help to the stability evaluation of stope and the prediction of coal mine dynamic disasters. In order to study the influence of different hard rock coefficients on the instability characteristics of composite samples, the triaxial tests with progressive varying confining pressure simulating the field loading condition were conducted on eight groups of composite samples with different hard rock coefficients. The bearing capacity of different samples was tested using the RMT-150B triaxial compression equipment, while the DS-5 type eight-channel acoustic emission monitoring system was employed for simultaneous monitoring of acoustic emission parameters. Additionally, the multifractal theory in mathematics is applied to the analysis of acoustic emission signals, exploring the multifractal characteristics of the time series of acoustic emission signals. The results show that the peak strength of the composite sample decreases first and then increases as the hard rock coefficient increases, which is consistent with the trend of the multifractal spectrum parameter $\Delta f\left(\alpha \right)$ Δ f α of the acoustic emission time series. A significant increase in the low-frequency and high-amplitude signal ratio can be used as a precursor to early indicate the instability in composite samples. The dynamic changes of multifractal parameters at different stages of the progressive varying confining pressure can reflect the influence of axial pressure and confining pressure on the crack propagation in the composite samples, and the two parameters at the hydrostatic pressure stage can be used as a rule-of-thumb for screening the testing samples. Simultaneously, the multifractal parameters can early warn the rock failure much more ahead of time than the conventional approach associated with the warning point obtained in the acoustic emission curves, and its head of time can be reaching 0.015 failure progress. HIGHLIGHTS: The influences of hard rock coefficient on the peak strength and failure mode of composite samples were studied. The multifractal characteristics of acoustic emission time series were analysed for composite samples with different hard rock coefficients. The multifractal parameters can be used to screen the testing sample with internal defects. Multifractal parameters can be used for early warning of rock failure. [ABSTRACT FROM AUTHOR]