Epigenetic silencing of LDHB promotes hepatocellular carcinoma by remodeling the tumor microenvironment.

Lactate dehydrogenase B (LDHB) reversibly catalyzes the conversion of pyruvate to lactate or lactate to pyruvate and expressed in various malignancies. However, the role of LDHB in modulating immune responses against hepatocellular carcinoma (HCC) remains largely unknown. Here, we found that down-regulation of lactate dehydrogenase B (LDHB) was coupled with the promoter hypermethylation and knocking down the DNA methyltransferase 3A (DNMT 3A) restored LDHB expression levels in HCC cell lines. Bioinformatics analysis of the HCC cohort from The Cancer Genome Atlas revealed a significant positive correlation between LDHB expression and immune regulatory signaling pathways and immune cell infiltrations. Moreover, immune checkpoint inhibitors (ICIs) have shown considerable promise for HCC treatment and patients with higher LDHB expression responded better to ICIs. Finally, we found that overexpression of LDHB suppressed HCC growth in immunocompetent but not in immunodeficient mice, suggesting that the host immune system was involved in the LDHB-medicated tumor suppression. Our findings indicate that DNMT3A-mediated epigenetic silencing of LDHB may contribute to HCC progression through remodeling the tumor immune microenvironment, and LDHB may become a potential prognostic biomarker and therapeutic target for HCC immunotherapy.

Precision Loading and Delivery of Molecular Cargo by Size-Controlled Coacervation of Gold Nanoparticles Functionalized with Elastin-like Peptides.

Thermoresponsive elastin-like peptides (ELPs) have been extensively investigated in biotechnology and medicine, but little attention has been paid to the process by which coacervation causes ELP-decorated particles to aggregate. Using gold nanoparticles (AuNPs) functionalized with a cysteine-terminated 96-repeat of the VPGVG sequence (V96-Cys), we show that the size of the clusters that reversibly form above the ELP transition temperature can be finely controlled in the 250 to 930 nm range by specifying the concentration of free V96-Cys in solution and using AuNPs of different sizes. We further find that the localized surface plasmon resonance peak of the embedded AuNPs progressively red-shifts with cluster size, likely due to an increase in particle-particle contacts. We exploit this fine control over size to homogeneously load precise amounts of the dye Nile Red and the antibiotic Tetracycline into clusters of different hydrodynamic diameters and deliver cargos near-quantitatively by deconstructing the aggregates below the ELP transition temperature. Beyond establishing a key role for free ELPs in the agglomeration of ELP-functionalized particles, our results provide a path for the thermally controlled delivery of precise quantities of molecular cargo. This capability might prove useful in combination photothermal therapies and theranostic applications, and to trigger spatially and temporally uniform responses from biological, electronic, or optical systems.

Research on the impact of equity incentive model on enterprise performance: A mediating effect analysis based on executive entrepreneurship.

In implementing the equity incentive system, this paper delves into the listed enterprises' selection of equity incentive models. While previous research has extensively covered the effects, models, and influencing factors of equity incentives, there needs to be more in-depth literature focusing on the diverse incentive models and their impact on corporate performance. Notably, there needs to be more literature on considering entrepreneurial spirit as a mechanism. It aims to explore the relationship between executives' choices under different incentive models, the entrepreneurial spirit fostered by these models, and their combined impact on corporate performance. The findings reveal that adopting the restricted stock incentive model by listed enterprises implementing the equity incentive system significantly positively affects enterprise performance. Mechanistic tests show that when a company implements the restricted stock incentive model, executives prioritize maximizing their interests, leading them to embrace more risk in their investment decisions. This behavior, in turn, stimulates the adventurous spirit of executives, positively impacting enterprise performance, particularly pronounced in companies with more concentrated executive power. Moreover, executives may be more inclined to invest in high-risk, high-reward innovative projects, a behavior indicative of innovation and more prevalent in firms with higher research and development (R&D) investment. However, the limitation of this paper is that the study evaluates the operation of the equity incentive system in China by taking listed companies in China as an example, which is not necessarily suitable for foreign developed capitalist countries. This study contributes to the study of principal-agent problems by exploring the relationship between executives, entrepreneurship and firm performance.

Relationship analysis between executive motivation and digital transformation in Chinese A-Share companies: An empirical study.

In the expanding global digital economy, the digital transformation of businesses has become a critical component of modern operations. This study investigates the relationship between executive incentives and the digital transformation in A-share-listed Chinese companies from 2011 to 2020. Using multi-period DID and linear regression models, we analyzed how equity and compensation incentives influence this transformation. We discovered an inverse U-shaped correlation between executive incentive intensity and corporate digital transformation. Additionally, the relationship between compensation incentives and digital transformation is initially non-positive but transitions to a non-linear positive association beyond a certain threshold. Our research also reveals that digital process innovation and digital business expansion mediate the relationship between executive motivation and digital transformation. These findings highlight the importance of appropriate executive rewards in fostering innovative thinking and advancing digital transformation. This study contributes to the understanding of the drivers and effects of digital transformation and the role of equity incentives in governance. It offers valuable insights for companies aiming to accelerate digital transformation, optimize industrial structure, and promote economic development. Based on this study, further research on this issue can be conducted in the future by refining the personality traits, educational background, and cognitive differences of executives.

Gastric cancer patient-derived organoids model for the therapeutic drug screening.

BACKGROUND: Gastric cancer (GC) is a highly heterogeneous disease featuring many various histological and molecular subtypes. Therefore, it is imperative to have well-characterized in vitro models for personalized treatment development. Gastric cancer patient-derived organoids (PDOs), re-capitulating in vivo conditions, exhibit high clinical efficacy in predicting drug sensitivity to facilitate the development of cancer precision medicine. METHODS: PDOs were established from surgically resected GC tumor tissues. Histological and molecular characterization of PDOs and primary tissues were performed via IHC and sequencing analysis. We also conducted drug sensitivity tests using PDO cultures with five chemotherapeutic drugs and twenty-two targeted drugs. RESULTS: We have successfully constructed a PDOs biobank that included EBV+, intestinal/CIN, diffuse/GS, mixed and Her2+ GC subtypes, and these PDOs captured the pathological and genetic characteristics of corresponding tumors and exhibited different sensitivities to the tested agents. In a clinical case study, we performed an additional drug sensitivity test for a patient who reached an advanced progressive stage after surgery. We discovered that the combination of napabucasin and COTI-2 exhibited a stronger synergistic effect than either drug alone. CONCLUSION: PDOs maintained the histological and genetic characteristics of original cancer tissues. PDOs biobank opens up new perspectives for studying cancer cell biology and personalized medicine as a preclinical study platform.