Extracellular Vesicle- and Mitochondria-Based Targeting of Non-Small Cell Lung Cancer Response to Radiation: Challenges and Perspectives.

During the cell life cycle, extracellular vesicles (EVs) transport different cargos, including organelles, proteins, RNAs, DNAs, metabolites, etc., that influence cell proliferation and apoptosis in recipient cells. EVs from metastatic cancer cells remodel the extracellular matrix and cells of the tumor microenvironment (TME), promoting tumor invasion and metastatic niche preparation. Although the process is not fully understood, evidence suggests that EVs facilitate genetic material transfer between cells. In the context of NSCLC, EVs can mediate intercellular mitochondrial (Mt) transfer, delivering mitochondria organelle (MtO), mitochondrial DNA (mtDNA), and/or mtRNA/proteinaceous cargo signatures (MtS) through different mechanisms. On the other hand, certain populations of cancer cells can hijack the MtO from TME cells mainly by using tunneling nanotubes (TNTs). This transfer aids in restoring mitochondrial function, benefiting benign cells with impaired metabolism and enabling restoration of their metabolic activity. However, the impact of transferring mitochondria versus transplanting intact mitochondrial organelles in cancer remains uncertain and the subject of debate. Some studies suggest that EV-mediated mitochondria delivery to cancer cells can impact how cancer responds to radiation. It might make the cancer more resistant or more sensitive to radiation. In our review, we aimed to point out the current controversy surrounding experimental data and to highlight new paradigm-shifting modalities in radiation therapy that could potentially overcome cancer resistance mechanisms in NSCLC.

ABCD4 is associated with mammary gland development in mammals.

BACKGROUND: Mammary gland development is a critical process in mammals, crucial for their reproductive success and offspring nourishment. However, the functional roles of key candidate genes associated with teat number, including ABCD4, VRTN, PROX2, and DLST, in this developmental process remain elusive. To address this gap in knowledge, we conducted an in-depth investigation into the dynamic expression patterns, functional implications, and regulatory networks of these candidate genes during mouse mammary gland development. RESULTS: In this study, the spatial and temporal patterns of key genes were characterized in mammary gland development. Using time-series single-cell data, we uncovered differences in the expression of A bcd4, Vrtn, Prox2, and Dlst in cell population of the mammary gland during embryonic and adult stages, while Vrtn was not detected in any cells. We found that only overexpression and knockdown of Abcd4 could inhibit proliferation and promote apoptosis of HC11 mammary epithelial cells, whereas Prox2 and Dlst had no significant effect on these cells. Using RNA-seq and qPCR, further analysis revealed that Abcd4 can induce widespread changes in the expression levels of genes involved in mammary gland development, such as Igfbp3, Ccl5, Tlr2, and Prlr, which were primarily associated with the MAPK, JAK-STAT, and PI3K-AKT pathways by functional enrichment. CONCLUSIONS: These findings revealed ABCD4 as a candidate gene pivotal for regulating mammary gland development and lactation during pregnancy by influencing PRLR expression.

A genome-wide CRISPR screening uncovers that TOB1 acts as a key host factor for FMDV infection via both IFN and EGFR mediated pathways.

The interaction between foot-and-mouth disease virus (FMDV) and the host is extremely important for virus infection, but there are few researches on it, which is not conducive to vaccine development and FMD control. In this study, we designed a porcine genome-scale CRISPR/Cas9 knockout library containing 93,859 single guide RNAs targeting 16,886 protein-coding genes, 25 long ncRNAs, and 463 microRNAs. Using this library, several previously unreported genes required for FMDV infection are highly enriched post-FMDV selection in IBRS-2 cells. Follow-up studies confirmed the dependency of FMDV on these genes, and we identified a functional role for one of the FMDV-related host genes: TOB1 (Transducer of ERBB2.1). TOB1-knockout significantly inhibits FMDV infection by positively regulating the expression of RIG-I and MDA5. We further found that TOB1-knockout led to more accumulation of mRNA transcripts of transcription factor CEBPA, and thus its protein, which further enhanced transcription of RIG-I and MDA5 genes. In addition, TOB1-knockout was shown to inhibit FMDV adsorption and internalization mediated by EGFR/ERBB2 pathway. Finally, the FMDV lethal challenge on TOB1-knockout mice confirmed that the deletion of TOB1 inhibited FMDV infection in vivo. These results identify TOB1 as a key host factor involved in FMDV infection in pigs.

Magnetic resonance imaging based on radiomics for differentiating T1-category nasopharyngeal carcinoma from nasopharyngeal lymphoid hyperplasia: a multicenter study.

PURPOSE: To investigate the role of magnetic resonance imaging (MRI) based on radiomics using T2-weighted imaging fat suppression (T2WI-FS) and contrast enhanced T1-weighted imaging (CE-T1WI) sequences in differentiating T1-category nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoid hyperplasia (NPH). MATERIALS AND METHODS: This study enrolled 614 patients (training dataset: n = 390, internal validation dataset: n = 98, and external validation dataset: n = 126) of T1-category NPC and NPH. Three feature selection methods were used, including analysis of variance, recursive feature elimination, and relief. The logistic regression classifier was performed to construct the radiomics signatures of T2WI-FS, CE-T1WI, and T2WI-FS + CE-T1WI to differentiate T1-category NPC from NPH. The performance of the optimal radiomics signature (T2WI-FS + CE-T1WI) was compared with those of three radiologists in the internal and external validation datasets. RESULTS: Twelve, 15, and 15 radiomics features were selected from T2WI-FS, CE-T1WI, and T2WI-FS + CE-T1WI to develop the three radiomics signatures, respectively. The area under the curve (AUC) values for radiomics signatures of T2WI-FS + CE-T1WI and CE-T1WI were significantly higher than that of T2WI-FS (AUCs = 0.940, 0.935, and 0.905, respectively) for distinguishing T1-category NPC and NPH in the training dataset (Ps all < 0.05). In the internal and external validation datasets, the radiomics signatures based on T2WI-FS + CE-T1WI and CE-T1WI outperformed T2WI-FS with no significant difference (AUCs = 0.938, 0.925, and 0.874 for internal validation dataset and 0.932, 0.918, and 0.882 for external validation dataset; Ps > 0.05). The radiomics signature of T2WI-FS + CE-T1WI significantly performed better than three radiologists in the internal and external validation datasets. CONCLUSION: The MRI-based radiomics signature is meaningful in differentiating T1-category NPC from NPH and potentially helps clinicians select suitable therapy strategies.