RESUMO
Endemic to Taiwan Province, China, Cotoneaster rosiflorus Kun-Cheng Chang & Fu-Yuan Lu 2011 (Rosaceae) holds significant ecological and ornamental importance. Despite its value, research on its molecular data and phylogenetic position has remained limited. In this study, we addressed this gap by sequencing the genome-skimming data, assembling its plastome, and investigating its phylogenetic position. The plastome, spanning 159,449 bp in length, consisted of a large single-copy (87,433 bp), a small single-copy (19,262 bp), and two inverted repeat regions (26,377 bp). We annotated a total of 128 functional genes, including 84 protein-coding genes, 36 transfer genes, and eight ribosomal RNA genes. The phylogenetic results indicated that C. rosiflorus is closely related to C. dammerii, suggesting that C. rosiflorus might have captured its chloroplast from C. dammerii through hybridization and introgression events. This study offered valuable insights for forthcoming phylogenetic and population genetic investigations of Cotoneaster.
RESUMO
Colorectal cancer is the second most prevalent and deadly cancer worldwide. The emergence of immune checkpoint therapy has provided a revolutionary strategy for the treatment of solid tumors. However, less than 5â¯% of colorectal cancer patients respond to immune checkpoint therapy. Thus, it is of great scientific significance to develop "potentiators" for immune checkpoint therapy. In this study, we found that knocking down different DNMT and HDAC isoforms could increase the expression of IFNs in colorectal cancer cells, which can enhance the effectiveness of immune checkpoint therapy. Therefore, the combined inhibition of DNMT and HDAC cloud synergistically enhance the effect of immunotherapy. We found that dual DNMT and HDAC inhibitors C02S could inhibit tumor growth in immunocompetent mice but not in immunocompromised nude mice, which indicates that C02S exerts its antitumor effects through the immune system. Mechanistically, C02S could increase the expression of ERVs, which generated the intracellular levels of dsRNA in tumor cells, and then promotes the expression of IFNs through the RIG-I/MDA5-MAVS signaling pathway. Moreover, C02S increased the immune infiltration of DCs and T cells in microenvironment, and enhanced the efficacy of anti-PD-L1 therapy in MC38 and CT26 mice model. These results confirmed that C02S can activate IFNs through the RIG-I/MDA5-MAVS signaling pathway, remodel the tumor immune microenvironment and enhance the efficacy of immune checkpoint therapy, which provides new evidence and solutions for the development of "potentiator" for colorectal cancer immunotherapy.
Assuntos
Antígeno B7-H1 , Neoplasias Colorretais , Inibidores de Histona Desacetilases , Inibidores de Checkpoint Imunológico , Microambiente Tumoral , Animais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Humanos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Camundongos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Camundongos Nus , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Feminino , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA (Citosina-5-)-Metiltransferases/genéticaRESUMO
A two-photon nanoparticle probe was designed and developed based on the principle of intermolecular interaction of the aggregation-induced locally excited emission luminescence mechanism. The probe has the advantages of simple synthesis, convenient use, strong atomic economy, good biocompatibility, and photobleaching resistance. It can produce a specific and sensitive response to formaldehyde, help detect FA in normal cells and cancer cells, and is expected to become a specific detection probe for FA in vitro and in vivo.