RESUMO
NH3 gas sensors operating at room temperature, consisting of Ag nanoparticles decorated ß-AgVO3 nanorods (Ag/ß-AgVO3 NRs), were fabricated via a facile hydrothermal method without the need for a template. The surface characteristics and compositions of Ag/ß-AgVO3 NRs were analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Ag nanoparticles, ranging in diameter from approximately 20 to 40 nm, were dispersed on the surface of monoclinic ß-AgVO3 NRs with diameters ranging from 50 to 105 nm and lengths from 0.3 to 1.3 µm. The NH3 gas sensing properties of Ag/ß-AgVO3 NRs were studied under both dry air and humid conditions at room temperature. Comparative analysis demonstrated that the Ag/ß-AgVO3 NRs exhibited a strong response to NH3 gas under 70% relative humidity (RH) at room temperature compared to α-AgVO3 NRs. Specifically, the response of the Ag/ß-AgVO3 NRs to 5 ppm NH3 increased by 2.25 times as the RH varied from 20% to 80% at room temperature. This enhanced response was attributed to the effects of formation of nanoheterojunctions, nano-metallic Ag activity and the conductivity of NH4+ and OH- ions induced by the presence of humidity. The room temperature NH3 gas sensors based on Ag/ß-AgVO3 NRs demonstrated strong responses to low NH3 concentrations, high selectivity, good reproducibility, and long-term stability, and show promise for the development of low-power and cost-effective NH3 gas sensors for practical applications even under high humidity.
RESUMO
MYB-NFIB fusion and NOTCH1 mutation are common hallmark genetic events in salivary gland adenoid cystic carcinoma (SACC). However, abnormal expression of MYB and NOTCH1 is also observed in patients without MYB-NFIB fusion and NOTCH1 mutation. Here, we explore in-depth the molecular mechanisms of lung metastasis through single-cell RNA sequencing (scRNA-seq) and exome target capture sequencing in two SACC patients without MYB-NFIB fusion and NOTCH1 mutation. Twenty-five types of cells in primary and metastatic tissues were identified via Seurat clustering and categorized into four main stages ranging from near-normal to cancer-based on the abundance of each cell cluster in normal tissue. In this context, we identified the Notch signaling pathway enrichment in almost all cancer cells; RNA velocity, trajectory, and sub-clustering analyses were performed to deeply investigate cancer progenitor-like cell clusters in primary tumor-associated lung metastases, and signature genes of progenitor-like cells were enriched in the "MYC_TARGETS_V2" gene set. In vitro, we detected the NICD1-MYB-MYC complex by co-immunoprecipitation (Co-IP) and incidentally identified retinoic acid (RA) as an endogenous antagonist of genes in the "MYC_TARGETS_V2" gene set. Following this, we confirmed that all-trans retinoic acid (ATRA) suppresses the lung metastasis of SACC by correcting erroneous cell differentiation mainly caused by aberrant NOTCH1 or MYB expression. Bioinformatic, RNA-seq, and immunohistochemical (IHC) analyses of primary tissues and metastatic lung tissues from patients with SACC suggested that RA system insufficiency partially promotes lung metastasis. These findings imply the value of the RA system in diagnosis and treatment.
Assuntos
Carcinoma Adenoide Cístico , Neoplasias Pulmonares , Neoplasias das Glândulas Salivares , Humanos , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Tretinoína/farmacologia , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Neoplasias Pulmonares/genética , Transdução de Sinais , Receptor Notch1/genéticaRESUMO
The roles of lamin A/C in adipocyte differentiation and skeletal muscle lipid metabolism are associated with familial partial lipodystrophy of Dunnigan (FPLD). We confirmed that LMNA knockdown (KD) in mouse adipose-derived mesenchymal stem cells (AD-MSCs) prevented adipocyte maturation. Importantly, in in vitro experiments, we discovered a significant increase in phosphorylated lamin A/C levels at serine 22 or 392 sites (pLamin A/C-S22/392) accompanying increased lipid synthesis in a liver cell line (7701 cells) and two hepatocellular carcinoma (HCC) cell lines (HepG2 and MHCC97-H cells). Moreover, HCC cells did not survive after LMNA knockout (KO) or even KD. Evidently, the functions of lamin A/C differ between the liver and adipose tissue. To date, the mechanism of hepatocyte lipid metabolism mediated by nuclear lamin A/C remains unclear. Our in-depth study aimed to identify the molecular connection between lamin A/C and pLamin A/C, hepatic lipid metabolism and liver cancer. Gain- and loss-of-function experiments were performed to investigate functional changes and the related molecular pathways in 7701 cells. Adenosine 5' monophosphate-activated protein kinase α (AMPKα) was activated when abnormalities in functional lamin A/C were observed following lamin A/C depletion or farnesyltransferase inhibitor (FTI) treatment. Active AMPKα directly phosphorylated acetyl-CoA-carboxylase 1 (ACC1) and subsequently inhibited lipid synthesis but induced glycolysis in both HCC cells and normal cells. According to the mass spectrometry analysis, lamin A/C potentially regulated AMPKα activation through its chaperone proteins, ATPase or ADP/ATP transporter 2. Lonafarnib (an FTI) combined with low-glucose conditions significantly decreased the proliferation of the two HCC cell lines more efficiently than lonafarnib alone by inhibiting glycolysis or the maturation of prelamin A.
Assuntos
Proteínas Quinases Ativadas por AMP , Carcinoma Hepatocelular , Lamina Tipo A , Neoplasias Hepáticas , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Homeostase , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Lipídeos/fisiologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismoRESUMO
Non-coding RNA 886 (nc886/VTRNA2-1) is a Pol III transcript and an atypical imprinted gene. Its exact function as a negative regulator of protein kinase R establishes its connection with innate immunity. Studies have shown that nc886 silencing is closely associated with prostate cancer progression. Previous work has constructed a cell model of stable nc886 overexpression ("mimic" or "nc886+ ") in PC-3M-1E8 cell lines (1E8), which are highly bone-metastatic human prostate cancer cells with low expression of nc886, and cells expressing the mimic were validated to have lower invasive and metastatic abilities than cells expressing the scramble transcript in vitro and in vivo. In this study, we directly injected mimic or scramble cells into the left ventricle of C57BL/C mice, an immunocompetent animal model, to elucidate the immune mechanisms of tumor-host interactions. Interestingly, we found that tumor cells induced the inflammation of many important organs due to xenogeneic antigen rejection; this inflammation was ultimately repaired by tissue fibrosis after 28 days, except for in the spleen. The reason is that mimic cells, as heterogeneous antigens, are mostly directly recognized by macrophages or T cells in blood, and few mimic cells enter the spleen compared with scramble cells. The induction of splenic macrophage polarization to M2 macrophages by scramble cells is a critical factor in maintaining chronic splenic inflammation. In addition, we recognize that nc886 broadly decreases the expression of some human leukocyte antigen molecules and antigen transporters. This evidence reveals the interesting role of nc886 in regulating tumor cell antigens.