Search

N6-methyladenosine (m6A) is the most predominant RNA epigenetic regulation in eukaryotic cells. Numerous evidence revealed that m6A modification exerts a crucial role in the regulation of tumor microenvironment (TME) cell infiltration in several tumors. Nevertheless, the potential role and mechanism of m6A modification in nasopharyngeal carcinoma (NPC) remains unknown. mRNA expression data and clinical information from GSE102349, and GSE53819 datasets obtained from Gene Expression Omnibus (GEO) was used for differential gene expression and subsequent analysis. Consensus clustering was used to identify m6A-related molecular patterns of 88 NPC samples based on prognostic m6A regulators using Univariate Cox analysis. The TME cell-infiltrating characteristics of each m6A-related subclass were explored using single-sample gene set enrichment (ssGSEA) algorithm and CIBERSORT algotithm. DEGs between two m6A-related subclasses were screened using edgeR package. The prognostic signature and predicated nomogram were constructed based on the m6A-related DEGs. The cell infiltration and expression of prognostic signature in NPC was determined using immunohistochemistry (IHC) analysis. Chi-square test was used to analysis the significance of difference of the categorical variables. And survival analysis was performed using Kaplan-Meier plots and log-rank tests. The NPC samples were divided into two m6A-related subclasses. The TME cell-infiltrating characteristics analyses indicated that cluster 1 is characterized by immune-related and metabolism pathways activation, better response to anit-PD1 and anti-CTLA4 treatment and chemotherapy. And cluster 2 is characterized by stromal activation, low expression of HLA family and immune checkpoints, and a worse response to antiPD1 and anti-CTLA4 treatment and chemotherapy. Furthermore, we identified 1558 DEGs between two m6A-related subclasses and constructed prognostic signatures to predicate the progression-free survival (PFS) for NPC patients. Compared to non-tumor samples, REEP2, TMSB15A, DSEL, and ID4 were upregulated in NPC samples. High expression of REEP2 and TMSB15A showed poor survival in NPC patients. The interaction between REEP2, TMSB15A, DSEL, ID4, and m6A regulators was detected. Our finding indicated that m6A modification plays an important role in the regulation of TME heterogeneity and complexity. [ABSTRACT FROM AUTHOR]

While the detailed mechanisms for how particulate matter (PM) causes adverse health effects in the lungs remain largely unknown, endoplasmic reticulum (ER) stress has been implicated in PM-induced lung injury. The present study was undertaken to examine how/if ER stress might regulate PM-induced inflammation, and to begin to define potential underlying molecular mechanisms. Here, ER stress hallmarks were examined in human bronchial epithelial (HBE) cells exposed to PM. To confirm roles of certain pathways, siRNA targeting ER stress genes and an ER stress inhibitor were employed. Expression of select inflammatory cytokines and related signaling pathway components by the cells were assessed as well. The results showed that PM exposure induced elevations in two ER stress hallmarks, i.e. GRP78 and IRE1a, in time-and/or dose-related manners in the HBE cells. Inhibition of ER stress by siRNA for GRP78 or IRE1a significantly alleviated the PM-induced effects. Further, ER stress appeared to regulate PM-induced inflammation -- likely through downstream autophagy and NF-jB pathways -- as implied by studies showing that inhibition of ER stress by siRNA of GRP78 or IRE1a caused significant amelioration of PM-induced autophagy and subsequent activation of NF-jB pathways. Moreover, the ER stress inhibitor 4-PBA were used to confirm the protective effects against PM-induced outcomes. Together, the results suggest ER stress plays a deleterious role in PM-induced airway inflammation, possibly through activation of autophagy and NF-jB signaling. Accordingly, protocols/treatments that could lead to inhibited ER stress could potentially be effective for treatment of PM-related airway disorders. [ABSTRACT FROM AUTHOR]

High entropy alloys (HEAs), consisting of five or more elements with nearly equal atomic composition with one another (5–35%), are new-generation alloys that have attracted signifi)cant interest since their advent in 2004 because of their unique structural and mechanical properties and thermodynamic and chemical stability. Some characteristics, including high mechanical strength at elevated temperatures, high ductility and fracture toughness at cryo)genic temperatures and high corrosion, erosion and wear resistance, have been demonstrated for HEAs that outperform traditional alloys and superalloys. Laser-cladding (LC) is an additive manufacturing technique that has good feasibility in designing and processing HEAs for advanced structural components and protective coatings. This overview provides a glimpse of recent advances in LC of HEAs in terms of design fundamentals, metallurgical phase and microstructure, specific properties for advanced coating applications and the effect of ceramic particles reinforcement in LC deposition of HEA coatings. [ABSTRACT FROM AUTHOR]

Context: Lily bulb and Rehmannia decoction (LBRD), consisting of Lilium henryi Baker (Liliaceae) and Rehmannia glutinosa (Gaertn) DC (Plantaginaceae), is a specialized traditional Chinese medicine formula for treating depression. However, the underlying mechanisms, especially the relationship between LBRD efficacy and metabolomics, remains unclear. Objective: This study was aimed to investigate the metabolic mechanism of LBRD in treating depression. Materials and methods: Network pharmacology was conducted using SwissTargetPrediction, DisGeNET, DrugBank, Metascape, etc., to construct component-target-pathway networks. The depression-like model was induced by intraperitoneal injection with lipopolysaccharide (LPS) (0.3 mg/kg) for 14 consecutive days. After the administration of LBRD (90 g/kg) and fluoxetine (2 mg/kg) for 14 days, we assessed behaviour and the levels of neurotransmitter, inflammatory cytokine and circulating stress hormone. Prefrontal metabolites of rats were detected by using liquid chromatography-mass spectrometry metabolomics method. Results: The results of network pharmacology showed that LBRD mainly acted on neurotransmitter and second messenger pathways. Compared to the model group, LBRD significantly ameliorated depressive phenotypes and increased the level of 5-HT (13.4%) and GABA (24.8%), as well as decreased IL-1β (30.7%), IL-6 (32.8%) and TNF-α (26.6%). Followed by LBRD treatment, the main metabolites in prefrontal tissue were contributed to retrograde endocannabinoid signalling, glycerophospholipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, autophagy signal pathway, etc. Discussion and conclusions: LBRD were effective at increasing neurotransmitter, attenuating proinflammatory cytokine and regulating glycerophospholipid metabolism and glutamatergic synapse, thereby ameliorating depressive phenotypes. This research will offer reference for elucidating the metabolomic mechanism underlying novel antidepressant agents contained LBRD formula. [ABSTRACT FROM AUTHOR]

In this study, a novel intelligent nanoplatform to integrate multiple imaging and therapeutic functions for targeted cancer theranostics. The nanoplatform, DOX@Gd-MFe3O4 NPs, was constructed Gd-doped mesoporous Fe3O4 nanoparticles following with the doxorubicin (DOX) loading in the mesopores of the NPs. The DOX@Gd-MFe3O4 NPs exhibited good properties in colloidal dispersity, photothermal conversion, NIR triggered drug release, and high T1/T2 relaxicity rate (r1=9.64mM-1s-1, r2= 177.71mM-1s-1). Benefiting from the high MR contrast, DOX@Gd-MFe3O4 NPs enabled simultaneous T1/T2 dual-modal MR imagining on 4T1 bearing mice in vivo and the MR contrast effect was further strengthened by external magnetic field. In addition, the DOX@Gd-MFe3O4 NPs revealed the strongest inhibition to the growth of 4T1 in vitro and in vivo under NIR irradiation and guidance of external magnetic field. Moreover, biosafety was also validated by in vitro and in vivo tests. Thus, the prepared DOX@Gd-MFe3O4 NPs would provide a promising intelligent nanoplatform for dual-modal MR imagining guided synergistic therapy in cancer theranostics. [ABSTRACT FROM AUTHOR]