Corrigendum: Single-cell RNA sequencing reveals the role of phosphorylation-related genes in hepatocellular carcinoma stem cells.

[This corrects the article DOI: 10.3389/fcell.2021.734287.].

LncRNAs Target Ferroptosis-Related Genes and Impair Activation of CD4+ T Cell in Gastric Cancer.

Gastric cancer (GC) is a malignant disease of the digestive tract and a life-threatening disease worldwide. Ferroptosis, an iron-dependent cell death caused by lipid peroxidation, is reported to be highly correlated with gastric tumorigenesis and immune cell activity. However, the underlying relationship between ferroptosis and the tumor microenvironment in GC and potential intervention strategies have not been unveiled. In this study, we profiled the transcriptome and prognosis data of ferroptosis-related genes (FRGs) in GC samples of the TCGA-STAD dataset. The infiltrating immune cells in GC were estimated using the CIBERSORT and XCELL algorithms. We found that the high expression of the hub FRGs (MYB, PSAT1, TP53, and LONP1) was positively correlated with poor overall survival in GC patients. The results were validated in an external GC cohort (GSE62254). Further immune cell infiltration analysis revealed that CD4+ T cells were the major infiltrated cells in the tumor microenvironment of GC. Moreover, the hub FRGs were significantly positively correlated with activated CD4+ T cell infiltration, especially Th cells. The gene features in the high-FRG score group were enriched in cell division, DNA repair, protein folding, T cell receptor, Wnt and NIK/NF-kappaB signaling pathways, indicating that the hub FRGs may mediate CD4+ T cell activation by these pathways. In addition, an upstream transcriptional regulation network of the hub FRGs by lncRNAs was also developed. Three lncRNAs (A2M-AS1, C2orf27A, and ZNF667-AS1) were identified to be related to the expression of the hub FRGs. Collectively, these results showed that lncRNA A2M-AS1, C2orf27A, and ZNF667-AS1 may target the hub FRGs and impair CD4+ T cell activation, which finally leads to poor prognosis of GC. Effective interventions for the above lncRNAs and the hub FRGs can help promote CD4+ T cell activation in GC patients and improve the efficacy of immunotherapy. These findings provide a novel idea of GC immunotherapy and hold promise for future clinical application.

Single-Cell RNA Sequencing Reveals the Role of Phosphorylation-Related Genes in Hepatocellular Carcinoma Stem Cells.

Abnormal activation of protein kinases and phosphatases is implicated in various tumorigenesis, including hepatocellular carcinoma (HCC). Advanced HCC patients are treated with systemic therapy, including tyrosine kinase inhibitors, which extend overall survival. Investigation of the underlying mechanism of protein kinase signaling will help to improve the efficacy of HCC therapy. Combining single-cell RNA sequencing data and TCGA RNA-seq data, we profiled the protein kinases, phosphatases, and other phosphorylation-related genes (PRGs) of HCC patients in this study. We found nine protein kinases and PRGs with high expression levels that were mainly detected in HCC cancer stem cells, including POLR2G, PPP2R1A, POLR2L, PRC1, ITBG1BP1, MARCKSL1, EZH2, DTYMK, and AURKA. Survival analysis with the TCGA dataset showed that these genes were associated with poor prognosis of HCC patients. Further correlation analysis showed that these genes were involved in cell cycle-related pathways that may contribute to the development of HCC. Among them, AURKA and EZH2 were identified as two hub genes by Ingenuity Pathway Analysis. Treatment with an AURKA inhibitor (alisertib) and an EZH2 inhibitor (gambogenic) inhibited HCC cell proliferation, migration, and invasion. We also found that both AURKA and EZH2 were highly expressed in TP53-mutant HCC samples. Our comprehensive analysis of PRGs contributes to illustrating the mechanisms underlying HCC progression and identifying potential therapeutic targets for future clinical trials.

A cross-sectional study of inpatients with late stage of dementia in Southeast China and the associations between biochemical parameters and apolipoprotein E genotypes.

BACKGROUND: The purpose of this study was to analyze the disease distribution of patients in the late stage of dementia through a cross-sectional investigation and to clarify the association between apolipoprotein E (APOE) genotypes and the serum levels of total cholesterol, total triglycerides, and blood glucose in the late-stage Alzheimer's disease (AD) patients. METHODS: Patients who were in the late stage of dementia in a mental health center were enrolled in this study. A broad battery of neuropsychological tests and neuroimaging was applied to make the diagnosis. The APOE genotype was determined by the multiplex amplification refractory mutation system polymerase chain reaction. The association between APOE genotype and the blood level of biochemical parameters was studied. RESULTS: A total of 155 patients were enrolled in this study. The majority of patients had AD (67.8%), followed by vascular dementia (15.5%), mixed dementia (9%), and others (7.7%). The APOE ε4 allele frequency was significantly different in the different groups. The serum level of total cholesterol (TC) in APOE ε4 carriers was higher than in non-carriers (P<0.05). No statistically significant differences were found in the blood glucose and triglycerides (TG) levels between these two groups. CONCLUSION: To our knowledge, this is the first paper to study the characteristics of late-stage dementia in hospital patients in Southeast China. We found that the disease distribution was quite consistent with previous prevalence studies. Moreover, we found that the serum level of TC was higher in APOE ε4 carriers group. However, no association was found between the APOE ε4 allele and serum levels of glucose, TC and TG in the late stage of AD.

Synthesis and Evaluation of Thermo-Sensitive, Magnetic Fluorescent Nanocomposite as Trifunctional Drug Delivery Carrier.

The thermo-sensitive magnetic fluorescent trifunctional nanocomposite (Fe3O4/ZnS@PNIPAM) has been synthesized via a facile route. The obtained biocompatible nanocomposite was composed of monodisperse heterostructural Fe3O4/ZnS core and a thermo-sensitive poly(N-isopropyl acrylamide) (PNIPAM) shell. Fe3O4/ZnS acted as magnetic response and fluorescence luminous body, PNIPAM acted as drug loaded platform which can adsorb and release drug controllably. Fe3O4/ZnS@PNIPAM was characterized and all of the results showed that it had excellent magnetic response, photostability and thermo-sensitivity. Moreover, the drug release studies in vitro showed that the release rate increased with increasing temperature. MTT assays in model HepG2 cells demonstrated that Fe3O4/ZnS@PNIPAM was practically non-toxic. Thus, our results revealed that Fe3O4/ZnS@PNIPAM would be used in biomedical fields such as targeted drug delivery, as well as cancer diagnosis and treatment in the nearly future.

[Seven-Point Correction Approach for Spectrum Measurement of Light Source with a Narrow Bandwidth].

The finite bandwidth of spectroradiometers always causes significant errors when the measured light source has a narrow bandwidth compared to that of spectroradiometers. In order to solve this problem, an improved correction approach which is called seven-point correction approach is proposed. Firstly, the seven-point correction formula is obtained with Taylor's series and related derivative formula. Secondly, the effect of seven-point formula is validated through a simulated spectrum with a sine function shape. Considering the sine function as true spectrum, we calculate the measured spectrum with the bandpass function of spectroradiometers. We also correct the measured spectrum with the seven-point formula. At last, we validate the seven-point formula experimentally with a LED lamp whose center wavelength is 365 nm. Using a double grating monochromator, we measure the irradiance of LED lamp when the bandwidth of spectroradiometer is 5 and 0.5 nm. We also obtain the corrected spectrum by applying seven-point formula to measured spectrum. The simulated results show that, the corrected value at the center wavelength could be above 99% of the true value. The experimental results show that, the corrected value at the center wavelength could reach above 95% of the true value. Above all, the proposed seven-point approach has an improved correction effect compared with three-point and five point approach. This correction approach could be widely applied in the field of spectrum measurement.

Fabrication of fluorescent magnetic Fe3O4@ZnS nanocomposites.

A novel Fe3O4@ZnS nanomaterial with fluorescent and superparamagnetic properties has been successfully fabricated via TOPO-TOP synthesis with an additional coordinating component (OAm). The adsorption of OAm on the preformed magnetite nanoparticles, which were prepared in phenyl ether with oleic acid and oleyl amine, played an essential role in directing the structure of the Fe3O4@ZnS composites. The obtained materials were characterized by FTIR, TEM, XRD, X-ray photoelectron spectroscopy (XPS), UV-vis, fluorescence spectrophotometer and VSM. The results indicated that the Fe3O4 nanoparticles were successfully combined with ZnS and the coating of ZnS can be controlled by adjusting the molar ratio of Fe3O4 to ZnS. The saturation magnetization values of Fe3O4, Fe3O4@ZnS (1:2) and Fe3O4@ZnS (1:5) nanoparticles are 57.0 emu g(-1), 44.4 emu g(-1) and 34.2 emu g(-1), respectively at 300 K and the nanocomposites exhibit better fluorescence without evident quenching. The combined magnetic and fluorescent properties endow the nanocomposites with great potential applications in "nano-conveyer-belt" platform technology for drug targeting, bioseparation, diagnostic analysis and so on.