[Expression Levels and Regulation of Selenoprotein Genes in Patients With Coronavirus Disease 2019].

Objective To investigate the expression levels of selenoprotein genes in the patients with coronavirus disease 2019 (COVID-19) and the possible regulatory mechanisms.Methods The dataset GSE177477 was obtained from the Gene Expression Omnibus,consisting of a symptomatic group (n=11),an asymptomatic group (n=18),and a healthy control group (n=18).The dataset was preprocessed to screen the differentially expressed genes (DEG) related to COVID-19,and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analysis were performed for the DEGs.The protein-protein interaction network of DEGs was established,and multivariate Logistic regression was employed to analyze the effects of selenoprotein genes on the presence/absence of symptoms in the patients with COVID-19.Results Compared with the healthy control,the symptomatic COVID-19 patients presented up-regulated expression of GPX1,GPX4,GPX6,DIO2,TXNRD1,SELENOF,SELENOK,SELENOS,SELENOT,and SELENOW and down-regulated expression of TXNRD2 and SELENON (all P<0.05).The asymptomatic patients showcased up-regulated expression of GPX2,SELENOI,SELENOO,SELENOS,SELENOT,and SELENOW and down-regulated expression of SELP (all P<0.05).The results of multivariate Logistic regression analysis showed that the abnormally high expression of GPX1 (OR=0.067,95%CI=0.005-0.904,P=0.042) and SELENON (OR=56.663,95%CI=3.114-856.999,P=0.006) was the risk factor for symptomatic COVID-19,and the abnormally high expression of SELP was a risk factor for asymptomatic COVID-19 (OR=15.000,95%CI=2.537-88.701,P=0.003).Conclusions Selenoprotein genes with differential expression are involved in the regulation of COVID-19 development.The findings provide a new reference for the prevention and treatment of COVID-19.

Salvia miltiorrhiza suppresses cardiomyocyte ferroptosis after myocardial infarction by activating Nrf2 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferroptosis, a recently identified non-apoptotic form of cell death reliant on iron, is distinguished by an escalation in lipid reactive oxygen species (ROS) that are iron-dependent. This phenomenon has a strong correlation with irregularities in iron metabolism and lipid peroxidation. Salvia miltiorrhiza Bunge (DS), a medicinal herb frequently utilized in China, is highly esteemed for its therapeutic effectiveness in enhancing blood circulation and ameliorating blood stasis, particularly during the treatment of cardiovascular diseases (CVDs). Numerous pharmacological studies have identified that DS manifests antioxidative stress effects as well as inhibits lipid peroxidation. However, ambiguity persists regarding the potential of DS to impede ferroptosis in cardiomyocytes and subsequently improve myocardial damage post-myocardial infarction (MI). AIM OF THE STUDY: The present work focused on investigating whether DS could be used to prevent the ferroptosis of cardiomyocytes and improve post-MI myocardial damage. MATERIALS AND METHODS: In vivo experiments: Through ligation of the left anterior descending coronary artery, we constructed both a wild-type (WT) and NF-E2 p45-related factor 2 knockout (Nrf2-/-) mouse model of MI. Effects of DS and ferrostatin-1 (Fer-1) on post-MI cardiomyocyte ferroptosis were examined through detecting ferroptosis and myocardial damage-related indicators as well as Nrf2 signaling-associated protein levels. In vitro experiments: Erastin was used for stimulating H9C2 cardiomyocytes to construct an in vitro ferroptosis cardiomyocyte model. Effects of DS and Fer-1 on cardiomyocyte ferroptosis were determined based on ferroptosis-related indicators and Nrf2 signaling-associated protein levels. Additionally, inhibitor and activator of Nrf2 were used for confirming the impact of Nrf2 signaling on DS's effect on cardiomyocyte ferroptosis. RESULTS: In vivo: In comparison to the model group, DS suppressed ferroptosis in cardiomyocytes post-MI and ameliorated myocardial damage by inducing Nrf2 signaling-related proteins (Nrf2, xCT, GPX4), diminishing tissue ferrous iron and malondialdehyde (MDA) content. Additionally, it enhanced glutathione (GSH) levels and total superoxide dismutase (SOD) activity, effects that are aligned with those of Fer-1. Moreover, the effect of DS on alleviating cardiomyocyte ferroptosis after MI could be partly inhibited through Nrf2 knockdown. In vitro: Compared with the erastin group, DS inhibited cardiomyocyte ferroptosis by promoting the expression of Nrf2 signaling-related proteins, reducing ferrous iron, ROS, and MDA levels, but increasing GSH content and SOD activity, consistent with the effect of Fer-1. Additionally, Nrf2 inhibition increased erastin-mediated ferroptosis of cardiomyocytes through decreasing Nrf2 signaling-related protein expressions. Co-treatment with DS and Nrf2 activator failed to further enhance the anti-ferroptosis effect of DS. CONCLUSION: MI is accompanied by cardiomyocyte ferroptosis, whose underlying mechanism is probably associated with Nrf2 signaling inhibition. DS possibly suppresses ferroptosis of cardiomyocytes and improves myocardial damage after MI through activating Nrf2 signaling.

A First-Principles Study of Anion Doping in LiFePO4 Cathode Materials for Li-Ion Batteries.

Doping anions into LiFePO4 can improve the electrochemical performance of lithium-ion batteries. In this study, structures, electronic properties and Li-ion migration of anion (F- , Cl- , and S2- ) doping into LiFePO4 were systematically investigated by means of density functional theory calculations. Anion substitution for oxygen atoms leads to an expansion of the LiFePO4 lattice, significantly facilitating Li-ion diffusion. For Cl- and F- anion doped into LiFePO4 , the energy barrier of Li-ion migration gets lowered to 0.209 eV and 0.283 eV from 0.572 eV. The introduction of anions narrows the forbidden band of LiFePO4 , enhancing its electronic conductivity. This work pays a way towards the rational design of high-performance lithium-ion batteries.

High SNHG expression may predict a poor lung cancer prognosis based on a meta-analysis.

BACKGROUND: An increasing number of small nucleolar RNA host genes (SNHGs) have been revealed to be dysregulated in lung cancer tissues, and abnormal expression of SNHGs is significantly correlated with the prognosis of lung cancer. The purpose of this study was to conduct a meta-analysis to explore the correlation between the expression level of SNHGs and the prognosis of lung cancer. METHODS: A comprehensive search of six related databases was conducted to obtain relevant literature. Relevant information, such as overall survival (OS), progression-free survival (PFS), TNM stage, lymph node metastasis (LNM), and tumor size, was extracted. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled to evaluate the relationship between SNHG expression and the survival outcome of lung cancers. Sensitivity and publication bias analyses were performed to explore the stability and reliability of the overall results. RESULTS: Forty publications involving 2205 lung cancer patients were included in this meta-analysis. The pooled HR and 95% CI values indicated a significant positive association between high SNHG expression and poor OS (HR: 1.890, 95% CI: 1.595-2.185), disease-free survival (DFS) (HR: 2.31, 95% CI: 1.57-3.39) and progression-free survival (PFS) (HR: 2.01, 95% CI: 0.66-6.07). The pooled odds ratio (OR) and 95% CI values indicated that increased SNHG expression may be correlated with advanced TNM stage (OR: 1.509, 95% CI: 1.267-1.799), increase risk of distant lymph node metastasis (OR: 1.540, 95% CI: 1.298-1.828), and large tumor size (OR: 1.509, 95% CI: 1.245-1.829). Sensitivity analysis and publication bias results showed that each result had strong reliability and robustness, and there was no significant publication bias or other bias. CONCLUSION: Most SNHGs are upregulated in lung cancer tissues, and high expression of SNHGs predicts poor survival outcomes in lung cancer. SNHGs may be potential prognostic markers and promising therapeutic targets.

[A Prediction Model for Human Immunodeficiency Virus Infection and Mother-to-Child Transmission Based on the Expression Levels of Selenoprotein Genes].

Objective To study the expression of selenoprotein genes in human immunodeficiency virus(HIV)infection and its mother-to-child transmission,so as to provide a theoretical basis for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.Methods The dataset GSE4124 was downloaded from the Gene Expression Omnibus(GEO).Two groups of HIV-positive mothers(n=25)and HIV-negative mothers(n=20)were designed.HIV-positive mothers included a subset of transmitter(TR)mothers(n=11)and non-transmitter(NTR)mothers(n=14).Then,t-test was carried out to compare the expression levels of selenoprotein genes between the four groups(HIV-positive vs. HIV-negative,NTR vs. HIV-negative,TR vs. HIV-negative,TR vs. NTR).Univariate and multivariate Logistic regression were adopted to analyze the effects of differentially expressed genes on HIV infection and mother-to-child transmission.R software was used to establish a nomogram prediction model and evaluate the model performance.Results Compared with the HIV-negative group,HIV-positive,NTR,and TR groups had 8,5 and 8 down-regulated selenoprotein genes,respectively.Compared with the NTR group,the TR group had 4 down-regulated selenoprotein genes.Univariate Logistic regression analysis showed that abnormally high expression of GPX1,GPX3,GPX4,TXNRD1,TXNRD3,and SEPHS2 affected HIV infection and had no effect on mother-to-child transmission.The multivariate Logistic regression analysis showed that the abnormally high expression of TXNRD3(OR=0.032,95%CI=0.002-0.607,P=0.022)was positively correlated with HIV infection.As for the nomogram prediction model,the area under the receiver-operating characteristic curve for 1-year survival of HIV-infected patients was 0.840(95%CI=0.690-1.000),and that for 3-year survival of HIV-infected patients was 0.870(95%CI=0.730-1.000).Conclusions Multiple selenoprotein genes with down-regulated expression levels were involved in the regulation of HIV infection and mother-to-child transmission.The abnormal high expression of TXNRD3 was positively correlated with HIV infection.The findings provide new ideas for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.

Multiple Dynamic Bonds-Driven Integrated Cathode/Polymer Electrolyte for Stable All-Solid-State Lithium Metal Batteries.

All-solid-state lithium metal batteries (LMBs) are considered as the promising higher-energy and improved-safety energy-storage systems. Nevertheless, the electrolyte-electrodes interfacial issues due to the limited solid physical contact lead to discontinuous interfacial charge transport and large interfacial resistance, thereby suffering from unsatisfactory electrochemical performance. Herein, we construct an integrated cathode/polymer electrolyte for all-solid-state LMBs under the action of polymer chains exchange and recombination originating from multiple dynamic bonds in our well-designed dynamic supramolecular ionic conductive elastomers (DSICE) molecular structure. The DSICE acts as polymer electrolytes with excellent electrochemical performance and mechanical properties, achieving the ultrathin pure polymer electrolyte thickness (12 µm). Notably, the DSICE also functions as lithium iron phosphate (LiFePO4 , LFP) cathode binders with enhanced adhesive capability. Such well-constructed Li|DSICE|LFP-DSICE cells generate delicate electrolyte-electrodes interfacial contact at the molecular level, providing continuous Li+ transport pathways and promoting uniform Li+ deposition, further delivering superior long-term charge/discharge stability (>600 cycles, Coulombic efficiency, >99.8 %) and high capacity retention (80 % after 400 cycles). More practically, the Li|DSICE|LFP-DSICE pouch cells show stable electrochemical performance, excellent flexibility and safety under abusive tests.

Pan-Cancer Study of the Prognosistic Value of Selenium Phosphate Synthase 1.

Objective: This study sought to determine the mean prognostic usefulness of seleniumphosphate synthase (SEPHS1) by investigating its expression in 33 human malignancies and its relationship to tumor immunity.Methods: The expression of selenophosphate synthase 1 (SEPHS1) in 33 human malignant tumors was examined using the Genotype-Tissue Expression (GTEx), Cancer Genome Atlas (TCGA), and TIMER databases. Furthermore, the TCGA cohort was used to investigate relationships between SEPHS1 and immunological checkpoint genes (ICGs), tumor mutation burden (TMB), microsatellite instability (MSI), and DNA mismatch repair genes (MMRs). To establish independent risk factors and calculate survival probabilities for liver hepatocellular carcinoma (LIHC) and brain lower-grade glioma (LGG), Cox regression models and Kaplan-Meier curves were utilized. Eventually, the Genomics of Cancer Drug Sensitivity (GDSC) database was used to evaluate the drug sensitivity in LGG and LIHC patients with high SEPHS1 expression.Results: Overall, in numerous tumor tissues, SEPHS1 was highly expressed, and it significantly linked with the prognosis of LGG, ACC, and LIHC (P < .05). Furthermore, in numerous cancers, SEPHS1 expression was linked to tumor-infiltrating immune cells (TIICs), TMB, MSI, and MMRs. According to univariate and multivariate Cox analyses, SEPHS1 expression was significant for patients with LGG and LIHC.Conclusion: High SEPHS1 expression has a better prognosis for LGG, while low SEPHS1 expression has a better prognosis for LIHC. Chemotherapy was advised for LGG patients, particularly for those with high SEPHS1 expression because it can predict how responsive patients will be to 5-Fluorouracil and Temozolomide. This interaction between SEPHS1 and chemoradiotherapy has a positive clinical impact and may be used as evidence for chemotherapy for LGG and LIHC patients.

A Prediction Model for Human Immunodeficiency Virus Infection and Mother-to-Child Transmission Based on the Expression Levels of Selenoprotein Genes / 中国医学科学院学报

Objective To study the expression of selenoprotein genes in human immunodeficiency virus(HIV)infection and its mother-to-child transmission,so as to provide a theoretical basis for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.Methods The dataset GSE4124 was downloaded from the Gene Expression Omnibus(GEO).Two groups of HIV-positive mothers(n=25)and HIV-negative mothers(n=20)were designed.HIV-positive mothers included a subset of transmitter(TR)mothers(n=11)and non-transmitter(NTR)mothers(n=14).Then,t-test was carried out to compare the expression levels of selenoprotein genes between the four groups(HIV-positive vs. HIV-negative,NTR vs. HIV-negative,TR vs. HIV-negative,TR vs. NTR).Univariate and multivariate Logistic regression were adopted to analyze the effects of differentially expressed genes on HIV infection and mother-to-child transmission.R software was used to establish a nomogram prediction model and evaluate the model performance.Results Compared with the HIV-negative group,HIV-positive,NTR,and TR groups had 8,5 and 8 down-regulated selenoprotein genes,respectively.Compared with the NTR group,the TR group had 4 down-regulated selenoprotein genes.Univariate Logistic regression analysis showed that abnormally high expression of GPX1,GPX3,GPX4,TXNRD1,TXNRD3,and SEPHS2 affected HIV infection and had no effect on mother-to-child transmission.The multivariate Logistic regression analysis showed that the abnormally high expression of TXNRD3(OR=0.032,95%CI=0.002-0.607,P=0.022)was positively correlated with HIV infection.As for the nomogram prediction model,the area under the receiver-operating characteristic curve for 1-year survival of HIV-infected patients was 0.840(95%CI=0.690-1.000),and that for 3-year survival of HIV-infected patients was 0.870(95%CI=0.730-1.000).Conclusions Multiple selenoprotein genes with down-regulated expression levels were involved in the regulation of HIV infection and mother-to-child transmission.The abnormal high expression of TXNRD3 was positively correlated with HIV infection.The findings provide new ideas for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.

Effects of miR-1290 mediated by ultrasound microbubbles on proliferation, apoptosis and invasion of ovarian cancer cells by regulating the expression of DKK3 / 中华内分泌外科杂志

Objective:To investigate the mechanism of miR-1290 mediated by ultrasound microbubbles on the proliferation, apoptosis and invasion of ovarian cancer cells by regulating the expression of DKK3.Methods:Logarithmic SKOV3 cells were divided into Control group, miR-1290 NC group, microbubble treatment (MB) group, miR-1290 inhibitor group and miR-1290 inhibitor-MB group. The targeting relationship between miR-1290 and DKK3 was verified by double luciferase assay; RT-PCR was used to detect the expression of miR-1290 and DKK3 mRNA in SKOV3 cells; the activity of SKOV3 cells was detected by MTT assay; the apoptosis of SKOV3 cells was detected by flow cytometry; cell scratch test and Transwell test were used to detect the migration and invasion abilities of SKOV3 cells; Western blot was used to detect the expression of protein.Results:The double luciferase experiment showed that miR-1290 had a targeting relationship with DKK3, and miR-1290 could negatively target DKK3; Compared with miR-1290 NC group [24, 48, 72 h: (0.53 ± 0.05), (0.82 ± 0.06), (1.24 ± 0.06) ], MB group [24, 48, 72 h: (0.43 ± 0.06), (0.71 ± 0.03), (1.03 ± 0.03) ], miR-1290 inhibitor group [24, 48, 72 h: (0.41 ± 0.03), (0.66 ± 0.04), (0.78 ± 0.05) ], miR-1290 inhibitor MB group [24, 48, 72 h: (0.33 ± 0.04), (0.54 ± 0.05), (0.67 ± 0.06) ] SKOV3 cell proliferation activity decreased significantly ( P<0.05), compared with the migration rate and invasion number of SKOV3 cells in miR-1290 NC group [ (45.98 ± 4.11) %, (235.14 ± 5.78) ], the migration rate and invasion number of SKOV3 cells in MB group [ (36.77 ± 4.24) %, (189.57 ± 4.58) ], miR-1290 inhibitor group [ (32.14 ± 3.78) %, (165.35 ± 5.01) ], and miR-1290 inhibitor MB group [ (20.40 ± 3.01) %, (86.21 ± 4.23) ] decreased significantly,the expression of DKK3 mRNA and protein, apoptosis rate, apoptosis promoting protein C-Caspase-3 and Bax in SKOV3 cells increased greatly ( P<0.05) ; the above indexes of SKOV3 cells in miR-1209 NC group and Control group had no great difference ( P>0.05) . Conclusion:MiR-1290 can negatively regulate the expression of DKK3, while ultrasound microbubble can down regulate the expression of miR-1290 and up regulate the expression of DKK3, thereby inhibiting the proliferation, migration and invasion of ovarian cancer SKOV3 cells and promoting the apoptosis of cancer cells.

SEPTIN9-SDC2-VIM methylation signature as a biomarker for the early diagnosis of colorectal cancer.

The accurate detection of colorectal cancer (CRC) at its initial stage can reduce mortality. However, the broad application of endoscopy has been limited due to the invasive procedure and patient noncompliance. Liquid biopsy with subsequent mapping of methylation in specific cell-free DNA (cfDNA) may represent an alternative approach for early diagnosis. In this study, we have developed a minimal-invasive blood-based test for detection of precancerous lesions and early-stage CRC. Using TCGA M450K methylation data, we identified candidate methylation sites with the highest Fold Change (FC) for three genes (SEPTIN9, SDC2 and VIM), which were selected from previous studies. Based on logistic regression models, we developed a 3-gene methylation signature for CRC diagnosis with high accuracy (Sensitivity =0.959, Specificity =1, AUC =0.997). Using independent public databases and data from blood samples, this model has demonstrated superior performance. The AUC was 0.919-1 and 0.905-0.916 in public tissue database for CRC and blood sample data, respectively. Thus, our proposed 3-gene methylation signature has a more reliable performance than other methods. Furthermore, signal enhancement effect of 3-gene methylation signature can improve the accuracy of early diagnosis for CRC, which demonstrates the potential for clinical application.

Biological Functions of Selenoprotein Iodothyronine Deiodinase and its Expression in Osteoarthritis.

Objective Iodothyronine deiodinases (DIOs) are important selenoproteins that play a key role in the bone and joint diseases. Osteoarthritis (OA) is the most prevalent joint disease especially in elders. This bioinformatic analysis was performed to explore the role of DIOs in OA pathogenesis. Methods The biological functions of selenoprotein DIOs were analyzed by bioinformatic techniques, including GenCLip 3.0, Database for Annotation, Visualization and Integrated Discovery (DAVID), STRING, Cytoscape, and Network Analyst. The expression of DIOs in the healthy individuals and OA patients was determined by mining OA-related microarray data in the gene expression omnibus (GEO) database of National Center for Biotechnology Information and performing a Meta-analysis of the data with Review Manager 5.3. Results Cluster analysis revealed that the function of the DIOs was associated with thyroid hormone receptor and iodothyronine; GO analysis showed that DIOs were mainly involved in biological processes, such as ethanol metabolism and phenol-containing compound metabolism and primarily involved in the cytochrome P450 metabolism of exogenous organisms and thyroid hormone signaling; SULT1A1 was the core node of the PPI network; miRNAs and thyroid hormones had some iterations with DIO1and DIO2; Meta-analysis showed that DIO3 expression was significantly up-regulated in OA patients (SMD = 0.31, 95%CI: 0.03, 0.59, P = 0.03). Conclusions The main biological functions of DIOs were closely associated with the regulation of thyroid hormone. And the up-regulated expression of DIO3 may have crucial impact on the occurrence of OA.

[Expression of Glutathione Peroxidases and Its Effect on Clinical Prognosis in Glioma Patients].

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.

Synthesis of Hierarchical Porous SAPO-34 and Its Catalytic Activity for 4,6-Dimethyldibenzothiophene.

Zeolite SAPO-34 has been widely used in the industry because of its special pore structure and wide distribution of acid sites in the pore channel. However, traditional SAPO-34 with a small pore size suffers from carbon deposition and deactivation in catalytic reactions, and its inability to catalytically convert bulky organic molecules limits its industrial application. Meanwhile, impurities of SAPO-5, which have weak acidity leading to rapid catalyst deactivation, appear in SAPO-34 zeolite. Therefore, it is of great significance to synthesize SAPO-34 zeolite with a mesoporous pore structure, which can significantly improve the transfer of molecules in zeolites. In this paper, SAPO-34 zeolite with a hierarchical pore structure was synthesized, and its hydrodesulfurization performance for 4,6-dimethyldibenzothiophene (4,6-DMDBT) was studied in a fixed bed reactor. The characteristic results show that BET-specific surface area, micropore volume, and mesoporous volume of synthesized SAPO-34 are 754 m2 g-1, 0.25, and 0.23 cm3 g-1 respectively, and the pore size is mainly concentrated at 4 nm. The catalytic conversion of 4,6-DMDMT with Co- and Mo-supported SAPO-34 is about 83%, which is much higher than the catalytic performance of Al2O3.

Crosstalk between CpG Methylation and Polymorphisms (CpG-SNPs) in the Promotor Region of DIO2 in Kashin-Beck Disease.

Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease (KBD). We also analyzed the interaction between the CpGs methylations and CpG-SNPs. Methods Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects. Four CpGs and two CpG-SNPs in the promoter regions of DIO2 were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The CpGs methylation levels were compared between samples from KBD patients and healthy subjects. The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes. Results The mRNA expression of DIO2 in whole blood of KBD patients was significnatly lower than in healthy controls (P <0.05). The methylation levels of DIO2-1_CpG_3 in KBD patients were significantly higher than those in healthy controls (P <0.05). The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls. The methylation level of DIO2-1_CpG_3 in the promoter region of DIO2 in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype (P <0.05). Conclusion The methylation level of DIO2 increases in KBD patients. Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs DIO2 rs955849187.

[Expression and Regulatory Mechanism of Autophagy-related Genes in Synovial Tissues of Patients with Rheumatoid Arthritis].

Objective To investigate the expression regulation of autophagy-related genes(ATG)and the mechanism of autophagy in rheumatoid arthritis(RA).Methods The differentially expressed genes(DEG)of RA were identified from GSE55235 and GSE55457,on the basis of which the differentially expressed autophagy-related genes(DE-ATG)were selected from the Human Autophagy Database.STRING 11.0 and GeneMANIA were used to establish protein-protein interaction networks.Further,the transcription factor-gene-miRNA co-expression network was established via NetworkAnalyst and Cytoscape.Finally,receiver operating characteristic(ROC)curve and DrugBank were employed to evaluate the efficacy of the predicted biomarkers and the performance of drugs targeting DE-ATG.GraphPad Prism 8.2.1 and R 4.0.3 were used for statistical analysis and graphics.Results A total of 485 DEG were enriched in signaling pathways such as T cell activation,hormone regulation,osteoclast differentiation,RA,and chemokines.Eleven DE-ATG regulated the expression of RUNX1,TP53,SOX2,and hsa-mir-155-5p in synovial tissues of RA patients and were involved in the response to environmental factors such as 2,3,7,8-tetrachlorodibenzodioxin and silicon dioxide.The ROC curve analysis identified the DE-ATG with good sensitivity and specificity,such as MYC,MAPK8,CDKN1A,and TNFSF10,which can be used to distinguish certain phenotypes and serve as novel biomarkers for RA.Conclusions In RA,down-regulated DE-ATG expression may promote apoptosis and lysis of chondrocytes.The identified novel biomarkers provides new ideas and methods for diagnosing and treating RA.The establishment of transcription factor-miRNA-gene co-expression network provides direct evidence for dissecting synovial inflammation and articular cartilage destruction.

[Effect of Selenoprotein Thioredoxin Reductase 3 on the Survival Prognosis of Tumor Patients].

Objective To investigate the expression of thioredoxin reductase 3(TXNRD3),a selenoprotein,in 33 human malignant tumors and then analyze its effect on the survival prognosis.Methods We employed the genotype-tissue expression project database,the cancer cell line encyclopedia,and the cancer genome atlas to explore the expression of TXNRD3 gene in 33 human malignant tumors and analyze its impact on the survival prognosis.Further,we explored the correlations of TXNRD3 with immune cells and immune infiltration in the tumor microenvironment,as well as with neoantigens,immune checkpoint genes,tumor mutational burden,and microsatellite instability.Subsequently,human samples were classified into high-and low-expression groups according to TXNRD3 gene expression levels,and the enrichment analysis of biological functions and signaling pathways was performed.Results The analysis with multiple databases showed that TXNRD3 was highly expressed in 15 tumors.The survival analysis showed that TXNRD3 was significantly associated with poor prognosis in pancreatic cancer patients.In addition,the expression level of TXNRD3 was correlated with immune infiltration in tumor microenvironment,neoantigens,immune checkpoint genes,tumor mutational burden,and microsatellite instability.TXNRD3 affected the expression of DNA mismatch repair genes.The gene set enrichment indicated that TXNRD3 was involved in regulating multiple signaling pathways associated with tumor metabolism and tumor immunity.Conclusion TXNRD3 is widely expressed in tumors and has a clinical value for the survival prognosis prediction and treatment of multiple tumors,demonstrating the potential of being a promising biomarker for targeted treatment of multiple tumors.

Application progress of single cell sequencing technology in diagnosis of genetic and reproductive / 国际生物医学工程杂志

The technique of prenatal diagnosis before embryo implantation has been greatly developed in assisted reproduction, especially for the people with abnormal genetic material to provide the technical possibility of eugenics and eugenics. As an emerging sequencing technology, single-cell sequencing can analyze the genome and transcriptome of cells from the level of a single cell, and reflect the heterogeneity between cells, thus helping to reveal the mechanism of the occurrence and development of diseases. Through prenatal diagnosis before embryo implantation and high-throughput sequencing of single cells obtained from embryo biopsy, euploidy of embryonic chromosomes can be effectively detected, and SNPs and chromosomal copy number variation, insertion, deletion and other variations can also be better detected. It can conduct the comprehensive detection and research of genomic polymorphism and mutation of individual and other species. In this paper, the single-cell sequencing technology and relevant methods was introduced, and the application scenarios of single-cell sequencing in genetic reproduction diagnosis were summarized. The applications of the technology in the field of genetic reproduction were described, and the future directions of the technology were discussed.

Expression of Glutathione Peroxidases and Its Effect on Clinical Prognosis in Glioma Patients / 中国医学科学院学报

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.

Crosstalk between CpG Methylation and Polymorphisms (CpG-SNPs) in the Promotor Region of DIO2 in Kashin-Beck Disease / 中国医学科学杂志(英文版)

Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease (KBD). We also analyzed the interaction between the CpGs methylations and CpG-SNPs. Methods Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects. Four CpGs and two CpG-SNPs in the promoter regions of DIO2 were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The CpGs methylation levels were compared between samples from KBD patients and healthy subjects. The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes. Results The mRNA expression of DIO2 in whole blood of KBD patients was significnatly lower than in healthy controls (P <0.05). The methylation levels of DIO2-1_CpG_3 in KBD patients were significantly higher than those in healthy controls (P <0.05). The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls. The methylation level of DIO2-1_CpG_3 in the promoter region of DIO2 in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype (P <0.05). Conclusion The methylation level of DIO2 increases in KBD patients. Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs DIO2 rs955849187.

Interference of P2X4 receptor expression in tumor-associated macrophages suppresses migration and invasion of glioma cells / 南方医科大学学报

OBJECTIVE@#To investigate the effect of interference of P2X4 receptor expression in tumor-associated macrophages (TAMs) on invasion and migration of glioma cells.@*METHODS@#C57BL/6 mouse models bearing gliomas in the caudate nucleus were examined for glioma pathology with HE staining and expressions of Iba-1 and P2X4 receptor with immunofluorescence assay. RAW264.7 cells were induced into TAMs using conditioned medium from GL261 cells, and the changes in mRNA expressions of macrophage polarization-related markers and the mRNA and protein expressions of P2X4 receptor were detected with RT-qPCR and Western blotting. The effect of siRNA-mediated P2X4 interference on IL-1β and IL-18 mRNA and protein expressions in the TAMs was detected with RT-qPCR and Western blotting. GL261 cells were cultured in the conditioned medium from the transfected TAMs, and the invasion and migration abilities of the cells were assessed with Transwell invasion and migration experiment.@*RESULTS@#The glioma tissues from the tumor-bearing mice showed a significantly greater number of Iba-1-positive cells, where an obviously increased P2X4 receptor expression was detected (P=0.001), than the brain tissues of the control mice (P < 0.001). The M2 macrophage markers (Arg-1 and IL-10) and M1 macrophage markers (iNOS and TNF-α) were both significantly up-regulated in the TAMs derived from RAW264.7 cells (all P < 0.01), but the up-regulation of the M2 macrophage markers was more prominent; the expression levels of P2X4 receptor protein and mRNA were both increased in the TAMs (P < 0.05). Interference of P2X4 receptor expression significantly lowered the mRNA(P < 0.01)and protein (P < 0.01, P < 0.05)expression levels of IL-1β and IL-18 in the TAMs and obviously inhibited the ability of the TAMs to promote invasion and migration of the glioma cells (P < 0.05).@*CONCLUSION@#Interference of P2X4 receptor in the TAMs suppresses the migration and invasion of glioma cells possibly by lowering the expressions of IL-1β and IL-18.