Association of dementia with immunoglobulin G N-glycans in a Chinese Han population

Immunoglobulin G (IgG) functionality can drastically change from anti- to proinflammatory by alterations in the IgG N-glycan patterns. Our previous studies have demonstrated that IgG N-glycans associated with the risk factors of dementia, such as aging, dyslipidemia, type 2 diabetes mellitus, hypertension, and ischemic stroke. Therefore, the aim is to investigate whether the effects of IgG N-glycan profiles on dementia exists in a Chinese Han population. A case–control study, including 81 patients with dementia, 81 age- and gender-matched controls with normal cognitive functioning (NC) and 108 non-matched controls with mild cognitive impairment (MCI) was performed. Plasma IgG N-glycans were separated by ultra-performance liquid chromatography. Fourteen glycan peaks reflecting decreased of sialylation and core fucosylation, and increased bisecting N-acetylglucosamine (GlcNAc) N-glycan structures were of statistically significant differences between dementia and NC groups after controlling for confounders (p \u3c 0.05; q \u3c 0.05). Similarly, the differences for these 14 initial glycans were statistically significant between AD and NC groups after adjusting for the effects of confounders (p \u3c 0.05; q \u3c 0.05). The area under the receiver operating curve (AUC) value of the model consisting of GP8, GP9, and GP14 was determined to distinguish dementia from NC group as 0.876 [95% confidence interval (CI): 0.815–0.923] and distinguish AD from NC group as 0.887 (95% CI: 0.819–0.936). Patients with dementia were of an elevated proinflammatory activity via the significant changes of IgG glycome. Therefore, IgG N-glycans might contribute to be potential novel biomarkers for the neurodegenerative process risk assessment of dementia

Role of ST-Segment Resolution Alone and in Combination With TIMI Flow After Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction

BACKGROUND: To evaluate the role of ST-segment resolution (STR) alone and in combination with Thrombolysis in Myocardial Infarction (TIMI) flow in reperfusion evaluation after primary percutaneous coronary intervention (PPCI) for ST-segment– elevation myocardial infarction by investigating the long-term prognostic impact.METHODS AND RESULTS: From January 2013 through September 2014, we studied 5966 patients with ST-segment–elevation myocardial infarction enrolled in the CAMI (China Acute Myocardial Infarction) registry with available data of STR evaluated at 120 minutes after PPCI. Successful STR included STR ≥50% and complete STR (ST-segment back to the equipotential line). After PPCI, the TIMI flow was assessed. The primary outcome was 2-year all-cause mortality. STR &lt; 50%, STR ≥50%, and complete STR occurred in 20.6%, 64.3%, and 15.1% of patients, respectively. By multivariable analysis, STR ≥50% (5.6%; adjusted hazard ratio [HR], 0.45 [95% CI, 0.36–0.56]) and complete STR (5.1%; adjusted HR, 0.48 [95% CI, 0.34–0.67]) were significantly associated with lower 2-year mortality than STR &lt;50% (11.7%). Successful STR was an independent predictor of 2-year mortality across the spectrum of clinical variables. After combining TIMI flow with STR, different 2-year mortality was observed in subgroups, with the lowest in successful STR and TIMI 3 flow, intermediate when either of these measures was reduced, and highest when both were abnormal.CONCLUSIONS: Post-PPCI STR is a robust long-term prognosticator for ST-segment–elevation myocardial infarction, whereas the integrated analysis of STR plus TIMI flow yields incremental prognostic information beyond either measure alone, support-ing it as a convenient and reliable surrogate end point for defining successful PPCI.</p

Role of ST-Segment Resolution Alone and in Combination With TIMI Flow After Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction

BACKGROUND: To evaluate the role of ST-segment resolution (STR) alone and in combination with Thrombolysis in Myocardial Infarction (TIMI) flow in reperfusion evaluation after primary percutaneous coronary intervention (PPCI) for ST-segment– elevation myocardial infarction by investigating the long-term prognostic impact.METHODS AND RESULTS: From January 2013 through September 2014, we studied 5966 patients with ST-segment–elevation myocardial infarction enrolled in the CAMI (China Acute Myocardial Infarction) registry with available data of STR evaluated at 120 minutes after PPCI. Successful STR included STR ≥50% and complete STR (ST-segment back to the equipotential line). After PPCI, the TIMI flow was assessed. The primary outcome was 2-year all-cause mortality. STR &lt; 50%, STR ≥50%, and complete STR occurred in 20.6%, 64.3%, and 15.1% of patients, respectively. By multivariable analysis, STR ≥50% (5.6%; adjusted hazard ratio [HR], 0.45 [95% CI, 0.36–0.56]) and complete STR (5.1%; adjusted HR, 0.48 [95% CI, 0.34–0.67]) were significantly associated with lower 2-year mortality than STR &lt;50% (11.7%). Successful STR was an independent predictor of 2-year mortality across the spectrum of clinical variables. After combining TIMI flow with STR, different 2-year mortality was observed in subgroups, with the lowest in successful STR and TIMI 3 flow, intermediate when either of these measures was reduced, and highest when both were abnormal.CONCLUSIONS: Post-PPCI STR is a robust long-term prognosticator for ST-segment–elevation myocardial infarction, whereas the integrated analysis of STR plus TIMI flow yields incremental prognostic information beyond either measure alone, support-ing it as a convenient and reliable surrogate end point for defining successful PPCI.</p

Role of ST-Segment Resolution Alone and in Combination With TIMI Flow After Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction

BACKGROUND: To evaluate the role of ST-segment resolution (STR) alone and in combination with Thrombolysis in Myocardial Infarction (TIMI) flow in reperfusion evaluation after primary percutaneous coronary intervention (PPCI) for ST-segment– elevation myocardial infarction by investigating the long-term prognostic impact.METHODS AND RESULTS: From January 2013 through September 2014, we studied 5966 patients with ST-segment–elevation myocardial infarction enrolled in the CAMI (China Acute Myocardial Infarction) registry with available data of STR evaluated at 120 minutes after PPCI. Successful STR included STR ≥50% and complete STR (ST-segment back to the equipotential line). After PPCI, the TIMI flow was assessed. The primary outcome was 2-year all-cause mortality. STR &lt; 50%, STR ≥50%, and complete STR occurred in 20.6%, 64.3%, and 15.1% of patients, respectively. By multivariable analysis, STR ≥50% (5.6%; adjusted hazard ratio [HR], 0.45 [95% CI, 0.36–0.56]) and complete STR (5.1%; adjusted HR, 0.48 [95% CI, 0.34–0.67]) were significantly associated with lower 2-year mortality than STR &lt;50% (11.7%). Successful STR was an independent predictor of 2-year mortality across the spectrum of clinical variables. After combining TIMI flow with STR, different 2-year mortality was observed in subgroups, with the lowest in successful STR and TIMI 3 flow, intermediate when either of these measures was reduced, and highest when both were abnormal.CONCLUSIONS: Post-PPCI STR is a robust long-term prognosticator for ST-segment–elevation myocardial infarction, whereas the integrated analysis of STR plus TIMI flow yields incremental prognostic information beyond either measure alone, support-ing it as a convenient and reliable surrogate end point for defining successful PPCI.</p

Role of ST-Segment Resolution Alone and in Combination With TIMI Flow After Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction

BACKGROUND: To evaluate the role of ST-segment resolution (STR) alone and in combination with Thrombolysis in Myocardial Infarction (TIMI) flow in reperfusion evaluation after primary percutaneous coronary intervention (PPCI) for ST-segment– elevation myocardial infarction by investigating the long-term prognostic impact.METHODS AND RESULTS: From January 2013 through September 2014, we studied 5966 patients with ST-segment–elevation myocardial infarction enrolled in the CAMI (China Acute Myocardial Infarction) registry with available data of STR evaluated at 120 minutes after PPCI. Successful STR included STR ≥50% and complete STR (ST-segment back to the equipotential line). After PPCI, the TIMI flow was assessed. The primary outcome was 2-year all-cause mortality. STR &lt; 50%, STR ≥50%, and complete STR occurred in 20.6%, 64.3%, and 15.1% of patients, respectively. By multivariable analysis, STR ≥50% (5.6%; adjusted hazard ratio [HR], 0.45 [95% CI, 0.36–0.56]) and complete STR (5.1%; adjusted HR, 0.48 [95% CI, 0.34–0.67]) were significantly associated with lower 2-year mortality than STR &lt;50% (11.7%). Successful STR was an independent predictor of 2-year mortality across the spectrum of clinical variables. After combining TIMI flow with STR, different 2-year mortality was observed in subgroups, with the lowest in successful STR and TIMI 3 flow, intermediate when either of these measures was reduced, and highest when both were abnormal.CONCLUSIONS: Post-PPCI STR is a robust long-term prognosticator for ST-segment–elevation myocardial infarction, whereas the integrated analysis of STR plus TIMI flow yields incremental prognostic information beyond either measure alone, support-ing it as a convenient and reliable surrogate end point for defining successful PPCI.</p

Profile of immunoglobulin G N-glycome in COVID-19 patients: A case-control study

Coronavirus disease 2019 (COVID-19) remains a major health challenge globally. Previous studies have suggested that changes in the glycosylation of IgG are closely associated with the severity of COVID-19. This study aimed to compare the profiles of IgG N-glycome between COVID-19 patients and healthy controls. A case-control study was conducted, in which 104 COVID-19 patients and 104 age- and sex-matched healthy individuals were recruited. Serum IgG N-glycome composition was analyzed by hydrophilic interaction liquid chromatography with the ultra-high-performance liquid chromatography (HILIC-UPLC) approach. COVID-19 patients have a decreased level of IgG fucosylation, which upregulates antibody-dependent cell cytotoxicity (ADCC) in acute immune responses. In severe cases, a low level of IgG sialylation contributes to the ADCC-regulated enhancement of inflammatory cytokines. The decreases in sialylation and galactosylation play a role in COVID-19 pathogenesis via the activation of the lectin-initiated alternative complement pathway. IgG N-glycosylation underlines the complex clinical phenotypes of SARS-CoV-2 infection

Enhancing LVRT Capability of DFIG-Based Wind Turbine Systems with SMES Series in the Rotor Side

The necessary Low Voltage Ride Through (LVRT) capability is very important to wind turbines. This paper presents a method to enhance LVRT capability of doubly fed induction generators- (DFIGs-) based wind turbine systems with series superconducting magnetic energy storage (SMES) in the rotor side. When grid fault occurs, series SMES in the rotor side is utilized to produce a desired output voltage and absorbs energy. Compared with other methods which enhance LVRT capability with Superconducting Fault-Current Limiter-Magnetic Energy Storage System (SFCL-MESS), this strategy can control the output voltage of SMES to suppress the transient AC voltage component in the rotor directly, which is more effective and rapid. Theoretical study of the DFIG under low voltage fault is developed; the simulation results are operated by MATLAB/Simulink

Identification of Potential Risk Genes and the Immune Landscape of Idiopathic Pulmonary Arterial Hypertension via Microarray Gene Expression Dataset Reanalysis

Gene dysfunction and immune cell infiltration play an essential role in the pathogenesis of idiopathic pulmonary arterial hypertension (IPAH). We aimed to investigate the immune landscape and novel differentially expressed genes (DEGs) of IPAH. In addition, potential druggable molecular targets for IPAH were also explored. In this study, the GSE117261 dataset was reanalyzed to explore the immune landscape and hub DEGs of IPAH. Lasso Cox regression analysis and receiver operating characteristic curve analysis were performed to detect the predictive value of IPAH. Additionally, the underlying drug targets for IPAH treatment were determined by drug–gene analysis. IPAH was significantly associated with the transforming growth factor-β (TGF-β) signaling pathway and Wnt signaling pathway as well as energetic metabolism dysfunction. We identified 31 upregulated and 39 downregulated DEGs in IPAH patients. Six hub genes, namely, SAA1, CCL5, CXCR1, CXCR2, CCR1, and ADORA3, were related to IPAH pathogenesis regardless of sex differences. Prediction model analysis showed that the area under the curve values of the hub DEGs except CXCR2 were all above 0.9 for distinguishing IPAH patients. In addition, the relative proportions of 5 subtypes of immune cells, namely, CD8+ T cells, CD4+ memory resting T cells, γ delta T cells, M1 macrophages, and resting mast cells, were significantly upregulated in the IPAH samples, while 6 subtypes of immune cells, namely, CD4+ naive T cells, resting NK cells, monocytes, M0 macrophages, activated mast cells, and neutrophils, were downregulated. Additionally, a total of 17 intersecting drugs targeting 5 genes, CCL5, CXCR1, CXCR2, CCR1, and ADORA3, were generated as potential druggable molecular targets for IPAH. Our study revealed the underlying correlations between genes and immune cells in IPAH and demonstrated for the first time that SAA1, CCL5, CXCR1, CCR1, and ADORA3 may be novel genetic targets for IPAH

JUN-induced super-enhancer RNA forms R-loop to promote nasopharyngeal carcinoma metastasis

Abstract Oncogenic super-enhancers (SEs) generate noncoding enhancer/SE RNAs (eRNAs/seRNAs) that exert a critical function in malignancy through powerful regulation of target gene expression. Herein, we show that a JUN-mediated seRNA can form R-loop to regulate target genes to promote metastasis of nasopharyngeal carcinoma (NPC). A combination of global run-on sequencing, chromatin-immunoprecipitation sequencing, and RNA sequencing was used to screen seRNAs. A specific seRNA associated with NPC metastasis (seRNA-NPCM) was identified as a transcriptional regulator for N-myc downstream-regulated gene 1 (NDRG1). JUN was found to regulate seRNA-NPCM through motif binding. seRNA-NPCM was elevated in NPC cancer tissues and highly metastatic cell lines, and promoted the metastasis of NPC cells in vitro and in vivo. Mechanistically, the 3’ end of seRNA-NPCM hybridizes with the SE region to form an R-loop, and the middle segment of seRNA-NPCM binds to heterogeneous nuclear ribonucleoprotein R (hnRNPR) at the promoter of distal gene NDRG1 and neighboring gene tribbles pseudokinase 1 (TRIB1). These structures promote chromatin looping and long-distance chromatin interactions between SEs and promoters, thus facilitating NDRG1 and TRIB1 transcription. Furthermore, the clinical analyses showed that seRNA-NPCM and NDRG1 were independent prognostic factors for NPC patients. seRNA-NPCM plays a critical role in orchestrating target gene transcription to promote NPC metastasis