Strategies for the detection of site-specific DNA methylation and its application, opportunities and challenges in the field of electrochemical biosensors.

DNA methylation is an epigenetic modification that plays a crucial role in various biological processes. Aberrant DNA methylation is closely associated with the onset of diseases, and the specific localization of methylation sites in the genome offers further insight into the connection between methylation and diseases. Currently, there are numerous methods available for site-specific methylation detection. Electrochemical biosensors have garnered significant attention due to their distinct advantages, such as rapidity, simplicity, high sensitivity, low cost, and the potential for miniaturization. In this paper, we present a systematic review of the primary sensing strategies utilized in the past decade for analyzing site-specific methylation and their applications in electrochemical sensors, from a novel perspective focusing on the localization analysis of site-specific methylation. These strategies include bisulfite treatment, restriction endonuclease treatment, other sensing strategies, and deamination without direct bisulfite treatment. We hope that this paper can offer ideas and references for establishing site-specific methylation electrochemical analysis in clinical practice.

Cardiovascular safety of febuxostat versus allopurinol among the Asian patients with or without gout: A systematic review and meta-analysis.

The cardiovascular (CV) safety of febuxostat compared to allopurinol for the treatment of hyperuricemia among Asian patients is uncertain. In this study, we conducted a systematic review and meta-analysis to compare the CV safety profiles of febuxostat with allopurinol in Asian patients with hyperuricemia. A total of 13 studies were included. On the basis of the pooled results of cohort studies, febuxostat users were at a significantly higher risk for acute coronary syndrome (ACS; hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 1.03-1.09, p < 0.01), atrial fibrillation (HR: 1.19, 95% CI: 1.05-1.35, p < 0.01) than allopurinol users, whereas no significant difference between febuxostat and allopurinol existed for urgent coronary revascularization (HR: 1.07, 95% CI: 0.98-1.16, p = 0.13), and stroke (HR: 0.96, 95% CI: 0.91-1.01, p = 0.13). Nevertheless, that difference in results of acute decompensated heart failure (ADHF; HR: 0.73, 95% CI: 0.35-1.53, p = 0.40) and all-cause death (HR = 0.86, 95% CI: 0.49-1.51, p = 0.60) was not significant based on randomized controlled trials. In the Chinese subgroup, febuxostat could increase the risk of ADHF (HR: 1.22, 95% CI: 1.01-1.48, p < 0.05), CV death (HR: 1.25, 95% CI: 1.03-1.50, p < 0.05), and all-cause mortality (HR: 1.07, 95% CI: 1.01-1.14, p < 0.05) compared to allopurinol. In conclusion, the use of febuxostat, compared with allopurinol among Asian patients, was associated with a significantly increased risk of adverse CV events.

Examining the Role of GLU/GABA to GLN Metabolic Cycle in the Pathogenesis of Post-Stroke Depressive Disorder and Insomnia.

Objective: This study aims to elucidate the potential links between the GLU/GABA to GLN metabolic cycle disruptions and the onset of depressive and insomnia disorders following a stroke. We particularly focus on understanding if these disorders share a common underlying pathogenic mechanism. Methods: We examined 63 patients with post-stroke insomnia, 62 patients with post-stroke depression, and 18 healthy individuals. The study involved assessing insomnia using the Acute Insomnia Scale (AIS) and depression using the Hamilton Depression Rating Scale. We measured serum concentrations of GLN, GLU, and GABA and analyzed their correlations with AIS and HAMD scores. Results: Our results indicate no significant difference in the serum levels of GLN, GLU, and GABA between the post-stroke insomnia and depression groups. However, these levels were notably lower in both patient groups compared to the healthy control group. A negative correlation between AIS scores and GABA levels was observed in the post-stroke insomnia group, suggesting a potential link between GABAergic disturbances and insomnia. Conversely, no significant correlation was found between Hamilton Depression Rating Scale scores and the levels of GABA, GLU, or GLN in the post-stroke depression group. Conclusion: The study highlights that abnormalities in the GLU/GABA to GLN metabolic cycle, particularly the levels of GLN, GABA, and GAD, might be intricately linked to the pathogenesis of post-stroke insomnia and depression. Our findings suggest that GABAergic imbalances could be indicative of post-stroke insomnia, serving as potential biological markers for differential diagnosis in clinical settings. Further research is warranted to explore these relationships in greater depth, potentially leading to new diagnostic and therapeutic approaches for post-stroke neuropsychiatric disorders.

A hard mask process and alignment device aims to achieve high consistency and mass-scale production of gas sensors based on spraying hydrothermal gas sensing material.

The material synthesized through the hydrothermal method has received extensive and in-depth study in recent years, with a large number of literature reporting their excellent performance in the fields of catalysis or gas sensitivity. In order to combine the hydrothermal material with micro-electro-mechanical system processes to achieve large-scale manufacturing of hydrothermal synthesized materials at the wafer-level, this paper proposes a series of processes for hard mask patterned electro-atomization spraying of hydrothermal materials and designs and manufactures an alignment device that achieves the alignment of silicon hard mask and electrode wafers based on the vacuum clamping principle. Through experiments, it has been verified that this device can achieve micrometer-level alignment between the hard mask and the electrode wafer. By conducting electro-atomization spraying, hard mask patterning, optical microscopy, and confocal laser scanning microscope measurements, as well as gas sensitivity testing on a CeO2/TiO2 hydrothermal composite material published in our previous research, it was further verified that this process has good film formation consistency (Sa and Sq are both less than 3 µm and the average film thickness deviation is less than 5 µm), excellent and consistent gas sensitivity performance, and good long-term working stability. This article provides a promising process method for the large-scale production of hydrothermal synthesis materials at the wafer-level.

Mechanism underlying treatment of ischemic stroke using acupuncture: transmission and regulation.

The inflammatory response after cerebral ischemia/reperfusion is an important cause of neurological damage and repair. After cerebral ischemia/reperfusion, microglia are activated, and a large number of circulating inflammatory cells infiltrate the affected area. This leads to the secretion of inflammatory mediators and an inflammatory cascade that eventually causes secondary brain damage, including neuron necrosis, blood-brain barrier destruction, cerebral edema, and an oxidative stress response. Activation of inflammatory signaling pathways plays a key role in the pathological process of ischemic stroke. Increasing evidence suggests that acupuncture can reduce the inflammatory response after cerebral ischemia/reperfusion and promote repair of the injured nervous system. Acupuncture can not only inhibit the activation and infiltration of inflammatory cells, but can also regulate the expression of inflammation-related cytokines, balance the effects of pro-inflammatory and anti-inflammatory factors, and interfere with inflammatory signaling pathways. Therefore, it is important to study the transmission and regulatory mechanism of inflammatory signaling pathways after acupuncture treatment for cerebral ischemia/reperfusion injury to provide a theoretical basis for clinical treatment of this type of injury using acupuncture. Our review summarizes the overall conditions of inflammatory cells, mediators, and pathways after cerebral ischemia/reperfusion, and discusses the possible synergistic intervention of acupuncture in the inflammatory signaling pathway network to provide a foundation to explore the multiple molecular mechanisms by which acupuncture promotes nerve function restoration.

Relationship between Aurora-A V57I Polymorphism and the Risk of Cancer: A Meta-Analysis and Trial Sequential Analysis.

Background: It is still conflicting for the correlation between cancer susceptibility and Aurora-A V57I (rs1047972) gene variant from the published researches. This meta-analysis was performed to access the correlation between cancer susceptibility and Aurora-A rs1047972 gene polymorphism by using meta-analysis methods. Methods: Eligible studies published before Nov 1, 2019 were systematically searched in PMC, PubMed, EMBASE, Web of Science, Cochrane Library Database, China National Knowledge Infrastructure, Wanfang databases, in order to collect qualified case-control or cohort studies. The odds ratio (OR) and its 95% confidence interval (95%CI) were used to evaluate the correlation between Aurora-A rs1047972 gene polymorphism and cancer risk. Sensitivity analysis was used to examine the stability of the results; Egger's test and Begg's funnel chart were used to assess possible publication bias. Trial sequential analysis (TSA) was used to access whether the sample size of our meta-analysis was sufficient. Results: The sample set extracted from 24 case-control studies involving 35,926 subjects (14,639 cases and 21,287 controls) for the association of Aurora-A rs1047972 gene polymorphism with cancer susceptibility. In our meta-analysis, Aurora-A rs1047972 polymorphism was associated with an increased risk of cancer susceptibility in overall populations (GA+GG vs. AA: P=0.039, OR=1.106; 95% CI 1.005-1.218; AA vs. GG: P=0.003, OR= 0.814; 95% CI, 0.710-0.934), and the GA/GG variant might be a risk factor for cancer susceptibility. In the stratified analysis by ethnicity, we found a significant association between Aurora-A rs1047972 variant and the susceptibility of the cancer in Caucasian population. In a subgroup analysis by cancer type, we observed a significantly increased susceptibility of lung cancer. In addition, an increased risk was found between Aurora-A rs1047972 polymorphism and cancer susceptibility in MALDI-TOF group and among population-based study (PB) patients. Our results were in a sufficiently large number of participants according to TSA and did not require more studies to confirm such association. Conclusion: Our meta-analysis revealed that the susceptibility of cancer was associated with Aurora-A rs1047972 polymorphism, especially in Caucasians. And the GA/GG variant might be a risk factor for cancer susceptibility.

Effects of IL-4-590C/T (rs2243250) Polymorphism on the Susceptibility of Smoking-Related Cancer: A Meta-Analysis Involving 11,407 Subjects.

BACKGROUND: Several previous studies have assessed the relationship between IL-4-590C/T gene polymorphism and smoking-related cancer in recent years; however, the results remain controversial. Based on it, the study intends to clarify whether IL-4-590C/T variant increases the risk of smoking-related cancer through meta-analysis. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library database, China National Knowledge Infrastructure, and Wanfang data information service platform to collect qualified case-control studies in strict accordance with the inclusion and exclusion standards. The 95% confidence interval (95% CI) and its odds ratio (OR) were adopted to access the relation between IL-4-590C/T gene polymorphism and smoking-related cancer; sensitivity analysis and publication bias assessment were carried out after the studies' quality evaluation. RESULTS: 17 studies were included in total, with 5,061 patients and 6,346 control cases. A significant association between IL-4-590C/T variant and smoking-related cancer in total population was revealed in our meta-analysis results, and IL-4-590C/T variant might have a relatively protective effect on smoking-related cancer (CT vs. TT: P=0.026, OR = 0.900, 95% CI: 0.820-0.987). Subgroup analysis by ethnicity showed that the IL-4-590C/T polymorphism was associated with a decreased risk of smoking-related cancer in the Asian population (CT vs. TT: P=0.008, OR = 0.878, 95% CI: 0.798-0.967; CC + CT vs. TT: P=0.030, OR = 0.903, 95% CI: 0.824-0.990). Subgroup analysis based on types of cancer demonstrated the IL-4-590C/T variant achieved a lower risk in renal cell cancer (CC vs. TT: P=0.046, OR = 0.640, 95% CI: 0.412-0.993). CONCLUSION: There is a conspicuous association between IL-4-590C/T polymorphism and decreased risk of smoking-related cancer, particularly in Asians. And IL-4-590C/T polymorphism may have a protective effect on renal cell cancer.

Association between TGF-ß1 rs1982073/rs1800469 polymorphism and lung cancer susceptibility: An updated meta-analysis involving 7698 cases and controls.

BACKGROUND: There have been several case-control studies to assess the relationship between the transforming growth factor-ß1 (TGF-ß1) T + 869C (rs1982073)/C-509T (rs1800469) gene polymorphism and lung cancer in recent years; however, the results remain controversial. In this study, we investigated the potential correlation between the TGF-ß1 T + 869C/C-509T polymorphism and increased risk of lung cancer through meta-analysis. METHODS: We searched the Cochrane Library database, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, and the Wanfang Data Information Service platform to identify relevant case-control studies in strict accordance with the inclusion and exclusion criteria. The odds ratio (OR) and its 95% confidence interval (95% CI) were used to evaluate the correlation between TGF-ß1 gene polymorphism and lung tumor risk. Sensitivity analysis and Egger test were used to evaluate the stability of the results and possible publication bias. RESULTS: A total of 8 studies, with 3680 patients and 4018 controls, were included. The meta-analysis revealed that there was no conspicuous correlation between the TGF-ß1 T + 869C (rs1982073)/C-509T (rs1800469) variant and lung cancer in the overall population. For TGF-ß1 C-509T, a significant decreased risk was identified in patients with nonsmall-cell lung cancer (NSCLC) in the analysis stratified by disease (TT vs CT + CC: P = .02, OR = 0.49, 95% CI 0.27-0.90). However, for TGF-ß1 T + 869C, subgroup analysis showed no correlation between the T + 869C polymorphism and lung cancer susceptibility in patients with NSCLC. In the subgroup analysis by ethnicity, no distinct association was observed between T + 869C (rs1982073)/C-509T (rs1800469) polymorphism and lung cancer susceptibility in the Asian and Caucasian groups. Moreover, no significant association was found in the analysis of groups stratified by age, sex, and smoking history. CONCLUSION: The TGF-ß1 T + 869C (rs1982073) and C-509T (rs1800469) polymorphisms are not implicated in lung cancer susceptibility in the overall population. However, our analysis indicated that the C-509T (rs1800469) polymorphism decreases the risk of lung cancer in patients with NSCLC.