A bioinspired heterostructured nanochannel based on dendrimer-gold network and aluminum oxide arrays for sensitive detection of miRNA.

BACKGROUND: MicroRNAs, as oncogenes or tumor suppressors, enable to up or down-regulate gene expression during tumorigenesis. The detection of miRNAs with high sensitivity is crucial for the early diagnosis of cancer. Inspired by biological ion channels, artificial nanochannels are considered as an excellent biosensing platform with relatively high sensitivity and stability. The current nanochannel biosensors are mainly based on homogeneous membranes, and their monotonous structure and functionality limit its further development. Therefore, it is necessary to develop a heterostructured nanochannel with high ionic current rectification to achieve highly sensitive miRNA detection. RESULTS: In this work, an asymmetric heterostructured nanochannel constructed from dendrimer-gold nanoparticles network and anodic aluminum oxide are designed through an interfacial super-assembly method, which can regulate ion transport and achieve sensitive detection of target miRNA. The symmetry breaking is demonstrated to endow the heterostructured nanochannels with an outstanding ionic current rectification performance. Arising from the change of surface charges in the nanochannels triggered by DNA cascade signal amplification in solution, the proposed heterogeneous nanochannels exhibits excellent DNA-regulated ionic current response. Relying on the nucleic acid's hybridization and configuration transformation, the target miRNA-122 associated with liver cancer can be indirectly quantified with a detection limit of 1 fM and a wide dynamic range from 1 fM to 10 pM. The correlation fitting coefficient R2 of the calibration curve can reach to 0.996. The experimental results show that the method has a good recovery rate (98%-105 %) in synthetic samples. SIGNIFICANCE: This study reveals how the surface charge density of nanochannels regulate the ionic current response in the heterostructured nanochannels. The designed heterogeneous nanochannels not only possess high ionic current rectification property, but also enable to induce superior transport performance by the variation of surface chemistry. The proposed biosensor is promising for applications in early diagnosis of cancers, life science research, and single-entity electrochemical detection.

CircPTK2 may be associated with depressive-like behaviors by influencing miR-182-5p.

BACKGROUND: Major depressive disorder (MDD) is a severe psychiatric disorder with uncertain causes. Recent studies have indicated correlations between circular RNAs (circRNAs) and psychiatric disorders. However, the potential role of circRNAs in MDD remains largely unknown. METHODS: We investigated the expression and diagnostic significance of circRNA protein tyrosine kinase 2 (circPTK2) by recruiting 50 MDD patients and 40 healthy subjects. Additionally, chronic unpredictable mild stress (CUMS) mouse model was established in animal experiments. QRT-PCR was adopted for circPTK2 and miR-182-5p levels. To investigate the role of circPTK2 in MDD, we utilized microinjection of circPTK2 adeno-associated virus into the mouse hippocampus. Depressive-like behaviors of mice were assessed through forced swim test and open field test. Additionally, the interaction between circPTK2 and miR-182-5p was validated using a dual luciferase reporter assay. RESULTS: Decreased expression of circPTK2 was found in peripheral blood mononuclear cells of MDD patients and in hippocampus of CUMS mice, which was useful for distinguishing MDD patients from healthy subjects. Notably, overexpression of circPTK2 was associated with depressive-like behaviors induced by CUMS. Further mechanism research demonstrated that circPTK2 functioned as the sponge for miR-182-5p, which may contribute to the beneficial effect of circPTK2. CONCLUSION: Collectively, our findings suggest the participation of circPTK2 and its underlying mechanism in MDD, which might provide a potential target for MDD therapy.

Association between stress hyperglycemia ratio and prognosis in acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Stress hyperglycemia is a relatively transient increase in blood glucose in response to inflammation of the body and neurohormonal disorders. It is still debated whether stress hyperglycemia ratio (SHR) in the acute phase, a new indicator of stress hyperglycemia, is related to poor prognosis in acute ischemic stroke (AIS) patients. This meta-analysis provides insight into the connection between SHR and prognosis in AIS patients. METHODS: We screened all potentially relevant studies using a comprehensive database search. The standardized mean difference (SMD) and 95% confidence interval (CI) were utilized to investigate the relationship between SHR in the acute phase and the prognosis of AIS. RESULTS: The pooled results revealed that AIS patients with poor prognoses had significantly higher SHR values than those with good prognoses (SMD = 0.56, 95%CI: 0.37-0.75, p<0.001). Subgroup analysis indicated that study design and differences in post-stroke treatment might be the sources of heterogeneity in this meta-analysis. CONCLUSIONS: High SHR in the acute period is related to poor prognosis after AIS. SHR may be a new predictor of poor outcomes in AIS patients.

Research landscape and trends of cerebral amyloid angiopathy: a 25-year scientometric analysis.

Background: Cerebral amyloid angiopathy (CAA), a cerebral small vessel disease affecting leptomeningeal and cortical small blood vessels, is a common cause of spontaneous lobar intracerebral hemorrhage and cognitive impairment, particularly in elderly patients. This study aims to investigate the field of CAA research from a scientometric perspective. Methods: Publications related to CAA from January 1st, 1999 to September 29th, 2023 were retrieved from the Web of Science Core Collection database. The scientometric software VOSviewer and CiteSpace were used to analyze and visualize the publication trends, countries/regions, institutions, authors, journals, cited references, and keywords of CAA. Results: A total of 2,798 publications related to CAA from 73 countries/regions, led by the United States, were included. The number of publications showed an increasing trend over time. Massachusetts General Hospital was the most productive institution, and authors Greenberg and Charidimou published the most papers and were most frequently co-cited. Journal of Alzheimer's Disease was the most prolific journal in this field, and Neurology was the most co-cited journal. Apart from "cerebral amyloid angiopathy", the most frequently used keywords were "Alzheimer's disease", "amyloid beta", "intracerebral hemorrhage", and "dementia". The burst keywords in recent years included "cortical superficial siderosis" and "dysfunction". Conclusions: This scientometric analysis provides a comprehensive overview of CAA research over the past 25 years, and offers important insights for future research directions and scientific decision-making in this field.

Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Monocyte-to-Lymphocyte Ratio in Depression: An Updated Systematic Review and Meta-Analysis.

Background: Research on neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in depression is still emerging and has increased 3-fold since the first meta-analysis. An updated meta-analysis with sufficient studies can provide more evidence for a potential relationship between NLR, PLR, MLR, and depression. Methods: We identified 18 studies from the PubMed, EMBASE, Cochrane library, and Web of Science databases. Meta-analyses were performed to generate pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) between patients with depression and controls. Sensitivity analysis, subgroup analysis, meta-regression, and publication bias were conducted. Results: A total of 18 studies including 2,264 depressed patients and 2,415 controls were included. Depressed patients had significantly higher NLR and PLR compared with controls (SMD = 0.33, 95% CI: 0.15-0.52, p < 0.001 and SMD = 0.24, 95% CI: 0.02-0.46, p < 0.05, respectively). MLR was slightly higher in depressed individuals compared to controls (SMD = 0.15, 95% CI: -0.26 to 0.55, p > 0.05), despite the absence of significance. Sensitivity analysis removing one study responsible for heterogeneity showed a higher and significant effect (SMD = 0.32, 95% CI: 0.20-0.44) of MLR. Three subgroup analyses of NLR, PLR, MLR, and depression revealed obvious differences in the inflammatory ratios between depressed patients and controls in China and the matched age and gender subgroup. Individuals with post-stroke depression (PSD) had higher NLR and MLR values as compared to non-PSD patients (SMD = 0.51, 95% CI: 0.36-0.67, p < 0.001 and SMD = 0.46, 95% CI: 0.12-0.79, p < 0.01, respectively). Meta-regression analyses showed that male proportion in the case group influenced the heterogeneity among studies that measured NLR values (p < 0.05). Conclusions: Higher inflammatory ratios, especially NLR, were significantly associated with an increased risk of depression. In the subgroup of China and matched age and gender, NLR, PLR, and MLR were all elevated in depressed patients vs. controls. Individuals with PSD had higher NLR and MLR values as compared to non-PSD patients. Gender differences may have an effect on NLR values in patients with depression.