A novel signal enhancement strategy for the detection of DNA oxidative damage biomarker 8-OHdG based on the synergy between ß-CD-CuNCs and multi-walled carbon nanotubes.

OBJECTIVE: To propose a novel signal enhancement strategy based on the synergy between ß-CD-CuNCs and multi-walled carbon nanotubes (MWCNTs) for the detection of DNA oxidative damage biomarker 8-Hydroxy-2'-deoxyguanosine (8-OHdG). METHODS: The sensor was constructed with the ß-CD-CuNCs-MWCNTs-nafion film and successfully used for the quantitative detection of 8-OhdG in the presence of biomolecules such as ascorbic acid (AA) and uric acid (UA). To investigate the surface morphology of the modified electrode, Transmission Electron Microscopy (TEM), Cyclic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS) were performed on bare and modified electrodes. RESULTS: According to Differential Pulse Voltammetry (DPV) results, there was a linear relationship between peak current and concentration of 8-OhdG, ranging from 1.0×10-7 to 1.0×10-6 mol/L (R2=0.9926) and 1.0×10-6 to 2.0×10-5 mol/L (R2=0.9933). The detection limit (S/N=3) was 33 nmol/L. CONCLUSIONS: The proposed sensor had been successfully applied to the determination of 8-OHdG in human urine samples with high recovery rates.

LINC00473 protects against cerebral ischemia reperfusion injury via sponging miR-15b-5p and miR-15a-5p to regulate SRPK1 expression.

BACKGROUND: Cerebral ischemia is associated with a high burden of neurological disability. Recently, emerging evidence has demonstrated that long non-coding RNAs (lncRNAs) are crucial regulators in cerebral ischemia reperfusion (I/R) injury. Herein, we investigated the function and potential mechanism of long intergenic non-protein coding RNA 473 (LINC00473) in cerebral I/R injury. METHODS: We established oxygen glucose deprivation/reperfusion (OGD/R) model in Neuro-2a (N2a) cells to mimic the cerebral I/R injury in vitro. RT-qPCR and Western blot assays were conducted to detect target gene expression. Functional assays measured the effects of LINC00473 on cell viability, apoptosis and reactive oxygen species (ROS) production. A series of mechanism assays were carried out to detect the potential mechanism of LINC00473 in cerebral I/R injury. RESULTS: LINC00473 was significantly down-regulated in OGD/R-induced injury model. LINC00473 overexpression reversed the reduced cell viability as well as the enhanced apoptosis and ROS level induced by OGD/R. Moreover, LINC00473 functioneds as a competing endogenous RNA (ceRNA) to sponge miR-15b-5p and miR-15a-5p and thereby regulated SRSF protein kinase 1 (SRPK1) expression. CONCLUSIONS: Our findings confirmed the protective role of LINC00473 in cerebral I/R injury, which might provide a novel target for treating ischemic brain injury.

Diagnosis of Schizophrenia Based on Deep Learning Using fMRI.

Schizophrenia is a brain disease that frequently occurs in young people. Early diagnosis and treatment can reduce family burdens and reduce social costs. There is no objective evaluation index for schizophrenia. In order to improve the classification effect of traditional classification methods on magnetic resonance data, a method of classification of functional magnetic resonance imaging data is proposed in conjunction with the convolutional neural network algorithm. We take functional magnetic resonance imaging (fMRI) data for schizophrenia as an example, to extract effective time series from preprocessed fMRI data, and perform correlation analysis on regions of interest, using transfer learning and VGG16 net, and the functional connection between schizophrenia and healthy controls is classified. Experimental results show that the classification accuracy of fMRI based on VGG16 is up to 84.3%. On the one hand, it can improve the early diagnosis of schizophrenia, and on the other hand, it can solve the classification problem of small samples and high-dimensional data and effectively improve the generalization ability of deep learning models.

Exhausting T Cells During HIV Infection May Improve the Prognosis of Patients with COVID-19.

T-cell reduction is an important characteristic of coronavirus disease 2019 (COVID-19), and its immunopathology is a subject of debate. It may be due to the direct effect of the virus on T-cell exhaustion or indirectly due to T cells redistributing to the lungs. HIV/AIDS naturally served as a T-cell exhaustion disease model for recognizing how the immune system works in the course of COVID-19. In this study, we collected the clinical charts, T-lymphocyte analysis, and chest CT of HIV patients with laboratory-confirmed COVID-19 infection who were admitted to Jin Yin-tan Hospital (Wuhan, China). The median age of the 21 patients was 47 years [interquartile range (IQR) = 40-50 years] and the median CD4 T-cell count was 183 cells/µl (IQR = 96-289 cells/µl). Eleven HIV patients were in the non-AIDS stage and 10 were in the AIDS stage. Nine patients received antiretroviral treatment (ART) and 12 patients did not receive any treatment. Compared to the reported mortality rate (nearly 4%-10%) and severity rate (up to 20%-40%) among COVID-19 patients in hospital, a benign duration with 0% severity and mortality rates was shown by 21 HIV/AIDS patients. The severity rates of COVID-19 were comparable between non-AIDS (median CD4 = 287 cells/µl) and AIDS (median CD4 = 97 cells/µl) patients, despite some of the AIDS patients having baseline lung injury stimulated by HIV: 7 patients (33%) were mild (five in the non-AIDS group and two in the AIDS group) and 14 patients (67%) were moderate (six in the non-AIDS group and eight in the AIDS group). More importantly, we found that a reduction in T-cell number positively correlates with the serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP), which is contrary to the reported findings on the immune response of COVID-19 patients (lower CD4 T-cell counts with higher levels of IL-6 and CRP). In HIV/AIDS, a compromised immune system with lower CD4 T-cell counts might waive the clinical symptoms and inflammatory responses, which suggests lymphocyte redistribution as an immunopathology leading to lymphopenia in COVID-19.

Phoenixin-20 Prevents ox-LDL-Induced Attachment of Monocytes to Human Aortic Endothelial Cells (HAECs): A Protective Implication in Atherosclerosis.

The exact cause of atherosclerosis is not known, and therefore, the current treatment options are limited. The activation of endothelial cells by oxidized low-density lipoprotein (ox-LDL) plays a key role in the initiation and progression of atherosclerosis. Phoenixin-20 is one of the newly identified neuropeptides with pleiotropic effects in the regulation of reproduction and other biological functions. G-protein receptor-coupled 173 (GPR173) is the putative receptor of Phoenixin-20. In the present study, we show that endothelial GPR173 is repressed upon ox-LDL stimulation in human aortic endothelial cells (HAECs). We further elaborate on the hypothesis that GPR173 could be involved in the pathogenesis of atherosclerosis through a series of experiments. Our results indicate that ox-LDL remarkably triggers the increase of ROS, NOX-4, pro-inflammatory cytokines IL-1ß, IL-8, and MCP-1 expression, as well as adhesion molecules ICAM-1 and VCAM-1 release. However, the agonism of GPR173 using Phoenixin-20 significantly ameliorates all of these harmful effects from ox-LDL by suppressing the NF-κB pathway. Furthermore, we show that agonism of GPR173 by Phoenixin-20 prevents the attachment of monocytes THP-1 to endothelial cells, which is an important therapeutic approach to preventing atherogenesis. In conclusion, our study demonstrates that GPR173 agonism by Phoenixin-20 plays a protective role against ox-LDL-induced endothelial dysfunction, implying that Phoenixin-20 may have therapeutic implications in atherosclerosis.

Clinical characteristics of chronic liver disease with coronavirus disease 2019 (COVID-19): a cohort study in Wuhan, China.

BACKGROUND: Previous work has described acute liver injury (ALI) in coronavirus disease 2019 (COVID-19) pneumonia patients, However, there is limited analyses available investigating chronic liver disease (CLD) in COVID-19 patients. This study aimed to investigate clinical characteristics and outcomes of CLD confirmed in COVID-19 patients. RESULTS: A total of 104 cases (each group containing 52 patients) were analyzed in this study. The CLD group showed an average of 14 (10.0~21.2) length of stay (LOS) days, compared to the group without CLD that only showed an average of 12.5 (10~16) LOS days (Relative Risk [RR] = 1.34, 95% CI (1.22~1.48), P<0.001; Adjusted Relative Risk was 1.24 (95% CI: 1.12~1.39)). The CLD group contained a higher mortality rate and slight liver injury. Furthermore, COX regression model analyses suggested that the neutrophil-to-lymphocyte ratio (NLR) was an independent predictor of mortality risk (P < 0.001) in the CLD group. Additionally, a high NLR significantly correlated with a shorter overall survival (P <0.001). CONCLUSIONS: COVID-19 patients also diagnosed with CLD suffered longer LOS, slight liver injuries and a higher mortality when compared to COVID-19 patients without CLD. The NLR was an independent risk factor for in-hospital deaths. Increased expression of NLR was an indicator of poor prognosis in COVID-19 patients with CLD. Thus, COVID-19 patients diagnosed with CLD and who show a higher NLR need additional care. METHODS: A retrospective cohort study was performed at the Wuhan Jin Yin-tan Hospital from February 2, 2020 to April 2, 2020. COVID-19 patients diagnosed with CLD or not diagnosed with CLD were enrolled in this study. The clinical characteristics and outcomes of these patients were compared.

Neuropsychological and neuroimaging assessments of early cognitive impairment in patients after mild ischemic stroke and transient ischemic attack.

This study aimed to identify markers of early cognitive impairment after acute mild ischemic cerebrovascular disease. To further explore the relationship between neuroimaging markers of vascular and neurodegenerative injuries and post-stroke cognitive impairment, 86 patients with transient ischemic attack/acute mild ischemic stroke were recruited. Demographic information, clinical data, stroke scale scores (Modified Rankin Scale, National Institutes of Health Stroke Scale), and neuroimaging parameters (medial temporal lobe atrophy, global cortical atrophy, white matter hyperintensities, location and number of acute infarcts) were collected. All participants underwent neuropsychological evaluation at the time of discharge. The neurocognitive assessment was conducted using the Montreal Cognitive Assessment-Basic and Trail-Making Test A. It was found that low Montreal Cognitive Assessment-Basic scores were associated with global cortical atrophy and lower education levels. The completion time on the Trail-Making Test A was significantly correlated with medial temporal lobe atrophy and less education. It is concluded that global cortical atrophy and lower education levels can be used as rapid indicators of early cognitive impairment in patients after a transient ischemic attack and acute mild ischemic stroke. Medial temporal lobe atrophy also appears to be associated with mental processing speed in patients after a transient ischemic attack and acute mild ischemic stroke.

Association of uric acid with stenosis of intracranial and extracranial arteries in elderly patients with cerebral infarction.

BACKGROUND: To determine whether uric acid (UA) and intracranial and extracranial atherosclerosis stenosis of elderly patients suffering from ischaemic stroke are inter-related. METHODS: Elderly patients with ischaemic stroke underwent computed tomography angiography (CTA) were enrolled between October 2015 and December 2017. We collected clinical assessment, image data, and laboratory tests, and divided patients into four groups: (1) intracranial stenosis atherosclerosis (ICAS) group, (2) combined intracranial and extracranial atherosclerosis stenosis (COAS) group, (3) extracranial carotid stenosis atherosclerosis (ECAS) group, and (4) non-cerebral stenosis atherosclerosis (NCAS) group. We used univariate and multiple logistic regression analyses to explore potential predictors. RESULTS: We included 408 patients in this study, then divided them into elder group (n = 196) and young- and middle-aged group (n = 212). In old stroke patients, 72 cases (36.73%) were classified as the ICAS group, 45 cases (22.96%) as the COAS group, 21 cases (10.71%) as the ECAS group, and 58 cases (29.59%) as the NCAS group. The level of UA was comparatively higher (p = 0.033) in ICAS than in NCAS. Compared with the group which had only one stenosis artery, UA was substantially increased in patients with more than one stenosis intracranial artery (p < 0.001). With a multivariable analysis, UA was an independent predictor for intracranial stenosis of elderly patients (OR = 1.003, p = 0.042), but the relationship between extracranial artery stenosis and uric acid was negative. CONCLUSIONS: Hyperuricaemia is a risk factor of intracranial artery stenosis rather than of ECAS in elderly patients with cerebral infarction.

Spectrum of SLC20A2, PDGFRB, PDGFB, and XPR1 mutations in a large cohort of patients with primary familial brain calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC.

Association of Apolipoprotein A1, B with Stenosis of Intracranial and Extracranial Arteries in Patients with Cerebral Infarction.

BACKGROUND: To investigate the distribution of stenosis of intracranial and extracranial arteries of Han population patients suffering from cerebral infarction in the city of Quanzhou in Fujian and to determine the correlation of apolipoprotein A1 and apolipoprotein B with intracranial and extracranial atherosclerosis stenosis. METHODS: For this study, we enrolled patients with cerebral infarction between December 2009 and October 2012 at the Neurology Department of The Second Affiliated Hospital of Fujian Medical University. All patients were examined by computed tomography angiography (CTA). Past medical history, demographic data, and biochemical markers were collected. Multiple logistic regression analysis was used to study the association between apo A1, apo B, and cerebral atherosclerosis stenosis. RESULTS: A total of 412 patients were included in this study. 137 cases (33.3%) were classified as the intracranial atherosclerosis stenosis (ICAS) group, 74 cases (18.0%) as the combined intracranial and extracranial atherosclerosis stenosis (COAS) group, 44 cases (0.7%) as the extracranial atherosclerosis stenosis (ECAS) group, and 157 cases (38.1%) as the non-cerebral atherosclerosis stenosis (NCAS) group. Middle cerebral arteries (43.8%) were the most common lesions of intracranial arterial atherosclerosis stenosis. Extracranial carotid stenosis (30.7%) were more likely to be stenoses in the extracranial internal carotid arteries. Compared with the NCAS group, apo B was significantly higher (p < 0.001), apo A1 was significantly lower in the ICAS group and COAS group (p = 0.02 and p = 0.030). Compared with the mild atherosclerosis stenosis group, apo B was higher in the severe extracranial atherosclerosis stenosis group (p = 0.03), apo A1 was lower in the severe intracranial atherosclerosis stenosis group (p < 0.001). The multiple logistic regression analyses showed that when apo A1 > 1.28 g/L, it was an independent protective factor of intracranial stenosis (OR, 0.39), apo B was an independent risk factor of the cerebral atherosclerosis stenosis group, and when apo B > 1.16, it is significantly associated with the cerebral atherosclerosis stenosis group (ICAS: OR, 6.41) (ECAS: OR, 5.15). CONCLUSIONS: 1. The occurrence of atherosclerosis stenosis in intracranial arteries is more frequent than that in extracranial arteries in population with cerebral infarction; 2. Apo B is an independent risk factor of intracranial and extracranial arterial stenosis, apo A1 is associated with the degree of intracranial stenosis and an independent protector of intracranial stenosis.