Bidirectionally promoting assembly order for ultrastiff and highly thermally conductive graphene fibres.

Macroscopic fibres assembled from two-dimensional (2D) nanosheets are new and impressing type of fibre materials besides those from one-dimensional (1D) polymers, such as graphene fibres. However, the preparation and property-enhancing technologies of these fibres follow those from 1D polymers by improving the orientation along the fibre axis, leading to non-optimized microstructures and low integrated performances. Here, we show a concept of bidirectionally promoting the assembly order, making graphene fibres achieve synergistically improved mechanical and thermal properties. Concentric arrangement of graphene oxide sheets in the cross-section and alignment along fibre axis are realized by multiple shear-flow fields, which bidirectionally promotes the sheet-order of graphene sheets in solid fibres, generates densified and crystalline graphitic structures, and produces graphene fibres with ultrahigh modulus (901 GPa) and thermal conductivity (1660 W m-1 K-1). We believe that the concept would enhance both scientific and technological cognition of the assembly process of 2D nanosheets.

Case report: Mild leukoencephalopathy caused by a new mutation of NOTCH3 gene.

BACKGROUND: Cerebral autosomal dominant arteriosis with subcortical infarction and leukoencephalopathy (CADASIL) is a single-gene small-vessel disease of the brain characterized by migraine, recurrent ischemic stroke, psychiatric disorders, progressive cognitive decline, and occasional intracerebral hemorrhage.[1]NOTCH3 was identified as a pathogenic gene for CADASIL.[2] The NOTCH3 gene encodes a membrane-bound receptor protein, and to date, several different NOTCH3 gene mutations have been identified.[3] Here, we report a case of CADASIL with a heterozygous mutation c.931T > G (thymine > guanine) on the exon region of the NOTCH3 gene, resulting in an amino acid change p.C311G (cysteine > glycine). CASE REPORT: We report a case of a female patient with CADASIL whose genetic sequencing revealed a mutation in the NOTCH3 gene. However, this patient did not exhibit any of the typical clinical findings of CADASIL but the patient's cerebral magnetic resonance imaging was consistent with the characteristic findings of CADASIL. CONCLUSIONS: This case reminds us that mutations caused by different mutation sites present different clinical symptoms.

A predictive model for disease severity among COVID-19 elderly patients based on IgG subtypes and machine learning.

Objective: Due to the increased likelihood of progression of severe pneumonia, the mortality rate of the elderly infected with coronavirus disease 2019 (COVID-19) is high. However, there is a lack of models based on immunoglobulin G (IgG) subtypes to forecast the severity of COVID-19 in elderly individuals. The objective of this study was to create and verify a new algorithm for distinguishing elderly individuals with severe COVID-19. Methods: In this study, laboratory data were gathered from 103 individuals who had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using a retrospective analysis. These individuals were split into training (80%) and testing cohort (20%) by using random allocation. Furthermore, 22 COVID-19 elderly patients from the other two centers were divided into an external validation cohort. Differential indicators were analyzed through univariate analysis, and variable selection was performed using least absolute shrinkage and selection operator (LASSO) regression. The severity of elderly patients with COVID-19 was predicted using a combination of five machine learning algorithms. Area under the curve (AUC) was utilized to evaluate the performance of these models. Calibration curves, decision curves analysis (DCA), and Shapley additive explanations (SHAP) plots were utilized to interpret and evaluate the model. Results: The logistic regression model was chosen as the best machine learning model with four principal variables that could predict the probability of COVID-19 severity. In the training cohort, the model achieved an AUC of 0.889, while in the testing cohort, it obtained an AUC of 0.824. The calibration curve demonstrated excellent consistency between actual and predicted probabilities. According to the DCA curve, it was evident that the model provided significant clinical advantages. Moreover, the model performed effectively in an external validation group (AUC=0.74). Conclusion: The present study developed a model that can distinguish between severe and non-severe patients of COVID-19 in the elderly, which might assist clinical doctors in evaluating the severity of COVID-19 and reducing the bad outcomes of elderly patients.

Diagnostic Performance of miR-485-3p in Patients with Parkinson's Disease and its Relationship with Neuroinflammation.

Parkinson's disease (PD) is one of the most common progressive neurodegenerative diseases. Some microRNAs (miRNAs) play critical roles in the development of many neurological diseases. This study aims to evaluate the clinical significance and biological function of miR-485-3p in the development and progression of PD. The expression of miR-485-3p in serum of PD patients was analyzed by quantitative real-time PCR (qRT-PCR). LPS-treated microglia BV2 cells were used to mimic neuroinflammation in the pathogenesis of PD. The levels of inflammatory cytokines, including IL-1ß, IL-6 and TNF-α, were detected by enzyme-linked immunosorbent assay (ELISA). The diagnosis value of miR-485-3p was evaluated by plotting receiver operating characteristic (ROC) curves. A luciferase reporter assay was performed to demonstrate the interaction between miR-485-3p and FBXO45. The results showed that miR-485-3p was significantly up-regulated in serum of PD patients compared with that in both Alzheimer's disease (AD) and healthy cases, and had diagnostic accuracy for PD screening. The activated microglia BV2 cells induced by LPS also had elevated miR-485-3p, and the knockdown of miR-485-3p inhibited the release of pro-inflammatory cytokines. FBXO protein 45 (FBXO45) served as a potential target of miR-485-3p, which was speculated to mediate the function of miR-485-3p. Our results suggest that the up-regulated expression of miR-485-3p in PD may be a novel diagnostic biomarker for PD. Reducing the expression level of miR-485-3p can inhibit the inflammatory responses of BV2 cells, which indicated that miR-485-3p, as a regulator of neuroinflammation, may have the potential as a therapeutic target in PD.

Clinical significance of miR-33b in glioma and its regulatory role in tumor cell proliferation, invasion and migration.

Background: This study aimed to investigate the clinical significance of microRNA-33b (miR-33b) in glioma patients and its biological function in tumor progression. Materials & methods: Expression of miR-33b was measured using quantitative real-time RT-PCR. Diagnostic and prognostic values of miR-33b were assessed by the receiver operating characteristics curve and Kaplan-Meier (KM) survival assay. The functional role of miR-33b was further analyzed. Results: Expression of miR-33b in glioma patients and cells was decreased. Expression of miR-33b had high diagnostic accuracy and could predict a poor prognosis. Overexpression of miR-33b led to suppressed glioma cell proliferation, migration and invasion. Conclusion: Decreased expression of miR-33b serves a promising biomarker in the diagnosis and prognosis of glioma, and may be a potential therapeutic target.

[The role of thromboxane A2 receptor gene promoter polymorphism in acute cerebral infarction].

OBJECTIVE: To investigate the association between thromboxane A2 receptor (TXA2R) gene promoter rs2271875, rs768963 polymorphism and acute cerebral infarction in Chinese Han population. METHODS: A prospective study was conducted. From October 2009 to May 2013, 223 patients with cerebral infarction (cerebral infarction group) and 142 cohorts with normal physical examination results (control group) from Taizhou City Central Hospital in Zhejiang Province were enrolled. Triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were determined by enzymatic colorimetry, whereas blood glucose was determined with hexokinase. The genotypes of rs2271875 and rs768963 polymorphism in TXA2R gene were detected by the polymerase chain reaction-ligase detection reaction (PCR-LDR) technique. Differences in gender, age, serum TG, TC, HDL-C, LDL-C, concentration of blood glucose, and blood pressure (systolic pressure, diastolic pressure) between cerebral infarction group and control group were compared as well as TXA2R promoter rs2271875, rs768963 genotype and allele frequencies distribution. RESULTS: The significant differences in males (147 cases vs. 57 cases, χ(2)=23.385, P=0.000), serum TG (2.02±1.14 mmol/L vs. 1.56±0.79 mmol/L, t=4.663, P=0.000), blood glucose (6.40±2.50 mmol/L vs. 5.28±0.92 mmol/L, t=6.084, P=0.000), systolic pressure (146.64±21.34 mmHg vs. 135.73±18.09 mmHg, t=5.234, P=0.000), diastolic blood pressure (86.29±11.79 mmHg vs. 80.74±11.23 mmHg, t=4.468, P=0.000) between cerebral infarction patients and controls were found. The results from multi-logistic regression analysis suggested that male was an independent risk factor for cerebral infarction [odds ratio (OR) 3.300, 95% confidence interval (95%CI) 1.905-5.175, P=0.000]. There were statistically significant differences between infarction group and the control group both in aspects of genotype (TT: 0.112 vs. 0.183, TC: 0.498 vs. 0.535, CC: 0.390 vs. 0.282, χ(2)=6.298, P=0.043) and the allele frequency distribution (T: 0.361 vs. 0.451, C: 0.639 vs. 0.549, χ(2)=5.839, P=0.016) of TXA2R gene rs768963. No statistical significant difference was found in rs2271875 in respect of genotype (GG: 0.336 vs. 0.352, GA: 0.480 vs. 0.451, AA: 0.184 vs. 0.197, χ (2)=0.302, P=0.859) and the allele frequency distribution (G: 0.576 vs. 0.577, A: 0.424 vs. 0.423, χ(2)=0.001, P=0.974). Coefficient of both linkage disequilibrium (D') of rs2271875 and rs768963 was 0.684. When the pair was haplotype AT, the frequency in the infarction group was significantly lower than that in the control group (0.034 vs. 0.081, χ(2)=7.883, P=0.005). CONCLUSIONS: rs768963 gene mutation, but not that of the rs2271875, showed significant correlation with the occurrence of cerebral infarction. There was a loose linkage disequilibrium between rs2271875 and rs768963 of TXA2R. Haplotype AT reduces the risk of cerebral infarction.