The interaction of global small vessel disease burden and Alzheimer's disease pathologies do not change the independent association of amyloid-beta with hippocampal volume: A longitudinal study on mild cognitive impairment subjects.

The purpose of this study was to investigate whether the co-existence of global small vessel disease (SVD) burdens and Alzheimer's disease (AD) pathologies change hippocampal volume (HV) and cognitive function of mild cognitive impairment (MCI) subjects. We obtained MRI images, cerebrospinal fluid biomarkers (Aß1-42 and p-tau), and neuropsychological tests of 310 MCI subjects from ADNI. The global SVD score was assessed. We used linear regression and linear mixing effect to analyze the effects of global SVD burdens, AD pathologies, and their interactions (SVD*AD) on baseline and longitudinal HV and cognition respectively. We used simple mediation effect to analyze the influencing pathways. After adjusting for global SVD and SVD*AD, Aß remained independently correlated with baseline and longitudinal HV (std ß = 0.294, p = .007; std ß = 0.292, p < .001), indicating that global SVD did not affect the correlation between Aß and HV. Global SVD score was correlated with longitudinal but not baseline HV (std ß = 0.470, p = .050), suggesting that global SVD may be more representative of long-term permanent impairment. Global SVD, AD pathologies, and SVD*AD were independently correlated with baseline and longitudinal cognitions, in which the association of Aß (B = 0.005, 95% CI: 0.005; 0.024) and p-tau (B = -0.002, 95% CI: -0.004; -0.000) with cognition were mediated by HV, suggesting that HV is more likely to explain the progression caused by AD pathology than SVD. The co-existence of global SVD and AD pathologies did not affect the individual association of Aß on HV; HV played a more important role in the influence of AD pathology on cognition than in SVD.

Large-area fluorescence enhancement of R6G based on a uniform PVA-Au plasmonic substrate.

With the development of surface enhanced fluorescence (SEF) spectroscopy technology, uniform and low-cost SEF substrate is urgently needed. In this paper, the nanocomposite films of poly (vinyl alcohol) (PVA) embedded with in-situ Au particles, their localized surface plasmon resonance (LSPR) bands locate at different wavelengths from 525 nm to 569 nm, were used as substrates to enhance the fluorescence of rhodamine 6 G (R6G). The results shows that the uniform light emission in large area can be measured, and the maximum enhancement factor (EF) is about 13 folds. With increasing concentration of R6G films, the EF first increases and then slowly decreases. It is demonstrated that the EF greatly depends on the matching degree of the emission/excitation of R6G and the LSPR band of PVA-Au substrate. All the results further suggests that the PVA-Au substrate not only realize the fluorescence enhancement but also attenuates the fluorescence quenching at higher concentration. In addition, the local electric distribution of the substrate is simulated by using three-dimensional finite different time-domain (FDTD) to further demonstrate the mechanism of the SEF. This substrate has good development prospects in the fields of fluorescent probes and fluorescence imaging, which can be beneficial to the development of uniform and low-cost SEF substrate.

Ag NPs/PMMA nanocomposite as an efficient platform for fluorescence regulation of riboflavin.

The fluorescence detection platform has broad application in many fields. In this paper, we report a simple and efficient fluorescence detection platform based on the synergistic effects of Ag nanoparticles (Ag NPs) and polymethylmethacrylate (PMMA). Ag NPs were introduced to realize the plasmon enhancement fluorescence and a thin PMMA layer was used to adjust the distance between Ag NPs and riboflavin. The thin PMMA layer not only enhances the fluorescence by enhancing adhesion of substrate, but also optimizes the plasmon enhancement fluorescence effect by serving as the spacer. The fluorescence enhancement factor based on this platform shows a trend of increasing with the decrease of the concentration of riboflavin, and the detection of riboflavin is realized based on this feature, the lowest detectable concentration is as low as 0.27 µM. In addition to the detection based on plasmon enhancement fluorescence, the detection of riboflavin at low concentrations can also be realized by the shift and broadening of the fluorescence peak due to the Ag NPs. The combination of the two ways of plasmon enhancement fluorescence and shift of the fluorescence spectra is used for the detection of riboflavin. These results show that the platform has great potential applications in the field of detection and sensing.

Lewy Body-Associated Proteins A-Synuclein (a-syn) as a Plasma-Based Biomarker for Parkinson's Disease.

Introduction: To explore the combined diagnostic value of plasma Lewy body-associated proteins (p-Asyn at ser129, total α-syn, and oligomeric α-syn) for the diagnosis of PD versus healthy controls (HCs) and other PD syndromes (PDs), as well as clinical characteristics prediction. Methods: This study included 145 participants: 79 patients with PD, 24 patients with PDs, and 42 HCs. A panel of plasma levels of p-Asyn, total α-syn, and oligomeric α-syn was measured by enzyme-linked immunosorbent assay (ELISA). The primary outcome was the discriminative accuracy of the combined three plasma biomarkers for PD. Results: The mean age was 65.43 (SD, 7.467) in the control group, 64.49 (SD, 8.224) in participants with PD, and 69.25 (SD, 7.952) in PDs. The plasma Lewy body-associated protein levels were significantly higher in patients with PD than in age-matched HCs, However, there was no difference in patients with PD and PDs. Of note, a combination of plasma p-Asyn, total α-syn, and oligomeric α-syn was a better biomarker for discriminating PD from HCs, with an AUC of 0.8552 (p < 0.0001, 95%CI, 0.7635-0.9409), which was significantly higher than plasma p-Asyn (ΔAUC, 0.1797), total α-syn (ΔAUC, 0.0891) and oligomeric α-syn (ΔAUC, 0.1592) alone. Meanwhile, Lewy body-associated proteins had no connections between different motor stages and dementia performances. Conclusion: Our results suggested that plasma Lewy body-associated proteins, may serve as a non-invasive biomarker to aid the diagnosis of PD from HCs. In addition, increased plasma Lewy body-associated proteins were not associated with the progression of motor and non-motor symptoms.

Neuroprotective effects of curcumin via autophagy induction in 6-hydroxydopamine Parkinson's models.

Curcumin, a polyphenolic compound extracted from curcuma longa, acts as a nontoxic matter with anti-oxidant and anti-inflammatory effects as well as antiproliferative activities. Here, our research aimed to explore the neuroprotective effects of curcumin both in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD) in vivo and 6-OHDA-lesioned PC12 cells in vitro. In vitro, 6-OHDA caused a distinct decrease in cell viability of PC12 cells (150 µM). With the incubation of curcumin (1 µM), 6-OHDA-induced apoptosis was suppressed, increasing the autophagy markers (LC3-II/LC3-I, Beclin-1) and inhibiting phosphor-AKT/AKT, phosphor-mTOR/mTOR. In vivo, curcumin (50 mg/kg) reduced the accumulation of a-synuclein and led to higher parkinsonian disability scores in 6-OHDA-lesioned PD rats, contributing to induction of autophagy through inhibiting AKT/mTOR signal pathway. Moreover, treatment with autophagy inhibitors, such as 3-MA and chloroquine, abolished the neuroprotective effects of curcumin as evidence by compromised autophagy and declined motor behavior in PD rats. In conclusion, the present study demonstrated that curcumin repressed PC12 cell death in vitro and improved parkinsonian disability scores in vivo by inhibiting AKT/mTOR signaling pathway which mediated by autophagy, indicating a potential value of curcumin in the therapeutic intervention of Parkinson's disease.

Identification of Biomarkers Based on Bioinformatics Analysis: The Expression of Ubiquitin-Conjugating Enzyme E2T (UBE2T) in the Carcinogenesis and Progression of Hepatocellular Carcinoma.

BACKGROUND The purpose of this study was to screen and identify key genes in the occurrence and development of hepatocellular carcinoma (HCC) based on bioinformatics analysis. MATERIAL AND METHODS Three Gene Expression Omnibus (GEO) series (GSE) - GSE121248, GSE87630, and GSE84598 - were downloaded from the GEO database. GEO2R was used to screen different genes and a Venn diagram was drawn to screen coexpressed differentially expressed genes (DEGs). Coexpressed DEGs were obtained by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, a protein-protein interaction network diagram was produced by Cytoscape, and module genes were calculated by the Molecular Complex Detection Cytoscape plug-in. Finally, overall survival, progression-free survival, and relapse-free survival analysis of the key genes selected were performed using the online Kaplan-Meier plotter. For the target genes, the online network UCSC Cancer Genome Browser was used to analyze the gene expression profiles of the grade and vascular invasion of HCC. RESULTS A total of 296 coexpressed DEGs were obtained from the 3 GSEs and 12 key genes were obtained from the modular analysis. Survival analysis showed that the upregulated genes UBE2T and FBLN5 were involved in the poor prognosis of HCC. Furthermore, the expression of UBE2T was significantly related to the grade and vascular invasion of HCC. CONCLUSIONS The expression of the UBE2T gene was significantly upregulated in HCC tissue compared to in normal liver tissue. UBE2T may be a new marker for the diagnosis and subsequent therapy of HCC.

Primary microcystic/reticular schwannoma of the frontal bone: illustrative case.

BACKGROUND: To the best of the authors' knowledge, this is the first case of microcystic/reticular schwannoma arising in the frontal bone. OBSERVATIONS: An 18-year-old man presented to the authors' orthopedic clinic with a complaint of a progressively enlarging, painless mass in the frontal bone. It showed significant hyperintensity on T2-weighted imaging with progressive enhancement. Computed tomography combined with three-dimensional reconstruction showed expansive bone destruction with a soft tissue mass in the left side of the frontal bone, without calcification inside or a sclerotic margin around it. The mass was a microcystic/reticular schwannoma as confirmed by surgical pathology. LESSONS: The authors report a rare case of a microcystic/reticular schwannoma arising in the frontal bone, with relatively comprehensive imaging data that enabled them to learn more about this tumor.