Causal Associations between Tea Consumption and Rapid Eye Movement Sleep Behavior Disorder: A Mendelian Randomization Study.

INTRODUCTION: Previous studies have shown that tea consumption may have a protective effect against neurodegenerative diseases. However, the exact causal relationship between tea consumption and the precursor stages of certain neurodegenerative diseases, namely, REM sleep behavior disorder (RBD), remains unclear. To evaluate the causal association between tea consumption and RBD, we employed a Mendelian randomization study. METHODS: We identified genetic instrumental variables that are significantly associated with tea consumption through genome-wide association studies (GWAS) in European populations. Bidirectional two-sample Mendelian randomization was utilized to determine the causal relationship between tea consumption and RBD, while sensitivity analyses were further employed to evaluate the robustness of the results. The multivariate Mendelian randomization method was used to assess the influence of relevant confounding factors on the results. RESULTS: In the MR analysis using the inverse-variance weighting method, a significant causal relationship between tea consumption and RBD was observed (OR = 0.046, 95% CI: 0.004-0.563, p = 0.016). The consistency of findings across maximum likelihood, MR Pleiotropy RESidual Sum and Outlier, and multivariate MR after adjusting for potential confounding further supports this causal association. Sensitivity analyses revealed no evidence of heterogeneity or pleiotropy. CONCLUSIONS: The findings of our study demonstrate a robust causal association between tea consumption and RBD, indicating that tea consumption may serve as a protective factor against the development of RBD.

The relationship between serum neurofilament light chain and glial fibrillary acidic protein with the REM sleep behavior disorder subtype of Parkinson's disease.

Studies have shown that rapid eye movement (REM) sleep behavior disorder (RBD) is a subtype of Parkinson's disease (PD) characterized by severe cognitive impairment and rapid disease progression. However, reliable biological markers are lacking presently. Neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) have been widely studied as biomarkers of cognition impairment. This study aimed to find biomarkers for the RBD subtype of PD by investigating the possible relationship between serum NFL, GFAP levels, and the RBD subtype. A total of 109 PD patients and 37 healthy controls (HCs) were included, and their clinical characteristics were evaluated. PD patients were divided into two groups based on whether they had probable RBD or not. Serum NFL and GFAP levels were measured using the ultrasensitive single molecule array (Simoa) platform. The obtained data were statistically analyzed using SPSS 25.0 (IBM, Chicago, IL, USA). NFL and GFAP in the PD-RBD group were elevated compared with the PD-nRBD and control groups. Moreover, serum NFL and GFAP levels positively correlated with RBD. The combination of NFL and GFAP showed good performance in identifying PD-RBD patients from PD-nRBD. After considering potential confounding factors such as age, and disease duration, serum NFL and GFAP emerged as independent risk factors for RBD. Serum NFL and GFAP were related to RBD in PD patients. Concludingly, serum NFL and GFAP might serve as promising biomarkers for the RBD subtype of PD.

Transcriptomic analysis of α-linolenic acid content and biosynthesis in Paeonia ostii fruits and seeds.

BACKGROUND: Paeonia ostii is a potentially important oilseed crop because its seed yield is high, and the seeds are rich in α-linolenic acid (ALA). However, the molecular mechanisms underlying ALA biosynthesis during seed kernel, seed testa, and fruit pericarp development in this plant are unclear. We used transcriptome data to address this knowledge gap. RESULTS: Gas chromatograph-mass spectrometry indicated that ALA content was highest in the kernel, moderate in the testa, and lowest in the pericarp. Therefore, we used RNA-sequencing to compare ALA synthesis among these three tissues. We identified 227,837 unigenes, with an average length of 755 bp. Of these, 1371 unigenes were associated with lipid metabolism. The fatty acid (FA) biosynthesis and metabolism pathways were significantly enriched during the early stages of oil accumulation in the kernel. ALA biosynthesis was significantly enriched in parallel with increasing ALA content in the testa, but these metabolic pathways were not significantly enriched during pericarp development. By comparing unigene transcription profiles with patterns of ALA accumulation, specific unigenes encoding crucial enzymes and transcription factors (TFs) involved in de novo FA biosynthesis and oil accumulation were identified. Specifically, the bell-shaped expression patterns of genes encoding SAD, FAD2, FAD3, PDCT, PDAT, OLE, CLE, and SLE in the kernel were similar to the patterns of ALA accumulation in this tissue. Genes encoding BCCP, BC, KAS I- III, and FATA were also upregulated during the early stages of oil accumulation in the kernel. In the testa, the upregulation of the genes encoding SAD, FAD2, and FAD3 was followed by a sharp increase in the concentrations of ALA. In contrast, these genes were minimally expressed (and ALA content was low) throughout pericarp development. CONCLUSIONS: We used three tissues with high, moderate, and low ALA concentrations as an exemplar system in which to investigate tissue-specific ALA accumulation mechanisms in P. ostii. The genes and TFs identified herein might be useful targets for future studies of ALA accumulation in the tree peony. This study also provides a framework for future studies of FA biosynthesis in other oilseed plants.

Simulation for efficiency improvement of a thuilium Q-switched ytterbium-doped all-fiber laser.

We theoretically explore the mechanism in a thulium Q-switched ytterbium-doped all-fiber fiber laser using a set of rate equations to model the correlations between the photons and the five energy levels of thulium involved in the Q switching mechanism. We demonstrate that by coupling with a gain-switched resonator, the Q-switched laser is stabilized up to the maximum pulsing rate that is limited by the lifetime of level 3H5. To the best of our knowledge, this is the first study that revealed that level 3H5 plays an essential role in reinitialization, achieving sequential pulses, and limiting the maximum repetition rate.

Functional MRI in Parkinson's disease with freezing of gait: a systematic review of the literature.

BACKGROUND: Freezing of gait (FOG), a common and disabling symptom of Parkinson's disease (PD), is characterized by an episodic inability to generate effective stepping. Functional MRI (fMRI) has been used to evaluate abnormal brain connectivity patterns at rest and brain activation patterns during specific tasks in patients with PD-FOG. This review has examined the existing functional neuroimaging literature in PD-FOG, including those with treatment. Summarizing these articles provides an opportunity for a better understanding of the underlying pathophysiology in PD-FOG. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a literature review of studies using fMRI to investigate the underlying pathophysiological mechanisms of PD-FOG. RESULTS: We initially identified 201 documents. After excluding the duplicates, reviews, and other irrelevant articles, 39 articles were finally identified, including 18 task-based fMRI studies and 21 resting-state fMRI studies. CONCLUSIONS: Studies using fMRI techniques to evaluate PD-FOG have found dysfunctional connectivity in widespread cortical and subcortical regions. Standardized imaging protocols and detailed subtypes of PD-FOG are furthered required to elucidate current findings.

Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice.

BACKGROUND: Dendritic cell-associated C-type lectin-1 (Dectin-1) receptor has been reported to be involved in neuroinflammation in Alzheimer's disease and traumatic brain injury. The present study was designed to investigate the role of Dectin-1 and its downstream target spleen tyrosine kinase (Syk) in early brain injury after ischemic stroke using a focal cortex ischemic stroke model. METHODS: Adult male C57BL/6 J mice were subjected to a cerebral focal ischemia model of ischemic stroke. The neurological score, adhesive removal test, and foot-fault test were evaluated on days 1, 3, 5, and 7 after ischemic stroke. Dectin-1, Syk, phosphorylated (p)-Syk, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) expression was analyzed via western blotting in ischemic brain tissue after ischemic stroke and in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. The brain infarct volume and Iba1-positive cells were evaluated using Nissl's and immunofluorescence staining, respectively. The Dectin-1 antagonist laminarin (LAM) and a selective inhibitor of Syk phosphorylation (piceatannol; PIC) were used for the intervention. RESULTS: Dectin-1, Syk, and p-Syk expression was significantly enhanced on days 3, 5, and 7 and peaked on day 3 after ischemic stroke. The Dectin-1 antagonist LAM or Syk inhibitor PIC decreased the number of Iba1-positive cells and TNF-α and iNOS expression, decreased the brain infarct volume, and improved neurological functions on day 3 after ischemic stroke. In addition, the in vitro data revealed that Dectin-1, Syk, and p-Syk expression was increased following the 3-h OGD and 0, 3, and 6 h of reperfusion in BV2 microglial cells. LAM and PIC also decreased TNF-α and iNOS expression 3 h after OGD/R induction. CONCLUSION: Dectin-1/Syk signaling plays a crucial role in inflammatory activation after ischemic stroke, and further investigation of Dectin-1/Syk signaling in stroke is warranted.

A clinical analysis on 40 cases of spontaneous intracranial hypotension syndrome.

OBJECTIVE: To investigate clinical and imaging features of 40 patients with spontaneous intracranial hypotension (SIH). METHODS: 40 cases of spontaneous intracranial hypotension (SIH) diagnosed in our hospital from June 2013 to September 2017 were collected and retrospectively analyzed. RESULTS: In our study, the male to female ratio was 2:3. The average age of onset was 43.0 ± 15.0 years. There were 12 (30.0%) patients with clear incentives, mostly catching cold. The average length of hospital stay was 11.2 ± 6.3 days. All the patients showed orthostatic headaches, 62.5% patients with nausea or vomiting, 40.0% patients with neck stiffness, 17.5% patients with dizziness and vertigo, 10.0% patients with numbness and weakness of limbs, 5% patients with neck discomfort, and 2.5% patients with visual symptoms (visual impairment, photophobia, diplopia). 24 patients underwent CT scans which showed no abnormalities in 20 cases (83.3%), subdural fluid accumulation in 3 cases (12.5%), and subdural haematoma in 1 case (2.5%). Cranial contrast-enhanced MR scans showed diffuse pachymeningeal enhancement (95.83%, 23/24), signs of pituitary hyperaemia in 5 cases (20.8%), subdural fluid accumulation and subdural hematoma in 4 cases (16.7%), sagging of the brain in 3 cases (12.5%), and engorgement of venous structures in 1 case (4.1%). Six patients underwent plain and contrast-enhanced spinal MR scans which showed varying degrees of dural thickening and enhanced performance in all the patients. 92.5% (37/40) of patients had cerebrospinal fluid pressure <60 mmH2O on lumbar puncture. 97.5% of patients underwent conservative treatment with drugs and had a good outcome. CONCLUSION: Orthostatic headache and cranial MRI diffuse pachymeningeal enhancement are characteristic features of SIH. Cranial contrast-enhanced MR scan is recognized as the first and non-invasive investigation in the diagnosis of SIH. Most patients had cerebrospinal fluid pressure <60 mmH2O. The vast majority of patients improved with fluid replacement.

Palmar approach with Kirschner-wire fixation in the treatment of children's distal radius extension type fracture.

PURPOSE: To explore the advantages of palmar approach with Kirschner-wire (K-wire) fixation in the treatment of children's distal radius extension type fracture. METHODS: Thirty patients, average age of 8.5 years ranging from 5 to 13 years, with distal radius extension type fracture and undergoing a failed manual reposition in our hospital were included, and treated by palmar approach with K-wire fixation between May 2014 and December 2017. Among these patients (21 male and 9 female), 5 patients had chronic injuries over 10 days, and 6 patients had fracture of the distal radius epiphysis. The time between injury and treatment ranged from 1 to 30 days. Among them, 11 patients with right-sided fractures and 19 patients with left-sided fractures were operated via the palmar longitudinal incision approach. RESULTS: The results were evaluated after an average of 18 months ranging from 5 to 36 months after operation. The recovery time of fracture was from 4 to 8 weeks and all incisions were primary healing with an average of 6 weeks. Nonunion, delayed union, early closure of distal radial epiphysis, and wrist varus/valgus deformity were not found in all the cases. Based on Gartland and Wereley wrist score assessment undertaken three months after operation, excellent scores were achieved in 24 cases, good scores in 3 cases, acceptable scores in 3 cases. CONCLUSION: The palmar approach with K-wire fixation via a front longitudinal incision in the treatment of children's distal radius extension type fracture has following advantages: (1) easy to reposition for both fresh and old fractures; (2) less damage to surrounding tissues and epiphysis; (3) quick recovery. It is suitable to treat children's distal radius extension type fracture.

ROS/TXNIP pathway contributes to thrombin induced NLRP3 inflammasome activation and cell apoptosis in microglia.

There is no effective therapy for intracerebral hemorrhage (ICH) because of poor understanding of the mechanisms of brain injury after hemorrhage. The NLRP3 inflammasome, as a vital component of innate immune system, which is associated with a wide range of human CNS disorders, including ICH. But its detailed mechanisms in ICH remain mainly unclear. In this study, BV2 cells with thrombin exposure were used to investigate the role of NLRP3 inflammasome in thrombin-induced brain injury. We used western blot to detect NLRP3 inflammasome activation and the expression of thioredoxin binding protein (TXNIP), DCFH-DA to investigate intracellular reactive oxygen species (ROS), flow cytometry to analyze apoptosis. Our results showed that ROS inhibitor N-acetyl-l-cysteine (NAC) suppressed the upregulation of intracellular ROS and TXNIP expression. Furthermore, the cell apoptosis and expression of apoptotic protein were significantly attenuated after treatment of thrombin with NAC or NLRP3 antagonist (MCC950). Thrombin activates ROS/TXNIP/NLRP3 signaling in BV2 cells, which may indicate a mechanism that pro-inflammatory and pro-apoptotic contributes to the development of ICH.

Hypereosinophilic syndrome with central nervous system involvement: Two case reports and literature review.

OBJECTIVE: To report two cases of hypereosinophilic syndrome (HES) with central nervous system involvement and explore its possible pathogenesis. METHODS: We have analysed the clinical data and relevant features of two patients who presented themselves to The Affiliated Hospital of Xuzhou Medical University between 2012 and 2015. We have reviewed the relevant literature, elaborated the possible pathogenesis, and discussed the treatment options. RESULTS: Both patients had consistently high levels of absolute eosinophil count which led to multiple cerebral infarcts in the arterial border zone and small-vessel disease. Blood tests were taken several times during their course of disease showing elevated eosinophils. Both patients underwent head computed tomography (CT), magnetic resonance imaging, and magnetic resonance angiography, which indicated small-vessel disease and watershed infarction. Glucocorticoids, improvement cycle, and neuro-nutrition treatments resulted in a significant improvement of their clinical state. CONCLUSION: HES can involve central nervous system by causing small-vessel disease and watershed infarction, which can be its presenting features. Repeated blood tests should be done to rule out HES in central nervous system lesion.

Thrombin-induced apoptosis in neurons through activation of c-Jun-N-terminal kinase.

CONTEXT: Studies have shown that thrombin activation played a central role in cell injuries associated with intracerebral hemorrhage (ICH). OBJECTIVE: Here, our study investigated the cytotoxicity of thrombin on neurons, and determined the involvement of JNK pathways in thrombin-induced neuronal apoptosis. MATERIALS AND METHODS: Primary cultured neurons were treated with different doses of thrombin. Some neurons were given either SP600125 or vehicle. LDH release assay and flow cytometry were used to measure neuronal apoptosis caused by thrombin. The activation of JNK and capases-3 were measured by Western blot. RESULTS: Our results showed large doses of thrombin that increased the LDH release, the level of cleaved caspase-3 and apoptosis rate of neurons. JNK was activated by thrombin in a time-dependent manner. Administration of SP600125 protects neurons from thrombin-induced apoptosis. CONCLUSION: These data indicate that the activation of JNK is crucial for thrombin-induced neuronal apoptosis, and inhibition of JNK may be a potential therapeutic target for ICH.

Neuroprotective Effects of 17ß-Estradiol against Thrombin-Induced Apoptosis in Primary Cultured Cortical Neurons.

AIMS: 17ß-estradiol (E2) is a powerful neuroprotective agent in the central nervous system; however, little is known about its effects on intracerebral hemorrhage. This study examined the effects of E2 on thrombin-induced apoptosis in vitro and investigated the potential mechanisms. METHODS: Primary cultured cortical neurons were treated with E2 or vehicle and then the cells were exposed to thrombin. Neuronal apoptosis was assessed by flow cytometry. The phosphorylated c-Jun-N-terminal kinase (p-JNK), phosphorylated extracellular signal-regulated kinases 1/2 (p-ERK1/2), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-3 were assayed by western blot. RESULTS: Consequently, we found that E2 has significantly reduced the apoptosis in thrombin-treated neurons. E2 also exhibited a downregulation in the ratio of Bax/Bcl-2, caspase-3 and p-JNK. However, E2 had little effect on p-ERK1/2 proteins activation. CONCLUSION: Taken together, E2 has shown neuroprotective effects on thrombin-induced neuronal apoptosis, and the molecular mechanisms may correlate with the inhibition of the JNK signaling pathway.

Utility of serum neurofilament light chain and glial fibrillary acidic protein as diagnostic biomarkers of freezing of gait in Parkinson's disease.

Freezing of gait (FOG) is one of the most distressing features of Parkinson's disease (PD), increasing the risks of fractures and seriously affecting patients' quality of life. We aimed to examine the potential diagnostic roles of serum neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) in PD patients with FOG (PD-FOG). We included 99 patients, comprising 54 PD patients without FOG (PD-NoFOG), 45 PD-FOG and 37 healthy controls (HCs). Our results indicated serum markers were significantly higher in PD-FOG and postural instability and gait difficulty (PIGD) motor subtype patients than in PD-NoFOG and non-PIGD subtype patients (P < 0.05), respectively. Patients with high concentrations of the markers NFL and GFAP had higher PIGD scores and greater FOG severity than those with low concentrations. Moreover, serum levels of both NFL and GFAP were significantly positively associated with age, FOG severity, PD-FOG status, and negatively associated with Mini-Mental State Examination (MMSE) scores. Logistic regression analysis identified serum levels of NFL and GFAP as independent risk factors for PD-FOG. Mediation analysis revealed that MMSE scores fully mediated the relationship between serum GFAP levels and FOG-Q scores, accounting for 33.33% of the total effects (indirect effect = 0.01, 95% CI 0.01-0.02). NFL levels differentiated PD-FOG from PD-NoFOG with reliable diagnostic accuracy (AUC 0.75, 95% CI 0.66-0.84), and the combination of NFL, GFAP, duration and MMSE scores demonstrated high accuracy (AUC 0.84, 95% CI 0.76-0.91). Our findings support the notion that NFL and GFAP may be potential biomarkers for the diagnosis of PD-FOG.

High-frequency rTMS over bilateral primary motor cortex improves freezing of gait and emotion regulation in patients with Parkinson's disease: a randomized controlled trial.

Background: Freezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson's disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD. Methods: This study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes. Results: Two patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1. Conclusion: High-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD.

Functional Localization of the Human Auditory and Visual Thalamus Using a Thalamic Localizer Functional Magnetic Resonance Imaging Task.

Functional magnetic resonance imaging (fMRI) of the auditory and visual sensory systems of the human brain is an active area of investigation in the study of human health and disease. The medial geniculate nucleus (MGN) and lateral geniculate nucleus (LGN) are key thalamic nuclei involved in the processing and relay of auditory and visual information, respectively, and are the subject of blood-oxygen-level-dependent (BOLD) fMRI studies of neural activation and functional connectivity in human participants. However, localization of BOLD fMRI signal originating from neural activity in MGN and LGN remains a technical challenge, due in part to the poor definition of boundaries of these thalamic nuclei in standard T1-weighted and T2-weighted magnetic resonance imaging sequences. Here, we report the development and evaluation of an auditory and visual sensory thalamic localizer (TL) fMRI task that produces participant-specific functionally-defined regions of interest (fROIs) of both MGN and LGN, using 3 Tesla multiband fMRI and a clustered-sparse temporal acquisition sequence, in less than 16 minutes of scan time. We demonstrate the use of MGN and LGN fROIs obtained from the TL fMRI task in standard resting-state functional connectivity (RSFC) fMRI analyses in the same participants. In RSFC analyses, we validated the specificity of MGN and LGN fROIs for signals obtained from primary auditory and visual cortex, respectively, and benchmark their performance against alternative atlas- and segmentation-based localization methods. The TL fMRI task and analysis code (written in Presentation and MATLAB, respectively) have been made freely available to the wider research community.

[Measuring three-dimensional displacement of tooth-supported rigid fixed bridge under oblique concentrated loading using digital laser speckle photography].

OBJECTIVE: To measure three-dimensional displacements of rigid fixed bridge under oblique concentrated loading and to analyze the effect of displacement on the stability of abutment teeth. METHODS: Right mandible of Beagle dog was used to establish the tooth-supported rigid fixed bridge. Digital laser speckle photography was employed to measure the three-dimensional displacements of the prosthesis under oblique concentrated loading ranging from 200 g to 3000 g. RESULTS: The displacements of prosthesis increased as the load increased. When the load was on the abutment, the buccolingual displacement of the abutment under loading was the biggest but no more than 100 microm. This was followed by mesiodistal and occlusallingual displacements. With slighter loadings, the buccolingual displacements of non-loaded abutment were greater than the mesiodistal displacements. However, as the loading increased greater mesiodistal displacements on non-loaded abutment were found compared to buccolingual displacements. When the bridge was loaded, the biggest displacements of the prosthesis were always shown on the buccolingual direction, followed by the mesiodistal direction and the occlusallingual direction. The displacements with loaded bridge were smaller than those when the load was applied on abutment. CONCLUSION: The displacements of rigid fixed bridge change with different loading positions. This has implications on the design of prosthesis. Lateral force should be minimized and early occlusion contact should be avoided, especially on the feeble abutment. This study has developed a new method for measuring bit shift of teeth.

Association of serum neurofilament light chain and glial fibrillary acidic protein levels with cognitive decline in Parkinson's disease.

OBJECTIVES: To investigate whether serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels are associated with motor and cognitive function in Parkinson's disease (PD). METHODS: This cross-sectional study recruited 140 participants, including 103 PD patients and 37 healthy controls (HC). Serum NfL and GFAP levels were measured using the ultrasensitive single-molecule array (Simoa) technique. Motor and cognitive function were evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) and Beijing version of the Montreal Cognitive Assessment (MoCA). Spearman's correlation analyses were used to determine the correlation between serum NfL and GFAP levels and clinical features in PD patients. Binary logistic regression analysis was used to assess the association between serum biomarkers and cognitive impairment in PD patients. RESULTS: We observed significantly higher serum NfL and GFAP levels in PD patients than in HC (p < 0.001). Serum NfL and GFAP levels were negatively correlated with MoCA scores (NfL: r =  - 0.472, p < 0.001; r = 0.395, p < 0.001) and multiple cognitive domains and showed no correlation with motor symptom severity after adjusting for age and sex. Binary logistic regression analysis showed that the serum NfL and GFAP levels were independent contributors to PD with dementia (p < 0.05). CONCLUSIONS: Both serum NfL and GFAP levels correlated with cognitive impairment, but not motor symptoms, in PD patients. Serum NfL and GFAP levels can serve as biomarkers for PD patients at risk of cognitive decline.

Association between serum neurofilament light chain levels and sleep disorders in patients with Parkinson's disease.

OBJECTIVES: This study aimed to investigate the levels of serum neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) in patients with Parkinson's disease (PD) and PD patients with sleep disorders (PD-SD), as well as the relationship between these proteins and sleep disorders in PD patients. METHODS: A total of 96 PD patients and 38 healthy controls (HC) were included in this study, of which 70 PD patients experienced sleep disorders. Both motor symptoms and sleep conditions were assessed in all PD patients. The ultrasensitive single molecule array (SIMOA) technique was used to quantify NFL and GFAP in the serum. All data were statistically analyzed using SPSS 23.0. RESULTS: Serum NFL and GFAP levels were significantly higher in PD patients than in HC. Similarly, PD-SD patients exhibited higher levels of these two proteins than PD patients without sleep disorders (PD-NSD). In addition, both serum GFAP and NFL were significantly associated with sleep-related scales in PD patients. After covariate-adjusted binary logistic regression analysis, NFL remained statistically significant in PD patients with or without sleep disorders, unlike GFAP. CONCLUSIONS: Our findings substantiate that serum NFL and GFAP levels are elevated in PD and PD-SD, suggesting neurological axon damage in PD patients, which may be more severe in PD-SD than in PD-NSD. These findings may affect disease diagnosis and provide the foothold for future studies on the underlying mechanisms.

Increased plasma levels of circPTP4A2 and circTLK2 are associated with stroke injury.

OBJECTIVE: Accumulating studies have shown that circulating circular RNAs (circRNAs) represent novel biomarkers for many human diseases. We investigated whether plasma circPTP4A2 and circTLK2 levels are associated with stroke severity, infarct volume, stroke etiology, and functional outcome in acute ischemic stroke (AIS) patients. METHODS: We applied quantitative real-time PCR (qPCR) to measure plasma circPTP4A2 and circTLK2 levels of 236 AIS patients within 72 h of symptoms onset and 136 healthy controls. We further assessed the National Institutes of Health Stroke Scale (NIHSS), infarct size, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification and the 90-day modified Rankin scale (mRS) for each patient. RESULTS: At admission, plasma circPTP4A2 and circTLK2 levels in patients with moderate to severe stroke were significantly higher compared to those with mild stroke. Logistic regression and receiver-operating characteristic (ROC) curve analyses indicated that they might function as predictive biomarkers for moderate to severe stroke. We also observed a medium positive correlation between these two circRNAs and NIHSS. Plasma circPTP4A2 and circTLK2 levels were slight positively correlated with cerebral infarct volume only in anterior circulation infarction (ACI) patients. Levels of both circPTP4A2 and circTLK2 were closely related with large artery atherosclerosis (LAA) stroke. Moreover, changes within 7 days after admission in circPTP4A2 and circTLK2 were able to predict unfavorable clinical outcome 90 days after AIS. INTERPRETATION: These results demonstrate that plasma circPTP4A2 and circTLK2 strongly correlated with severity, subtypes and prognosis of AIS, and they could serve as promising biomarkers.

Early activation of Toll-like receptor-3 reduces the pathological progression of Alzheimer's disease in APP/PS1 mouse.

BACKGROUND: Toll-like receptor 3 (TLR3) plays an important role in the immune/inflammatory response in the nervous system and is a main pathological feature of Alzheimer's disease (AD). This study investigates the role of early activation of TLR3 in the pathophysiological process of AD. METHODS: In the experiment, the agonist of TLR3, Poly(I:C), was intraperitoneally injected into the APP/PS1 mouse model of AD and wild-type control mice starting from the age of 4 to 9 months. At the age of 14 months, behavioral tests were conducted. Western blot and immunohistochemistry staining were used to evaluate the level of amyloid ß-protein (Aß), the activation of inflammatory cells, and neuron loss. In addition, the levels of inflammatory cytokines were measured using a quantitative polymerase chain reaction. RESULTS: The results demonstrated that the early activation of TLR3 attenuated neuronal loss and neurobehavioral dysfunction. Moreover, the early activation of TLR3 reduced Aß deposition, inhibited the activation of microglia and astrocytes, and decreased the transcription of pro-inflammatory factors in the hippocampus. CONCLUSIONS: The results indicated that the activation of TLR3 by Poly (I:C) in the early stage of development of AD in a mouse model attenuated neuron loss and improved neurobehavioral functions. The underlying mechanisms could be attributed to its role in Aß clearance, the inhibition of glial cells, and the regulation of neuroinflammation in the hippocampus.