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Background: Previous research has suggested that pathogen infections may serve as potential contributors to dementia. Objective: Consequently, the study aimed to evaluate whether pathogen exposure heightens the risk of dementia. Methods: Between 2006 and 2010, a total of 8,144 individuals from the UK Biobank had data on pathogen antibodies and were included in the baseline assessment. Cox proportional hazard models were employed for the analysis. Results: Out of the 8,144 participants, 107 eventually developed dementia, while 55 participants were diagnosed with Alzheimer's disease (AD). Multivariate Cox regression analysis revealed that the levels of pathogen antibody titers of EBV and C. trachomatis were associated with an increased risk of dementia/AD. The highest quartile of EBV EBNA-1 and EBV VCA p18, and the second quartile of H. pylori VacA significantly increased the risk of dementia compared lower quartile (EBV EBNA-1: HR = 1.938, p = 0.018; EBV VCA p18: HR = 1.824, p = 0.040; H. pylori VacA: HR = 1.890, p = 0.033). Besides, the highest quartile of EBV VCA p18 had a higher risk of AD compared lower quartile (HR = 2.755, p = 0.029). Conclusions: The study demonstrated that exposure to EBV, H. pylori, and C. trachomatis substantially elevated the risk of dementia/AD. Despite the relatively widespread occurrence of EBV infection in the population, elevated pathogen antibody titers were still found to increase the risk of dementia/AD. Besides, since C. trachomatis and C. pneumoniae are quite homologous, this study found that trachomatis (C. trachomatis/C. pneumoniae) may be significantly associated with the risk of AD/dementia. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Abnormalities in the peripheral immune system in ALS have been paid attention; however, the results of changes in peripheral immune parameters were inconsistent. A total of 1109 ALS patients were enrolled in the study. All patients received clinical evaluation and peripheral immune parameters measurement. The outcomes were analyzed by correlation analysis, multiple linear regression and cox survival analysis. We found that ALS patients had significantly higher percentage of CD4+ T cells (39.3 vs. 37.1%, p < 0.001) and CD4+/CD8+ ratio (1.88 vs. 1.72, p = 0.011), significantly lower IgG (11.73 vs.12.82, p < 0.001) and IgA (2130.70 vs. 2284.8, p = 0.013) compared with the health controls. In the multivariate linear model, we found that each increase of 1.262, 0.278, and 4.44E-4 in ALSFRS-R scores were significantly associated with each increment of lymphocyte count, IgG, and IgA, respectively. However, each decrease of 0.341, 0.068, and 0.682 in ALSFRS-R score was associated with each increment in neutrophils, CD4+ T cells, and CD4+/CD8+ ratio, respectively. Cox survival regression analysis showed that the death risk of ALS patients was related to the levels of C3 (HR 0.592, 95% CI 0.361–0.973). We found that there were differences in peripheral immune parameters of ALS patients with the severity of the disease, especially neutrophil, lymphocyte, CD4+ T, and IgG; C3 is an independent predictor of survival in ALS patients. More studies are needed to elucidate the mechanisms associated with altered immune parameters in ALS. [ABSTRACT FROM AUTHOR]

K2TiF6:Mn4+ is an attractive narrow‐band red‐emitting phosphor for warm white light‐emitting diodes (LEDs). Nevertheless, the hexafluoride phosphor is liable to deliquesce in moist environments, which leads to a sharp deterioration performance of luminescence. Surface modification of K2TiF6:Mn4+ phosphor with SrF2 coating has been introduced, with the aid of KHF2 transition layer to moderate the lattice mismatch. The reaction mechanism is discussed in detail, as so as the influence of SrF2 coating on the luminescence intensity. The SrF2 coating is able to prevent the hydrolysis of internal [MnF6]2− group; thereby, the luminescence intensity retains over 90% of initial value after being immersed in distilled water for 2 h. The LED devices fabricated with commercial Y3Al5O12:Ce3+ and as‐modified K2TiF6:Mn4+ phosphors exhibit bright white light with tunable chromaticity coordinate, correlated color temperature, and color rendering index. It enlightens a convenient method to enhance the moisture resistance of Mn4+ doped fluoride phosphors for commercial application in the field of white LEDs. [ABSTRACT FROM AUTHOR]

Background: The association between cytokines in peripheral blood and clinical symptoms of multiple system atrophy (MSA) has been explored in only a few studies with small sample size, and the results were obviously controversial. Otherwise, no studies have explored the diagnostic value of serum cytokines in MSA., Methods: Serum cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α), were measured in 125 MSA patients and 98 healthy controls (HCs). Correlations of these serum cytokines with clinical variables were analyzed in MSA patients. Diagnostic value of cytokines for MSA was plotted by receiver operating curves., Results: No significant differences were found in sex and age between the MSA group and the HCs. TNF-α in MSA patients were significantly higher than those in HCs (area under the curve (AUC) 0.768), while IL-6 and IL-8 were not. Only Hamilton Anxiety Scale (HAMA) has a positive correlation between with TNF-α in MSA patients with age and age at onset as covariates. Serum IL-6 was associated with HAMA, Hamilton Depression Scale (HAMD), the Unified MSA Rating Scale I (UMSARS I) scores, the UMSARS IV and the Instrumental Activity of Daily Living scores. However, IL-8 was not associated with all clinical variables in MSA patients. Regression analysis showed that HAMA and age at onset were significantly associated with TNF-α, and only HAMA was mild related with IL-6 levels in MSA patients., Conclusion: Serum TNF-α and IL-6 levels in MSA patients may be associated with anxiety symptom; however, only TNF-α was shown to be a useful tool in distinguishing between MSA and HCs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Chen, Lai, Fu, Yang, Ou, Zhang, Wei, Guo and Shang.)

Silent information regulator 1 (SIRT1) mediates many effects of caloric restriction (CR) on an organism's lifespan and metabolic pathways. Recent reports have also emphasized its role in vascular function. The present study was designed to investigate the effects of SIRT1 on the properties of mouse spleen derived endothelial progenitor cells (EPCs). SIRT1 in EPCs was significantly increased by serum and by vascular endothelial growth factor (VEGF). Moreover, an adenovirus (Ad) vector expressing SIRT1 (Ad-SIRT1)-mediated overexpression of SIRT1 directly enhanced migration and proliferation of EPCs, whereas silencing of endogenous SIRT1 in EPCs inhibited cell functions. In addition, LY294002 (a PI3K inhibitor), sc-221226 (an Akt inhibitor), and L-NAME (an NOS inhibitor) abolished Ad-SIRT1-induced migration and proliferation of EPCs, and prevented nitric oxide (NO) production. Phosphorylation of Akt, PI3K, and endothelial nitricoxide synthase (eNOS) were up-regulated by Ad-SIRT1, which was attenuated by LY294002, sc-221226, and L-NAME. Together, the results suggested that through the PI3K/Akt/eNOS signaling pathway, SIRT1 plays an important role in the biological properties of EPCs.

The hippocampal neurons of Sprague-Dawley rat (post natal days 7 to 14) were acutely isolated using trypsin and mechanical dissociation. AgNO3 staining was performed to identify them. Voltage-dependent inward calcium currents were recorded by employing the patch-clamp technique in the whole-cell voltage-clamp mode. With different stimulation processes, we studied the changes of low voltage activated (LVA) calcium currents, the transient and sustained components of high voltage-activated calcium currents (HVA) in the hippocampal neuron membrane. The effects of CL on the peak currents in the neuron membrane were assessed and analyzed. The main sustained components ofHVA were L-type calcium currents. The HVA calcium currents were slowly inactivated in 300 ms. The changes of the current amplitude of the sustained components of HVA were insignificant with the holding potential of -100 mV and -50 mV which indicated that the inactivation could be removed with the potential of -50 mV. The HVA calcium currents were evoked by depolarizing voltage steps over the range of -70 mV to +50 mV for 300ms with the holding potential of -50 mV and the threshold potential of -40 mV or so. The HVA and LVA calcium currents were evoked by the same stimulation with the holding potential of -100 mV and the total calcium currents appeared at the potential of -60 mV. The amplitude of peak currents significantly increased (P<0.05). The transient LVA calcium currents as the peak calcium currents were evoked by depolarizing voltage steps over the range of -70 mV to -30 mV with the holding potential of -100 mV. Both HVA and LVA calcium currents appeared over the range of -30 mV to +10 mV. The HVA calcium currents mainly appeared above the membrane potential of +10 mV. There was no obvious borderline between these components. About 3 minutes after the application of CL, the peak density of LVA calcium currents in 20 microl/ml and 40 microl/ml CL group increased respectively (75.56% +/- 23.09% vs. 66.12% +/- 19.09%) (P<0.05). CL increased the peak density of HVA calcium currents in a concentration-dependent way, with enhancement by 18.15% +/- 4.98% (P<0.05) and 32.80% +/- 3.58% (P<0.01) after the application of 20 microl/ml and 40 microl/ml CL. The effects of CL on the calcium currents will contribute to the enhanced excitability of hippocampal neurons, modulate some calcium-dependent processes and boost epileptic discharges. All of them play an important role in the CL-induced epileptogenesis.

We instituted an investigation to elucidate the role of Ca2+ and calcium channels in epileptogenesis and to analyze the mechanism by which coriaria lactone (CL) regulates intracellular Ca2+ concentration. The hippocampal neurons of Sprague-Dawley rats (post natal days 7 to 14) were acutely isolated and loaded with calcium-sensitive fluorescent indicator Fluo-3/AM. Intracellular calcium concentration ([Ca2+]i) changes were measured using laser scanning confocal microscopy. The study included five groups, namely the CL group, the NiCl2 plus CL group, the Nifedipine plus CL group, the NiCl2+ Nifedipine plus CL group, and the control group. The results indicated that 20 microl/ml CL induced a significant increase of [Ca2+]i in hippocampal neurons when compared to the control (P < 0.01), the mean fluorescent intensity of intracellular calcium displaying an increase from 5.46 +/- 2.37 to 34.03 +/- 3.45. Although the increase of relative intracellular fluorescent intensity was delayed by 3 or 4 minutes in the NiCl2 plus CL group, the Nifedipine plus CL group, and the NiCl2+ Nifedipine plus CL group, yet the use to 20 microl/ml CL in these 3 groups caused a significant ascending level of the fluorescent intensities (from 3.94 +/- 1.75 to 30.18 +/- 4.22; from 3.38 +/- 1.11 to 36.39 +/- 3.97; from 3.05 +/- 1.02 to 28.05 +/- 2.71), and the effect was comparable to that observed in the CL group (P > 0.05). So CL can increase [Ca2+]i in acutely isolated rat hippocampal neurons. This effect can be delayed but can not be completely blocked by NiCl2 and Nifedipine. These findings indicate that CL can increase [Ca2+]i by other means besides T- and L-type voltage-gated calcium channels, and that CL can increase the excitability of neurons and play a role in the epileptogenesis process.