Molecules of senescent glial cells differentiate Alzheimer's disease from ageing

BACKGROUND: Ageing is a major risk factor for Alzheimer's disease (AD), which is accompanied by cellular senescence and thousands of transcriptional changes in the brain. OBJECTIVES: To identify the biomarkers in the cerebrospinal fluid (CSF) that could help differentiate healthy ageing from neurodegenerative processes. METHODS: Cellular senescence and ageing-related biomarkers were assessed in primary astrocytes and postmortem brains by immunoblotting and immunohistochemistry. The biomarkers were measured in CSF samples from the China Ageing and Neurodegenerative Disorder Initiative cohort using Elisa and the multiplex Luminex platform. RESULTS: The cyclin-dependent kinase inhibitors p16/p21-positive senescent cells in human postmortem brains were predominantly astrocytes and oligodendrocyte lineage cells, which accumulated in AD brains. CCL2, YKL-40, HGF, MIF, S100B, TSP2, LCN2 and serpinA3 are biomarkers closely related to human glial senescence. Moreover, we discovered that most of these molecules, which were upregulated in senescent glial cells, were significantly elevated in the AD brain. Notably, CSF YKL-40 (β=0.5412, p<0.0001) levels were markedly elevated with age in healthy older individuals, whereas HGF (β=0.2732, p=0.0001), MIF (β=0.33714, p=0.0017) and TSP2 (β=0.1996, p=0.0297) levels were more susceptible to age in older individuals with AD pathology. We revealed that YKL-40, TSP2 and serpinA3 were useful biomarkers for discriminating patients with AD from CN individuals and non-AD patients. DISCUSSION: Our findings demonstrated the different patterns of CSF biomarkers related to senescent glial cells between normal ageing and AD, implicating these biomarkers could identify the road node in healthy path off to neurodegeneration and improve the accuracy of clinical AD diagnosis, which would help promote healthy ageing

Performance analysis of a new baseline-based SS-Y extensometer

In order to solve the problems in the observation with the SS-Y extensometer, such as background noise and discontinuity of earth tide curve, this paper proposed to improve the stability of the instrument and the smoothness of the earth tide curve by improving the baseline structure of the instrument. In this study, a new φ20*1.2 invar tube was introduced in replacement of the existing φ6 invar rod as the baseline of the instrument and compared with the existing φ6 invar rod on the instrument's linearity, sensitivity and other indexes. Firstly, the SS-Y extensometers using φ6 invar rod and φ20*1.2 invar tube were tested. Test results were then calculated, and accuracy errors of the instruments based on the two baselines were obtained. Finally, their accuracy errors and earth tide curves were compared. Results showed that, compared with the extensometer based on the existing φ6 invar rod, the extensometer based on the new φ20*1.2 invar tube was superior in performance, with linearity error reducing to 0.495% from 0.937%, sensitivity increasing to 68.65 mV/μm from 65.46 mV/μm, and earth tide curve growing more stable and continuous. Keywords: Invar tube, Extensometer, Ground deformation, Background noise, Earth tid

Effects of Queen Cell Size and Caging Days of Mother Queen on Rearing Young Honey Bee Queens Apis mellifera L.

This study aims to investigate the effect of queen cell size (9.4 mm, 9.6 mm, 9.8 mm and 10.0 mm) and mother queen caged time (0 day, 2 days and 4 days) on rearing young queens without grafting larvae. The birth weight, ovarian tubes, thorax length and width were significantly increased with the increasing diameter of queen cell size. The expression level of Vitellogenin (Vg) in young queen ovaries was also up-regulated with the increased queen cell size diameter. These results indicate that the queen cell size can strongly affect the rearing queen quality and reproductive ability. Moreover, the weight, length and width of laying eggs rose with the mother queen caging time, and young queens reared with the hatched larvae from these eggs were also increased in terms of birth weight, ovarian tubes, thorax length and width. Furthermore, the expression level of Vg in reared queen ovaries was also up-regulated with the caged time. These results reveal that the caged time of queens could significantly influence egg size and their relative queen quality

Monocular-Vision-Based Precise Runway Detection Applied to State Estimation for Carrier-Based UAV Landing

Improving the level of autonomy during the landing phase helps promote the full-envelope autonomous flight capability of unmanned aerial vehicles (UAVs). Aiming at the identification of potential landing sites, an end-to-end state estimation method for the autonomous landing of carrier-based UAVs based on monocular vision is proposed in this paper, which allows them to discover landing sites in flight by using equipped optical sensors and avoid a crash or damage during normal and emergency landings. This scheme aims to solve two problems: the requirement of accuracy for runway detection and the requirement of precision for UAV state estimation. First, we design a robust runway detection framework on the basis of YOLOv5 (you only look once, ver. 5) with four modules: a data augmentation layer, a feature extraction layer, a feature aggregation layer and a target prediction layer. Then, the corner prediction method based on geometric features is introduced into the prediction model of the detection framework, which enables the landing field prediction to more precisely fit the runway appearance. In simulation experiments, we developed datasets applied to carrier-based UAV landing simulations based on monocular vision. In addition, our method was implemented with help of the PyTorch deep learning tool, which supports the dynamic and efficient construction of a detection network. Results showed that the proposed method achieved a higher precision and better performance on state estimation during carrier-based UAV landings

Effect of SCM and Nano-Particles on Static and Dynamic Mechanical Properties of UHPC

In this paper, fiber-matrix interfacial bond and static and dynamic mechanical properties of non-fibrous UHPC matrix and UHPC containing 2% steel fibers made with different types of supplementary cementitious materials (SCMs) and nano-particles were investigated. A mixture containing 20% silica fume, by mass of binder, was used as a reference. Five other mixtures prepared with 20% silica fume as well as 20% fly ash, 20% slag, combination of 20% fly ash and 20% slag, 3.2% nano-CaCO3, or 1% nano-SiO2 were also investigated. The drop weight impact testing method was used to evaluate the impact flexural properties. The static flexural behavior was also investigated using specimens with the same size. Mercury intrusion porosimetry (MIP) was used to examine the microstructure of the matrix. Test results indicated that the incorporation of 20% silica fume in addition to either SCMs or nano-particles resulted in improvement in fiber-matrix bond and mechanical properties of UHPC. This can be attributed to the optimization of hydration products and densification of microstructure. The highest fiber-matrix bond and flexural strengths were found in the UHPC mixture containing 20% slag or 3.2% nano-CaCO3. Their 28d fiber-matrix bonds were increased by 30%–48% compared to the reference mixture, while 20%–30% greater for the 7d impact flexural strength. Therefore, slag and nano-CaCO3 are recommended for enhancing the flexural properties of UHPC

Association between platelet count and hepatocellular carcinoma overall survival: a large retrospective cohort study

Objectives To explore the non-linear relationship between platelet count (PLT) and hepatocellular carcinoma (HCC) overall survival (OS).Setting The study was done in Sun Yat-sen University Cancer Center (SYSUCC) from January 2007 to May 2012, a total of 5005 consecutive participants at SYSUCC were retrospectively reviewed, and 979 patients with Barcelona clinic liver cancer (BCLC) stage B were selected for the final analysis.Participants A total of 979 newly diagnosed patients with HCC with BCLC stage B were identified for the secondary analysis. Eight cases were excluded for missing data of PLT.Main outcome measures Cox proportional hazard regression models were used to calculate multivariable-adjusted HRs and 95% CIs for HCC. The non-linear relationship was estimated through a restricted cubic spline regression, and a two-piecewise Cox proportional hazards model was further performed to calculate the threshold effect. We used multiple imputation to deal with the missing data.Results In the multivariate analysis, Log PLT was associated with a 91% risk increase in death (HR 1.91; 1.28 to 2.85) with adjustment for gender, Child-Pugh class, age × diameter of main tumour, both lobe with lesions × number of the intrahepatic lesions, alpha-fetoprotein (&lt;25, ≥25) and lactic dehydrogenase (&lt;245, ≥245). We also found a U-shape relationship between PLT and HCC OS at the inflexion point of 67.6×109/L. The HR was 0.12 (95% CI 0.03 to 0.52) for Log PLT≤10.83 and 3.07 (CI 1.91 to 4.92) for Log PLT&gt;10.83 after adjusting for potential confounders. The core results were consistent with those from the sensitivity analysis. Besides, a significantly higher hazard risk was found in the patients with age &lt;55, both lobes with lesions, tumour diameter &gt;50, haemoglobin ≥120 and C reactive protein &gt;10.Conclusion PLT was nonlinearly associated with HCC OS