Autophagy is involved in oligodendroglial precursor-mediated clearance of amyloid peptide

BACKGROUND: Accumulation of β-amyloid peptides is an important hallmark of Alzheimer\u27s disease (AD). Tremendous efforts have been directed to elucidate the mechanisms of β-amyloid peptides degradation and develop strategies to remove β-amyloid accumulation. In this study, we demonstrated that a subpopulation of oligodendroglial precursor cells, also called NG2 cells, were a new cell type that can clear β-amyloid peptides in the AD transgene mice and in NG2 cell line. RESULTS: NG2 cells were recruited and clustered around the amyloid plaque in the APPswe/PS1dE9 mice, which is Alzheimer\u27s disease mouse model. In vitro, NG2 cell line and primary NG2 cells engulfed β-amyloid peptides through the mechanisms of endocytosis in a time dependent manner. Endocytosis is divided into pinocytosis and phagocytosis. Aβ(42) internalization by NG2 cells was mediated by actin-dependent macropinocytosis. The presence of β-amyloid peptides stimulated the autophagic pathway in NG2 cells. Once inside the cells, the β-amyloid peptides in NG2 cells were transported to lysosomes and degraded by autophagy. CONCLUSIONS: Our findings suggest that NG2 cells are a new cell type that can clear β-amyloid peptides through endocytosis and autophagy

PACT/RAX Regulates the Migration of Cerebellar Granule Neurons in the Developing Cerebellum

PACT and its murine ortholog RAX were originally identified as a protein activator for the dsRNA-dependent, interferon-inducible protein kinase PKR. Recent studies indicated that RAX played a role in embryogenesis and neuronal development. In this study, we investigated the expression of RAX during the postnatal development of the mouse cerebellum and its role in the migration of cerebellar granule neurons (CGNs). High expression of RAX was observed in the cerebellum from postnatal day (PD) 4 to PD9, a period when the CGNs migrate from the external granule layer (EGL) to the internal granule layer (IGL). The migration of the EGL progenitor cells in vivo was inhibited by RAX knockdown on PD4. This finding was confirmed by in vitro studies showing that RAX knockdown impaired the migration of CGNs in cerebellar microexplants. PACT/RAX-regulated migration required its third motif and was independent of PKR. PACT/RAX interacted with focal adhesion kinase (FAK) and PACT/RAX knockdown disturbed the FAK phosphorylation in CGNs. These findings demonstrated a novel function of PACT/RAX in the regulation of neuronal migration

CFDEM simulation on the linkage effect between floor faults failure and roof collapse in ultra-thick coal seam

The ultra-thick coal seam has a large mining space and a wide range of overburden disturbance. The strong disturbance of loading and unloading caused by the roof collapse can easily exacerbate the failure of floor faults. Studying the mechanism of the linkage effect between water inrush from the floor fault and roof collapse in ultra-thick coal seam through numerical simulation is the basis for water hazard prevention and control. The key lies in understanding the coupling characteristics of progressive rock failure and fracture flow under loading and unloading. In this study, the evolution equations of tension and shear damage under loading and unloading were constructed, and combined with the yield criterion and plastic potential function with effective partial/spherical stress as the basic variable, the plastic-damage constitutive model of intact rock was obtained. The relationship between plastic displacement and strength deterioration during tension/shear/mixed loading and unloading was established, using the square tensile shear stress and B-K criterion as initial and complete fracture criteria, the fracture constitutive model of non-penetrating fracture was formed. The separation, compression and shear criteria of discrete rock blocks were put forward, and the extrusion, shear friction constitutive and dilation equations between discrete blocks were established based on experimental data. Based on the conservation of mass/momentum, the equation of state, and combined with the method of fluid volume and immersion boundary, the simulation theory of gas-water two-phase flow in the fractured rock mass was formed. Thus, the CFDEM numerical calculation program was developed, and the plastic damage, fracture, extrusion/friction, and fluid properties under loading and unloading were assigned to solid elements (rock blocks), cohesion elements (non-penetrating cracks), contact pairs (penetrating cracks), and Euler units (water and gas) respectively. According to the engineering geological conditions in the northern mining area of Ningwu coalfield, a numerical calculation model of linkage effect between water inrush from floor fault and roof collapse in extra-thick coal seam was established. The results indicate that ① the CFDEM coupling program and corresponding theoretical models can numerically achieve the transformation of overlying rocks and floor faults in ultra-thick coal seams from quasi-continuous to discrete rock, as well as the migration of groundwater in fractures. ② Under simulated conditions, the mining fractures envelope line of the fault floor of the ultra-thick coal seam is w-shaped, with the deepest point exceeding 55 m located on the fault and its hanging wall, the shallowest point 23 m located on the footwall of the fault, and the failure depth at the intact floor is 24−36 m, which has already connected to the Ordovician limestone aquifer. ③ Secondary damage is commonly observed on the floor of ultra-thick coal seam. The failure depth of the intact floor at the advanced working face is 24.0−29.3 m, but it generally increases to 31.5−36.0 m in the goaf. The total cracks opening of the fault and its hanging wall at the advanced working face is 0.34−0.86 m, but it rapidly increases to 3.6 m in the goaf, forming a dominant channel for water inrush. ④ The linkage effect of water inrush from floor fault and roof collapse is rooted in the collapse instability of key strata in overlying strata, the sinking of masonry beams and the secondary fracture, which leads to the secondary damage of floor and aggravates the risk of water inrush

Age of onset correlates with clinical characteristics and prognostic outcomes in neuromyelitis optica spectrum disorder

ObjectiveNeuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease preferentially affects the optic nerve and the spinal cord. The first attack usually occurs in the third or fourth decade, though patients with disease onset in the fifties or later are not uncommon. This study aimed to investigate the clinical characteristics and prognosis in patients with different age of onset and to explore the correlations between age of onset and clinical characteristics and prognostic outcomes.MethodWe retrospectively reviewed the medical records of 298 NMOSD patients diagnosed according to the 2015 updated version of diagnostic criteria. Patients were divided into early-onset NMOSD (EO-NMOSD) (<50 years at disease onset) and late-onset NMOSD (LO-NMOSD) (≥50 years at disease onset) based on the age of disease onset. LO-NMOSD patients were divided into two subgroups: relative-late-onset NMOSD (RLO-NMOSD) (50~70 years at disease onset) and very-late-onset NMOSD (≥70 years at disease onset). Clinical characteristics, laboratory findings, neuroimaging features, and prognostic outcomes were investigated.ResultsCompared to EO-NMOSD patients, patients with LO-NMOSD showed more frequent transverse myelitis (TM) (58.20% vs. 36.00%, p = 0.007) while less frequent optic neuritis (ON) (23.10% vs. 34.80%, p = 0.031) and brainstem/cerebral attacks (7.50% vs. 18.30%, p = 0.006) as the first attack. Patients with LO-NMOSD showed less frequent relapses, higher Expanded Disability Status Scale (EDSS) score at the last follow-up, fewer NMOSD-typical brain lesions, and longer segments of spinal cord lesions. Patients with older onset age showed a higher proportion of increased protein levels in cerebrospinal fluid during the acute phase of attacks. Age at disease onset positively correlated with length of spinal cord lesions at first attack and at last follow-up, negatively correlated with ARR-1 (ARR excluding the first attack, calculated from disease onset to final follow-up), irrespective of AQP4-IgG serostatus. Patients with older age at disease onset progressed to severe motor disability sooner, and age of onset positively correlated with EDSS score at the last follow-up, irrespective of AQP4-IgG serostatus.ConclusionAge of disease onset affects clinical characteristics and prognosis outcomes of patients with NMOSD

Real-time evolution of oil shale meso-structure under triaxial stress condition

It is significant to research the mechanical properties and micro-fracture evolution characteristics of oil shales with different bedding directions under the condition of in-situ triaxial stress loading for understanding the internal micro-characteristics of oil shales. Triaxial stress loading tests of cylindrical oil shales were carried out in two loading directions perpendicular to and parallel to the bedding, which is the S1 and S2 samples. Our results demonstrate that the oil shales are typical anisotropic and brittle fracture characteristics. The triaxial compressive strength of S1 is higher than that of S2, but the elastic modulus is almost the same. Based on the reconstructed 3D-CT image, we analyzed the dynamic evolution law of the fracture inside the sample in the horizontal and vertical directions, and obtained the distribution of the fracture in the loading process, finally revealing the internal micro-characteristics of oil shales under the different loading conditions

ZEB1‐AS1 mediates bone metastasis through targeting miR‐320b/BMPR1A axis in lung cancer

Abstract Objective This study aimed to explore the role and regulatory mechanism of lncRNA ZEB1‐AS1 in lung cancer. Methods The expression of ZEB1‐AS1 and miR‐320b was determined by qRT‐PCR. Cell viability, proliferation migration, and invasion were assessed using the CCK‐8, colony‐forming, and Transwell assay. EMT markers were quantified using western blot. The growth of subcutaneous tumor growth and metastatic bone tumors was evaluated in mouse model of lung cancer. Additionally, metastatic bone tumors were examined using H&E staining. Results ZEB1‐AS1 expression was upregulated, while miR‐320b levels were downregulated in lung cancer. Knockdown of ZEB1‐AS1 resulted in a significant suppression of cell viability, proliferation, migration, invasion, and EMT in A549 cells. Furthermore, we confirmed the targeting relationship between ZEB1‐AS1 and miR‐320b, as well as between miR‐320b and BMPR1A. Our findings suggested that ZEB1‐AS1 regulated cell viability, proliferation, migration, and invasion, as well as EMT, in lung cancer cells by targeting the miR‐320b/BMPR1A axis. Moreover, our in vivo experiments confirmed that ZEB1‐AS1 mediated bone metastasis through targeting miR‐320b/BMPR1A axis in mice with lung cancer. Conclusion ZEB1‐AS1 mediated bone metastasis through targeting miR‐320b/BMPR1A axis in lung cancer

CI-UNet: Application of Segmentation of Medical Images of the Human Torso

The study of human torso medical image segmentation is significant for computer-aided diagnosis of human examination, disease tracking, and disease prevention and treatment. In this paper, two application tasks are designed for torso medical images: the abdominal multi-organ segmentation task and the spine segmentation task. For this reason, this paper proposes a net-work model CI-UNet improve the accuracy of edge segmentation. CI-UNet is a U-shaped network structure consisting of encoding and decoding networks. Firstly, it replaces UNet’s double convolutional backbone network with a VGG16 network loaded with Transfer Learning. It feeds image information from two adjacent layers in the VGG16 network into the decoding grid via information aggregation blocks. Secondly, Polarized Self-Attention is added at the decoding network and the hopping connection, which allows the network to focus on the compelling features of the image. Finally, the image information is decoded by convolution and Up-sampling several times to obtain the segmentation results. CI-UNet was tested in the abdominal multi-organ segmentation task using the Chaos (Combined CT-MR Healthy Abdominal Organ Segmentation) open challenge dataset and compared with UNet, Attention UNet, PSPNet, DeepLabv3+ prediction networks, and dedicated network for MRI images. The experimental results showed that the average intersegmental union (mIoU) and average pixel accuracy (mPA) of organ segmentation were 82.33% and 90.10%, respectively, higher than the above comparison network. Meanwhile, we used CI-UNet for the spine dataset of the Guizhou branch of Beijing Jishuitan Hospital. The average intersegmental union (mIoU) and average pixel accuracy (mPA) of organ segmentation were 87.97% and 93.48%, respectively, which were approved by the physicians for both tasks