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IntroductionAlzheimer's disease (AD) and Parkinson's disease (PD) involve tau pathology. Tau is detectable in blood, but its clearance from neuronal cells and the brain is poorly understood.MethodsTau efflux from the brain to the blood was evaluated by administering radioactively labeled and unlabeled tau intracerebroventricularly in wild-type and tau knock-out mice, respectively. Central nervous system (CNS)-derived tau in L1CAM-containing exosomes was further characterized extensively in human plasma, including by single molecule array technology with 303 subjects.ResultsThe efflux of Tau, including a fraction via CNS-derived L1CAM exosomes, was observed in mice. In human plasma, tau was explicitly identified within L1CAM exosomes. In contrast to AD patients, L1CAM exosomal tau was significantly higher in PD patients than controls and correlated with cerebrospinal fluid tau.ConclusionsTau is readily transported from the brain to the blood. The mechanisms of CNS tau efflux are likely different between AD and PD.

Sonic Hedgehog (SHH) subgroup of medulloblastoma (MB) accounts for about 25% of all subgroups of MB. Tumor microenvironment (TME) may play a key role in the tumor progression and therapeutic resistance. Tumor‐associated astrocytes (TAAs) are reshaped to drive tumor progression through multiple paracrine signals. However, the mechanism by which TAAs modulate MB cells remains elusive. Here, we illuminated that TAAs showed a specific and dynamic pattern during SHH‐MB development. Most TAAs gathered to the tumor margin during the tumor progression, rather than evenly distributed in the early‐stage tumors. We further demonstrated that lipocalin‐2 (LCN2) secreted by TAAs could promote the tumor growth and was correlated with the poor prognosis of MB patients. Knocking down LCN2 in TAAs in vitro impeded the proliferation and migration abilities of MB cells. In addition, we identified that TAAs accelerated the tumor growth by secreting LCN2 via STAT3 signaling pathway. Accordingly, blockade of STAT3 signaling by its inhibitor WP1066 and AAV‐Lcn2 shRNA, respectively, in TAAs abrogated the effects of LCN2 on tumor progression in vitro and in vivo. In summary, we for the first time clarified that LCN2, secreted by TAAs, could promote MB tumor progression via STAT3 pathway and has potential prognostic value. Our findings unveiled a new sight in reprogramming the TME of SHH‐MB and provided a potential therapeutic strategy targeting TAAs. [ABSTRACT FROM AUTHOR]

The variable thickness hybrid square (VTHS) tubes are used to improve the energy absorption under oblique loading and the relative advantages compared with the uniform thickness hybrid square (UTHS) tubes are studied. First, a oblique compression test and finite element model were established to analyze the deformation mode and load-displacement curve of VTHS tube. Then, the parameter studies of VTHS and UTHS tubes were carried out. The results show that increasing thickness leads the structures to be prone to global bending mode, and the energy absorption performance is reduced. Compared with UTHS, VTHS tubes can increase the specific energy absorption when the progressive crushing mode occurred at the same loading angle. Meanwhile, the progressive crushing deformation with excellent energy absorption performance can still appear when the loading angle exceeds 30°. Finally, a unified equation for the relationship between the dimensionless mean crushing force and the loading angle was proposed. [ABSTRACT FROM AUTHOR]

Square-circle hybrid section (SCHS) tubes under axial loading which combine the advantage of square tubes and circular tubes are investigated. Firstly, effective finite element models of SCHS tubes are established to study the crashworthiness characteristics. Through a series of finite element models, the influence of the geometry on the behaviour of crashworthiness is studied, including relative size of square and circular sections in SCHS tubes and the position of connecting plates. The results show that compared with corresponding traditional multi-cell tubes, SCHS tubes improve the performance in energy absorption, with a maximum increase of 40.49%, while reducing peak force and improving crushing load efficiency. Moreover, the deformation of elements constituting the SCHS tube is analysed, and deformation of arc-plate elements could be classified into three typical modes. According to the observed deformation modes, the theoretical model is proposed to predict the mean crushing force of SCHS tubes. The theoretical results show that it is in good agreement with the numerical results. [ABSTRACT FROM AUTHOR]

Based on the theoretical crashworthiness model of variable thickness rectangular section tubes, this article simplified the super-folding element to analyze the energy absorption characteristics of variable thickness 12 right-angles section (VTTRS) tubes during axial crushing. To discuss the deformation mode of VTTRS tubes, a series of finite element models were built based on the verified finite element model of variable thickness rectangle section tubes. Then, the deformation of VTTRS tubes was studied to obtain the structures deforming in stable mode which have a great performance in energy absorption. Meanwhile, a theoretical solution of the mean crushing force for VTTRS tubes was proposed and verified by establishing three groups of finite element models with different thicknesses and thickness gradients. Finally, a prediction for crash box was presented and the results showed the great potential of VTTRS tubes in energy absorption and explained the important role played by the theoretical model for vehicle during concept design stage. [ABSTRACT FROM AUTHOR]

New York esophageal squamous cell carcinoma 1 (NY‐ESO‐1) is aberrantly expressed in multiple myeloma (MM) patients, however, its role remains largely unknown. The present study aimed to investigate the effect of NY‐ESO‐1 knockdown on MM impact and provide evidence for targeting treatment of MM. Human MM U266 cells were infected with lentivirus‐based small hairpin RNA‐targeting NY‐ESO‐1 (LV‐shNY‐ESO‐1). Cellular proliferation, colony‐forming, migration, and invasion assays were employed. The expressions of cell cycle and epithelial–mesenchymal transition (EMT)‐related molecules, MM growth, and mouse osteolytic lesions were evaluated. The results showed that the LV‐shNY‐ESO‐1‐U266 cells had a lower expression of NY‐ESO‐1 and a higher expressions of p21 and E‐cadherin, and a weaker abilities of colony formation, drug‐resistant to adriamycin, migration, and invasion than those of the control cells. Importantly, the knockdown of NY‐ESO‐1 inhibited significantly the U266 cell‐induced MM growth and osteolytic lesions along with increasing the expressions of E‐cadherin, p21, and p53 in mice challenged with LV‐shNY‐ESO‐1‐U266 cells. Collectively, our findings demonstrate that knockdown of NY‐ESO‐1 suppressed the U266 cell‐induced MM growth and osteolytic lesions by inhibition of the MMs cell cycle and EMT. The NY‐ESO‐1 knockdown may be considered for future clinical trials in MM. [ABSTRACT FROM AUTHOR]