In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and ...neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aβ. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aβ deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aβ deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing β-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aβ toxicity and would be a novel therapeutic target and biomarker for AD.
Lymph node metastasis is related to poor prognosis in oral squamous cell carcinoma (OSCC), and few studies have explored the relevance of postoperative drainage fluid (PDF) in metastasis. ...Extracellular vesicles (EVs) are nanosized vesicles that can transfer oncogenic molecules to regulate tumorigenesis. However, the proteomic profile of postoperative drainage fluid–derived EVs (PDF-EVs) in OSCC has not been elucidated. Herein, we collected drainage fluid from OSCC patients after neck dissection to investigate the difference in PDF-EVs between patients with metastatic lymph nodes (the LN+ group) and nonmetastatic lymph nodes (the LN− group). The proteomic profile of PDF-EVs from the LN+ and LN− groups was compared using label-free liquid chromatography tandem-mass spectrometry–based protein quantification. The results revealed that PDF-EVs were mainly derived from epithelial cells and immune cells. A total of 2,134 proteins in the PDF-EVs were identified, and 313 were differentially expressed between the LN+ and LN− groups. Metabolic proteins, such as EHD2 and CAVIN1, were expressed at higher levels in the LN+ group than in the LN− group, and the levels of EHD2 and CAVIN1 in the postoperative drainage fluid were positively correlated with lymph node metastasis. Our study revealed previously undocumented postoperative drainage fluid–associated proteins in patients with metastatic OSCC, providing a starting point for understanding their role in metastatic and nonmetastatic OSCC.
The collaborative oscillation of conductive electrons in metal nanoparticles results in a surface plasmon resonance that makes them useful for various applications including biolabeling. We ...investigate the coupling between pairs of elliptical metal particles by simulations and experiments. The results demonstrate that the resonant wavelength peak of two interacting particles is red-shifted from that of a single particle because of near-field coupling. It is also found that the shift decays approximately exponentially with increasing particle spacing and become negligible when the gap between the two particles exceeds about 2.5 times the particle short-axis length.
Towards super-clean graphene Lin, Li; Zhang, Jincan; Su, Haisheng ...
Nature communications,
04/2019, Letnik:
10, Številka:
1
Journal Article
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Impurities produced during the synthesis process of a material pose detrimental impacts upon the intrinsic properties and device performances of the as-obtained product. This effect is especially ...pronounced in graphene, where surface contamination has long been a critical, unresolved issue, given graphene's two-dimensionality. Here we report the origins of surface contamination of graphene, which is primarily rooted in chemical vapour deposition production at elevated temperatures, rather than during transfer and storage. In turn, we demonstrate a design of Cu substrate architecture towards the scalable production of super-clean graphene (>99% clean regions). The readily available, super-clean graphene sheets contribute to an enhancement in the optical transparency and thermal conductivity, an exceptionally lower-level of electrical contact resistance and intrinsically hydrophilic nature. This work not only opens up frontiers for graphene growth but also provides exciting opportunities for the utilization of as-obtained super-clean graphene films for advanced applications.
We report experimental and theoretical studies on the plasmon resonances of finite one-dimensional chains of Au nanoparticles excited by evanescent light waves with polarization parallel to the ...chains. The experimental results show that the plasmon resonance peak wavelengths of these finite 1D chains are significantly red-shifted in comparison to that of single Au nanoparticle. Contrary to previous findings, the peak wavelengths are observed to be a nonmonotonic function of particle numbers in the chain. This phenomenon is reproduced in the theoretical results obtained by using the transfer-matrix method and is shown to occur only for larger particles where phase retardation effects are important in plasmon coupling.
The CDEX-1 experiment conducted a search of low-mass (< 10GeV/c super(2)) weakly interacting massive particles dark matter at the China Jinping Underground Laboratory using a p-type point-contact ...germanium detector with a fiducial mass of 915 g at a physics analysis threshold of 475 eVee. We report the hardware setup, detector characterization, data acquisition, and analysis procedures of this experiment. No excess of unidentified events is observed after the subtraction of the known background. Using 335.6 kg-days of data, exclusion constraints on the weakly interacting massive particle-nucleon spin-independent and spin-dependent couplings are derived.
This article proposes a novel targeted-location drug delivery system for lower gastrointestinal (GI) tract (such as the small intestine) capsule robots. The proposed system takes a "2-in-1" approach ...that enables both the magnetically actuated anchoring and drug release by using only one internal magnet. The integrated design consists of a magnetically actuated decoupling module, an anchoring module, and a drug release module. The magnetically actuated decoupling module is equipped with two decoupling mechanisms at both ends, which can, respectively, provide one-way rotation for anchoring and drug release functions. The two functions can be decoupled controlled. The anchoring module can simultaneously extend two C-shaped anchoring legs, which can help the capsule anchor at a given position inside the GI tract without damaging it. The drug release module can load 1.6-mL liquid drug and quickly release all the drugs under the control of an external magnet. A capsule robot prototype of the proposed design has been built with 16-mm diameter and 50-mm length. Phantom and in vitro experiments on anchoring and drug release modules have been conducted and have validated the effectiveness of the proposed design and control method.
Pituitary stalk interruption syndrome (PSIS) is a rare congenital defect manifesting with varying degrees of pituitary hormone deficiency. The signs and symptoms of PSIS during the neonatal period ...and infancy are often overlooked and therefore diagnosis is delayed. The typical manifestations of PSIS can be detected by magnetic resonance imaging. Several genes in the Wnt, Notch and Shh signalling pathways related to hypothalamic‐pituitary development, such as PIT1, PROP1, LHX3/LHX4, PROKR2, OTX2, TGIF and HESX1, have been found to be associated with PSIS. Nevertheless, the aetiology in the majority of cases still remains unknown. In the present review, we provide an overview of clinical features of PSIS and summarise our current understanding of the underlying pathogenic mechanisms for this rare syndrome. Furthermore, we propose future research directions that may help our understanding of the aetiology of PSIS.
This article proposes a direct power control strategy based on bang-bang funnel control (BBFC-DPC) for the three-phase grid-connected voltage-source inverters. The BBFC has inherently robust nature ...due to its model-free design. It can provide time-optimal dynamics and effectively constrain the tracking error of output variables within the prespecified funnels. The BBFC-DPC approach is implemented based on a newly established DPC model in the abc frame, which enables satisfying decoupled power control without using coordinate transformations and feedforward decoupling terms. Built upon the merits of BBFC, the BBFC-DPC features high-quality static output performance, promoted dynamic responses, stronger robustness against parameter uncertainties, and pleasing resilience to slight grid disturbances. Moreover, an extended BBFC-DPC scheme equipped with reactive power support and current limitation functions is developed as a feasible alternative to tackle unbalanced network conditions in weak grid. Finally, both the simulation and experimental results are well in line with the theoretical expectations, which validates the effectiveness of the proposed method.
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