Epidermal growth factor receptor (EGFR) activation is involved in blood spinal cord barrier (BSCB) disruption and secondary injury after spinal cord injury (SCI). However, the underlying mechanisms ...of EGFR activation mediating BSCB disruption and secondary injury after SCI remain unclear. An in vitro model of oxygen and glucose deprivation/reoxygenation (OGD/R) induced BSCB damage and in vivo rat SCI model were employed to define the role of EGFR/p38/NF-κB signal pathway activation and its induced inflammatory injury in main cellular components of BSCB. Genetic regulation (lentivirus delivered shRNA and overexpression system) or chemical intervention (agonist or inhibitor) were applied to activate or inactivate EGFR and p38 in astrocytes and microvascular endothelial cells (MEC) under which conditions, the expression of pro-inflammatory factors (TNF-α, iNOS, COX-2, and IL-1β), tight junction (TJ) protein (ZO-1 and occludin), nuclear translocation of NF-κB and permeability of BSCB were analyzed. The pEGFR was increased in astrocytes and MEC which induced the activation of EGFR and p38 and NF-κB nuclear translocation. The activation of EGFR and p38 increased the TNF-α, iNOS, COX-2, and IL-1β responsible for the inflammatory injury and reduced the ZO-1 and occludin which caused BSCB disruption. While EGFR or p38 inactivation inhibited NF-κB nuclear translocation, and markedly attenuated the production of pro-inflammatory factors and the loss of TJ protein. This study suggests that the EGFR activation in main cellular components of BSCB after SCI mediates BSCB disruption and secondary inflammatory injury via the EGFR/p38/NF-κB pathway.
•Epidermal growth factor receptor (EGFR) phosphorylation is the main event in BSCB after SCI.•pEGFR in astrocytes and microvascular endothelial cells after SCI mediates BSCB disruption and secondary inflammatory injury.•EGFR/p38/NF-κB signaling pathway activation after SCI contributes to the regulation of BSCB TJ integrity.
Nanographenes with zigzag edges, for example, anthenes, exhibit a unique nonbonding π‐electron state, which can be described as a spin‐polarized edge state that yields specific magnetic ground state. ...However, prior researches on the magnetism of anthenes with varying lengths on a surface is lacking. This study systematically fabricated anthenes with inherent zigzag carbon atoms of different lengths ranging from bisanthene to hexanthene. Their magnetic evolution on the Au(111) surface was analyzed through bond‐resolved scanning probe techniques and density functional theory calculations. The analyses revealed a transition in magnetic properties associated with the length of the anthenes, arising from the imbalance between hybridization energy and the Coulomb repulsion between valence electrons. With the increasing length of the anthenes, the ground state transforms gradually from a closed‐shell to an antiferromagnetic open‐shell singlet, exhibiting a weak exchange coupling of 4 meV and a charge transfer‐induced doublet. Therefore, this study formulated a chemically tunable platform to explore size‐dependent π magnetism at the atomic scale, providing a framework for research in organic spintronics.
We successfully fabricated atomically precise anthenes with varying lengths ranging from 2 to 6 anthryls. With increasing lengths, the ground states switch from S=0 (closed‐shell bisanthene) to S=0 (open‐shell teranthene). In longer anthenes, the charge transfer can switch magnetism from S=0 to S=1/2.
AIM: To investigate the histological characteristics and ultrastructure of recurrent Chinese R124L mutated corneal dystrophy after keratoplasty.
METHODS: The subjects were enrolled from a Chinese ...family of corneal dystrophy with R124L heterozygous gene mutation and with a history of consanguineous marriage. Normal corneal samples were used as controls.
RESULTS: In this family, 2 patients (3 eyes) underwent penetrating keratoplasty (PKP) and 2 patients (4 eyes) underwent lamellar keratoplasty (LKP). They had recurrence at 33.5±3.0 (range 30-36)mo after keratoplasty. Among them, 1 patient (1 eye) underwent PKP again and 1 patient (2 eyes) underwent LKP again. In the R124L mutated recurrent corneal dystrophy, the corneal turbidity was mainly distributed from the upper corneal cortex to the anterior stroma; the corneal epithelium surface was rougher and more uneven; and, the corneal erosions were larger. Hematoxylin-eosin staining showed that the thickness of the corneal epithelium was uneven; the arrangement of the epithelial cells was disordered; and, some corneal epithelial cells were swollen. The results of Congo red staining, Masson’s trichrome staining and Periodic acid-Schiff staining were positive, while that of Alcian blue staining was negative. Under a transmission electron microscope, deposition of high electron density substances between epithelial and basal cells, and, apoptosis of basal cells were observed. Many high electron density depositions were observed in the sub-epithelial and anterior corneal matrix.
CONCLUSION: In the Chinese family of recurrent corneal dystrophy with R124L gene mutation, the corneal epithelia of the recurrent cases are rougher, and the corneal depositions are extracellular amyloid fibrin.
Quorum sensing (QS) is a phenomenon of intercellular communication discovered mainly in bacteria. A QS system consisting of QS signal molecules and regulatory protein components could control ...physiological behaviors and virulence gene expression of bacterial pathogens. Therefore, QS inhibition could be a novel strategy to combat pathogens and related diseases. QS inhibitors (QSIs), mainly categorized into small chemical molecules and quorum quenching enzymes, could be extracted from diverse sources in marine environment and terrestrial environment. With the focus on the exploitation of marine resources in recent years, more and more QSIs from the marine environment have been investigated. In this article, we present a comprehensive review of QSIs from marine bacteria. Firstly, screening work of marine bacteria with potential QSIs was concluded and these marine bacteria were classified. Afterwards, two categories of marine bacteria-derived QSIs were summarized from the aspects of sources, structures, QS inhibition mechanisms, environmental tolerance, effects/applications, etc. Next, structural modification of natural small molecule QSIs for future drug development was discussed. Finally, potential applications of QSIs from marine bacteria in human healthcare, aquaculture, crop cultivation, etc. were elucidated, indicating promising and extensive application perspectives of QS disruption as a novel antimicrobial strategy.
Dynamic precipitation phenomena are usually observed in Cu- and Ag-based thermoelectric compounds undergoing a temperature rise, affecting the stability and thermoelectric figure of merit zT. The ...present work demonstrates that rational controlling of the Cu content would eliminate unstable factors in BaCu2Te2, beneficial for achieving stable and reliable thermoelectric materials. Over-stoichiometric Cu in BaCu2Te2 can not only optimize the hole concentration approaching the optimal one, but also lead to the stable degenerate semiconducting behaviors. More importantly, despite the intrinsically low lattice thermal conductivity originating from the small phonon group velocities and mean free path, the excess Cu content generates widely distributed Cu-rich nano-precipitates with a size of 20–50 nm. These nano-precipitates significantly contribute to low-frequency phonon scattering for further reducing the thermal conductivity, and thus more than 25% of the κ reduction has been achieved at room temperature (0.95 W m−1 K−1 for BaCu2Te2 and 0.70 W m−1 K−1 for BaCu2.08Te2). A high figure of merit zT = 1.31 at 833 K has been realized for the sample BaCu2+xTe2 (x = 0.04), which is superior to the state of the art p-type Zintl phase thermoelectric materials.
Hepatocellular carcinoma (HCC) accounts for more than 80% of primary liver cancers and is one of the leading causes of cancer-related death in many countries. Cancer cell-derived exosomes are shown ...to mediate communications between cancer cells and the microenvironment, promoting tumorigenesis. Hedgehog signaling pathway plays important roles in cancer development of HCC.
Exosomes were isolated from culture medium of HCC cell lines PLC/PRF/5 and MHCC-97H and were found to promote cancer cell growth measured with cell proliferation and colony formation assay. HCC cells cultured with cancer cell-derived exosome had increased cancer stem cell (CSC) population demonstrated by increased cell sphere formation CSC marker expressions. Hedgehog protein Shh was found to be highly expressed in these two HCC cell lines and preferably carried by exosomes. When Shh was knocked down with shRNA, the resulting exosomes had a reduced effect on promoting cancer cell growth or CSC population increase compared to normal cell-derived exosomes.
The ability of PLC/PRF/5 cells to form tumor in a xenograft model was increased by the addition of the exosomes from control cancer cells but not the exosomes from Shh knocked down cancer cells. Finally, the higher plasma Exo-Shh levels were associated with later tumor stages, higher histological grades, multiple tumors, and higher recurrence rates.
This study demonstrated that HCC cells secreted Shh
exosome and promote tumorigenesis through the activated Hedgehog pathway.
Nano-sized nickel oxides have been synthesized in a water-in-oil microemulsion. The as-synthesized samples were characterized by powder X-ray diffraction (XRD), transmission electronic microscopy ...(TEM) and nitrogen adsorption/desorption. The particle size of nickel oxide can be controlled from 11.5 to 31.5nm by varying the proportion of water, surfactant and oil in the microemulsion, mixing method, and calcining temperature. Gas sensors based on as-synthesized nickel oxide are fabricated and investigated. They exhibit much higher sensitivities to hydrogen sulfide, ethanol and nitrogen dioxide, compared to those based on the conventional bulk NiO. Furthermore, the response of as-synthesized materials to various kinds of target gases increases with the decreasing of the particle size of gas sensors. It is noted that the NiO sensor with particle size of 11.5nm displays high degree of selectivity, coupled with high response value, making it particularly interesting for H2S-monitoring applications.
► Nano-sized nickel oxides have been synthesized in a microemulsion system. ► The particle size of nickel oxide can be controlled from 11.5 to 31.5nm. ► They exhibit higher sensitivities to H2S, C2H5OH and NO2 in contrast to bulk NiO. ► The response to all target gases increases with the decreasing of the particle size. ► The NiO sensor (11.5nm) displays outstanding sensitivity and selectivity to H2S
El Niño-Southern Oscillation (ENSO) features strong warm events in the eastern equatorial Pacific (EP), or mild warm and strong cold events in the central Pacific (CP), with distinct impacts on ...global climates. Under transient greenhouse warming, models project increased sea surface temperature (SST) variability of both ENSO regimes, but the timing of emergence out of internal variability remains unknown for either regime. Here we find increased EP-ENSO SST variability emerging by around 2030 ± 6, more than a decade earlier than that of CP-ENSO, and approximately four decades earlier than that previously suggested without separating the two regimes. The earlier EP-ENSO emergence results from a stronger increase in EP-ENSO rainfall response, which boosts the signal of increased SST variability, and is enhanced by ENSO non-linear atmospheric feedback. Thus, increased ENSO SST variability under greenhouse warming is likely to emerge first in the eastern than central Pacific, and decades earlier than previously anticipated.
The smart grid introduces new privacy implications to individuals and their family due to the fine-grained usage data collection. For example, smart metering data could reveal highly accurate ...real-time home appliance energy load, which may be used to infer the human activities inside the houses. One effective way to hide actual appliance loads from the outsiders is Battery-based Load Hiding (BLH), in which a battery is installed for each household and smartly controlled to store and supply power to the appliances. Even though such technique has been demonstrated useful and can prevent certain types of attacks, none of existing BLH works can provide probably privacy-preserving mechanisms. In this paper, we investigate the privacy of smart meters via differential privacy. We first analyze the current existing BLH methods and show that they cannot guarantee differential privacy in the BLH problem. We then propose a novel randomized BLH algorithm which successfully assures differential privacy, and further propose the Multitasking-BLH-Exp3 algorithm which adaptively updates the BLH algorithm based on the context and the constraints. Results from extensive simulations show the efficiency and effectiveness of the proposed method over existing BLH methods.
In the operation of a nuclear plant system, a distorted inflow of a reactor coolant pump appears owing to the steam generator channel head and multi-bend, leading to the deterioration of pump ...performance and stability. In the present study, three-dimensional numerical calculations of three model geometries are carried out using block grid technology, with RNG k-ε and DDES model applied in the steady and transient simulation. The simulation results are validated with an experiment testing the pump with a short inlet pipe. As for the results, under the distorted inflow condition, the pump head and efficiency are reduced by 4% and 5.2% respectively at the nominal flow rate. Additionally, when the pump is coupled with upstream structures, the inlet flow becomes distorted and more chaotic, and the swirl and radial flow are produced by asymmetric pressure difference. Meanwhile, a pair of local vortices appears in the inlet section, forming re-distributed mass flow rates. As the distorted flow enters the pump, the blade inlet pressure and flow rate are unevenly distributed. Moreover, the evolution process of the vortex is accompanied with strong non-uniformity in the impeller channel, and thus asymmetric tangential force is imposed on the blades, increasing the risk of the fatigue breakdown of the impeller.
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