Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, ...apoptosis, and chemotherapy resistance of mutant p53 LC cells.
Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53).
Mutant p53 cells exhibited increased expression of the C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and inositol-requiring enzyme-1α (IRE1α). The Mutant p53 cells were also found to be sensitive to chemotherapy and displayed decreased expression of PI3K, Akt, and mTOR. The mutant p53 cell lines were treated with tunicamycin to induce ERS and rapamycin in order to inhibit mTOR. Both agents increased the expression of CHOP, GRP78, IRE1α, LC3-II/LC3-I, Atg5, Atg7, caspase-3, caspase-12, cleaved caspase-3, cleaved caspase-12, as well as decreases in cell proliferation as well as the expression levels of PI3K, Akt, and mTOR. Enhanced levels of cell apoptosis and reduced chemotherapy resistance were also detected.
The findings of our study suggest that ERS promotes autophagy and apoptosis, while acting to reduce chemotherapy resistance in mutant p53 LC cells by downregulating the PI3K/Akt/mTOR signaling pathway.
Double-skin composite walls have been increasingly applied in high-rise buildings. The behavior of connection to the wall under seismic action is essential to the performance of the whole structures. ...This paper investigated the experimental seismic behavior of four proposed connections to an innovative double-skin composite wall. The wall employs steel trusses as internal connectors. Large-scaled cyclic tests were performed on connections with different configurations. The seismic behavior was evaluated in terms of failure mode, hysteretic response, stiffness degradation, ductility, and energy dissipation ability. The test results found that all specimens exhibited stable and plentiful hysteretic performance without noticeable pinching effect. Reasonable stiffness degradation, good ductility and satisfying energy absorbing capacity were also observed. Strain distributions at key locations were analyzed to evaluate the strain development at beam, stiffener, and wall face. It is concluded that the connection with vertical stiffeners has good seismic behavior. The application of vertical plate or additional cover plate is also acceptable. In addition, the use of through plate should be careful as the welding quality is important to the behavior of connections.
•New connection details were proposed for composite walls.•Cyclic tests were conducted on full-scaled specimens.•Influence of connection configuration on performance was discussed.
To obtain high quality of drinking water free from biocontaminants is especially important issue. A new strategy employing smectic liquid‐crystalline ionic membranes exhibiting 2D structures of ...layered nanochannels for water treatment is proposed for efficient virus removal and sufficient water flux. The smectic A (SmA) liquid‐crystalline membranes obtained by in situ polymerization of an ionic mesogenic monomer are examined for removal of three distinct viruses with small size: Qβ bacteriophage, MS2 bacteriophage, and Aichi virus. The semi‐bilayer structure of the SmA significantly obstructs the virus penetration with an average log reduction value of 7.3 log10 or the equivalent of reducing 18 million viruses down to 1. Furthermore, the layered nanochannels of the SmA liquid crystal allow efficient water permeation compared to other types of liquid‐crystalline membrane consisting of nanopores.
A 2D virus removal membrane for water treatment based on polymeric self‐assembling liquid crystal is developed. The obtained polymer membrane shows excellent virus removal with 99.999994% efficiency. The liquid crystal forms 2D lamellar nanochannels allowing superior virus removal while maintaining improved permeation.
Carbon nanohoop compounds have attracted extensive attention recently due to their aesthetically pleasing structures and unique properties. In order to reveal the structure-property relationship ...between the size-dependent effect and the nonlinear optical (NLO) response, a series of carbon nanohoops consisting of zigzag carbon nanotubes (CNTs), named D-CM2P
n
P-A (
n
= 4, 6, 8, 10, and 12), are systematically designed and investigated using density functional theory (DFT). Significantly, the first hyperpolarizability (
β
tot
) of the system increases with the increasing structure size, which is primarily the result of the charge transfer transition. Subsequently, the major electronic transition changes from local excitation to charge transfer as the size of the structure increases, indicating that charge transfer becomes stronger significantly. Furthermore, a two-level model and the absorption spectrum can well explain the trend of the
β
tot
value. In addition, the unit sphere representation (USR) and hyper-Rayleigh scattering (HRS) are used to further explain the nature of the second-order NLO response. More importantly, adding a π-bridge as an effective strategy further enhances the second-order NLO responses of the system. The relevant results are expected to provide a new perspective on the structure-NLO property correlation of donor (D)-conjugated bridge (π)-acceptor (A) type carbon nanohoops and theoretical guidance for the rational design and synthesis of fascinating carbon nanohoops as NLO materials.
The nonlinear optical responses of carbon nanohoop derivatives increase significantly with the increasing number and the length of π-bridges.
This paper presented an experimental and theoretical studies on double-skin truss-reinforced composite wall (DSTCW) subjected to eccentric compression. Five full-scale DSTCWs with different loading ...eccentricities, height-width ratios and truss spacing were conducted under uniaxial eccentric compressive. The effects of those variations on the failure mode, load- axial displacement curve, lateral deflection, strain distribution were discussed. Subsequently, the finite element (FE) models were built and verified to discuss the working mechanism of DSTCWs under eccentric compression, and an extensive parametric analysis was performed to find the vital parameters on the mechanical behavior of DSTCWs subjected to eccentric compression. Finally, based on Eurocode standard EC4, the Interaction model for DSTCW was proposed to estimate the bearing capacity subjected to eccentric compression. The proposed Interaction model was validated against the results from FE model analysis and experiments.
Traditional casting preparation of Cu-Fe alloy is difficult, especially when Fe content is relatively high, because there is a metastable immiscible region of liquid components between copper (Cu) ...and iron (Fe), which causes serious compositional segregation in Cu-Fe alloys and leads to low strength and undesirable electrical conductivity of the alloys. In this study, Cu-50Fe alloy was fabricated by chemical co-precipitation and powder metallurgy. Cu-Fe mixed powders prepared by chemical co-precipitation have an average particle size of about 3.5 µm and a near-spherical shape. Copper and iron phases in the fabricated alloy intertwine with each other. After cold deformation, copper and iron phases are elongated along the cold deformation direction to form strips. During aging treatment, a number of Fe particles with diameter of 10–50 nm precipitate in Cu phases in the alloy. The tensile strength and electrical conductivity of the deformed and aged Cu-50Fe alloy are 651 MPa and 41.5%IACS, respectively.
Brain capillaries are crucial for cognitive functions by supplying oxygen and other nutrients to and removing metabolic wastes from the brain. Recent studies have demonstrated that constriction of ...brain capillaries is triggered by beta-amyloid (Aβ) oligomers via endothelin-1 (ET1)-mediated action on the ET1 receptor A (ETRA), potentially exacerbating Aβ plaque deposition, the primary pathophysiology of Alzheimer’s disease (AD). However, direct evidence is still lacking whether changes in brain capillaries are causally involved in the pathophysiology of AD. Using APP/PS1 mouse model of AD (AD mice) relative to age-matched negative littermates, we identified that reductions of density and diameter of hippocampal capillaries occurred from 4 to 7 months old while Aβ plaque deposition and spatial memory deficit developed at 7 months old. Notably, the injection of ET1 into the hippocampus induced early Aβ plaque deposition at 5 months old in AD mice. Conversely, treatment of ferulic acid against the ETRA to counteract the ET1-mediated vasoconstriction for 30 days prevented reductions of density and diameter of hippocampal capillaries as well as ameliorated Aβ plaque deposition and spatial memory deficit at 7 months old in AD mice. Thus, these data suggest that reductions of density and diameter of hippocampal capillaries are crucial for initiating Aβ plaque deposition and spatial memory deficit at the early stages, implicating the development of new therapies for halting or curing memory decline in AD.
This paper presents a research on the axial compressive behavior of double skin composite wall(DSCW) with steel truss, which is a novel type of composite wall. The steel truss is constructed by two ...angles and kinked rebar is acting as the interface connector. Experimental study was introduced briefly and software ABAQUS was adopted for numerical simulation analysis. By comparing with the experimental results, the accuracy of the finite element model was verified and then structural behavior of the walls was comprehensively evaluated. A parametric study was carried out to investigate the influences of the strength of steel plate and infilled concrete, truss horizontal spacing to thickness ratio on the compression responses of the composite wall. The results show that the better ductility of the composite wall can be achieved by the lower concrete strength and higher steel plate strength. Besides, the strength of the concrete and the steel plate tends to have a linear correlation with the load-carrying capacity. The horizontal spacing to thickness ratio has the significant influence on the failure mode of the composite wall and local buckling of steel plate can be avoided when the ratio is less than a certain value. In addition, the calculation formula for the axial compressive load-carrying capacity of the composite wall was proposed to provide a reference basis for the application of this type of composite walls in practice.
miR-126
which is considered one of the most important miRNAs for maintaining vascular integrity, plays an important role in neuroprotection after cerebral ischemia–reperfusion (I-R). Moreover, ...vascular endothelial growth factor A (VEGFA), sprouty-related EVH1 domain-containing protein 1 (SPRED1), and Raf-1 are also involved in physiological processes of vascular endothelial cells (ECs). This study investigated how
miR-126
changes with reperfusion time in different brain tissues after global cerebral ischemia and focal cerebral ischemia and examined the underlying mechanism
miR-126
involving VEGFA, SPRED1, and Raf-1 after I-R. The results indicated decreases in the levels of
miR-126-3p
and
miR-126-5p
expression in
mice
and
gerbils
after I-R, consistent with the results after oxygen and glucose deprivation and reperfusion (OGD/R) in PC12 cells. Glial cells were activated as neuronal damage gradually increased after I-R. Inhibition of
miR-126-3p
exacerbated the OGD/R-induced cell death and reduced cell viability. After
miR-126-3p
inhibition, the levels of SPRED1 and VEGFA expression were increased, and
p
-Raf-1 expression was decreased after OGD/R. Moreover, based on the intervention of
miR-126-3p
inhibition, we found that the expression of
p
-Raf-1 was significantly increased after the intervention of
siSPRED1
, while it was not statistically significant after intervention of
siVEGFA
. The reduction of
miR-126
expression after global and focal cerebral ischemia exacerbated neuronal death, which was closely related to increasing the SPRED1 activation and inhibiting the Raf-1 expression.
Sandwich composite walls are composed of two external steel faceplates and concrete infill and have been increasingly applied in infrastructure to resist either gravity or lateral loads. They combine ...the advantages of both steel and concrete and offer excellent structural behavior. In this paper, the performance of a new type of T-shaped sandwich composite walls with truss connectors was studied. Three full-scaled specimens with T-section were tested under eccentric compression. The failure mode was identified as the sectional strength failure. Load versus axial and out-of-plane displacement responses, buckling stress, axial stiffness, ductility, and strength utilization were discussed. Based on CECS 159, the interaction model between the compression and bending moment was proposed to estimate the sectional strength of sandwich composite walls under eccentric compression. The comparison between the test data and the proposed curve shows that the proposed method offers reasonable and conservative predictions on the strength of sandwich composite walls.
•Full-scaled test was conducted on new type of T-shaped sandwich wall.•Structural performance was comprehensively discussed.•Design method was proposed.
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