825 research outputs found
Interpretation of unsaturated soil behaviour in the stress-saturation space. II: Constitutive relationships and validations
Based on the equations for volume change and saturation variation proposed in the companion paper [37], an alternative constitutive framework is presented for interpreting coupled hydro-mechanical behaviour for unsaturated soils. In this new framework, all constitutive laws are built in the space of stress vs. degree of saturation. Suction is not involved explicitly in the constitutive model for unsaturated soils. The loading-collapse yield surface is derived based on the proposed volume change equation in the plane of the effective degree of saturation and the Bishop effective stress. The proposed volume change equation and the corresponding yield surface are generalised to three-dimensional stress states by incorporating with the Modified Cam-clay model, following the same procedure introduced in the Sheng–Fredlund–Gens (SFG) model. The basic properties and performance of the proposed constitutive model are then illustrated through numerical examples with various drying/wetting/loading paths. Finally, the proposed model is validated against a variety of experimental data including drained and undrained tests, isotropic and triaxial tests and reconstituted and compacted soils
Hsa_circ_0006571 promotes spinal metastasis through sponging microRNA-138 to regulate sirtuin 1 expression in lung adenocarcinoma
Copyright © 2009 - 2021 AME Publishing Company. All rights reserved. Open Access Statement:This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/Background: Circular RNAs (circRNAs) are known to participate in lung cancer. However, their role in spinal metastasis (SM) of lung adenocarcinoma remains elusive. In this study, we determined that hsa_circ_0006571 serves as a sponge for miR-138, which targets sirtuin 1 (Sirt1) in the development of SM.
Methods: A human circRNA microarray was performed to compare SM and lung adenocarcinoma samples. The expression of hsa_circ_0006571 and miR-138 was determined using quantitative polymerase chain reaction (qPCR) in vitro and in vivo. Cell proliferation was performed by Cell Counting Kit-8 (CCK-8) and apoptosis was analyzed by Annexin V/PI staining. RNA-pulldown and RNA immunoprecipitation (RIP) were used to analyze the interaction between hsa_circ_0006571. Tumor metastasis was determined through a xenograft experiment in vivo.
Results: Hsa_circ_0006571 was observed to be significantly upregulated in SM tissues through circRNA microarray and qPCR. We detected a lower expression of miR-138 in SM tissues compared with lung adenocarcinoma. Hsa_circ_0006571 silencing suppressed lung cancer cell proliferation and migration while promoting apoptosis. Hsa_circ_0006571 interacted with miR-138 to promote expression of Sirt1, leading to activation of epithelial-mesenchymal transition (EMT). Xenograft experiments showed that downregulation of hsa_circ_0006571 delayed the SM of lung adenocarcinoma cells via the miR-138-Sirt1 axis.
Conclusions: Hsa_circ_0006571 promoted tumor cell migration and invasion via the miR-138/Sirt1 pathway. Our observations indicate that circRNAs are possible novel therapeutic targets for SM of lung adenocarcinoma.This work was supported by the National Natural Science Foundation of China (81572629, 81772855 and 81701370).info:eu-repo/semantics/publishedVersio
Superconductivity Induced by Site-Selective Arsenic Doping in MoSi
Arsenic doping in silicides has been much less studied compared with
phosphorus. In this study, superconductivity is successfully induced by As
doping in MoSi. The superconducting transition temperature ()
reaches 7.7 K, which is higher than those in previously known WSi-type
superconductors. MoSiAs is a type-II BCS superconductor with upper and
lower critical fields of 6.65 T and 22.4 mT, respectively. In addition, As
atoms are found to selectively take the 8 sites in MoSiAs. The
emergence of superconductivity is possibly due to the shift of Fermi level as a
consequence of As doping, as revealed by the specific heat measurements and
first-principles calculations. Our work provides not only another example of As
doping, but also a practical strategy to achieve superconductivity in silicides
through Fermi level engineering.Comment: Supporting Information available at the corresponding DO
Identification of prognostic cancer-associated fibroblast markers in luminal breast cancer using weighted gene co-expression network analysis
BackgroundCancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression and are known to mediate endocrine and chemotherapy resistance through paracrine signaling. Additionally, they directly influence the expression and growth dependence of ER in Luminal breast cancer (LBC). This study aims to investigate stromal CAF-related factors and develop a CAF-related classifier to predict the prognosis and therapeutic outcomes in LBC.MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to obtain mRNA expression and clinical information from 694 and 101 LBC samples, respectively. CAF infiltrations were determined by estimating the proportion of immune and cancer cells (EPIC) method, while stromal scores were calculated using the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm. Weighted gene co-expression network analysis (WGCNA) was used to identify stromal CAF-related genes. A CAF risk signature was developed through univariate and least absolute shrinkage and selection operator method (LASSO) Cox regression model. The Spearman test was used to evaluate the correlation between CAF risk score, CAF markers, and CAF infiltrations estimated through EPIC, xCell, microenvironment cell populations-counter (MCP-counter), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms. The TIDE algorithm was further utilized to assess the response to immunotherapy. Additionally, Gene set enrichment analysis (GSEA) was applied to elucidate the molecular mechanisms underlying the findings.ResultsWe constructed a 5-gene prognostic model consisting of RIN2, THBS1, IL1R1, RAB31, and COL11A1 for CAF. Using the median CAF risk score as the cutoff, we classified LBC patients into high- and low-CAF-risk groups and found that those in the high-risk group had a significantly worse prognosis. Spearman correlation analyses demonstrated a strong positive correlation between the CAF risk score and stromal and CAF infiltrations, with the five model genes showing positive correlations with CAF markers. In addition, the TIDE analysis revealed that high-CAF-risk patients were less likely to respond to immunotherapy. Gene set enrichment analysis (GSEA) identified significant enrichment of ECM receptor interaction, regulation of actin cytoskeleton, epithelial-mesenchymal transition (EMT), and TGF-β signaling pathway gene sets in the high-CAF-risk group patients.ConclusionThe five-gene prognostic CAF signature presented in this study was not only reliable for predicting prognosis in LBC patients, but it was also effective in estimating clinical immunotherapy response. These findings have significant clinical implications, as the signature may guide tailored anti-CAF therapy in combination with immunotherapy for LBC patients
Proton strangeness form factors in (4,1) clustering configurations
We reexamine a recent result within a nonrelativistic constituent quark model
(NRCQM) which maintains that the uuds\bar s component in the proton has its
uuds subsystem in P state, with its \bar s in S state (configuration I). When
the result are corrected, contrary to the previous result, we find that all the
empirical signs of the form factors data can be described by the lowest-lying
uuds\bar s configuration with \bar s in P state that has its uuds subsystem in
state (configuration II). Further, it is also found that the removal of the
center-of-mass (CM) motion of the clusters will enhance the contributions of
the transition current considerably. We also show that a reasonable description
of the existing form factors data can be obtained with a very small probability
P_{s\bar s}=0.025% for the uuds\bar s component. We further see that the
agreement of our prediction with the data for G_A^s at low-q^2 region can be
markedly improved by a small admixture of configuration I. It is also found
that by not removing CM motion, P_{s\bar s} would be overestimated by about a
factor of four in the case when transition dominates over direct currents.
Then, we also study the consequence of a recent estimate reached from analyzing
the existing data on quark distributions that P_{s\bar s} lies between 2.4-2.9%
which would lead to a large size for the five-quark (5q) system, as well as a
small bump in both G^s_E+\eta G^s_M and G^s_E in the region of q^2 =< 0.1
GeV^2.Comment: Prepared for The Fifth Asia-Pacific Conference on Few-Body Problems
in Physics 2011 in Seoul, South Korea, 22-26 August 201
Altered spontaneous brain activity patterns in patients with unilateral acute open globe injury using amplitude of low-frequency fluctuation: a functional magnetic resonance imaging study
Strong-Coupling Superconductivity with 10.8 K Induced by P Doping in the Topological Semimetal MoSi
By performing P doping on the Si sites in the topological semimetal
MoSi, we discover strong-coupling superconductivity in
MoSiP (0.5 2.0). MoSi crystallizes in
the WSi-type structure with space group of (No. 140), and is
not a superconductor itself. Upon P doping, the lattice parameter decreases
while increases monotonously. Bulk superconductivity is revealed in
MoSiP (0.5 2.0) from resistivity,
magnetization, and heat capacity measurements. in
MoSiP reaches as high as 10.8 K, setting a new record among
the WSi-type superconductors. The upper and lower critical fields for
MoSiP are 14.56 T and 105 mT, respectively. Moreover,
MoSiP is found to be a fully gapped superconductor with
strong electron-phonon coupling. First-principles calculations suggest that the
enhancement of electron-phonon coupling is possibly due to the shift of the
Fermi level, which is induced by electron doping. The calculations also reveal
the nontrivial band topology in MoSi. The and upper critical
field in MoSiP are fairly high among pseudobinary compounds.
Both of them are higher than those in NbTi, making future applications
promising. Our results suggest that the WSi-type compounds are ideal
platforms to search for new superconductors. By examinations of their band
topologies, more candidates for topological superconductors can be expected in
this structural family.Comment: 15 pages, 5 figures. Supplementary Information availabe at the
corresponding DO
Guideline adherence of β-blocker initiating dose and its consequence in hospitalized patients with heart failure with reduced ejection fraction
Background: We aim to investigate the guideline adherence of β-blocker (BB) initiating dose in Chinese hospitalized patients with heart failure with reduced ejection fraction (HFrEF) and whether the adherence affected the in-hospital outcomes.Methods: This was a retrospective study of patients hospitalized with HFrEF who had initiated BBs during their hospitalization. We defined adherence to clinical practice guidelines as initiating BB with standard dose and non-adherence to guidelines if otherwise, and examined the association between adherence to guidelines and in-hospital BB-related adverse events. Subgroup analyses based on sex, age, coronary heart disease, and hypertension were performed.Results: Among 1,104 patients with HFrEF initiating BBs during hospitalization (median length of hospitalization, 12 days), 304 (27.5%) patients received BB with non-adherent initiating dose. This non-adherence was related to a higher risk (hazard ratio [95% confidence interval]) of BB dose reduction or withdrawal (1.78 [1.42 to 2.22], P < 0.001), but not significantly associated with risks of profound bradycardia, hypotension, cardiogenic shock requiring intravenous inotropes, and severe bronchospasm requiring intravenous steroid during hospitalization.Conclusion: This study identified that over a fourth of patients had received BBs with an initiating dose that was not adherent to guidelines in Chinese hospitalized patients with HFrEF, and this non-adherence was associated with BB dose reduction or withdrawal during hospitalization
Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy?
Blood-Brain Barrier (BBB) disruption is an important pathophysiological process of acute ischemic stroke (AIS), resulting in devastating malignant brain edema and hemorrhagic transformation. The rapid activation of immune cells plays a critical role in BBB disruption after ischemic stroke. Infiltrating blood-borne immune cells (neutrophils, monocytes, and T lymphocytes) increase BBB permeability, as they cause microvascular disorder and secrete inflammation-associated molecules. In contrast, they promote BBB repair and angiogenesis in the latter phase of ischemic stroke. The profound immunological effects of cerebral immune cells (microglia, astrocytes, and pericytes) on BBB disruption have been underestimated in ischemic stroke. Post-stroke microglia and astrocytes can adopt both an M1/A1 or M2/A2 phenotype, which influence BBB integrity differently. However, whether pericytes acquire microglia phenotype and exert immunological effects on the BBB remains controversial. Thus, better understanding the inflammatory mechanism underlying BBB disruption can lead to the identification of more promising biological targets to develop treatments that minimize the onset of life-threatening complications and to improve existing treatments in patients. However, early attempts to inhibit the infiltration of circulating immune cells into the brain by blocking adhesion molecules, that were successful in experimental stroke failed in clinical trials. Therefore, new immunoregulatory therapeutic strategies for acute ischemic stroke are desperately warranted. Herein, we highlight the role of circulating and cerebral immune cells in BBB disruption and the crosstalk between them following acute ischemic stroke. Using a robust theoretical background, we discuss potential and effective immunotherapeutic targets to regulate BBB permeability after acute ischemic stroke
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