Abnormal metabolism of tumour cells is closely related to the occurrence and development of breast cancer, during which the expression of NF‐E2‐related factor 2 (Nrf2) is of great significance. ...Metastatic breast cancer is one of the most common causes of cancer death worldwide; however, the molecular mechanism underlying breast cancer metastasis remains unknown. In this study, we found that the overexpression of Nrf2 promoted proliferation and migration of breast cancers cells. Inhibition of Nrf2 and overexpression of Kelch‐like ECH‐associated protein 1 (Keap1) reduced the expression of glucose‐6‐phosphate dehydrogenase (G6PD) and transketolase of pentose phosphate pathway, and overexpression of Nrf2 and knockdown of Keap1 had opposite effects. Our results further showed that the overexpression of Nrf2 promoted the expression of G6PD and Hypoxia‐inducing factor 1α (HIF‐1α) in MCF‐7 and MDA‐MB‐231 cells. Overexpression of Nrf2 up‐regulated the expression of Notch1 via G6PD/HIF‐1α pathway. Notch signalling pathway affected the proliferation of breast cancer by affecting its downstream gene HES‐1, and regulated the migration of breast cancer cells by affecting the expression of EMT pathway. The results suggest that Nrf2 is a potential molecular target for the treatment of breast cancer and targeting Notch1 signalling pathway may provide a promising strategy for the treatment of Nrf2‐driven breast cancer metastasis.
In recent decades, reactions of inexpensive and abundantly available alcohols (C−OH) with nucleophilic P(O)−H compounds, leading to the construction of C−P bonds, have emerged as one of the most ...efficient strategies as it is an atom‐economical and environmental benign approach with water as the only by‐product. Various organophosphorus compounds bearing C(sp3)−P, C(aryl)−P and C(alkenyl)−P bonds have been achieved via this direct dehydrative cross‐couplings under Brønsted or Lewis acid catalysis. This review article aims to summarize the recent advances in such dehydrative and related C−P bond forming strategies, to briefly discuss the reaction mechanisms and challenges, and to outline synthetic opportunities that are still open.
•The interface fatigue life of multi-layer coated conductor tapes was evaluated.•The displacement-energy model (DEM) approach can capture the damage-evolution in the interfaces simultaneously.•For ...the SuperPower tapes (the most typical commercial tapes), a critical interface fatigue life of 3.9372×105 cycles was found on three points fatigue bending tests.
Rare-earth barium copper oxide (REBCO) coated conductor (CC) tapes in high-field magnet applications usually experience fatigue due to a variety of cyclic mechanical and thermal loads. Therefore, estimation of the fatigue life of a particular REBCO CC is vital for the successful development and applications of high-field magnets devices, which are crucial components for aerospace, automotive, and maglev train transportation. For these needs, the authors evaluated the interfaces fatigue crack growth rate, and fatigue life of multilayered yttrium barium copper oxide (YBCO) coated conductor (CC) tape at room temperature via a displacement-energy model (DEM) approach. The DEM approach can measure the damage initiation and propagation rate in specific interfaces of a multi-layer film structure simultaneously. It assumed transverse intrinsic tensile/compressive cyclic loading and adopted the linear-elastic damage law with the maximum normal stress failure criterion to characterize the degradation in the tape. With an initial Eigenfunction (W0) (a parameter equivalent to the stress loading amplitude range) set as 2.30 × 10-12 m, the computed results show a strain (ε) range from 0.35 to 0.46 % and fatigue ratio range from 0.002 to 0.07 in the interfaces of the tape. Under the given parameters, it was found out that the tape has a critical interface fatigue crack growth rate of 2.54 pm/cycle corresponding to fatigue life of 3.9372 × 105 cycles. According to our previous studies, the results on the DEM approach has good agreement with those on the Finite Element Method (FEM) counterpart model, closed-form solution (CFS) model, and X-ray diffraction method (XRD). This technique can help to avoid enormous resources usually spent experimentally on the calculation of fatigue life of REBCO CC tapes.
Background. Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease, as well as a worldwide medical problem with a substantial socioeconomic burden. In China, ...Chinese patent medicines (CPMs) have been widely utilized as promising and effective therapy options for NAFLD. Traditional Chinese medicine (TCM) is a particular kind of medical science reliant on real-world clinical practices and evidence. Therefore, using the real-world data extracted from pragmatic randomized controlled trials (PRCTs) have more reference value for the application of CPMs in NAFLD. Method. Six databases were searched from their inception up to March 18, 2022. The methodological quality of the included study was evaluated by the Cochrane risk-of-bias tool. Then, The STATA 13.0 program was then used to do a network meta-analysis (NMA) of real-world studies. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Results. Forty-three PRCTs (4997 cases in total) were identified. Da-Huang-Li-Dan capsule (DHLD), Dan-Ning tablet (DN), Dang-Fei-Li-Gan-Ning capsule (DFLGN), Qiang-Gan capsule (QG), and Hua-Zhi-Rou-Gan granule (HZRG) were among the five CPMs tested. As far as the clinical effective rate of the primary outcome index was concerned, the top three CPMs were DN + CDs: OR = 0.19, 95% CIs: 0.12, 0.31 (SUCRA: 81.8%); DFLGN + CDs: OR = 0.21, 95% CIs: 0.09, 0.46 (SUCRA: 74.9%), and DHLD + CDs: OR = 0.26, 95% CIs: 0.10, 0.67 (SUCRA: 61.1%). In terms of liver function index, DN + CDs ranked first in ALT index: MD = 15.81, 95% CIs: 10.05, 21.57 (SUCRA: 85.5%), DFLGN + CDs ranked first in AST index: MD = 14.94, 95% CIs: 4.77, 25.11 (SUCRA: 83.6%), HZRG + CDs ranked first in TC index: MD = 0.53, 95% CIs: 0.28, 1.03 (SUCRA: 87.1%) and TG index: MD = 1.8, 95% CIs: 1.41, 2.30 (SUCRA: 79.9%). Conclusion. Using CPMs as a coadjuvant treatment might be positive efficacious intervention from which patients with NAFLD will derive benefits. When it came to the clinical effective rate and other outcomes, DN + CDs demonstrated a significant improvement in individuals with NAFLD.
Copper oxide is a promising anode material for lithium-ion batteries. However, rapid capacity fading associated with huge volume variation upon the (de)lithiation of CuO has limited its practical ...application. To address this problem, herein, we report the fabrication of one-dimensional CuO nanochains
via
a facile wet chemical route. The chain structure consists of particles, with an average crystallite dimension of
ca.
20-25 nm, connected through well-knit junctions, which helps to promote charge transfer at the electrode|electrolyte interface and accommodate the volume variation of the oxide. Due to these structural merits, the CuO nanochains exhibited excellent rate performance and stable electrochemistry
versus
Li, which could be promising anode materials for high-power Li-ion batteries.
1D CuO nanochains promote charge transfer at the electrode|electrolyte interface and exhibit excellent rate performance and stable electrochemistry.
Colorectal cancer (CRC) is the third‐leading cause of cancer mortality worldwide. HACE1 function as a tumor‐suppressor gene and is downregulated in several kinds of cancers. However, the distribution ...and clinical significance of HACE1 in CRC is still not clarified. In this study, we found that the HACE1 expression is greatly downregulated in CRC tissues and cell lines. Moreover, the HACE1 expression was significantly associated with inhibition of CRC cell proliferation, metastasis, and invasion. HACE1 inhibited epithelial–mesenchymal transition in CRC cells. Furthermore, we found that
HACE1 altered the protein expression of the Hippo pathway by downregulation of YAP1. HACE1 suppresses the invasive ability of CRC cells by negatively regulating the YAP1 pathway. Our data indicates that HACE1 directly targets YAP1 and induces downregulation of YAP1, thereby increasing the activity of the Hippo pathway. In summary, these findings demonstrated that HACE1–YAP1 axis had an important part in the CRC development and progression.
Loss of HACE1 promoted epithelial–mesenchymal transition (EMT), migration and invasion in CRC cells. Loss of HACE1 upregulated YAP1 expression in CRC cells. Knockdown of HACE1, via YAP1‐mediated EMT, is involved in cancer cell migration in CRC cells
Zhisou Powder (ZSP), a traditional Chinese medicine (TCM) prescription, has been widely used in the clinic for the treatment of post-infectious cough (PIC). However, the exact mechanism is not clear.
...The aim of this study was to investigate the ameliorative effect of ZSP on PIC in mice. The possible mechanisms of action were screened based on network pharmacology, and the potential mechanisms were explored through molecular docking and in vivo experimental validation.
Lipopolysaccharide (LPS) (80μg/50 μL) was used to induce PIC in mice, followed by daily exposure to cigarette smoke (CS) for 30 min for 30 d to establish PIC model. The effects of ZSP on PIC mice were observed by detecting the number of coughs and cough latency, peripheral blood and bronchoalveolar lavage fluid (BALF) inflammatory cell counts, enzyme-linked immunosorbent assay (ELISA), and histological analysis. The core targets and key pathways of ZSP on PIC were analyzed using network pharmacology, and TRPA1 and TRPV1 were validated using RT-qPCR and western blotting assays.
ZSP effectively reduced the number of coughs and prolonged the cough latency in PIC mice. Airway inflammation was alleviated by reducing the expression levels of the inflammatory mediators TNF-α and IL-1β. ZSP modulated the expression of Substance P, Calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) in BALF. Based on the results of network pharmacology, the mechanism of action of ZSP may exert anti-neurogenic airway-derived inflammation by regulating the expression of TRPA1 and TRPV1 through the natural active ingredients α-spinastero, shionone and didehydrotuberostemonine.
ZSP exerts anti-airway inflammatory effects through inhibition of TRPA1/TRPV1 channels regulating neuropeptides to alleviate cough hypersensitivity and has a favorable therapeutic effect on PIC model mice. It provides theoretical evidence for the clinical application of ZSP.
Workflow diagram of the research. Display omitted
•ZSP has significant potential as a therapeutic intervention for PIC.•ZSP may alleviate post-infectious cough by regulating TRPA1/TRPV1 channels reducing neuropeptides and cytokines in BALF.•ZSP may activate TRPA1/TRPV1 channels via the active ingredients α-spinastero, shionone and didehydrotuberostemonine.
•Simulates the extent of fabrication defects in coated conductor tapes with different materials and architecture.•The interlayer interactions of layers cause severe lattice mismatch during deposition ...of films.•The lattice mismatch in the form of losses of bonding strength was computed using modified Hamaker models.•Computed results show that samples with more number of layers suffer comparatively higher losses of bonding strength.
In this study, the authors carried out an inspection of the extent of fabrication defects in rare-earth barium copper oxide (REBCO) coated conductors (CC) using the displacement-energy model (DEM) approach. The DEM approach can simulate the creation, propagation, and distribution of interfacial defects during the deposition of films onto a substrate, thereby save researchers the enormous resources needed to carry out similar studies experimentally. Defects in a sample originate from the interlayer interactions such as the thermal mismatch and eigenstates of layers as a function of temperature and time, respectively. The induced strains or gaps (determined by an increase in a lattice constant) between an interface in a sample caused by the interlayer interactions are computed as losses of bonding energy between interacting molecules using modified Hamaker models. The samples used for the simulation are based on the tape architecture of three leading industrial manufacturers of coated conductors (SuperPower Incorporated, Bruker High-Temperature Superconductors, and American superconductors). Also, in the simulation of this study, it assumes the samples from the manufacturers have a similar size (length x width) and fabrication method (chemical deposition method) to determine a tape architecture with comparatively lesser fabrication defects under similar fabrication conditions. Primarily, simulation results show that samples with more number of layers suffer relatively higher losses of bonding energy. According to this study and previous studies, the computed results on the DEM approach are consistent with those on several valuable experiments and models in the literature.
•A 1D nonlinear elasto-thermo-magnetic hysteresis constitutive model is proposed.•This model shows a good agreement with experimental results.•The proposed model has not piecewise functions and ...implicit functions.
Based on the thermodynamic theory, by introducing the Weiss molecular field and considering current eddy loss, a 1D nonlinear elasto-thermo-magnetic multi-field coupling hysteresis constitutive model is proposed for giant magnetostrictive materials. This new model can fully describe the effects of the stress, frequency and ambient temperature not only on the curves of magnetostriction and magnetization under the static frequency, but also on the hysteresis characteristics of magnetostriction and magnetization at the dynamic frequency. This model, which has more concise mathematical form compared with other related models, shows a good agreement with experimental results on the magnetostrictive strain and magnetization hysteresis loops. Furthermore, the predicted results have indicated the necessary of considering the Weiss molecular field. This model is of convenient for both theoretical researches and engineering applications of magnetostrictive materials due to being without piecewise function and implicit functions in magnetostrictive constitutive relations.
Glioma is a common malignant tumours in the central nervous system (CNS), that exhibits high morbidity, a low cure rate, and a high recurrence rate. Currently, immune cells are increasingly known to ...play roles in the suppression of tumourigenesis, progression and tumour growth in many tumours. Therefore, given this increasing evidence, we explored the levels of some immune cell genes for predicting the prognosis of patients with glioma.
We extracted glioma data from The Cancer Genome Atlas (TCGA). Using the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm, the relative proportions of 22 types of infiltrating immune cells were determined. In addition, the relationships between the scales of some immune cells and sex/age were also calculated by a series of analyses. A P-value was derived for the deconvolution of each sample, providing credibility for the data analysis (P < 0.05). All analyses were conducted using R version 3.5.2. Five-year overall survival (OS) also showed the effectiveness and prognostic value of each proportion of immune cells in glioma; a bar plot, correlation-based heatmap (corheatmap), and heatmap were used to represent the proportions of immune cells in each glioma sample.
In total, 703 transcriptomes from a clinical dataset of glioma patients were drawn from the TCGA database. The relative proportions of 22 types of infiltrating immune cells are presented in a bar plot and heatmap. In addition, we identified the levels of immune cells related to prognosis in patients with glioma. Activated dendritic cells (DCs), eosinophils, activated mast cells, monocytes and activated natural killer (NK) cells were positively related to prognosis in the patients with glioma; however, resting NK cells, CD8
T cells, T follicular helper cells, gamma delta T cells and M0 macrophages were negatively related to prognosis in the patients with glioma. Specifically, the proportions of several immune cells were significantly related to patient age and sex. Furthermore, the level of M0 macrophages was significant in regard to interactions with other immune cells, including monocytes and gamma delta T cells, in glioma tissues through sample data analysis.
We performed a novel gene expression-based study of the levels of immune cell subtypes and prognosis in glioma, which has potential clinical prognostic value for patients with glioma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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