The transcription factor Grainyhead-like 2 (GRHL2) is a critical transcription factor for epithelial tissues that has been reported to promote cancer growth in some and suppress aspects of cancer ...progression in other studies. We investigated its role in different breast cancer subtypes. In breast cancer patients, GRHL2 expression was increased in all subtypes and inversely correlated with overall survival in basal-like breast cancer patients. In a large cell line panel, GRHL2 was expressed in luminal and basal A cells, but low or absent in basal B cells. The intersection of ChIP-Seq analysis in 3 luminal and 3 basal A cell lines identified conserved GRHL2 binding sites for both subtypes. A pathway analysis of ChIP-seq data revealed cell-cell junction regulation and epithelial migration as well as epithelial proliferation, as candidate GRHL2-regulated processes and further analysis of hub genes in these pathways showed similar regulatory networks in both subtypes. However, GRHL2 deletion in a luminal cell line caused cell cycle arrest while this was less prominent in a basal A cell line. Conversely, GRHL2 loss triggered enhanced migration in the basal A cells but failed to do so in the luminal cell line. ChIP-Seq and ChIP-qPCR demonstrated GRHL2 binding to CLDN4 and OVOL2 in both subtypes but not to other GRHL2 targets controlling cell-cell adhesion that were previously identified in other cell types, including CDH1 and ZEB1. Nevertheless, E-cadherin protein expression was decreased upon GRHL2 deletion especially in the luminal line and, in agreement with its selectively enhanced migration, only the basal A cell line showed concomitant induction of vimentin and N-cadherin. To address how the balance between growth reduction and aspects of EMT upon loss of GRHL2 affected in vivo behavior, we used a mouse basal A orthotopic transplantation model in which the GRHL2 gene was silenced. This resulted in reduced primary tumor growth and a reduction in number and size of lung colonies, indicating that growth suppression was the predominant consequence of GRHL2 loss. Altogether, these findings point to largely common but also distinct roles for GRHL2 in luminal and basal breast cancers with respect to growth and motility and indicate that, in agreement with its negative association with patient survival, growth suppression is the dominant response to GRHL2 loss.
Objectives
Neighborhood walkability has been found to be positively related to physical activity and negatively associated with risks of noncommunicable diseases. However, limited studies have ...examined its association with sarcopenia in older adults. Thus, this study aimed to examine the association between neighborhood walk score and risks of sarcopenia in a sample of older Taiwanese adults.
Design and setting
This study was a cross-sectional investigation using telephone-based survey.
Participants
A nationwide telephone-based survey targeting older adults (≥ 65 years) was conducted in Taiwan.
Measurements
Data on neighborhood walkability (determined by walk score of residential neighborhood), sarcopenia scores (measured by SARC-F), and personal characteristics were obtained. The relationships between walk score and risks of sarcopenia were examined using generalized additive models.
Results
A total of 1,056 older adults participated in the survey. In model 1 (sex and age) and model 2 (full-adjusted model), a nonlinear association between neighborhood walk score and risks of sarcopenia was observed. Results showed that risks of sarcopenia appear to be lower in neighborhoods with a 40-walk score (Car-Dependent; most errands require a car) and an 80-walk score (Very Walkable) and highest in the neighborhood with a 60-walk score (Somewhat Walkable).
Conclusions
The study revealed a nonlinear relationship between neighborhood walkability and risks of sarcopenia in older adults in Asian context. Results provided information to urban designers and public health practitioners that more walkable neighborhood may not necessarily protect older adults from risks of sarcopenia.
We present the improved constraints on couplings of solar axions and more generic bosonic dark matter particles using 737.1 kg days of data from the CDEX-1B experiment. The CDEX-1B experiment, ...located at the China Jinping Underground Laboratory, primarily aims at the direct detection of weakly interacting massive particles using a p-type point-contact germanium detector. We adopt the profile likelihood ratio method for analysis of data in the presence of backgrounds. An energy threshold of 160 eV was achieved, much better than the 475 eV of CDEX-1A with an exposure of 335.6 kg days. This significantly improves the sensitivity for the bosonic dark matter below 0.8 keV among germanium detectors. Limits are also placed on the coupling gAe < 2.48 × 10−11 from Compton, bremsstrahlung, atomic-recombination, and deexcitation channels and geffAN × gAe < 4.14 × 10−17 from a 57Fe M1 transition at 90% confidence level.
The main purpose of this study is to evaluate the feasibility to use Unmanned Aerial Vehicle (UAV) technology for solar panel applications and to propose a reliable, economical and fast method of ...fault detection. In this experiment, the UAV was used to inspect the panels of a solar farm. For this purpose, a set of tools were selected including an infrared camera and a High Definition (HD) photographic lens to scan solar panel assembly. The infrared images were immediately transmitted back with backhaul HD for analysis. The infrared image display can be roughly divided into three health conditions. The first one is the normal operation of the solar panel. In the second case, the infrared image represents an abnormal situation of the solar panel. The third one is a blurred case in which the infrared image cannot be determined to be normal or abnormal. Under this kind of situation, the Matlab® image analysis was used in this study to determine the health condition of solar panels. The results show that it is effective and efficient to use UAV to capture the thermal image and to detect different faults of solar modules. Moreover, this process is fast, low cost, and can detect defects that are not noticeable by visible light. It may provide maintenance personnel with a tool to prevent solar module failure.
Summary
The mu‐opioid receptor (MOR), a membrane‐bound G protein‐coupled receptor, is the main target for opioids in the nervous system. MOR1 has been found in several types of cancer cells and ...reported to be involved in tumor progression and metastasis. However, the expression and clinical significance of MOR1 in esophageal squamous cell carcinoma (ESCC) remain unclear. In our study, the expression of MOR1 was confirmed in ESCC cell lines (KYSE180, KYSE150, and EC109) by Western blot. MOR1 was also detected on tissue microarrays of ESCC samples in 239 cases using immunohistochemical staining. We found that MOR1 was mainly located in the cytoplasm and occasionally occurred in the membrane or nucleus of ESCC cells. Moreover, results indicated that MOR1 expression in the cytoplasm was associated with lymph node metastasis (R = 0.164, P = 0.008, Kendall's tau‐b‐test). No more associations were found between MOR1 expression status and other clinical parameters. However, no statistical significant differences were found between MOR1 expression in the cytoplasm, nucleus/membrane, and the overall survival of ESCC patients (P = 0.848; P = 0.167; P = 0.428, respectively, log‐rank test). Our results suggest that the cytoplasmic MOR1 may be a high‐risk factor for lymph node metastasis of ESCC patients. We also hypothesize that MOR1 agonists used in ESCC patients should be prudent, and opioid receptor antagonists may be novel therapeutic drugs for ESCC patients.
Experimental insights into a reverse switching charge for antiferroelectric (AFE) Hf 0.1 Zr 0.9 O 2 are validated by pulse measurement and capacitance-voltage (C-V). The difference between saturation ...polarization (<inline-formula> <tex-math notation="LaTeX">\text{P}_{\mathrm {S}} </tex-math></inline-formula>) and remnant polarization (<inline-formula> <tex-math notation="LaTeX">\text{P}_{\mathrm {r}} </tex-math></inline-formula>) plays an important role in the model and is confirmed by the steep and gradual slope of the P-V loop, which is made by AFE and antiferroelectric-dielectric (AFE-DE), respectively. AFE capacitor yield far superior released charge (<inline-formula> <tex-math notation="LaTeX">\text{Q}_{\mathrm {D}} </tex-math></inline-formula>) than capacitor of AFE-DE bilayers due to strong reverse switching of <inline-formula> <tex-math notation="LaTeX">\text{P}_{\mathrm {S}} </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">\text{P}_{\mathrm {r}} </tex-math></inline-formula> difference. A nonhysteretic <inline-formula> <tex-math notation="LaTeX">\text{Q}_{\mathrm {D}} </tex-math></inline-formula> scheme is proposed by alternating bipolar AFE operation without a DE to achieve a bidirectional enhancement. This work demonstrates an experimental <inline-formula> <tex-math notation="LaTeX">\text{Q}_{\mathrm {D}} </tex-math></inline-formula> enhancement by an AFE system and supports the reverse switching concept.
We found a novel marine drug, SZ-685C, that was isolated from the secondary metabolites of a mangrove endophytic fungus (No. 1403) collected from the South China Sea, which has been reported to ...inhibit the proliferation of certain tumor cells. However, its anticancer mechanism remains unknown. The aims of this study were to observe the effectiveness of SZ-685C on pituitary adenoma cells and determine the underlying mechanisms of action.
A rat prolactinoma cell line, MMQ, was used in this study. A dose escalation of SZ-685C was performed on this cell line, and cell viability was assessed using an MTT assay. Hoechst 33342, Annexin V-FITC/PI, TUNEL staining and flow cytometry were used to evaluate the extent of apoptosis at each concentration of SZ-685C. The effect of SZ-685C on prolactin expression was also evaluated using RT-PCR and immunoblotting. Quantitative RT-PCR was used to detect the expression of miR-200c in SZ-685C-stimulated MMQ cells and pituitary adenoma tissues. This miRNA was then overexpressed in MMQ cells via transfection of a miR-200c mimic to identify the mechanism underling the anti-tumor effect of SZ-685C.
SZ-685C inhibited MMQ cell growth in a dose-dependent manner but showed little toxicity toward rat pituitary cells (RPCs). The IC50s of SZ-685C in MMQ cells and RPCs were 13.2 ± 1.3 mM and 49.1 ± 11.5 mM, respectively, which was statistically significant. Increasing numbers of apoptotic cells were observed in response to escalating concentrations of SZ-685C, and the expression level of prolactin (PRL) was inhibited. Nevertheless, the level of PRL mRNA was unchanged. Additionally, miR-200c was upregulated in MMQ cells compared with RPCs, and downregulation of miR- 200c was observed in SZ-685C-treated MMQ cells. Furthermore, the overexpression of miR-200c weakened the effect of SZ-685C-induced apoptosis of MMQ cells.
Our results suggest that SZ-685C induces MMQ cell apoptosis in a miR-200c-dependent manner. Therefore, SZ-685C might be a useful alternative treatment for pituitary adenoma.
A double-HZO (HfZrO 2 ) FeFET (ferroelectric FET) with nonidentical ferroelectric thicknesses is experimentally demonstrated with as low as <inline-formula> <tex-math notation="LaTeX">\vert ...{V}_{P/{E}}\vert = {5} </tex-math></inline-formula> V, 2-bit endurance > 10 5 cycles and retention > 10 4 s. Inserting an insulator to separate the ferroelectric layers and avoid the monoclinic formation of a thick Fe-HZO (ferroelectric-HZO) is a useful method to enhance the MW (memory window) for MLC (multilevel cell) applications. Double-HZO has a lower ER (error rate) and shows a 600X improvement compared to single-HZO. The stacked HZO FeFET has potential as an MLC for high-density NVM (nonvolatile memory) applications.
Essentials
ARHGEF10 single‐nucleotide polymorphism provides risk of ischemic and atherothrombotic stroke.
The role of ARHGEF10 in platelet function was examined using ARHGEF10 knockout mice.
ARHGEF10 ...deficiency inhibits platelet function and arterial thrombus formation.
ARHGEF10 knockout protects mice from stroke‐induced infarction.
Summary
Background
ARHGEF10, a member of the Rho guanine nucleotide exchange factor (GEF) family, stimulates Rho GTPases. Rho GTPases have been reported to regulate a variety of cellular behaviors, such as cell polarity, cytoskeletal organization, and gene transcription. ARHGEF10 single‐nucleotide polymorphisms are linked to the risk of ischemic stroke. However, the role of ARHGEF10 in platelet function remains unknown.
Objective
To examine the role of ARHGEF10 in platelet function.
Methods
ARHGEF10−/−were generated. We examined the in vitro and in vivo effects of ARHGEF10 knockout on platelet function and arterial thrombosis formation.
Results
ARHGEF10−/− mice had normal platelet counts, but showed altered aggregation in response to thrombin, collagen, ADP, protease‐activated receptor‐4 peptide, and U46619 stimulation. ARHGEF10 knockout influenced platelet spreading on fibrinogen‐coated surfaces, and caused the platelets to show less lamellipodia‐like extension than wild‐type platelets. ARHGEF10 knockout also inhibited platelet clot retraction induced by thrombin stimulation. ARHGEF10 knockout resulted in prolonged tail bleeding time and inhibited the stable thrombus formation induced by FeCl3 in the carotid artery.
Conclusions
ARHGEF10 serves as an important regulator in platelet shape change, spreading, and aggregation. Moreover, ARHGEF10 also plays an important role in arterial thrombosis formation.
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