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0.371342 |
09e0a3a21ee04caa8ac68904e96c1cde
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Overview of the MobiliSense data collection. GPS, Global Positioning System.
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PMC8971765
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bmjopen-2021-048706f01.jpg
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0.399917 |
8d774830073f44dc833d2bcd5263e3ee
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Sensors and devices used in the MobiliSense data collection.
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PMC8971765
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bmjopen-2021-048706f02.jpg
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0.434166 |
f0b7a5ee0cf541869d17ea424bd5e6b6
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Examples of natural and
synthetic cannabinoids with their chemical
structures.
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PMC8973111
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ao2c00635_0001.jpg
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0.4323 |
ce164300d0d44431adf7c46965a6f922
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GERD-HRQLQ questionnaire
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PMC8973483
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JMAS-18-248-g001.jpg
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0.466616 |
9151732703f74c24ab88fd6740a03524
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Position of the ports
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PMC8973483
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JMAS-18-248-g002.jpg
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0.444019 |
c7457b53e90a449e9a62542785cff06d
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Mesh in its U-shaped configuration
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PMC8973483
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JMAS-18-248-g003.jpg
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0.491374 |
ba7eb26eacb54461b14f4d9b045c91e3
|
Results of the SF-36. Physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH)
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PMC8973483
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JMAS-18-248-g004.jpg
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0.416996 |
2ff8479891c34443b1df9305d84711f2
|
Inhibition of SHP2 counteracts acquired resistance to PI3K inhibition in PI3K mutant breast cancer cells. a Multiple growth factors confer resistance to BYL719 in PI3K mutant T47D breast cancer cells. Top: colony formation. Bottom: quantification of crystal violet staining intensity of three independent colony formation experiments. Significance between indicated conditions was calculated by one-way ANOVA. ***p ≤ 0.001, ****p ≤ 0.0001. pBYL719: 2 μM. NRG1, EGF and FGF10: 50 ng/ml. UT: vehicle-treated. b Western blot showing the biochemical effects on PI3K and MAPK signaling after BYL719, NRG1, EGF or FGF10 treatments in T47D cells for 4, 24 or 48 h. BYL719: 2 μM. NRG1, EGF and FGF10: 50 ng/ml. Relative gel band intensities of phosphorylated proteins are indicated below each row. Significant differences (p ≤ 0.05) in signaling in comparison to the untreated condition are marked with an *. c Western blot showing SHP2 phosphorylation of Y542 upon NRG1, EGF and FGF10 treatment in T47D cells. BYL719: 2 μM. NRG1, EGF and FGF10: 50 ng/ml. Significant differences (p ≤ 0.05) in induction of SHP2 phosphorylation in comparison to the untreated condition are marked with an *. d SHP099 reverses growth factor-induced BYL719 resistance in T47D. Top: colony formation. Bottom: quantification of crystal violet staining intensity of three colony formation experiments. Significance between indicated conditions was calculated by one-way ANOVA. ***p ≤ 0.001, ****p ≤ 0.0001. BYL719: 2 μM. EGF and NRG1: 50 ng/ml. SHP099: 5 μM. e SHP099 reverses growth factor-induced BYL719 resistance in MCF7 and MDA-MB-453 cells. Quantifications of crystal violet staining intensity of three colony formation experiments are shown. Significance between indicated conditions was calculated by one-way ANOVA. ****p ≤ 0.0001. BYL719: 5 μM (MCF7) and 1 μM (MDA-MB-453). EGF and NRG1: 50 ng/ml. SHP099: 5 μM. f Western blot showing the biochemical effects on PI3K and MAPK signaling after BYL719, NRG1 and SHP099 treatment in T47D cells. BYL719: 2 μM. NRG1: 50 ng/ml. SHP099: 5 μM. Significant differences (p ≤ 0.05) in signaling in comparison to the untreated condition are marked with an *. g Colony formations with two independent T47D SHP2 knockout clones treated with BYL719 (2 μM), NRG1 and EGF (both 50 ng/ml)
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PMC8974145
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13058_2022_1521_Fig1_HTML.jpg
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0.458156 |
a6fa861649264a96b5c6e1e25cda7ace
|
SHP2 confers resistance to PI3K inhibition upon overexpression and long-term PI3K inhibitor exposure. a MCF7 cells overexpressing wild type SHP2 (SHP2-WT) are resistant to BYL719 (5 μM) treatment. MCF7-pCMV-EGFP (EGFP) cells serve as control. Quantification of crystal violet staining intensity of three colony formation experiments is shown. Significance between indicated conditions was calculated by one-way ANOVA. ****p ≤ 0.0001. b Biochemical analysis by western blot of the effect on PI3K and MAPK signaling in cells overexpressing SHP2. Significant differences (p ≤ 0.05) in p-SHP2, SHP2 and p-ERK in comparison to the untreated condition in parental cells are marked with an *. BYL719: 5 μM. c Long-term treatment with BYL719 of MCF7, T47D and MDA-MB-453 cells (for 38, 50 and 50 days, respectively) results in outgrowth of resistant clones. BYL719/SHP099 combination treatment prevents outgrowth of BYL719 resistant clones. Vehicle (UT) and SHP099-only treated cells serve as control. BYL719: 5 μM (MCF7), 2 μM (T47D) and 1 μM (MDA-MB-453). SHP099: 5 μM (MCF7 and MDA-MB-453), 10 μM (T47D). d Biochemical analysis of SHP2, PI3K and MAPK signaling of ten BYL719 resistant T47D clones. Parental cells were treated with BYL719 for 24 h. BYL719: 2 μM. Significant differences (p ≤ 0.05) in signaling in comparison to the untreated condition in parental cells are marked with an *. e Colony formation (top) and quantification of three colony formation experiments (bottom) of two BYL719-resistant T47D clones that are co-treated with BYL719 and SHP099. Significance between indicated conditions was calculated by one-way ANOVA. ****p ≤ 0.0001. BYL719: 2 μM. SHP099: 10 μM. f Biochemical effects of BYL719 (2 μM) and SHP099 (10 μM) combination treatment on PI3K and MAPK signaling in BYL719-resistant T47D clone #1. Significant differences (p ≤ 0.05) in signaling in comparison to the untreated condition in parental cells are marked with an *
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PMC8974145
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13058_2022_1521_Fig2_HTML.jpg
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0.454677 |
8ec689ea02c443109e409fad6fb856fc
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Targeting SHP2 effectively combats intrinsic resistance to PI3K inhibitor in TNBC cells. a A panel of PI3K inhibitor-resistant TNBC cell lines treated with BYL719. Quantification of crystal violet staining intensity of three independent colony formation experiments is shown. BYL719: 5 μM (HCC1806, MDA-MB-468, HCC1937, BT549), 2 μM (CAL-51, SUM159). b Western blot showing the biochemical effects on PI3K and MAPK signaling upon BYL719 treatment in HCC1806 (5 μM), MDA-MB-468 (5 μM) and SUM159 (2 μM) cells. Significant differences (p ≤ 0.05) in signaling in comparison to the untreated condition are marked with an *. c BYL719 treatment induces phosphorylation of SHP2 on residue Y542 in HCC1806 (5 μM BYL719), MDA-MB-468 (5 μM) and SUM159 (2 μM) cells. Significant differences (p ≤ 0.05) in induction of SHP2 phosphorylation in comparison to the untreated condition are marked with an *. d RTK arraying of HCC1806 cells treated with 5 μM BYL719 for 48 h reveals activation of several RTKs. e BYL719/SHP099 combination treatment in HCC1806, MDA-MB-468, SUM159 and CAL51 cells prevents resistance to BYL719. Quantifications of crystal violet staining intensity of three independent colony formation experiments. Significance between indicated conditions was calculated by one-way ANOVA. **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. BYL719: 5 μM (HCC1806, MDA-MB-468), 2 μM (SUM159, CAL51). SHP099: 10 μM (HCC1806), 15 μM (SUM159), 20 μM (MDA-MB-468, CAL51). f PI3K and MAPK signaling is abrogated in HCC1806 cells that are treated with the combination of BYL719 and SHP099. BYL719: 5 μM. SHP099: 10 μM. Significant differences (p ≤ 0.05) in signaling in comparison to the untreated condition are marked with an *
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PMC8974145
|
13058_2022_1521_Fig3_HTML.jpg
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0.429199 |
7de13ab762924ce6b0b32b00a6cc9cb9
|
The phosphatase SHP2 is indispensable for mediating BYL719 resistance in TNBC cells. a Left: Colony formation with HCC1806 parental cells and two independent SHP2 knockout clones treated with 5 μM BYL719. Right: crystal violet intensity quantification of three experiments. Significance between indicated conditions was calculated by one-way ANOVA. ****p ≤ 0.0001. b Western blot analysis showing the biochemical effects on PI3K and MAPK signaling in HCC1806 parental versus SHP2 knockout cells after 5 μM BYL719 treatment. Significant differences (p ≤ 0.05) in signaling in comparison to the untreated condition in parental cells are marked with an *. c Colony formation with HCC1806 SHP2 knockout clone 2.C, reconstituted with either wild type SHP2 (pCMV-SHP2-WT) or a phosphatase-dead mutant (pCMV-SHP2-C459S), treated with 5 μM BYL719. HCC1806 parental and 2.C cells serve as controls. d Biochemical effects on PI3K and MAPK signaling pathways in HCC1806 parental, SHP2 KO 2.C and in wild type SHP2 and phosphatase-dead SHP2 reconstituted cells after treatment with 5 μM BYL719. Significant differences (p ≤ 0.05) in signaling in comparison to the untreated condition in parental cells are marked with an *
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PMC8974145
|
13058_2022_1521_Fig4_HTML.jpg
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0.443676 |
cef1fdb797c24c7e8c8860e868890bcb
|
Dual PI3K/SHP2 inhibition blocks 3D organoid formation in two patient-derived breast cancer models and tumor growth in a xenograft model. a Representative images of organoids grown from patient-derived PIK3CA mutant HBCx4B TNBC cells after 10 days of treatment with BYL719, SHP099 or the combination thereof with the indicated concentrations. Magnification: 400×. b Normalized quantification of HBCx4B organoid formation in (a). Organoid diameter of 40 μm was taken as cut-off. Inhibition of organoid formation in the BYL719/SHP099 combination treatment is significant (p ≤ 0.01), calculated by one-way ANOVA. Experiment was performed on two biological replicates. c Normalized luminescence after CellTiter-Glo cell viability assay on the HBCx4B organoids of (a). Organoids treated with BYL719/SHP099 have significantly lower luminescence (p ≤ 0.01) compared to the monotreatments, calculated by one-way ANOVA. RLU: Relative Light Unit. Experiment was performed on three biological replicates. d Average tumor volume over time in nude mice injected with 2 × 106 HCC1806 cells, treated with either vehicle, 15 mg/kg BYL719, 75 mg/kg SHP099 or the combination of 15 mg/kg BYL719 + 75 mg/kg SHP099. Three mice per group were treated daily starting at day 10 after injection. Inhibition of tumor growth in the BYL719/SHP099 combination treatment is significant (p ≤ 0.05), calculated by one-way ANOVA
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PMC8974145
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13058_2022_1521_Fig5_HTML.jpg
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0.485382 |
48899b84ad2a4e0cb31d2fe310202e4d
|
Stillbirth rate per 1000 total births in Eurostat cause of death statistics and Euro-Peristat by country in 2015, distinguishing between stillbirths and TOP and sorted by rates of stillbirth using Euro-Peristat data (solid red bar).
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PMC8975542
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ckac001f1.jpg
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0.548049 |
bc8389b2e1434c4687d888302093b748
|
The course of HRS-AKI in the whole cohort. Of the 116 patients, 75 were responders, and 41 were non-responders. In the responder group, 46 patients achieved a complete response, and 29 patients achieved a partial response. Of the 41 non-responders, 29 required renal replacement therapy, and those requiring RRT succumbed. Nine patients of the non-responders were treated with octreotide and midodrine, and the rest were treated with noradrenaline. HRS-AKI hepatorenal syndrome acute kidney injury, CR complete response, PR partial response, LT liver transplantation, TFS transplant free survival, TIPS transjugular intrahepatic portosystemic shunt, OCT/MID octreotide with midodrine, CKD chronic kidney disease.
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PMC8976022
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41598_2022_9505_Fig1_HTML.jpg
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0.411257 |
c6f7039619d2441a94725e11cc8f6829
|
KUCaP2 is a PDX line as a model for androgen receptor-dependent castration-resistant prostate cancer.a, b Individual growth curves of KUCaP2 tumors in intact (a) and castrated (b) mice. Arrow indicates surgical castration. c Serum prostate-specific antigen (PSA) levels in androgen-dependent (AD) and castration-resistant (CR) tumor-bearing mice (n = 4 each). d Western blotting of indicated proteins in AD and CR KUCaP2 tumors. Two antibodies for androgen receptor (AR) recognizing distinct epitopes on N-terminus (N20) and C-terminus (C19) were used. LNCaP, PC3, and 22RV1 prostate cancer cell lines act as controls. ACTB; β-actin. e, f Serum testosterone (e) and dihydrotestosterone (DHT, f) levels in mice bearing AD and CR KUCaP2 tumors. g, h Growth curves of AD (g) and CR (h) KUCaP2 tumors treated with control (siNTC) or siRNAs for AR (siAR#1 and siAR#2). **P < 0.01 (ANOVA). i, j Western blotting of indicated proteins in AD (i) and CR (j) KUCaP2 tumors treated with control or siRNAs for AR. k, l Representative microphotographs of hematoxylin and eosin (H&E) stain and immunohistochemical stains for AR and PSA in AD (k) and CR (l) KUCaP2 tumors treated with control or siRNAs for AR. Bars indicate 50 μm.
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PMC8976065
|
42003_2022_3227_Fig1_HTML.jpg
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0.452948 |
78a205f0a67849ed9594ecb9c3a011da
|
Chromatin-immunoprecipitation sequence (ChIP seq) using antibody against androgen receptor (AR).a Top: Experimental schemes. KUCaP tumors under androgen-dependent (AD) and castration-resistant (CR) growth were obtained. Bottom: LNCaP cells cultured in FBS, charcoal-strip FBS (CSFBS) and CSFBS supplemented with 1 nM dihydrotestosterone (CSFBS + DHT) as well as AILNCaP cultured in CSFBS were subject to CHiP seq. b Quality controls for ChIP seq binding data. Bar files were generated after MAT analysis of AR whole-genome ChIP seq raw data from LNCaP cells cultured in FBS, charcoal-strip FBS (CSFBS), and CSFBS supplemented with 1 nM dihydrotestosterone (DHT). AR-binding peaks at the promoter regions (unless otherwise indicated) of indicated genes13 are shown. KLK3 p; KLK3 (PSA) promoter, KLK3 e; KLK3 (PSA) enhancer, FKBP5 3', 3' UTR region of FKBP5. c Venn diagrams showing AR-binding sites in KUCaP2 AD and CR tumors (top), and LNCaP and AILNCaP cells (bottom). We identified 3131 differential AR-binding sites for KUCaP AD tumors, 1850 for KUCaP2 CR tumors, 2,938 for LNCaP cells, and 717 for AILNCaP cells, which were defined as having fold change ≤ 0.5 or ≥2 compared with each counterpart. There were 6102 AR-binding sites commonly identified in KUCaP2 AD and CR tumors and 1751 in LNCaP and AILNCaP cells. d Reactome pathways for genes exclusively identified for KUCaP2 CR tumors annotated by AR-binding sites in AR-ChIP seq with regard to entities p-values (−log[p-value]). e, f Venn diagrams depicting differentially and commonly identified genes harboring AR-binding site in AD (e) and CR (f) models including PDX (the present study), human PCa tissue22, and cell lines13.
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PMC8976065
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42003_2022_3227_Fig2_HTML.jpg
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0.401951 |
8ef5dfb44a3540f3a1ae6e35c8d520b4
|
RNA sequence KUCaP2 AD and CR tumors.Among 30 most significantly upregulated genes in RNA seq of KUCaP2 CR compared with AD tumors, seven genes that were reported to be frequently amplified in PCa were picked up. Likewise, among 30 most significantly downregulated genes in KUCaP2 CR tumors, five genes that were reported to be frequently altered (deep deletion, and truncating and missense mutations) in CRPC were picked up. a Dot plot of log10[fkpm] indicating the 12 genes. b Landscape of alterations (amplification, deep deletion, and truncating and missense mutations) of the 12 genes primary PCa24. c Summarized results from integrated genomics including RNA seq of KUCaP2 tumors (AD vs CR), cDNA microarray of KUCaP2 tumors (AD vs CR)16, ChIP seq of KUCaP2 tumors (AD and CR), and ChIP seq of AILNCaPs (four independent sublines) and LNCaP cells cultured in FBS (LNCaP_FBS), charcoal-stripped FBS (LNCaP_CSFBS), and CSFBS supplemented with 1 nM dihydrotestosterone (LNCaP_CSFBS + DHT). d–j Quantitative RT-PCR in human PCa cell lines. Expressions of TRPA1 (d), CP (e), CLSTN2 (f), MGLL (g), OPRK1 (h), NMNAT2 (i), and ROBO1 (j) normalized by that of GAPDH in the indicated PCa cell lines.
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PMC8976065
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42003_2022_3227_Fig3_HTML.jpg
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0.441396 |
8806475b44194e8ba806d19265881a7a
|
AR suppression upregulates OPRK1, which underpin androgen-independent growth of androgen-independent derivatives of LNCaP cells.a, b Expressions of AR in LNCaP, AILNCaP2 (AI2), AILNCaP3 (AI3), and AILNCaP4 (AI4) treated with siRNA for GFP (siControl) and AR (siAR#1 and siAR#2) assessed by quantitative RT-PCR (a) and western blot (b). **P < 0.01, Normalized by GAPDH (a) and β-actin (ACTB, b). c Expression of OPRK1 in LNCaP, AILNCaP2 (AI2), AILNCaP3 (AI3), and AILNCaP4 (AI4) treated with siRNA for GFP (siControl) and AR (siAR#1 and siAR#2) assessed by quantitative RT-PCR. **P < 0.01, Normalized by GAPDH. d Expression of AR (left) and OPRK1 (right) in LNCaP cultured in media supplemented with 10%FBS, charcoal-stripped FBS (CSFBS), and CSFBS plus 1 nM dihydrotestosterone. **P < 0.01, Normalized by GAPDH. e Chromatin immunoprecipitation (ChIP) using anti-AR antibody and control IgG followed by quantitative RT-PCR using two primers for OPRK1 promoter (OPRK1-a, and -b) in LNCaP cells cultured as in d. **P < 0.01. f, g ChIP using anti-AR antibody and control IgG followed by quantitative RT-PCR using two primers for OPRK1 promoter (OPRK1-a, and -b) in KUCaP2 AD (f) and CR (g) tumors. **P < 0.01. h Expression of AR in LNCaP, AILNCaP2 (AI2), AILNCaP3 (AI3), and AILNCaP4 (AI4) treated with siRNA for GFP (siControl) and OPRK1 (siOPRK1#1 and siOPRK1#2) assessed by quantitative RT-PCR. Normalized by GAPDH. i Expression of ORPK1 normalized by GAPDH (left) and cell proliferation (right) in LNCaP, AILNCaP2 (AI2), AILNCaP3 (AI3), and AILNCaP4 (AI4) treated with siRNA for GFP (siControl) and OPRK1 (siOPRK1#1 and siOPRK1#2). *P < 0.05, **P < 0.01. j Summarized cell proliferation rates of indicated cells with regard to the concentration of supplemented nor-BNI, OPRK1 inhibitor. *P < 0.05.
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PMC8976065
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42003_2022_3227_Fig4_HTML.jpg
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0.49242 |
691fc9eb0c5546649f317a02fd09e8b8
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AR suppression upregulates OPRK1, which underpins androgen-independent growth of androgen-independent derivatives of VCaP cells.a, b Expressions of AR in VCaP treated with siRNA for GFP (siControl) and AR (siAR#1 and siAR#2) assessed by quantitative RT-PCR (a) and western blot (b). **P < 0.01, Normalized by GAPDH (a) and β-actin (ACTB, b). c Expression of OPRK1 in VCaP treated with siRNA for GFP (siControl) and AR (siAR#1 and siAR#2) assessed by quantitative RT-PCR. **P < 0.01, Normalized by GAPDH. d Expression of AR (left) and OPRK1 (right) in VCaP cultured in media supplemented with 10% FBS, charcoal-stripped FBS (CSFBS), and CSFBS plus 1 nM dihydrotestosterone (DHT) assessed by quantitative RT-PCR. **P < 0.01, Normalized by GAPDH. e Summarized results of quantitative RT-PCR for full-length AR (AR-FL), AR variant 7 (AR-V7), KLK3, and OPRK1 normalized by GAPDH in indicated cells. **P < 0.01. f Western blot of indicated proteins in VCaP, PC3, AIVCaP1, AIVCaP2, and AIVaP3. β-actin (ACTB) acted as loading control. g Summarized results of proliferation rates of VCaP and AIVCaP2 (AIVCaP) treated with siRNA for GFP (siControl) and AR (siAR#1 and siAR#2). h Summarized results of proliferation rates of VCaP and AIVCaP2 treated with siRNA for GFP (siControl) and OPRK1 (siOPRK1#1 and siOPRK1#2). i Summarized cell proliferation rates of VCaP and AIVCaP2 (AIVCaP) with regard to the concentration of supplemented nor-BNI, OPRK1 inhibitor. *P < 0.05. j Cell proliferation in VCaP (left) and AIVCaP2 (AIVCaP) treated with siRNA for GFP (siControl), AR (siAR) OPRK1 (siOPRK1), or siAR plus siOPRK1. *P < 0.05, **P < 0.01. k Summarized results of migration (scratch) assay with greater distance indicating higher migration ability. VCaP, AIVCaP, and AILNCaP cells were treated with indicated siRNA and subject to the assay. **P < 0.01.
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PMC8976065
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42003_2022_3227_Fig5_HTML.jpg
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0.410809 |
c90ff81d50bd40b1bfb4f4a188bf51ce
|
Pharmacological inhibition of OPRK1 suppresses tumor growth in multiple in vivo castration-resistant prostate cancer models.a Mice bearing VCaP cell-derived xenograft were castrated. Four weeks later, when the tumor started castration-resistant growth, mice were untreated or treated with OPRK1 inhibitor nor-BNI (n = 5 each). b Mice bearing VCaP cell-derived xenograft were castrated and untreated or treated with nor-BNI (n = 5 each) at the same time. c AILNCaP cells were inoculated to castrated mice. When the cell-derived xenograft tumors were engrafted and started growing, mice were untreated or treated with nor-BNI (n = 5 each). d Single-sample GSEA (ssGSEA) showing differentially enriched gene sets in VCaP cells treated with siRNA for AR (siAR) alone vs those treated with siAR and siRNA for OPRK1 (siORPK1). A gene set involved in SMAD6 pathway (red column) is enriched as well as some gene sets involved in neuronal pathways (light blue) and G-protein-related pathways (magenta). e Expressions of six genes involved in the SMAD6 pathway (JEON_SMAD6_TARGETS_UP) were evaluated using quantitative RT-PCR in VCaP or AIVCaP cells under AR signal suppression between siNTC and siOPRK1 treatments. f Representative photomicrograph images of hematoxylin and eosin (H&E) and immunohistochemical stains for OPRK1 in non-cancer prostate (benign), castration-sensitive (CSPC) prostate cancer, prostate cancer treated with neoadjuvant androgen deprivation therapy (NAADT), and castration-resistant prostate cancer (CRPC) tissues. g Immunostainability of OPRK1 classified into negative (none), weakly (weak), and strongly (strong) positive in benign, hormone-naïve (HNPC), PCa after neoadjuvant hormone therapy (NAHT), and CRPC. h Immunostainability of OPRK1 in HNPC tissues with regard to AR immunostainability. i Immunostainability of OPRK1 in CRPC tissues with regard to AR immunostainability.
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PMC8976065
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42003_2022_3227_Fig6_HTML.jpg
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0.396915 |
0cd0f65d514240b6b12378d3523e2bac
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(a) Abdominal CT showed small bowel obstruction with an adhesion band (white arrow). (b) Loculated fluid accumulation around the appendix with perifocal infiltration, which rupture appendicitis was suspected.
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PMC8976137
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gr1.jpg
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0.480761 |
188c0b02c94243eea0629ba87189f278
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(a) One of the fibrotic bands (white arrow) causing small bowel obstructive ileus which compatible with CT image Fig. 1a. (b) The terminal ileum mesenteric tumor and the suspicious involved appendix with irregular surface (yellow circle). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
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PMC8976137
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gr2.jpg
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0.458643 |
5020fc8454aa46cfbf871cabc449d6ec
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H&E stains revealed spindles cells in both compact and loose myxoid stroma (400×).
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PMC8976137
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gr3.jpg
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0.47415 |
86078e49eab44b9a9e6c56362356ca20
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Joint sites with swelling or tenderness by sex. The prevalence of subjects who had no symptoms of arthritis was 18.5% (n = 5) for males and 36.0% (n = 18) for females. No participants complained of hip, toe, or waist swelling or tenderness. Fingers include both hands and feet
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PMC8976395
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40101_2022_283_Fig1_HTML.jpg
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0.506103 |
68db0dd14b714eb8a7186e5ccd239922
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Flow-chart of patient enrollment for this study. CTpre, pre-enhanced CT value; CTpost, enhanced CT value; AA, adrenal adenoma; PHEO, pheochromocytoma; sPHEO, subclinical pheochromocytoma; LPA, lipid poor adenoma; HU, Hounsfield Unit.
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PMC8977471
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fendo-13-833413-g001.jpg
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0.398658 |
7904734660c44e51b3985299fe5a80c7
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Axial pre-enhanced and enhanced CT images of a patient with lipid-poor adenomas (LPA) (Case 95) and a patient with subclinical pheochromocytoma (sPHEO) (Case 21) showing left adrenal mass at the tumor largest dimensions. On pre-enhanced images, the LPA appeared as an irregular mass with intermediate heterogeneous density (A), while the sPHEO was an elliptical mass with relatively homogeneous density (B). After injection of contrast medium (65s), the LPA was markedly more heterogeneous, with obvious cystic and necrotic areas (C), while the sPHEO showed a mildly heterogeneous enhancement pattern (D).
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PMC8977471
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fendo-13-833413-g002.jpg
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0.47517 |
a787ad34b50f4cad929044fc7632170f
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The receiver operating characteristic (ROC) curves and nomograms for the models based on the CT imaging features. The ROC curves were based on predictions from the validation data in five times of cross-validations, while the nomograms were drawn based on predictions from all data used for deriving the model. The average and standard deviation of the predictive performance measures in five times of cross-validations were shown. (A, B) refer to model M1 with features of “CTpre + Shape + Necrosis or Cystic (N/C)”; (C, D) refer to model M2 with features of “CTpre + Shape + Homogeneity (Homo)”.
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PMC8977471
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fendo-13-833413-g003.jpg
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0.49961 |
de27845808fd46969ab2f73570aa6ff2
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CONSORT flow diagram. AE, adverse event; HCP, health care professional; OH, orthostatic hypotension; Pt, participant.
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PMC8977979
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JCSM-13-858-g001.jpg
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0.457437 |
75ad9168a99a401ea05fc2c845df4b6f
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Subgroup analyses for primary outcome. (A) Perindopril versus placebo. (B) Leucine versus placebo. Positive values of short physical performance battery (SPPB) denote improvement relative to control group.
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PMC8977979
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JCSM-13-858-g002.jpg
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0.404761 |
a93d2cced33445a9a1a55e801dd695d8
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Correlation coefficients of serum creatinine level with urine biomarkers of tubular injury, secretory clearance, and BNP within 24 hours of admission for acute decompensated heart failure and that of serum creatinine level with admission serum BNP level. (N for serum creatinine and BNP = 61). Abbreviations: BNP, B-type natriuretic peptide; IL-18, interleukin 18; KIM-1, kidney injury molecule 1; L-FABP, liver fatty acid–binding protein; NAG, N-acetyl-β-glucosaminidase; NGAL, neutrophil gelatinase-associated lipocalin; TIMP2∗IGFBP7, tissue inhibitor of metalloproteinase 2 and insulin-like growth factor–binding protein 7 product.
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PMC8978138
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gr1.jpg
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0.452131 |
0505109ff5e841b59d47b65ca05fe5c6
|
Weekly averages for LgATP values in the intervention and control groups of schools.Week 2 corresponds with the week of January 6, 2020, when the schools resumed after winter break, and the study began.
|
PMC8978505
|
41370_2022_427_Fig1_HTML.jpg
|
0.590966 |
32b3968538004114b2dd844e3d809015
|
Predicted propability of absence due to gastrointestinal illness plotted against weekly average LgATP.Association between weekly probability of absence due to gastrointestinal illness and school level average LgATP.
|
PMC8978505
|
41370_2022_427_Fig2_HTML.jpg
|
0.402386 |
27783f8676ca4c46a9c2a73aabb4670a
|
The inhibitory activity of JGF on the interactions between SARS-CoV-2 spike (S) protein and ACE2 receptor. (A) Validation of the cytotoxicity of JGF. BHK-21 and Calu-3 cells were treated with indicated amounts of JGF and cell viability was examined by LDH assay. The control group represented the non-treatment group, serving as a negative control. The treatment with Triton-100 was used as a positive control. The data were presented as the mean ± SD; error bars indicated SD. n. s indicated non-significant, compared to the control group. (B) The expression of ACE2 in Calu-3 cells were treated with 40 μg/ml of JGF was analyzed by Western blot assay (upper panel). The level of ACE2 expression was quantified after normalization with α-tubulin. The quantification analysis from three independent experiments was shown in bottom panel. * represents p < 0.05. (C) The cell-cell fusion of SARS-CoV-2 S protein-expressing BHK cells and ACE2-expressing Calu-3 cells was visualized in the presence of indicated amounts of JGF. (D) The formation of syncytium was quantified for various concentrations of JGF. Compared with the control, syncytium formation was significantly inhibited after 20–80 μg/ml JGF treatments. * represents p < 0.05.
|
PMC8978714
|
fphar-13-744439-g001.jpg
|
0.467266 |
67d0e925866f4e61944c11a6445b2811
|
The effect of JGF on the cell viability of lung fibroblast WI-38 and MR/C-5 cells. WI-38 (A) and MRC-5 (B) cells were treated with various low concentrations of JGF (0–20 μg/ml) for 48 and 72 h. Each group of JGF-treated samples was normalized against an untreated control. Cell viability was determined using a crystal violet assay. Data were representative of three separated experiments and were presented as the mean ± SD; error bars indicated SDs.
|
PMC8978714
|
fphar-13-744439-g002.jpg
|
0.502837 |
3f202ec93c2f46b390c6ca70964e6b27
|
JGF induces lysosome dependent degradation of ACE2. (A) WI-38 and MRC-5 cells were treated with three dosages of JGF (0–20 μg/ml) for 3 and 24 h. Western blotting was subsequently performed with whole cell lysates to detect expression of ACE2. Actin was used as the internal control. (B) Quantification of the intensities of the bands of ACE2 was representative of three separate determinations using ImageJ (National Institute of Mental Health, Bethesda, MD, United States). The data were presented as the mean ± SD; error bars indicated SD. Significant differences were shown (*p < 0.05 compared to the control group). (C) Time course for ACE2 degradation after the addition of cycloheximide (CHX; 100 μg/ml) in the presence or absence of JGF (10 μg/ml) for 0–180 min in WI-38 cells as analyzed by Western blotting. Right panel: The levels of ACE2 in the three-independent experiments were quantified by ImageJ and the results were presented as the mean ± SD; error bars indicate SDs. Significant differences were shown (*p < 0.05 compared to the control DMSO group). (D) WI-38 cells were pretreated with DMSO (vehicle control) or BafA1 (10 μM) for 30 min, followed by incubation with JGF (10 μg/ml) for 2 h.
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PMC8978714
|
fphar-13-744439-g003.jpg
|
0.503814 |
a458abbee6a44f509f5d2e5dad9aeea1
|
JGF reduces TMPRSS2 levels in WI-38 cells. (A) WI-38 cells were treated with JGF (0–20 μg/ml) for 3 and 24 h. Western blotting was subsequently performed with whole cell lysates to detect the expression of TMPRSS2. Actin was used as the internal control. (B) Quantification of the intensities of the bands of TMPRSS2 was representative of three separated determinations by ImageJ. (C) WI-38 cells were treated with JGF (0, 10 and 20 μg/ml) for 24 h. The mRNA levels of TMPRSS2 were determined by qRT-PCR. The data was presented as the mean ± SD; error bars indicated SD. Significant differences were shown (*p < 0.05 compared to the control group).
|
PMC8978714
|
fphar-13-744439-g004.jpg
|
0.472466 |
52205627d353469d8b62cc28566c2e89
|
JGF reduces ACE2 and TMPRSS2 on lung tissues of mouse model. (A) Scheme for mouse receiving JGF via oral gavage. (B) ACE2 and TMPRSS2 levels in lung tissues of mice receiving JGF via oral gavage. (C) Scheme for mouse receiving JGF via steam spray method. (D) ACE2 and TMPRSS2 levels in lung tissue of mice receiving JGF via steam spray. (E) The body weight changes (%) for mice receiving JGF via oral gavage every other day. (F,G) The AST and ALT (hepatic function; F) as well as BUN and Creatinine (renal function; G) of mice sera were analyzed on Day 1 and Day 17.
|
PMC8978714
|
fphar-13-744439-g005.jpg
|
0.402033 |
c790df02f29742c58000f84e8f83abf3
|
JGF inhibits plaque formation for SARS-CoV-2 in Vero E6 cells. (A) Vero E6 cells were treated with various concentrations of JGF (0–800 μg/ml) for 72 h. Each group of JGF-treated samples was normalized against an untreated control. Cell viability was determined using the MTT assay. (B) Vero E6 cells were pre-treated with JGF (0–200 μg/ml) for 3 h and then infected with SARS-CoV-2 for 3 days (C) The plaque was stained with crystal violet. Data were representative of three separate experiments and were presented as the mean ± SD; error bars indicated SDs.
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PMC8978714
|
fphar-13-744439-g006.jpg
|
0.43257 |
5d95aab82c1344fbbe3cd7f2c3283fbb
|
Patient was instructed to close both eyes. Right eye significant lagophthalmos with poor Bell's reflex was observed. Note also the right lower lid ectropion.
|
PMC8979774
|
gr1_lrg.jpg
|
0.400056 |
e5d6b1b4d9f3432fb5f7da016ba9659a
|
Patient was instructed to lift the eye brows. Right facial nerve palsy was evidence with failure of raising the right eye brow, right lower lid ectropion and loss of right nasolabial fold.
|
PMC8979774
|
gr2_lrg.jpg
|
0.401428 |
a0474bf9f99840f4a0174b999d0e277a
|
Schematic illustration of formation procedure for Fe3O4@PDA@Ag.
|
PMC8981012
|
d1ra09187e-f1.jpg
|
0.455326 |
f1870118206e43b481bbbfa1f57c6a32
|
SEM, TEM images and particle size of (a–c) Fe3O4, (d–f) Fe3O4@PDA core–shell NPs, (g and h) Fe3O4@PDA@Ag. (i) Particle size distribution of Ag NPs.
|
PMC8981012
|
d1ra09187e-f2.jpg
|
0.47504 |
64ad3692ba804595bf5548c58467841a
|
(a) XRD patterns. (b) VSM of Fe3O4, Fe3O4@PDA and Fe3O4@PDA@Ag. (c) XPS of Fe3O4@PDA@Ag. (d) High-resolution XPS spectra of Ag 3d.
|
PMC8981012
|
d1ra09187e-f3.jpg
|
0.643102 |
4ff2c42b990a492e816525628b85d20a
|
TG curve of Fe3O4 and Fe3O4@PDA@Ag.
|
PMC8981012
|
d1ra09187e-f4.jpg
|
0.386237 |
ba84fe9c869e4707954ce596e2441eee
|
(a) Reaction scheme and color change. (b) UV-vis spectra of different durations. (c) Plots of ln(Ct/C0) against the reaction time. (d) Plots of Ct/C0 against the reaction time.
|
PMC8981012
|
d1ra09187e-f5.jpg
|
0.418306 |
b81194e774ff4bdbae0efbc1880b2f42
|
(a) Catalytic reuse efficiency of Fe3O4@PDA@Ag. (b) TEM of catalyst after 10 cycles.
|
PMC8981012
|
d1ra09187e-f6.jpg
|
0.461657 |
72395c14ad3b4e10a0e70f26f6c42993
|
UV-vis spectra of (a) MB and (b) MO with various durations. Plots of ln(Ct/C0) against the reaction time for (c) MB and (d) MO.
|
PMC8981012
|
d1ra09187e-f7.jpg
|
0.456422 |
c9de4d1db8a44b14ad9fab2b658a1ff3
|
Map of Nigeria showing the 36 states and the federal capital territory, by the geopolitical zones.
|
PMC8981288
|
bmjopen-2021-051791f01.jpg
|
0.413436 |
37fcb916df2b42018c6e0cae0d9a6b94
|
A decomposition analysis of factors associated with increase in SBA utilisation from 2003 to 2018 by states in Nigeria. SBA, skilled birth attendants; SES, socioeconomic status.
|
PMC8981288
|
bmjopen-2021-051791f02.jpg
|
0.420624 |
a5eeee7d73c446b9b70d3c20bf860442
|
A decomposition analysis of factors associated with decrease in SBA utilisation from 2003 to 2018 by states in Nigeria. SBA, skilled birth attendants; SES, socioeconomic status.
|
PMC8981288
|
bmjopen-2021-051791f03.jpg
|
0.483338 |
0053804ade474f1ca75b9444a3a64b63
|
ThPOK is downregulated in the tissues and cells of gastric cancer. A ThPOK mRNA and protein expression in the tissues of gastric cancer patients and adjacent normal tissues was assessed using RT-qPCR analysis and western blotting. B The mRNA and protein levels of ThPOK in gastric cancer cells (HGC-27, SNU-1) and normal gastric mucosal cells (GES-1) were assessed by RT-qPCR and western blotting. C Kaplan–Meier Plotter (https://kmplot.com/analysis/) was used to predict the prognosis in gastric cancer patients with high or low level of ThPOK. *p < 0.05, **p < 0.01
|
PMC8981657
|
12865_2022_485_Fig1_HTML.jpg
|
0.444167 |
ba5e56e07b644b3f8bb3538f99a47977
|
ThPOK inhibits the immune escape of gastric cancer cells. A ThPOK expression in gastric cancer cells transfected with OE-ThPOK and OE-NC was measured by RT-qPCR. B Gastric cancer cell viability was determined by CCK-8 assays after ThPOK overexpression. C and D Flow cytometry analysis was used to detect T cell proliferation and proportion of IFN-γ+ T cells after coculture with gastric cancer cells (HGC-27, SNU-1). *p < 0.05, **p < 0.01, ***p < 0.001
|
PMC8981657
|
12865_2022_485_Fig2_HTML.jpg
|
0.467189 |
ed84998e82e24a35a5d3cac1115a6ec1
|
ThPOK induces upregulation of STPG1 in gastric cancer cells at the transcription level. A STPG1 level in gastric cancer tissues (n = 21) and adjacent normal tissues (n = 21) was assessed by RT-qPCR. B The expression of STPG1 in gastric cancer cells (HGC-27, SNU-1) and normal gastric mucosal cells (GES-1) was assessed by RT-qPCR. C RT-qPCR and western blotting were used to measure the knockdown efficiency of ThPOK in gastric cancer cells. D STPG1 mRNA and protein expression in gastric cancer cells posttransfection of sh-ThPOK#1/2. E The binding between ThPOK and the promoter region of STPG1 after the transfection of sh-ThPOK#1/2 was explored by luciferase reporter assay. F ChIP assay was used to verify the binding between ThPOK and STPG1 promoter. *p < 0.05, **p < 0.01, ***p < 0.001
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PMC8981657
|
12865_2022_485_Fig3_HTML.jpg
|
0.457231 |
6bd8c82ba1bb4a6fa02775fbf209ce63
|
STPG1 inhibits the immune escape of gastric cancer cells. A STPG1 expression in gastric cancer cells posttransfection of OE-STPG1 or OE-NC was detected by RT-qPCR. B CCK-8 assay was conducted to assess the viability of gastric cancer cells with overexpression of STPG1. C and D Flow cytometry analysis was used to detect the percentage of proliferated CD3+ T cells and the proportion of IFN-γ+ T cells after co-culture with gastric cancer cells (HGC-27, SNU-1) which were transfected with STPG1 overexpression vectors. *p < 0.05, **p < 0.01, ***p < 0.001
|
PMC8981657
|
12865_2022_485_Fig4_HTML.jpg
|
0.424103 |
3ed1cdbcaad9439cbd1eb545ff7ae951
|
ThPOK and STPG1 inactivate the ERK pathway. A and B p-ERK-1/2 and ERK-1/2 levels in gastric cancer cells after coculture with T cells. C and D Western blotting was used to detect the protein levels of p-ERK-1/2 and ERK-1/2 in gastric cancer cells transfected with OE-ThPOK or OE-NC. E and F The protein levels of p-ERK-1/2 and ERK-1/2 in gastric cancer cells after the transfection of OE-STPG1 or OE-NC. ***p < 0.001
|
PMC8981657
|
12865_2022_485_Fig5_HTML.jpg
|
0.443895 |
106c24ffd1104f6b978be3156311da24
|
ThPOK promotes T cell activation by STPG1. A Viability of gastric cancer cells under the conditions of OE-NC, OE-ThPOK, and OE-ThPOK + sh-STPG1 was detected by CCK-8 assay. Flow cytometry analysis was used to detect B and D the percentage of proliferated CD3+ T cells and C and E the proportion of IFN-γ+ T cells after coculture with gastric cancer cells (HGC-27, SNU-1) under the conditions of OE-NC, OE-ThPOK, and OE-ThPOK + sh-STPG1. *p < 0.05, **p < 0.01
|
PMC8981657
|
12865_2022_485_Fig6_HTML.jpg
|
0.398489 |
dcb1f60c9b424c78bf77983d2be841b5
|
The effect of pore structure of the 3D host on Li plating. SEM images of a,d,g) HSPR host, b,e,h) HSCR host, and c,f,i) HCFR host, respectively. Embedded images are the corresponding pore size distribution of each host. a–c) and d–f) are the top view and the cross‐section view of fresh hosts, respectively. g–i) are the cross‐section view of hosts after 5 mAh cm−2 lithium plating at a current density of 1 mA cm−2 in LEDV. Note the difference in scalebars between (g) and (h–i).
|
PMC8981896
|
ADVS-9-2104829-g001.jpg
|
0.469734 |
a15cbcfbc39741db943c6d790a2becc4
|
Full‐cell electrochemical performance of HCFR host paired with NMC811 in LDME electrolyte with saturated RbNO3. a) Full cell tests of Cu foil and HCFR host with NMC811 as cathode cycled at C/2, e/c ratio is 3 g Ah−1. b,c) are the voltage profiles of Cu foil‐NMC811 and HCFR‐NMC811 cells, respectively. The voltage range is 2.8−4.3 V. d) Comparison of pouch cell thickness variation before and after cycling with Cu or HCFR as the anode assuming a capacity of 1 mAh cm−2.
|
PMC8981896
|
ADVS-9-2104829-g002.jpg
|
0.495425 |
b750653eb2a348cab47f51c79bb88589
|
Schematic diagram of 3D hosts for Li metal delineating the effect of pore size and lithiophilicity offered by RbNO3. a) Cu foil where Li deposits as Li dendrites; b) the design guideline for 3D host where high loading Li deposits inside the host. A host made of Super P only is not lithiophilic enough. Adding nitrates will enhance lithiophilicity but the host pore sizes are too small. VGCF decorated with nitrates provides optimum combination of pore size and lithiophilicity; and c) the fabrication of high‐porosity 3D host with nitrates and large pore size by slurry casting. A 33‐µm thick coating houses 5 mAh cm−2 of lithium, close to its theoretical capacity.
|
PMC8981896
|
ADVS-9-2104829-g003.jpg
|
0.425624 |
20aaa0bfa9674864ab34340280a87980
|
RbNO3 works as an additive in 3D lithium hosts. Cross‐sectional SEM images of pristine a) SPC host and e) SPR host. Cross‐sectional SEM images of 1 mAh cm−2 lithium deposition in b–d) SPC host and f–h) SPR host at a current density of 0.5, 1.0, and 2.0 mA cm−2, respectively.
|
PMC8981896
|
ADVS-9-2104829-g005.jpg
|
0.463232 |
4b08566a9d5a4beba195a046f4bafc9b
|
Electrochemical performance of HCFR host in LDME electrolyte with saturated RbNO3. a) Coulombic efficiency of HCFR host, VGCF host, and Cu foil, respectively, at a current density of 1 mA cm−2 for 1 mAh cm−2; Cross‐sectional SEM images of cycled b) HCFR host, c) VGCF host, and d) Cu foil; e) Coulombic efficiency and the Li plating/stripping voltage profiles (inset) of HCFR host, Cu foil, respectively, at a current density of 3 mA cm−2 for 3 mAh cm−2. f) Comparison of 3D lithium anode electrochemical performance. Cumulative capacity is capacity per volume per cycle multiplied by cycle number.
|
PMC8981896
|
ADVS-9-2104829-g006.jpg
|
0.462613 |
94f77c5e652d46d5afe9aedf2cf6e660
|
Biophysical characterization of C.1086 base constructs(A) Schematic representation of different C.1086 base constructs tested in the study.(B) SEC profiles of 293F-expressed, GNL affinity-purified C.1086 base constructs. Trimeric peak (black arrow) elution volume and proportion (percentage, area under the curve [AUC]). Agg, aggregate/oligomeric peak. 2D class averages of the UFO and UFO-v2 trimers monitored by negative-stain electron microscopy shown at the bottom right of corresponding traces with total particles imaged (%native-like and %non-native like malformed trimers).(C) Trimeric proportion of C.1086 variants (mean [value indicated on top of bar] ± SD [error bars]) of at least three independent transfection/purifications estimated from SEC profiles. Student’s t test (two-tailed) for statistical comparisons, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.000.(D) Comparison of binding affinities of UFO and NFL trimers for various env-specific mAbs. For instances where the KD could not be calculated due to no observable dissociation in the experimental setting, Kon was used for comparison. A fold change in affinity within 3-fold range is shaded gray and not considered a significant change.(E) Similar plot as described in (C) but comparing UFO-v2 versus UFO.(F) Bio-layer interferometry (BLI) responses of 200 nM C.1086 UFO, UFO-v2 designs to CD4i non-nAbs, and CD4-IgG2.(G) KD (nM) of C.1086 variants against various bnAbs. Mean (at least two independent experiments) ± SD.(D–G) All binding affinities estimated by BLI. All C.1086 constructs carried K160N/V295N/N334S changes.
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PMC8982139
|
nihms-1785216-f0001.jpg
|
0.44029 |
6f942f6f47f34f1c9e8f4d7aa6f4d753
|
Sequence-guided mutations at the V2 hotspot region improve properties of well-formed trimmers(A) V2 hotspot (V2-HS) region (res. 166–173) of clade C consensus sequence (n = 22,415) with corresponding C.1086 region mentioned below. C.1086 residues differing from the consensus sequence are in red.(B) Influence of indicated V2-HS modifications in C.1086 UFO-v2 protein on binding to various mAbs, monitored by ELISA. The data are the average of more than two independent experiments.(C) Trimeric proportion of C.1086 UFO-v2 (left) and BG505 SOSIP.664 V2-HS (right) variants; mean (value indicated) ± SD (error bars) estimated from SEC profiles of at least two independent purifications. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 (Student’s t test, two-tailed), (left) p value indicated on top of bar denotes comparison with UFO-v2, which has 166K,170H,173H.(D) Blue native PAGE (BN-PAGE) of purified C.1086 proteins with molecular weight standard.(E) BLI responses of different C.1086-purified designs (400 nM each) against V1/V2 trimer apex-specific PGT145 bnAbs.(F) Comparison between binding affinities of optimized UFO-v2 V2-HS mutants relative to UFO-v2 against various env-specific mAbs. *KonUFO-v2/Kon UFO-v2 V2-HS for PGT121, as KD could not be calculated due to no observable dissociation. A fold change in affinity within 3-fold range is shaded gray and not considered a significant change.
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PMC8982139
|
nihms-1785216-f0002.jpg
|
0.499988 |
3304ccb9d00045dcaf30235129671cc2
|
Structural properties of C.1086 UFO-v2-RQ(H/Y)173 trimers measured by HDX-MS and time-dependent BLI experiments(A) Top: butterfly plots of BG505 SOSIP.664 and C.1086 UFO-v2-RQH173 proteins showing the percentage of exchange or the deuterium uptake for homologous peptide segments (indicated from N to C terminus) of the trimers detected in the experiment at each time point. Bottom: differences in percentage of exchange or deuterium uptake of homologous peptide segments of C.1086 UFO-v2-RQH173 relative to the BG505 SOSIP.664 trimer.(B) Time-dependent fold reduction in binding affinity (KD t hr/KD 0 h) of C.1086 UFO-v2-RQH173 and UFO-v2-RQY173 immunogens against various env-specific mAbs measured by BLI at 25°C. In case of PGT121, fold reduction in association rate (Kon 0 h/Kon t hr) was plotted, as KD could not be calculated due to no observable dissociation. Bars show mean, error bars SD of at least three independent experiments. Student’s t test (two-tailed) for statistical comparisons, *p < 0.05, **p < 0.01, ***p<0.001,****p<0.0001.
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PMC8982139
|
nihms-1785216-f0003.jpg
|
0.413885 |
9e94c773730b4cf8b7686e48094c232f
|
166R and 170Q modifications in V2-HS of UFO-v2 (UFO-v2-RQH173) enhance induction of moderate anti-viral antibody responses and binding to membrane-anchored tier2 envs(A–C) Schematic overview of the immunogenicity regimen tested in rabbits (n = 4 per immunization group). Serum binding antibody responses against (B) C.1086 WT and trimeric UFO-v2-RQH173 proteins measured by binding antibody-mediated multiplex assay (BAMA; indicated by area under the curve [AUC]) and ELISA, respectively and (C) the V3 peptide (left) and normalized to total trimer-specific responses (right).(D and E) Neutralizing antibody titer against tier1 and tier2 HIV-1 envs. See Table S3 for responses against other tier2 envs, which were mostly negligible. The concentration of purified IgG required to achieve 50% neutralization (IC50 μg/mL) is shown.In (E) IC50 >1,480 assigned 1,500 for ease of visualization in the graph.(F) Binding of purified IgG (1 μg/mL) from immunized rabbits to broad multi-clade HIV-1 full-length envs expressed on transiently transfected 293T cells. See Figure S6D for representative flow plot and gating of env+ live cells. Normalized frequency of env+ live cells is plotted (see STAR Methods). Combined plot and env+ frequencies measured against each env in the panel for each rabbit.(G) Spearman’s correlation between binding responses to membrane-anchored envs (C.1086 and 25710), and concentration of IgG required for 50% neutralization of the corresponding env-specific pseudovirus.(H) Percentage of reduction in replication of clade C tier2 SHIV1157ipd3N4 virus in human peripheral blood mononuclear cells (PBMCs) by purified IgGs (250 μg/mL) from various immunized groups (percentage of ADCVI activity). Each data point represents the averaged data for a rabbit IgG from three independent experiments, each done in duplicate.(B–H) All analyses correspond to serum collected 2 weeks post final protein boost. Refer to (A) for color coding of the immunization groups.(I) V2-HS region of various tier-categorized consensus clade C sequences (Rademeyer et al., 2016).(B, E, F, and H) Box and whisker plots where box extends from 25th to 75th percentile, median indicated by line, and minimum and maximum values indicated by whiskers. Statistical comparisons between groups by Mann-Whitney test (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, p values color coded by group correspond to comparison with WT). All values plotted are the average of at least two independent experiments.
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PMC8982139
|
nihms-1785216-f0004.jpg
|
0.429372 |
9559685024554efb98e3e4ebaf4b6efe
|
173Y modification in UFO-v2-RQH173 enhances the breadth of V1V2-scaffold-specific responses(A) Serum binding antibody responses of the immunized groups against gp70 C.1086 RQ(H/Y)173 V1V2 proteins. Plotted values are the average of two independent experiments.(B) BAMA analyses (binding the AUC) of serially diluted immunized serum to V1V2 scaffolds from 16 cross-clade HIV-1 isolates (see Figure S6G). The combined plot uses the AUC values obtained against the panel for each rabbit.(C) V1V2 breadth magnitude curves of all immunized rabbits (dotted line) with mean response of a group (bold line). Refer to (A) for color coding of the immunization groups. Unpaired two-tailed Kolmogorov-Smirnov test was used to see statistical difference between UFO-v2-RQH173 and UFO-v2-RQY173 groups.(D) Principal component analyses (PCAs; using R) of serum characterization data obtained for all immunized rabbits. All analyses correspond to serum collected 2 weeks post final protein boost. Mann-Whitney test for statistical comparisons between groups was used. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. p values color coded by group correspond to a comparison with the WT group, and in (B), those colored green correspond to a comparison with the UFO group.(A and B) Box and whisker plots where box extends from 25th to 75th percentile, median indicated by line, and minimum and maximum values indicated by whiskers.
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PMC8982139
|
nihms-1785216-f0005.jpg
|
0.448863 |
d3c681ffb9dd4c80ad53066749966097
|
Mapping binding specificity of Abs elicited in rabbits immunized with C.1086 variants(A) Representative BLI traces of competition binding experiment for purified IgG (rabbit #537) against env-specific mAbs.(B) Heatmap showing percentage of competition of rabbit-purified IgGs with env-specific mAbs to bind to C.1086 UFO-v2-RQH173 trimers and gp70 C.1086 V1V2 in the case of 697-30D V2i mAbs.(A and B) Purified IgGs from 2 weeks after final protein boost used for analyses. Values <40%, false positive. Not determined (ND) due to <1.5-fold difference in signals between background (buffer + purified IgG) and positive (buffer + trimer) control binding signals for the mAbs. C.1086 K160N RQH173 neutralization IC50 values (concentration of IgG required for 50% neutralization of the virus) of rabbit-purified IgG (filled squares color coded based on IC50 values; see Figure 4D) are mentioned above the rabbit codes. Data are representative of at least three independent experiments.(C) Spearman’s correlation (two-tailed) between C.1086 K160N RQH173 neutralization IC50 and competition (%) with NIH45-46 (estimated in B). Shaded orange area represents 95% confidence band. IC50 >1,480 assigned 1,500 for ease of visualization in the graph (shaded gray area).
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PMC8982139
|
nihms-1785216-f0006.jpg
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0.448028 |
0cc8e4cdeb2a451cad884f08169ae780
|
HIV, pregnancy and preterm birth. Maternal HIV infection is associated with preterm birth and the factors that may be linked to preterm birth include acute and chronic inflammation often associated with HIV infection. Immune dysfunction including skewed T cell differentiation, perturbed effector function and altered cellular homeostasis. Co-infections including opportunistic infections due to immunodeficiencies. Certain antiretroviral treatment regimens have been linked to preterm birth and timing of treatment initiation can impact birth outcomes. Poor placental development possibly linked to defective deep placentation. Placental dysfunction including poor perfusion and placental insufficiency and obstetric complications. Created in Biorender.com.
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PMC8982913
|
fgwh-03-820759-g0001.jpg
|
0.422864 |
0927e932251b411892866e881e21dcfe
|
Possible immune perturbances in the maternal decidua in women with HIV. Maternal HIV infection could lead to immune perturbances in the maternal decidua. This immune dysfunction could increase the risk for preterm birth in women with HIV. Created in Biorender.com.
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PMC8982913
|
fgwh-03-820759-g0002.jpg
|
0.451319 |
148dcd30e9df4b93a2bf09e43912ba74
|
Mean distribution of [11C]carfentanil BPND in the sample
|
PMC8983533
|
13415_2021_960_Fig1_HTML.jpg
|
0.383529 |
3ebf3ac483444aabbddb4fed06e6c211
|
Posterior distributions of the regression coefficients for sex drive dependent variability in MOR availability (a) and cortical density (b). Thick lines show 80% and thin lines 95% posterior intervals. ACC = anterior cingulate cortex, Dcaud = Dorsal caudate nucleus, MCC = middle cingulate cortex, PFC = orbitofrontal cortex, PCC = posterior cingulate cortex, VST = ventral striatum
|
PMC8983533
|
13415_2021_960_Fig2_HTML.jpg
|
0.413862 |
213ab93827774cce95a8af901bdae5a0
|
Brain regions where MOR availability was associated with sex drive. The data were thresholded at p < 0.05, FDR corrected. Scatterplots show least-squares-regression lines with 95% confidence intervals in representative regions. PCC = posterior cingulate cortex, VST = ventral striatum
|
PMC8983533
|
13415_2021_960_Fig3_HTML.jpg
|
0.443682 |
b1d90dfca2104f4e99e6c2a951c2bbb0
|
Brain regions where cortical density was associated with sex drive. The data are thresholded at p < 0.05, FDR corrected
|
PMC8983533
|
13415_2021_960_Fig4_HTML.jpg
|
0.460386 |
2722dfe51db14174a47710df40c4d67f
|
Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow chart of the study identification and selection process.
|
PMC8984187
|
fnhum-16-843481-g001.jpg
|
0.472397 |
61d8a7a4ab7749ddb612afefaf946466
|
Risk of bias graph.
|
PMC8984187
|
fnhum-16-843481-g002.jpg
|
0.371755 |
746846b1906c45c3afafafbea2211e02
|
Result of meta-analysis. (A) Timed Up and Go (TUG), (B) one-leg stance with open eyes (OLS-O), (C) functional reach test (FRT), and (D) gait speed (GS).
|
PMC8984187
|
fnhum-16-843481-g003.jpg
|
0.54342 |
1be0dfecfb31412ca42e9a9f9c32da81
|
Funnel plots.
|
PMC8984187
|
fnhum-16-843481-g004.jpg
|
0.493733 |
047d8c11bc1940d19dd0dd463f29877b
|
(A) Structures of the natural products HMNQ, HQNO, as well as the common ubiquinone surrogate DCIP. (B) Reactions catalyzed by Class II DHODHs.
|
PMC8984913
|
d1cb00255d-f1.jpg
|
0.415509 |
21fec0269a434788936ff4bffa46d38e
|
(A) Overview of the EcDHODH fold. The semi-flexible N-terminal loop (residues 30–40) is marked with an asterisk. (B) Substrate binding pocket, depicting the stacked FMN and ORO groups, as well as the ubiquinone binding tunnel. The positions of HQNO and DCIP are overlaid for context. (C) Overlay of the HQNO and HMNQ binding modes observed in crystallo. (D–F) 2-D interaction diagrams for DCIP (D), HMNQ (E), and HQNO (F).
|
PMC8984913
|
d1cb00255d-f2.jpg
|
0.475335 |
ade34a21786c412b8a9f255925bd9ffa
|
(A) Overlay of the ubiquinone docking model with the HQNO-bound structure depicting substantial similarities in binding mode. (B) 2-D interaction diagram for the truncated ubiquinone construct.
|
PMC8984913
|
d1cb00255d-f3.jpg
|
0.500289 |
202bb4550e014fc2b6aafcc84e123c58
|
Incidence of Eosinophilic Oesophagitis in children aged 0–17 in North Denmark Region in the period 2007–2017
|
PMC8985292
|
12887_2022_3258_Fig1_HTML.jpg
|
0.501538 |
797181137a294407ae90304f1a2461a3
|
Upper endoscopies in children in NDR (2007–2017) on any indication. The total number of endoscopies was obtained from the regional registry using the procedures codes for “upper endoscopies without biopsies”, “upper endoscopies with biopsies”, and age groups < 18 years
|
PMC8985292
|
12887_2022_3258_Fig2_HTML.jpg
|
0.409407 |
bcc60f8e02db46bd80f52992a3c4f788
|
Clinical manifestations among children at their first hospital visit related to Eosinophilic Oesophagitis. School-aged children were defined as children aged 3–12, and adolescents were children aged 13–17. Remarkably, no infants or toddlers aged 0–2 were diagnosed in the period 2007–2017
|
PMC8985292
|
12887_2022_3258_Fig3_HTML.jpg
|
0.402104 |
4d19e09f410d46f68385c8ed9f57fe3c
|
Diagnostic and second biopsy delay, and symptomatic and histologic remission delay in children with Eosinophilic Oesophagitis in North Denmark Region. Diagnostic delay is the time from first symptom to diagnosis. Second biopsy delay is the time from initial biopsy to second biopsy. Symptomatic remission delay is the time from initial treatment to symptomatic remission and histologic remission delay is the time from initial treatment to first oesophageal biopsy showing histologic remission (< 15 EOS/HPF)
|
PMC8985292
|
12887_2022_3258_Fig4_HTML.jpg
|
0.418066 |
b61a4e7e689441d6abe9f3f66ea33319
|
Initial treatment and follow-up of Eosinophilic Oesophagitis in children in North Denmark Region. Effective treatment is defined as achieving both symptomatic and histologic remission and having a long-term treatment plan for maintenance. Long-term treatment is defined as treatment that maintains remission. Abbreviations: EoE, Eosinophilic Oesophagitis; n, Number
|
PMC8985292
|
12887_2022_3258_Fig5_HTML.jpg
|
0.387598 |
54c532c5ec2f4c01abbb28ff522acbde
|
POPDC1 co-localises with PDE4. A. Immunofluorescence showing colocalization of DAPI (nucleus, blue), PDE4A4-VSV (green; polyclonal against human PDE4A) and POPDC1-FLAG (red: polyclonal against POPDC1) in transiently transfected HEK293 (Pearson's coefficient = 0.6., n = 4) and NRVMs (polyclonal against rodent PDE4A, (Pearson's coefficient = 0.6, n = 4).). B. Proximity ligation analysis shows that POPDC1 and PDE4A colocalized in transfected HEK293 cells, NRVMs and ARVMs (upper panels). (same antibodies as in A, n = 4). No background was detected in controls where only the secondary antibodies were used (lower panels). Red dots indicate co-localisation of PODC1 and PDE4A5 and green is wheat germ agglutinin staining to show positions of relevant cells. C, D. POPDC1 and PDE4A5 are detected in the membrane fraction after subcellular fractionation of cell lysate isolated from (C) transfected HEK293 cells or (D) NRVMs (blots typical of experiments done n = 3). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
|
PMC8986152
|
gr1.jpg
|
0.415824 |
3e18f0b5c09644169c221cdc4e27ac28
|
PDE4A and POPDC1 bind directly to each other. A. Myc-immunoprecipitation identifying POPDC1 in a complex with PDE4A5-VSV from transiently transfected HEK293 overexpressing PDE4A5-VSV and POPDC1-myc and B. POPDC1-immunopurification from NRVMs blotted for PDE4A5. C and D Recombinant purified POPDC1-GST and PDE4A4-MBP were mixed at equal concentrations prior to co-immunoprecipitations using amylose resin, that binds to the MBP tag (C.) or glutathione-agarose beads (D.). E. Far Western blotting where recombinant purified POPDC1-GST, UBC9-GST and P75-GST proteins were run on SDS-PAGE and blotted for GST, to ensure the proteins had been successfully transferred, and for MBP, to ensure there was no non-specific binding. F. Membranes were then overlaid with recombinant purified PDE4A4-MBP and re-probed with MBP to detect any interaction between the ‘bait’ proteins and the overlaid PDE4. G and H. A negative control experiment was carried out in the same manner but utilizing recombinant purified RHE PfPdx1-GST protein as it has not been shown to interact with PDE4A4. All blots in Fig. 2 are a representative of experiments done n = 3.
|
PMC8986152
|
gr2.jpg
|
0.465145 |
f5b6dd5758a44011bcbdd09195174d4d
|
Mapping the PDE4 docking region on POPDC1. A. Peptide arrays encompassing the full sequence of the POPDC1 protein were overlain with lysate from HEK293 cells over-expressing PDE4A4-VSV or PDE4D9-VSV. Each spot contains an immobilized 25mer sequence derived from the POPDC1 sequence. Dark spots indicate peptides that interacted with PDE4 (blotted for VSV tag). B. The initial binding site identified in A. (POPDC1 aa154 – aa178) was further interrogated by alanine scanning to identify single amino acids required for the interaction, conditions as in 3A. C. A motif scan array was constructed to evaluate the importance of the RLSILLK motif discovered in B. This was overlaid with PDE4A4-VSV, conditions as in 3A. D. To confirm whether the binding motif RLSILLK was important for the PDE4 interaction, an N-terminal truncation or E. a C-terminal truncation peptide array was analysed, conditions as in 3A. For all peptide array experiments negative control experiment was performed using mock transfected HEK293 cell lysate.
|
PMC8986152
|
gr3.jpg
|
0.469896 |
13f9fc41d8c147749b9f026b41520bba
|
POPDC1 binds to a site within the PDE4 UCR1 domain. A. A peptide array of 25mers shifted by 5 amino acids covering the full PDE4A4 sequence was overlaid with purified recombinant protein consisting of the Popeye domain of POPDC1 tagged with GST. A binding region was identified in the UCR1 domain of PDE4A and the modular structure of PDE4A is shown. A mock control was treated under same conditions but with BSA added instead of GST-Popeye domain. (n = 1) B. The Popeye binding domain in UCR1 contains 6 divergent regions (termed motifs 1–6 in red) when sequences from PDE4 A,B,C and are compared. Divergent amino acids are identified in bold and underlined. C. An alanine scanning array of the popeye binding domain was overlaid with purified recombinant protein consisting of the Popeye domain of POPDC1 tagged with GST. Amino acids that are alanised (or changed to Asp if alanine) are shown in red. Control array (Mock) was treated in same manner but the purified Popeye domain was replaced with BSA. D. A C-terminal truncation array was overlaid with purified recombinant protein consisting of the Popeye domain of POPDC1 tagged with GST. Control array (Mock) was treated in same manner but the purified Popeye domain was replaced with BSA. E. An alanine scanning array of the Popeye binding domain was overlaid with purified recombinant protein consisting of full length POPDC1 tagged with GST to identify essential amino acids where dark spots are attenuated. Amino acids that are alanised (or changed to glycine if alanine) are shown in light blue. Divergent amino acids are shown in red. Control array (GST) was treated in same manner but the purified Popeye domain was replaced with GST. Control and test arrays were both blotted for GST F. Spot arrays that compared POPDC1 binding sites from PDE4A and PDE4D overlaid with purified recombinant protein consisting of full length POPDC1 tagged with GST to identify role of divergent sequences (motifs 1–6). Each of the divergent motif was sequentially alanised (or changed to glycine if alanine, shown in light blue) and binding of POPDC1 determined by blotting for GST. Divergent amino acids are shown in red. Control array (GST) was treated in same manner but the purified Popeye domain was replaced with GST. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
|
PMC8986152
|
gr4.jpg
|
0.468528 |
d820bb0222cd40bfa66faa9199cc8ac9
|
POPDC1 interacts preferentially with the PDE4A sub-family. A. Co-immunoprecipitations were done using HEK293 cell lysate transiently transfected with POPDC1-myc and PDE4A4-VSV, PDE4B1-VSV or PDE4D7-VSV. Myc-agarose resin was used to precipitate POPDC1 and any interacting PDE4 was detected using VSV tag. Western blotting for both myc confirmed pull down of POPDC and VSV confirming successful transfection of PDE4 isoforms. Negative control immunoprecipitation experiments were performed using cell lysate from mock transfected HEK293. B. Specificity of the POPDC1 interaction for endogenous PDE4 isoforms was examined in NRVMs using PanPDE4A, PDE4B and PDE4D antibodies by PLA analysis. Red dots indicate co-localisation. C. Images were quantified using ImageJ. The intensity of the red (PLA) signal was taken for each cell by drawing around each individual cell using the wheat germ agglutinin as the cell boundary. Data represents an n of 3 with each n consisting of 15–20 cells. Significance was evaluated using a one-way ANOVA with Tukeys post-hoc analysis, ****p = 0.0001, compared to PDE4A control. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
|
PMC8986152
|
gr5.jpg
|
0.412682 |
91632eb3af9b45aeb86cc4c30c963fb8
|
A cell penetrating disruptor peptide dissociates the POPDC1-PDE4 complex. A. HEK293 cells transiently transfected with POPDC1-myc and PDE4A5-VSV were treated with 10 μM scrambled or disruptor peptide. Co-immunoprecipitations of POPDC1 and PDE4A5 performed using Myc-conjugated resin was used to evaluate ability of scrambled or disruptor peptide to compete with PDE4-POPDC1 interaction. The figure is a representative example chosen from three replicate experiments. B. HEK293 cells transiently transfected with POPDC1-myc and PDE4A5-VSV were treated with 10 μM scrambled peptide or disruptor peptide prior to fixation. After PLA staining of HEK293 cells, images were analysed using ImageJ. C. Significance was evaluated using a one-way ANOVA with Tukeys post-hoc analysis, ****p = 0.0001, compared to untreated and scrambled peptide controls. D. The experiment was repeated in NRVM staining endogenous proteins. E. After PLA staining of NRVMs, images were analysed in ImageJ for quantification of PLA signal per condition. The intensity of the red (PLA) signal was taken for each cell by drawing around each individual cell using the wheat germ agglutinin as the cell boundary. Data represents an n of 3 with each n consisting of 15–20 cells. Significance was evaluated using a one-way ANOVA with Tukeys post-hoc analysis, ****p = 0.0001, compared to untreated control and scrambled peptide control. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
|
PMC8986152
|
gr6.jpg
|
0.426165 |
f82ba5aeaa1746e599ac34d01fee42d4
|
Disruption of the POPDC1-PDE4 complex reduces TREK1 binding. A. HEK293 cells stably expressing PDE4A4 were transiently transfected with POPDC-CFP and TREK1-YFP. After treatment with 25 μM Forskolin or 10 μM Rolipram, static measurements were taken every 5 s for 300 s per cell. Test data was normalised to mean data from an identical but untreated control group of cells. B. FRET ratio calulated as mean ± SEM, control n = 9 cells, forskolin n = 15 cells, rolipram n = 15 cells per experiment (n = 3). Significance was evaluated using a one-way ANOVA with Tukeys post-hoc analysis, ** p ≤0.005, ***p = 0.001, compared to control C. Calculation of FRET ratio after treatment with 10 μM scrambled peptide or 10 μM disruptor peptide. Static measurements were taken every 5 s for 300 s. Background fluorescence was subtracted from mean intensities and are plotted as mean subtracted intensities. Results represented as mean ± SEM, untreated n = 11 cells, scrambled peptide n = 11 cells, disruptor peptide n = 20 cells per experiment (n = 3). A one-way ANOVA with Tukey's post-hoc was used to analyze the FRET ratios.
|
PMC8986152
|
gr7.jpg
|
0.423649 |
e3247077e44c402bb63b583513134898
|
POPDC1-PDE4 disrupting peptide accelerates spontaneous Ca2+ transient frequency in isolated mouse SAN (A) Examples of spontaneous Ca2+ fluctuations recorded by 2-D confocal imaging in Fluo-4-loaded individual SAN cells embedded within the intact SAN. The SAN was incubated for 1 h with 5 μM disrupting peptide prior to Ca2+ measurements in normal Tyrode solution (Control) and in the presence of isoproterenol (Iso, 10 nM). (B) Representative traces of spontaneous Ca2+ transients in SAN cells incubated with 5 μM scrambled peptide (left) or 5 μM disrupting peptide (right) in control and Iso 10 nM conditions. Fluorescence traces are expressed as F/F0, where F is the fluorescence signal and F0 the diastolic fluorescence. (C) Average cycle length (time between two consecutive spontaneous Ca2+ peaks) in 6 SAN incubated with 5 μM scrambled peptide and 6 SAN incubated with 5 μM disrupting peptide in control and Iso 10 nM. Bars are mean values ± SEM. **: p < 0.01; ****: p < 0.0001; $$$: p < 0.001. Two-way ANOVA followed by a Sidak's post-hoc test.
|
PMC8986152
|
gr8.jpg
|
0.439584 |
1895caca94724d869dfed14a8dc1fd04
|
Supplementary Fig. 1. Expression pattern of PDE4A5 and POPDC1 in adult rabbit ventricular myocytes. Immunofluorescence showing colocalization of DAPI (nucleus, blue), PDE4A5 (green: PDE4A5 specific polyclonal) and POPDC1 (red: POPDC1 polyclonal) in ARVMs. (Pearson's coefficient = 0.21).
|
PMC8986152
|
mmc1.jpg
|
0.400567 |
ca28f961599f408996e1f05d626003d0
|
Supplementary Fig. 2. Expression pattern of PDE4A5 and TREK-1 in adult rabbit ventricular myocytes. Immunofluorescence showing colocalization of DAPI (nucleus, blue), TREK-1 (green: TREK1 polyclonal) and POPDC1 (red: POPDC1 polyclonal) in ARVMs. (Pearson's coefficient = 0.54).
|
PMC8986152
|
mmc2.jpg
|
0.458728 |
1f0be56b69a24e099f920596ee2e1a96
|
Supplementary Fig. 3. Relative levels of colocalisation between PDE4 and POPDC1 in ARVMS evaluated by PLA. A. ARVM cells were subjected to PLA following staining with antibodies against POPDC1 and either PDE4A5, pan-PDE4B or pan-PDE4D. B. PLA signals from 3 cells were counted for each treatment and a mean value plotted as PLA signals per cell (n = 1).
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PMC8986152
|
mmc3.jpg
|
0.432627 |
5dfaa6a2afc14775aa4327309bfef4cd
|
Supplementary Fig. 4. PDE4 activity or phosphorylation by PKA is not affected by POPDC1 association. A. Increasing amounts of Purified recombinant POPDC1-GST and PDE4A4-MBP were incubated together in a PDE assay. The activity of PDE4A4 was recorded. Graphs were constructed using GraphPad Prism 6™. Results are displayed in pmol cAMP/ min and are represented as a mean ± SEM, n = 3. B. Purified recombinant POPDC1-GST (purple) or GST (blue) were incubated with PDE4A4-MBP in a PDE assay containing increasing concentrations of Rolipram (blue). The activity of PDE4A4 was recorded and graphs were constructed using GraphPad Prism 6™. Results are represented as a mean ± SEM, n = 3. C. Equal molar concentrations of POPDC1-GST and PDE4A4-MBP were incubated with PKA catalytic subunit. Samples were separated by SDS-PAGE and probed via western-blotting for indicated proteins. D. The gel depicted in C. was blotted for phosphorylated-PKA substrates and a phospho-PDE4 UCR1 to detect changes in the level of PDE4 phosphorylation. E. Intensities from phospho-PKA substrate blots were evaluated using ImageJ and normalised to controls. n of 3, mean ± SEM. F. Intensities from phospho-UCR1 blots were evaluated using ImageJ and normalised to controls. n of 3, mean ± SEM.
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PMC8986152
|
mmc4.jpg
|
0.416506 |
7b6b989d3ade47f89ea5a1cbb88f0d72
|
Supplementary Fig. 5. The POPDC1-PDE4 complex influences action potential duration. A. Measurements were collected from 4 points during the repolarization phase. The action potential duration (APD) of ARVMs was determined following treatment with the POPDC1-PDE4A disruptor and scrambled control peptides. B. A representative trace of action potentials with scrambled control peptide and disruptor peptide. Measurements of APD across the action potential repolarization phase (C) APD30, (D) APD 50, (E) APD75, and (F) APD90 were collected from cells which were paced at 1 Hz under baseline conditions and displayed on scatter plot graphs with bars ± SEM. Untreated cells, n = 19, scrambled peptide n = 37 and disruptor peptide n = 42 cells. One-way ANOVA with Tukey's post-hoc analysis, performed using GraphPad Prism™ ****p < 0.0001, **p < 0.01. E. (F) Contraction duration at 50% contraction to 50% relaxation was measured after 2 h of treatment with either 10 μM scrambled or disruptor peptide. Each point represents the mean value from one cell. From one rabbit. One-way ANOVA with Tukey's post-hoc analysis.
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PMC8986152
|
mmc5.jpg
|
0.450901 |
dbe2339242674c03bf860e9391597749
|
Supplementary Fig. 6. Measurements of contraction in NRVMS. A. Representative traces of contraction. UT = untreated, Scrambled = scrambled peptide control, disruptor = disruptor peptide B. Contraction duration at 50% contraction to 50% relaxation was measured after 2 h of treatment with either 10 μM scrambled or disruptor peptide. Each point represents the mean value from one cell. Untreated cells, n = 39, scrambled peptide n = 67 and disruptor peptide n = 50 cells. From 2 rabbits. One-way ANOVA with Tukey's post-hoc analysis.
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PMC8986152
|
mmc6.jpg
|
0.47308 |
b61b72a09bb74a328653d8fbb96f00b2
|
Supplementary Fig. 7. Full gels for Figs. 1E, F, 2A and B. Note that nitrocellulose for Figs. 1E, F and 2A was split for concomitant western blotting of proteins at different weights.
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PMC8986152
|
mmc7.jpg
|
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