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0.483649 |
9d90c28d35664819b11221dcfe3d4938
|
Survey question on measuring disease team–based productivity (N = 454).
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PMC9328455
|
jadpro-13-507-g003.jpg
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0.487965 |
c97fdfe2126a41f3af05d77ee6718b5b
|
NBP was identified as a chondrogenic inducer that increased ECM anabolism of human OA chondrocytes in vitro. (a) Chemical structure of NBP. (b) Alcian blue staining (scale bar, 100 μm). (c) Immunofluorescence staining of COLII (scale bar, 100 μm). (d) The CCK8 assay measured the cytotoxicity of NBP on chondrocytes at different concentrations for 24 h. (e, f) The protein expressions of COL2A1 and ACAN were detection by Western blot analysis after chondrocytes were treated with NBP for 24 h. (g) The mRNA levels of COL2A1, ACAN, PRG4, and SOX9 were detected using qRT-PCR. (h, i) The expressions of COLII and ACAN were detected by the immunofluorescence assay (scale bar, 100 μm). All data are expressed as the mean ± standard deviation (SD). ∗P < 0.05, ∗∗P < 0.01, and∗∗∗P < 0.001.
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PMC9329036
|
OMCL2022-9468040.001.jpg
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0.436134 |
83b76798b0a94f7ba70d996ab894559c
|
NBP promoted ECM anabolism in OA cartilage explants. (a) Proteoglycan content was measured by the safranin O-fast green staining after incubation with NBP for 2 w (scale bar, 100 μm). (b) COLII content was measured by immunohistochemistry staining (scale bar, 100 μm). (c) Average optical density values of proteoglycan content determined by safranin O-fast green staining. (d, e) GAG and DNA content per wet weight were assessed after NBP (0.1 μM) treatment for 2 w. (f–i) The mRNA levels of COL2A1, ACAN, PRG4, and SOX9 were detected using qRT-PCR after NBP (0.1 μM) treatment for 2 w. All data are expressed as the mean ± standard deviation (SD). ∗P < 0.05, ∗∗P < 0.01, and∗∗∗P < 0.001.
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PMC9329036
|
OMCL2022-9468040.002.jpg
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0.438024 |
3b6d4719271f4273948418a0d0785e2f
|
NBP inhibited the development of knee OA after intra-articular injection of NBP in a rat model of DMM+ACLT for 8 w. (a) Representative images of HE for cartilage destruction, safranin O-fast green for cartilage regeneration, and immunohistochemistry staining for COLII expression, respectively. (b) OARSI scores in different treatment groups (n = 6). (c) Pain response time when rats were placed onto a 55°C hot plate after the surgery (n = 6). (d) The differences in two hind limb weights after the surgery in rats (n = 6). All data are expressed as the mean ± standard deviation (SD). ∗P < 0.05, ∗∗P < 0.01, and∗∗∗P < 0.001.
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PMC9329036
|
OMCL2022-9468040.003.jpg
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0.408182 |
92ef4866719c4a119746aa759af3c415
|
NBP inhibited apoptosis and oxidative stress of human OA chondrocytes. (a, c) Apoptosis was analyzed by flow cytometry and apoptosis rates are expressed in the respective group. (b, d) Apoptotic assay by TUNEL staining was observed under a microscope, and TUNEL-positive cells were calculated (n = 3, scale bar, 100 μm). (e, f) The mRNA levels of Bcl-2 and Bax were measured by qRT-PCR. (g) The protein expressions of CAT, SOD2, Bcl-2, Bax, and Caspase 3 were determined after treatment with NBP (0-10 μM) for 24 h by Western blot analysis. (h, i) The expression levels of SOD and GSH in chondrocytes treated with NBP (0-10 μM) for 24 h. (j, k) The mRNA levels of SOD2 and CAT were measured by qRT-PCR. All data are expressed as the mean ± standard deviation (SD). ∗P < 0.05, ∗∗P < 0.01, and∗∗∗P < 0.001.
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PMC9329036
|
OMCL2022-9468040.004.jpg
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0.432943 |
2e8c0f449f0341739f5834d68501e971
|
Bioinformatics analysis based on network pharmacology and transcriptome sequencing result after treated with NBP. (a–c) Network pharmacology. (a) Venn diagram of NBP-OA. (b) Bubble plot of the enrichment analysis results: cell components. (c) Signaling pathways. (d–f) Transcriptome sequencing. (d) Volcano plots of differentially expressed genes in the transcriptome. (e) Gene Ontology (GO) analysis of the transcriptome of chondrocytes administrated with NBP. (f) Pathway analysis from the chondrocyte transcriptome.
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PMC9329036
|
OMCL2022-9468040.005.jpg
|
0.389644 |
94a9d0fcfdbf476dab24506aff43a979
|
NBP regulated the PI3K/AKT/FoxO3a pathway in human OA chondrocytes. (a, b) The protein expressions of FoxO1, FoxO3a, p-FoxO3a, FoxO4, PI3K, p-PI3K, AKT, and p-AKT were determined by Western blot assay. (c–e) The mRNA levels of FoxO1, FoxO3a, and FoxO4 were measured using qRT-PCR. (f) Immunofluorescence staining of FoxO3a and ACTIN (scale bar, 20 μm). All data are expressed as the mean ± standard deviation (SD). ∗P < 0.05, ∗∗P < 0.01, and∗∗∗P < 0.001.
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PMC9329036
|
OMCL2022-9468040.006.jpg
|
0.412843 |
a7a67ef886f04d5c83e319bf9b528c2b
|
NBP increases ECM anabolism in human OA chondrocytes by regulating FoxO3a. (a, b) The protein and mRNA levels of FoxO3a were evaluated by Western blot and qRT-PCR after treated with and/or Lv-FoxO3a for 24 h. (c) Proteins expressions of ACAN and COL2A1 were detected by Western blot. (d) Immunofluorescence staining for COLII (scale bar, 50 μm). (e–h) The mRNA levels of COL2A1, ACAN, SOX9, and PRG4 were determined by qRT-PCR. All data are expressed as the mean ± standard deviation (SD). ∗P < 0.05, ∗∗P < 0.01, and∗∗∗P < 0.001.
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PMC9329036
|
OMCL2022-9468040.007.jpg
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0.426209 |
754dc57e771043c3bca347570ac3fe34
|
NBP inhibited apoptosis of human OA chondrocytes by upregulating FoxO3a. (a) Cluster analysis of mRNA levels of downstream genes in the FoxO pathway. (b, c) The mRNA levels Bcl-2 and Bax were determined. (d) The protein expressions of Bcl-2, Bax, and Caspase 3 were determined. All data are expressed as the mean ± standard deviation (SD). ∗P < 0.05, ∗∗P < 0.01, and∗∗∗P < 0.001.
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PMC9329036
|
OMCL2022-9468040.008.jpg
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0.457058 |
e55200614da9467aa74a44dca694a629
|
Molecular mechanism of NBP on inhibiting OA development. NBP possesses protective effect on human OA chondrocytes from apoptosis by regulating PI3K/AKT/FoxO3a pathway (created with https://biorender.com/).
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PMC9329036
|
OMCL2022-9468040.009.jpg
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0.407693 |
38251cde27664a5ea1f876f0c7147ca0
|
Research process and flow chart. LN, lymph node.
|
PMC9329631
|
fsurg-09-956346-g001.jpg
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0.441578 |
499fd295a5844d13bbcfb96d0d307027
|
Puncture port placement.
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PMC9329631
|
fsurg-09-956346-g002.jpg
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0.500461 |
e184714d0d704fd3a433b87c81621562
|
Schematic diagram of the scope of 4sb lymph node dissection. The yellow area is the experimental group, and the yellow plus purple area is the control group.
|
PMC9329631
|
fsurg-09-956346-g003.jpg
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0.463468 |
ca511dabb67442b4b6e32c89b9143f44
|
Schematic diagram of the scope of 12a lymph node dissection. The yellow area is the experimental group, and the yellow plus purple area is the control group.
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PMC9329631
|
fsurg-09-956346-g004.jpg
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0.470567 |
c1edfbff833040418e1d56df58840edc
|
Schematic diagram of preparation of Ebs@dZnONPs/HGT hydrogel and its application in the treatment of infected wounds.
|
PMC9329969
|
gels-08-00463-g001.jpg
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0.389231 |
e2ddc141171a4cb8aff5a13296f1f765
|
(A) TEM of dZnONPs; (B) FTIR of dZnONPs, Ebs, and Ebs@dZnONPs; (C) 1H-NMR of HA and HA-GMA; (D) Cross-sectional SEM of HG hydrogel and HGT hydrogel; (E) Pore size distribution of HG hydrogel and HGT hydrogel; (F) Mechanical macrographs of HG hydrogel and HGT hydrogel; (G) Single compressive stress-strain curves of HG hydrogel and HGT hydrogel; (H) Resilience-time diagram of HG hydrogel and HGT hydrogel (10 compression cycles).
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PMC9329969
|
gels-08-00463-g002.jpg
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0.378071 |
82821b023414490b80185f4766534eff
|
(A) Macroscopic image and cross-sectional SEM of Ebs/HGT hydrogel; (B) Macroscopic image and cross-sectional SEM of Ebs@dZnONPs/HGT hydrogel; (C) Injectability of Ebs@dZnONPs/HGT hydrogel; Frequency sweep testing of HG (D), HGT (E), Ebs/HGT (F) and Ebs@dZnONPs/HGT (G) hydrogels; (H) Equilibrium swelling of hydrogels in PBS solution (pH = 7.4); (I) Water retention of hydrogels after 12 h; (J) In vitro degradation of hydrogels; (K) In vitro release of Ebs. Data are presented as mean ± standard (n = 3), * means p < 0.05.
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PMC9329969
|
gels-08-00463-g003.jpg
|
0.41758 |
41a56ab6ff7f444c84c79bd6d97c8e44
|
(A) Bacteriostatic zone testing of hydrogels; (B) Quantitative analysis of the zone of inhibition. Data are presented as mean ± standard (n = 3), * means p < 0.05, *** means p < 0.001.
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PMC9329969
|
gels-08-00463-g004.jpg
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0.399266 |
d935db48a14a4f9fae812115a126149b
|
Quantitative analysis of the antibacterial properties of hydrogels: Colony-counting assay of hydrogels against S. aureus (A) and E. coli (B); (C) Antibacterial rate of hydrogels against S. aureus and E. coli (quantitative analysis of colony statistics); Quantitative analysis of photometric method against E. coli (D) and S. aureus (E). Data are presented as mean ± standard (n = 3), * means p < 0.05, ** means p < 0.01, *** means p < 0.001.
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PMC9329969
|
gels-08-00463-g005.jpg
|
0.501813 |
13d1a469f28a4bd1bbd46d04fb715051
|
Cytocompatibility of hydrogels. (A) Morphology of HUVECs on day 4 and day 7; (B) Survival rates of HUVECs on days 1, 4, and 7; (C) Survival rates of L929 cells on days 1, 4, and 7. Data are presented as mean ± standard (n = 3).
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PMC9329969
|
gels-08-00463-g006.jpg
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0.398151 |
bc6cf0fdc5434befaa3680840cd7002d
|
In vivo experiments of hydrogels. (A) Macroscopic images of wound healing on days 0, 7, and 14 of treatment; (B) Wound closure rates on days 7 and 14 of treatment. Results of HE staining of the new skin after 7 days of treatment: (C) Blank group, (D) HG hydrogel group, (E) HGT hydrogel group, (F) Ebs/HGT hydrogel group, (G) Ebs@dZnONPs/HGT hydrogel group, (H) Quantitative analysis of epidermal layer thickness. Data are presented as mean ± standard (n = 3), * means p < 0.05, *** means p < 0.001.
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PMC9329969
|
gels-08-00463-g007.jpg
|
0.387295 |
7d4ef4fa762144d8a482f0c318b2cc99
|
Results of Masson’s trichrome staining after 7 days of treatment. (A) Blank group, (B) HG hydrogel group, (C) HGT hydrogel group, (D) Ebs/HGT hydrogel, (E) Ebs@dZnONPs/HGT hydrogel, (F) Quantitative analysis of collagen deposition area. Data are presented as mean ± standard (n = 3).
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PMC9329969
|
gels-08-00463-g008.jpg
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0.454459 |
a3d449222f29443a98e75787825e7a75
|
Interface specimens. (a) concrete specimen; (b) natural section of rhyolite; (c) interface specimen.
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PMC9330250
|
materials-15-05164-g001.jpg
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0.475715 |
e62fa797fac5456c900c4b427d8d932e
|
Loading equipment: (a) MTS 322; (b) RMT-150B.
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PMC9330250
|
materials-15-05164-g002.jpg
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0.479116 |
518ccc6705f74d428575b3189cb2e55f
|
Stress–strain curves of specimens under different strain rates. (a) Mortar; (b) interface; (c) concrete.
|
PMC9330250
|
materials-15-05164-g003a.jpg
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0.456064 |
6e1fdcc1f2f6473e9b6c036f54837de6
|
Corresponding relation between tensile elastic modulus and parallel bond effective modulus.
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PMC9330250
|
materials-15-05164-g004.jpg
|
0.444121 |
2347e3f69f5242b9853b42a8398fb692
|
Corresponding relationship between the compression modulus and the linear bond effective modulus.
|
PMC9330250
|
materials-15-05164-g005.jpg
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0.425857 |
64eb1488ef0542d3aff621f9a6d32d6a
|
Relation between Poisson’s ratio and parallel bond stiffness ratio.
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PMC9330250
|
materials-15-05164-g006.jpg
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0.451969 |
4e50c2e3d1514a1287de7697b292069c
|
Comparison of discrete fractures under different values of the bond ratio: (a) compressive failure of sandstone; (b) r¯s=0.1; (c) r¯s=0.5; (d) r¯s=1.0; (e) r¯s=1.2; (f) r¯s=1.5; (g) r¯s=2.0; (h) r¯s=5.0.
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PMC9330250
|
materials-15-05164-g007.jpg
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0.39491 |
7d5ccdc180f84baa9933475e5404502e
|
Corresponding relation between tensile strength and parallel bond cohesion.
|
PMC9330250
|
materials-15-05164-g008.jpg
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0.422899 |
a9b2902bbb4046cb851425e9972f3802
|
Concrete specimen: (a) CT scanning image of the specimen section; (b) PFC numerical model; (c) tension crack development; (d) fracture after tensile failure.
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PMC9330250
|
materials-15-05164-g009.jpg
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0.477508 |
975802f12bcd48788af780ca9bd2b958
|
Numerical results of stress–strain curves of concretes under different strain rates.
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PMC9330250
|
materials-15-05164-g010.jpg
|
0.442484 |
b5b7cedd502c4a3096b5886da9e48813
|
The crack propagation process of concrete under tension failure. (a) 95% peak stress; (b) 100% peak stress; (c) 70% peak stress after peak; (d) 10% peak stress after peak.
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PMC9330250
|
materials-15-05164-g011.jpg
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0.485455 |
703f4ec514024b74bbfedc3f24482e76
|
Energy evolution under different strain rates: (a) energy evolution at strain rate 1 × 10−1; (b) energy evolution at strain rate 1 × 10−2; (c) comparison of strain energy and dissipated energy.
|
PMC9330250
|
materials-15-05164-g012.jpg
|
0.43855 |
2dd9ee7fdafb4155ad97390a70d2e0e2
|
Relation between the parallel bond elastic modulus ratio of the ITZ to the mortar and the tensile strength of concrete.
|
PMC9330250
|
materials-15-05164-g013.jpg
|
0.470593 |
eb17b90fcb6d45ccbdf701d06668a9f0
|
Sampling location of the Wild (site 1) and Cultured (site 2) Barramundi fish in Bangladesh.
|
PMC9330387
|
toxics-10-00410-g001.jpg
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0.437289 |
b349e996ccee4e27b44a9284571aeb0e
|
Concentration of metals in muscle, liver and gill tissue of cultured and wild Barramundi fish.
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PMC9330387
|
toxics-10-00410-g002.jpg
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0.367845 |
a3674d71641a4341987d151d06691ccd
|
The intrahepatic levels of alpha-fetoprotein protein are elevated in injured livers. A: Immunohistochemistry and hematoxylin and eosin (H&E) staining analyzed alpha-fetoprotein (AFP) expression and pathological changes, respectively, in liver tissues of patients with chronic hepatitis B (CHB, n = 34), trauma (n = 8) or hepatocellular carcinoma (HCC, the positive control group, n = 8). The upper panels display immunohistochemical staining, and the lower panels exhibit H&E staining in sequential tissue sections. The positive expression of AFP was stained with brownish yellow by immunohistochemistry and indicated by the arrows; B: The relative levels of AFP protein expression were analyzed by Western blot in the liver specimens indicated. H&E: Hematoxylin and eosin; IHC-P: Immunohistochemistry-paraffin; AFP: Alpha-fetoprotein; HCC: Hepatocellular carcinoma; CHB: Chronic hepatitis B. bP < 0.01, compared with the control group.
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PMC9331527
|
WJG-28-3201-g001.jpg
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0.407807 |
412dcc1432444256bd6ce94c49d1f26f
|
Administration with carbon tetrachloride induces alpha-fetoprotein expression, endoplasmic reticulum stress and liver injury in mice. Male BALB/c mice were untreated (NC), or administrated with olive oil (control) or carbon tetrachloride (CCl4) for 24 h, or 8 wk. A: Serum alanine aminotransferase levels; B: Serum total bilirubin levels; C: Hematoxylin and eosin staining analysis of pathological changes in mouse liver tissues at 24-h and 8-wk post CCl4; D: Chemiluminescence immunoassay of serum alpha-fetoprotein (AFP) levels; E: Western blot analysis of the relative levels of AFP expression in liver tissues of mice; F: Immunohistochemical staining of AFP expression in liver tissue of mice at 24-h post CCl4, the positive expression of AFP was stained with brownish yellow and indicated by a plus sign; G: Western blot analysis of the relative levels of protein kinase R-like endoplasmic reticulum kinase phosphorylation and activating transcription factor-6 expression in liver tissues of mice. AFP: Alpha-fetoprotein; ALT: Alanine aminotransferase; ATF6: Activating transcription factor-6; CCl4: Carbon tetrachloride; H&E: Hematoxylin and eosin; PERK: Protein kinase R-like endoplasmic reticulum kinase; TBil: Total bilirubin. bP < 0.01 compared with the control group.
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PMC9331527
|
WJG-28-3201-g002.jpg
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0.413456 |
52a761a7e8354eee92ce391a6543465c
|
Endoplasmic reticulum stress up-regulates alpha-fetoprotein expression in hepatocytes. Male BALB/c mice were untreated (NC), or treated with phosphate buffer saline (control) or TM for 24 h or 48 h. LO2 cells were untreated (NC), or treated with dimethyl sulfoxide (control) or thapsigargin (TG) for 24 h, and 48 h. A: Serum alanine aminotransferase levels; B: Serum total bilirubin levels; C: Western blot analysis of the relative levels of proteins; D: Immunohistochemical analysis of alpha-fetoprotein (AFP) expression and hematoxylin and eosin staining analysis of liver injury in mice at 24 h post endoplasmic reticulum stress. The positive expression of AFP was stained with brownish yellow and indicated by a plus sign. Hash sign indicates the area of necrosis; E: Chemiluminescence immunoassay of serum AFP levels in mice; F: The levels of AFP in the supernatants of cultured cells; G: Cell counting kit-8 analysis of the cell viability; H: Western blot analysis of the relative levels of p-protein kinase R-like endoplasmic reticulum kinase, ATF6 and AFP expression in LO2 cells. AFP: Alpha-fetoprotein; ALT: Alanine aminotransferase; ATF6: Activating transcription factor-6; CCl4: Carbon tetrachloride; CCK-8: Cell counting kit-8; DMSO: Dimethyl sulfoxide; H&E: Hematoxylin and eosin; IHC-P: Immunohistochemistry-paraffin; PBS: Phosphate buffer saline; p-PERK: Phosphorylated protein kinase R-like endoplasmic reticulum kinase; TBil: Total Bilirubin; TM: Tunicamycin; TG: Thapsigargin. bP < 0.01, compared with the control group; dP < 0.01, compared with the 0 h group in HepG2 cells.
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PMC9331527
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WJG-28-3201-g003.jpg
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0.479399 |
7c12f4520807472eaa23efa7640faaa5
|
Activating transcription factor-6 silencing inhibits the expression of alpha-fetoprotein induced by thapsigargin in
vitro. LO2 cells were transfected with control shRNA, protein kinase R-like endoplasmic reticulum kinase (PERK)-shRNA, or activating transcription factor-6 (ATF6)-shRNA for 48 h, and treated with dimethyl sulfoxide (control) or thapsigargin for 24 h. A: Cell counting kit-8 (CCK-8) analysis of cell viability; B: Western blot analysis of p-PERK, phosphorylated eukaryotic translational initiation factor 2 alpha, and alpha-fetoprotein expression; C: CCK-8 analysis of cell viability; D: Western blot analysis of the relative levels of ATF6 and AFP protein expression. AFP: Alpha-fetoprotein; ATF6: Activating transcription factor-6; CCK-8: Cell counting kit-8; DMSO: Dimethyl sulfoxide; p-eIF2α: Phosphorylated eukaryotic translational initiation factor 2 alpha; p-PERK: Phosphorylated protein kinase R-like endoplasmic reticulum kinase; TG: Thapsigargin. aP < 0.05, bP < 0.01, compared with these two groups.
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PMC9331527
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WJG-28-3201-g004.jpg
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0.477762 |
b96bae96b58e46dd95fd3a0ce1933089
|
Silencing of alpha-fetoprotein exacerbates the thapsigargin-induced LO2 cell injury. A: Western blot determined alpha-fetoprotein silencing in LO2 cells; B: Cell counting kit-8 analysis of LO2 cell viability; C: Western blot for the relative levels of indicated protein expression in LO2 cells; D: Western blot for the relative levels of endoplasmic reticulum stress-related protein. AFP: Alpha-fetoprotein; CCK-8: Cell counting kit-8; ER: Endoplasmic reticulum; TG: Thapsigargin; p-MLKL: Phosphorylated mixed lineage kinase domain-like pseudokinase; p-PERK: Phosphorylated protein kinase R-like endoplasmic reticulum kinase. Data are typical images or expressed as the mean ± SD of each group from 3 separate experiments. bP < 0.01 compared with these two groups.
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PMC9331527
|
WJG-28-3201-g005.jpg
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0.416751 |
036d40ace2b24c6f814d04236a20b2a7
|
Silencing of alpha-fetoprotein increases liver injury in mice following CCl4 administration. A: Western blot for the protein levels of alpha-fetoprotein (AFP) in the liver tissues of mice; B: Serum alanine aminotransferase levels; C: Serum levels of total bilirubin; D: Liver sections stained by hematoxylin and eosin and measurements of necrotic areas in mice; E: Western blot for the relative levels of AFP, cleaved caspase-3, and phosphorylated mixed lineage kinase domain-like pseudokinase expression in the liver tissues; F: TUNEL analysis of hepatocyte apoptosis; G: The relative levels of phosphorylated protein kinase R-like ER kinase, activating transcription factor-6 and C/enhancer binding protein homologous protein protein in liver tissues. AFP: Alpha-fetoprotein; ALT: Alanine aminotransferase; ATF6: Activating transcription factor-6; CCl4: Carbon tetrachloride; CHOP: C/enhancer binding protein homologous protein; H&E: Hematoxylin and eosin; p-MLKL: Phosphorylated mixed lineage kinase domain-like pseudokinase; p-PERK: Phosphorylated protein kinase R-like ER kinase; TBil: Total bilirubin; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. bP < 0.01 compared with these two groups.
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PMC9331527
|
WJG-28-3201-g006.jpg
|
0.463575 |
edc47c771e1644f397b022685511d25f
|
Normal surfactant clearance (blue) and changes occurring in PAP (red). In PAP, there are abnormal antibodies against the granulocyte macrophage colony stimulating factor that impair the normal function of lung macrophages with the accumulation of undegraded surfactant. Gas exchange is altered at the level of the lung alveoli, and this can lead to hypoxemia.
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PMC9331898
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medicina-58-00984-g001.jpg
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0.443415 |
9013e65f75e549d5b4197c9c0e048a90
|
All the specialists contribute to the interdisciplinary management of lung cancer.
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PMC9332145
|
jcm-11-04326-g001.jpg
|
0.413033 |
8dd541481b44436abae13007172f7fb8
|
The study of moderators (trait-like characteristics; biotypes; left), the study of mechanisms of action (state-like changes; right), and their integration (bottom). Integrating the two fields of research of moderators and mechanisms of action is critical for identifying individual-specific mechanisms of action in the progress toward precision medicine.
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PMC9332605
|
jpm-12-01197-g001.jpg
|
0.450413 |
f526c2a52125427cb772eb9b48fc715d
|
Example 1: SL–TL distinction in the case of right amygdala activation in fear vs. neutral faces. The figure is based on the predicted values from the models fitted on real data of actual patients who were enrolled in the RCT. The y-axis is the outcome variable defined as the predicted rate of HRSD change over time in units of log of week (the scaling of time, in log, was chosen according to the model that showed the optimal level of fit to the data). Lower levels on the y-axis refer to greater symptom reduction. The x-axis refers to the trait-like levels (baseline levels before the manipulation). The different lines refer to the state-like levels (amount of change that occurred from baseline to post-expectancy manipulation before the start of treatment). The black line indicates the increase in activation (one SD above no change in activation), the red line refers to no change in activation (about 39% of the patients showed less than one standard deviation away from 0 in the amount of change), and the green line refers to decrease in activation (one SD below no change in activation). The error bars represent 95% confidence intervals.
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PMC9332605
|
jpm-12-01197-g002.jpg
|
0.460307 |
68ac4d9adbf949b9b3457444c534a92b
|
Example 2: SL–TL distinction in the case of left pallidum activation in response to reward cues. The figure is based on the predicted values from the models fitted on real data of actual patients who were enrolled in the RCT. The y-axis is the outcome variable defined as the predicted rate of HRSD change over time in units of log of week (the scaling of time, in log, was chosen according to the model that showed the optimal level of fit to the data). Lower levels on the y-axis refer to greater symptom reduction. The x-axis refers to the trait-like levels (baseline levels before the manipulation). The different lines indicate the state-like levels (amount of change that occurred from baseline to post-expectancy manipulation before the start of treatment). The black line indicates increase in activation (one SD above no change in activation), the red line refers to no change in activation (about 14% of the patients showed less than one standard deviation away from 0 in the amount of change), and the green line refers to decrease in activation (one SD below no change in activation). The error bars represent the 95% confidence intervals.
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PMC9332605
|
jpm-12-01197-g003.jpg
|
0.43811 |
2e232dad6d0b459c8bebef1428d70820
|
Flowchart of study enrollment.Note: The database providing contact information for the 1100 Veterans provided mailing addresses for all Veterans aged 43–75 deployed to the Persian Gulf as part of Operation Desert Storm/Desert Shield between 1990 and 1991 who lived in our catchmant area. This was not a clean dataset with many Veterans having multiple addresses listed, addresses that were not current, addresses for Veterans who no longer live in our catchment area, and addresses that were innacurately recorded. This lead to needing to mail a large number of letters to reach a small number of Veterans.
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PMC9333223
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pone.0268479.g001.jpg
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0.414778 |
2fac59476efb4359902460fb87ecb9e0
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Relative abundance bar plot of the top 8 phyla by aggregated by week and GWI status.
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PMC9333223
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pone.0268479.g002.jpg
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0.516166 |
623b89c2d4b043b2af39a0f80b6f4a44
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Linear mixed-effects modeling of alpha diversity by week.Red line is those with GWI and blue line is the controls. Lighter bands represent the 95% confidence interval of the regression line.
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PMC9333223
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pone.0268479.g003.jpg
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0.362029 |
ef15c92295d545fb805561ca3ce428dc
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Alpha diversity by week and GWI status stratified by the presence of moderate/severe gastrointestinal symptoms (Yes/No).
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PMC9333223
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pone.0268479.g004.jpg
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0.609878 |
f2ef51b89d1943c082272e93fed454ec
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NMDS plot of the Bray-Curtis dissimilarity matrix by week and GWI status.
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PMC9333223
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pone.0268479.g005.jpg
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0.454126 |
26a8e73d26c5475db4b2a07c0ffae4e5
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Unadjusted survival after implantable cardioverter‐defibrillator (ICD) generator change (GC).Among patients with ICD GCs, survival after the GC is shown to vary significantly based on whether the LVEF is >35% or ≤35% (A) and the quartile of the Seattle Heart Failure Model (SHFM) (B). The separation of the survival curves is greater in (B). Prob. indicates probability.
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PMC9333379
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JAH3-11-e023743-g001.jpg
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0.452886 |
5c2c63744c4d465ebfb0144b9b575401
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Seattle Heart Failure Model (SHFM)‐adjusted survival stratified by proportional risk of arrhythmic death (PRAD)/Seattle Proportional Risk Model (SPRM) and implantable cardioverter‐defibrillator (ICD) generator change status.SHFM‐adjusted survival curves with stratification by PRAD/SPRM quartiles and cohort (ICD‐PP‐GC vs HF‐NO‐ICD) are shown. The potential survival benefit for patients with generator changes versus control patients appears to be limited to SPRM quartile (Q) 3 and Q4 (SPRM above the median) based on the separation of ICD‐PP‐GC and HF‐NO‐ICD survival curves in these quartiles. HF‐NO‐ICD indicates heart failure group without implantable cardioverter‐defibrillator; and ICD‐PP‐GC, primary prevention first implantable cardioverter‐defibrillator–generator change group.
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PMC9333379
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JAH3-11-e023743-g002.jpg
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0.415513 |
c40cddfbabb349a9a3d510f834d0dafb
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Implantable cardioverter‐defibrillator (ICD) generator change (GC) hazard ratio versus Seattle Proportional Risk Model (SPRM)‐predicted proportional risk of sudden death (PRAD).The ICD‐GC‐HR as a function of the PRAD at the time of GC is plotted with 95% confidence bounds for patients with left ventricular ejection fraction (LVEF) ≤35%. This hazard ratio is defined as the time‐dependent hazard associated with the ICD‐GC divided by the corresponding hazard for similar patients (based on Seattle Heart Failure Model adjustment) in the control group without an ICD GC. The strongest indication of benefit or harm corresponds to PRAD values for which the 95% confidence bounds for this hazard ratio does not include 1. ICD‐GC‐HR indicates hazard ratio associated with ICD generator change; LCB, lower confidence bound; and UCB, upper confidence bound.
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PMC9333379
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JAH3-11-e023743-g003.jpg
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0.476377 |
5ea0a934a2ad458bb1c013c6079e3ec4
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Dynamic nature of risk scores from the time of initial implant to the time of implantable cardioverter‐defibrillator (ICD) generator change (GC).Based on linked records in Versions 1 and 2 of the ICD Registry, box plots are shown with the median and interquartile ranges for Seattle Heart Failure Model–predicted annual mortality at the time of the initial implant (A) and the time of the generator change (B) grouped by whether the patient was alive or dead at the time of last follow‐up after the replacement ICD. The change in this parameter for each patient stratified by those who survived or died following the replacement ICD is shown in (C). A similar analysis is shown based on the Seattle Proportional Risk Model–predicted proportional risk of sudden death at the time of the initial ICD implant (D) and the time of the generator change (E) based on patient records linked across registries. Again, a comparison of this parameter based on the change for each patient stratified by those who survived or died following the replacement ICD is shown in (F). abs. indicates absolute; and PRAD, proportional risk of arrhythmic death.
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PMC9333379
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JAH3-11-e023743-g004.jpg
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0.427857 |
38ca55ed14e44b44a414190c0e17074e
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Unadjusted survival after implantable cardioverter‐defibrillator (ICD) generator change (GC) based on Seattle Heart Failure Model score change (SHFMC) from initial implant to GC.Survival curves are stratified by quartiles of the change in the Seattle Heart Failure Model (SHFM) score from the time of the initial ICD implant to the time of the ICD GC in the cohort of patients with linkage between the initial implant in Version 1 and the first ICD GC in Version 2 of the ICD Registry. Markedly worse survival was observed in the quartile of patients with the most unfavorable change in SHFM (greatest increase in predicted annual mortality) from the time of the initial ICD implant to the time of the first generator change. Prob. indicates probability.
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PMC9333379
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JAH3-11-e023743-g005.jpg
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0.443089 |
3afd3b2b927a4efdb3c41e39d11af133
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Trial profileBaricitinib unavailable and baricitinib considered unsuitable are not mutually exclusive. *Number recruited overall during period that adult participants could be recruited into the baricitinib comparison.
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PMC9333998
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gr1.jpg
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0.431774 |
4c9bd1f14bb44955af6ca4b08c834767
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Effect of allocation to baricitinib on 28-day mortality
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PMC9333998
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gr2.jpg
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0.491684 |
2f069619a0ae44219af9f06f450ad2fa
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Effect of allocation to baricitinib on 28-day mortality by baseline characteristicsSubgroup-specific rate ratio estimates are represented by squares (with areas of the squares proportional to the amount of statistical information) and the lines through them correspond to the 95% CIs. The days since onset and use of corticosteroids subgroups exclude those with missing data, but these patients are included in the overall summary diamond.
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PMC9333998
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gr3.jpg
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0.503454 |
290ef96ad1854e159ca0f746e93c0aa6
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Meta-analysis of mortality in randomised controlled trials of a JAK inhibitor in patients hospitalised with COVID-19JAK=Janus kinase. O–E=observed–expected. Var=variance. RR=mortality rate ratio. Details of the individual studies, including the use of placebo or other treatments in the control group are shown in the appendix (p 62). *For RECOVERY, the O–E and and its variance are calculated from the age-adjusted log RR and its standard error. For the other trials, the O–E statistics and their variances are calculated from 2 × 2 tables. Rate ratio is calculated by taking ln rate ratio to be (O–E)/V with normal variance 1/V, where V=Var (O–E). Subtotals or totals of (O–E) and of V yield inverse-variance weighted averages of the ln rate ratio values. †These trials assessed a JAK inhibitor other than baricitinib. If the meta-analysis was restricted to RECOVERY plus the three other trials of baricitinib, the RR would be 0·81 (95% CI 0·73–0·91). ‡For balance, controls in the n:1 studies count n times in the control totals and subtotals, but only count once when calculating their O–E or V values.
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PMC9333998
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gr4.jpg
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0.419758 |
282480da4afa466486a0d3584ce26685
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Developing the effective saponin+ compound derived from Chinese medicine mixture to optimally induce the differentiation of hiPS into cardiomyocytes. a Gene expression of unpurified hiPS-CMs optimally induced by Chinese medicine mixture at different intervention time points. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses of the expression levels of undifferentiated cell marker genes (NANOG, POU5F1, FGF4, ESG1, DPPA2, and DPPA4) and cardiac marker genes (cTNI, ACTN1, TNNT2, GJA1, NKX2.5, GATA4, and MEF2C). *P < 0.05. b Flow cytometry was used to detect the positive rate of unpurified hiPS-CMs optimally induced by Chinese medicine mixture. Representative histogram of hiPS-CMs after differentiation showed the proportion of cTnI-expressing cells. c Identification of active ingredients in Chinese medicine mixture using LC–IT-TOF-MS. Core chemical structures of main ingredients a-g were shown. d Exploring the optimal concentration of each active ingredient in Chinese medicine mixture to induce P19 cells to differentiate into cardiomyocytes by drug screening system based on Myh6 promoter. The bar graphs represented averages and standard deviations, each performed in triplicate. The asterisk denoted statistical significance (P < 0.05). e Exploring the optimal combinations of active ingredients in Chinese medicine mixture to induce P19 cells to differentiate into cardiomyocytes by drug screening system based on Myh6 promoter. f Schematic representation of the differentiation procedure and sequential morphological changes (day 0–15) of hiPS differentiation into cardiomyocytes induced by effective saponin+ compound. Scale bars = 50 μm. hiPS, human-induced pluripotent stem cell
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PMC9334380
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41392_2022_1045_Fig1_HTML.jpg
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0.384187 |
aaddb5a2bf594f4d936201368e272320
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Gene expression profiling of the standard and compound induced hiPS-CMs from hiPSC lines UC (reprogrammed from urine cells). a RNA-Seq gene expression profiles of cardiomyocyte maturation markers GATA4, Nkx2.5, α-MHC, and c-TNI at day 0, 5, and 15 of the standard and compound-induced hiPS differentiation. Log2FC on the y-axis indicated the magnitude of gene differences between groups (STD-CMs, COMP-CMs) at two separate differentiation time points (day 5, day 15). Fold-change (FC) represented the differential fold-change in the differential mRNA between the two groups. Log2FC was obtained by taking the logarithm of FC at the base of 2. b GO functional classification of the standard and compound induced hiPS-CMs at day 5 and day 15. GO terms assigned to biological process, cellular component, and molecular functions. c KEGG functional classification of the standard and compound induced hiPS-CMs at day 5 and day 15. COMP-D5, the compound induced hiPS-CMs at day 5; STD-D5, the standard induced hiPS-CMs at day 5; COMP-D15, the compound induced hiPS-CMs at day 15; STD-D15, the standard induced hiPS-CMs at day 15. d Principal component analysis (PCA) was performed based on the shared genes of STD (D15), COMP (D15), Fetal and Adult. The first three principle components (PC) separated STD, COMP from Fetal and Adult. The first two axes accounted for 61.96% of variance. The first principal component (PC) explained 44.45% of the variance in the expression values and effectively separated the STD, COMP, Fetal, and Adult. The combination of the second and third principal components further separated the STD, COMP, Fetal, and Adult. Each symbol represented one sample. e Schematic representation of correlation matrix. Spearman correlation between different samples. The square color gradient effect showed the correlation coefficient. The correlation matrix values range from −1 to 1, representing either a completely negative or positive correlation, respectively. f Venn diagram showed the overlap between Fetal genes derived from GEO datasets and genes in STD (D15), or genes in COMP (D15). Fetal shared 17,174 and 17,059 genes with STD and COMP, respectively. g Heatmap showed the expression of the early and late-stage signature genes of heart development in overlap genes of “STD vs. Fetal” and “COMP vs. Fetal”, which indicated that the expression of the identified genes had different expression patterns in these types of samples. Expression is indicated as the z-score normalized. h Stacked column bar graphs depict the average gene expression at the early and late-stage of heart development. COMP expressed a larger proportion of late-stage genes of heart development than STD, showing more mature characteristics
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PMC9334380
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41392_2022_1045_Fig2_HTML.jpg
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0.396315 |
8404e16cdf294e3bbb1deb55c1100334
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Comparison of extracellular electrograms and intracellular Ca2+ measurement as well as structure and functional maturity of the standard and compound induced hiPS-CMs from hiPSC lines UC (reprogrammed from urine cells). a An activation map serving as a visual representation of the activation sequence recorded by means of the MEA data acquisition system. The map activation time (the time duration between the first and last activations) is represented by the lower scale at the bottom of the map. The color strip below the map represents the color spectrum and its scaling according to time. Color coding: red-early; blue-late. b A representative display of electrograms recorded from the entire MEA array. Spontaneously beating cardiomyocytes were verified by extracellular electrograms recorded on the 3rd day after cell seeding and culture. c MEA micro matrix electrode system to detect the changes of field potential and phase waveform during depolarization/repolarization of hiPS-CMs. d Electrical properties of the cells were studied with MEA, which revealed the differences between the standard and compound induced hiPS-CMs group. FPD, field potential duration. e Calcium flux in hiPS-CMs at day 15 of the induction. Calcium transients were recorded at the basal condition. Images showed traces of calcium transients. Calcium transient frequency at the basal state (n = 4-5). Data were presented as the means ± SEM. *P < 0.05. f Morphological and structural characteristics of mitochondria in living hiPS-CMs labeled with mitochondrial green fluorescent probe (MTG). Scale bars = 50 μm. g The fluorescence intensity of TMRE, Rhod-2 and cyto C staining were quantified using ImageJ, *P < 0.05. h Ultrastructural examination of hiPS-CMs myofilament, microfilament, and mitochondria. Red arrow indicated myofilament. Black arrow indicated microfilament. Yellow arrows indicated mitochondria. Purple arrow indicated endoplasmic reticulum. Red circle indicated glycogen accumulation. Scale bars = 1 μm
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PMC9334380
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41392_2022_1045_Fig3_HTML.jpg
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0.403781 |
4cd140475f184714ae4f76546dc0eacc
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Effects of the standard and compound induced hiPS-CMs transplantation on cardiac function and myocardial energy metabolism. a Study protocol of the hiPS-CMs transplantation experiments in heart failure mice. b In vivo fluorescence imaging of mice demonstrated that the exogenously delivered compound induced hiPS-CMs labeled with CM-DiL could quickly gather to injured myocardium. Quantification of fluorescence intensity showed a longer cardiac aggregation effect in the compound induced hiPS-CMs than the standard induced hiPS-CMs transplantation group. Quantitative fluorescence intensity was shown on the right, n = 4 for each group. c Electrocardiogram (ECG) was performed 4 and 8 weeks after hiPS-CMs transplantation. n = 4–6 for each group. Representative traces from mice telemetric ECG recordings showed normal sinus rhythm. d Effects of the standard and compound induced hiPS-CMs on ventricular structure and function of heart failure mice at 4 and 8 weeks by echocardiography. Representative M-mode images from each group where the numbers used for calculations were derived. n = 5–7 for each group. EF, ejection fraction; FS, fractional shortening; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular end-systolic volume; LVIDd, left ventricular internal diastolic dimension; LVIDs, left ventricular internal systolic dimension; LVPWd, left ventricular posterior wall dimension in diastole; LVPWs, left ventricular posterior wall dimension in systole. e Myocardial metabolism was assessed via 18F-DPA-714 uptake by micro-PET/CT. n = 3 for each group. Representative 3D reconstruction images from global, transverse and other views from each group were shown. The higher glucose uptake level was shown as the increase in the intensity of white and red as indicated on the color scale bar shown in each image. Calculation of SUVmax and uptake ratio showed that the compound induced hiPS-CMs transplantation group had a significantly increased glucose uptake level. STD, standard induced hiPS-CMs transplantation group; COMP, compound induced hiPS-CMs transplantation group
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PMC9334380
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41392_2022_1045_Fig4_HTML.jpg
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0.413685 |
ceaaf247e967414bba3c3e621e23cf6c
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Effects of the compound induced hiPS-CMs on cardiac structure and expression of peripheral blood secretion factors after 8 weeks of transplantation. a Preliminary safety evaluation by macroscopic comparison of important organs morphology. b Diameter analysis at 8 weeks post-transplantation showed significantly smaller sizes of the heart in the compound induced hiPS-CMs transplantation group than in the heart failure model group. c Neither macroscopic nor microscopic analysis revealed any evidence of tumor formation at 4 and 8 weeks after hiPS-CMs transplantation. d Ultrastructural changes in cardiomyocytes of control, model and hiPS-CMs transplanted groups were revealed by transmission electron microscope analysis at low (scale bar: 5 μm) and high (scale bar: 1 μm) magnifications. e TUNEL assay was performed to detect the myocardial apoptosis. Apoptotic nuclei were stained green, and normal nuclei were stained blue. Scale bar: 50 μm. f Microvascular neo-angiogenesis at 8 weeks post hiPS-CMs transplantation. Immunofluorescent staining for micro-vessels positive for α-smooth muscle actin (α-SMA) and CD31 in the left ventricle. Scale bar: 200 μm. g Representative photographs of myocardial fibrosis, which were determined by Masson’s trichrome staining. The blue color represented the distribution of collagens. h Statistical analysis of myocardial apoptosis, microvascular neo-angiogenesis and fibrosis staining were quantified using ImageJ. i The expression of c-TNI protein was analyzed by Western blotting and normalized to GAPDH. j Real-time PCR was used to assess cardiac transcription factor GATA4 and Nkx2.5 mRNA levels in the heart. k Expression of myocardial injury markers in peripheral blood. CK, CK-MB and LDH are very sensitive and specific indicators of damage to the myocardium. l Expression of secretory factors in peripheral blood. BNP is a factor released into the blood by injured myocardium, and its concentration changes reflect the severity of heart failure. VEGF, HGF and TGF-β are feedback-activated factors during ventricular pathological remodeling in failing myocardium. n = 3-4 mice per group and * indicated that P < 0.05. STD, standard induced hiPS-CMs transplantation group; COMP, compound induced hiPS-CMs transplantation group
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PMC9334380
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41392_2022_1045_Fig5_HTML.jpg
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0.400524 |
9205a781ebf24d74aa607a7db54d12ff
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Gene expression profiling of the heart by RNA-seq after hiPS-CMs transplantation treatment. a Venn diagram showing that the upregulated differentially expressed genes (DEGs) of “COMP1M vs. M” group overlap with the downregulated DEGs of “M vs. C” group, for a total of 12 overlapping genes. b Venn diagram showing the intersection of upregulated DEGs in the “M vs. C” group and the downregulated DEGs in the “COMP1M vs. M” group, with a total of 313 intersecting genes. c Gene ontology (GO) enrichment analysis of the 12 and 313 DEGs obtained above. The biological pathways that were enriched among genes were ranked based on –log10(P-value). Enrichment was performed using the DAVID database. The eight of the most significantly enriched biological process GO terms were shown (P < 0.05). d Venn diagram showing 231 overlapping genes between the downregulated DEGs of “M vs. C” and upregulated DEGs of “COMP2M vs. M” groups. e Venn diagram of upregulated DEGs of “M vs. C” group compared with downregulated DEGs of “COMP2M vs. M” group. A total of 1196 shared genes. f Enrichment of GO biological processes identified from 231 and 1196 shared DEGs, respectively. g Venn diagram showing “STD2M vs. M” and “COMP2M vs. M” shared DEGs, with a total of 304 shared DEGs in both groups. h The most differentially overrepresented biological processes in “COMP2M vs. M” compared with “STD2M vs. M” were displayed. Three mice per group. “Count” means that the enriched DEGs numbers in the pathway. “RichFactor” represents the number of DEGs relative to total number of genes in the pathway, with larger RichFactors indicating greater enrichment. COMP1M, one month after the saponin+ compound induced hiPS-CMs transplantation treatment group; COMP2M, two months after the saponin+ compound induced hiPS-CMs transplantation treatment group; STD2M, two months after the standard induced hiPS-CMs transplantation treatment group; M, heart failure model group; C, control group. COMP1M vs. M, DEGs in the saponin+ compound induced hiPS-CMs transplantation group treated for 1 month compared with the model group; COMP2M vs. M, DEGs in the saponin+ compound induced hiPS-CMs transplantation group treated for 2 months compared with the model group; STD2M vs. M, DEGs in the standard induced hiPS-CMs transplantation group treated for 2 months compared with the model group; M vs. C, DEGs in the model group compared with the control group
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PMC9334380
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41392_2022_1045_Fig6_HTML.jpg
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0.412888 |
fce7623eaaf44d6395c4d7dbc6ccdf9f
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PDGF-BB secreted from the compound induced hiPS-CMs from hiPSC lines UC (reprogrammed from urine cells) rescued the hypoxia-triggered injury model of HCMs by regulating PI3K/Akt pathway in vitro and played a key role in the recovery of cardiac function in vivo. a Heat map demonstrated relative expressions of biomarkers from screening cytokine antibody array in the supernatant of the compound and standard induced hiPS-CMs derived from two different generations of hiPS cells (passage 24, 26). The upregulated cytokines were shown in red and downregulated cytokines in green. b Representative photomicrographs of TUNEL (green) and DAPI (blue) -stained HCMs were shown. Scale bars = 50 μm. c Changes of myocardial specific protein c-TNI expression level in hypoxia-injured HCMs was detected by immunofluorescence assay. Scale bars = 50 μm. d Quantification of IF staining for TUNEL+ HCMs showed that PDGF-BB in the conditioned medium of the compound induced hiPS-CMs was the core cytokine that inhibited the apoptosis of HCMs. e Quantitative analysis by CCK-8 assay of cell viability. Values were expressed as the mean ± SD of three independent experiments. f The protein expression of CK-MB in the extracellular medium of hypoxia-injured HCMs was detected by ELISA. g PI3K, p-PI3K, Akt, p-Akt and β-actin levels of hypoxia-injured HCMs in Control, HYP, HYP + COMP, HYP + PDGF-BB and HYP + COMP + PDGF-BBAb groups were analyzed by Western blot. h The protein expression levels were normalized to those of β-actin. All data shown as mean ± SD, *P < 0.05. i PDGF-BBAb counteracted most of the protective effects of compound induced hiPS-CMs on cardiac function in vivo at 4 and 8 weeks by echocardiography. n = 4 for each group. HCMs, human cardiac myocytes; HYP: Hypoxia; COMP, the conditioned medium of the compound induced hiPS-CMs; PDGF-BB, platelet-derived-growth-factor-BB; PDGF-BBAb, neutralizing antibody against PDGF-BB; c-TNI: cardiac Troponin I; COMP-P24, the conditioned medium from cardiomyocytes induced by the 24th generation of hiPS by the compound induction scheme; COMP-P26, the conditioned medium from cardiomyocytes induced by the 26th generation of hiPS by the compound induction scheme; STD-P24, the conditioned medium from cardiomyocytes induced by the 24th generation of hiPS by the standard induction scheme; STD-P26, the conditioned medium from cardiomyocytes induced by the 26th generation of hiPS by the standard induction scheme; p-PI3K: phospho-phosphatidylinositol 3-kinase; PI3K: phosphatidylinositol 3-kinase; p-Akt: phospho- protein kinase B; Akt: protein kinase B
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PMC9334380
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41392_2022_1045_Fig7_HTML.jpg
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0.491156 |
f91535c0ff04459d8b6b5464d65c2317
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repRNA vaccination elicits humoral and cellular immunity to CCHFV. WT C57BL6/J mice were given (a) prime boost vaccinations at days -56 and -28 relative to CCHFV challenge on day 0. On day 0 groups of four mice vaccinated with 2.5μg (sham, repNP, repGPC) or 5μg (repNP + repGPC) of RNA were evaluated for immune responses to CCHFV. CCHFV-specific antibody was measured by whole-virion ELISA for total IgG (b) or specific isotypes (c). Dashed line indicates background absorbance of wells that received no serum. Serum neutralization activity was measured by a microneutralization assay against infectious CCHFV strain Hoti (d). Dashed line indicates limit of detection and statistical significance calculated using a one-way ANOVA with Dunnett's multiple comparison test. CCHFV-specific T-cell responses were measured by IFNγ ELISpot (e – g). Cumulative SFCs against peptide pools spanning the entire NP or GPC, the mitogen concanavalin a (CA) or DMSO vehicle alone (veh) are shown. Statistical comparisons calculated using a two-way ANOVA with Dunnett's multiple comparison test (c – e) Heat maps showing the distribution of measured IFNγ SFCs against NP (e) or GPC (f) peptide pools. ns P > 0.05, *** P < 0.001. (b – e) Data shown as mean plus standard deviation.
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PMC9335360
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gr1.jpg
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0.445011 |
9c015a1c0fdf490db1af19bc573ef14c
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repNP vaccination confers significant protection against CCHFV. Groups of WT mice given indicated prime-boost vaccinations were treated with MAR1-5A3 to blockade type I IFN and infected with CCHFV strain UG3010. Mice were weighed daily (a), monitored for survival (b) and body temperature continuously monitored via telemetry system (c). N = 8 mice per group. Statistical comparisons were calculated using a two-way ANOVA with Dunnett's multiple comparison test (a) or Log-Rank test with Bonferonni's correction for multiple comparisons (b). Statistical significance compared to sham vaccinated animals is shown with symbols: * (repNP), # (repGPC) and + (repNP + repGPC). Viral loads in indicated tissues at day 5 p.i was quantified by qRT-PCR. Dashed line indicates limit of detection (d). N = 6 mice per group Statistical comparisons calculated using a one-way ANOVA with Tukey's multiple comparison test. ns P > 0.05, * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001. (a, c, d) Data shown as mean plus standard deviation.
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PMC9335360
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gr2.jpg
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0.400775 |
71c4eb6dbf864b9ab8e97c57c43993d3
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repNP vaccination protects against liver pathology in CCHFV infected mice. Groups of WT mice given indicated prime-boost vaccinations were treated with MAR1-5A3 to blockade type I IFN and infected with CCHFV strain UG3010. On day +5 p.i. mice were euthanized, liver collected and formalin fixed. Sections were H&E stained or probed for presence of viral antigen via immunohistochemistry (IHC). Representative images for each group are shown at 100x or 400x (inset) magnification and scale bars indicate 100μm or 20μm respectively. Complete findings are provided in Supplemental Table 1.
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PMC9335360
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gr3.jpg
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0.481976 |
189d3ade4df946418146714aa360a947
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Single-immunization with repRNA induces humoral and cellular immunity to CCHFV. Groups of 4 WT mice were vaccinated with indicated cumulative doses of repNP + repGPC RNA in a prime-boost regimen as before or in a prime-only regimen. Four weeks after last vaccination, vaccine-induced immune responses to vaccination were measured by ELISA (a) or IFNγ ELISpot (b). CCHFV-specific IgG responses were measured by whole virion ELISA (a). Dashed line indicates background absorbance of wells receiving no serum. Statistical comparisons calculated using a two-way ANOVA using Tukey's multiple comparisons test. The summary P value of each vaccine group individually compared against sham-vaccinated animals is also shown. (b) CCHFV-specific T-cell responses were measured by IFNγ ELISpot and cumulative SFCs against the NP or GPC peptide pools is shown. Indicated statistical comparisons calculated using a two-way ANOVA with Tukey's multiple comparisons test. ns P > 0.05, * P < 0.05, ** P < 0.01, *** P < 0.001. Data shown as mean plus standard deviation.
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PMC9335360
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gr4.jpg
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0.526942 |
3ca7d706600e4dc09f7caabc6610752d
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Prime-only vaccination protects against CCHFV challenge. Groups of WT mice receiving indicated vaccinations were treated with MAR1-5A3 to abolish type I IFN signaling and challenged with CCHFV strain UG3010. Mice were weighed daily (a), monitored for survival (b) and body temperature monitored continuously via telemetry system (c). N = 8 mice per group except for sham-vaccinated telemetry data where N = 6. Statistical comparison to sham-vaccinated mice performed using a two-way ANOVA with Dunnett's multiple comparisons test or log-rank test with Bonferroni's correction for multiple comparisons (b). At day 5 p.i., viral loads in indicated tissues were quantified by qRT-PCR (d) or TCID50 assay (e) and statistical comparison between sham vaccinated mice and repRNA-vaccinated mice calculated using one-way ANOVA with Dunnett's multiple comparisons test. Statistical comparisons between sham-vaccinated and every repNP-vaccinated groups were significant. N = 6 per group. ns P >0.05, * P < 0.05, ** P < 0.01, *** P <0.001, **** P < 0.0001. (a, c, d, e) Data shown as mean plus standard deviation.
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PMC9335360
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gr5.jpg
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0.481479 |
8b89f1a82e054f9b93a84f65ce01d8f5
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Humoral immunity is required for protection from CCHFV challenge. Groups of WT or B-cell deficient μMT mice were vaccinated with 1μg of repNP + repGPC RNA or sham vaccinated in a prime-only vaccination four weeks prior to CCHFV challenge (a). On days -5 and -2 relative to CCHFV challenge, groups of repNP + repGPC vaccinated mice were treated with an isotype control or antibodies to deplete CD4 T-cells (α-CD4), CD8 T-cells (α-CD8) or both (α-CD4/ α-CD8) (a). Mice were weighed daily (b), monitored for survival (c) and body temperature monitored continuously using telemetry system (d). N = 16 for sham and 6-8 mice per other groups. Statistical comparisons performed using a two-way ANOVA with Dunnett's multiple comparisons test (b) or log-rank test with Bonferroni's correction for multiple comparisons (c). At day 5 p.i., viral loads in indicated tissues were quantified by qRT-PCR (e) and indicated statistical comparisons calculated using one-way ANOVA with Dunnett's multiple comparisons test. N = 6 per group. (b, d, e) Data shown as mean plus standard deviation. * P < 0.05, ** P < 0.01, *** P < 0.001.
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PMC9335360
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gr6.jpg
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0.479889 |
e5294dadd3a3424c84183838b2aeb402
|
Study Flow Diagram. TH/LD, Triamcinolone Hexacetonide group; LD, Lidocaine group.
|
PMC9335385
|
gr1.jpg
|
0.470544 |
3e05c0b726454d75bfa5300b204ee60a
|
Schematic representation of the PCSK9-induced LDLR and CD36 degradation in endosomes/lyosomes under regular or high fat diet. (A) LDLR degradation requires the catalytic subunit of PCSK9. Under high fat diet: (B) the absence of PCSK9 results in enhanced cell surface levels of the LDLR and CD36, and accumulaion of intracellular lipid droplets (LD); and (C) cell surface CD36 is partially reduced likely due to its ability to bind the PCSK9-CHRD and to enter endosomes even in the presence of a PCSK9 mAb targeting its catalytic subunit. The various LDLR domains are emphasized, as reported [93]. For PCSK9, the prodomain, catalytic, hinge (h) and CHRD M1, M2 and M3 subdomains are also shown
|
PMC9335453
|
11883_2022_1057_Fig1_HTML.jpg
|
0.4292 |
23d349000b554d07b10a62f399c1791f
|
Potential solvent exposed R-X-E motifs in MHC-II (A) α- and (B) β-chains both expressed on human chromosome 6. The predicted 3D structures are shown, and the variable positions of the framed R-X-E motifs are emphasized
|
PMC9335453
|
11883_2022_1057_Fig2_HTML.jpg
|
0.422382 |
73796012e7c94fac869f15c2d24a2de7
|
Effect of simazine concentration on cell concentration (A) and chlorophyll a content (B) of Aphanothece halophytica after various incubation durations.
|
PMC9335942
|
fbioe-10-904101-g001.jpg
|
0.508625 |
af0c6660a99341c6ae17334073b39cdc
|
Effect of simazine concentration on H2 production rate (A) and O2 production rate (B) by Aphanothece halophytica after 2 h of incubation under the light (open square) and under darkness (solid square). Data are presented as means ± SD (n = 3). Different letters above the columns indicate a significant difference according to Duncan’s multiple range test at p < 0.05.
|
PMC9335942
|
fbioe-10-904101-g002.jpg
|
0.407613 |
01f685b2c1e1491ab14d7e18131b1733
|
Long-term H2 accumulation of Aphanothece halophytica treated with and without 25 µM simazine during 10 days of dark anaerobic incubation. Aphanothece halophytica grown in BG11 for 7 days was harvested by centrifugation and suspended in BG110. Cells were incubated in BG110 under the light for 24 h before treatment with 25 µM simazine. Cells were purged with argon for 10 min and incubated at 30°C for 10 days under darkness. Cells without simazine treatment and simazine without cells were used as controls.
|
PMC9335942
|
fbioe-10-904101-g003.jpg
|
0.425955 |
076df9c161ca4e1394050f253dcbee40
|
Characteristics of DMU-214 loaded liposomes and non-loaded analog formulations: a) liposome size expressed as z-average (nm) and polydispersity index (PDI), b) DMU-214 encapsulation efficiency (%) and concentration in liposomal formulations (µM), c) zeta potential (mV), d) in vitro release profiles of DMU-214-loaded formulations at 0.3 D/L ratio – open circles represent experimentally determined values, lines – correspond to data predicted from Peppas-Sahlin mathematical model. Standard deviations were obtained from measurements (a, b, c) or experiments (d) repeated three times.
|
PMC9336483
|
IDRD_A_2103210_F0001_C.jpg
|
0.436059 |
c467314b1edb4b00bdc68421e736f975
|
Effect of free DMU-214 and DMU-214 loaded into three liposomal formulations DMPC (A), DPPC (B) and POPC (C) on the SK-OV-3 monolayer cultured cells. DMPC/DPPC/POPC blank: liposomes with DMPC/DPPC/POPC but without DMU-214, diluted by the same dilution factor as the liposomal formulations. The viability was measured using the MTT test after 72 h of drug exposure. IC50 values were calculated following a normalized dose-response inhibition curve fitting. Data represent mean values from three independent experiments ± SD.
|
PMC9336483
|
IDRD_A_2103210_F0002_C.jpg
|
0.433584 |
dc8f7ed17c5f4d1cb36f9c327f5f520c
|
Effect of free DMU-214 and DMU-214 loaded into three liposomal formulations DMPC (A, D), DPPC (B, E), POPC (C, F) on the SK-OV-3 and P-3 patient-derived spheroids. DMPC/DPPC/POPC blank: liposomes with DMPC/DPPC/POPC but without DMU-214, diluted by the same dilution factor as the liposomal formulations. Spheroid viability was measured using CellTiter Glo 3 D after 72 h exposure to the drugs. IC50 values were calculated following a normalized dose-response inhibition curve fitting. Data represent mean values from three independent experiments ± SD.
|
PMC9336483
|
IDRD_A_2103210_F0003_C.jpg
|
0.410803 |
c469f757483641aa827731b618938cca
|
Spheroids growth and morphology upon treatment with DMU-214 liposomal formulations (DMPC/DPPC/POPC). Spheroids were pre-formed for 7 days with 5 000 SK-OV-3 cells and treated with the indicated concentrations of DMU-214 formulations. The images were acquired 72 hours after administration of the formulation with the Olympus ix73 inverted microscope.
|
PMC9336483
|
IDRD_A_2103210_F0004_B.jpg
|
0.526996 |
bbfd34fc3c794567b936eb6ff302849e
|
GC–MS chromatogram of (A) chloroform and (B) hexane extracts of Cassia occidentalis. GC–MS = gas chromatography–mass spectrometry.
|
PMC9336676
|
jfda-24-03-508f1.jpg
|
0.404106 |
481d90d53d6f4bbbaf9fee03125538e1
|
HPTLC fingerprinting profile of Cassia occidentalis. HPTLC = high-performance thin layer chromatography.
|
PMC9336676
|
jfda-24-03-508f2.jpg
|
0.385008 |
0ff2f791b8664171859617460a338af7
|
mTOR and TSC1 mRNA expression in CD4+ T cells in CLP, lck-mTOR, and lck-TSC1 mice. Agarose gel electrophoresis of colony PCR (a) mTOR and (b) TSC1 genotyping.
|
PMC9338879
|
MI2022-6077570.001.jpg
|
0.471313 |
4561a92912fa47c996e6ea6852c3a548
|
Survival curves. Survival rates between CLP, CLP+NAC, CLP+C23, CLP+4-PBA, Lck-TSC1+CLP, and Lck-mTOR+CLP groups. During the first 18 hours after CLP operation, the survival conditions were regularly monitored every 2 hours and then observed every 6 hours. Median survival time of CLP was 64 h, and LCK-TSC1+CLP group was 56 h, while Lck-mTOR+CLP had a significantly prolonged median survival time of 104 h (Kaplan-Meier with log rank test). n = 10-14 mice per group. x-axis: survival time; y-axis: survival rate. P1 = LCK-TSC1+CLP vs. Lck-mTOR+CLP; P2 = CLP vs. Lck-mTOR+CLP. NAC = N-acetyl-L-cysteine; 4-PBA = sodium phenylbutyrate; C23 = CIRP-Ab; CIRP = cold-inducible RNA-binding protein.
|
PMC9338879
|
MI2022-6077570.002.jpg
|
0.430519 |
e820e962a5ca49be95e2b30af9bdc7f7
|
Expression levels of mTOR pathway proteins, ERS-associated proteins, and apoptosis-associated proteins in WT, CLP, and CLP+4-PBA mouse groups. After purifying the CD4+ T cells from mouse spleen lymphocytes, whole cell lysates were assessed for the protein expression of (a) patterns of mTOR pathway proteins, including mTOR, P-mTOR, downstream effectors p70s6k, p-p70s6k, 4EBP, and P-4EBP; (b) ERS-associated proteins, including GRP78 and CHOP; (c) apoptosis-associated proteins, including caspase-3, Bax, and Bcl-2. The protein expression was detected by immunoblotting. Data are mean ± SD. n = 4 biologically independent experiments (one-way ANOVA Tukey's post hoc test). ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001.
|
PMC9338879
|
MI2022-6077570.003.jpg
|
0.373193 |
6e8516276e1248c7af4e4a32f8971767
|
ERS-induced apoptosis leads to CD4+ T cell apoptosis in CLP mice. Apoptosis in CD4+ T cells from WT, CLP, and CLP+4-PBA mice was assessed by flow cytometry analysis. Apoptosis ratios are the early apoptosis percentage plus the late apoptosis percentage (a). x-axis: V-FITC; y-axis: PI. Left panel: gating strategy for apoptosis cells; right panel: percentage of apoptotic cells in the left panel. Graphs show means ± SD, four to six mice per group. Representative images of ER in CD4+ T cells from WT, CLP, and CLP+4-PBA mice, as observed by electron microscopy (b). Data are mean ± SD, n = 4 (one-way ANOVA Dunnett's post hoc test). Blue arrows represent normal-sized ER. Red arrows represent dilation and vesiculation of the ER. Scale bars = 0.5 μm. FITC: fluorescein isothiocyanate; PI: propidium iodide.
|
PMC9338879
|
MI2022-6077570.004.jpg
|
0.446404 |
26146534dff54233b12151741236825a
|
Role played by mTOR in ERS and CD4+ T cell apoptosis. CD4+ T cell apoptosis percentage was assessed by flow cytometry (a). Left panel: gating strategy for apoptosis cells; right panel: percentage of apoptotic cells in the left panel. Graphs show means ± SD, four mice per group. mRNA expression level of BIM in CD4+ T cells was analyzed by RT-PCR (b). Representative images of ER in CD4+ T cells from CLP, LCK-TSC1+CLP, and Lck-mTOR+CLP mice, as observed by electron microscopy (c). Data are mean ± SD, n = 4, analyzed using one-way ANOVA. Blue arrows represent the normal-sized ER. Red arrows represent dilation of the ER. Scale bars = 0.5 μm.
|
PMC9338879
|
MI2022-6077570.005.jpg
|
0.463059 |
efb72042d48b4ce7aa5e4777360c2518
|
CD4+ T cells were assessed for the expression of mTOR pathway-associated proteins, ERS-associated proteins, and apoptosis-associated proteins in WT, LCK-mTOR, LCK-TSC1, CLP, CLP+CIRP-Ab, CLP+NAC, LCK-TSC1+CLP, and Lck-mTOR+CLP mouse groups. Data are mean ± SD. Number of mice per group = 4 (one-way ANOVA Tukey's post hoc test). CD4+ T cells were purified from CIRP-Ab-treated mice, NAC-treated mice, TSC1 knockout mice, and mTOR mouse spleen lymphocytes. Total proteins were western blotted to identify the expression patterns of mTOR pathway proteins (P-mTOR, mTOR, p70s6k, p-p70s6k, P-4EBP, and 4EBP) (a); CIRP and ERS-associated proteins (GRP78 and CHOP) (b); and apoptosis-related proteins (caspase-3, Bax, and Bcl-2) (c).
|
PMC9338879
|
MI2022-6077570.006.jpg
|
0.412515 |
c75404ae7e294aa4b7ed6887b2a563d7
|
Role played by ROS in ERS and CD4+ T cell apoptosis. The apoptosis percentage of CD4+ T cell from WT, CLP, CLP+CIRP-Ab, and CLP+NAC mice was flow cytometrically determined (a). Left panel: gating strategy for apoptosis cells; right panel: percentage of apoptotic cells in the left panel. Data represent the mean ± SD. Graphs show means ± SD, four mice per group. CD4+ T cells were treated with CM-H2DCFDA for 45 min prior to ROS analysis by flow cytometry (b). Representative images of ER in CD4+ T cells from CLP, CLP+CIRP-Ab, and CLP+NAC mice, as observed by electron microscopy (c). Data are mean ± SD of 4 independent experiments (one-way ANOVA Tukey's post hoc test). Blue arrows indicate normal-sized ER. Red arrows indicate dilatation and vesiculation of the ER. Magnification, ×20,000; scale bars = 0.5 μm.
|
PMC9338879
|
MI2022-6077570.007.jpg
|
0.430911 |
472805f7a96644d88536087eb1a1cb93
|
Minimum spanning tree of the SARS-CoV-2 variants identified in samples (n = 21) collected in August 2020 and July 2021.
|
PMC9339135
|
GHEG2022-2270965.001.jpg
|
0.466543 |
917674b6f7f74f2097955423c3a320fd
|
Evolution of the SARS-CoV-2 variant in Texas over one year (August 2020 to July 2021).
|
PMC9339135
|
GHEG2022-2270965.002.jpg
|
0.403349 |
2743f497dac0440b8482200f8c29c04b
|
Two-dimensional ultrasound image. (A and B) 2D ultrasonography Transverse scan 2D gray scale shows normal size and shape of the right testis with no significant abnormalities in the parenchymal echogenicity, and color Doppler flow imaging (CDFI) shows scattered dotted and striped blood flow signals in the right testis. (C–F) Cross-sectional scan in two-dimensional grayscale showed parenchymal echogenicity in the left testis, with an area of approximately 16 × 11 × 10 mm of inhomogeneous hypoechogenic areas detected within the left testis. CDFI showed no significant blood flow signal within the inhomogeneous hypoechogenic lesion in the left testis, with a slightly abundant blood flow signal in the surrounding parenchyma. CDE showed no significant energy signal within the hypoechogenic lesion.
|
PMC9340090
|
gr1.jpg
|
0.411084 |
d5dc9d2049864bca8b793fd1cbde03e5
|
Left testis 45 s, 60 s, and 80 s CEUS plots. (A–C) CEUS: The ultrasound contrast agent was SonoVue (sulfur hexafluoride microbubble) from Bracco, Italy. 2.5 mL of sulfur hexafluoride microbubble suspension + 5 mL of sodium chloride injection was pushed through the patient left median elbow vein. In the arterial, venous, and delayed phases of the left testicular parenchyma, a 20 × 15 mm patch of the unenhanced area is seen (red star position in Figure 2), with contrast filling of the tissue around the unenhanced area starting at 45 s, peaking at 60 s and fading at 80 s (yellow arrow in Figure 2). (Color version of figure is available online.)
|
PMC9340090
|
gr2.jpg
|
0.391899 |
55b984526e504945bf51d3b7ca8d5cd2
|
Graph of ultrasonographic data analysis results. (A) Plot of fitted curve (TIC); (B) plot of time to peak (TTP) data analysis; (C) plot of maximum intensity (IMAX) analysis; (D) plot of rise time (RT) analysis. (E) Electrocardiogram. Quantitative ultrasonographic analysis: Access the Sonoliver workstation, retrieve the patient's CEUS motion picture and select the reference area and the analysis area. The reference area is the normal testicular tissue surrounding the area of interest; the analysis area is the target area of interest and is no smaller than 2 cm2. The system fits the contrast perfusion curve (TIC fit curve) according to a built-in function (Figure 3A). The TIC fitted curve gives a more realistic picture of the tissue perfusion information. The mean values of the quantitative parameters IMAX, RT, and TTP are obtained. The contrast peak time was 18.42 s (Figure 3B), the rise time was 11.67 s (Figure 3D), and the maximum peak concentration was 100% (Figure 3C), while the contrast peak time in the region of interest was 29.32 s, the rise time was 5.67 s, and the maximum peak concentration was 61.9%, which indicates that the region of interest is an ischaemic hypoperfusion zone. Atrial fibrillation with a heart rate of about 90 beats/min (Figure 3E).
|
PMC9340090
|
gr3.jpg
|
0.420626 |
3b39e20204374641961e4e41f6f2931d
|
Scrotal ultrasound findings at three months postoperatively. (A, B) 2D gray scale showed bilateral contrast of the testes and a reduction in the size of the left testis; (C, D) CDFI and energy Doppler showed good blood flow and energy signal in the right testis, and no significant blood flow and energy signal in the hypoechoic zone of the left testis; (E) elastography measured that the hypoechoic zone of the left testis was harder than the surrounding normal tissue; (F) CEUS showed a three-stage area of no enhancement in the left testis. The left testis was found to be reduced in size and hypoechoic in the left testis (considered to be a post-treatment change of segmental testicular infarction), while the right testis was of acceptable size and shape with no significant abnormalities in parenchymal echogenicity.
|
PMC9340090
|
gr4.jpg
|
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