Background and Aims
Although many studies revealed transcriptomic subtypes of HCC, concordance of the subtypes are not fully examined. We aim to examine a consensus of transcriptomic subtypes and ...correlate them with clinical outcomes.
Approach and Results
By integrating 16 previously established genomic signatures for HCC subtypes, we identified five clinically and molecularly distinct consensus subtypes. STM (STeM) is characterized by high stem cell features, vascular invasion, and poor prognosis. CIN (Chromosomal INstability) has moderate stem cell features, but high genomic instability and low immune activity. IMH (IMmune High) is characterized by high immune activity. BCM (Beta‐Catenin with high Male predominance) is characterized by prominent β‐catenin activation, low miRNA expression, hypomethylation, and high sensitivity to sorafenib. DLP (Differentiated and Low Proliferation) is differentiated with high hepatocyte nuclear factor 4A activity. We also developed and validated a robust predictor of consensus subtype with 100 genes and demonstrated that five subtypes were well conserved in patient‐derived xenograft models and cell lines. By analyzing serum proteomic data from the same patients, we further identified potential serum biomarkers that can stratify patients into subtypes.
Conclusions
Five HCC subtypes are correlated with genomic phenotypes and clinical outcomes and highly conserved in preclinical models, providing a framework for selecting the most appropriate models for preclinical studies.
Microglial cells are endowed with different potassium ion channels but their expression and specific functions have remained to be fully clarified. This study has shown Kv1.2 expression in the ...amoeboid microglia in the rat brain between 1 (P1) and 10 (P10) days of age. Kv1.2 expression was localized in the ramified microglia at P14 and was hardly detected at P21. In postnatal rats exposed to hypoxia, Kv1.2 immunoreactivity in microglia was markedly enhanced. Quantitative RT-PCR analysis confirmed Kv1.2 mRNA expression in microglial cells in vitro. It was further shown that Kv1.2 and protein expression coupled with that of interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α) was significantly increased when the cells were subjected to hypoxia. The same increase was observed in cells exposed to adenosine 5'-triphosphate (ATP) and lipopolysaccharide (LPS). Concomitantly, the intracellular potassium concentration decreased significantly. Blockade of Kv1.2 channel with rTityustoxin-Kα (TsTx) resulted in partial recovery of intracellular potassium concentration accompanied by a reduced expression of IL-1β and TNF-α mRNA and protein expression and intracellular reactive oxygen species (ROS) production. We conclude that Kv1.2 in microglia modulates IL-1β and TNF-α expression and ROS production probably by regulating the intracellular potassium concentration.
Percutaneous ventricular restoration therapy with the use of a left ventricle (LV)–partitioning Parachute device has emerged as a clinical treatment option for LV apical aneurysm after extensive ...anterior myocardial infarction (AMI). We assessed changes of diastolic mechanics and functional improvements following LV Parachute device implantation by means of cardiac computerized tomography (CCT).
CCT data were obtained from 28 patients before and after LV Parachute device implantation. Diastolic functional indices were determined by means of quantitative CCT assessment: 1) transmitral velocities in early (E) and late (A) diastole and ratio (E/A); 2) early diastolic mitral septal tissue velocity (Ea) and E/Ea; and 3) vortex formation time (VFT). Functional improvements were assessed with the use of New York Heart Association (NYHA) functional classification. Among the study patients, there were no significant differences in all transmitral velocities and E/A, though there was significantly increased Ea, reduced E/Ea, and greater VFT 6 months after LV Parachute device implantation. Finally, the improvement of diastolic functional indices after Parachute treatment correlated with observed clinical functional alterations (Δ E/Ea and Δ NYHA functional class:, r = 0.563; P = .002; Δ VFT and Δ NYHA functional class: r = −0.507; P = .006).
LV Parachute device implantation therapy in heart failure caused by AMI and LV apical aneurysm formation showed improvements in several diastolic functional mechanics according to CCT-based measures.
New near-infrared-luminescent mesoporous materials were prepared by linking ternary lanthanide (Er
3+, Nd
3+, Yb
3+, Sm
3+, Pr
3+) complexes to the ordered mesoporous MCM-41 through a functionalized ...1,10-phenanthroline (phen) group 5-(
N,
N-bis-3-(triethoxysilyl)propyl)ureyl-1,10-phenanthroline. The resulting materials (denoted as Ln(hfth)
3phen–M41 and Pr(tfnb)
3phen–M41; Ln
=
Er, Yb, Nd, Sm; hfth
=
4,4,5,5,6,6,6-heptafluoro-1-(2-thienyl)hexane-1,3-dionate; tfnb
=
4,4,4-trifluoro-1-(2-naphthyl)-1,3-butanedionate) were characterized by powder X-ray diffraction, N
2 adsorption/desorption, and elemental analysis. Luminescence spectra of these lanthanide-complex functionalized materials were recorded, and the luminescence decay times were measured. Upon excitation at the absorption of the organic ligands, all these materials show the characteristic NIR luminescence of the corresponding lanthanide (Er
3+, Nd
3+, Yb
3+, Sm
3+, Pr
3+) ions by sensitization from the organic ligands moiety. The good luminescent performances enable these NIR-luminescent mesoporous materials to have possible applications in optical amplification (operating at 1300 or 1500
nm), laser systems, or medical diagnostics.
Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) commonly coexist with overlapping pathophysiology like left atrial (LA) remodeling, which might differ given ...different underlying mechanisms.
We sought to investigate the different patterns of LA wall remodeling in AF vs. HFpEF.
We compared LA wall characteristics including wall volume (LAWV), wall thickness (LAWT), and wall thickness heterogeneity (LAWTSD) and LA structure, function among the controls (without AF or HFpEF,
= 115), HFpEF alone (
= 59), AF alone (
= 37), and HFpEF+AF (
= 38) groups using multi-detector computed tomography and echocardiography.
LA wall remodeling was most predominant and peak atrial longitudinal strain (PALS) was worst in HFpEF+AF patients as compared to the rest. Despite lower E/e' (9.8 ± 3.8 vs. 13.4 ± 6.4) yet comparable LA volume, LAWT and PALS in AF alone vs. HFpEF alone, LAWV 12.6 (11.6-15.3) vs. 12.0 (10.2-13.7);
= 0.01 and LAWT(SD) 0.68 (0.61-0.71) vs. 0.60 (0.56-0.65);
< 0.001 were significantly greater in AF alone vs. HFpEF alone even after multi-variate adjustment and propensity matching. After excluding the HFpEF+AF group, both LAWV and LAWT SD provided incremental values when added to PALS or LAVi (all p for net reclassification improvement <0.05) in discriminating AF alone, with LAWTSD yielding the largest C-statistic (0.78, 95% CI: 0.70-0.86) among all LA wall indices.
Despite a similar extent of LA enlargement and dysfunction in HFpEF vs. AF alone, larger LAWV and LAWT SD can distinguish AF from HFpEF alone, suggesting the distinct underlying pathophysiological mechanism of LA remodeling in AF vs. HFpEF.
The crystal structures of ternary Ln(DBM)3phen complexes (DBM = dibenzoylmethane, phen = 1,10-phenanthroline, and Ln = Nd, Yb) and their in situ syntheses via the sol−gel process are reported. The ...properties of the Ln(DBM)3phen complexes and their corresponding Ln3+/DBM/phen-co-doped luminescent hybrid gels obtained via an in situ method (Ln−D−P gel) have been studied. The results reveal that the lanthanide complexes are successfully in situ synthesized in the corresponding Ln−D−P gels. Both Ln(DBM)3phen complexes and Ln−D−P gels display sensitized near-infrared (NIR) luminescence upon excitation at the maximum absorption of the ligands, which contributes to the efficient energy transfer from the ligands to the Ln3+ ions (Ln = Nd, Yb), an antenna effect. The radiative properties of the Nd3+ ion in a Nd−D−P gel are discussed using Judd−Ofelt analysis, which indicates that the 4F3/2 → 4I11/2 transition of the Nd3+ ion in the Nd−D−P gel can be considered as a possible laser transition.
Chronic enteritis can produce an excess of reactive oxygen species resulting in cellular damage. Stanniocalcin-1(STC-1) reportedly possesses anti-oxidative activity, the aim of this study was to ...define more clearly the direct contribution of STC-1 to anti-oxidative stress in cattle. In this study, primary intestinal epithelial cells (IECs) were exposed to hydrogen peroxide (H2O2) for different time intervals to mimic chronic enteritis-induced cellular damage. Prior to treatment with 200 µM H2O2, the cells were transfected with a recombinant plasmid for 48 h to over-express STC-1. Acridine orange/ ethidium bromide (AO/EB) double staining and trypan blue exclusion assays were then performed to measure cell viability and apoptosis of the cells, respectively. The expression of STC-1 and apoptosis-related proteins in the cells was monitored by real-time PCR and Western blotting. The results indicated that both STC-1 mRNA and protein expression levels positively correlated with the duration of H2O2 treatment. H2O2 damaged the bovine IECs in a time-dependent manner, and this effect was attenuated by STC-1 over-expression. Furthermore, over- expression of STC-1 up-regulated Bcl-2 protein expression and slightly down-regulated caspase-3 production in the damaged cells. Findings from this study suggested that STC-1 plays a protective role in intestinal cells through an antioxidant mechanism.
The ternary lanthanide complexes Ln(hfth)
3phen (Ln
=
Er, Nd, Yb, Sm) and Pr(tfnb)
3phen have been successfully covalently attached in the ordered SBA-15 mesoporous materials via a functionalized ...1,10-phenanthroline group 5-(
N,
N-bis-3-(triethoxysilyl)propyl)ureyl-1,10-phenanthroline (Phen-Si). The derivative materials denoted as Ln(hfth)
3phen–S15 and Pr(tfnb)
3phen–S15; Ln
=
Er, Yb, Nd, Sm; hfth
=
4,4,5,5,6,6,6-heptafluoro-1-(2-thienyl)hexane-1,3-dionate; tfnb
=
4,4,4-trifluoro-1-(2-naphthyl)-1,3-butanedionate were characterized by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), and N
2 adsorption/desorption. The fluorescence spectra and luminescence lifetimes of these lanthanide-complex-functionalized materials were also recorded. After ligand-mediated excitation, the emission spectra of the Ln(hfth)
3phen–S15 and Pr(tfnb)
3phen–S15 materials all display the characteristic NIR luminescence of the corresponding lanthanide ions through the intramolecular energy transfer from the ligands to the lanthanide ions. With these lanthanide-complex-functionalized materials, the luminescent spectral region from 1300 to 1600
nm, which is of particular interest for telecommunication applications, can be covered completely.
Abstract Aim To describe the relationship between a novel measurement of peri-arotic root fat and ultrasound measures of carotid artery remodeling. Materials and methods We studied 1492 consecutive ...subjects (mean age: 51.04 ± 8.97 years, 27% females) who underwent an annual cardiovascular risk survey in Taiwan. Peri-aortic root fat (PARF) was assessed by cardiac CT using three-dimensional (3D) volume assessment. Carotid artery morphology and remodeling were assessed by ultrasound. We explored the relationships between PARF volumes, cardiometabolic risk profiles and carotid morphology and remodeling. Results Mean PARF volume in current study was 20.8 ± 10.6 ml. PARF was positively correlated with measures of general adiposity, systemic inflammation, and several traditional cardiometabolic risk profiles (all p < 0.001) and successfully predicted metabolic syndrome (MetS) (AUROC: 0.75, 95%, confidence interval: 0.72–0.77). Higher PARF was independently associated with increased carotid artery intima-media thickness (IMT) (β-coef.: 0.08) and diameter (β-coef.: 0.08, both p < 0.05) after accounting for age, sex, BMI and other cardiovascular risk factors. The addition of PARF beyond metabolic syndrome components significantly provided incremental prediction value for abnormal IMT (ΔAUROC: 0.053, p = 0.0021). Conclusion Peri-aortic root fat is associated with carotid IMT, even after adjustment for cardiometabolic risks, age and coronary atherosclerosis. Further research studies are warranted to identify the mediators of downstream pathophysiologic effects on carotid arteries by PARF and understand the mechanisms related to this correlation.
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