Systemic transplantation of adipose-derived stem cells (ASCs) is emerging as a novel therapeutic option for functional recovery of diverse damaged tissues. This study investigated the effects of systemic transplantation of human ASCs (hASCs) on bone repair. We found that hASCs secrete various bone cell-activating factors, including hepatocyte growth factor and extracellular matrix proteins. Systemic transplantation of hASCs into ovariectomized mice induced an increased number of both osteoblasts and osteoclasts in bone tissue and thereby prevented bone loss. We also observed that conditioned medium from hASCs is capable of stimulating proliferation and differentiation of osteoblasts via Smad/extracellular signal-regulated kinase (ERK)/JNK (c-jun NH(2) -terminal kinase) activation as well as survival and differentiation of osteoclasts via ERK/JNK/p38 activation in vitro. Overall, our findings suggest that paracrine factors secreted from hASCs improve bone repair and that hASCs can be a valuable tool for use in osteoporosis therapy.

This study sought to determine the correlation between baseline cardiac medications and cardiovascular outcomes in patients with obstructive coronary artery disease (CAD) diagnosed by coronary computed tomographic angiography (CCTA).

Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) enables state-of-the-art in vivo evaluations of myocardial fibrosis. Although LGE patterns have been well described in asymmetrical septal hypertrophy, conflicting results have been reported regarding the characteristics of LGE in apical hypertrophic cardiomyopathy (ApHCM). This study was undertaken to determine 1) the frequency and distribution of LGE and 2) its prognostic implication in ApHCM.

We aimed to evaluate effect of heart rate (HR) reduction on left ventricular reverse remodeling (LVRR) in Korean patients with heart failure with reduced ejection fraction (HFrEF).

Cytokines and chemokines are transcriptionally regulated by inflammatory transcription factors such as nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and interferon regulatory factor (IRF)-3. A daidzein derivative compound, 8-hydroxydaidzein (8-HD), isolated from soy products, has recently gained attention due to various pharmacological benefits, including anti-inflammatory activities. However, regulation of the inflammatory signaling mechanism for 8-HD is still poorly understood, particularly with respect to the IRF-3 signaling pathway. In this study, we explored the molecular mechanism of 8-HD in regulating inflammatory processes, with a focus on the IRF-3 signaling pathway using a lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid [Poly (I:C)] stimulated murine macrophage cell line (RAW264.7). The 8-HD downregulated the mRNA expression level of IRF-3-dependent genes by inhibiting phosphorylation of the IRF-3 transcription factor. The inhibitory mechanism of 8-HD in the IRF-3 signaling pathway was shown to inhibit the kinase activity of IKKε to phosphorylate IRF-3. This compound can also interfere with the TRIF-mediated complex formation composed of TRAF3, TANK, and IKKε leading to downregulation of AKT phosphorylation and reduction of IRF-3 activation, resulted in inhibition of IRF-3-dependent expression of genes including IFN-β, C-X-C motif chemokine 10 (CXCL10), and interferon-induced protein with tetratricopeptide repeats 1 (IFIT1). Therefore, these results strongly suggest that 8-HD can act as a promising compound with the regulatory function of IRF-3-mediated inflammatory responses.

Small objects of an alloy tool steel were built by selective laser melting at different scan speeds, and their microstructures were analyzed using electron backscatter diffraction (EBSD). To present an explicit correlation with the local thermal cycles in the objects, prior austenite grains were reconstructed using the EBSD mapping data. Extensive growth of austenitic grains after solidification could be detected by the disagreement between the networks of carbides and austenite grain boundaries. A rapid laser scan at 2000 mm/s led to less growth, but retained a larger amount of austenite than a slow one at 50 mm/s. The rapid scan also exhibited definite evolution of Goss-type textures in austenite, which could be attributed to the growth of austenitic grains under a steep temperature gradient. The local variations in the microstructures and the textures enabled us to speculate the locally different thermal cycles determined by the different process conditions, that is, scan speeds.

Adiponectin is an adipocytokine with insulin-sensitizing, anti-inflammatory, anti-atherosclerotic, and anti-aging properties. Compounds with the ability to promote adiponectin secretion are of interest for the development of anti-aging drugs to improve skin-aging phenotypes. In the phenotypic assay to measure adiponectin secretion during adipogenesis in human adipose tissue-derived mesenchymal stem cells (hAT-MSCs), kojyl cinnamate ester derivatives increased adiponectin secretion. A target identification study showed that the kojyl cinnamate ester derivatives competitively bound to peroxisome proliferator-activated receptor α/γ (PPARα/γ). The upregulation of adiponectin production induced by kojyl cinnamate ester derivatives was significantly correlated with PPARα and PPARγ binding activities. Kojyl cinnamate ester derivatives significantly increased the transcription of genes encoding cholesterol and fatty acid synthesizing enzymes in hAT-MSCs. Notably, the kojyl cinnamate esters upregulated the gene transcription of lipid metabolic enzymes in human epidermal keratinocytes, which are important in the integrity of skin permeability barrier. In addition, the kojyl cinnamate esters that function as PPARα/γ dual modulators inhibited ultraviolet B irradiation-induced inflammation in human epidermal keratinocytes. Therefore, kojyl cinnamate ester derivatives are a novel class of PPARα/γ dual agonists with the potential to improve skin-aging phenotypes.

CTCF is crucial to the organization of mammalian genomes into loop structures. According to recent studies, the transcription apparatus is compartmentalized and concentrated at super-enhancers to form phase-separated condensates and drive the expression of cell-identity genes. However, it remains unclear whether and how transcriptional condensates are coupled to higher-order chromatin organization. Here, we show that CTCF is essential for RNA polymerase II (Pol II)-mediated chromatin interactions, which occur as hyperconnected spatial clusters at super-enhancers. We also demonstrate that CTCF clustering, unlike Pol II clustering, is independent of liquid-liquid phase-separation and resistant to perturbation of transcription. Interestingly, clusters of Pol II, BRD4, and MED1 were found to dissolve upon CTCF depletion, but were reinstated upon restoration of CTCF, suggesting a potent instructive function for CTCF in the formation of transcriptional condensates. Overall, we provide evidence suggesting that CTCF-mediated chromatin looping acts as an architectural prerequisite for the assembly of phase-separated transcriptional condensates.

Trimethylamine N-oxide (TMAO), a gut microbe-dependent metabolite, has been implicated as a novel risk factor for cardiovascular events related to obesity and type 2 diabetes mellitus (T2DM). The aim of the study was to test the hypothesis if TMAO is associated with the reduction of cardiovascular disease in the Korean obese patients who underwent bariatric surgery. From a subgroup of a multicenter, nonrandomized, controlled trial, titled KOBESS, 38 obese patients, 18 with and 20 without T2DM, who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were investigated. Bariatric surgery is indicated for Korean patients with a body mass index (BMI) ≥ 35 kg/m2 or for Korean patients with a BMI ≥ 30 kg/m2 who have comorbidities. Serum levels of TMAO and its precursors, betaine, carnitine, and choline were measured before and six months after bariatric surgery. The levels of TMAO and its precursors did not differ between obese patients with T2DM and non-T2DM at baseline. However, TMAO increased more than twofold in patients with T2DM after RYGB surgery, but not in patients without T2DM. Choline levels were decreased by half in all patients after RYGB. In patients with T2DM who underwent SG, TMAO, betaine, and carnitine levels did not change after the surgery. Furthermore, in obese patients who underwent bariatric surgery, increased TMAO levels were associated with both T2DM and RYGB, while reduced choline levels were associated with RYGB. These associations need to be further elucidated in follow-up studies to gain further insights into the relationship between TMAO levels and bariatric surgery outcomes.

Atherosclerosis-related adverse events are commonly observed even in conditions with low cardiovascular (CV) risk. Longitudinal data regarding the association of normal systolic blood pressure maintenance (SBPmaintain ) with coronary plaque volume changes (PVC) has been limited in adults without traditional CV disease.

Although rarefaction of myocardial angiogenesis has been shown to be associated with left ventricular (LV) systolic dysfunction in animal models of ventricular hypertrophy, this relationship has not been investigated in depth nor validated in humans. We aimed to analyze the relationship of myocardial angiogenesis with various functional and structural ventricular remodeling parameters in moderate to severe aortic stenosis (AS) patients with normal LV ejection fraction (LVEF).

Despite a rich choice of two-dimensional materials, which exists these days, heterostructures, both vertical (van der Waals) and in-plane, offer an unprecedented control over the properties and functionalities of the resulted structures. Thus, planar heterostructures allow p-n junctions between different two-dimensional semiconductors and graphene nanoribbons with well-defined edges; and vertical heterostructures resulted in the observation of superconductivity in purely carbon-based systems and realisation of vertical tunnelling transistors. Here we demonstrate simultaneous use of in-plane and van der Waals heterostructures to build vertical single electron tunnelling transistors. We grow graphene quantum dots inside the matrix of hexagonal boron nitride, which allows a dramatic reduction of the number of localised states along the perimeter of the quantum dots. The use of hexagonal boron nitride tunnel barriers as contacts to the graphene quantum dots make our transistors reproducible and not dependent on the localised states, opening even larger flexibility when designing future devices.

Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent ≥ 64-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n = 690) were matched 1:1:1 to those with 1 component (n = 690) and 2 components (n = 690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p < 0.05), while those with 2 components did not (10.5% vs 13.8%, 2.8% vs 4.5% and 1.3% vs 2.3%, respectively; p > 0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p = 0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p = 0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome.

Obesity-induced chronic low-grade inflammation, in particular in adipose tissue, contributes to the development of insulin resistance and type 2 diabetes. However, the mechanism by which obesity induces adipose tissue inflammation has not been completely elucidated. Recent studies suggest that alteration of the nuclear lamina is associated with age-associated chronic inflammation in humans and fly. These findings led us to investigate whether the nuclear lamina regulates obesity-mediated chronic inflammation. In this study, we show that lamin A/C mediates inflammation in macrophages. The gene and protein expression levels of lamin A/C are significantly increased in epididymal adipose tissues from obese rodent models and omental fat from obese human subjects compared to their lean controls. Flow cytometry and gene expression analyses reveal that the protein and gene expression levels of lamin A/C are increased in adipose tissue macrophages (ATMs) by obesity. We further show that ectopic overexpression of lamin A/C in macrophages spontaneously activates NF-κB, and increases the gene expression levels of proinflammatory genes, such as Il6, Tnf, Ccl2, and Nos2. Conversely, deletion of lamin A/C in macrophages reduces LPS-induced expression of these proinflammatory genes. Importantly, we find that myeloid cell-specific lamin A/C deficiency ameliorates obesity-induced insulin resistance and adipose tissue inflammation. Thus, our data suggest that lamin A/C mediates the activation of ATM inflammation by regulating NF-κB, thereby contributing to the development of obesity-induced insulin resistance.

To develop, demonstrate and evaluate an automated deep learning method for multiple cardiovascular structure segmentation.

Phase transition points can be used to critically reduce the ionic migration activation energy, which is important for realizing high-performance electrolytes at low temperatures. Here, we demonstrate a route toward low-temperature thermionic conduction in solids, by exploiting the critically lowered activation energy associated with oxygen transport in Ca-substituted bismuth ferrite (Bi1-xCaxFeO3-δ) films. Our demonstration relies on the finding that a compositional phase transition occurs by varying Ca doping ratio across xCa ≃ 0.45 between two structural phases with oxygen-vacancy channel ordering along <100> or <110> crystal axis, respectively. Regardless of the atomic-scale irregularity in defect distribution at the doping ratio, the activation energy is largely suppressed to 0.43 eV, compared with ~0.9 eV measured in otherwise rigid phases. From first-principles calculations, we propose that the effective short-range attraction between two positively charged oxygen vacancies sharing lattice deformation not only forms the defect orders but also suppresses the activation energy through concerted hopping.

Cell labeling technologies are required to monitor the fate of transplanted cells in vivo and to select target cells for the observation of certain changes in vitro. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been transplanted for the treatment of heart injuries or used in vitro for preclinical cardiac safety assessments. Cardiomyocyte (CM) labeling has been used in these processes to facilitate target cell monitoring. However, the functional effect of the labeling agent on hiPSC-CMs has not been studied. Therefore, we investigated the effects of labeling agents on CM cellular functions. 3'-Dioctadecyloxacarbocyanine perchlorate (DiO), quantum dots (QDs), and a DNA plasmid expressing EGFP using Lipo2K were used to label hiPSC-CMs. We conclude that the hiPSC-CM labeling with DiO and QDs does not induce arrhythmogenic effects but rather improves the mRNA expression of cardiac ion channels and Ca2＋ influx by L-type Ca2＋ channels. Thus, DiO and QD labeling agents may be useful tools to monitor transplanted CMs, and further in vivo influences of the labeling agents should be investigated in the future.

Differential diagnosis of left ventricular hypertrophy (LVH) is often obscure on echocardiography and requires numerous additional tests. We aimed to develop a deep learning algorithm to aid in the differentiation of common etiologies of LVH (i.e. hypertensive heart disease [HHD], hypertrophic cardiomyopathy [HCM], and light-chain cardiac amyloidosis [ALCA]) on echocardiographic images. Echocardiograms in 5 standard views (parasternal long-axis, parasternal short-axis, apical 4-chamber, apical 2-chamber, and apical 3-chamber) were obtained from 930 subjects: 112 with HHD, 191 with HCM, 81 with ALCA and 546 normal subjects. The study population was divided into training (n = 620), validation (n = 155), and test sets (n = 155). A convolutional neural network-long short-term memory (CNN-LSTM) algorithm was constructed to independently classify the 3 diagnoses on each view, and the final diagnosis was made by an aggregate network based on the simultaneously predicted probabilities of HCM, HCM, and ALCA. Diagnostic performance of the algorithm was evaluated by the area under the receiver operating characteristic curve (AUC), and accuracy was evaluated by the confusion matrix. The deep learning algorithm was trained and verified using the training and validation sets, respectively. In the test set, the average AUC across the five standard views was 0.962, 0.982 and 0.996 for HHD, HCM and CA, respectively. The overall diagnostic accuracy was significantly higher for the deep learning algorithm (92.3%) than for echocardiography specialists (80.0% and 80.6%). In the present study, we developed a deep learning algorithm for the differential diagnosis of 3 common LVH etiologies (HHD, HCM and ALCA) by applying a hybrid CNN-LSTM model and aggregate network to standard echocardiographic images. The high diagnostic performance of our deep learning algorithm suggests that the use of deep learning can improve the diagnostic process in patients with LVH.

Owing to the destruction of ozone layer, the increased exposure to UV on the earth adversely affects not only skin diseases but also wound healing. Although the demand for sunscreens is increasing to protect the human skin from these adverse effects, commercially available sunscreens have some limitations in safety. In this study, silk fibroin (SF) composite with biocompatibility and blood coagulation activity was prepared for a highly safe sunscreen. However, the SF has a disadvantage in that it is difficult to dissolve in water. To improve the solubility of SF, butyl glycidyl ether (BGE) was reacted with the side chain of SF to prepare a freely water-soluble SF (mSF) derivative, and the phase behavior according to the mixing ratio of SF derivative and tannic acid (TA) was observed. In addition, ZnO nanoparticles were added to the mSF-TA solution to form a hydrogel through the coordination bonding. The UV blocking, hemostatic, antibacterial and antioxidant effects of the mSF/TA/ZnO composite hydrogel were evaluated, and the excellent skin compatibility of multifunctional hydrogel sunscreen was confirmed through a skin irritation test.

Dendritic cells are antigen-presenting cells orchestrating innate and adaptive immunity. The crucial role of transcription factors and histone modifications in the transcriptional regulation of dendritic cells has been extensively studied. However, it is not been well understood whether and how three-dimensional chromatin folding controls gene expression in dendritic cells. Here we demonstrate that activation of bone marrow-derived dendritic cells induces extensive reprogramming of chromatin looping as well as enhancer activity, both of which are implicated in the dynamic changes in gene expression. Interestingly, depletion of CTCF attenuates GM-CSF-mediated JAK2/STAT5 signaling, resulting in defective NF-κB activation. Moreover, CTCF is necessary for establishing NF-κB-dependent chromatin interactions and maximal expression of pro-inflammatory cytokines, which prime Th1 and Th17 cell differentiation. Collectively, our study provides mechanistic insights into how three-dimensional enhancer networks control gene expression during bone marrow-derived dendritic cells activation, and offers an integrative view of the complex activities of CTCF in the inflammatory response of bone marrow-derived dendritic cells.