Recent studies suggest an association between diabetes and increased risk of heart failure (HF). However, the associations among obesity status, glycemic status, and risk of HF are not known. In this ...study, we analyzed whether the risk of HF increases in participants according to baseline glycemic status and whether this increased risk is associated with obesity status.
We analyzed the risk of HF according to baseline glycemic status (normoglycemia, impaired fasting glucose IFG, and diabetes) in 9,720,220 Koreans who underwent Korean National Health Screening in 2009 without HF at baseline with a median follow-up period of 6.3 years. The participants were divided into five and six groups according to baseline body mass index (BMI) and waist circumference, respectively.
Participants with IFG and those with diabetes showed a 1.08- and 1.86-fold increased risk of HF, respectively, compared to normoglycemic participants. Compared to the normal weight group (BMI, 18.5 to 22.9 kg/m²), the underweight group (BMI <18.5 kg/m²) showed a 1.7-fold increased risk of HF, and those with BMI ≥30 kg/m² showed a 1.1-fold increased risk of HF, suggesting a J-shaped association with BMI. When similar analyses were performed for different glycemic statuses, the J-shaped association between BMI and HF risk was consistently observed in both groups with and without diabetes.
Participants with IFG and diabetes showed a significantly increased HF risk compared to normoglycemic participants. This increased risk of HF was mostly prominent in underweight and class II obese participants than in participants with normal weight.
Dabie bandavirus (severe fever with thrombocytopenia syndrome virus SFTSV) induces an immunopathogenic disease with a high fatality rate; however, the mechanisms underlying its clinical ...manifestations are largely unknown. In this study, we applied targeted proteomics and single-cell transcriptomics to examine the differential immune landscape in SFTS patient blood. Serum immunoprofiling identified low-risk and high-risk clusters of SFTS patients based on inflammatory cytokine levels, which corresponded to disease severity. Single-cell transcriptomic analysis of SFTS patient peripheral blood mononuclear cells (PBMCs) at different infection stages showed pronounced expansion of B cells with alterations in B-cell subsets in fatal cases. Furthermore, plasma cells in which the interferon (IFN) pathway is downregulated were identified as the primary reservoir of SFTSV replication. This study identified not only the molecular signatures of serum inflammatory cytokines and B-cell lineage populations in SFTSV-induced fatalities but also plasma cells as the viral reservoir. Thus, this suggests that altered B-cell function is linked to lethality in SFTSV infections.
SFTSV is an emerging virus discovered in China in 2009; it has since spread to other countries in East Asia. Although the fatality rates of SFTSV infection range from 5.3% to as high as 27%, the mechanisms underlying clinical manifestations are largely unknown. In this study, we demonstrated that SFTSV infection in fatal cases caused an excessive inflammatory response through high induction of proinflammatory cytokines and chemokines and the aberrant inactivation of adaptive immune responses. Furthermore, single-cell transcriptome sequencing (RNA-seq) analysis of SFTS patient PBMCs revealed that SFTSV targets the B-cell lineage population, especially plasma cells, as the potential viral reservoir in patients for whom the infection is fatal. Thus, SFTSV infection may inhibit high-affinity antibody maturation and secretion of plasma B cells, suppressing neutralizing antibody production and thereby allowing significant virus replication and subsequent fatality.
Background
We examined the incidence and predictors of clinical outcomes in metabolic dysfunction‐associated fatty liver disease (MAFLD), focusing on anthropometric parameters.
Methods
Adult patients ...with MAFLD were identified in nationwide databases and a hospital cohort. Primary endpoints were atherosclerotic cardiovascular disease (ASCVD) and advanced fibrosis. Logistic and Cox regression analyses were used to analyse the association between anthropometric parameters and endpoints.
Results
In total, 4407 of 15 256 (28.9%) and 6274 of 25 784 subjects (24.3%) had MAFLD in the nationwide database; of these, 403 (9.2%) and 437 (7.0%) subjects were of lean/normal weight, respectively. Compared to the overweight/obese group, the lean/normal weight group had a significantly lower muscle mass (15.0 vs. 18.9 kg) and handgrip strength (31.9 vs. 35.1 kg) and had a higher ASCVD risk (9.0% vs. 6.3% and 15.9% vs. 8.5%; Ps < 0.001). Sarcopenia (odds ratio OR, 6.66; 95% confidence interval CI, 1.79–24.80) and handgrip strength (OR, 0.92; 95% CI, 0.86–0.97; Ps = 0.005) were associated with the ASCVD risk in the lean/normal weight group. In a hospital cohort (n = 1363), the ASCVD risk was significantly higher in the lean/normal weight group than in the overweight/obese group (median follow‐up, 39.1 months). Muscle mass was inversely correlated with the ASCVD risk (hazard ratio HR, 0.72; 95% CI, 0.56–0.94), while visceral adiposity was associated with advanced fibrosis (HR, 1.36; 95% CI, 1.10–1.69; Ps < 0.05).
Conclusions
Muscle mass/strength was significantly associated with the ASCVD risk in patients with MAFLD. Visceral adiposity was an independent predictor of advanced fibrosis.
Exercise is recommended for type 2 diabetes mellitus (T2DM) patients to prevent cardiovascular disease. However, the effects of physical activity (PA) for reducing the risk of heart failure (HF) has ...yet to be elucidated. We aimed to assess the effect of changes in patterns of PA on incident HF, especially in newly diagnosed diabetic patients.
We examined health examination data and claims records of 294,528 participants from the Korean National Health Insurance Service who underwent health examinations between 2009 and 2012 and were newly diagnosed with T2DM. Participants were classified into the four groups according to changes in PA between before and after the diagnosis of T2DM: continuously inactive, inactive to active, active to inactive, and continuously active. The development of HF was analyzed until 2017.
As compared with those who were continuously inactive, those who became physically active after diagnosis showed a reduced risk for HF (adjusted hazard ratio aHR, 0.79; 95% confidence interval CI, 0.66 to 0.93). Those who were continuously active had the lowest risk for HF (aHR, 0.77; 95% CI, 0.62 to 0.96). As compared with those who were inactive, those who exercised regularly, either performing vigorous or moderate PA, had a lower HF risk (aHR, 0.79; 95% CI, 0.69 to 0.91).
Among individuals with newly diagnosed T2DM, the risk of HF was reduced in those with higher levels of PA after diagnosis was made. Our results suggest either increasing or maintaining the frequency of PA after the diagnosis of T2DM may lower the risk of HF.
Osteoblasts and osteoclasts play crucial roles in bone formation and bone resorption. We found that plum-derived exosome-like nanovesicles (PENVs) suppressed osteoclast activation and modulated ...osteoblast differentiation. PENVs increased the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells and osteoblasts from mouse bone marrow cultures. Notably, PENVs elevated the expression of osteoblastic transcription factors and osteoblast differentiation marker proteins in MC3T3-E1 cells. Higher levels of phosphorylated BMP-2, p38, JNK, and smad1 proteins were detected in PENV-treated MC3T3-E1 cells. Additionally, the number of TRAP-positive cells was significantly decreased in PENV-treated osteoclasts isolated from osteoblasts from mouse bone marrow cultures. Importantly, osteoclastogenesis of marker proteins such as PPAR-gamma, NFATc1, and c-Fos were suppressed by treatment with PENVs (50 μg/mL). Taken together, these results demonstrate that PENVs can be used as therapeutic targets for treating bone-related diseases by improving osteoblast differentiation and inhibiting osteoclast activation for the first time.
Background
In a previous study, the modified Marsh and Schnider models respectively showed negatively‐ and positively‐biased predictions in underweight patients. To overcome this drawback, we ...developed a new pharmacokinetic propofol model‐the Choi model‐for use in underweight patients. In the present study, we evaluated the predictive performance of the Choi model.
Methods
Twenty underweight patients undergoing elective surgery received propofol via TCI using the Choi model. The target effect‐site concentrations (Ces) of propofol were 2.5, 3, 3.5, 4, 4.5, and 2 μg/mL. Arterial blood samples were obtained at least 10 minutes after achieving pseudo‐steady‐state. Predicted propofol concentrations with the modified Marsh, Schnider, and Eleveld pharmacokinetic models were obtained by simulation (Asan pump, version 2.1.3; Bionet Co. Ltd., Seoul, Korea). The predictive performance of each model was assessed by calculation of four parameters: inaccuracy, divergence, bias, and wobble.
Results
A total of 119 plasma samples were used to determine the predictive performance of the Choi model. Our evaluation showed that the pooled median (95% CI) bias and inaccuracy were 4.0 (−4.2 to 12.2) and 23.9 (17.6‐30.3), respectively. The pooled biases and inaccuracies of the modified Marsh, Schnider, and Eleveld models were clinically acceptable. However, the modified Marsh and Eleveld models consistently produced negatively biased predictions in underweight patients. In particular, the Schnider model showed greater inaccuracy at a target Ce ≥ 3 µg/mL.
Conclusion
The new propofol pharmacokinetic model (the Choi model) developed for underweight patient showed adequate performance for clinical use.
Abstract Currently approved surgical tissue glues do not satisfy the requirements for ideal bioadhesives due to limited adhesion in wet conditions and severe cytotoxicity. Herein, we report a new ...light-activated, mussel protein-based bioadhesive (LAMBA) inspired by mussel adhesion and insect dityrosine crosslinking chemistry. LAMBA exhibited substantially stronger bulk wet tissue adhesion than commercially available fibrin glue and good biocompatibility in both in vitro and in vivo studies. Besides, the easily tunable, light-activated crosslinking enabled an effective on-demand wound closure and facilitated wound healing. Based on these outstanding properties, LAMBA holds great potential as an ideal surgical tissue glue for diverse medical applications, including sutureless wound closures of skin and internal organs.
Nutrient deprivation strategies have been proposed as an adjuvant therapy for cancer cells due to their increased metabolic demand. We examined the specific inhibitory effects of amino acid ...deprivation on the metastatic phenotypes of the human triple-negative breast cancer (TNBC) cell lines MDA-MB-231 and Hs 578T, as well as the orthotopic 4T1 mouse TNBC tumor model. Among the 10 essential amino acids tested, methionine deprivation elicited the strongest inhibitory effects on the migration and invasion of these cancer cells. Methionine deprivation reduced the phosphorylation of focal adhesion kinase, as well as the activity and mRNA expression of matrix metalloproteinases MMP-2 and MMP-9, two major markers of metastasis, while increasing the mRNA expression of tissue inhibitor of metalloproteinase 1 in MDA-MB-231 cells. Furthermore, methionine restriction downregulated the metastasis-related factor urokinase plasminogen activatior and upregulated plasminogen activator inhibitor 1 mRNA expression. Animals on the methionine-deprived diet showed lower lung metastasis rates compared to mice on the control diet. Taken together, these results suggest that methionine restriction could provide a potential nutritional strategy for more effective cancer therapy.
In spintronics, two-dimensional van der Waals crystals constitute a most promising material class for long-distance spin transport or effective spin manipulation at room temperature. To realize ...all-vdW-material-based spintronic devices, however, vdW materials with itinerant ferromagnetism at room temperature are needed for spin current generation and thereby serve as an effective spin source. We report theoretical design and experimental realization of a iron-based vdW material, Fe
GeTe
, showing a nearly room temperature ferromagnetic order, together with a large magnetization and high conductivity. These properties are well retained even in cleaved crystals down to seven layers, with notable improvement in perpendicular magnetic anisotropy. Our findings highlight Fe
GeTe
and its nanometer-thick crystals as a promising candidate for spin source operation at nearly room temperature and hold promise to further increase
in vdW ferromagnets by theory-guided material discovery.
Populus trichocarpa
has been studied as a model poplar species through biomolecular approaches and was the first tree species to be genome sequenced. In this study, we employed a high throughput ...RNA-sequencing (RNA-seq) mediated leaf transcriptome analysis to investigate the response of four different
Populus davidiana
cultivars to drought stress. Following the RNA-seq, we compared the transcriptome profiles and identified two differentially expressed genes (DEGs) with contrasting expression patterns in the drought-sensitive and tolerant groups, i.e., upregulated in the drought-tolerant
P. davidiana
groups but downregulated in the sensitive group. Both these genes encode a 9-cis-epoxycarotenoid dioxygenase (
NCED
), a key enzyme required for abscisic acid (ABA) biosynthesis. The high-performance liquid chromatography (HPLC) measurements showed a significantly higher ABA accumulation in the cultivars of the drought-tolerant group following dehydration. The Arabidopsis
nced3
loss-of-function mutants showed a significantly higher sensitivity to drought stress, ~90% of these plants died after 9 days of drought stress treatment. The real-time PCR analysis of several key genes indicated a strict regulation of drought stress at the transcriptional level in the
P. davidiana
drought-tolerant cultivars. The transgenic
P. davidiana
NCED3 overexpressing (OE) plants were significantly more tolerant to drought stress as compared with the NCED knock-down RNA interference (RNAi) lines. Further, the NCED OE plants accumulated a significantly higher quantity of ABA and exhibited strict regulation of drought stress at the transcriptional level. Furthermore, we identified several key differences in the amino acid sequence, predicted structure, and co-factor/ligand binding activity of NCED3 between drought-tolerant and susceptible
P. davidiana
cultivars. Here, we presented the first evidence of the significant role of
NCED
genes in regulating ABA-dependent drought stress responses in the forest tree
P. davidiana
and uncovered the molecular basis of
NCED3
evolution associated with increased drought tolerance.
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