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This cross-sectional study enrolled 267 patients with metabolic risk factors and established non-alcoholic fatty liver disease in the prospective cohort. The performance of fibrosis-4 (FIB-4) score (≥1.3) to diagnose advanced fibrosis using transient elastography (liver stiffness measurement [LSM] ≥8 kPa) was analyzed. Comparing patients with type 2 diabetes (T2D, n=87) and without (n=180), not FIB-4, but LSM was significantly higher in T2D (P=0.026). The prevalence of advanced fibrosis was 17.2% in T2D and 12.8% in non-T2D. FIB-4 exhibited higher proportion of false negatives in T2D patients (10.9%) than those without (5.2%). The diagnostic performance of FIB-4 was suboptimal in T2D (area under curve [AUC], 0.653; 95% confidence interval [CI], 0.462 to 0.844) compared to that in non-T2D (AUC, 0.826; 95% CI, 0.724 to 0.927). In conclusion, patients with T2D might be beneficial to conduct transient elastography without screening to avoid missing advanced fibrosis.

The prevalence of diabetes in Korea is increasing and presents significant challenges to the healthcare system, the economy, and society. Some experts had predicted that the number of patients with diabetes would exceed 6 million by 2050, but this number has been reached three decades earlier than expected in Korea. This tremendous increase is due to accumulation of diabetic patients as the population ages and obesity prevalence rapidly increases. According to the Diabetes Fact Sheet of 2022, the percentage of people with diabetes was more than 30% in the population older than 65 years. To address these challenges, preemptive strategies such as rigorous screening and risk stratifications are necessary. The Korean Diabetes Association has lowered the age for diabetes screening from 45 to 35 years. In support of this, young-onset diabetes is more threatening than that in older people due to higher glucose level at diagnosis, greater obesity, and poor adherence. To prevent diabetes, appropriate education and publicity programs for proper eating habits and increased physical activity are needed. Awareness must be increased on the importance of proper care in young-onset diabetes. In conclusion, the increase in diabetes in Korea is a significant health issue that requires urgent attention.

Background: To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus.Methods: This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed.Results: The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by –0.68%±1.39% and –1.91±3.37 kg (both P

Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic condition that affects nearly one billion people globally, characterized by triacylglycerol accumulation in the liver as a consequence of metabolic abnormalities (obesity and impaired glucose regulation). Low-grade inflammation, oxidative stress, mitochondrial dysfunction, and dysbiosis in gut microbiota are involved in the etiology of MAFLD, and both cardiovascular events and hepatic complications are the long-term consequences. In the absence of approved therapies for this condition, sodium-glucose cotransporter 2 inhibitors (SGLT-2 Is) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have the specific advantage of lowering body weight and providing cardiovascular benefits. Here, we discuss potential roles for SGLT-2 Is and GLP-1 RAs in the prevention and treatment of intrahepatic triacylglycerol accumulation and associated inflammation and/or fibrosis.

Diabetes is one of the major comorbidities associated with increased risk of mortality and severe clinical outcomes in coronavirus disease 19 (COVID-19) patients. Thus, timely and appropriate vaccination is the most effective strategy for mitigating the risk of COVID-19 infection in people with diabetes. Recent studies have shown that immune response after vaccination is significant in both diabetes and non-diabetes groups, but slightly lower in patients with diabetes. Inadequate glucose control might impair the immune response. Blood glucose monitoring is required more often than usual for several days after vaccination. If a patient’s blood glucose is not controlled adequately, appropriate management should be provided.

Background: The aim of this study was to evaluate the 10-year efficacy and safety of laser ablation (LA) for the treatment of solitary papillary thyroid microcarcinoma (PTMC). Methods: LA was perfo...

Endocrine-disrupting chemical perfluorooctane sulfonate (PFOS) acute exposure stimulates insulin secretion from pancreatic β-cells. However, chronic exposure to PFOS on pancreatic β-cells, its role in insulin secretion, and the underlying mechanisms have not been studied. We used rat insulinoma INS-1 and human 1.1b4 islet cells to investigate the chronic effects of PFOS on glucose-stimulated insulin secretion and toxicity implicated in the downregulation of β-cell functionality. Chronic exposure of INS-1 cells or human pancreatic 1.1b4 β-cells to PFOS stimulated the small G-protein RAC1-guanosine triphosphate-dependent nicotinamide adenine dinucleotide phosphate oxidase (NOX2/gp91phox) subunit expression and activation. Upregulated NOX2/gp91phox activation led to elevated reactive oxygen species (ROS) production with a decrease in the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway in both cell types. Inhibition of cAMP/PKA signaling induces β-cell mitochondrial dysfunction and endoplasmic stress via the loss of PDX1-SERCA2B and glucose-stimulated insulin release. Inhibiting RAC1-NOX2/gp91phox activation or elevating cAMP by pentoxifylline, a Food and Drug Administration-approved phosphodiesterase inhibitor, significantly reduced PFOS-induced ROS production and restored insulin secretory function of pancreatic β-cells. Enhanced secretory function in pentoxifylline-treated cells was associated with increased stability of PDX1-SERCA2B protein levels. Intriguingly, inhibition of cAMP/PKA signaling impaired pentoxifylline-induced insulin secretion caused by the activation of ROS production and mitochondrial dysfunction. Overall, our findings show that PFOS has a new and first-ever direct chronic effect on pancreatic β-cell failure through increased RAC1-NOX2/gp91phox activation and pentoxifylline-induced cAMP/PKA signaling, which inhibits PFOS-mediated mitochondrial dysfunction.

This study aimed to evaluate the effect of early glycaemic variability (GV) on 28-day mortality in critically ill patients with pneumonia.This single-centre retrospective study included patients admitted to the intensive care unit (ICU) due to pneumonia between 2018 and 2019. A total of 282 patients (mean age, 68.6 years) with blood sugar test (BST) results measured more than three times within 48 h after hospitalization and haemoglobin A1c (HbA1c) levels recorded within 2 months were enrolled. Coefficient of variation (CV) was calculated using the BST values. The effects of GV on 28-day mortality and prolonged ICU stay (14 days) were also assessed.The mean age was 60.6 years (male to female ratio, 2.5:1). The 28-day mortality rate was 31.6% (High GV within 48 h of ICU admission was associated with an increased 28-day mortality risk and prolonged ICU stay. Early phase GV should be carefully managed in critically ill patients with pneumonia.KEY MESSAGESThe presence of diabetes or HbA1c alone is insufficient to predict 28-day mortality and prolonged ICU stay in critically ill patients with pneumonia.High glycaemic variability (GV) within 48 h of ICU admission increases 28-day mortality and prolongs ICU stay, which is consistent after adjusting for severity of illness and treatment strategy.Patients with high GV, especially those with DM or low HbA1c levels (7.5%) should be more carefully treated to reduce mortality.

arped disk galaxies are classified into two morphologies: S- and U-types. Conventional theories routinely attribute both types to galactic tidal interaction and/or gas accretion, but reproducing of U-types in simulations is extremely challenging. Here we investigate whether both types are governed by the same mechanisms using the most extensive sample of $\sim$8000 nearby (0.02\,$$\,$10^9$) edge-on disks from SDSS. We find that U-types show on average bluer optical colors and higher specific star formation rate (sSFR) than S-types, with more strongly warped U-types having higher sSFR. We also find that while the S-type warp properties correlate with the tidal force by the nearest neighbor regardless of the environment, there is no such correlation for U-types in groups/clusters, suggesting a non-tidal environmental could be at play for U-types, such as ram pressure stripping (RPS). Indeed, U-types are more common in groups/clusters than in fields and they have stellar mass, gas fraction, sSFR enhancement and phase-space distribution closely analogous to RPS-induced jellyfish galaxies in clusters. We furthermore show that the stellar disks of most RPS galaxies in the IllustirsTNG simulation are warped in U-shape and bent in opposite direction of stripped gas tails, satisfying theoretical expectations for stellar warps embeded in jellyfishes. We therefore suggest that despite the majority of U-types that live in fields being still less explained, RPS can be an alternative origin for those in groups/clusters., 28 pages, 15 figures, accpeted for publication in ApJ

Myostatin (MSTN) is a well-reported negative regulator of muscle growth and a member of the transforming growth factor (TGF) family. MSTN has important functions in skeletal muscle (SM), and its crucial involvement in several disorders has made it an important therapeutic target. Several strategies based on the use of natural compounds to inhibitory peptides are being used to inhibit the activity of MSTN. This review delivers an overview of the current state of knowledge about SM and myogenesis with particular emphasis on the structural characteristics and regulatory functions of MSTN during myogenesis and its involvements in various muscle related disorders. In addition, we review the diverse approaches used to inhibit the activity of MSTN, especially in silico approaches to the screening of natural compounds and the design of novel short peptides derived from proteins that typically interact with MSTN.

Background: One of the leading causes of chronic kidney disease, DKD is associated with increased oxidative stress and chronic inflammation. CU01-10is dimethyl fumarate (DMF) which being developed for treatment of DKD. DMF attenuated renal fibrosis via the Nrf2-mediated inhibition of TGF-b/Smad3 signaling in an antioxidant response element independent manner in preclinical model, suggesting that DMF can be potentially effective against kidney damage. In this study, we investigated the efficacy and safety of CU01-10in patient with DKD. Methods: For this randomized, double-blinded phase 2a clinical trial for the efficacy and safety assessment, we enrolled 42 adults with DKD (estimated glomerular filtration rate (eGFR) 30 to 89 ml/min/1.73m2) with albuminuria to be treated with CU01-10 (120mg twice a day) or placebo. We measured the change from baseline in urine albumin creatinine ratio (uACR) and eGFR at 12 weeks for primary outcomes. Results: A total of 39 patients were evaluated for primary efficacy analysis. CU01-10group showed significant increase of eGFR (+ 3.80±8.72 ml/min/1.73m2at week 12, from baseline) , and there was a significant intergroup difference of eGFR at 6 and 12 weeks (p=0.0349 and p=0.0121, respectively) . CU01-10group was statistically significantly decreased in the mean ACR (p=0.0441) but not for placebo group (p=0.1336) , and after 12 weeks, CU01-10group (-39.65 mg/g) showed lower median uACR from the baseline than placebo (-16.90 mg/g) . In DMF group, no severe adverse events were reported during the trial and the most common adverse events were nausea (n=3) and skin flushing (n=3) . Conclusion: CU01-10showed an improvement of uACR and eGFR compared to placebo for patients with DKD, with no major drug-related adverse events. Disclosure J.Moon: None. K.Won: None. M.Kim: None. I.Lee: n/a. S.Kwon: None. J.Pyo: None. J.Kang: None. Y.Kwon: None. H.Seo: None.

AimWe explored the prospective relationship between continuous glucose monitoring (CGM) metrics and clinical outcomes in patients admitted to the intensive care unit (ICU).Materials and MethodsWe enrolled critically ill patients admitted to the medical ICU. Patients with an Acute Physiology and Chronic Health Evaluation (APACHE) score ≤9 or ICU stay ≤48 h were excluded. CGM was performed for five days, and standardized CGM metrics were analyzed. The duration of ICU stay and 28-day mortality rate were evaluated as outcomes.ResultsA total of 36 patients were included in this study (age [range], 49–88 years; men, 55.6%). The average APACHE score was 25.4 ± 8.3; 33 (91.7%) patients required ventilator support, and 16 (44.4%) patients had diabetes. The duration of ICU stay showed a positive correlation with the average blood glucose level, glucose management indicator (GMI), time above range, and GMI minus (-) glycated hemoglobin (HbA1c). Eight (22.2%) patients died within 28 days, and their average blood glucose levels, GMI, and GMI-HbA1c were significantly higher than those of survivors (pConclusionThe acute glycemic gap, assessed as GMI-HbA1c, is an independent risk factor for longer ICU stay and 28-day mortality rate. In the ICU setting, CGM of critically ill patients might be beneficial, irrespective of the presence of diabetes.

BACKGROUND: The glomerular filtration rate (GFR) and albumin-to-creatinine ratio (ACR) have been widely used to identify and manage diabetic kidney disease (DKD). However, classifications based on these two indices do not always concur in terms of DKD diagnosis; for example, cases of high ACR with normal GFR or normal ACR with low GFR may occur. A recent study suggested that critical shear stress (CSS), a hemorheological parameter to represent aggregating force of red blood cells (RBCs), is a potential screening index for DKD. In the present study, we investigated the diagnostic potential of CSS for DKD according to the KDIGO 2012 Guideline. METHODS: A total of 378 patients with type 2 diabetes who visited Yeungnam University Hospital between 2014 and 2017 were included. CSS was measured using a transient microfluidic hemorheometer, Rheoscan-D300® (Rheomeditech, Seoul, Republic of Korea) with whole blood. Patients who were DKD negative (green zone) were compared with patients who were DKD positive (red zone) as Model 1 and patients at risk for (orange zone) and red zones as Model 2, respectively. RESULTS: After exclusion criteria such as eGFR

We present a numerical evidence supporting the scenario that the peculiar alignments of the galaxy stellar spins with the major principal axes of the local tidal tensors are produced during the quiescent evolution period when the galaxies experience no recent merger events. Analyzing the merger tree from the TNG300-1 simulation of the IllustrisTNG project, we find the latest merger epochs, $a(z_{m})$, of the galaxies, and create four $a(z_{m})$-selected samples that are controlled to share the identical mass and density distributions. For each sample, we determine the spin and shape vectors of the galaxy stellar, cold and hot gas, and dark matter components separately, and compute the average strengths of their alignments with the principal directions of the local tidal fields as well as their mutual alignment tendencies. It is found that the stellar (cold gas) spin axes of the galaxies whose latest merger events occur at earlier epochs are more strongly aligned (weakly anti-aligned) with the major principal axes of the tidal fields. It is also shown that although the mass-dependent transition of the galaxy DM spins have little connection with the merger events, the morphologies, spin-shape and shape-shear alignment strengths of the galaxy four components sensitively depend on $a(z_{m})$. Noting that the stellar components of the galaxies which undergo long quiescent evolution have distinctively oblate shapes and very strong spin-shape alignments, we suggest that the local tidal field might be traced by using the stellar shapes of galaxies without signatures of mergers as a proxy of their stellar spins., accepted for publication in ApJ, 11 figures, revised version

We report the discovery of a rare early-type dwarf galaxy (dE), SDSS J125651.47+163024.2 (hereafter dE1256), possessing a tidal feature that was likely built up by accretion of an even smaller dwarf galaxy. dE1256 is located in a nearly isolated environment, at the outskirt of the Virgo cluster. A detailed morphological examination reveals that the accreted stellar population is mainly deposited in the outer part of dE1256, where the tidal tail is most prominent. The inner part of dE1256 is perfectly modeled with a simple S\'ersic function of index n = 0.63 and half-light radius R$_{h}$ = 0.6 kpc, but in contrast, the entire galaxy has a size of R$_{h}$ = 1.2 kpc. The mass ratio between the host and the putative accreted dwarf galaxy is calculated to be 5:1, assuming that the observed two components, inner S\'ersic, and outer tidal tail residual, represent the host's and accreted galaxy's stellar populations, respectively. We suggest that while the accretion contributes only 20% of the overall stellar population, the size of dE1256 grew by a factor of two via the accretion event. Our results provide, for the first time, strong observational evidence that a dE is undergoing a two-phase growth, a common phenomenon for massive galaxies., Comment: Accepted for publication in MNRAS

Chronic oxidative stress, which is caused by aberrant non-receptor tyrosine kinase (c-Abl) signaling, plays a key role in the progression of β-cell loss in diabetes mellitus. Recent studies, however, have linked ferroptotic-like death to the β-cell loss in diabetes mellitus. Here, we report that oxidative stress-driven reduced/oxidized glutathione (GSH/GSSG) loss and proteasomal degradation of glutathione peroxidase 4 (GPX4) promote ferroptotic-like cell damage through increased lipid peroxidation. Mechanistically, treatment with GNF2, a non-ATP competitive c-Abl kinase inhibitor, selectively preserves β-cell function by inducing the orphan nuclear receptor estrogen-related receptor gamma (ERRγ). ERRγ-driven glutaminase 1 (GLS1) expression promotes the elevation of the GSH/GSSG ratio, and this increase leads to the inhibition of lipid peroxidation by GPX4. Strikingly, pharmacological inhibition of ERRγ represses the expression of GLS1 and reverses the GSH/GSSG ratio linked to mitochondrial dysfunction and increased lipid peroxidation mediated by GPX4 degradation. Inhibition of GLS1 suppresses the ERRγ agonist DY131-induced GSH/GSSG ratio linked to ferroptotic-like death owing to the loss of GPX4. Furthermore, immunohistochemical analysis showed enhanced ERRγ and GPX4 expression in the pancreatic islets of GNF2-treated mice compared to that in streptozotocin-treated mice. Altogether, our results provide the first evidence that the orphan nuclear receptor ERRγ-induced GLS1 expression augments the glutathione antioxidant system, and its downstream signaling leads to improved β-cell function and survival under oxidative stress conditions.

We explore how the galaxy stellar spins acquire a peculiar tendency of being aligned with the major principal axes of the local tidal fields, in contrast to their DM counterparts which tend to be perpendicular to them, regardless of their masses. Analyzing the halo and subhalo catalogs from the IllustrisTNG 300 hydrodynamic simulations at $z\le 1$, we determine the cosines of the alignment angles, $\cos\alpha$, between the galaxy stellar and DM spins. Creating four $\cos\alpha$-selected samples of the galaxies and then controlling them to share the same density and mass distributions, we determine the average strengths of the alignments between the galaxy stellar spins and the tidal tensor major axes over each sample. It is clearly shown that at $z\le 0.5$ the more severely the galaxy stellar spin directions deviate from the DM counterparts, the stronger the peculiar tidal alignments become. Taking the ensemble averages of such galaxy properties as central blackhole to stellar mass ratio, specific star formation rate, formation epoch, stellar-to-total mass ratio, velocity dispersions, average metallicity, and degree of the cosmic web anisotropy over each sample, we also find that all of these properties exhibit either strong correlations or anti-correlations with $\cos\alpha$. Our results imply that the peculiar tidal alignments of the galaxy stellar spins may be caused by anisotropic occurrence of some baryonic process responsible for discharging stellar materials from the galaxies along the tidal major directions at $z, Comment: accepted for publication in ApJ, 11 figures, 1 tables, minor revision

In the published publication [...]

Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are synthetic chemicals that have been used in various industries and household products. These can easily accumulate in the human body, causing adverse effects on human health. In this study, a high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous analysis of PFOA and linear PFOS in human serum. Owing to a lack of PFOA- and PFOS-free human serum

We investigated the long-term effect of changes in hepatic steatosis on the risk of developing T2DM.We evaluated 3510 participants from the 2001-2016 Korean Genome and Epidemiology Study. Those with significant alcohol consumption or T2DM during 2001-2004 were excluded. Steatosis was defined as non-alcoholic fatty liver disease-liver fat score (NAFLD-LFS) of over -0.64, and baseline values were assessed between 2001 and 2002. Differences in NAFLD-LFS (ΔLFS) and changes in steatosis status (no, intermittent [resolved or incident], and persistent steatosis) were assessed between 2003 and 2004. Changes in the risk of diabetes status were observed until 2016.Over 52,650 person-years of follow-up, T2DM developed in 296 participants (8.4%). The incidence of diabetes in those with no steatosis, intermittent steatosis, and persistent steatosis during follow-up increased by 5.1%, 14.1%, and 27.1% respectively. Multivariate-adjusted analysis revealed that the risk was higher in those with persistent steatosis than those with no steatosis and intermittent steatosis. Baseline NAFLD-LFS and ΔLFS was associated with increased risk of incident T2DM.Initial severity as well as aggravation of steatosis is an independent predictor of incident T2DM. Strategies aimed at reducing liver fat may prevent future development of diabetes among patients with NAFLD.

A numerical detection of the mass-dependent spin transition of the galaxies is presented. Analyzing a sample of the galaxies with stellar masses in the range of $10^{9}< (M_{\star}/M_{\odot})\le 10^{11}$ from the IllustrisTNG300-1 simulations, we explore the alignment tendency between the galaxy baryon spins and the three eigenvectors of the linearly reconstructed tidal field as a function of $M_{\star}$ and its evolution in the redshift range of $0\le z \le 1.5$. Detecting a significant signal of the occurrence of the mass-dependent transition of the galaxy spins, we show that the centrals differ from the satellites in their spin transition type. As $M_{\star}$ increases beyond a certain threshold mass, the preferred directions of the central galaxy spins transit from the minor to the intermediate tidal eigenvectors (type two) at $z=0.5$ and $1$, while those of the satellites transit from the minor to the major tidal eigenvectors (type one) at $z=1$ and $1.5$. It is also shown that the mass range and type of the spin transition depend on the galaxy morphology, degree of the alignments between the baryon and total spin vectors as well as on the environmental density. Meanwhile, the stellar spins of the galaxies are found to yield a weak signal of the T1 transitions at $z=0$, whose strength and trend depend on the degree of the alignments between the stellar and baryon spins. The possible mechanisms responsible for the T1 and T2 spin transitions are discussed., Accepted for publication in ApJ, 16 figures, 5 tables, improved analysis, focus switched to the baryon spins