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Aim: To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add-on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D)., Materials and Methods: This multicentre, randomized, 104-week, open-label trial randomized 105 patients with drug-naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104., Results: HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was -2.56% in the TCT group vs. -2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well-tolerated and had fewer adverse events than SAT., Conclusions: Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined., Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months., Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Due to the increasing demand for the development of efficient renewable energy supply systems to reduce the mismatch between energy demand and utilization, supercapacitors have attracted increasing attention in the energy industry. However, the development of energy storage electrode materials to be applied at the industrial level is still challenging due to the unsatisfactory durability and scalable production issues. This study suggested a facile and scalable one-pot fabrication method of using graphene/hexagonal boron nitride (G/BN)-based one-dimensional (1D) van der Waals superlattice heterostructures (vdWSLs) as highly stable electrode materials to enhance the energy storage performance by improving the mesopore volume content, specific surface area, electrical properties, and interfacial interaction between the stacked G/BN layers. The G/BN-based vdWSLs were fabricated by a simple scrolling process through the electromagnetic interaction between the attached magnetic iron oxide nanoparticles (Fe 3 O 4 NPs) on the surface of a G/BN vdW heterostructure (vdWH) and the applied magnetic field. The investigation results demonstrate that the changed morphology of the fabricated G/Fe/BN(NS) strongly affects the fine pore distribution, electrochemical performance, and electrical properties. Consequently, as a synergistic effect of an increased mesopore volume content, specific surface area, and C-B-N heterojunction interfacial area, the fabricated G/Fe/BN(NS) electrode showed a 100% enhancement of specific capacitance (207 F g -1 at 0.5 A g -1 ) and almost 7 times enhancement of electrical conductivity (800 S cm -1 ) with a nearly 2.3 times increase of carrier mobility (716 cm 2 V -1 s -1 ) compared to that of the G/Fe/BN electrode. Furthermore, it exhibited outstanding long-term cycling stability with almost 119% capacitance retention even after 100 000 charge-discharge cycles. These results suggest that G/Fe/BN(NS) has tremendous potential as an electrode to fabricate high-performance supercapacitors with excellent cycling stability.

Transforming growth factor β (TGFβ) is present in blood of patients who do not respond to anti-programmed cell death (ligand) 1 [PD-(L)1] treatment, and through synergy with vascular endothelial growth factor (VEGF), it helps to create an environment that promotes tumor immune evasion and immune tolerance. Therefore, simultaneous inhibition of TGFβ/VEGF is more effective than targeting TGFβ alone. In this study, the dual inhibitory mechanism of TU2218 was identified through in vitro analysis mimicking the tumor microenvironment, and its antitumor effects were analyzed using mouse syngeneic tumor models. TU2218 directly restored the activity of damaged cytotoxic T lymphocytes (CTLs) and natural killer cells inhibited by TGFβ and suppressed the activity and viability of regulatory T cells. The inactivation of endothelial cells induced by VEGF stimulation was completely ameliorated by TU2218, an effect not observed with vactosertib, which inhibits only TGFβ signaling. The combination of TU2218 and anti-PD1 therapy had a significantly greater antitumor effect than either drug alone in the poorly immunogenic B16F10 syngeneic tumor model. The mechanism of tumor reduction was confirmed by flow cytometry, which showed upregulated VCAM-1 expression in vascular cells and increased influx of CD8 + CTLs into the tumor. As another strategy, combination of anti-CTLA4 therapy and TU2218 resulted in high complete regression (CR) rates in CT26 and WEHI-164 tumor models. In particular, immunological memory generated by the combination of anti-CTLA4 and TU2218 in the CT26 model prevented the development of tumors after additional tumor cell transplantation, suggesting that the TU2218-based combination has therapeutic potential in immunotherapy., (© 2024. The Author(s).)

This research designs a triphasic Ni 2 P-Ni 12 P 5 -Ru heterostructure with amorphous interface engineering strongly coupled by a cobalt nano-surface (Co@Ni m P n -Ru) to form a hierarchical 3D interconnected architecture. The Co@Ni m P n -Ru material promotes unique reactivities toward hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline media. The material delivers an overpotential of 30 mV for HER at 10 mA cm -2 and 320 mV for OER at 50 mA cm -2 in freshwater. The electrolyzer cell derived from Co@Ni m P n -Ru (+,-) requires a small cell voltage of only 1.43 V in alkaline freshwater or 1.44 V in natural seawater to produce 10 mA cm -2 at a working temperature of 80 °C, along with high performance retention after 76 h. The solar energy-powered electrolyzer system also shows a prospective solar-to-hydrogen conversion efficiency and sufficient durability, confirming its good potential for economic and sustainable hydrogen production. The results are ascribed to the synergistic effects by an exclusive combination of multi-phasic crystalline Ni 2 P, Ni 12 P 5 , and Ru clusters in presence of amorphous phosphate interface attached onto cobalt nano-surface, thereby producing rich exposed active sites with optimized free energy and multi open channels for rapid charge transfer and ion diffusion to promote the reaction kinetics., (© 2024 Wiley‐VCH GmbH.)

Background: Effective bowel cleansing is essential for a successful colonoscopy. Laxatives, such as polyethylene glycol, are commonly used for bowel preparation. Vomiting is a frequent complication during bowel preparation, and forceful vomiting can potentially lead to esophageal perforation, as reported in several previous cases. However, pharyngeal perforation during bowel preparation has not been previously documented. Here, we present a case of pharyngeal perforation induced by forceful vomiting during bowel preparation., Case Summary: A 38-year-old man with a history of hypertension, dyslipidemia, diabetes mellitus, and end-stage renal disease on hemodialysis was admitted for evaluation of recurrent abdominal pain. The patient complained of sudden pain in the neck, throat, and anterior chest following forceful vomiting during bowel preparation. Physical examination revealed crepitus under the skin of the neck and anterior chest on palpation, and upper gastrointestinal endoscopy revealed pharyngeal perforation. The perforation site was located above the upper esophageal sphincter, which distinguished it from Boerhaave's syndrome. Conservative medical management was chosen after consultation with a thoracic surgeon and an otolaryngologist, considering the patient's mild symptoms, stable vital signs, and the small size of the lesion; the perforation resolved without endoscopic or surgical intervention. The patient was discharged from hospital two weeks after the perforation., Conclusion: Despite its rarity, pharyngeal perforation should be considered a potential complication of bowel preparation for colonoscopy., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

High-performance production of green hydrogen gas is necessary to develop renewable energy generation technology and to safeguard the living environment. This study reports a controllable engineering approach to tailor the structure of nickel-layered double hydroxides via doped and absorbed platinum single atoms (Pt SA ) promoted by low electronegative transition metal (Mn, Fe) moieties (Pt SA -Mn,Fe-Ni LDHs). We explore that the electron donation from neighboring transition metal moieties results in the well-adjusted d -band center with the low valence states of Pt SA(doped) and Pt SA(ads.) , thus optimizing adsorption energy to effectively accelerate the H 2 release. Meanwhile, a tailored local chemical environment on transition metal centers with unique charge redistribution and high valence states functions as the main center for H 2 O catalytic dissociation into oxygen. Therefore, the Pt SA -Mn,Fe-Ni LDH material possesses a small overpotential of 42 and 288 mV to reach 10 mA·cm -2 for hydrogen and oxygen evolution, respectively, superior to most reported LDH-based catalysts. Additionally, the mass activity of Pt SA -Mn,Fe-Ni LDHs proves to be 15.45 times higher than that of commercial Pt-C. The anion exchange membrane electrolyzer stack of Pt SA -Mn,Fe-Ni LDHs (+,-) delivers a cell voltage of 1.79 V at 0.5 A·cm -2 and excellent durability over 600 h. This study presents a promising electrocatalyst for a practical water splitting process.

Background: Progressive deterioration of β-cell function is a characteristic of type 2 diabetes mellitus (T2DM). We aimed to investigate the relative contributions of clinical factors to β-cell function in T2DM., Methods: In a T2DM cohort of 470 adults (disease duration 0 to 41 years), β-cell function was estimated using insulinogenic index (IGI), disposition index (DI), oral disposition index (DIO), and homeostasis model assessment of β-cell function (HOMA-B) derived from a 75 g oral glucose tolerance test (OGTT). The relative contributions of age, sex, disease duration, body mass index, glycosylated hemoglobin (HbA1c) levels (at the time of the OGTT), area under the curve of HbA1c over time (HbA1c AUC), coefficient of variation in HbA1c (HbA1c CV), and antidiabetic agents use were compared by standardized regression coefficients. Longitudinal analyses of these indices were also performed., Results: IGI, DI, DIO, and HOMA-B declined over time (P<0.001 for all). Notably, HbA1c was the most significant factor affecting IGI, DI, DIO, and HOMA-B in the multivariable regression analysis. Compared with HbA1c ≥9%, DI was 1.9-, 2.5-, 3.7-, and 5.5-fold higher in HbA1c of 8%-<9%, 7%-<8%, 6%-<7%, and <6%, respectively, after adjusting for confounding factors (P<0.001). Conversely, β-cell function was not affected by the type or duration of antidiabetic agents, HbA1c AUC, or HbA1c CV. The trajectories of the IGI, DI, DIO, and HOMA-B mirrored those of HbA1c., Conclusion: β-Cell function declines over time; however, it is flexible, being largely affected by recent glycemia in T2DM.

The high theoretical energy density (2600 Wh kg -1 ) and low cost of lithium-sulfur batteries (LSBs) make them an ideal alternative for the next-generation energy storage system. Nevertheless, severe capacity degradation and low sulfur utilization resulting from shuttle effect hinder their commercialization. Herein, Single-atom Ru-doped 1T/2H MoS 2 with enriched defects decorates V 2 C MXene (Ru-MoS 2 /MXene) produced by a new phase-engineering strategy employed as sulfur host to promote polysulfide adsorption and conversion reaction kinetics. The Ru single atom-doped adjusts the chemical environment of the MoS 2 /MXene to anchor polysulfide and acts as an efficient center to motivate the redox reaction. In addition, the rich defects of the MoS 2 and ternary boundary among 1T/2H MoS 2 and V 2 C accelerate the charge transfer and ion movements for the reaction. As expected, the Ru-MoS 2 /MXene/S cathode-based cell exhibits a high-rate capability of 684.3 mAh g -1 at 6 C. After 1000 cycles, the Ru-MoS 2 /MXene/S cell maintains an excellent cycling stability of 696 mAh g -1 at 2 C with a capacity degradation as low as 0.02% per cycle. Despite a high sulfur loading of 9.5 mg cm -2 and a lean electrolyte-to-sulfur ratio of 4.3, the cell achieves a high discharge capacity of 726 mAh g -1 ., (© 2024 Wiley‐VCH GmbH.)

Backgruound: To investigate the prevalence, incidence, comorbidities, and management status of diabetic kidney disease (DKD) and diabetes-related end-stage kidney disease (ESKD) in South Korea., Methods: We used the Korea National Health and Nutrition Examination Survey data (2019 to 2021, n=2,665) for the evaluation of prevalence, comorbidities, control rate of glycemia and comorbidities in DKD, and the Korean Health Insurance Service-customized database (2008 to 2019, n=3,950,857) for the evaluation of trends in the incidence and prevalence rate of diabetes-related ESKD, renin-angiotensin system (RAS) blockers and sodium glucose cotransporter 2 (SGLT2) inhibitors use for DKD, and the risk of atherosclerotic cardiovascular disease (ASCVD) and mortality according to DKD stages. DKD was defined as albuminuria or low estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 in patients with diabetes mellitus., Results: The prevalence of DKD was 25.4% (albuminuria, 22.0%; low eGFR, 6.73%) in patients with diabetes mellitus aged ≥30 years. Patients with DKD had a higher rate of comorbidities, including hypertension, dyslipidemia, and central obesity; however, their control rates were lower than those without DKD. Prescription rate of SGLT2 inhibitors with reduced eGFR increased steadily, reaching 5.94% in 2019. Approximately 70% of DKD patients were treated with RAS blockers. The prevalence rate of diabetesrelated ESKD has been steadily increasing, with a higher rate in older adults. ASCVD and mortality were significantly associated with an in increase in DKD stage., Conclusion: DKD is prevalent among Korean patients with diabetes and is an independent risk factor for cardiovascular morbidity and mortality, which requiring intensive management of diabetes and comorbidities. The prevalence of diabetes-related ESKD has been increasing, especially in the older adults, during past decade.

Radioactive 131 I (RAI) therapy has potential effects for the treatment of Graves disease (GD). However, whether RAI therapy for GD increases cancer risk remains controversial in medicine and public health. We aimed to investigate whether the risk of cancer increases in patients with GD receiving RAI therapy compared with those who did not. Methods: We used the Korean National Health Insurance Service's National Health Information Database from 2004 to 2020 and defined GD as prescribing antithyroid drugs, RAI, or thyroidectomy as a treatment for GD ( International Classification of Diseases, 10th revision, E05 group). We investigated the hazard ratios (HRs) of overall and site-specific cancers associated with RAI in patients with GD. Subsequent cancer was defined as a primary malignancy treated at least 1 y after RAI therapy. Results: In total, 10,737 patients with GD who received RAI therapy (7,193 women, 67.0%; mean age, 43.7 ± 13.4 y) were matched to 53,003 patients with GD who had never received RAI treatment (35,471 women, 66.9%; mean age, 43.8 ± 13.2 y) in a 1:4-5 ratio by age, sex, and health checkup data. The median follow-up duration was 8.7 y (interquartile range, 5.2-12.1 y), and the median cumulative RAI dose was 555 MBq (interquartile range, 370-630 MBq) in the RAI therapy group. During 2004-2020, the overall subsequent cancer rates were 5.66 and 5.84 per 1,000 person-years in the RAI and non-RAI groups, respectively, with an unadjusted HR of 0.97 (95% CI, 0.88-1.06); this remained at 0.96 (95% CI, 0.83-1.10) after adjustment for multiple clinical confounding factors. For cancer subtypes, the risk of leukemia was significantly increased, with an HR of 2.39 (95% CI, 1.17-4.91). However, a loss of statistical significance was observed after adjusting for confounding factors, which may be attributed to the limited number of absolute events. Moreover, cancer-specific mortality was not different between the RAI and the non-RAI groups, with an adjusted HR of 0.99 (95% CI, 0.66-1.47). Conclusion: This study identified that the overall cancer risk in patients with GD who received RAI therapy compared with those who did not was not significant in Korea. Further long-term studies are needed to determine the risks and advantages of RAI therapy in patients with GD., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Rational design of highly efficient noble-metal-unbound electrodes for hydrogen and oxygen production at increased current density is crucial for robust water-splitting. A facile hydrothermal and room-temperature aging method is presented, followed by chemical vapor deposition (CVD), to create a self-sacrificed hybrid heterostructure electrocatalyst. This hybrid material, (Mn-(Co,Ni) 2 P/CoP/(N,S)-C), comprises manganese-doped cobalt nickel phosphide (Mn-(Co,Ni) 2 P) nanofeathers and cobalt phosphide (CoP) nanocubes embedded in a nitrogen and sulfur co-doped carbon matrix (N,S)-C on nickel foam. The catalyst exhibits excellent performance in both the hydrogen evolution reaction (HER; η 10 = 61 mV) and oxygen evolution reaction (OER; η 10 = 213 mV) due to abundant active sites, high porosity, and enhanced hetero-interface interaction between Mn-(Co 2 P-Ni 2 P) CoP, and (N,S)-C supported by significant synergistic effects observed among different phases through density functional theory (DFT) calculations. Impressively, (Mn-(Co,Ni) 2 P/CoP/(N,S)-C (+,-) shows an extra low cell voltage of 1.49 V@10 mA cm -2 . Moreover, the catalyst exhibits remarkable stability at 100 and 300 mA cm -2 when operating as a single stack cell electrolyzer. The superior electrochemical activity is attributed to the enhanced electrode-electrolyte interface among the multiple phases of the hybrid structure., (© 2023 Wiley‐VCH GmbH.)

Backgruound: Recent diabetes management guidelines recommend that sodium-glucose cotransporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1RAs) with proven cardiovascular benefits should be prioritized for combination therapy in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD). This study was aimed at evaluating SGLT2i or GLP-1RA usage rates and various related factors in patients with T2DM and established CVD., Methods: We enrolled adults with T2DM aged ≥30 years who were hospitalized due to established CVD from January 2019 to May 2020 at 13 secondary and tertiary hospitals in Korea in this retrospective observational study., Results: Overall, 2,050 patients were eligible for analysis among 2,107 enrolled patients. The mean patient age, diabetes duration, and glycosylated hemoglobin level were 70.0 years, 12.0 years, and 7.5%, respectively. During the mean follow-up duration of 9.7 months, 25.7% of the patients were prescribed SGLT2is after CVD events. However, only 1.8% were prescribed GLP-1RAs. Compared with SGLT2i non-users, SGLT2i users were more frequently male and obese. Furthermore, they had a shorter diabetes duration but showed worse glycemic control and better renal function at the time of the event. GLP-1RA users had a longer duration of diabetes and worse glycemic control at the time of the event than GLP-1RA non-users., Conclusion: The SGLT2i or GLP-1RA prescription rates were suboptimal in patients with T2DM and established CVD. Sex, body mass index, diabetes duration, glycemic control, and renal function were associated with the use of these agents.

Aims: Omega-3 fatty acids and fenofibrates have shown some beneficial cardiovascular effects; however, their efficacy has not been compared. This study aimed to compare the effectiveness of currently available omega-3 fatty acids and fenofibrate for reducing major adverse cardiovascular events (MACE)., Methods and Results: From a nationwide population-based cohort in South Korea (2008-2019), individuals with metabolic syndrome (≥30 years) who received statin with omega-3 fatty acids and those receiving statin with fenofibrate were matched by propensity score (n = 39 165 in both groups). The primary outcome was MACE, including ischaemic heart disease (IHD), ischaemic stroke (IS), and death from cardiovascular causes. The risk of MACE was lower [hazard ratio (HR), 0.79; 95% confidence interval (CI), 0.74-0.83] in the fenofibrate group than in the omega-3 fatty acid group. Fenofibrate was associated with a lower incidence of IHD (HR, 0.72; 95% CI, 0.67-0.77) and hospitalization for heart failure (HR, 0.90; 95% CI, 0.82-0.97), but not IS (HR, 0.90; 95% CI, 0.81-1.00) nor death from cardiovascular causes (HR, 1.07; 95% CI, 0.97-1.17). The beneficial effect of fenofibrate compared to omega-3 fatty acids was prominent in patients with preexisting atherosclerotic cardiovascular disease and those receiving lower doses of omega-3 fatty acids (≤2 g per day)., Conclusion: In a real-world setting, fenofibrate use was associated with a lower risk of MACE compared with low-dose omega-3 fatty acids when added to statins in people with metabolic syndrome., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Type 2 diabetes (T2D) is a progressive disease in which it is challenging to achieve long-term durable glycemic control. However, intensive glycemic control is crucial for preventing diabetes-related complications. Previous studies showed that monotherapy with a stepwise add-on approach was seldom effective for long-term durable glycemic control. Combination therapy, which refers to the use of two or more drugs to control hyperglycemia, has multiple benefits, including the ability to target a variety of pathophysiological processes underlying hyperglycemia. In clinical trials, initial combination therapy showed better glycemic control than monotherapy or a stepwise approach. Emerging evidence indicates that initial combination therapy is associated with preserved β-cell function and fewer complications in T2D. However, cost-effectiveness and adverse events with combination therapy are issues that should be considered. Therefore, initial combination therapy is an important option for patients with T2D that clinicians should consider with a view toward balancing benefits and potential harms. In this review, we summarize the literature addressing initial combination therapy in T2D, and we suggest optimal strategies based on clinical situations and patient characteristics.

Two different nanostructures of two dissimilar highly-potent active electrocatalysts, P-dopped metallic-(1T)-Fe-VSe 2 (P,Fe-1T-VSe 2 ) nanosheet and P-dopped Fe-CoSe 2 (P,Fe-CoSe 2 ) nanorods are hybridized and integrated into a single heterostructure (P,Fe-(VCo)Se 2 ) on Ni-foam for high-performance water splitting (WS). The catalytic efficiency of VSe 2 nanosheets is first enhanced by enriching metallic (1T)-phase, then forming bimetallic Fe-V selenide, and finally by P-doping. Similarly, the catalytic efficiency of CoSe 2 nanorods is boosted by first fabricating Fe-Co bimetallic selenide and then P-doping. To develop super-efficient electrocatalysts for WS, two individual electrocatalysts P,Fe-1T-VSe 2 nanosheet and P,Fe-CoSe 2 are hybridized and integrated to form a heterostructure (P,Fe-(VCo)Se 2 ). Metallic (1T)-phase of transition metal dichalcogenides has much higher conductivity than the 2H-phase, while bimetallization and P-doping activate basal planes, develop various active components, and form heterostructures that develop a synergistic interfacial effect, all of which, significantly boost the catalytic efficacy of the P,Fe-(VCo)Se 2 . P,Fe-(VCo)Se 2 shows excellent performance requiring very low overpotential (η HER = 50 mV@10 mAcm -2 and η OER = 230 mV@20 mAcm -2 ). P,Fe-(VCo)Se 2 (+, -) device requires a cell potential of 1.48 V to reach 10 mA cm -2 for overall WS., (© 2023 Wiley-VCH GmbH.)

Futuristic wearable electronics desperately need power sources with similar flexibility and durability. In this regard, the authors, therefore, propose a scalable PAN-PMMA blend-derived electrospinning protocol to fabricate free-standing electrodes comprised of cobalt hexacyanoferrate nanocube cathode and tin metal organic framework-derived nanosphere anode, respectively, for flexible sodium-ion batteries. The resulting unique inter-networked nanofiber mesh offers several advantages such as robust structural stability towards repeated bending and twisting stresses along with appreciable electronic/ionic conductivity retention without any additional post-synthesis processing. The fabricated flexible sodium ion full cells deliver a high working voltage of 3.0 V, an energy density of 273 Wh·kg -1 , and a power density of 2.36 kW·kg -1 . The full cells retain up to 86.73% of the initial capacity after 1000 cycles at a 1.0 C rate. After intensive flexibility tests, the full cells also retain 78.26% and 90.78% of the initial capacity after 1000 bending and twisting cycles (5 mm radius bending and 40 o axial twisting), respectively. This work proves that the proposed approach can also be employed to construct similar robust, free-standing nanofiber mesh-based electrodes for mass-producible, ultra-flexible, and durable sodium ion full cells with commercial viability., (© 2023 Wiley-VCH GmbH.)

Novel strategies are required to reduce the risk of developing diabetes and/or clinical outcomes and complications of diabetes. In this regard, the role of the circadian system may be a potential candidate for the prevention of diabetes. We reviewed evidence from animal, clinical, and epidemiological studies linking the circadian system to various aspects of the pathophysiology and clinical outcomes of diabetes. The circadian clock governs genetic, metabolic, hormonal, and behavioral signals in anticipation of cyclic 24-hour events through interactions between a "central clock" in the suprachiasmatic nucleus and "peripheral clocks" in the whole body. Currently, circadian rhythmicity in humans can be subjectively or objectively assessed by measuring melatonin and glucocorticoid levels, core body temperature, peripheral blood, oral mucosa, hair follicles, rest-activity cycles, sleep diaries, and circadian chronotypes. In this review, we summarized various circadian misalignments, such as altered light-dark, sleep-wake, rest-activity, fasting-feeding, shift work, evening chronotype, and social jetlag, as well as mutations in clock genes that could contribute to the development of diabetes and poor glycemic status in patients with diabetes. Targeting critical components of the circadian system could deliver potential candidates for the treatment and prevention of type 2 diabetes mellitus in the future.

This paper proposes a novel phase-resolved partial discharge (PRPD) sensor embedded in a MV-class bushing for high-accuracy insulation analysis. The design, fabrication, and evaluation of a PRPD sensor embedded in a MV-class bushing aimed to achieve the detection of partial discharge (PD) pulses that are phase-synchronized with the applied primary HV signal. A prototype PRPD sensor was composed of a flexible printed circuit board (PCB) with dual-sensing electrodes, utilizing a capacitive voltage divider (CVD) for voltage measurement, the D-dot principle for PD detection, and a signal transducer with passive elements. A PD simulator was prepared to emulate typical PD defects, i.e., a metal protrusion. The voltage measurement precision of the prototype PRPD sensor was satisfied with the accuracy class of 0.2 specified in IEC 61869-11, as the maximum corrected voltage error ratios and corrected phase errors in 80%, 100%, and 120% of the rated voltage (13.2 kilovolts (kV)) were less than 0.2% and 10 min, respectively. In addition, the prototype PRPD sensor had good linearity and high sensitivity for PD detection compared with a conventional electrical detection method. According to performance evaluation tests, the prototype PRPD sensor embedded in the MV-class bushing can measure PRPD patterns phase-synchronized with the primary voltage without any additional synchronization equipment or system. Therefore, the prototype PRPD sensor holds potential as a substitute for conventional commercial PD sensors. Consequently, this advancement could lead to the enhancement of power system monitoring and maintenance, contributing to the digitalization and minimization of power apparatus.

Agastache rugosa, also known as Korean mint, is a perennial plant from the Lamiaceae family that is traditionally used for various ailments and contains antioxidant and antibacterial phenolic compounds. Molecular breeding of A. rugosa can enhance secondary metabolite production and improve agricultural traits, but progress in this field has been delayed due to the lack of chromosome-scale genome information. Herein, we constructed a chromosome-level reference genome using Nanopore sequencing and Hi-C technology, resulting in a final genome assembly with a scaffold N50 of 52.15 Mbp and a total size of 410.67 Mbp. Nine pseudochromosomes accounted for 89.1% of the predicted genome. The BUSCO analysis indicated a high level of completeness in the assembly. Repeat annotation revealed 561,061 repeat elements, accounting for 61.65% of the genome, with Copia and Gypsy long terminal repeats being the most abundant. A total of 26,430 protein-coding genes were predicted, with an average length of 1,184 bp. The availability of this chromosome-scale genome will advance our understanding of A. rugosa's genetic makeup and its potential applications in various industries., (© 2023. The Author(s).)

Objective: Diabetes mellitus (DM) and sarcopenia (SP) are growing public health concerns in an aging society, which share common pathophysiological mechanisms and are associated with serious health consequences. We investigated the impact of DM and SP on all-cause and cardiovascular mortalities in a longitudinal nationwide population-based study., Methods: The study analyzed data from the Korea National Health and Nutrition Examination Survey conducted between 2008 and 2011, including information on appendicular skeletal muscle mass data. Mortality data up to December 2020 were retrieved from the National Death Registry., Results: Among the 17,920 participants, 14,737 (82.2 %) had neither DM nor SP (DM-/SP-), 1349 (7.5 %) had only DM (DM+/SP-), 1425 (8.0 %) had only SP (DM-/SP+), and 409 (2.3 %) had both DM and SP (DM+/SP+). Compared to the DM-/SP- group, the DM-/SP+ and DM+/SP+ groups demonstrated increased all-cause mortality with adjusted hazard ratios (HRs) of 1.47 (95 % confidence interval [CI]: 1.14-1.89) and 1.85 (95 % CI: 1.28-2.69), respectively, while the DM+/SP- group did not (HR 1.29, 95 % CI: 0.97-1.74). The DM+/SP+ group demonstrated the highest risk of overall mortality (p-for-trend <0.001). Compared to the DM-/SP- group, only the DM+/SP+ group demonstrated increased cardiovascular mortality with HRs of 2.10 (95 % CI: 1.11-4.00) while the DM+/SP- (HR 1.35, 95 % CI: 0.79-2.30) and DM-/SP+ (HR 1.42, 95 % CI: 0.84-2.43) groups did not., Conclusions: The coexistence of DM and SP additively increased the risk of all-cause and cardiovascular mortality. Individuals with either disease may require more careful management to prevent the development of the other disease to reduce mortality., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: We investigated whether modulation of white adipose tissue (WAT) vasculature regulates rebound weight gain (RWG) after caloric restriction (CR) in mice fed a high-fat diet (HFD)., Main Methods: We compared changes in energy balance, hypothalamic neuropeptide gene expression, and characteristics of WAT by RT-qPCR, ELISA, immunohistochemistry, and adipose-derived stromal vascular fraction spheroid sprouting assay in obese mice fed a HFD ad libitum (HFD-AL), mice under 40 % CR for 3 or 4 weeks, mice fed HFD-AL for 3 days after CR (CRAL), and CRAL mice treated with TNP-470, an angiogenic inhibitor., Key Findings: WAT angiogenic genes were expressed at low levels, but WAT vascular density was maintained in the CR group compared to that in the HFD-AL group. The CRAL group showed RWG, fat regain, and hyperphagia with higher expression of angiogenic genes and reduced pericyte coverage of the endothelium in WAT on day 3 after CR compared to the CR group, indicating rapidly increased angiogenic activity after CR. Administration of TNP-470 suppressed RWG, fat regain, and hyperphagia only after CR compared to the CRAL group. Changes in circulating leptin levels and hypothalamic neuropeptide gene expression were correlated with changes in weight and fat mass, suggesting that TNP-470 suppressed hyperphagia independently of the hypothalamic melanocortin system. Additionally, TNP-470 increased gene expression related to thermogenesis, fuel utilization, and browning in brown adipose tissue (BAT) and WAT, indicating TNP-470-induced increase in thermogenesis., Significance: Modulation of the WAT vasculature attenuates RWG after CR by suppressing hyperphagia and increasing BAT thermogenesis and WAT browning., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Backgruound: A substantial cardiovascular disease risk remains even after optimal statin therapy. Comparative predictiveness of major lipid and lipoprotein parameters for cardiovascular events in patients with type 2 diabetes mellitus (T2DM) who are treated with statins is not well documented., Methods: From the Korean Nationwide Cohort, 11,900 patients with T2DM (≥40 years of age) without a history of cardiovascular disease and receiving moderate- or high-intensity statins were included. The primary outcome was the first occurrence of major adverse cardiovascular events (MACE) including ischemic heart disease, ischemic stroke, and cardiovascular death. The risk of MACE was estimated according to on-statin levels of low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), highdensity lipoprotein cholesterol (HDL-C), and non-HDL-C., Results: MACE occurred in 712 patients during a median follow-up period of 37.9 months (interquartile range, 21.7 to 54.9). Among patients achieving LDL-C levels less than 100 mg/dL, the hazard ratios for MACE per 1-standard deviation change in ontreatment values were 1.25 (95% confidence interval [CI], 1.07 to 1.47) for LDL-C, 1.31 (95% CI, 1.09 to 1.57) for non-HDL-C, 1.05 (95% CI, 0.91 to 1.21) for TG, and 1.16 (95% CI, 0.98 to 1.37) for HDL-C, after adjusting for potential confounders and lipid parameters mutually. The predictive ability of on-statin LDL-C and non-HDL-C for MACE was prominent in patients at high cardiovascular risk or those with LDL-C ≥70 mg/dL., Conclusion: On-statin LDL-C and non-HDL-C levels are better predictors of the first cardiovascular event than TG or HDL-C in patients with T2DM.

Backgruound: To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM)., Methods: This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints., Results: A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (-63.90±6.89 vs. -55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, -8.47; 95% confidence interval, -16.44 to -0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185)., Conclusion: In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

Backgruound: There was limited evidence to evaluate the association between lifestyle habits and continuous glucose monitoring (CGM) metrics. Thus, we aimed to depict the behavioral and metabolic determinants of CGM metrics in insulin-treated patients with type 2 diabetes mellitus (T2DM)., Methods: This is a prospective observational study. We analyzed data from 122 insulin-treated patients with T2DM. Participants wore Dexcom G6 and Fitbit, and diet information was identified for 10 days. Multivariate-adjusted logistic regression analysis was performed for the simultaneous achievement of CGM-based targets, defined by the percentage of time in terms of hyper, hypoglycemia and glycemic variability (GV). Intake of macronutrients and fiber, step counts, sleep, postprandial C-peptide-to-glucose ratio (PCGR), information about glucose lowering medications and metabolic factors were added to the analyses. Additionally, we evaluated the impact of the distribution of energy and macronutrient during a day, and snack consumption on CGM metrics., Results: Logistic regression analysis revealed that female, participants with high PCGR, low glycosylated hemoglobin (HbA1c) and daytime step count had a higher probability of achieving all targets based on CGM (odds ratios [95% confidence intervals] which were 0.24 [0.09 to 0.65], 1.34 [1.03 to 1.25], 0.95 [0.9 to 0.99], and 1.15 [1.03 to 1.29], respectively). And participants who ate snacks showed a shorter period of hyperglycemia and less GV compared to those without., Conclusion: We confirmed that residual insulin secretion, daytime step count, HbA1c, and women were the most relevant determinants of adequate glycemic control in insulin-treated patients with T2DM. In addition, individuals with snack consumption were exposed to lower times of hyperglycemia and GV.

Pseudomonas aeruginosa is the primary opportunistic human pathogen responsible for a range of acute and chronic infections; it poses a significant threat to immunocompromised patients and is the leading cause of morbidity and mortality for nosocomial infections. Its high resistance to a diverse array of antimicrobial agents presents an urgent health concern. Among the mechanisms contributing to resistance in P. aeruginosa , the horizontal acquisition of antibiotic resistance genes (ARGs) via mobile genetic elements (MGEs) has gained recognition as a substantial concern in clinical settings, thus indicating that a comprehensive understanding of ARG dissemination within the species is strongly required for surveillance. Here, two approaches, including a systematic literature analysis and a genome database survey, were employed to gain insights into ARG dissemination. The genome database enabled scrutinizing of all the available sequence information and various attributes of P. aeruginosa isolates, thus providing an extensive understanding of ARG dissemination within the species. By integrating both approaches, with a primary focus on the genome database survey, mobile ARGs that were linked or correlated with MGEs, important sequence types (STs) carrying diverse ARGs, and MGEs responsible for ARG dissemination were identified as critical factors requiring strict surveillance. Although human isolates play a primary role in dissemination, the importance of animal and environmental isolates has also been suggested. In this study, 25 critical mobile ARGs, 45 critical STs, and associated MGEs involved in ARG dissemination within the species, are suggested as critical factors. Surveillance and management of these prioritized factors across the One Health sectors are essential to mitigate the emergence of multidrug-resistant (MDR) and extensively resistant (XDR) P. aeruginosa in clinical settings.

Background: Unhealthy body composition, including high fat mass, low muscle mass and low bone mass, is a critical health issue in adults. The weight-adjusted waist index (WWI) estimates fat and muscle mass and may have implications for bone health. We examined its association with body composition outcomes in a large Korean adult cohort., Methods: This study used data from the Korean National Health and Nutrition Examination Survey (2008-2011). WWI was calculated as waist circumference (cm) divided by the square root of body weight (kg). Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD), appendicular lean mass (ALM) and total body fat percentage. Unhealthy body composition was defined as combined presence of high fat mass, low bone mass and low muscle mass., Results: A total of 5983 individuals (3034 men [50.7%] and 2949 women [49.3%]; mean age: 63.5 ± 8.7 years) were included. WWI was positively correlated with total body fat percentage (r = 0.478, P < 0.001) and inversely with ALM/weight (r = -0.485, P < 0.001) and BMD at the lumbar spine (r = -0.187, P < 0.001), femoral neck (r = -0.269, P < 0.001) and total hip (r = -0.255, P < 0.001). Higher WWI quartiles correlated with lower BMD, T-scores and ALM/weight, along with increased total body fat, evident in both genders and more pronounced in women, even after adjusting for confounders. This trend remained statistically significant across WWI quartiles for all analyses (P < 0.001). Higher WWI quartiles were also significantly associated with higher odds of unhealthy body composition, with adjusted odds ratio in the highest WWI group of 18.08 (95% CI, 4.32-75.61) in men and 6.36 (95% CI, 3.65-11.07) in women. The optimal cutoff values of WWI for unhealthy body composition were 10.4 cm/√kg in men and 10.5 cm/√kg in women., Conclusions: In community-dwelling adults, high WWI values are associated with unfavourable body composition outcomes, indicating high fat mass, low muscle mass and low bone mass. WWI can potentially serve as an integrated index of body composition, underscoring the need for further research to validate its use in clinical settings., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

P-type Cu-Se thin films were deposited on glass substrates at room temperature using radio frequency magnetron sputtering by a single multi-component CuSe 2 target. When using a multi-component target, the impact of the sputtering power on the homogeneity and stoichiometry within the thin films should be investigated in the depth direction to demonstrate a secondary effect on the electrical and optical properties of the thin films. Systematic characterization of the Cu-Se thin films, including the morphology, microstructure, chemical composition, and depth-directional chemical bonding state and defect structure of the thin films, revealed that the sputtering power played an important role in the homogeneity and stoichiometry of the thin films. At very low and very high sputtering power levels, the Cu-Se thin films exhibited more deviations from stoichiometry, while an optimized sputtering power resulted in more homogenous thin films with improved stoichiometry across the entire thin film thickness in the X-ray photoelectron spectroscopy depth profile, despite showing Se deficiency at all depths. A rapid decrease in carrier concentration, indicating a reduction in the net effect of total defects, was obtained at the optimized sputtering power with less deviation from stoichiometry in the Cu-Se thin films and the closest stoichiometric ratio at an intermediate depth.

In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.

Aims: To compare the effectiveness and safety of empagliflozin and dulaglutide in patients with type 2 diabetes (T2D) inadequately controlled by oral triple therapy., Methods: In this 24-week, multi-center, randomized trial, patients with T2D and HbA 1c level ≥7.5% (58 mmol/mol) on metformin, sulfonylurea, and dipeptidyl peptidase 4 inhibitor (DPP4-i) were randomly assigned into two groups: daily empagliflozin add-on or once-weekly dulaglutide switched from DPP4-i. The primary endpoint was changes from baseline HbA 1c at 24 weeks., Results: In total, 152 patients were recruited to the empagliflozin-added quadruple group (n = 76) or the switched-to-dulaglutide triple group (n = 76). At week 24, both groups showed significant reduction in HbA1c level from baseline with greater reduction with empagliflozin (the mean treatment difference: -0.27% [95% CI -0.50 to -0.04, p = 0.024]) (-2.88 mmol/mol [95% CI -5.37 to -0.39], p = 0.024). Empagliflozin significantly reduced body weight from baseline to week 24 (-1.72 kg [95% CI -1.98 to -0.59, p < 0.001]). No serious adverse events were reported with either empagliflozin or dulaglutide., Conclusions: Empagliflozin, compared with once-weekly dulaglutide switched from DPP4-i, demonstrated greater HbA 1c reduction and weight loss in patients with T2D inadequately controlled with metformin, sulfonylurea, and DPP4-i., Trial Registration: cris.nih.go.kr (KCT0006157)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Effective health interventions for North Korean refugees vulnerable to metabolic disorders are currently unelucidated., Objective: This study aimed to evaluate the effects of digital health interventions in North Korean refugees using a wearable activity tracker (Fitbit device)., Methods: We conducted a prospective, randomized, open-label study on North Korean refugees aged 19-59 years between June 2020 and October 2021 with a 12-week follow-up period. The participants were randomly assigned to either an intervention group or a control group in a 1:1 ratio. The intervention group received individualized health counseling based on Fitbit data every 4 weeks, whereas the control group wore the Fitbit device but did not receive individualized counseling. The primary and secondary outcomes were the change in the mean daily step count and changes in the metabolic parameters, respectively., Results: The trial was completed by 52 North Korean refugees, of whom 27 and 25 were in the intervention and control groups, respectively. The mean age was 43 (SD 10) years, and 41 (78.8%) participants were women. Most participants (44/52, 95.7%) had a low socioeconomic status. After the intervention, the daily step count in the intervention group increased, whereas that in the control group decreased. However, there were no significant differences between the 2 groups (+83 and -521 steps in the intervention and control groups, respectively; P=.500). The effects of the intervention were more prominent in the participants with a lower-than-average daily step count at baseline (<11,667 steps/day). After the 12-week study period, 85.7% (12/14) and 46.7% (7/15) of the participants in the intervention and control groups, respectively, had an increased daily step count (P=.05). The intervention prevented the worsening of the metabolic parameters, including BMI, waist circumference, fasting blood glucose level, and glycated hemoglobin level, during the study period., Conclusions: The wearable device-based physical activity intervention did not significantly increase the average daily step count in the North Korean refugees in this study. However, the intervention was effective among the North Korean refugees with a lower-than-average daily step count; therefore, a large-scale, long-term study of this intervention type in an underserved population is warranted., Trial Registration: Clinical Research Information Service KCT0007999; https://cris.nih.go.kr/cris/search/detailSearch.do/23622., (©Ji Yoon Kim, Kyoung Jin Kim, Kyeong Jin Kim, Jimi Choi, Jinhee Seo, Jung-Been Lee, Jae Hyun Bae, Nam Hoon Kim, Hee Young Kim, Soo-Kyung Lee, Sin Gon Kim. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 19.07.2023.)

Background: Current evidence regarding the mortality outcomes associated with calcium supplementation with or without low-dose vitamin D is conflicting., Objectives: To investigate the effects of calcium supplementation with or without vitamin D on all-cause and cause-specific mortalities in a large-scale cohort., Methods: This study used data from the Korean National Health Insurance System database and National Death Registry. A total of 27,846 participants aged >55 years who had taken calcium supplements with or without vitamin D for at least 90 days (calcium supplementation only [CaO], n = 6256; calcium supplementation in combination with vitamin D [CaD], n = 21,590) were matched in a 1:1 ratio to those who did not take calcium or vitamin D supplements (control group) using propensity scores., Results: No difference in all-cause mortality risk was found between the CaO and control groups: (adjusted hazard ratio [HR] = 1.00; 95% confidence interval [CI]: 0.92-1.10). However, all-cause mortality was lower in the CaD group (HR = 0.85; 95% CI: 0.80-0.89) compared with that in the control group. Mortality risk associated with cardiovascular disease (CVD) was decreased in the CaD group when the daily vitamin D dose received was less than 1000 IU (HR = 0.72; 95% CI: 0.64-0.81). Subgroup analysis showed significant effect of vitamin D with calcium in individuals who were female, aged ≥65 years or had previous history of cancer or CVD., Conclusion: In combination with calcium, vitamin D supplementation provides better outcomes for all-cause mortality, particularly CVD-associated mortality, in a duration-dependent manner., (© 2023 The Association for the Publication of the Journal of Internal Medicine.)

The pseudocapacitive metal oxide anchored nanocarbon-based three-dimensional (3D) materials are considered attractive electrode materials for high-performance supercapacitor applications. However, the complex multistep synthesis approaches raise production costs and act as a major barrier to the practical real-world field. To overcome this limitation, in this study, an easily scalable and effective fabrication approach for the development of iron oxide (Fe 3 O 4 ) anchored highly porous carbon nanotube hybrid foam (f-Fe 3 O 4 /O-CNTF) with micro/mesoporous structure was suggested to improve the durability and energy storage performance. The surface morphology-tuned f-Fe 3 O 4 /O-CNTF (f-Fe 3 O 4 /O-CNTF(M)) was fabricated through electromagnetic interaction between the anchored magnetic Fe 3 O 4 on the CNT surface and the applied magnetic field. The obtained results clearly demonstrated that the changed surface morphology of the f-Fe 3 O 4 /O-CNTF(M) strongly affected the meso- and micropore structure, electrochemical performance, and durability. Consequently, the f-Fe 3 O 4 /O-CNTF(M) showed an almost 120% enhanced specific surface area and nearly 1.9 times increased specific capacitance compared to that of the f-Fe 3 O 4 /O-CNTF. Furthermore, the changed surface morphology successfully prevented the re-aggregation of the initial structure and significantly improved durability. As a result, f-Fe 3 O 4 /O-CNTF(M) showed outstanding cycling stability, maintaining almost 100% capacitance retention after 14,000 cycles. Consequently, the assembled symmetric supercapacitor device delivered an energy density of 20.1 Wh·kg -1 at a power density of 0.37 kW·kg -1 with good cycling stability. These results suggest that the f-Fe 3 O 4 /O-CNTF(M) can potentially be used as an electrode for supercapacitors with good durability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: As the metabolic significance of sarcopenic obesity (SO) is revealed, finding an appropriate index to detect SO is important, especially for type 2 diabetes mellitus (T2DM) patients with accompanying metabolic dysfunction., Methods: Participants (n=515) from the Korea Guro Diabetes Program were included to compare how well waist circumference (WC), waist hip ratio (WHR), waist height ratio (WHtR), and the weight-adjusted waist index (WWI) predict SO in newly diagnosed T2DM patients. Sarcopenia was defined based on guidelines from the 2019 Asian Working Group for Sarcopenia as both low muscle mass (appendicular skeletal muscle [ASM]/height 2 <7.0 kg/m 2 for men, <5.4 kg/m 2 for women) and strength (handgrip strength <28.0 kg for men, <18.0 kg for women) and/or reduced physical performance (gait speed <1.0 m/sec). Obesity was defined as a WC ≥90 cm in men and ≥85 cm in women. The WHR, WHtR, and WWI were calculated by dividing the WC by the hip circumference, height, and √ weight, respectively., Results: The WC, WHR, and WHtR correlated positively with the fat and muscle mass represented by truncal fat amount (TFA) and ASM, whereas the WWI was proportional to the TFA and inversely related to ASM. Of the four indices, the WWI showed the highest area under the receiver operative characteristic curve for SO. The WWI also exhibited a positive correlation with albuminuria and the mean brachial-ankle pulse wave velocity, especially in patients aged ≥65 years., Conclusion: The WWI is the preferable anthropometric index for predicting SO in T2DM patients, and it might be a proper index for predicting cardiometabolic risk factors in elderly people.

Foot-and-mouth disease (FMD) is a highly contagious animal disease that occurs in cloven-hoofed animals including pigs. To prevent FMD, vaccines and adjuvants are routinely used to induce an immune response; however, it requires an extended period of time to produce sufficient antibodies to prevent viral infection. In this study, we evaluated the increased effectiveness of the FMD vaccine structural protein (SP) antibody by administrating the Amino-Zn adjuvant to 100 pigs from 3 test pig farms in their feed. The FMD vaccine antibody titer and immunological index were analyzed using an enzyme-linked immunosorbent assay (ELISA) kit, and the hematological and blood biochemical parameters were analyzed using an automatic blood analyzer. The titer of the FMD vaccine SP antibodies in the 0.2% Amino-Zn-administered group was significantly increased compared to that of the positive control group only injected with FMD vaccine at 4 weeks after the first vaccination and at 4, 8, and 16 weeks after the second vaccination ( p < 0.05). The FMD vaccine SP antibody positive rate was 100% until shipment. The IFN-γ and IgA levels were significantly increased by Amino-Zn administration 4 weeks after the first vaccination and 4 weeks after the second vaccination ( p < 0.05). On the other hand, serum AST, and CPK ( p < 0.001) were significantly decreased by Amino-Zn administration. These results show that the administration of Amino-Zn is effective in enhancing the antibody titer and immunogenicity of the FMD vaccine and can be used as an oral adjuvant (OrAd) to prevent viral diseases, such as FMD.

Background: We aimed to investigate whether the risk of second primary malignancy (SPM) in patients with thyroid cancer (TC) receiving radioactive iodine (RAI) therapy rises in a cumulative, dose-dependent manner compared with those not undergoing RAI., Methods: Using the Korean National Health Insurance Service National Health Information Database (2002-2019), we investigated hazard ratios of SPM associated with RAI in TC. SPM was defined as a second primary malignancy diagnosed at least 1 year after TC diagnosis., Results: Of 217 777 patients with TC (177 385 women and 40 392 men; mean [SD] age, 47.2 [11.6] years), 100 448 (46.1%) received RAI therapy. The median (IQR) follow-up duration was 7.7 (5.5-10.3) years, and the median (IQR) cumulative RAI dose was 3.7 (1.9-5.6) GBq. From 2004 to 2019, SPM incidence rates were 7.30 and 6.56 per 1000 person-years in the RAI and non-RAI groups, respectively, with an unadjusted hazard ratio of 1.09 (95% confidence interval = 1.05 to 1.13); this rate remained at 1.08 (95% confidence interval = 1.04 to 1.13) after adjustment for multiple clinical confounding factors. Notably, SPM risk increased significantly, from 3.7 GBq with full adjustments, and a strong linear association between cumulative RAI dose and SPM was observed in the restricted cubic spline analysis. Regarding cancer subtypes, myeloid leukemia and salivary gland, trachea, lung and bronchus, uterus, and prostate cancers were the most significantly elevated risks in patients who underwent RAI therapy., Conclusions: This study identified that SPM risk increased linearly in a dose-dependent manner in patients with TC undergoing RAI therapy compared with those not undergoing RAI therapy., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Chemotherapy-induced cachexia causes severe metabolic abnormalities independently of cancer and reduces the therapeutic efficacy of chemotherapy. The underlying mechanism of chemotherapy-induced cachexia remains unclear. Here we investigated the cytarabine (CYT)-induced alteration in energy balance and its underlying mechanisms in mice. We compared energy balance-associated parameters among the three groups of mice: CON, CYT, and PF (pair-fed mice with the CYT group) that were intravenously administered vehicle or CYT. Weight gain, fat mass, skeletal muscle mass, grip strength, and nocturnal energy expenditure were significantly lowered in the CYT group than in the CON and PF groups. The CYT group demonstrated less energy intake than the CON group and higher respiratory quotient than the PF group, indicating that CYT induced cachexia independently from the anorexia-induced weight loss. Serum triglyceride was significantly lower in the CYT group than in the CON group, whereas the intestinal mucosal triglyceride levels and the lipid content within the small intestine enterocyte were higher after lipid loading in the CYT group than in the CON and PF groups, suggesting that CYT inhibited lipid uptake in the intestine. This was not associated with obvious intestinal damage. The CYT group showed increased zipper-like junctions of lymphatic endothelial vessel in duodenal villi compared to that in the CON and CYT groups, suggesting their imperative role in the CYT-induced inhibition of lipid uptake. CYT worsens cachexia independently of anorexia by inhibiting the intestinal lipid uptake, via the increased zipper-like junctions of lymphatic endothelial vessel., Competing Interests: Conflict of interest The authors declare no conflict of interests with this article contents., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Beneficial role of fibroblast growth factor 1 (FGF1) in the regulation of glucose metabolism and adipose tissue remodeling was suggested in rodents. This study aimed to investigate the association between serum FGF1 levels and metabolic parameters in adults with glucose intolerance., Methods: Serum FGF1 levels were examined using an enzyme-linked immunosorbent assay in 153 individuals with glucose intolerance. Associations between serum FGF1 levels and metabolic parameters, including body mass index (BMI), glycated hemoglobin (HbA1c), and 75 g oral glucose tolerance test-derived parameters, including insulinogenic index (IGI), Matsuda insulin sensitivity index (ISI), and disposition index (DI), were examined., Results: Serum FGF1 was detected in 35 individuals (22.9%), possibly due to the autocrine/paracrine nature of the peptide. IGI and DI levels were significantly lower in individuals with higher FGF1 levels than in those with lower FGF1 levels or undetectable FGF1 (p=0.006 and 0.005 for IGI and DI, respectively, after adjustment for age, sex, and BMI). Univariable and multivariable analyses using the Tobit regression model also revealed a negative association between FGF1 levels and IGI and DI. The regression coefficients per 1-SD of log-transformed IGI and DI were -0.461 (p=0.013) and -0.467 (p=0.012), respectively, after adjustment for age, sex, and BMI. In contrast, serum FGF1 levels were not significantly associated with ISI, BMI, or HbA1c., Conclusions: The serum concentration of FGF1 was significantly elevated in individuals with low insulin secretion, suggesting a possible interaction between FGF1 and beta cell function in humans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Choi, Kwon, Park, Kim and Kim.)

Aim: This study aimed to determine the association between fenofibrate added to statin therapy and diabetic retinopathy progression., Methods: In this propensity-matched study using the Korean National Health Insurance Service cohort (2002-2019), patients with type 2 diabetes and metabolic syndrome (≥ 30 years) receiving statin therapy were matched 1:2 by propensity score into the statin plus fenofibrate group (n = 22,395) and statin-only group (n = 43,191). The primary outcome was a composite of diabetic retinopathy progression including vitreous hemorrhage, vitrectomy, laser photocoagulation, intravitreous injection therapy and retinal detachment., Results: The median (quartiles) follow-up duration was 44.0 (27.6-70.6) months. For the primary outcome, the incidence rate per 1,000 person-years was 9.66 in the statin-only group and 8.68 in the statin-plus-fenofibrate group. The risk of the primary outcome was significantly lower (hazard ratio [HR]=0.88; 95% confidence interval [0.81;0.96] P = 0.005) in the statin-plus-fenofibrate group than in the statin-only group. Only patients with pre-existing retinopathy showed benefits from fenofibrate treatment (HR=0.83 [0.73;0.95] P = 0.006). In addition, the statin plus fenofibrate group exhibited significantly lower risks of vitreous hemorrhage (HR= 0.86 [0.75;0.995] P = 0.042), laser photocoagulation (HR=0.86 [0.77;0.96] P = 0.009) and intravitreous injection therapy (HR=0.73 [0.59;0.90] P = 0.003) than those in the statin-only group. There was no significant interaction between the different characteristics at baseline and the treatment effect., Conclusion: The addition of fenofibrate to statins was associated with significantly lower risk of diabetic retinopathy progression than statin therapy alone in patients with type 2 diabetes and metabolic syndrome., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Aims: Metformin improves glucose regulation through various mechanisms in the periphery. Our previous study revealed that oral intake of metformin activates several brain regions, including the hypothalamus, and directly activates hypothalamic S6 kinase in mice. In this study, we aimed to identify the direct effects of metformin on glucose regulation in the brain. Materials and methods: We investigated the role of metformin in peripheral glucose regulation by directly administering metformin intracerebroventricularly in mice. The effect of centrally administered metformin (central metformin) on peripheral glucose regulation was evaluated by oral or intraperitoneal glucose, insulin, and pyruvate tolerance tests. Hepatic gluconeogenesis and gastric emptying were assessed to elucidate the underlying mechanisms. Liver-specific and systemic sympathetic denervation were performed. Results: Central metformin improved the glycemic response to oral glucose load in mice compared to that in the control group, and worsened the response to intraperitoneal glucose load, indicating its dual role in peripheral glucose regulation. It lowered the ability of insulin to decrease serum glucose levels and worsened the glycemic response to pyruvate load relative to the control group. Furthermore, it increased the expression of hepatic G6pc and decreased the phosphorylation of STAT3, suggesting that central metformin increased hepatic glucose production. The effect was mediated by sympathetic nervous system activation. In contrast, it induced a significant delay in gastric emptying in mice, suggesting its potent role in suppressing intestinal glucose absorption. Conclusion: Central metformin improves glucose tolerance by delaying gastric emptying through the brain-gut axis, but at the same time worsens it by increasing hepatic glucose production via the brain-liver axis. However, with its ordinary intake, central metformin may effectively enhance its glucose-lowering effect through the brain-gut axis, which could surpass its effect on glucose regulation via the brain-liver axis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jin, Kim, Oh, Ha, Jeong, Choi, Lee, Kim and Kim.)

Aim: To investigate the longitudinal changes in brain volume and cognitive function associated with diabetes at midlife, and to examine whether long-term hyperglycaemia, insulin resistance or secretory function is associated with brain atrophy and cognitive decline., Materials and Methods: We used data from 2377 participants with both baseline and 4-year follow-up brain magnetic resonance images and neuropsychological measures from the Ansan cohort of the Korean Genome Epidemiology Study. Time-weighted mean glycaemic values were calculated using all measurements over an average duration of 10.6 years from cohort initiation to baseline visits., Results: Type 2 diabetes was associated with greater white matter volume reduction (adjusted volume difference = -1.96 ml, 95% CI: -3.73, -0.18) and executive function decline (adjusted Z score difference = -0.14, 95% CI: -0.23, -0.05) during the follow-up period of 4.2 years. Decline of verbal and visual memory or verbal fluency was not associated with diabetes. Greater executive function decline was associated with higher time-weighted mean HbA1c level over the preceding 10.6 years (P < .001), but not with insulin resistance markers in the diabetes group. Participants with diabetes, whose time-weighted average HbA1c level was maintained above 6.5% over the previous decade, showed greater decline in executive function and global cognition than the normal glucose group., Conclusions: Long-term hyperglycaemia was a major independent factor associated with rapid cognitive decline in middle-aged adults with diabetes. Maintaining ideal glucose levels in diabetes at midlife might prevent later rapid cognitive decline., (© 2022 John Wiley & Sons Ltd.)

Rechargeable zinc-air batteries (ZABs) are promising energy storage systems due to their low-cost and safety. However, the working principle of ZABs is based on oxygen evolution reaction (OER) and oxygen reduction reaction (ORR), which display sluggish kinetic and low stability. Herein, this work proposes a novel method to design a heterogeneous CoP/CoO electrocatalyst on mesopore nanobox carbon/carbon nanotube (CoP/CoO@MNC-CNT) that enriched active sites and synergistic effect. Moreover, the well-defined heterointerfaces could lower the energy barrier for intermediate species adsorption and promote OER and ORR electrochemical performances. The CoP/CoO@MNC-CNT electrocatalyst presents a high half-wave potential of 0.838 V for ORR and a small overpotential of 270 mV for OER. The ZABs-based CoP/CoO@MNC-CNT air-cathode shows an open-circuit voltage of 1.409 V, the long-term cycle life of 500 h with a small voltage difference change of 7.7%. Additionally, the flexible ZABs exhibit highly mechanical stability, demonstrating their application potential in wearable electronic devices., (© 2023 Wiley-VCH GmbH.)

The development of trifunctional electrocatalyst for oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and hydrogen evolution reaction (HER) with deeply understanding the mechanism to enhance the electrochemical performance is still a challenging task. In this work, the distorted metastable hybrid-phase induced 1T'/1T Co,PSnS 2 nanosheets on carbon cloth (1T'/1T Co,PSnS 2 @CC) is prepared and examined. The density functional theoretical (DFT) calculation suggests that the distorted 1T'/1T Co,PSnS 2 can provide excellent conductivity and strong hydrogen adsorption ability. The electronic structure tuning and enhancement mechanism of electrochemical performance are investigated and discussed. The optimal 1T'/1T Co,PSnS 2 @CC catalyst exhibits low overpotential of ≈94 and 219.7 mV at 10 mA cm -2 for HER and OER, respectively. Remarkably, the catalyst exhibits exceptional ORR activity with small onset potential value (≈0.94 V) and half-wave potential (≈0.87 V). Most significantly, the 1T'/1T Co,PSnS 2 ||Co,PSnS 2 electrolyzer required small cell voltages of ≈1.53, 1.70, and 1.82 V at 10, 100, and 400 mA cm -2 , respectively, which are better than those of state-of-the-art Pt-C||RuO 2 (≈1.56 and 1.84 V at 10 and 100 mA cm -2 ). The present study suggests a new approach for the preparation of large-scalable, high performance hierarchical 3D next-generation trifunctional electrocatalysts., (© 2023 Wiley-VCH GmbH.)

In this study, the composition of lead-free piezoelectric ceramics (1 - x)(Bi 0.5 Na 0.5 )TiO 3 -x(Ba 0.5 Sr 0.5 )TiO 3 with excellent piezoelectric properties was investigated. Crystal analysis and electrical and piezoelectric properties were analyzed according to the content of the BST composition. A phase change from rhombohedral to tetragonal structure was observed in 0.12 BST, and the densest and most uniform microstructure was confirmed in this composition. The dielectric constant increased from 905 to 1692 as the composition of BST increased to 0.12 BST. Afterward, as the composition of BST increased, the permittivity tended to decrease. Additionally, at 0.12 BST, P r was the highest at 23.34 μC/cm 2 . The piezoelectric charge constant (d 33 ) and the electromechanical coupling coefficient (k p ) were 152 pC/N and 0.37, respectively, and showed the highest values at 0.12 BST. Curie temperature (T m ) was analyzed 242 °C at 0.12 BST, the optimal composition. It was confirmed that the characteristics of 0.12 BST were excellent in all conditions. Therefore, it was confirmed that 0.12 BST is the optimal composition for (1 - x)BNT-xBST piezoelectric ceramics.

Backgruound: We aimed to investigate the moderating effects of obesity, age, and sex on the association between sleep duration and the development of diabetes in Asians., Methods: We analyzed data from a cohort of the Korean Genome and Epidemiology Study conducted from 2001 to 2020. After excluding shift workers and those with diabetes at baseline, 7,407 participants were stratified into three groups according to sleep duration: ≤5 hours/night, >5 to 7 hours/night (reference), and >7 hours/night. The Cox proportional hazards analyses were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes mellitus (T2DM). Subgroup analyses were performed according to obesity, age, and sex., Results: During 16 years of follow-up, 2,024 cases of T2DM were identified. Individuals who slept ≤5 h/night had a higher risk of incident diabetes than the reference group (HR, 1.17; 95% CI, 1.02 to 1.33). The subgroup analysis observed a valid interaction with sleep duration only for obesity. A higher risk of T2DM was observed in the ≤5 hours/night group in non-obese individuals, men, and those aged <60 years, and in the >7 hours/night group in obese individuals (HRs were 1.34 [95% CI, 1.11 to 1.61], 1.22 [95% CI, 1 to 1.49], and 1.18 [95% CI, 1.01 to 1.39], respectively)., Conclusion: This study confirmed the effect of sleep deprivation on the risk of T2DM throughout the 16-year follow-up period. This impact was confined to non-obese or young individuals and men. We observed a significant interaction between sleep duration and obesity.

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<0.0001), respectively. In addition, shorter disease duration, absence of dyslipidemia, and higher baseline HbA1c levels were identified as the clinical features characteristic of a "responder" to empagliflozin therapy., Conclusion: Empagliflozin is a safe and potent glucose-lowering drug in routine use among Korean patients with type 2 diabetes mellitus. It is expected to have better glycemic efficacy in Korean patients with poorly controlled type 2 diabetes mellitus.

Low-density lipoprotein cholesterol (LDL-C)-lowering therapy that increases LDL receptor expression in several ways robustly reduces the risk of atherosclerotic cardiovascular disease (CVD). However, a substantial risk of CVD still remains after intensive LDL-C reduction, which requires new treatment modalities for dyslipidemia and cardiovascular risk management. Triglycerides (TGs) and triglyceride-rich lipoproteins (TRLs) have received attention as indicators of residual cardiovascular risk and as direct causal factors for atherosclerosis and CVDs. Advances in understanding TG and TRL metabolism and their association with clinically evident CVDs have led to the development of novel therapeutic targets, including apolipoprotein C-III (apoC-III) and angiopoietin-like protein 3 (ANGPTL3). Genetic association studies have indicated that both apoC-III and ANGPTL3 play a causal role in the development of atherosclerotic CVD. Both molecules contribute to lipid dysregulation and atherosclerosis primarily by inhibiting lipoprotein lipase; however, recent evidence has shown that novel pathways exist in relation to their lipid-modifying activities. Notably, recent progress in therapeutic approaches, such as monoclonal antibodies or antisense oligonucleotides, has led to several novel therapeutics targeting apoC-III and ANGPTL3. This review summarized the recent updates and discussions related to apoC-III and ANGPTL3 expression., Competing Interests: Conflict of Interest: Nam Hoon Kim is Deputy Editor, and Ji Yoon Kim is editor of Journal of Lipid and Atherosclerosis. However, they were not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported., (Copyright © 2023 The Korean Society of Lipid and Atherosclerosis.)