ALK5/VEGFR2 dual inhibitor TU2218 alone or in combination with immune checkpoint inhibitors enhances immune-mediated antitumor effects.

Transforming growth factor ß (TGFß) 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 TGFß/VEGF is more effective than targeting TGFß 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 TGFß 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 TGFß 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.

Vomiting-induced pharyngeal perforation during bowel preparation for colonoscopy: A case report.

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.

A facile and scalable fabrication method of scrolled graphene/boron nitride-based van der Waals superlattice heterostructure materials for highly stable supercapacitor electrode application.

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 (Fe3O4 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 cm2 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.

Recent Glycemia Is a Major Determinant of ß-Cell Function in Type 2 Diabetes Mellitus.

Background: Progressive deterioration of ß-cell function is a characteristic of type 2 diabetes mellitus (T2DM). We aimed to investigate the relative contributions of clinical factors to ß-cell function in T2DM. Methods: In a T2DM cohort of 470 adults (disease duration 0 to 41 years), ß-cell function was estimated using insulinogenic index (IGI), disposition index (DI), oral disposition index (DIO), and homeostasis model assessment of ß-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, ß-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: ß-Cell function declines over time; however, it is flexible, being largely affected by recent glycemia in T2DM.

Realizing the Tailored Catalytic Performances on Atomic Pt-Promoted Transition Metal Moieties Implanted Layered Double Hydroxides for Water Electrolysis.

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 (PtSA) promoted by low electronegative transition metal (Mn, Fe) moieties (PtSA-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 PtSA(doped) and PtSA(ads.), thus optimizing adsorption energy to effectively accelerate the H2 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 H2O catalytic dissociation into oxygen. Therefore, the PtSA-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 PtSA-Mn,Fe-Ni LDHs proves to be 15.45 times higher than that of commercial Pt-C. The anion exchange membrane electrolyzer stack of PtSA-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.

Efficacy and tolerability of initial triple combination therapy with metformin, dapagliflozin and saxagliptin compared with stepwise add-on therapy in drug-naïve patients with type 2 diabetes (TRIPLE-AXEL study): A multicentre, randomized, 104-week, open-label, active-controlled trial.

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.

Ru Single Atom Dispersed on MoS2/MXene for Enhanced Sulfur Reduction Reaction in Lithium-Sulfur Batteries.

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 MoS2 with enriched defects decorates V2C MXene (Ru-MoS2/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 MoS2/MXene to anchor polysulfide and acts as an efficient center to motivate the redox reaction. In addition, the rich defects of the MoS2 and ternary boundary among 1T/2H MoS2 and V2C accelerate the charge transfer and ion movements for the reaction. As expected, the Ru-MoS2/MXene/S cathode-based cell exhibits a high-rate capability of 684.3 mAh g-1 at 6 C. After 1000 cycles, the Ru-MoS2/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.

Cancer Risk in Graves Disease with Radioactive 131I Treatment: A Nationwide Cohort Study.

Radioactive 131I (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.

2023 Diabetic Kidney Disease Fact Sheet in Korea.

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.

Triphasic Ni2P-Ni12P5-Ru with Amorphous Interface Engineering Promoted by Co Nano-Surface for Efficient Water Splitting.

This research designs a triphasic Ni2P-Ni12P5-Ru heterostructure with amorphous interface engineering strongly coupled by a cobalt nano-surface (Co@NimPn-Ru) to form a hierarchical 3D interconnected architecture. The Co@NimPn-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@NimPn-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 Ni2P, Ni12P5, 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.

Attention to Innate Circadian Rhythm and the Impact of Its Disruption on Diabetes.

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.

Real-World Treatment Patterns according to Clinical Practice Guidelines in Patients with Type 2 Diabetes Mellitus and Established Cardiovascular Disease in Korea: Multicenter, Retrospective, Observational Study.

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.

An Ultra-Flexible Sodium-Ion Full Cell with High Energy/Power Density and Unprecedented Structural Stability.

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 40o 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.

Initial Combination Therapy in Type 2 Diabetes.

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 ß-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.

Synchronous Surface-Interface and Crystal-Phase Engineered Multifaceted Hybrid Nanostructure of Fe-(1T)-VSe2 Nanosheet and Fe-CoSe2 Nanorods Doped with P for Rapid HER and OER, Kinetics.

Two different nanostructures of two dissimilar highly-potent active electrocatalysts, P-dopped metallic-(1T)-Fe-VSe2 (P,Fe-1T-VSe2 ) nanosheet and P-dopped Fe-CoSe2 (P,Fe-CoSe2 ) nanorods are hybridized and integrated into a single heterostructure (P,Fe-(VCo)Se2 ) on Ni-foam for high-performance water splitting (WS). The catalytic efficiency of VSe2 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 CoSe2 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-VSe2 nanosheet and P,Fe-CoSe2 are hybridized and integrated to form a heterostructure (P,Fe-(VCo)Se2 ). 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)Se2 . P,Fe-(VCo)Se2 shows excellent performance requiring very low overpotential (ηHER = 50 mV@10 mAcm-2 and ηOER = 230 mV@20 mAcm-2 ). P,Fe-(VCo)Se2 (+, -) device requires a cell potential of 1.48 V to reach 10 mA cm-2 for overall WS.

Associations of omega-3 fatty acids vs. fenofibrate with adverse cardiovascular outcomes in people with metabolic syndrome: propensity matched cohort study.

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.

Manganese-Doped Bimetallic (Co,Ni)2P Integrated CoP in N,S Co-Doped Carbon: Unveiling a Compatible Hybrid Electrocatalyst for Overall Water Splitting.

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)2P/CoP/(N,S)-C), comprises manganese-doped cobalt nickel phosphide (Mn-(Co,Ni)2P) 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; η10 = 61 mV) and oxygen evolution reaction (OER; η10 = 213 mV) due to abundant active sites, high porosity, and enhanced hetero-interface interaction between Mn-(Co2P-Ni2P) CoP, and (N,S)-C supported by significant synergistic effects observed among different phases through density functional theory (DFT) calculations. Impressively, (Mn-(Co,Ni)2P/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.

The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study.

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 ß-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.

The Design, Fabrication, and Evaluation of a Phase-Resolved Partial Discharge Sensor Embedded in a MV-Class Bushing.

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.