Myrosinase isogenes in wasabi (Wasabia japonica Matsum) and their putative roles in glucosinolate metabolism.

BACKGROUND: Wasabi, a Brassicaceae member, is well-known for its unique pungent and hot flavor which is produced from glucosinolate (GSL) degradation. Myrosinase (MYR) is a principle enzyme catalyzing the primary conversion of GSLs to GSL hydrolysis products (GHPs) which is responsible for plant defense system and food quality. Due to the limited information in relation to MYRs present in wasabi (Wasabia japonica M.), this study aimed to identify the MYR isogenes in W. japonica and analyze their roles in relation to GSL metabolism. RESULTS: In results, WjMYRI-1 was abundantly expressed in all organs, whereas WjMYRI-2 showed only trace expression levels. WjMYRII was highly expressed in the aboveground tissues. Interestingly, WjMYRII expression was significantly upregulated by certain abiotic factors, such as methyl jasmonate (more than 40-fold in petioles and 15-fold in leaves) and salt (tenfold in leaves). Young leaves and roots contained 97.89 and 91.17 µmol‧g-1 of GSL, whereas less GSL was produced in mature leaves and petioles (38.36 and 44.79 µmol‧g-1, respectively). Similar pattern was observed in the accumulation of GHPs in various plant organs. Notably, despite the non-significant changes in GSL production, abiotic factors treated samples enhanced significantly GHP content. Pearson's correlation analysis revealed that WjMYRI-1 expression significantly correlated with GSL accumulation and GHP formation, suggesting the primary role of WjMYRI-1-encoding putative protein in GSL degradation. In contrast, WjMYRII expression level showed no correlation with GSL or GHP content, suggesting another physiological role of WjMYRII in stress-induced response. CONCLUSIONS: In conclusions, three potential isogenes (WjMYRI-1, WjMYRI-2, and WjMYRII) encoding for different MYR isoforms in W. japonica were identified. Our results provided new insights related to MYR and GSL metabolism which are important for the implications of wasabi in agriculture, food and pharmaceutical industry. Particularly, WjMYRI-1 may be primarily responsible for GSL degradation, whereas WjMYRII (clade II) may be involved in other regulatory pathways induced by abiotic factors.

Lower Atrial Fibrillation Risk With Sodium-Glucose Cotransporter 2 Inhibitors Than With Dipeptidyl Peptidase-4 Inhibitors in Individuals With Type 2 Diabetes: A Nationwide Cohort Study.

BACKGROUND AND OBJECTIVES: Accumulating evidence shows that sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce adverse cardiovascular outcomes. However, whether SGLT2i, compared with other antidiabetic drugs, reduce the new development of atrial fibrillation (AF) is unclear. In this study, we compared SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4is) in terms of reduction in the risk of AF in individuals with type 2 diabetes. METHODS: We included 42,786 propensity score-matched pairs of SGLT2i and DPP-4i users without previous AF diagnosis using the Korean National Health Insurance Service database between May 1, 2016, and December 31, 2018. RESULTS: During a median follow-up of 1.3 years, SGLT2i users had a lower incidence of AF than DPP-4i users (1.95 vs. 2.65 per 1,000 person-years; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.97; p=0.028]). In individuals without heart failure, SGLT2i users was associated with a decreased risk of AF incidence (HR, 0.70; 95% CI, 0.52-0.94; p=0.019) compared to DPP-4i users. However, individuals with heart failure, SGLT2i users was not significantly associated with a change in risk (HR, 1.04; 95% CI, 0.44-2.44; p=0.936). CONCLUSIONS: In this nationwide cohort study of individuals with type 2 diabetes, treatment with SGLT2i was associated with a lower risk of AF compared with treatment with DPP-4i.

Intravascular Imaging-Guided Optimization of Complex Percutaneous Coronary Intervention by Sex: A Subgroup Analysis of the RENOVATE-COMPLEX-PCI Trial.

Importance: There have been heterogeneous results related to sex differences in prognosis after percutaneous coronary artery intervention (PCI) for complex coronary artery lesions. Objective: To evaluate potential differences in outcomes with intravascular imaging-guided PCI of complex coronary artery lesions between women and men. Design, Setting, and Participants: This prespecified substudy evaluates the interaction of sex in the investigator-initiated, open-label, multicenter RENOVATE-COMPLEX-PCI randomized clinical trial, which demonstrated the superiority of intravascular imaging-guided PCI compared with angiography-guided PCI in patients with complex coronary artery lesions. The trial was conducted at 20 sites in Korea. Patients with complex coronary artery lesions undergoing PCI were enrolled between May 2018 and May 2021, and the median (IQR) follow-up period was 2.1 (1.4-3.0) years. Data were analyzed from December 2022 to December 2023. Interventions: After diagnostic coronary angiography, eligible patients were randomly assigned in a 2:1 ratio to receive intravascular imaging-guided PCI or angiography-guided PCI. The choice and timing of the intravascular imaging device were left to the operators' discretion. Main Outcomes and Measures: The primary end point was target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Secondary end points included individual components of the primary end point. Results: Of 1639 included patients, 339 (20.7%) were women, and the mean (SD) age was 65.6 (10.2) years. There was no difference in the risk of the primary end point between women and men (9.4% vs 8.3%; adjusted hazard ratio [HR], 1.39; 95% CI, 0.89-2.18; P = .15). Intravascular imaging-guided PCI tended to have lower incidence of the primary end point than angiography-guided PCI in both women (5.2% vs 14.5%; adjusted HR, 0.34; 95% CI, 0.15-0.78; P = .01) and men (8.3% vs 11.7%; adjusted HR, 0.72; 95% CI, 0.49-1.05; P = .09) without significant interaction (P for interaction = .86). Conclusions and Relevance: In patients undergoing complex PCI, compared with angiographic guidance, intravascular imaging guidance was associated with similar reduction in the risk of target vessel failure among women and men. The treatment benefit of intravascular imaging-guided PCI showed no significant interaction between treatment strategy and sex. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.

Protective effect of increased O-GlcNAc cycling against 6-OHDA induced Parkinson's disease pathology.

This study aimed to elucidate the role of O-GlcNAc cycling in 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD)-like neurodegeneration and the underlying mechanisms. We observed dose-dependent downregulation of O-GlcNAcylation, accompanied by an increase in O-GlcNAcase following 6-OHDA treatment in both mouse brain and Neuro2a cells. Interestingly, elevating O-GlcNAcylation through glucosamine (GlcN) injection provided protection against PD pathogenesis induced by 6-OHDA. At the behavioral level, GlcN mitigated motor deficits induced by 6-OHDA, as determined using the pole, cylinder, and apomorphine rotation tests. Furthermore, GlcN attenuated 6-OHDA-induced neuroinflammation and mitochondrial dysfunction. Notably, augmented O-GlcNAcylation, achieved through O-GlcNAc transferase (OGT) overexpression in mouse brain, conferred protection against 6-OHDA-induced PD pathology, encompassing neuronal cell death, motor deficits, neuroinflammation, and mitochondrial dysfunction. These collective findings suggest that O-GlcNAcylation plays a crucial role in the normal functioning of dopamine neurons. Moreover, enhancing O-GlcNAcylation through genetic and pharmacological means could effectively ameliorate neurodegeneration and motor impairment in an animal model of PD. These results propose a potential strategy for safeguarding against the deterioration of dopamine neurons implicated in PD pathogenesis.

Super-Toughness Carbon Nanotube Yarns by Bio-Inspired Nano-Coiling Engineering.

Lightweight structural materials are commonly used as effective fillers for advanced composites with high toughness. This study focused on enhancing the toughness of direct-spun carbon nanotube yarns (CNTYs) by controlling the micro-textural structure using a water-gap-based direct spinning. Drawing inspiration from the structural features of natural spider silk fibroin, characterized by an α-helix in the amorphous region and ß-sheet in the crystalline region, multiscale bundles within CNTYs are reorganized into a unique nano-coil-like structure. This nano-coiled structure facilitated the efficient dissipation of external mechanical loads through densification with the rearrangement of multiscale bundles, improving specific strength and strain. The resulting CNTYs exhibited exceptional mechanical properties with toughness reaching 250 J g-1, making them promising alternatives to commercially available fibers in lightweight, high-toughness applications. These findings highlight the significance of nano-coiling engineering for emulating bio-inspired micro-textural structures, achieving remarkable enhancement in the toughness of CNTYs.

Prognostic Role of Initial Thromboelastography in Emergency Department Patients with Primary Postpartum Hemorrhage: Association with Massive Transfusion.

BACKGROUND: The early prediction of the need for massive transfusions (MTs) and the preparation of blood products are essential for managing patients with primary postpartum hemorrhage (PPH). Thromboelastography (TEG) enables a thorough evaluation of coagulation status and is useful for guiding the treatment of hemorrhagic events in various diseases. We investigated the role of TEG in predicting the need for MT in patients with primary PPH. METHODS: A retrospective observational study was conducted in the emergency department (ED) of a university-affiliated, tertiary referral center between November 2015 and August 2023. TEG was performed upon admission. We defined MT as the requirement for transfusion of more than 10 units of packed red blood cells within the first 24 h. The primary outcome was the need for MT. RESULTS: Among the 184 patients with initial TEG, 34 (18.5%) required MT. Except for lysis after 30 min, the MT and non-MT groups had significantly different TEG values. Based on multivariate analysis, an angle < 60 was an independent predictor of MT (odds ratio (OR) 7.769; 95% confidence interval (CI), 2.736-22.062), along with lactate (OR, 1.674; 95% CI, 1.218-2.300) and shock index > 0.9 (OR, 4.638; 95% CI, 1.784-12.056). Alpha angle < 60 degrees indicated the need for MT with 73.5% sensitivity, 72.0% specificity, and 92.3% negative predictive value. CONCLUSIONS: Point-of-care testing of TEG has the potential to be a useful tool in accurately predicting the necessity for MT in ED patients with primary PPH at an early stage.

Cost-Effectiveness of Intravascular Imaging-Guided Complex PCI: Prespecified Analysis of RENOVATE-COMPLEX-PCI Trial.

BACKGROUND: Although clinical benefits of intravascular imaging-guided percutaneous coronary intervention (PCI) in patients with complex coronary artery lesions have been observed in previous trials, the cost-effectiveness of this strategy is uncertain. METHODS: RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance vs Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention) was conducted in Korea between May 2018 and May 2021. This prespecified cost-effectiveness substudy was conducted using Markov model that simulated 3 states: (1) post-PCI, (2) spontaneous myocardial infarction, and (3) death. A simulated cohort was derived from the intention-to-treat population, and input parameters were extracted from either the trial data or previous publications. Cost-effectiveness was evaluated using time horizon of 3 years (within trial) and lifetime. The primary outcome was incremental cost-effectiveness ratio (ICER), an indicator of incremental cost on additional quality-adjusted life years (QALYs) gained, in intravascular imaging-guided PCI compared with angiography-guided PCI. The current analysis was performed using the Korean health care sector perspective with reporting the results in US dollar (1200 Korean Won, ₩=1 dollar, $). Willingness to pay threshold was $35 000 per QALY gained. RESULTS: A total of 1639 patients were included in the trial. During 3-year follow-up, medical costs ($8661 versus $7236; incremental cost, $1426) and QALY (2.34 versus 2.31; incremental QALY, 0.025) were both higher in intravascular imaging-guided PCI than angiography-guided PCI, resulting incremental cost-effectiveness ratio of $57 040 per QALY gained within trial data. Conversely, lifetime simulation showed total cumulative medical cost was reversed between the 2 groups ($40 455 versus $49 519; incremental cost, -$9063) with consistently higher QALY (8.24 versus 7.89; incremental QALY, 0.910) in intravascular imaging-guided PCI than angiography-guided PCI, resulting in a dominant incremental cost-effectiveness ratio. Consistently, 70% of probabilistic iterations showed cost-effectiveness of intravascular imaging-guided PCI in probabilistic sensitivity analysis. CONCLUSIONS: The current cost-effectiveness analysis suggests that imaging-guided PCI is more cost-effective than angiography-guided PCI by reducing medical cost and increasing quality-of-life in complex coronary artery lesions in long-term follow-up. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03381872.

Comparison of Modified Shock Index and Shock Index for Predicting Massive Transfusion in Women with Primary Postpartum Hemorrhage: A Retrospective Study.

BACKGROUND The modified shock index (MSI) is calculated as the ratio of heart rate (HR) to mean arterial pressure (MAP) and has been used to predict the need for massive transfusion (MT) in trauma patients. This retrospective study from a single center aimed to compare the MSI with the traditional shock index (SI) to predict the need for MT in 612 women diagnosed with primary postpartum hemorrhage (PPH) at the Emergency Department (ED) between January 2004 and August 2023. MATERIAL AND METHODS The patients were divided into the MT group and the non-MT group. The predictive power of MSI and SI was compared using the areas under the receiver operating characteristic curve (AUC). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated. RESULTS Out of 612 patients, 105 (17.2%) required MT. The MT group had higher median values than the non-MT group for MSI (1.58 vs 1.07, P<0.001) and SI (1.22 vs 0.80, P<0.001). The AUC for MSI, with a value of 0.811 (95% confidence interval [CI], 0.778-0.841), did not demonstrate a significant difference compared to the AUC for SI, which was 0.829 (95% CI, 0.797-0.858) (P=0.066). The optimal cutoff values for MSI and SI were 1.34 and 1.07, respectively. The specificity and PPV for MT were 77.1% and 40.2% for MSI, and 83.2% and 45.9% for SI. CONCLUSIONS Both MSI and SI were effective in predicting MT in patients with primary PPH. However, MSI did not demonstrate superior performance to SI.

Current evidence for prognostic benefit of intravascular imaging-guided percutaneous coronary intervention in chronic total occlusion intervention.

Although percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) has been increasing in recent years, CTO PCI is still one of the most challenging procedures with relatively higher rates of procedural complications and adverse clinical events after PCI. Due to the innate limitations of invasive coronary angiography, intravascular imaging (IVI) has been used as an adjunctive tool to complement PCI, especially in complex coronary artery disease. Considering the complexity of CTO lesions, the role of IVI is particularly important in CTO intervention. IVI has been a useful adjunctive tool in every step of CTO PCI including assisted wire crossing, confirmation of wire location within CTO segment, and stent optimization. The meticulous use of IVI has been one of the greatest contributors to recent progress of CTO PCI. Nevertheless, studies evaluating the role of IVI during CTO PCI are limited. The current review provides a comprehensive overview of the mechanistic advantages of IVI in CTO PCI, summarizes previous studies and trials, and presents future perspective of IVI in CTO PCI.

Understanding the Impact of Nitrogen Availability: A Limiting Factor for Enhancing Fucoxanthin Productivity in Microalgae Cultivation.

This study aimed to investigate the regulation of fucoxanthin (FX) biosynthesis under various nitrogen conditions to optimize FX productivity in Phaeodactylum tricornutum. Apart from light, nitrogen availability significantly affects the FX production of microalgae; however, the underlying mechanism remains unclear. In batch culture, P. tricornutum was cultivated with normal (NN, 0.882 mM sodium nitrate), limited (LN, 0.22 mM), and high (HN, 8.82 mM) initial nitrogen concentrations in f/2 medium. Microalgal growth and photosynthetic pigment production were examined, and day 5 samples were subjected to fucoxanthin-chlorophyll a/c-binding protein (FCP) proteomic and transcriptomic analyses. The result demonstrated that HN promoted FX productivity by extending the exponential growth phase for higher biomass and FX accumulation stage (P1), showing a continuous increase in FX accumulation on day 6. Augmented FX biosynthesis via the upregulation of carotenogenesis could be primarily attributed to enhanced FCP formation in the thylakoid membrane. Key proteins, such as LHC3/4, LHCF8, LHCF5, and LHCF10, and key genes, such as PtPSY, PtPDS, and PtVDE, were upregulated under nitrogen repletion. Finally, the combination of low light and HN prolonged the P1 stage to day 10, resulting in maximal FX productivity to 9.82 ± 0.56 mg/L/day, demonstrating an effective strategy for enhancing FX production in microalgae cultivation.

Selective estrogen receptor modulators (SERMs) with vitamin D composite agent can prevent fracture better than SERMs treatment: based on the National Health Claims Database 2017-2019.

With the analysis of nationwide health claim data, treatment with the composite agent of SERMs and vitamin D reduces the risk of osteoporotic fracture and hip fracture better compared to SERMs treatment in women with osteoporosis aged ≥ 50 years. PURPOSE: This study compared the potential of the composite agent of selective estrogen receptor modulators (SERMs) and vitamin D (SERM + VitD) with that of SERMs-only for fracture prevention and mortality reduction in women aged ≥ 50 years. METHODS: The incidence of osteoporotic fracture (fractures of the vertebrae, hip, wrist, or humerus) and all-cause death after treatment with SERM + VitD and SERMs were characterized using the Korean National Health Insurance Service database 2017-2019. The participants were divided into two groups (SERM + VitD vs SERMs). After exclusion and propensity score matching, 2,885 patients from each group were included in the analysis. Fracture incidence was compared between groups. Kaplan-Meier curves were used to compare mortality. Cox proportional hazards regression analysis was used to compare the risks of fracture occurrence and mortality between the groups. RESULTS: The incidence rate (138.6/10,000 vs. 192.4/10,000 person-years), and risk of osteoporotic fractures (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61-0.97; p = 0.024) were lower in the SERM + VitD group than in the SERMs group. Analysis for specific fractures showed a lower hazard of hip fracture in the SERM + VitD group (HR, 0.25; 95% CI, 0.09-0.71; p = 0.009). No difference was observed between the groups regarding mortality. CONCLUSION: The risk of osteoporotic fractures, especially hip fractures, was lower in the SERM + VitD group than in the SERMs group. Therefore, the composite agent of SERMs and vitamin D can be considered as a viable option for postmenopausal women with a relatively low fracture risk.

First report of wilt disease caused by Pythium myriotylum on peanut plants in Korea.

Peanut (Arachis hypogaea L.) has long been cultivated worldwide as an important crop for oil and protein production. Among the various diseases in peanut plants, wilt diseases caused by soil-borne pathogens such as Ralstonia solanacearum and Verticillium dahliae are especially destructive and substantially diminish both quantity and quality in peanut production (Kokalis-Burelle et al., 1997; Thiessen et al., 2012). In July 2022, wilt symptoms were observed in 1 to 3% of the area of peanut fields in Yeoju-si, Korea (37°23´04.0˝N; 127°33´43.0˝E). The xylem in the stems of the wilted plants was dark brown at the soil-surface, which is a representative symptom of vascular wilt pathogens (Yadeta et al. 2013). To isolate the causative pathogens, the stems exhibiting dark lesions were disinfected with 1% NaOCl for 1 min, rinsed with sterile distilled water, and placed on potato dextrose agar medium. The plates were incubated at 25℃ for 2 days, and white hyphae that grew out from the tissues were subcultured twice on V8 juice agar (V8A) medium. Among the 3 isolates, morphological characteristics of the representative strain YJ1-2 were observed under a microscope. The sporangia were terminal intercalary, filamentous, inflated lobulate, and ranging from 37.4 to 73.6 µm in diameter. The antheridia were diclinous, with clavate, elongate, and crook-necked shapes. The oogonia were mostly globose, with an average of 27.1 µm (range from 20.2 to 35.2 µm, n = 50) in diameter, and mated with one to several antheridia. Both plerotic or aplerotic oospores were observed. Overall, the morphological characteristics of the sporangia, antheridia, oogonia, and oospores indicated that YJ1-2 belongs to the genus Pythium. To genetically characterize YJ1-2, genomic DNA was extracted using cetyltrimethylammonium bromide buffer, and the internal transcribed spacer (ITS) region and cytochrome c oxidase subunit I (cox1) gene were amplified by PCR using primer sets ITS4/ITS5 and OomCoxI-Levlo/ OomCoxI-Levup, respectively (White et al., 1990; Robideau et al. 2011), sequenced, and identified using BLASTN (NCBI, National Center for Biotechnology Information). The ITS sequence (NCBI Acc. No. OR125595) of YJ1-2 has 99% similarity with that of P. myriotylum isolate PY39 (NCBI Acc. No. KX671096). A neighbor-joining phylogenetic tree was constructed from aligned cox1 sequence (NCBI Acc. No. OR224334) of the 10 Pythium species strains including YJ1-2 by CLUSTALW method was used as an outgroup. The YJ1-2 was most closely related to P. myriotylum isolate PM30 (NCBI Acc. No. MT823167). To substantiate the pathogenicity of YJ1-2, the crown roots of peanut plants grown in pots for 4 weeks were wounded using a sterile tweezer, and the mycelial plugs of YJ1-2 cultured for 5 days on V8A were inoculated on the wounds. The inoculated plants were cultivated in a growth chamber at 30℃ and 70% relative humidity with a 12-h photoperiod. The infected peanut plants exhibited wilt symptoms 11 days after inoculation, consistent with the initial observation, while uninoculated plants remained healthy. To satisfy Koch's postulates, white mycelia were re-isolated from the stems of inoculated plants and axenically cultured in V8A. The morphologies and ITS sequences of the re-isolates were consistent with those of YJ1-2. P. myriotylum has been reported as a causal pathogen of peanut pod rot in the United States and China. However, to the best of our knowledge, this is the first report of wilt disease in peanut plants caused by P. myriotylum in Korea. To prevent the incidence of wilt disease, we will continue our investigations to develop control strategies, including the selection of appropriate agrochemicals.

Intravascular Imaging-Guided Percutaneous Coronary Intervention Before and After Standardized Optimization Protocols.

BACKGROUND: Although benefits of intravascular imaging (IVI) in percutaneous coronary intervention (PCI) have been observed in previous studies, it is not known whether changes in contemporary practice, especially with application of standardized optimization protocols, have improved clinical outcomes. OBJECTIVES: The authors sought to investigate whether clinical outcomes of IVI-guided PCI are different before and after the application of standardized optimization protocols in using IVI. METHODS: 2,972 patients from an institutional registry (2008-2015, before application of standardized optimization protocols, the past group) and 1,639 patients from a recently published trial (2018-2021 after application of standardized optimization protocols, the present group) were divided into 2 groups according to use of IVI. The primary outcome was 3-year target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization. RESULTS: Significant reduction of TVF was observed in the IVI-guided PCI group compared with the angiography-guided PCI group (10.0% vs 6.7%; HR: 0.77; 95% CI: 0.61-0.97; P = 0.027), mainly driven by reduced cardiac death or myocardial infarction in both past and present IVI-guided PCI groups. When comparing past IVI and present IVI groups, TVF was significantly lower in the present IVI group (8.5% vs 5.1%; HR: 0.63; 95% CI: 0.42-0.94; P = 0.025), with the difference being driven by reduced target vessel revascularization in the present IVI group. Consistent results were observed in inverse-probability-weighting adjusted analysis. CONCLUSIONS: IVI-guided PCI improved clinical outcomes more than angiography-guided PCI. In addition, application of standardized optimization protocols when using IVI further improved clinical outcomes after PCI. (Intravascular Imaging- Versus Angiography-Guided Percutaneous Coronary Intervention For Complex Coronary Artery Disease [RENOVATE-COMPLEX-PCI]; NCT03381872; and the institutional cardiovascular catheterization database of Samsung Medical Center: Long-Term Outcomes and Prognostic Factors in Patient Undergoing CABG or PCI; NCT03870815).

Glucosamine increases macrophage lipid accumulation by regulating the mammalian target of rapamycin signaling pathway.

Elevated blood glucose is associated with an increased risk of atherosclerosis. Data from the current study showed that glucosamine (GlcN), a normal glucose metabolite of the hexosamine biosynthetic pathway (HBP), promoted lipid accumulation in RAW264.7 macrophage cells. Oleic acid- and lipopolysaccharide (LPS)-induced lipid accumulation was further enhanced by GlcN in RAW264.7 cells, although there was no a significant change in the rate of fatty acid uptake. GlcN increased acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), scavenger receptor class A, liver X receptor, and sterol regulatory elementbinding protein-1c (SREBP-1c) mRNA expression, and; conversely, suppressed ATP-binding cassette transporter A1 (ABCA-1) and ABCG-1 expression. Additionally, GlcN promoted O-GlcNAcylation of nuclear SREBP-1 but did not affect its DNA binding activity. GlcN stimulated phosphorylation of mammalian target of rapamycin (mTOR) and S6 kinase. Rapamycin, a mTOR-specific inhibitor, suppressed GlcN-induced lipid accumulation in RAW264.7 cells. The GlcN-mediated increase in ACC and FAS mRNA was suppressed, while the decrease in ABCA-1 and ABCG-1 by GlcN was not significantly altered by rapamycin. Together, our results highlight the importance of the mTOR signaling pathway in GlcN-induced macrophage lipid accumulation and further support a potential link between mTOR and HBP signaling in lipogenesis. [BMB Reports 2024; 57(2): 92-97].

Changes in alcohol consumption habits and risk of atrial fibrillation: a nationwide population-based study.

AIMS: Heavy alcohol consumption is an established risk factor for atrial fibrillation (AF). However, the association between habitual changes in heavy habitual drinkers and incident AF remains unclear. The aim of this study was to evaluate whether absolute abstinence or reduced drinking decreases incident AF in heavy habitual drinkers. METHODS AND RESULTS: Atrial fibrillation-free participants with heavy alcohol consumption registered in the Korean National Health Insurance Service database between 2005 and 2008 were enrolled. Habitual changes in alcohol consumption between 2009 and 2012 were classified as sustained heavy drinking, reduced drinking, and absolute abstinence. The primary outcome measure was new-onset AF during the follow-up. To minimize the effect of confounding variables on outcome events, inverse probability of treatment weighting (IPTW) analysis was performed. Overall, 19 425 participants were evaluated. The absolute abstinence group showed a 63% lower incidence of AF (IPTW hazard ratio: 0.379, 95% confidence interval: 0.169-0.853) than did the sustained heavy drinking group. Subgroup analysis identified that abstinence significantly reduced incident AF in participants with normal body mass index and without hypertension, diabetes, dyslipidaemia, heart failure, stroke, chronic kidney disease, or coronary artery disease (all P-value <0.05). There was no statistical difference in incident AF in participants with reduced drinking compared with sustained heavy alcohol group. CONCLUSION: Absolute abstinence could reduce the incidence of AF in heavy alcohol drinkers. Comprehensive clinical measures and public health policies are warranted to motivate alcohol abstinence in heavy drinkers.

In this study of 19 425 participants, we investigated whether alcohol consumption reduction was associated with lower risk of incident atrial fibrillation (AF) in individuals with chronic heavy alcohol consumption. The absolute abstinence significantly reduced incident AF, but reducing alcohol consumption was not associated with a lower incident AF. The benefit of absolute abstinence for incidence of AF was significantly identified in participants with normal body mass index and without hypertension, diabetes, dyslipidaemia, heart failure, stroke, chronic kidney disease, or coronary artery disease.

Respiratory rate­oxygenation (ROX) index for predicting high-flow nasal cannula failure in patients with and without COVID-19.

BACKGROUND: The predictive value of the respiratory rate­oxygenation (ROX) index for a high-flow nasal cannula (HFNC) in patients with COVID-19 with acute hypoxemic respiratory failure (AHRF) may differ from patients without COVID-19 with AHRF, but these patients have not yet been compared. We compared the diagnostic accuracy of the ROX index for HFNC failure in patients with AHRF with and without COVID-19 during acute emergency department (ED) visits. METHODS: We performed a retrospective analysis of patients with AHRF treated with an HFNC in an ED between October 2020 and April 2022. The ROX index was calculated at 1, 2, 4, 6, 12, and 24 h after HFNC placement. The primary outcome was the failure of the HFNC, which was defined as the need for subsequent intubation or death within 72 h. A receiver operating characteristic (ROC) curve was used to evaluate discriminative power of the ROX index for HFNC failure. RESULTS: Among 448 patients with AHRF treated with an HFNC in an ED, 78 (17.4%) patients were confirmed to have COVID-19. There was no significant difference in the HFNC failure rates between the non-COVID-19 and COVID-19 groups (29.5% vs. 33.3%, p = 0.498). The median ROX index was higher in the non-COVID-19 group than in the COVID-19 group at all time points. The prognostic power of the ROX index for HFNC failure as evaluated by the area under the ROC curve was generally higher in the COVID-19 group (0.73-0.83) than the non-COVID-19 group (0.62-0.75). The timing of the highest prognostic value of the ROX index for HFNC failure was at 4 h for the non-COVID-19 group, whereas in the COVID-19 group, its performance remained consistent from 1 h to 6 h. The optimal cutoff values were 6.48 and 5.79 for the non-COVID-19 and COVID-19 groups, respectively. CONCLUSIONS: The ROX index had an acceptable discriminative power for predicting HFNC failure in patients with AHRF with and without COVID-19 in the ED. However, the higher ROX index thresholds than those in previous publications involving intensive care unit (ICU) patients suggest the need for careful monitoring and establishment of a new threshold for patients admitted outside the ICU.

Therapeutic Nanodiamonds Containing Icariin Ameliorate the Progression of Osteoarthritis in Rats.

In present study, icariin (ICA)/tannic acid (TA)-nanodiamonds (NDs) were prepared as follows. ICA was anchored to ND surfaces with absorbed TA (ICA/TA-NDs) and we evaluated their in vitro anti-inflammatory effects on lipopolysaccharide (LPS)-activated macrophages and in vivo cartilage protective effects on a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). The ICA/TA-NDs showed prolonged release of ICA from the NDs for up to 28 days in a sustained manner. ICA/TA-NDs inhibited the mRNA levels of pro-inflammatory elements, including matrix metalloproteinases-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and increased the mRNA levels of anti-inflammatory factors (i.e., IL-4 and IL-10) in LPS-activated RAW 264.7 macrophages. Animal studies exhibited that intra-articular injection of ICA/TA-NDs notably suppressed levels of IL-6, MMP-3, and TNF-α and induced level of IL-10 in serum of MIA-induced OA rat models in a dose-dependent manner. Furthermore, these noticeable anti-inflammatory effects of ICA/TA-NDs remarkably contributed to the protection of the progression of MIA-induced OA and cartilage degradation, as exhibited by micro-computed tomography (micro-CT), gross findings, and histological investigations. Accordingly, in vitro and in vivo findings suggest that the prolonged ICA delivery of ICA/TA-NDs possesses an excellent latent to improve inflammation as well as defend against cartilage disorder in OA.

Clinical Benefit of Intravascular Imaging Compared With Conventional Angiography in Left Main Coronary Artery Intervention.

BACKGROUND: The RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention) demonstrated that intravascular imaging-guided percutaneous coronary intervention (PCI) improved clinical outcome compared with angiography-guided PCI for patients with complex coronary artery lesions. This study aims to assess whether the prognostic benefit of intravascular imaging-guided procedural optimization persists in patients undergoing PCI for left main coronary artery disease. METHODS: Of 1639 patients enrolled in the RENOVATE-COMPLEX-PCI, 192 patients with left main coronary artery disease were selected for the current prespecified substudy. Selected patients were randomly assigned to either the intravascular imaging-guided PCI group (n=138) or the angiography-guided PCI group (n=54). The primary end point was target vessel failure defined as a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. RESULTS: At a median follow-up of 2.1 years (interquartile range 1.1 to 3.0 years), intravascular imaging-guided PCI was associated with lower incidence of primary end point compared with angiography-guided PCI (6.8% versus 25.1%; hazard ratio, 0.31 [95% CI, 0.13-0.76]; P=0.010). This significant reduction in primary end point was mainly driven by a lower risk of cardiac death or spontaneous target vessel-related myocardial infarction (1.6% versus 12.7%; hazard ratio, 0.16 [95% CI, 0.03-0.82]; P=0.028). Intravascular imaging-guided PCI was independently associated with a lower risk of primary end point, even after adjusting for various clinical factors (hazard ratio, 0.29 [95% CI, 0.12-0.72]; P=0.007). CONCLUSIONS: Intravascular imaging-guided PCI showed clinical benefit over angiography-guided PCI for left main coronary artery disease in reducing the risk of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03381872.

Intravascular Imaging in Patients With Complex Coronary Lesions and Chronic Kidney Disease.

Importance: As patients with chronic kidney disease (CKD) are more likely to have complex coronary lesions, intravascular imaging guidance in percutaneous coronary intervention (PCI) for this population could be potentially beneficial. Objectives: To investigate whether the outcomes of intravascular imaging-guided procedural optimization would be different according to the presence of CKD. Design, Setting, and Participants: This was a prespecified substudy of RENOVATE-COMPLEX-PCI, a recently published multicenter randomized clinical trial in Korea studying the benefits of intravascular imaging for complex coronary lesions. Patients with complex coronary lesions, with or without CKD, were enrolled between May 2018 and May 2021. Data were analyzed from January to June 2023. Interventions: PCI in each group was done either under the guidance of intravascular imaging or angiography alone. Main Outcomes and Measures: The primary end point was target vessel failure (TVF) at the 3-year point, defined as a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Results: A total of 1639 patients (1300 male [79.3%]) treated with PCI for complex coronary lesions were stratified into CKD (296 participants) and non-CKD (1343 participants) groups. The mean (SD) age of each group was 70.3 (9.4) and 64.5 (10.1) years, and mean (SD) estimated serum creatinine was 2.9 (5.3) and 0.8 (0.2) mg/dL for CKD and non-CKD groups, respectively. Intravascular imaging-guided revascularization was associated with significantly lower incidence of the primary end point compared with angiography-guided revascularization in both CKD (13.3% vs 23.3%; hazard ratio [HR], 0.51; 95% CI, 0.27-0.93; P = .03) and non-CKD (6.4% vs 9.9%; HR, 0.66; 95% CI, 0.44-0.99; P = .05) groups. The significantly lower incidence of the primary end point was mainly associated with the lower risk of cardiac death or target vessel-related myocardial infarction (9.4% vs 22.2%; HR, 0.39; 95% CI, 0.20-0.76; P = .006) in the CKD group and by target vessel revascularization (3.0% vs 5.5%; HR, 0.55; 95% CI, 0.30-0.99; P = .05) in the non-CKD group. Those with a glomerular filtration rate of at least 30 mL/min/1.73m2 and less than 60 ml/kg/1.73m2 showed the greatest benefit from imaging-guided complex PCI (8.8% vs 21.2%; HR, 0.28; 95% CI, 0.11-0.68; P = .02). Conclusions and Relevance: In this prespecified cohort substudy of the Randomized Controlled Trial of Intravascular Imaging Guidance versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention trial, intravascular imaging guidance showed clinical benefit over angiography guidance in reducing the risk of TVF, regardless of the presence of CKD. The greatest benefits of imaging-guided complex PCI were observed in stage 3 CKD. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.