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Abstract Cerebral hyperperfusion syndrome (CHS) is a serious complication after bypass surgery in Moyamoya disease (MMD), with autoregulatory dysfunction being a major pathogenesis. This study investigated the change of perioperative autoregulation and preoperative prognostic potentials in MMD with postoperative CHS. Among 26 hemispheres in 24 patients with adult MMD undergoing combined bypass, 13 hemispheres experienced postoperative CHS. Arterial blood pressure and cerebral blood flow velocity were perioperatively measured with transcranial Doppler ultrasound during resting and the Valsalva maneuver (VM). Autoregulation profiles were discovered in both the CHS and non-CHS groups using mean flow index (Mxa), VM Autoregulatory Index (VMAI), and a new metric termed VM Overshooting Index (VMOI). The CHS group had inferior autoregulation than the non-CHS group as indicated by VMOI on preoperative day 1 and postoperative 3rd day. Deteriorated autoregulation was observed via Mxa in the CHS group than in the non-CHS group on the postoperative 3rd and discharge days. Postoperative longitudinal autoregulation recovery in the CHS group was found in a logistic regression model with diminished group differences over the time course. This work represents a step forward in utilizing autoregulation indices derived from physiological signals, to predict the postoperative CHS in adult MMD.

Abstract Background and objectives This study aimed to analyze and present updated trends in atrial fibrillation (AF) epidemiology within the Korean population, providing a foundation for planning and implementing appropriate management and treatment strategies for patients with AF. Patients and methods We used the Korean National Health Insurance Service database to evaluate the prevalence, incidence, comorbidities, and clinical adverse outcomes of patients with AF in Korea between 2013 and 2022. Results AF prevalence in Korean adults aged ≥ 20 years doubled (1.1 to 2.2%) between 2013 and 2022, with significant increases observed across various sex and age groups. Similarly, the number of newly diagnosed patients with AF per year increased steadily, with the incidence rising from 184 to 275 per 100,000 person-years, particularly among older populations. Over this period, the mean age of patients with AF increased from 67.7 to 70.3 years, and comorbidities prevalence and CHA2DS2-VASc score rose significantly, indicating a higher stroke risk. Compared with patients without AF, AF was associated with an increased risk of mortality (hazard ratio [HR]: 1.78), ischemic stroke (HR: 2.39), major bleeding (HR: 2.10), myocardial infarction (HR: 1.44), and heart failure admission (HR: 2.42). Conclusion AF prevalence and incidence have steadily increased between 2013 and 2022, with a more pronounced increase in older patients. Patients with AF are increasingly becoming a high-risk population and are at increased risk of clinical adverse outcomes compared to non-AF patients. Therefore, a sustained national effort to improve AF awareness and comprehensive care quality for patients with AF is required.

Background We hypothesized that analysis of serial ECGs could predict new‐onset atrial fibrillation (AF) more accurately than analysis of a single ECG by detecting the subtle cardiac remodeling that occurs immediately before AF occurrence. Our aim in this study was to compare the performance of 2 types of machine learning (ML) algorithms. Methods and Results Standard 12‐lead ECGs of patients selected by cardiologists between January 2010 and May 2021 were used for ML model development. Two ML models (single ECG and serial ECG) were developed using a light gradient boosting machine‐learning algorithm. Model performance was evaluated based on the area under the receiver operating characteristic curve, sensitivity, specificity, accuracy, and F1 score. We trained the ML models on 415 964 ECGs from 176 090 patients. When testing the 2 ML models using external validation data sets, the performance of the serial‐ML model was significantly better than that of the single‐ML model for predicting new‐onset AF (single‐ versus serial‐ML model: sensitivity 0.744 versus 0.810; specificity 0.742 versus 0.822; accuracy 0.743 versus 0.816; F1 score 0.743 versus 0.815; area under the receiver operating characteristic curve 0.812 versus 0.880; P

Abstract The necessity of bilateral bypass in adult moyamoya disease (MMD) remains unclear despite its recommendation for pediatric and hemorrhagic cases. We aimed to investigate the natural course of hemodynamically stable unoperated hemispheres after bypass surgery for symptomatic and hemodynamically unstable hemispheres in adult patients with ischemic MMD. Among 288 patients, the mean age at the first operation of the unstable hemispheres was 40.8 ± 12.2 years. The mean follow-up period was 62.9 ± 46.5 months. 45 patients (15.6%) experienced stroke events in the unoperated hemisphere, consisting of hemorrhagic stroke in 8 (2.8%) and ischemic stroke in 37 (12.8%), including progressive transient ischemic attack in 25 (8.7%) and infarction in 12 (4.2%). Among them, 39 patients (13.5%) underwent bypass surgery. The annual risk of total stroke is 3.0%/patient-year, with 2.5% for ischemic stroke and 0.5% for hemorrhagic stroke. The 5- and 10-year cumulative risks of ischemic stroke were 13.4% and 18.3%, respectively, and those of hemorrhagic stroke were each 3.2%. The natural course of hemodynamically stable hemispheres contralateral to the operated ones appeared fairly good. Additional bypass surgery on the unoperated hemispheres should be considered for symptomatic and hemodynamically unstable hemispheres in adult patients with ischemic MMD during the follow-up.

BackgroundData on off-label reduced dose risk among patients with atrial fibrillation (AF) who qualify for a single-dose reduction of apixaban is scarce.ObjectivesWe prospectively assessed apixaban dosing and clinical characteristics in AF patients meeting a dose reduction criterion.MethodsThe multicentre, prospective cohort study, the efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE), encompasses patients with AF who met the criteria for a single-dose reduction of apixaban and were given varying doses of apixaban, either the on-label standard dose or the off-label reduced dose.ResultsOf 2,000 patients (mean age 74.3 ± 7.9 years, 55.8% women), 29.7% were ≥80 years, 62.6% weighed ≤60 kg, and 7.8% had serum creatinine ≥1.5 mg/dL. Of these, 51.3% were prescribed an off-label reduced dose of apixaban. The off-label group was characterized with older age, more comorbidities, and antiplatelet agents, while the on-label group had more prior strokes. Physicians preferred off-label reduced dose in the “marginal zone,” defined as age 75–80 years, weight 60–65 kg, and creatinine levels 1.2–1.5 mg/dL.ConclusionsIn real-world clinical setting of the Korean population, off-label reduced dose apixaban was administered to nearly half of the patients who qualified for a single dose reduction. This reduced dosage was more commonly prescribed to patients with frail characteristics, while patients with a history of stroke were more often given the standard dose as per the label. A future study is planned to contrast the safety and effectiveness of the standard dose against the reduced dose of apixaban in this population.

Background: The peptidyl-prolyl isomerase (PIN1) plays a vital role in cellular processes, including intracellular signaling and apoptosis. While oxidative stress is considered one of the primary mechanisms of pathogenesis in brain ischemic injury, the precise function of PIN1 in this disease remains to be elucidated. Objective: We constructed a cell-permeable PEP-1–PIN1 fusion protein and investigated PIN1’s function in HT-22 hippocampal cells as well as in a brain ischemic injury gerbil model. Methods: Transduction of PEP-1–PIN1 into HT-22 cells and signaling pathways were determined by Western blot analysis. Intracellular reactive oxygen species (ROS) production and DNA damage was confirmed by DCF-DA and TUNEL staining. Cell viability was determined by MTT assay. Protective effects of PEP-1-PIN1 against ischemic injury were examined using immunohistochemistry. Results: PEP-1–PIN1, when transduced into HT-22 hippocampal cells, inhibited cell death in H2O2-treated cells and markedly reduced DNA fragmentation and ROS production. This fusion protein also reduced phosphorylation of mitogen-activated protein kinase (MAPK) and modulated expression levels of apoptosis-signaling proteins in HT-22 cells. Furthermore, PEP-1–PIN1 was distributed in gerbil hippocampus neuronal cells after passing through the blood–brain barrier (BBB) and significantly protected against neuronal cell death and also decreased activation of microglia and astrocytes in an ischemic injury gerbil model. Conclusions: These results indicate that PEP-1–PIN1 can inhibit ischemic brain injury by reducing cellular ROS levels and regulating MAPK and apoptosis-signaling pathways, suggesting that PIN1 plays a protective role in H2O2-treated HT-22 cells and ischemic injury gerbil model.

Background The ECG is a simple, noninvasive screening method for cardiovascular disease and arrhythmia. The impact of ECG abnormality on mortality is not certain in low‐risk populations. To address this, we evaluated the association between ECG abnormality and mortality. Methods and Results We retrospectively assessed baseline ECG and all‐cause mortality and cardiovascular mortality in 660 383 patients presenting for medical check‐ups. Baseline ECG abnormalities were classified according to the Minnesota Code. Among the total 660 383 participants, 23 609 (3.6%) had major and 110 038 (16.7%) had minor ECG abnormalities. All‐cause mortality occurred in 7751 patients (1.1%) and cardiovascular mortality in 1180 (0.18%) over a median follow‐up period of 8.8 years. Major ECG abnormalities were associated with all‐cause mortality (hazard ratio [HR], 1.11 [95%, 1.03–1.2]) and cardiovascular mortality (HR, 1.92 [95% CI, 1.63–2.27]) compared with no ECG abnormalities. All‐cause mortality was associated with right atrial enlargement (HR, 2.11 [95% CI, 1.1–4.07]), left atrial enlargement (HR, 1.76 [95% CI, 1.1–2.84]), sinus tachycardia (HR, 1.52 [95% CI, 1.15–2.01]), complete atrioventricular block (HR, 2.1 [95% CI, 1.05–4.2]), atrial fibrillation (HR, 1.52 [95% CI, 1.26–1.84]), and left ventricular hypertrophy (HR, 1.15 [95% CI, 1.02–1.3]). Cardiovascular mortality was associated with left atrial enlargement (HR, 4.52 [95% CI, 2.15–9.5]), atrial fibrillation (HR, 3.22 [95% CI, 2.33–4.46]), left ventricular hypertrophy (HR, 1.72 [95% CI, 1.35–2.19]), major Q‐wave abnormality (HR, 1.6 [95% CI, 1.08–2.39]), and major ST‐T abnormality (HR, 1.76 [95% CI, 1.01–3.04]). Conclusions ECG abnormalities, including left atrial enlargement, left ventricular hypertrophy, atrial fibrillation, and major Q‐wave and ST‐T abnormalities, were associated with cardiovascular mortality in a low‐risk population.

CKLF-like MARVEL transmembrane domain-containing 3 (CMTM3), a member of the CMTM family that is closely related to tumor occurrence and progression, plays crucial roles in the immune system, cardiovascular system, and male reproductive system. Recently, CMTM3 has emerged as a potential target for treating diseases related to bone formation. However, additional studies are needed to understand the mechanisms by which CMTM3 regulates the process of osteogenic differentiation. In this study, we observed a significant downregulation of Cmtm3 expression during the transdifferentiation of C2C12 myoblasts into osteoblasts induced by BMP4. Cmtm3 overexpression suppressed proliferation and osteogenic differentiation in BMP4-induced C2C12 cells, whereas its knockdown conversely facilitated the process. Mechanistically, Cmtm3 overexpression upregulated both the protein and mRNA levels of p53 and p21. Conversely, Cmtm3 knockdown exerted the opposite effects. Additionally, we found that Cmtm3 interacts with p53 and increases protein stability by inhibiting proteasome-mediated ubiquitination and degradation. Notably, Trp53 downregulation abrogated the inhibitory effect of Cmtm3 on BMP4-induced proliferation and osteogenic differentiation of C2C12 myoblasts. Collectively, our findings provide key insights into the role of CMTM3 in regulating myoblast proliferation and transdifferentiation into osteoblasts, highlighting its significance in osteogenesis research.

Peptide-based drug development is a promising direction due to its excellent biological activity, minimal immunogenicity, high in vivo stability, and efficient tissue penetrability. GV1001, an amphiphilic peptide, has proven effective as an anti-cancer vaccine, but its effect on osteoblast differentiation is unknown. To identify proteins interacting with GV1001, biotin-conjugated GV1001 was constructed and confirmed by mass spectrometry. Proteomic analyses were performed to determine GV1001’s interaction with osteogenic proteins. GV1001 was highly associated with peptidyl-prolyl isomerase A and co-immunoprecipitation assays revealed that GV1001 bound to peptidyl-prolyl cis-trans isomerase 1 (Pin1). GV1001 significantly increased alkaline phosphatase (ALP) activity, bone nodule formation, and the expression of osteogenic gene markers. GV1001-induced osteogenic activity was enhanced by Pin1 overexpression and abolished by Pin1 knockdown. GV1001 increased the protein stability and transcriptional activity of Runx2 and Osterix. Importantly, GV1001 administration enhanced bone mass density in the OVX mouse model, as verified by µCT analysis. GV1001 demonstrated protective effects against bone loss in OVX mice by upregulating osteogenic differentiation via the Pin1-mediated protein stabilization of Runx2 and Osterix. GV1001 could be a potential candidate with anabolic effects for the prevention and treatment of osteoporosis.

Abstract Background Although rhythm control could be the best for symptomatic atrial fibrillation (AF), some patients fail to achieve sinus rhythm (SR). This study aimed to identify clinical risk factors of failed electrical cardioversion (ECV). Methods A total of 248 patients who received ECV for persistent AF or atrial flutter (AFL) were retrospectively reviewed. Patients were divided into three groups: Group 1 maintained SR for > 1 year, group 2 maintained SR ≤ 1 year after ECV, and group 3 failed ECV. SR maintenance was assessed using regular electrocardiography or Holter monitoring. Results Patients were divided into group 1 (73, 29%), group 2 (146, 59%), and group 3 (29, 12%). The mean age of patients was 60 ± 10 years, and 197 (79%) were male. Age, sex, and baseline characteristics were similar among groups. However, increased cardiac size, digoxin use, heart failure (HF), and decreased left ventricular ejection fraction (LVEF) were more common in group 3. Univariate analysis of clinical risk factors for failed ECV was increased cardiac size [hazard ratio (HR) 2.14 (95% confidence interval [CI], 1.06–4.34, p = 0.030)], digoxin use [HR 2.66 (95% CI, 1.15–6.14), p = 0.027], HF [HR 2.60 (95% CI, 1.32–5.09), p = 0.005], LVEF

Abstract We demonstrate continuous fabrication of flexible transducer devices consisting of interdigitated (IDT) Ag microelectrodes interconnected by ZnO nanowires (ZNWs), created via serially connected solution-processable micro- and nanofabrication processes. On an Ag layer obtainable from the mild thermal reduction of an ionic Ag ink coating, the roll-to-roll-driven photolithography process [termed photo roll lithography (PRL)] followed by wet-etching can be applied to continuously define the IDT microelectrode structure. Conformal ZNWs can then be grown selectively on the Ag electrodes to interconnect them via an Ag-mediated hydrothermal ZNW growth that does not require high-temperature seed sintering. Given that all of these constitutive processes are vacuum-free and solution-processable at a low temperature, and are compatible with continuous processing onto flexible substrates, they can be eventually configured into the roll-to-roll-processable progressive assembly. Through parametric optimizations of processes consisting of the roll-to-roll-configurable, solution-based progressive assembly of nanostructures (ROLSPAN), a flexible transducer consisting of ZNW-interconnected, PRL-ed IDT Ag electrodes can be developed. This flexible architecture faithfully performs UV sensing as well as optoelectronic transduction. The ROLSPAN concept along with its specific applicability to flexible devices may inspire many diverse functional systems requiring high-throughput low-temperature fabrication over large-area flexible substrates.

Abstract Background The balance of stroke risk reduction and potential bleeding risk associated with antithrombotic treatment (ATT) remains unclear in atrial fibrillation (AF) at non‐gender CHA2DS2‐VASc scores 0–1. A net clinical benefit (NCB) analysis of ATT may guide stroke prevention strategies in AF with non‐gender CHA2DS2‐VASc scores 0–1. Methods This multi‐center cohort study evaluated the clinical outcomes of treatment with a single antiplatelet (SAPT), vitamin K antagonist (VKA), and non‐VKA oral anticoagulant (NOAC) in non‐gender CHA2DS2‐VASc score 0–1 and further stratified by biomarker‐based ABCD score (Age [≥60 years], B‐type natriuretic peptide [BNP] or N‐terminal pro‐BNP [≥300 pg/mL], creatinine clearance [

Typical atrial flutter commonly occurs in patients with atrial fibrillation (AF). Limited information exists regarding the effects of concurrent atrial flutter on the long-term outcomes of rhythm control. This study investigated the association between concurrent typical atrial flutter and cavotricuspid isthmus (CTI) ablation and the recurrence of atrial arrhythmia. The data were obtained from a multicenter registry of cryoballoon ablation for AF (n = 2,689). Patients who were screened for typical atrial flutter were included in the analysis (n = 1,907). All the patients with typical atrial flutter underwent CTI ablation. The primary endpoint was the late recurrence of atrial arrhythmia, including AF, atrial flutter, and atrial tachycardia. Among the 1,907 patients, typical atrial flutter was detected in 493 patients (25.9%). Patients with concurrent atrial flutter had a lower incidence of persistent AF and a smaller size of the left atrium. Patients with atrial flutter had a significantly lower recurrence rate of atrial arrhythmia (19.7% vs. 29.9%, p

ABSTRACTA gecko foot-inspired, mushroom-shaped artificial dry adhesive exploiting intermolecular forces between microstructure and surface has drawn research attention for its strong adhesive force. However, the high pull-off strength corresponding to the adhesive force matters when detaching fragile substrates. In this study, we report a vacuum-powered soft actuator having oblique air chambers and a dry adhesive. The soft actuator performs coupled contraction and twisting by applying negative pneumatic pressure inward and exhibits not only high pull-off strength but also easy detachment. This effective detachment can be achieved thanks to the twisting motion of the soft actuator. The detachment performances of the actuator models are assessed using a 6-degrees-of-freedom robot arm. Results show that the soft actuators exhibit remarkable pull-off strength decrement from ~20 N cm−2 to ~2 N cm−2 due to the twisting. Finally, to verify a feasible application of this study, we utilize the inherent compliance of the actuators and introduce a glass transfer system for which a glass substrate on a slope is gripped by the flexibility of the soft actuators and delivered to the destination without any fracture.

In recent years, the bakery industry has been exploring alternative fats to replace traditional solid fats. Shortening, a common baking ingredient, is produced through the hydrogenation of vegetable oils, resulting in high levels of saturated and trans fatty acids, despite its vegetable oil origin. The excessive consumption of these fats has been associated with negative health effects, including dyslipidemia and cardiovascular issues. Oleogels, incorporating hydroxypropyl methylcellulose (HPMC), xanthan gum (XG), and olive oil, were utilized to replace shortening in the production of white pan bread. The substitution of shortening with oleogel in the white pan bread preparation demonstrated potential reductions in saturated fat, trans fat, and the ratio of saturated fat to unsaturated fatty acids. Specifically, with the complete substitution of shortening with oleogel, saturated fatty acids decreased by 52.46% and trans fatty acids by 75.72%, with unsaturated fatty acids increasing by 57.18%. Our findings revealed no significant difference in volume between bread made with shortening and bread with up to 50% shortening substitution. Moreover, when compared to bread made with shortening and 50% oleogel substitution, no adverse effects on the quality characteristics of volume and expansion properties were observed, and the retrogradation rate was delayed. This study suggests that incorporating oleogels, formed with hydrocolloids such as HPMC and XG, to replace shortening in bread, in conjunction with traditional solid fats, provides positive effects on the quality and nutritional aspects of the bread compared to using oleogel alone. Through this study, we demonstrate the use of oleogels as a healthier alternative to shortening, without reducing the bread’s quality, thus offering a practical solution to reduce unhealthy fats in bakery products.

Abstract Background The association between bundle branch block (BBB) and recurrence of atrial fibrillation (AF) after catheter ablation is unclear. The aim of this study was to determine whether AF combined with BBB is associated with AF recurrence after catheter ablation. Methods A total of 477 consecutive AF patients who underwent catheter ablation were included. The AF patients were divided into three groups according to BBB: AF without BBB (n = 427), AF with right bundle branch block (AF with RBBB) (n = 16), and AF with intraventricular conduction delay (AF with IVCD) (n = 34). Results Of the 477 AF patients (mean age 57 years, 81% men, median CHA2DS2‐VASc score of 1), 16 (3.4%) patients had RBBB, and 34 (7.1%) patients had IVCD. During a mean follow‐up of 15.2 ± 6.7 months, 119 patients (24.9%) had recurrence of AF. Of these, 111 (26%) patients were in the AF without BBB group, with 2 (12.5%) and 6 (17.6%) patients in the RBBB and IVCD groups, respectively. The Kaplan–Meier estimate of the rate of recurrent AF was not significantly different among the three groups (p = .39). Multivariable analysis showed that persistent AF (HR 1.7, 95% CI 1.15–2.50, p = .007), chronic kidney disease (HR 2.94, 95% CI 1.20–7.17, p = .01), and left atrial diameter (HR 1.04, 95% CI 1.009–1.082, p = .01) were significantly associated with AF recurrence. Conclusion AF with BBB was not significantly associated with the recurrence of AF after catheter ablation in middle‐aged patients with low‐risk cardiovascular profile.

Objective: Mitophagy removes damaged mitochondria to maintain cellular homeostasis. Aryl hydrocarbon receptor (AhR) expression in the liver plays a crucial role in supporting normal liver functions, but its impact on mitochondrial function is unclear. Here, we identified a new role of AhR in the regulation of mitophagy to control hepatic energy homeostasis. Methods: In this study, we utilized primary hepatocytes from AhR knockout (KO) mice and AhR knockdown AML12 hepatocytes. An endogenous AhR ligand, kynurenine (Kyn), was used to activate AhR in AML12 hepatocytes. Mitochondrial function and mitophagy process were comprehensively assessed by MitoSOX and mt-Keima fluorescence imaging, Seahorse XF-based oxygen consumption rate measurement, and Mitoplate S-1 mitochondrial substrate utilization analysis. Results: Transcriptomic analysis indicated that mitochondria-related gene sets were dysregulated in AhR KO liver. In both primary mouse hepatocytes and AML12 hepatocyte cell lines, AhR inhibition strongly suppressed mitochondrial respiration rate and substrate utilization. AhR inhibition also blunted the fasting response of several essential autophagy genes and the mitophagy process. We further identified BCL2 interacting protein 3 (BNIP3), a mitophagy receptor that senses nutrient stress, as an AhR target gene. AhR is directly recruited to the Bnip3 genomic locus, and Bnip3 transcription was enhanced by AhR endogenous ligand treatment in wild-type liver and abolished entirely in AhR KO liver. Mechanistically, overexpression of Bnip3 in AhR knockdown cells mitigated the production of mitochondrial reactive oxygen species (ROS) and restored functional mitophagy. Conclusions: AhR regulation of the mitophagy receptor BNIP3 coordinates hepatic mitochondrial function. Loss of AhR induces mitochondrial ROS production and impairs mitochondrial respiration. These findings provide new insight into how endogenous AhR governs hepatic mitochondrial homeostasis.

Abstract Background Data on whether physical activity (PA) levels are related to nonalcoholic fatty liver disease (NAFLD) when considering body mass index (BMI) are scarce. We assessed whether PA affects the development or resolution of NAFLD in conjunction with BMI changes. Methods Overall, 130,144 participants who underwent health screening during 2011–2016 were enrolled. According to the PA level in the Korean version of the validated International PA Questionnaire Short Form, participants were classified into the inactive, active, and health-enhancing PA (HEPA) groups. Results In participants with increased BMI, the hazard ratio (HR) and 95% confidence interval after multivariable Cox hazard model for incident NAFLD was 0.97 (0.94–1.01) in the active group and 0.94 (0.89–0.99) in the HEPA group, whereas that for NAFLD resolution was 1.03 (0.92–1.16) and 1.04 (0.88–1.23) (reference: inactive group). With increased BMI, high PA affected only new incident NAFLD. PA enhancement or maintenance of sufficient PA prevented new incident NAFLD. In participants with decreased BMI, the HRs were 0.98 (0.90–1.07) and 0.88 (0.78–0.99) for incident NAFLD and 1.07 (0.98–1.17) and 1.33 (1.18–1.49) for NAFLD resolution in the active and HEPA groups, respectively. With decreased BMI, high PA reduced incident NAFLD and increased NAFLD resolution. Maintenance of sufficient PA led to a considerable resolution of NAFLD. Conclusion In this large longitudinal study, PA prevented incident NAFLD regardless of BMI changes. For NAFLD resolution, sufficient PA was essential along with BMI decrease. Maintaining sufficient PA or increasing the PA level is crucial for NAFLD prevention or resolution.

Abstract It is unclear which factors are associated with progressive sinus node dysfunction after cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL) ablation. We sought to evaluate the incidence and predictors for permanent pacemaker (PPM) implantation after CTI-dependent AFL ablation. Between January 2011 and June 2021, 353 patients underwent CTI-dependent AFL ablation were studied. During a median follow-up of 31.6 months, 30 patients (8.5%) received PPM implantation, 24 for sick sinus syndrome and 6 for atrioventricular block. In multivariable model, prior atrial fibrillation (AF) (HR 3.570; 95% CI 1.034–12.325; P = 0.044), lowest previous sinus heart rate (HR 0.942; 95% CI 0.898–0.988; P = 0.015), and left atrial volume index (LAVI) (HR 1.067; 95% CI 1.024–1.112; P = 0.002) were independently associated with PPM implantation after CTI-dependent AFL ablation. The best cut-off points for predicting PPM implantation were 60.1 ml/m2 for LAVI and 46 beats per minute for lowest previous sinus heart rate. Among the patients discharged without PPM implantation after ablation, sinus pause over three seconds at AFL termination during ablation was an independent predictor of PPM implantation (HR 17.841; 95% CI 4.626–68.807; P

Cyclophilin E (CypE) belongs to the cyclophilin family and exhibits peptidyl-prolyl cis-trans isomerase (PPIase) activity. It participates in various biological processes through the regulation of peptidyl-prolyl isomerization. However, the specific role of CypE in osteoblast differentiation has not yet been elucidated. In this study, we first discovered the positive impact of CypE on osteoblast differentiation through gain or loss of function experiments. Mechanistically, CypE enhances the transcriptional activity of Runx2 through its PPIase activity. Furthermore, we identified the involvement of the Akt signaling pathway in CypE’s function in osteoblast differentiation. Taken together, our findings indicate that CypE plays an important role in osteoblast differentiation as a positive regulator by increasing the transcriptional activity of Runx2.

Ehretia tinifolia (E. tinifolia) L., an evergreen tree with substantial biological activity, including antioxidant and anti-inflammatory effects, has been used in many herbal and traditional medicines. To elucidate its antioxidant and anti-inflammatory activity and the underlying mechanisms, we applied a methanol extract of E. tinifolia (ETME) to lipopolysaccharide (LPS)-stimulated mouse immortalized Kupffer cells. ETME suppressed the LPS-induced increase in nitric oxide, a mediator for oxidative stress and inflammation, and restored LPS-mediated depletion of total glutathione level by stabilizing antioxidative nuclear factor erythroid 2-related factor 2 (Nrf2) and the subsequent increase in heme oxygenase-1 levels. Furthermore, ETME inhibited the LPS-induced production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The inhibitory effects of ETME on pro-inflammatory responses were regulated by ETME-mediated dephosphorylation of mitogen-activated protein kinases (MAPKs: p38, p44/p42, and stress-associated protein kinase/c-Jun N-terminal kinase) and inhibition of nuclear localization of nuclear factor kappa B (NF-κB). These results suggest that ETME is a possible candidate for protecting Kupffer cells from LPS-mediated oxidative stress and excessive inflammatory responses by activating antioxidant Nrf2/HO-1 and inhibiting pro-inflammatory NF-κB and MAPKs, respectively.

Lactobacillus acidophilus is a gram-positive, microaerophilic, and acidophilic bacterial species. L. acidophilus strains in the gastrointestinal tracts of humans and other animals have been profiled, but strains found in the canine gut have not been studied yet. Our study helps in understanding the genetic features of the L. acidophilus C5 strain found in the canine gut, determining its adaptive features evolved to survive in the canine gut environment, and in elucidating its probiotic functions. To examine the canine L. acidophilus C5 genome, we isolated the C5 strain from a Korean dog and sequenced it using PacBio SMRT sequencing technology. A comparative genomic approach was used to assess genetic relationships between C5 and six other strains and study the distinguishing features related to different hosts. We found that most genes in the C5 strain were related to carbohydrate transport and metabolism. The pan-genome of seven L. acidophilus strains contained 2,254 gene families, and the core genome contained 1,726 gene families. The phylogenetic tree of the core genes in the canine L. acidophilus C5 strain was very close to that of two strains (DSM20079 and NCFM) from humans. We identified 30 evolutionarily accelerated genes in the L. acidophilus C5 strain in the ratio of non-synonymous to synonymous substitutions (dN/dS) analysis. Five of these thirty genes were associated with carbohydrate transport and metabolism. This study provides insights into genetic features and adaptations of the L. acidophilus C5 strain to survive the canine intestinal environment. It also suggests that the evolution of the L. acidophilus genome is closely related to the host’s evolutionary adaptation process.

BackgroundPostoperative atrial fibrillation (POAF) is related to mortality after non-cardiac surgery. Left atrial volume index (LAVI) is known to be associated with prognosis and development of atrial fibrillation, but it has not been fully investigated in patients undergoing non-cardiac surgery.Materials and methodsA total of 203,787 consecutive adult patients underwent non-cardiac surgery at our institution between January 2011 and June 2019. After identifying those with available LAVI estimated during preoperative echocardiography, we divided them into those with LAVI higher and lower than 34 mL/m2. The primary outcome was incidence of POAF.ResultsA total of 83,097 patients were enrolled in this study. The study patients were divided into the low (57,838 [69.6%]) and high (25,259 [30.4%]) LAVI groups. After an adjustment, higher LAVI was associated with increased incidence of POAF (5.1% vs. 8.1%; odds ratio [OR], 1.33; 95% confidence interval [CI], 1.25–1.41; p < 0.001). In 24,549 pairs of propensity-score-matched population, the result was similar (6.2% vs. 7.9%; OR, 1.30; 95% CI, 1.21–1.39; p < 0.001). The estimated threshold of LAVI associated with POAF was 36.4 mL/m2 with an area under the curve of 0.571. Subgroup analysis in non-thoracic and thoracic surgery showed that the association between preoperative LAVI and POAF significantly interacted with diastolic dysfunction (p for interaction < 0.001), and the observed association was valid in patients without diastolic dysfunction.ConclusionPreoperative LAVI was shown to be associated with POAF in non-cardiac surgery. Our result needs verification in further studies.

In this study, a fish metabolic accelerator (a combination of butaphosphan and cyanocobalamin [BPC]) was injected into the muscle of the olive flounder, Paralichthys olivaceus, to investigate its effect on immunity and stress in fish maintained at low temperatures. A single dose of BPC was injected (100 mg/kg body weight) into the olive flounder, and its immunity and stress were observed after one and two weeks. Immunity tests revealed the presence of lysozyme (LZM), nitroblue tetrazolium (NBT), myeloperoxidase (MPO), anti-protease (AP), glutathione peroxidase (GPx), and total immunoglobulin (TIg). BPC injection was found to increase immunity activity compared to the control group. In particular, there was significantly high GPx activity. There was similarly high activity for MPO and GPx in the first week following the injection, followed by significant differences between the BPC-injected and control groups in the second week. There was a reduced low water-temperature stress response in the BPC-injected fish, as evidenced by the cortisol and glucose levels of the control and BPC groups. Lower levels were also observed in the BPC group than the control group during the second week. Cortisol levels were significantly lower in the BPC group than the control group. Histological examinations were conducted in the first and second weeks after the intramuscular injection of the recommended BPC dose to confirm the safety of BPC in aquaculture. There were no abnormalities observed in any tissue samples. This study confirms that the injection of BPC is safe even when used in a culture situation. BPC helps relieve stress and improves non-specific immune responses (innate immunity) in the olive flounder.

Metallothionein 3 (MT3), also known as a neuronal growth-inhibitory factor, is a member of the metallothionein family and is involved in a variety of biological functions, including protection against metal toxicity and reactive oxygen species (ROS). However, less is known about the role of MT3 in the differentiation of 3T3-L1 cells into adipocytes. In this study, we observed that MT3 levels were downregulated during 3T3-L1 adipocyte differentiation. Mt3 overexpression inhibited adipocyte differentiation and reduced the levels of the adipogenic transcription factors C/EBPα and PPARγ. Further analyses showed that MT3 also suppressed the transcriptional activity of PPARγ, and this effect was not mediated by a direct interaction between MT3 with PPARγ. In addition, Mt3 overexpression resulted in a decrease in ROS levels during early adipocyte differentiation, while treatment with antimycin A, which induces ROS generation, restored the ROS levels. Mt3 knockdown, on the other hand, elevated ROS levels, which were suppressed upon treatment with the antioxidant N-acetylcysteine. Our findings indicate a previously unknown role of MT3 in the differentiation of 3T3-L1 cells into adipocytes and provide a potential novel target that might facilitate obesity treatment.

BackgroundNo study has assessed association between cigarette smoking and new-onset diabetes mellitus (NODM) incidence using two different smoking classification systems: self-reported questionnaire and urine cotinine. The objective of this longitudinal study was to evaluate NODM risk using the above two systems in Korean adults.MethodsAmong individuals enrolled in Kangbuk Samsung Health Study and Cohort Study who visited between 2011 and 2012 at baseline and 2014 at follow-up, 78,212 participants without baseline diabetes mellitus were followed up for a median of 27 months. Assessment of NODM incidence was made at the end of follow-up period. Cotinine-verified current smoking was having urinary cotinine ≥50 ng/mL.ResultsPercentages of self-reported and cotinine-verified current smokers were 25.9% and 23.5%, respectively. Overall incidence of NODM was 1.5%. According to multivariate regression analyses, baseline self-reported current smoking (relative risk [RR], 1.33; 95% confidence interval [CI], 1.07 to 1.65) and cotinine-verified current smoking (RR, 1.27; 95% CI, 1.08 to 1.49) increased NODM risk compared to baseline self-reported never smoking and cotinine-verified current non-smoking. Higher daily amount and longer duration of smoking were also associated with increased NODM risk (P for trends

Abstract Background A compact passive oxide layer can grow on tantalum (Ta). It has been reported that this oxide layer can facilitate bone ingrowth in vivo though the development of bone-like apatite, which promotes hard and soft tissue adhesion. Thus, Ta surface treatment on facial implant materials may improve the tissue response, which could result in less fibrotic encapsulation and make the implant more stable on the bone surface. The purposes of this study were to verify whether surface treatment of facial implant materials using Ta can improve the biohistobiological response and to determine the possibility of potential clinical applications. Methods Two different and commonly used implant materials, silicone and expanded polytetrafluoroethylene (ePTFE), were treated via Ta ion implantation using a Ta sputtering gun. Ta-treated samples were compared with untreated samples using in vitro and in vivo evaluations. Osteoblast (MG-63) and fibroblast (NIH3T3) cell viability with the Ta-treated implant material was assessed, and the tissue response was observed by placing the implants over the rat calvarium (n = 48) for two different lengths of time. Foreign body and inflammatory reactions were observed, and soft tissue thickness between the calvarium and the implant as well as the bone response was measured. Results The treatment of facial implant materials using Ta showed a tendency toward increased fibroblast and osteoblast viability, although this result was not statistically significant. During the in vivo study, both Ta-treated and untreated implants showed similar foreign body reactions. However, the Ta-treated implant materials (silicone and ePTFE) showed a tendency toward better histological features: lower soft tissue thickness between the implant and the underlying calvarium as well as an increase in new bone activity. Conclusion Ta surface treatment using ion implantation on silicone and ePTFE facial implant materials showed the possibility of reducing soft tissue intervention between the calvarium and the implant to make the implant more stable on the bone surface. Although no statistically significant improvement was observed, Ta treatment revealed a tendency toward an improved biohistological response of silicone and ePTFE facial implants. Conclusively, tantalum treatment is beneficial and has the potential for clinical applications.

Abstract Decidualization is characterized by the differentiation of endometrial stromal cells (eSCs), which is critical for embryo implantation and maintenance of pregnancy. In the present study, we investigated the possible effect of simulated microgravity (SM) on the process of proliferation and in vitro decidualization using primary human eSCs. Exposure to SM for 36 h decreased the proliferation and migration of eSCs significantly, without inducing cell death and changes in cell cycle progression. The phosphorylation of Akt decreased under SM conditions in human eSCs, accompanied by a simultaneous decrease in the level of matrix metalloproteinase (MMP)-2 and FOXO3a. Treatment with Akti, an Akt inhibitor, decreased MMP-2 expression, but not FOXO3a expression. The decreased level of FOXO3a under SM conditions impeded autophagic flux by reducing the levels of autophagy-related genes. In addition, pre-exposure of eSCs to SM significantly inhibited 8-Br-cAMP induced decidualization, whereas restoration of the growth status under SM conditions by removing 8-Br-cAMP remained unchanged. Treatment of human eSCs with SC-79, an Akt activator, restored the reduced migration of eSCs and decidualization under SM conditions. In conclusion, exposure to SM inhibited decidualization in eSCs by decreasing proliferation and migration through Akt/MMP and FOXO3a/autophagic flux.

Neurally mediated syncope (NMS) is a common clinical problem. The underlying genetic factors of NMS remain controversial. We hypothesized that cardiac syncope-related genes may contribute to NMS in patients with previous frequent syncopal episodes and/or a family history of syncope. A total of 54 consecutive patients diagnosed with NMS were prospectively enrolled between 2013 and 2016. Inclusion criteria were more than five syncopal episodes with a family history of syncope (n = 17) or more than five syncopal episodes with no family history of syncope (n = 37). Ninety-eight cardiac syncope-related genes (channelopathy: 43 genes, cardiomyopathy: 50 genes, primary pulmonary hypertension: 5 genes) were screened by exome sequencing. All identified variants were classified according to the standards and guidelines by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Of the 54 patients, 17 patients (31.5%) had a family history of syncope. Two patients (3.7%) had pathogenic and likely pathogenic variants (PV/LPV) in cardiac syncope-related genes TTN and MYH7. We investigated genetic variation in patients with frequent NMS with a positive family history of syncope in Korea. PV/LPVs in genes related to cardiomyopathy were associated with recurrent NMS in Korean patients. Closer follow-up of these patients might be needed.

In this research, we investigated the effects of reduction atmospheres on the creation of the Mo-Si-B intermetallic compounds (IMC) during the heat treatments. For outstanding anti-oxidation and elevated mechanical strength at the ultrahigh temperature, we fabricated the uniformly dispersed IMC powders such as Mo5SiB2 (T2) and Mo3Si (A15) phases using the two steps of chemical reactions. Especially, in the second procedure, we studied the influence of the atmospheres (e.g. vacuum, argon, and hydrogen) on the synthesis of IMCs during the reduction. Furthermore, the newly produced IMCs were observed by SEM, XRD, and EDS to identify the phase of the compounds. We also calculated an amount of IMCs in the reduced powders depending on the atmosphere using the Reitveld refinement method. Consequently, it is found that hydrogen atmosphere was suitable for fabrication of IMC without other IMC phases.

Several studies have shown that fibroblast growth factor-2 (FGF2) can directly affect axon regeneration after peripheral nerve damage. In this study, we performed sensory tests and histological analyses to study the effect of recombinant human FGF-2 (rhFGF2) treatment on damaged mental nerves. The mental nerves of 6-week-old male Sprague-Dawley rats were crush-injured for 1 minute and then treated with 10 or 50 μg/mL rhFGF2 or PBS in crush injury area with a mini Osmotic pump. Sensory test using von Frey filaments at 1 week revealed the presence of sensory degeneration based on decreased gap score and increased difference score. However, at 2 weeks, the gap score and difference score were significantly rebounded in the mental nerve crush group treated with 10 μg/mL rhFGF2. Interestingly, treatment with 10 μg/mL rhFGF had a more obviously positive effect on the gap score than treatment with 50 μg/mL rhFGF2. In addition, retrograde neuronal tracing with Dil revealed a significant increase in nerve regeneration in the trigeminal ganglion at 2 and 4 weeks in the rhFGF2 groups (10 μg/mL and 50 μg/mL) than in the PBS group. The 10 μg/mL rhFGF2 group also showed an obviously robust regeneration in axon density in the mental nerve at 4 weeks. Our results demonstrate that 10 μg/mL rhFGF induces mental nerve regeneration and sensory recovery after mental nerve crush injury.

In this paper, we report a new method for continuous fabrication of dry adhesives composed of microstructures with mushroom-shaped ends. Conventional mushroom microstructure fabrication is performed with a simple molding technique using a reversed phase master. In a typical fabrication process, thin- and wide-tip portions may be ripped during demolding, making it difficult to use in a continuous process. It is also difficult to apply the mushroom structure master to a continuous process system in roll form. Here, a continuous fabrication process was developed by applying the method of fabricating a wide tip using a tip inking method after forming a micropillar. Through the continuous process, the dry adhesive was successfully fabricated and the durability was measured with a reasonable pull-off strength (13 N/cm2). In addition to the reasonable adhesion, high durability is guaranteed, and fabricated dry adhesives are expected to be used in various fields.

A soundwave is transmitted by adjacent molecules in the medium, and depending on the type of sound, it exhibits various characteristics such as frequency, sound pressure, etc. If the acoustic wavelength of the soundwave is sufficiently long compared with the size of an acoustic element, physical analysis within the sound element could be simplified regardless of the shape of the acoustic element: this is called “long wavelength approximation”. A Helmholtz resonator, a representative acoustic element which satisfies the “long wavelength theory”, consists of a neck part and a cavity part. The Helmholtz resonators can absorb certain frequencies of sound through resonance. To exhibit attenuation properties at ultrasound range, the Helmholtz resonator should be made into a microscale since Helmholtz resonators should satisfy the “long wavelength approximation”. In this study, Helmholtz resonator inspired acoustic elements were fabricated using MEMS technology, and acoustic attenuation experiments in a water bath were conducted using various shapes and materials. As a result, the fabricated samples showed admirable attenuation properties up to ~13 dB mm−1 at 1 MHz. The results were analyzed to derive the necessary conditions for the fabrication of acoustic elements with acoustic attenuation properties in ultrasound range.

Aucklandia lappa Decne., known as “Mok-hyang” in Korea, has been used for the alleviation of abdominal pain, vomiting, diarrhea, and stress gastric ulcers in traditional oriental medicine. We investigated the anti-inflammatory and antioxidative effects of the ethanol extract of Aucklandia lappa Decne. (ALDE) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. ALDE significantly inhibited the LPS-induced nitric oxide (NO) production and reduced inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. The production of other proinflammatory mediators, including COX-2, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, was reduced by ALDE in LPS-stimulated RAW 264.7 cells. The mechanism underlying the anti-inflammatory effects of ALDE was elucidated to be the suppression of LPS-induced nuclear translocation of p65, followed by the degradation of IκB and the inhibition of the phosphorylation of mitogen-activated protein kinases (MAPK). In addition, ALDE showed enhanced radical scavenging activity. The antioxidant effect of ALDE was caused by the enhanced expression of heme oxygenase (HO-1) via stabilization of the expression of the nuclear transcription factor E2-related factor 2 (Nrf2) pathway. Collectively, these results indicated that ALDE not only exerts anti-inflammatory effects via the suppression of the NF-κB and MAPK pathways but also has an antioxidative effect through the activation of the Nrf2/HO-1 pathway.

Background: Conventional stripping is considered to be the standard procedure for great saphenous vein (GSV) varicosities, but many other alternative treatments such as cryostripping, endovenous laser therapy (EVLT), radiofrequency ablation, and ultrasound-guided foam sclerotherapy have been developed. Among them, both cryostripping and laser therapy have been reported to be less traumatic, with lower rates of complications and recurrences when compared to conventional stripping. To compare the efficacy of these treatments, we have analyzed and compared the mid-term clinical outcomes of cryostripping and EVLT. Methods: Patients diagnosed with varicose veins of the GSV and treated with cryostripping or laser therapy between September 2008 and April 2013 were enrolled in this study. Duplex ultrasonography was used for the diagnosis and evaluation of varicosity and reflux, and the clinical-etiology-anatomy-pathophysiology classification was used to measure the clinical severity. The symptoms, Venous Clinical Severity Score (VCSS), recurrence rates, and complication rates of the cryostripping and laser therapy groups were analyzed and compared. Results: A total of 68 patients were enrolled in this study. 32 patients were treated with cryostripping, and 36 patients were treated with laser therapy. The median follow-up period was 29.6 months. Recurrence was noted in three patients from the cryostripping group and in two patients from the EVLT group. There was no difference in the VCSS score, operative time, duration of hospital stay, and complication rate between the cryostripping group and the EVLT group. Conclusion: The mid-term clinical outcomes of cryostripping were not inferior to those of EVLT. Further, considering its cost-effectiveness, cryostripping seems to be a safe and feasible method for the treatment of varicose veins.

Pectus excavatum (PE), the most common skeletal anomaly of chest wall, sometimes requires a surgical correction but recurrent PE is not uncommon. PE usually has a benign course; however, this chest deformity may be associated with symptomatic tachyarrhythmias due to mechanical compression. We report a case of a patient with recurrent PE after surgical correction presenting with palpitation and electrocardiogram (ECG) showing ST-segment elevation on the right precordial leads, which could be mistaken for a Brugada syndrome (BrS).

To understand the corneal regeneration induced by bevacizumab,we investigated the structure changes of stroma andbasement membrane regeneration. A Stick soaked in 0.5 NNaOH onto the mouse cornea and 2.5 mg/ml of bevacizumabwas delivered into an alkali-burned cornea (2 μl) by subconjunctivalinjections at 1 hour and 4 days after injury. At 7 daysafter injury, basement membrane regeneration was observedby transmission electron microscope. Uneven and thin epithelialbasement membrane, light density of hemidesmosomes,and edematous collagen fibril bundles are shown in thealkali-burned cornea. Injured epithelial basement membraneand hemidesmosomes and edematous collagen fibril bundlesresulting from alkali-burned mouse cornea was repaired bybevacizumab treatment. This study demonstrates that bevacizumabcan play an important role in wound healing in thecornea by accelerating the reestablishment of basementmembrane integrity that leads to barriers for scar formation.[BMB Reports 2013; 46(4): 195-200]

FK506 binding protein 12 (FK506BP) belongs to a family ofimmunophilins, and is involved in multiple biologicalprocesses. However, the function of FK506BP in cornealdisease remains unclear. In this study, we examined theprotective effects on dry eye disease in a Botulinum toxin A(BTX-A) induced mouse model, using a cell-permeablePEP-1-FK506BP protein. PEP-1-FK506BP efficiently transducedinto human corneal epithelial cells in a time- anddose-dependent manner, and remained stable in the cells for48 h. In addition, we demonstrated that topical application ofPEP-1-FK506BP was transduced into mouse cornea andconjunctiva by immunohistochemistry. Furthermore, topicalapplication of PEP-1-FK506BP to BTX-A-induced mouse modelmarkedly inhibited expression levels of pro-inflammatorycytokines such as interleukin-1β (IL-1β), tumor necrosisfactor-α (TNF-α) and macrophage inhibitory factor (MIF) incorneal and conjunctival epithelium. These results suggestPEP-1-FK506BP as a potential therapeutic agent for dry eyediseases. [BMB Reports 2013; 46(2): 124-129]

Background Microalbuminuria is associated with cardiovascular disease (CVD) mortality, but whether lower levels of urine albumin excretion similarly predict CVD is uncertain. We investigated associations between urine albumin:creatinine ratio (UACR)

Abstract A 51-year-old woman had severe restrictive cardiomyopathy with heart failure. The first symptoms had started 12 years ago, and her symptoms gradually worsened. She was treated with diuretics, intermittent but repetitive thoracentesis, and paracentesis due to recurrent pleural effusion and ascites. Consequently, a collapse of the right lower lobe (RLL) was noted. We stopped thoracentesis and paracentesis and added continuous intravenous diuretics for 3 months before heart transplantation (HT). Finally, she underwent HT. However, her RLL remained collapsed and chest tube drainage persisted. We performed a RLL lobectomy with video-assisted thoracic surgery. No specific pathologic findings were noted except pulmonary necrotic lesions. We report a rare case of pulmonary necrosis caused by mechanical compression due to chronic pleural effusion after HT.

Several critical ocular diseases that can lead to blindness are due to retinal disorders. Subretinal drug delivery has been developed recently for the treatment of retinal disorders such as hemorrhage because of the specific ocular structure, namely, the blood retinal barrier (BRB). In the present study, we developed an Arched Micro-injector (ARCMI) for subretinal drug delivery with minimal retinal tissue damage. ARCMIs were fabricated using three major techniques: reverse drawing lithography, controlled air flow, and electroplating. In order to achieve minimal retinal tissue damage, ARCMIs were fabricated with specific features such as a 0.15 mm(-1) curvature, 45° tip bevel, 5 mm length, inner diameter of 40 µm, and an outer diameter of 100 µm. These specific features were optimized via in-vitro experiments in artificial ocular hemispherical structures and subretinal injection of indocyanine green in porcine eye ex-vivo. We confirmed that the ARCMI was capable of delivering ocular drugs by subretinal injection without unusual subretinal tissue damage, including hemorrhage.

Introduction: Schinus terebinthifolia (ST) is a plant belonging to the cashew family Anacardiaceae, native to subtropical and tropical South America. ST is commonly called Brazil pepper and aroeira. Several reports have been made on the biological activities of ST, but studies on leaf extracts, especially lectins, have mainly been reported. Objectives: Our study analyzed the active compounds, antioxidant activities, xanthine oxidase inhibitory, elastase inhibitory, and tyrosinase inhibitory activities of S. terebinthifolia (ST) bark extract. Results: Hot water extracts showed the strongest electron donating ability (84.46%) and tyrosinase inhibitory activity (67.1%). Eighty percent ethanol extract showed the highest reducing power, total phenolic, xanthine oxidase (91.7%) and elastase inhibitory ability (85.44%). Catechin, α–amyrin, β–amyrone and 11-Oxo-.α-amyrin were identified through HPLC and GCMS analysis, while eighty percent extract contained the highest amount of catechin. Catechin, α–amyrin, and β–amyrone are considered to be the main xanthine oxidase inhibitors, while β–amyrone is considered to be the main inhibitor of xanthine oxidase and elastase. Conclusion: Through this study, we reported the basic information that S. terebinthifolia bark extract was used in folk medicine as an anti-inflammatory, anti-gout, and skin disease improvement material. S. terebinthifolia bark extract could be used as an anti-gout natural drug or cosmetic material. [ABSTRACT FROM AUTHOR]