Outcomes with T-wave discordance of left bundle branch block and preserved or mildly reduced ejection fraction.

AIMS: Left bundle branch block (LBBB) is associated with an increased risk of adverse outcomes for patients with heart failure. The prognosis of LBBB in patients with a preserved ejection fraction (EF) remains controversial. This study investigated the predictive value of T-wave discordance for the prognosis of patients with LBBB and preserved or mildly reduced EF. METHODS AND RESULTS: We enrolled 707 patients with complete LBBB and left ventricular (LV) EF ≥ 40% observed using electrocardiograms (ECGs) and echocardiograms between January 2010 and December 2018. Their serial ECGs were reviewed during the follow-up period. The T-wave pattern was classified as discordant LBBB (dLBBB) or concordant LBBB (cLBBB) according to the 12-lead ECG T-wave morphology. The primary outcome was the composite of cardiovascular death or hospitalization for heart failure during a median follow-up period of 3.1 years. A multivariable Cox regression analysis was used to evaluate the independent predictors of the primary outcome. Patients with dLBBB had more comorbidities, a higher heart rate, a longer QRS and QTc duration, a larger LV end-systolic volume and left atrial dimension, a lower LVEF, and a higher mitral E/A ratio and E/e', compared with those with cLBBB. Older age [hazard ratio (HR) = 1.023, 95% confidence interval (CI) = 1.001-1.046, P = 0.023], history of heart failure (HR = 2.440, 95% CI = 1.524-3.905, P = 0.001), chronic kidney disease (HR = 1.917, 95% CI = 1.182-3.110, P = 0.008), larger LV end-systolic volume (HR = 1.046, 95% CI = 1.017-1.075, P = 0.002), lower LVEF (HR = 0.916, 95% CI = 0.885-0.948, P = 0.001), and presence of dLBBB (HR = 1.63, 95% CI = 1.011-2.628, P = 0.032) were independent predictors of the primary outcome in patients with LBBB and LVEF ≥ 40%. The discordant or concordant T-wave morphology of LBBB could transform from one subtype to the other in up to 23% of the study population during the follow-up period, and individuals with persistent or transformed dLBBB faced an increased risk of cardiovascular death or non-fatal heart failure hospitalization. CONCLUSIONS: In patients with LBBB and EF ≥ 40%, dLBBB serves as an independent predictor of a higher risk of cardiovascular death or non-fatal heart failure hospitalization.

Predicting Impaired Cardiopulmonary Exercise Capacity in Patients with Atrial Fibrillation Using a Simple Echocardiographic Marker.

BACKGROUND: Exercise intolerance is a common symptom associated with atrial fibrillation (AF). However, echocardiographic markers that can predict impaired exercise capacity are lacking. OBJECTIVE: To investigate the association between echocardiographic parameters and exercise capacity assessed via cardiopulmonary exercise testing (CPET) in patients with AF. METHODS: This single-center prospective study enrolled patients with AF who underwent echocardiography and CPET to evaluate exercise capacity at a tertiary center for AF management from 2020 to 2022. Patients with valvular heart disease, reduced left ventricular ejection fraction, or documented cardiomyopathy were excluded. RESULTS: Among the 188 patients, 134 (71.2%) exhibited impaired exercise capacity (peak oxygen consumption [VO2] ≤85%), including 4 (2.1%) having poor exercise capacity (peak VO2 <50%). Echocardiographic findings revealed that these patients had an enlarged left atrial (LA) size, smaller left ventricular end-diastolic diameter (LVEDD), and increased relative wall thickness, tricuspid regurgitation velocity, and LA/LVEDD and E/e' ratios. Additionally, they exhibited lower peak systolic velocity of the mitral annulus and LA reservoir strain. In the multivariate regression model, LA/LVEDD remained the only significant echocardiographic parameter after adjusting for age, sex, and body mass index (P=0.020). This significance persisted even after incorporating heart rate reserve, N-terminal pro-B-type natriuretic peptide level, and beta-blocker use into the model. CONCLUSION: In patients with AF, LA/LVEDD is strongly associated with exercise capacity. Further follow-up and validation are necessary to clarify its clinical implications in patient care.

Biomimetic nanodrug targets inflammation and suppresses YAP/TAZ to ameliorate atherosclerosis.

Atherosclerosis, a chronic inflammatory disease, is the primary cause of myocardial infarction and ischemic stroke. Recent studies have demonstrated that dysregulation of yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) contributes to plaque development, making YAP/TAZ potential therapeutic targets. However, systemic modulation of YAP/TAZ expression or activities risks serious off-target effects, limiting clinical applicability. To address the challenge, this study develops monocyte membrane-coated nanoparticles (MoNP) as a targeted delivery system for activated and inflamed endothelium lining the plaque surface. The MoNP system is used to deliver verteporfin (VP), aimed at inhibiting YAP/TAZ specifically within arterial regions prone to atherosclerosis. The results reveal that MoNP significantly enhance payload delivery to inflamed endothelial cells (EC) while avoiding phagocytic cells. When administered in mice, MoNP predominantly accumulate in intima of the atheroprone artery. MoNP-mediated delivery of VP substantially reduces YAP/TAZ expression, thereby suppressing inflammatory gene expression and macrophage infiltration in cultured EC and mouse arteries exposed to atherogenic stimuli. Importantly, this targeted VP nanodrug effectively decreases plaque development in mice without causing noticeable histopathological changes in major organs. Collectively, these findings demonstrate a lesion-targeted and pathway-specific biomimetic nanodrug, potentially leading to safer and more effective treatments for atherosclerosis.

Sex-based differences in obstructive sleep apnea and atrial fibrillation: Implication of atrial fibrillation burden.

Background: Obstructive sleep apnea (OSA) is a risk factor for atrial fibrillation (AF); however, it is unclear whether AF increases the risk of OSA. Furthermore, sex differences among patients with both AF and OSA remain unclear. We aimed to determine the association between an increased AF burden and OSA and investigate the differences in clinical characteristics between women and men with AF and OSA. Methods: This was a descriptive, cross-sectional analysis from a prospective cohort study. Patients with non-valvular AF were recruited from the cardiac electrophysiology clinic of a tertiary center; they underwent a home sleep apnea test and 14-day ambulatory electrocardiography. Moderate-to-severe OSA was defined as an apnea-hypopnea index of ≥15. Results: Of 320 patients with AF, 53.4% had moderate-to-severe OSA, and the mean body mass index (BMI) was 25.6 kg/m2. Less women (38.2%) had moderate-to-severe OSA than men (59.3%) (p < 0.001). In the multivariate analysis, age, being a man, and BMI were significantly associated with moderate-to-severe OSA. AF burden was associated with moderate-to-severe OSA only in men (odds ratio: 1.008; 95% confidence interval: 1.001-1.014). Women and men with OSA had similar BMI (p = 0.526) and OSA severity (p = 0.754), but women were older than men (70.1 ± 1.3 vs. 63.1 ± 0.9 years, p < 0.001). Women with moderate-to-severe OSA had a lower AF burden than men did (27.6 ± 7.1 vs. 49.5 ± 3.9%, p = 0.009). Conclusions: AF burden is a sex-specific risk factor for OSA and is limited to men. In contrast, women with both AF and OSA have a lower AF burden than men, despite being older and having similar OSA severity and body habitus. Thus, AF may develop later in women with OSA than in men.

Ezetimibe treatment reduces oxidized low-density lipoprotein in biliary cirrhotic rats.

BACKGROUND: In liver cirrhosis, chronic inflammation is associated with an increase in oxidative stress, and subsequently an increase in the concentration of oxidized low-density lipoprotein (ox-LDL). Ezetimibe is a lipid-lowering agent with anti-inflammation and anti-oxidative stress activities. This study aimed to investigate the effect of ezetimibe treatment on ox-LDL in cirrhotic rats. METHODS: Biliary cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). Sham-operated rats served as surgical controls. Ezetimibe (10 mg/kg/day) or vehicle was administered in the sham-operated or BDL rats for 4 weeks, after which hemodynamic parameters, biochemistry data, oxidative stress were evaluated. Plasma and intrahepatic ox-LDL levels were also examined, and hepatic proteins were analyzed to explore the mechanism of ezetimibe treatment. RESULTS: The BDL rats had typical features of cirrhosis including jaundice, impaired liver function, hyperlipidemia and elevated ox-LDL levels compared to the sham-operated rats. Ezetimibe treatment did not affect hemodynamics, liver biochemistry or plasma lipid levels. However, it significantly reduced oxidative stress, plasma levels of ox-LDL and tumor necrosis factor α. In addition, ezetimibe upregulated the hepatic protein expression of an ox-LDL scavenger (lectin-like oxidized low-density lipoprotein rececptor-1), which resulted in reductions in intrahepatic ox-LDL and fat accumulation in the BDL rats. Nevertheless, ezetimibe treatment did not ameliorate hepatic inflammation or liver fibrosis. CONCLUSION: Ezetimibe reduced plasma and intrahepatic ox-LDL levels in the cirrhotic rats. Furthermore, it ameliorated intrahepatic fat accumulation and oxidative stress. However, ezetimibe did not alleviate hepatic fibrosis or inflammation in the biliary cirrhotic rats.

Mac-2-Binding Protein Glycosylation Isomer to Albumin Ratio Predicts Bacterial Infections in Cirrhotic Patients.

INTRODUCTION: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel biomarker for liver fibrosis, but little is known about its role in cirrhosis-associated clinical outcomes. This study aimed to investigate the predictive role of M2BPGi in cirrhosis-associated complications. METHODS: One hundred and forty-nine cirrhotic patients were retrospectively enrolled. Patients were followed up for 1 year, and cirrhosis-associated clinical events were recorded. Receiver operating characteristic curve (ROC) analysis was used to establish the values of the predictive models for cirrhotic outcomes, and Cox proportional hazards regression models were used to identify predictors of clinical outcomes. RESULTS: Sixty (40.3%) patients experienced cirrhosis-associated clinical events and had higher M2BPGi levels compared to those without events (8.7 vs. 5.1 cutoff index, p < 0.001). The most common cirrhosis-associated complications were bacterial infections (24.2%). On ROC analysis, M2BPGi to albumin ratio (M2BPGi/albumin) had comparable discriminant abilities for all cirrhosis-associated events (area under the ROC curve [AUC] = 0.74) compared with M2BPGi, Child-Pugh, model for end-stage liver disease, albumin-bilirubin scores, and neutrophil-to-lymphocyte ratio and was superior to M2BPGi alone for all bacterial infectious events (AUC = 0.80). Cox regression analysis revealed that the M2BPGi/albumin, but not M2BPGi alone, independently predicted all cirrhosis-associated events (hazard ratio [HR] = 1.34, p = 0.038) and all bacterial infectious events (HR = 1.51, p = 0.011) within 1 year. However, M2BPGi/albumin did not predict other cirrhotic complications and transplant-free survival. DISCUSSION/CONCLUSION: M2BPGi/albumin might serve as a potential prognostic indicator for patients with cirrhosis, particularly for predicting bacterial infections.

Hepatic encephalopathy: From novel pathogenesis mechanism to emerging treatments.

Hepatic encephalopathy (HE) is one of the major complications of liver disease and significantly affects the quality of life (QOL) of patients. HE is common and frequently relapses in cirrhotic patients. The management of HE is supportive, and precipitating conditions should be eliminated. Most drugs used to treat HE are conventional and include nonabsorbable disaccharides such as lactulose, and antibiotics such as rifaximin. However, their therapeutic efficacy is still suboptimal, and novel therapeutic agents are urgently needed. In addition, the optimal management and diagnosis of minimal HE/covert HE are under debate. In this review, we focus on novel pathogenetic mechanisms such as central nervous system clearance, and emerging therapeutic targets of HE, such as fecal material transplantation. We also discuss different classifications and etiologies of HE.

Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial.

OBJECTIVE: This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC). DESIGN: Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression. RESULTS: Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL. CONCLUSION: EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D. TRIAL REGISTRATION NUMBER: NCT01970748.

Assuring safety of fecal microbiota transplantation in the COVID-19 era: A single-center experience.

Background and Aim: Fecal microbiota transplantation (FMT) is used to treat recurrent or refractory Clostridioides difficile infection (CDI). In the past, screening of fecal donors required surveillance of personal behavior, medical history, and diseases that could be transmitted by the blood or fecal-oral route. In addition, the exclusion of multidrug-resistant organisms (MDROs) has been recommended since 2018. This task has become more complicated in the era of the coronavirus disease-2019 (COVID-19) pandemic. To prevent fecal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is crucial to commence screening for SARS-CoV-2, alongside other traditional tests. Our aim was to investigate whether hidden carriers of SARS-CoV-2 were enrolled for stool donation, and the status of the presence or incidence of MDRO during fecal donation in Taiwan. Methods: Fecal products collected from March 2019 to December 2022 were tested for MDRO and nucleic acid amplification tests for SARS-CoV-2 using the pooling method. The period of fecal product collection crossed the time before and during the COVID pandemic in Taiwan. Results: A total of 151 fecal samples were collected. The fecal products were tested using polymerase chain reaction (PCR) to detect SARS-CoV-2. The results were negative for all stocks. This was similar to the results of MDRO testing. The safety of FMT products has been guaranteed during the pandemic. Conclusion: Our FMT center produced MDRO-free and COVID-19-free products before and during the COVID-19 outbreak in Taiwan. Our protocol was effective for ensuring the safety of FMT products.

Synthesis, characterization, and biological verification of asialoglycoprotein receptor-targeted lipopolysaccharide-encapsulated PLGA nanoparticles for the establishment of a liver fibrosis animal model.

Liver fibrosis is generally preceded by various liver injuries and often leads to chronic liver diseases and even cirrhosis. Therefore, a liver fibrosis animal model is the cornerstone for the development of therapeutic strategies for hepatic diseases. Although administration of hepatotoxic substances and/or bile duct ligation have been widely performed to construct the in vivo model over the last decades, they are seriously hindered by time-consuming protocols, high mortality, and instability, indicating that an effective and safe approach for the induction of liver fibrosis is still urgently needed nowadays. In this study, we have developed asialoglycoprotein receptor (ASGPR)-targeted lipopolysaccharide (LPS)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles named ALPNPs for establishing an animal model of liver fibrosis. The ALPNPs are characterized as having a spherical nanostructure with size of 182.9 ± 8.89 nm and surface charge of -8.3 ± 1.48 mV. An anti-ASGPR antibody bound to the surface of the nanoparticles with a crosslinking efficiency of 95.03% allows ALPNPs to have hepatocyte-binding specificity. In comparison to free LPSs, the ALPNPs can induce higher aspartate aminotransferase and total bilirubin concentrations in plasma, reduce the blood flow rate in the portal system and the kidneys, and increase vascular resistance in the liver, kidneys, and collateral shunting vasculature. Based on histological and RNA-seq analyses, the ALPNPs can provide similar capability on inducing hepatic inflammation and fibrosis compared to free LPS but possess higher liver targetability than the naked drug. In addition, the ALPNPs are less toxic in organs other than the liver in comparison to free LPS, demonstrating that the ALPNPs do not elicit off-target effects in vivo. Given the aforementioned efficacies with other merits such as biocompatibility and drug release controllability provided by PLGA, we anticipate that the developed ALPNPs are highly applicable in establishing animal models of liver fibrosis in pre-clinical studies.

The outcomes and prognostic factors of patients with hepatocellular carcinoma and Child-Turcotte-Pugh class B.

BACKGROUND: The Child-Turcotte-Pugh (CTP) score is widely used for assessing the liver's functional reserve in patients with advanced chronic liver disease (ACLD) and hepatocellular carcinoma (HCC). This study aims to explore the outcomes of patients with HCC and CTP class B and to investigate the prognostic accuracy of prediction models for ACLD in these patients. METHODS: We retrospectively enrolled 1143 patients with HCC and CTP class B between 2007 and 2022. We divided the patients into three subgroups based on their CTP scores: CTP-B7, CTP-B8, and CTP-B9. We compared the corrected Akaike information criterion among each mortality prediction model, including the CTP score, albumin-bilirubin (ALBI) score, modified ALBI score, the model for end-stage liver disease (MELD), and MELD 3.0. RESULTS: Among the enrolled patients, 576 (50.3%) were in the CTP-B7 group, 363 (31.8%) were in the CTP-B8 group, and 204 (17.9%) were in the CTP-B9 group. After a median follow-up of 4.6 months (interquartile range IQR 1.8-17.2 months), 963 patients died, and the 5-year overall survival (OS) rate was 11.4%. The 5-year OS rates were 11.6%, 13.6%, and 8.3% in the CTP-B7, CTP-B8, and CTP-B9 groups, respectively. Patients in the CTP-B7 group and CTP-B8 group had comparable OS ( p = 0.089), both of which were better than those in the CTP-B9 group ( p < 0.001). Furthermore, the MELD 3.0 score had the lowest corrected akaike information criteria value and provided a more accurate mortality prediction than the MELD score, ALBI grade, modified ALBI grade, and CTP score. CONCLUSION: Patients in the CTP-B7 and CTP-B8 groups had comparable OS, both of which were better than those in the CTP-B9 group. Moreover, MELD 3.0 provided the most accurate mortality prediction in patients with HCC and CTP class B.

Psychometric properties of the Chinese Mandarin version of the Borderline Symptom List, short form (BSL-23) in suicidal adolescents.

BACKGROUND: The short form of the Borderline Symptom List (BSL-23) is a self-rated instrument developed from the initial 95-item German version of the Borderline Symptom List (BSL-95). It is widely used among Chinese adults, but its applicability, factor structure and validity remain uncertain in adolescents. This study aimed to evaluate the psychometric properties of the Chinese Mandarin version of the BSL-23 in a sample of suicidal adolescents. METHODS: The Chinese Mandarin BSL-23 was given to 279 outpatient adolescents with self-injurious thoughts or behaviors. The factor structure, reliability, convergent validity, criterion-related validity and cut-off value were investigated. RESULTS: The Chinese Mandarin version of the BSL-23 demonstrated a one-factor structure and replicated the original version. The scale had high reliability and good test-retest stability. The Chinese Mandarin BSL-23 was correlated with depression, hopelessness, impulsivity, emotional dysregulation, self-esteem, loneliness, childhood trauma and parental bonding patterns evaluated with a variety of scales. The measure showed good criterion-related validity and predictive accuracy (AUC = 0.87) for self-injurious and suicidal adolescents with borderline personality disorder (BPD) at a cut-off point of 60/61 (mean score 2.60/2.65), with a sensitivity of 0.76 and specificity of 0.83. CONCLUSIONS: The Chinese Mandarin version of the BSL-23 is a reliable and valid self-reported instrument to assess BPD symptomatology among suicidal adolescents.

Minimal Fluoroscopic Catheter Ablation for Adult Patients with Paroxysmal Supraventricular Tachycardia without the Assistance of Intracardiac Echocardiography.

Background: Radiation exposure during fluoroscopic procedures increases the risk of cancer for both patients and operators. Objectives: The aim of this study was to investigate the safety and efficacy of adopting a three-dimensional electroanatomical mapping (3D EAM) system during ablation for paroxysmal supraventricular tachycardia (PSVT), without the assistance of intracardiac echocardiography (ICE), for both right- and left-chamber cardiac procedures. Methods: We retrospectively enrolled all patients with PSVT from September 2018 to December 2020. The patients were grouped according to the use of the 3D EAM system (3D-guided group, n = 102 vs. conventional group, n = 226). Results: The acute success rates were high in both groups (100% vs. 99.1%). The fluoroscopy time was significantly lower in the 3D-guided group than in the conventional group (2.4 ± 4.4 vs. 19.0 ± 10.8 min); the procedure time was significantly increased in the 3D-guided group (104.5 ± 29.9 vs. 94.0 ± 31.9 min), and this was associated with the post-electrophysiology test diagnosis after adjustment for multiple variables [standardized B coefficient (ß) 0.188]. There was no learning curve for each electrophysiologist in terms of fluoroscopy and procedure times. Conclusions: The 3D EAM system, without the assistance of ICE, was safe and effective in guiding PSVT ablation in both left- and right-chamber ablation.

Optimization of Ternary InxGa1-xN Quantum Wells on GaN Microdisks for Full-Color GaN Micro-LEDs.

Red, green, and blue light InxGa1-xN multiple quantum wells have been grown on GaN/γ-LiAlO2 microdisk substrates by plasma-assisted molecular beam epitaxy. We established a mechanism to optimize the self-assembly growth with ball-stick model for InxGa1-xN multiple quantum well microdisks by bottom-up nanotechnology. We showed that three different red, green, and blue lighting micro-LEDs can be made of one single material (InxGa1-xN) solely by tuning the indium content. We also demonstrated that one can fabricate a beautiful InxGa1-xN-QW microdisk by choosing an appropriate buffer layer for optoelectronic applications.

Dual angiotensin receptor and neprilysin inhibitor reduced portal pressure through peripheral vasodilatation and decreasing systemic arterial pressure in cirrhotic rats.

BACKGROUND: Portal hypertension develops along with the progression of liver cirrhosis. Natriuretic peptides have been shown to reduce portal pressure but concomitantly activate the renin-angiotensin-aldosterone system (RAAS). Angiotensin receptor-neprilysin inhibitors (ARNIs) upregulate natriuretic peptides and avoid the adverse effects of RAAS activation. ARNIs have been shown to reduce portal pressure in rats with pre-hepatic portal hypertension, which involves relatively little liver injury. This study aimed to evaluate the relevant effects of an ARNI in rats with both liver cirrhosis and portal hypertension. METHODS: Male Sprague-Dawley rats received common bile duct ligation to induce liver cirrhosis and portal hypertension. Sham-operated rats served as surgical controls. All rats were randomly allocated into three groups to receive distilled water (vehicle), LCZ696 (an ARNI), or valsartan for 4 weeks. Portal hypertension and relevant derangements were assessed after treatment. RESULTS: Portal hypertension and hyperdynamic circulation developed in the cirrhotic rats. In the rats with cirrhosis and portal hypertension, both LCZ696 and valsartan reduced portal hypertension, mean arterial pressure, and systemic vascular resistance. The decrease in portal pressure was highly associated with the reduction in arterial pressure and systemic vascular resistance. Blood flow in hepatic, splanchnic, and portosystemic collateral systems was not altered. LCZ696 did not significantly influence liver injury or plasma cytokine levels. Liver fibrosis and splanchnic angiogenesis were not affected. CONCLUSION: ARNI treatment exerted portal pressure lowering effects via peripheral vasodilatation and decreasing systemic arterial pressure in the rats with liver cirrhosis and portal hypertension. Caution should be taken when using ARNIs in liver cirrhosis.

Lesion-specific suppression of YAP/TAZ by biomimetic nanodrug ameliorates atherosclerosis development.

Atherosclerosis, characterized by the buildup of lipid-rich plaque on the vessel wall, is the primary cause of myocardial infarction and ischemic stroke. Recent studies have demonstrated that dysregulation of yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) contributes to plaque development, making YAP/TAZ potential therapeutic targets. However, systemic modulation of YAP/TAZ expression or activities risks serious off-target effects, limiting clinical applicability. To address the challenge, this study develops monocyte membrane-coated nanoparticles (MoNP) as a drug delivery vehicle targeting activated endothelium lining the plaque surface and utilizes MoNP to deliver verteporfin (VP), a potent YAP/TAZ inhibitor, for lesion-specific treatment of atherosclerosis. The results reveal that MoNP significantly enhance payload delivery to inflamed endothelial cells (EC) while avoiding phagocytic cells, and preferentially accumulate in atherosclerotic regions. MoNP-mediated delivery of VP substantially reduces YAP/TAZ expression, suppressing inflammatory gene expression and macrophage infiltration in cultured EC and mouse arteries exposed to atherogenic stimuli. Importantly, this lesion-targeted VP nanodrug effectively decreases plaque development in mice without causing noticeable histopathological changes in major organs. Collectively, these findings demonstrate a plaque-targeted and pathway-specific biomimetic nanodrug, potentially leading to safer and more effective treatments for atherosclerosis.

Substrate-Induced Anisotropic Growth of CuAlO2 Platelets in a Liquid-Solid Reaction.

This study reports a simplified method to grow CuAlO2 crystals of submillimeter sizes with a highly anisotropic shape of a platelet. The solid-state reaction of forming CuAlO2 at ca. 1373 K in the first stage of the conventional flux method is no longer required. The CuAlO2 platelets nucleated directly onto the (0001)sapphire surface in a melt of Cu2O saturated with Al2O3 at 1473 K. The excess flux was mostly removed by the capped alumina plate on cooling with a limited amount of residue which can be leached afterward. The CuAlO2 platelets all have a 3R crystal structure with no line and planar defects observed by TEM. The CuAlO2 crystals emit a luminescence at 3.49 eV associated with resonant Raman effect resulted from a band-to-band transition in room-temperature PL measurement. The facile fabrication method for growing highly anisotropic CuAlO2 crystals paves the way for their practical application in photoelectrochemical devices.

Association between atrial fibrillation burden and cognitive function in patients with atrial fibrillation.

BACKGROUND: Accumulating evidence has demonstrated an association between clinical atrial fibrillation (AF) and cognitive impairment. This study aimed to further clarify the impact of AF burden on cognitive function based on detailed electrophysiological recordings and standardized assessments of cognitive function. METHODS: This prospective cohort study, conducted at the Cardiac Electrophysiology Clinic of a tertiary center, included patients with non-valvular AF. AF burden was evaluated using 14-day patch-based electrocardiography. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). RESULTS: Enrolled patients (n = 253) were grouped according to the median AF burden (13.52%). Patients with higher AF burden were significantly older and had larger left atrium size, a worse ejection fraction, and a lower MoCA score than those with lower AF burden. Predictors of MoCA score included age, CHA2DS2-VASc score, AF burden, and Center for Epidemiologic Studies Depression Scale scores. The association between MoCA scores and AF burden remained significant after adjustment for demographic characteristics, underlying diseases, and echocardiographic parameters (standardized beta coefficient: -0.159, 95% confidence interval: -0.020 to -0.004, p = 0.004). CONCLUSION: AF burden is associated with cognitive function in patients with AF. Further studies are required to determine whether reducing AF burden can preserve cognitive function in these patients.