Ac2-26 reduced the liver injury after cardiopulmonary bypass in rats via AKT1/GSK3ß/eNOS pathway.

OBJECTIVE: About 10% of patients after cardiopulmonary bypass (CPB) would undergo acute liver injury, which aggravated the mortality of patients. Ac2-26 has been demonstrated to ameliorate organic injury by inhibiting inflammation. The present study aims to evaluate the effect and mechanism of Ac2-26 on acute liver injury after CPB. METHODS: A total of 32 SD rats were randomized into sham, CPB, Ac, and Ac/AKT1 groups. The rats only received anesthesia, and rats in other groups received CPB. The rats in Ac/AKT1 were pre-injected with the shRNA to interfere with the expression of AKT1. The rats in CPB were injected with saline, and rats in Ac and Ac/AKT1 groups were injected with Ac2-26. After 12 h of CPB, all the rats were sacrificed and the peripheral blood and liver samples were collected to analyze. The inflammatory factors in serum and liver were detected. The liver function was tested, and the pathological injury of liver tissue was evaluated. RESULTS: Compared with the sham group, the inflammatory factors, liver function, and pathological injury were worsened after CPB. Compared with the CPB group, the Ac2-26 significantly decreased the pro-inflammatory factors and increased the anti-inflammatory factor, improved liver function, and ameliorated the pathological injury. All the therapeutic effects of Ac2-26 were notably attenuated by the shRNA of AKT1. The Ac2-26 increased the GSK3ß and eNOS, and this promotion was inhibited by the shRNA. CONCLUSION: The Ac2-26 significantly treated the liver injury, inhibited inflammation, and improved liver function. The effect of Ac2-26 on liver injury induced by CPB was partly associated with the promotion of AKT1/GSK3ß/eNOS.

Real-world effectiveness of early insulin therapy on the incidence of cardiovascular events in newly diagnosed type 2 diabetes.

Early insulin therapy is capable to achieve glycemic control and restore ß-cell function in newly diagnosed type 2 diabetes (T2D), but its effect on cardiovascular outcomes in these patients remains unclear. In this nationwide real-world study, we analyzed electronic health record data from 19 medical centers across China between 1 January 2000, and 26 May 2022. We included 5424 eligible patients (mean age 56 years, 2176 women/3248 men) who were diagnosed T2D within six months and did not have prior cardiovascular disease. Multivariable Cox regression models were used to estimate the associations of early insulin therapy (defined as the first-line therapy for at least two weeks in newly diagnosed T2D patients) with the incidence of major cardiovascular events including coronary heart disease (CHD), stroke, and hospitalization for heart failure (HF). During 17,158 persons years of observation, we documented 834 incident CHD cases, 719 stroke cases, and 230 hospitalized cases for HF. Newly diagnosed T2D patients who received early insulin therapy, compared with those who did not receive such treatment, had 31% lower risk of incident stroke, and 28% lower risk of hospitalization for HF. No significant difference in the risk of CHD was observed. We found similar results when repeating the aforesaid analysis in a propensity-score matched population of 4578 patients and with inverse probability of treatment weighting models. These findings suggest that early insulin therapy in newly diagnosed T2D may have cardiovascular benefits by reducing the risk of incident stroke and hospitalization for HF.

Association between Body Iron Status and Cognitive Task Performance in a Nationally Representative Sample of Older Adults.

Iron is an essential micronutrient that is necessary for proper cognitive function. However, the dose-response relationship between body iron status and cognitive function remains unclear. The objective of this study was to investigate the association between serum ferritin concentrations, an indicator of body iron status, and cognitive function in older adults. Based on the National Health and Nutrition Examination Survey (NHANES) 1999 -2002 in the United States, nationally representative data was collected from 2,567 adults aged 60 years and older who had objectively measured serum ferritin levels and cognitive performance. High ferritin levels were defined as a serum ferritin level >200 ng/mL in women and >300 ng/mL in men. Low ferritin levels were defined as a serum ferritin level <30 ng/mL. The digit symbol substitution test (DSST) was employed to assess cognitive function. Multivariable logistic regression analyses with survey weights were performed after the DSST was dichotomized at the median score. The weighted prevalence of adults with normal, low, and high serum ferritin levels were 73.98%, 9.12%, and 16.91%, respectively. A U-shaped association between serum ferritin concentrations and cognitive task performance was observed. After adjusting for demographic, socioeconomic, lifestyle, and C-reactive protein factors, the odds ratio (95% confidence intervals) for lower cognitive performance was 1.39 (1.11, 1.74) in adults with high ferritin levels and 1.38 (0.86, 2.22) in adults with low ferritin levels, compared with those with normal ferritin levels. The association between serum ferritin levels and lower cognitive performance was stronger in adults aged 60 to 69 years old than those aged 70 years and older. In conclusion, in a nationally representative sample of older adults in the United States, a high serum ferritin level was significantly associated with worse cognitive task performance. Thus, the relationship between low serum ferritin concentrations and cognitive task performance warrants further investigation.

Ac2-26 activated the AKT1/GSK3ß pathway to reduce cerebral neurons pyroptosis and improve cerebral function in rats after cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) results in brain injury, which is primarily caused by inflammation. Ac2-26 protects against ischemic or hemorrhage brain injury. The present study was to explore the effect and mechanism of Ac2-26 on brain injury in CPB rats. METHODS: Forty-eight rats were randomized into sham, CPB, Ac, Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups. Rats in sham group only received anesthesia and in the other groups received standard CPB surgery. Rats in the sham and CPB groups received saline, and rats in the Ac, Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups received Ac2-26 immediately after CPB. Rats in the Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups were injected with shRNA, inhibitor and agonist of GSK3ß respectively. The neurological function score, brain edema and histological score were evaluated. The neuronal survival and hippocampal pyroptosis were assessed. The cytokines, activity of NF-κB, S100 calcium-binding protein ß(S100ß) and neuron-specific enolase (NSE), and oxidative were tested. The NLRP3, cleaved-caspase-1 and cleaved-gadermin D (GSDMD) in the brain were also detected. RESULTS: Compared to the sham group, all indicators were aggravated in rats that underwent CPB. Compared to the CPB group, Ac2-26 significantly improved neurological scores and brain edema and ameliorated pathological injury. Ac2-26 reduced the local and systemic inflammation, oxidative stress response and promoted neuronal survival. Ac2-26 reduced hippocampal pyroptosis and decreased pyroptotic proteins in brain tissue. The protection of Ac2-26 was notably lessened by shRNA and inhibitor of GSK3ß. The agonist of GSK3ß recovered the protection of Ac2-26 in presence of shRNA. CONCLUSIONS: Ac2-26 significantly improved neurological function, reduced brain injury via regulating inflammation, oxidative stress response and pyroptosis after CPB. The protective effect of Ac2-26 primarily depended on AKT1/ GSK3ß pathway.

Topological valley Hall polariton condensation.

A photonic topological insulator features robust directional propagation and immunity to defect perturbations of the edge/surface state. Exciton-polaritons, that is, the hybrid quasiparticles of excitons and photons in semiconductor microcavities, have been proposed as a tunable nonlinear platform for emulating topological phenomena. However, mainly due to excitonic material limitations, experimental observations so far have not been able to enter the nonlinear condensation regime or only show localized condensation in one dimension. Here we show a topological propagating edge state with polariton condensation at room temperature and without any external magnetic field. We overcome material limitations by using excitonic CsPbCl3 halide perovskites with a valley Hall lattice design. The polariton lattice features a large bandgap of 18.8 meV and exhibits strong nonlinear polariton condensation with clear long-range spatial coherence across the critical pumping density. The geometric parameters and material composition of our nonlinear many-body photonic system platform can in principle be tailored to study topological phenomena of other interquasiparticle interactions.

Genome-Wide Identification and Hormone Response Analysis of the COBL Gene Family in Barley.

Barley (Hordeum vulgare L.), a diverse cereal crop, exhibits remarkable versatility in its applications, ranging from food and fodder to industrial uses. The content of cellulose in barley is significantly influenced by the COBRA genes, which encode the plant glycosylphosphatidylinositol (GPI)-anchored protein (GAP) that plays a pivotal role in the deposition of cellulose within the cell wall. The COBL (COBRA-Like) gene family has been discovered across numerous species, yet the specific members of this family in barley remain undetermined. In this study, we discovered 13 COBL genes within the barley genome using bioinformatics methods, subcellular localization, and protein structure analysis, finding that most of the barley COBL proteins have a signal peptide structure and are localized on the plasma membrane. Simultaneously, we constructed a phylogenetic tree and undertook a comprehensive analysis of the evolutionary relationships. Other characteristics of HvCOBL family members, including intraspecific collinearity, gene structure, conserved motifs, and cis-acting elements, were thoroughly characterized in detail. The assessment of HvCOBL gene expression in barley under various hormone treatments was conducted through qRT-PCR analysis, revealing jasmonic acid (JA) as the predominant hormonal regulator of HvCOBL gene expression. In summary, this study comprehensively identified and analyzed the barley COBL gene family, aiming to provide basic information for exploring the members of the HvCOBL gene family and to propose directions for further research.

Association of cerebral palsy with autism spectrum disorder and attention-deficit/hyperactivity disorder in children: a large-scale nationwide population-based study.

OBJECTIVE: To examine the association of cerebral palsy with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), providing evidence for interdisciplinary medical service for children with cerebral palsy. DESIGN: A large-scale nationwide population-based study. SETTING: The National Health Interview Survey (NHIS). PATIENTS: 177 899 children aged 3-17 years among NHIS participants from 1997 to 2003 and 2008 to 2018. RESULTS: Among the 177 899 children included in this analysis, 602 (0.33%) had cerebral palsy, 1997 (1.16%) had ASD, and 13 697 (7.91%) had ADHD. Compared with children without cerebral palsy, children with cerebral palsy had a higher prevalence of ASD (6.09% vs 1.15%; p<0.001) and ADHD (15.91% vs 7.89%; p<0.001). After adjustment for age, sex, race/ethnicity, family highest education level, family income level and geographical region, the OR among children with cerebral palsy, compared with children without cerebral palsy, was 5.07 (95% CI 3.25 to 7.91) for ASD (p<0.001) and 1.95 (95% CI 1.43 to 2.66) for ADHD (p<0.001). Furthermore, the association of cerebral palsy with ASD and ADHD remained significant in all subgroups stratified by age, sex and race. CONCLUSION: In a large, nationally representative sample of US children, this study shows that children with cerebral palsy are at an increased risk of ASD and ADHD.

Does the Cognitive Reflection Test Work with Chinese College Students? Evidence from a Time-Limited Study.

The cognitive reflection test (CRT) is an experiment task commonly used in Western countries to test intuitive and analytical thinking styles. However, the validity of this task for Chinese participants has not been explored. Therefore, this study recruited Chinese college students to finish CRT tasks with various experimental designs. To gauge the accuracy of the CRT tasks, 438 Chinese college students first completed online questionnaires. Participants were then invited to participate in an offline laboratory with the same experimental settings. Finally, time pressure was used to strictly control intuition and analytical thinking to explore the performance of Chinese college students on CRT tasks. The results show that of the three experiments, Chinese college students had the highest accuracy in the offline test, and the CRT's intuitive conflict problem still applies to Chinese students under the time-limited condition. This study demonstrates the validity of the CRT in China and proves that time pressure is an effective method for identifying individuals with strong logic ability.

Exposure to Polybrominated Diphenyl Ethers and Risk of All-Cause and Cause-Specific Mortality.

Importance: Polybrominated diphenyl ethers (PBDEs) are an important group of persistent organic pollutants with endocrine-disrupting properties. However, prospective cohort studies regarding the association of PBDE exposure with long-term health outcomes, particularly mortality, are lacking. Objective: To examine the association of environmental exposure to PBDEs with risk of all-cause and cause-specific mortality. Design, Setting, and Participants: This nationally representative cohort study used data from the National Health and Nutrition Examination Survey 2003 to 2004 and linked mortality information through December 31, 2019. Adults aged 20 years or older with available data on PBDE measurements and mortality were included. Statistical analysis was performed from February 2022 to April 2023. Exposures: PBDE analytes in serum samples were measured using solid phase extraction and isotope dilution gas chromatography high-resolution mass spectrometry. Main Outcomes and Measures: All-cause mortality, cancer mortality, and cardiovascular mortality. Results: This study included 1100 participants (mean [SE] age, 42.9 [0.6] years; proportion [SE] female, 51.8% [1.6%]; proportion [SE] Hispanic, 12.9% [2.7%]; proportion [SE] non-Hispanic Black, 10.5% [1.6%]; proportion [SE] non-Hispanic White, 70.8% [3.7%]; proportion [SE] other race and ethnicity, 5.8% [1.1%]). During 16 162 person-years of follow-up (median [IQR] follow-up, 15.8 [15.2-16.3] years; maximum follow-up, 17 years), 199 deaths occurred. Participants with higher serum PBDE levels were at higher risk for death. After adjustment for age, sex, and race and ethnicity, lifestyle and socioeconomic factors, and body mass index, participants with the highest tertile of serum PBDE levels had an approximately 300% increased risk of cancer mortality (HR, 4.09 [95% CI, 1.71-9.79]) compared with those with the lowest tertile of serum PBDE levels. No significant association of PBDE exposure with all-cause mortality (HR, 1.43 [95% CI, 0.98-2.07]) or cardiovascular mortality (HR, 0.92 [95% CI, 0.41-2.08]) was observed. Conclusions and Relevance: In this nationally representative cohort study, PBDE exposure was significantly associated with an increased risk of cancer mortality. Further studies are needed to replicate the findings and determine the underlying mechanisms.

The role of TGF-ß signaling in muscle atrophy, sarcopenia and cancer cachexia.

Skeletal muscle, comprising a significant proportion (40 to 50 percent) of total body weight in humans, plays a critical role in maintaining normal physiological conditions. Muscle atrophy occurs when the rate of protein degradation exceeds protein synthesis. Sarcopenia refers to age-related muscle atrophy, while cachexia represents a more complex form of muscle wasting associated with various diseases such as cancer, heart failure, and AIDS. Recent research has highlighted the involvement of signaling pathways, including IGF1-Akt-mTOR, MuRF1-MAFbx, and FOXO, in regulating the delicate balance between muscle protein synthesis and breakdown. Myostatin, a member of the TGF-ß superfamily, negatively regulates muscle growth and promotes muscle atrophy by activating Smad2 and Smad3. It also interacts with other signaling pathways in cachexia and sarcopenia. Inhibition of myostatin has emerged as a promising therapeutic approach for sarcopenia and cachexia. Additionally, other TGF-ß family members, such as TGF-ß1, activin A, and GDF11, have been implicated in the regulation of skeletal muscle mass. Furthermore, myostatin cooperates with these family members to impair muscle differentiation and contribute to muscle loss. This review provides an overview of the significance of myostatin and other TGF-ß signaling pathway members in muscular dystrophy, sarcopenia, and cachexia. It also discusses potential novel therapeutic strategies targeting myostatin and TGF-ß signaling for the treatment of muscle atrophy.

Exosomal MALAT1 from macrophages treated with high levels of glucose upregulates LC3B expression via miR-204-5p downregulation.

BACKGROUND: Metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1 ) plays a critical role in the pathophysiology of diabetes-related complications. However, whether macrophage-derived MALAT1 affects autophagic activity under hyperglycemic conditions is unclear. Therefore, we investigated the molecular regulatory mechanisms of macrophage-derived MALAT1 and autophagy under hyperglycemic conditions. METHODS: Hyperglycemia was induced by culturing macrophages in 25 mM glucose for 1 hour. Exosomes were extracted from the culture media. A rat model of carotid artery balloon injury was established to assess the effect of MALAT1 on vascular injury. Reverse transcription, real-time quantitative polymerase chain reaction, western blotting, immunohistochemical staining, and luciferase activity assays were performed. RESULTS: Stimulation with high levels of glucose significantly enhanced MALAT1 expression in macrophage-derived exosomes. MALAT1 inhibited miR-204-5p expression in macrophage-derived exosomes under hyperglycemic conditions. siRNA-induced silencing of MALAT1 significantly reversed macrophage-derived exosome-induced miR-204-5p expression. Hyperglycemic treatment caused a significant, exosome-induced increase in the expression of the autophagy marker LC3B in macrophages. Silencing MALAT1 and overexpression of miR-204-5p significantly decreased LC3B expression induced by macrophage-derived exosomes. Overexpression of miR-204-5p significantly reduced LC3B luciferase activity induced by macrophage-derived exosomes. Balloon injury to the carotid artery in rats significantly enhanced MALAT1 and LC3B expression, and significantly reduced miR-204-5p expression in carotid artery tissue. Silencing MALAT1 significantly reversed miR-204-5p expression in carotid artery tissue after balloon injury. MALAT1 silencing or miR-204-5p overexpression significantly reduced LC3B expression after balloon injury. CONCLUSION: This study demonstrated that hyperglycemia upregulates MALAT1 . MALAT1 suppresses miR-204-5p expression and counteracts the inhibitory effect of miR-204-5p on LC3B expression in macrophages to promote vascular disease.

Zeb1-controlled metabolic plasticity enables remodeling of chromatin accessibility in the development of neuroendocrine prostate cancer.

Cell plasticity has been found to play a critical role in tumor progression and therapy resistance. However, our understanding of the characteristics and markers of plastic cellular states during cancer cell lineage transition remains limited. In this study, multi-omics analyses show that prostate cancer cells undergo an intermediate state marked by Zeb1 expression with epithelial-mesenchymal transition (EMT), stemness, and neuroendocrine features during the development of neuroendocrine prostate cancer (NEPC). Organoid-formation assays and in vivo lineage tracing experiments demonstrate that Zeb1+ epithelioid cells are putative cells of origin for NEPC. Mechanistically, Zeb1 transcriptionally regulates the expression of several key glycolytic enzymes, thereby predisposing tumor cells to utilize glycolysis for energy metabolism. During this process, lactate accumulation-mediated histone lactylation enhances chromatin accessibility and cellular plasticity including induction of neuro-gene expression, which promotes NEPC development. Collectively, Zeb1-driven metabolic rewiring enables the epigenetic reprogramming of prostate cancer cells to license the adeno-to-neuroendocrine lineage transition.

Efficient removal of tetracycline and Cu2+ by honeycomb derived magnetic carbon: Adsorption mechanism and advanced oxidation regeneration mechanism.

The honeycomb magnetic carbons (xFe@HCNs) were prepared by sacrificial template method novelty using polyacrylamide resin (PAAS) as template and ammonium pyrrolidine dithioate/Fe3+ complex (APDC-Fe) as carbon skeleton and metal source. Tetracycline (TC) and copper (Cu2+) as target pollutants were used to investigate the adsorption properties of xFe@HCNs in single or binary TC and Cu2+ systems. The adsorption capacity sequence for TC among the adsorbents was (mmol·g-1): 2Fe@HCNs (0.088) > 8Fe@HCNs (0.061) > HCNs (0.054) > RC (0.036), and for Cu2+ was (mmol·g-1): 2Fe@HCNs (1.120) > 8Fe@HCNs (1.026) > RC (0.792) > HCNs (0.681). 2Fe@HCNs demonstrated notable affinity for adsorbing both TC and Cu2+. Additionally, the influence of hydrochemical factors (i.e., cation species, anion species, and pH) on the adsorption properties of 2Fe@HCNs. Combined with advanced oxidation technology, the regeneration methods of magnetic adsorbent were explored using oxidizing agents (e.g., H2O2 and peroxymonosulfate) as eluents which could increase the adsorption sites of magnetic carbon adsorbents during the regenerating process, which was the novelty of the study. Furthermore, the regeneration mechanisms of H2O2 as eluent were investigated. This study discussed the application and regeneration methods of magnetic adsorbents in water treatment, offering new insights into environmental remediation using magnetic materials.

Predictive value of placental real-time shear wave elastography combined with 3-dimensional power Doppler index for preeclampsia.

This study aimed to investigate the value of placental real-time shear wave elastography combined with three-dimensional power Doppler index (3D-PDI) in the prediction of preeclampsia. We conducted a retrospective study selecting 60 pregnant women diagnosed with preeclampsia as the experimental group and 60 normal pregnant women as the control group from January 2021 to December 2022. The elastic modulus values of different regions of the placenta and placental 3D-PDI were detected and compared between the two groups. The ROC curve was used to evaluate the diagnostic value of each parameter, alone or in combination, for preeclampsia. The study findings demonstrated that the elastic modulus values of different regions of the placenta and 3D-PDI of the two groups have statistical significance. The values of SWE, VI, FI, and VFI are different in prediction of preeclampsia, and the combination of various parameters can improve the prediction value. Overall, our study provides a valuable method for the prediction of preeclampsia with the advantages of non-invasiveness, efficiency, and simplicity.

Preparation and property analysis of antioxidant of carbazole derivatives.

Carbazole derivatives can be used as antioxidants in the lubricating oil industry. The alkylation of carbazole with 2-chloro-2-methylpropane and 2-bromopropane catalyzed by anhydrous aluminum chloride was studied. Initially, 3,6-di-iso-propylcarbazole and 3,6-di-tert-butylcarbazole were using dichloromethane and dibromomethane as solvents at room temperature, respectively. The synthesis conditions were optimized. Subsequently, the effects of reaction time, catalyst dosage, and molar ratio of carbazole to alkylating agent were investigated, and orthogonal experiments were performed. The structures of the carbazole derivatives were characterized by Fourier infrared spectroscopy (FT-IR), mass spectrum (MS) and nuclear magnetic resonance spectroscopy (NMR). The thermal stability of the synthesized carbazole derivatives was investigated by differential scanning calorimetry (DSC). The carbazole derivatives were added into the lubricating oil with a mass fraction of 0.8% and the miscibility, stability and oxidation resistance of the mixed system were evaluated by mechanical stirring and a rotary pressure vessel oxidation test (RPVOT). The DSC results showed that there was good thermal stability for the carbazole derivatives. The mechanical stirring method revealed good solubility and stability for the mixture of oil and carbazole derivatives. The RPVOT results showed that isopropyl carbazole derivatives could increase the oxidation induction period of lubricating oil to 1.39 times, and tert-butyl carbazole derivatives could increase the oxidation induction period of lubricating oil to 1.91 times. The antioxidant effect of tert-butyl carbazole derivatives was better than that of isopropyl carbazole derivatives.

DNA methylation characteristics associated with chemotherapy resistance in epithelial ovarian cancer.

Objective: The high mortality rate of epithelial ovarian cancer (EOC) is often attributed to the frequent development of chemoresistance. DNA methylation is a predictive biomarker for chemoresistance. Methods: This study utilized DNA methylation profiles and relevant information from GEO and TCGA to identify different methylated CpG sites (DMCs) between chemoresistant and chemosensitive patients. Subsequently, we constructed chemoresistance risk models with DMCs. The genes corresponding to candidate DMCs in chemoresistance risk models were further analyzed to identify different methylated gene symbols (DMGs) associated with chemoresistance. The DMGs that showed a strong correlation with the corresponding DMCs were analyzed through immunohistochemistry. Results: Compared to chemosensitive EOC patients, chemoresistant patients showed 423 hypermethylated CpGs and 1445 hypomethylated CpGs. The chemoresistance risk models based on DMCs have shown the improved predictive ability for chemoresistance in EOC (AUC = 65.0-76.2%). The methylations of cg25510164, cg13154880, cg15362155 and cg08665359 were strongly associated with decreased risk of chemoresistance. Conversely, the methylation of cg08872590 and cg14739437 significantly increased the risk. We identified 13 DMGs, from 47 DMCs corresponding genes, between chemosensitive and chemoresistant samples. Among the DMGs, the expression levels of DDR2 and OPCML exhibited strong correlations with the corresponding DMCs. DDR2 and OPCML both showed enhanced expression in chemoresistant ovarian microarray tissue. Conclusions: Hypomethylated CpGs may play a significant role in DNA methylation associated with chemoresistance in EOC. The epigenetic modification of DDR2 could have important implications for the development of chemoresistance. Our study provides valuable insights for future research on DNA methylation in the chemoresistance of EOC.

Predictors of improvement in left ventricular systolic function after catheter ablation in patients with persistent atrial fibrillation complicated with heart failure.

AIMS: The current management of patients with atrial fibrillation (AF) and concomitant heart failure (HF) remains a significant challenge. Catheter ablation (CA) has been shown to improve left ventricular ejection fraction (LVEF) in these patients, but which patients can benefit from CA is still poorly understood. The aim of our study was to determine the predictors of improved ejection fraction in patients with persistent atrial fibrillation (PeAF) complicated with HF undergoing CA. METHODS AND RESULTS: A total of 435 patients with persistent AF underwent an initial CA between January 2019 and March 2023 in our hospital. We investigated consecutive patients with left ventricular systolic dysfunction (LVEF < 50%) measured by transthoracic echocardiography (TTE) within one month before CA. According to the LVEF changes at 6 months, these patients were divided into an improved group (fulfilling the '2021 Universal Definition of HF' criteria for LVEF recovery) and a nonimproved group. Eighty patients were analyzed, and the improvement group consisted of 60 patients (75.0%). In the univariate analysis, left ventricular end-diastolic diameter (P = 0.005) and low voltage zones in the left atrium (P = 0.043) were associated with improvement of LVEF. A receiver operating characteristic analysis determined that the suitable cutoff value for left ventricular end-diastolic diameter (LVDd) was 59 mm (sensitivity: 85.0%, specificity: 55.0%, area under curve: 0.709). A multivariate analysis showed that LVDd (OR = 0.85; 95% CI: 0.76-0.95, P = 0.005) and low voltage zones (LVZs) (OR = 0.26; 95% CI: 0.07-0.96, P = 0.043) were significantly independently associated with the improvement of LVEF. Additionally, parameters were significantly improved regarding the left atrial diameter, LVDd and ventricular rate after radiofrequency catheter ablation (all p < 0.05). CONCLUSIONS: The improvement of left ventricular ejection fraction (LVEF) occurred in 75.0% of patients. Our study provides additional evidence that LVDd < 59 mm and no low voltage zones in the left atrium can be used to jointly predict the improvement of LVEF after atrial fibrillation ablation.

Bisphenol S, bisphenol F, bisphenol a exposure and body composition in US adults.

Bisphenol S (BPS) and bisphenol F (BPF) are increasingly used to replace bisphenol A (BPA), an endocrine-disrupting chemical with putative obesogenic properties; whether and how BPS and BPF affect adiposity in humans remains to be determined. Therefore, we examined the association of BPA, BPS， and BPF with body composition among US adults. We included 1787 participants aged 20-59 years old in the National Health and Nutrition Examination Survey 2013-2016 who had information on urinary BPA, BPS, and BPF concentrations, and body composition measured using dual-energy x-ray absorptiometry. After full adjustment for potential confounders in linear regression models, BPA was significantly associated with the % body fat of the whole body, arm, and leg, with the ß (95% CI) for the highest quartile vs. the lowest quartile of 1.34 (95%CI [0.11, 2.58], P = 0.03), 1.60 (95%CI [0.20, 3.00], P = 0.03), and 1.63 (95%CI [0.24, 3.02], P = 0.02), respectively. No association between BPA and lean mass was found. For BPS, significant associations were found for % body fat of the whole body (ß [95% CI] = 1.42 [0.49, 2.36], P = 0.004), trunk (ß[95% CI] = 1.92 [0.86, 2.97], P = 0.001), and arm (ß [95% CI] = 1.60 [0.49, 2.70], P = 0.01), as well as lean mass of the whole body (ß [95% CI] = 2610.6 [1324.3, 3896.8], P < 0.001), trunk (ß [95% CI] = 1467.0 [745.3, 2188.7], P < 0.001), arm (ß [95% CI] = 113.4 [10.3, 216.5], P = 0.03), and leg (ß [95% CI] = 431.5 [219.6, 643.4], P < 0.001), comparing the third quartile vs. the lowest quartile. No significant association was observed between BPF and % body fat and lean mass. Results suggest that higher BPA levels were significantly associated with greater % body fat of the whole body and limbs, and there was suggestive evidence that BPS levels were associated with both % body fat and lean mass of the whole body and body parts in a nonmonotonic relationship.

Experimental study and finite element analysis of heavy-duty escalator truss under full load conditions.

The performance of the heavy-duty escalator truss greatly affects the stability and service life of the whole escalator system, and the manufacturing cost of truss structure accounts for more than 1/5. Thus, how to design the truss structure reasonably is a pivotal issue drawing the attention of numerous engineers and researchers. In this work, the experimental research of heavy-duty escalators under full load conditions were performed in terms of the end restraints, the docking port clearances, and the deflection. Based on the experimental results, the three-dimensional simulation model of truss structure was created, and the influences of various factors such as the internal chamfer of truss member, the lower deviation of truss member, the dead weight of escalator, and the pretension force of each bolt at the docking port were analyzed and quantified. Finally, the finite element model which can almost completely characterize the actual structure was obtained with slight difference. The conclusions drawn in this work provide the basis for the efficient design, correct simulation, low cost production and rapid installation of the heavy-duty escalator truss.

A pH-responsive cetuximab-conjugated DMAKO-20 nano-delivery system for overcoming K-ras mutations and drug resistance in colorectal carcinoma.

Cetuximab (Cet) and oxaliplatin (OXA) are used as first-line drugs for patients with colorectal carcinoma (CRC). In fact, the heterogeneity of CRC, mainly caused by K-ras mutations and drug resistance, undermines the effectiveness of drugs. Recently, a hydrophobic prodrug, (1E,4E)-6-((S)-1-(isopentyloxy)-4-methylpent-3-en-1-yl)-5,8-dimethoxynaphthalene-1,4­dione dioxime (DMAKO-20), has been shown to undergo tumor-specific CYP1B1-catalyzed bioactivation. This process results in the production of nitric oxide and active naphthoquinone mono-oximes, which exhibit specific antitumor activity against drug-resistant CRC. In this study, a Cet-conjugated bioresponsive DMAKO-20/PCL-PEOz-targeted nanocodelivery system (DMAKO@PCL-PEOz-Cet) was constructed to address the issue of DMAKO-20 dissolution and achieve multitargeted delivery of the cargoes to different subtypes of CRC cells to overcome K-ras mutations and drug resistance in CRC. The experimental results demonstrated that DMAKO@PCL-PEOz-Cet efficiently delivered DMAKO-20 to both K-ras mutant and wild-type CRC cells by targeting the epidermal growth factor receptor (EGFR). It exhibited a higher anticancer effect than OXA in K-ras mutant cells and drug-resistant cells. Additionally, it was observed that DMAKO@PCL-PEOz-Cet reduced the expression of glutathione peroxidase 4 (GPX4) in CRC cells and significantly inhibited the growth of heterogeneous HCT-116 subcutaneous tumors and patient-derived tumor xenografts (PDX) model tumors. This work provides a new strategy for the development of safe and effective approaches for treating CRC. STATEMENT OF SIGNIFICANCE: (1) Significance: This work reports a new approach for the treatment of colorectal carcinoma (CRC) using the bioresponsible Cet-conjugated PCL-PEOz/DMAKO-20 nanodelivery system (DMAKO@PCL-PEOz-Cet) prepared with Cet and PCL-PEOz for the targeted transfer of DMAKO-20, which is an anticancer multitarget drug that can even prevent drug resistance, to wild-type and K-ras mutant CRC cells. DMAKO@PCL-PEOz-Cet, in the form of nanocrystal micelles, maintained stability in peripheral blood and efficiently transported DMAKO-20 to various subtypes of colorectal carcinoma cells, overcoming the challenges posed by K-ras mutations and drug resistance. The system's secure and effective delivery capabilities have also been confirmed in organoid and PDX models. (2) This is the first report demonstrating that this approach simultaneously overcomes the K-ras mutation and drug resistance of CRC.