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1.
J Geriatr Cardiol ; 21(6): 651-657, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38973824

RESUMO

BACKGROUND: Cardioneuroablation (CNA) has shown encouraging results in patients with vasovagal syncope (VVS). However, data on different subtypes was scarce. METHODS: This observational study retrospectively enrolled 141 patients [mean age: 40 ± 18 years, 51 males (36.2%)] with the diagnosis of VVS. The characteristics among different types of VVS and the outcomes after CNA were analyzed. RESULTS: After a mean follow-up of 4.3 ± 1.5 years, 41 patients (29.1%) experienced syncope/pre-syncope events after CNA. Syncope/pre-syncope recurrence significantly differed in each subtype (P = 0.04). The cardioinhibitory type of VVS had the lowest recurrence rate after the procedure (n = 6, 16.7%), followed by mixed (n = 26, 30.6%) and vasodepressive (n = 9, 45.0%). Additionally, a significant difference was observed in the analyses of the Kaplan-Meier survival curve (P = 0.02). Syncope/pre-syncope burden was significantly reduced after CNA in the vasodepressive type (P < 0.01). Vasodepressive types with recurrent syncope/pre-syncope after CNA have a lower baseline deceleration capacity (DC) level than those without (7.4 ± 1.0 ms vs. 9.0 ± 1.6 ms, P = 0.01). Patients with DC < 8.4 ms had an 8.1 (HR = 8.1, 95% CI: 2.2-30.0, P = 0.02) times risk of syncope/pre-syncope recurrence after CNA compared to patients with DC ≥ 8.4 ms, and this association still existed after adjusting for age and sex (HR = 8.1, 95% CI: 2.2-30.1, P = 0.02). CONCLUSIONS: Different subtypes exhibit different event-free rates. The vasodepressive type exhibited the lowest event-free rate, but those patients with DC ≥ 8.4 ms might benefit from CNA.

2.
Beilstein J Org Chem ; 20: 1497-1503, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978749

RESUMO

We report a practical and sustainable electrophotochemical metal-catalyzed protocol for decarboxylative cyanation of simple aliphatic carboxylic acids. This environmentally friendly method features easy availability of substrates, broad functional group compatibility, and directly converts a diverse range of aliphatic carboxylic acids including primary and tertiary alkyl acids into synthetically versatile alkylnitriles without using chemical oxidants or costly cyanating reagents under mild reaction conditions.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38955995

RESUMO

BACKGROUND: The guidelines recommend conventional cold snare polypectomy (C-CSP) for diminutive and small colorectal polyps (≤ 10 mm). However, it remains unclear whether CSP with sub-mucosal injection (SI-CSP) achieves comparable efficacy to C-CSP for managing these lesions. This study compares SI-CSP with C-CSP for patients with diminutive and small colorectal polyps. METHODS: An electronic literature search was conducted to retrieve articles comparing resection outcomes between SI-CSP and C-CSP in diminutive and small colorectal polyps (registration number INPLASY2023100096). Our primary outcomes of interest were the complete resection rate (CRR), complications (namely immediate bleeding, delayed bleeding and perforation) and polypectomy time. Mean differences with 95% confidence intervals (CI) were employed for continuous variables, while odds ratios (OR) with 95% CI were calculated for categorical variables. Data was analyzed using a random effects model and the I2 test was utilized to assess heterogeneity. RESULTS: Eight studies involving 1470 patients with 2223 polyps were included in our analysis. The CRR was not significantly higher in the SI-CSP group, with an OR of 95% CI 0.50 (0.22, 1.15). The incidences of immediate bleeding (OR 95% CI 0.60 [0.26-1.40]) and delayed bleeding (OR 95% CI 0.88 [0.32-2.42]) did not differ significantly between the two groups. On average, the mean polypectomy time was 64.75 seconds shorter in the C-CSP group (95% CI, - 102.96 to - 26.53). Notably, no perforation events were reported in the included studies. CONCLUSIONS: The use of SI-CSP was not superior to C-CSP in managing diminutive and small colorectal polyps and the procedure required significantly more time.

4.
Ann Med Surg (Lond) ; 86(7): 3880-3886, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38989172

RESUMO

Background: Syncope is a serious consequence in patients with hypertrophic obstructive cardiomyopathy (HOCM). Percutaneous endocardial septal radiofrequency ablation (PESA) has emerged as a promising intervention to alleviate symptoms and enhance the quality of life for HOCM patients. However, little is known about the effects of PESA on syncope in HOCM. The authors aimed to study the effects of PESA on syncope in patients with HOCM. Materials and methods: Nineteen patients with HOCM and syncope were enrolled. The left ventricular outflow tract gradient (LVOTG) of the patients was more than 50 mmHg despite medication. The participants underwent PESA under the guidance of intracardiac echocardiography (ICE) combined with a three-dimensional electrophysiological mapping system. The patients were followed for 3 (3-5.5) months. Results: The mean age of the patients was 54.8±13.7 years. Out of the 19 participants, 7 (37%) were females. During the follow-up, the syncope was completely alleviated in 14 patients (73.7%) or the syncope episodes were reduced greater than or equal to 80% in 16 patients (84.2%). The mean NYHA functional class significantly improved from 2.2±0.7 at baseline to 1.7±0.6 during follow-up (P=0.002). The LVOTG and septal thickness showed a decreasing trend from baseline to follow-up (LVOTG: P=0.083, septal thickness: P=0.086). Conclusion: The authors' investigation provides evidence supporting the effectiveness of PESA in reducing syncope episodes in patients with HOCM.

5.
ESC Heart Fail ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38887208

RESUMO

AIMS: To retrospectively compare the long-term outcomes following atrial fibrillation (AF) ablation between heart failure (HF) with preserved ejection fraction (EF) (HFpEF) and reduced/mildly reduced EF (HFr-mrEF) patients, and to identify novel predictors of adverse clinical events. METHODS: In total, 1402 AF patients with HF who underwent successful ablation were consecutively enrolled. Adverse clinical events including all-cause death, HF hospitalization, and stroke were followed up. Cox proportional hazards models were used to assess the associations between clinical factors and events. Kaplan-Meier analysis was performed to estimate the cumulative incidences of these events. A receiver operating characteristic curve was used to test the ability of these predictors. RESULTS: During a follow-up period of 42 ± 15 months, 265 (18.9%) patients experienced adverse clinical events after ablation. The cumulative incidence of adverse clinical events was significantly higher in HFr-mrEF than in HFpEF (25.4% vs. 15.7%, P < 0.001), the similar tendency was observed on all-cause death (10.5% vs. 6.5%, P = 0.011) and HF hospitalization (17.2% vs. 10.1%, P < 0.001). After multivariate adjustment, non-paroxysmal AF [hazard ratio (HR) 1.922, 95% confidence interval (CI) 1.130-3.268, P = 0.016], LAD ≥ 45 mm (HR 2.197, 95% CI 1.206-4.003, P < 0.001), LVEF (HR 0.959, 95% CI 0.946-0.981, P < 0.001), and RAD ≥ 45 mm (HR 2.044, 95% CI 1.362-3.238, P < 0.001) remained the independent predictors for developing adverse clinical events. A predictive model performed with non-paroxysmal AF, LAD ≥ 45 mm and RAD ≥ 45 mm yielded an area under curve of 0.728 (95% CI 0.696-0.760, P < 0.001). CONCLUSIONS: AF patients with HFpEF had better long-term outcomes than those with HFr-mrEF, and moderate/severe biatrial dilation could predict adverse clinical events following catheter ablation in AF and HF patients.

6.
Front Immunol ; 15: 1387811, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911870

RESUMO

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Ferritinas , Infecções por Henipavirus , Mesocricetus , Nanopartículas , Vírus Nipah , Vacinas Virais , Animais , Vírus Nipah/imunologia , Infecções por Henipavirus/prevenção & controle , Infecções por Henipavirus/imunologia , Ferritinas/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Cricetinae , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Feminino , Humanos , Nanovacinas
7.
Clin Hypertens ; 30(1): 17, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946010

RESUMO

BACKGROUND: This study explores the impact of intensive blood pressure (BP) control on left ventricular hypertrophy (LVH) incidence and evaluates the prognostic implications of LVH status (pre-existing/new-onset/persistent/regression) using Systolic Blood Pressure Intervention Trial (SPRINT) Electrocardiogram Data. METHODS: Poisson regression was used to assess new-onset LVH and LVH regression rates. Multivariable-adjusted Cox proportional hazard models determined the risk of adverse cardiovascular events (ACE), a composite of myocardial infarction (MI), non-MI acute coronary syndrome, stroke, heart failure, or cardiovascular death, alongside safety adverse events. RESULTS: In 8,016 participants, intensive BP control significantly reduced new-onset LVH (8.27 vs. 14.79 per 1000-person years; adjusted p<0.001) and increased LVH regression (14.89 vs. 11.89 per 1000-person years; adjusted p<0.001). Elevated ACE risk was notable in participants with pre-existing LVH [adjusted HR: 1.94 (95% CI: 1.25-2.99); p = 0.003], new-onset LVH [adjusted 1.74 (95% CI: 1.16-2.60); p = 0.007], and persistent LVH[adjusted HR: 1.96 (95% CI: 1.11-3.46); p = 0.020], compared to those without LVH. Intriguingly, LVH regression attenuated this risk increment [adjusted HR: 1.57 (95% CI: 0.98-2.53); p = 0.062]. Achieving a BP target of < 120/80 mmHg nullified the increased ACE risk in those with pre-existing LVH. CONCLUSIONS: Intensive BP control is instrumental in both reducing the emergence of LVH and fostering its regression. Pre-existing, new-onset LVH and persistent LV remain a predictor of adverse cardiovascular prognosis, whereas LVH regression and achieving on-treatment BP < 120/80 mmHg in pre-existing LVH individuals may further mitigate residual cardiovascular risk. CLINICAL TRIAL REGISTRATION: URL: ClinicalTrials.gov Unique Identifier: NCT01206062.

8.
Environ Sci Pollut Res Int ; 31(24): 35553-35566, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38733444

RESUMO

Volatile organic compounds (VOCs) frequently pose a threat to the biosphere, impacting ecosystems, flora, fauna, and the surrounding environment. Industrial emissions of VOCs often include the presence of water vapor, which, in turn, diminishes the adsorption capacity and efficacy of adsorbents. This occurs due to the competitive adsorption of water vapor, which competes with target pollutants for adsorption sites on the adsorbent material. In this study, hydrophobic activated carbons (BMIMPF6-AC (L), BMIMPF6-AC (g), and BMIMPF6-AC-H) were successfully prepared using 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6) to adsorb toluene under humidity environment. The adsorption performance and mechanism of the resulting ionic liquid-modified activated carbon for toluene in a high-humidity environment were evaluated to explore the potential application of ionic liquids as hydrophobic modifiers. The results indicated that BMIMPF6-AC-H exhibited superior hydrophobicity. The toluene adsorption capacity of BMIMPF6-AC-H was 1.53 times higher than that of original activated carbon, while the adsorption capacity for water vapor was only 37.30% of it at 27 °C and 77% RH. The Y-N model well-fitted the dynamic adsorption experiments. To elucidate the microscopic mechanism of hydrophobic modification, the Independent Gradient Model (IGM) method was employed to characterize the intermolecular interactions between BMIMPF6 and toluene. Overall, this study introduces a new modifier for hydrophobic modification of activated carbon, which could enhance the efficiency of activated carbon in treating industrial VOCs.


Assuntos
Umidade , Líquidos Iônicos , Tolueno , Compostos Orgânicos Voláteis , Líquidos Iônicos/química , Adsorção , Tolueno/química , Compostos Orgânicos Voláteis/química , Carvão Vegetal/química , Poluentes Atmosféricos/química , Interações Hidrofóbicas e Hidrofílicas , Imidazóis/química
9.
Hum Gene Ther ; 35(11-12): 374-387, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38717950

RESUMO

The ongoing advancements in CRISPR-Cas technologies can significantly accelerate the preclinical development of both in vivo and ex vivo organ genome-editing therapeutics. One of the promising applications is to genetically modify donor organs prior to implantation. The implantation of optimized donor organs with long-lasting immunomodulatory capacity holds promise for reducing the need for lifelong potent whole-body immunosuppression in recipients. However, assessing genome-targeting interventions in a clinically relevant manner prior to clinical trials remains a major challenge owing to the limited modalities available. This study introduces a novel platform for testing genome editing in human lungs ex vivo, effectively simulating preimplantation genetic engineering of donor organs. We identified gene regulatory elements whose disruption via Cas nucleases led to the upregulation of the immunomodulatory gene interleukin 10 (IL-10). We combined this approach with adenoviral vector-mediated IL-10 delivery to create favorable kinetics for early (immediate postimplantation) graft immunomodulation. Using ex vivo organ machine perfusion and precision-cut tissue slice technology, we demonstrated the feasibility of evaluating CRISPR genome editing in human lungs. To overcome the assessment limitations in ex vivo perfused human organs, we conducted an in vivo rodent study and demonstrated both early gene induction and sustained editing of the lung. Collectively, our findings lay the groundwork for a first-in-human-organ study to overcome the current translational barriers of genome-targeting therapeutics.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Pulmão , Edição de Genes/métodos , Humanos , Pulmão/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Animais , Vetores Genéticos/genética , Vetores Genéticos/administração & dosagem
10.
Heart Rhythm ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734226

RESUMO

BACKGROUND: The implantable cardioverter-defibrillator (ICD) prevents sudden cardiac death in patients with ischemic cardiomyopathy (ICM). Catheter ablation has been shown to effectively reduce ventricular tachycardia (VT) recurrence, yet its efficacy in patients without an ICD implantation remains uncertain. OBJECTIVE: We aimed to investigate the outcomes of ablation for VT in patients with ICM without a backup ICD. METHODS: Patients with ICM who received ablation for VT without an ICD implantation were included in this study. Ablation was guided by either activation mapping or substrate mapping. Endocardial ablation was the primary strategy; epicardial access was considered when endocardial ablation failed. The primary end point was VT recurrence during follow-up; secondary end points included cardiovascular rehospitalization, all-cause mortality, and a composite of these events. RESULTS: A total of 114 patients were included, with the mean age of 58.2 ± 11.1 years, 102 of whom (89.5%) were male. Twelve patients (10.5%) underwent endo-epicardial ablation, whereas the rest received endocardial ablation. With a median follow-up of 53.8 months (24.8-84.2 months), VT recurred in 45 patients (39.5%), and 6 patients (5.3%) died, including 2 sudden cardiac deaths. The recurrence rate of VT was significantly lower in patients undergoing endo-epicardial ablation than in those with endocardial ablation only (8.3% vs 43.1%; log-rank P = .032). After multivariate adjustment, epicardial ablation remained associated with a reduced risk of VT recurrence (hazard ratio, 0.14; 95% confidential interval, 0.02-0.98; P = .048). CONCLUSION: Patients with ICM undergoing VT ablation without a backup ICD experienced a notably low rate of arrhythmic death. Most recurrences proved nonlethal.

11.
Materials (Basel) ; 17(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38591477

RESUMO

The scarcity of high-quality data presents a major challenge to the prediction of material properties using machine learning (ML) models. Obtaining material property data from experiments is economically cost-prohibitive, if not impossible. In this work, we address this challenge by generating an extensive material property dataset comprising thousands of data points pertaining to the elastic properties of Fe-C alloys. The data were generated using molecular dynamic (MD) calculations utilizing reference-free Modified embedded atom method (RF-MEAM) interatomic potential. This potential was developed by fitting atomic structure-dependent energies, forces, and stress tensors evaluated at ground state and finite temperatures using ab-initio. Various ML algorithms were subsequently trained and deployed to predict elastic properties. In addition to individual algorithms, super learner (SL), an ensemble ML technique, was incorporated to refine predictions further. The input parameters comprised the alloy's composition, crystal structure, interstitial sites, lattice parameters, and temperature. The target properties were the bulk modulus and shear modulus. Two distinct prediction approaches were undertaken: employing individual models for each property prediction and simultaneously predicting both properties using a single integrated model, enabling a comparative analysis. The efficiency of these models was assessed through rigorous evaluation using a range of accuracy metrics. This work showcases the synergistic power of MD simulations and ML techniques for accelerating the prediction of elastic properties in alloys.

12.
Infection ; 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38679664

RESUMO

BACKGROUND: The stress hyperglycemia ratio (SHR), adjusted for average glycemic status, is suggested for assessing actual blood glucose levels. Its link with adverse outcomes is known in certain populations, yet its impact on sepsis patients' prognosis is unclear. This study explores the association between SHR and mortality in sepsis. METHODS: We included 13,199 sepsis patients in this study and categorized SHR into distinct groups. Additionally, we utilized restricted cubic spline analysis to evaluate the correlation between SHR as a continuous variable and mortality. The primary outcome was 1-year all-cause mortality. Logistic regression and Cox proportional hazards models were employed to assess the associations between the SHR and both in-hospital mortality and 1-year mortality, respectively. RESULTS: Among the study participants, 4,690 (35.5%) patients died during the 1-year follow-up. After adjusting for confounding variables, we identified a U-shaped correlation between SHR and 1-year mortality. Using an SHR of 0.99 as the reference point, the hazard ratio for predicted 1-year mortality increased by 1.17 (95% CI 1.08 to 1.27) per standard deviation above 0.99, whereas each standard deviation increase predicted the hazard ratio of 0.52 (95% CI 0.39 to 0.69) below 0.99. Furthermore, we found that SHR could enhance the predictive performance of conventional severity scores. CONCLUSION: There exists a U shaped association between SHR and mortality in sepsis patients, where both low and high SHR values are associated with an increased risk of poor outcomes.

13.
Nature ; 627(8003): 301-305, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38448596

RESUMO

Solid-state Li-S batteries (SSLSBs) are made of low-cost and abundant materials free of supply chain concerns. Owing to their high theoretical energy densities, they are highly desirable for electric vehicles1-3. However, the development of SSLSBs has been historically plagued by the insulating nature of sulfur4,5 and the poor interfacial contacts induced by its large volume change during cycling6,7, impeding charge transfer among different solid components. Here we report an S9.3I molecular crystal with I2 inserted in the crystalline sulfur structure, which shows a semiconductor-level electrical conductivity (approximately 5.9 × 10-7 S cm-1) at 25 °C; an 11-order-of-magnitude increase over sulfur itself. Iodine introduces new states into the band gap of sulfur and promotes the formation of reactive polysulfides during electrochemical cycling. Further, the material features a low melting point of around 65 °C, which enables repairing of damaged interfaces due to cycling by periodical remelting of the cathode material. As a result, an Li-S9.3I battery demonstrates 400 stable cycles with a specific capacity retention of 87%. The design of this conductive, low-melting-point sulfur iodide material represents a substantial advancement in the chemistry of sulfur materials, and opens the door to the practical realization of SSLSBs.

14.
Fa Yi Xue Za Zhi ; 40(1): 64-69, 2024 Feb 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38500463

RESUMO

Biological evidence is relatively common evidence in criminal cases, and it has strong probative power because it carries DNA information for individual identification. At the scene of fire-related cases, the complex thermal environment, the escape of trapped people, the firefighting and rescue operations, and the deliberate destruction of criminal suspects will all affect the biological evidence in the fire scene. Scholars at home and abroad have explored and studied the effectiveness of biological evidence identification in fire scenes, and found that the blood stains, semen stains, bones, etc. are the main biological evidence which can be easily recovered with DNA in fire scenes. In order to analyze the research status and development trend of biological evidence in fire scenes, this paper systematically sorts out the relevant research, mainly including the soot removal technology, appearance method of typical biological evidence, and possibility of identifying other biological evidence. This paper also prospects the next step of research direction, in order to provide reference for the identification of biological evidence and improve the value of biological evidence in fire scenes.


Assuntos
Manchas de Sangue , Líquidos Corporais , Incêndios , Humanos , Sêmen , DNA/genética
15.
Cell Biochem Funct ; 42(2): e3965, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38457283

RESUMO

A highly efficient chlorobenzene-degrading strain was isolated from the sludge of a sewage treatment plant associated with a pharmaceutical company. The strain exhibited a similarity of over 99.9% with multiple strains of Paenarthrobacter ureafaciens. Therefore, the strain was suggested to be P. ureafaciens LY. This novel strain exhibited a broad spectrum of pollutant degradation capabilities, effectively degrading chlorobenzene and other organic pollutants, such as 1, 2, 4-trichlorobenzene, phenol, and xylene. Moreover, P. ureafaciens LY co-metabolized mixtures of chlorobenzene with 1, 2, 4-trichlorobenzene or phenol. Evaluation of its degradation efficiency showed that it achieved an impressive degradation rate of 94.78% for chlorobenzene within 8 h. The Haldane-Andrews model was used to describe the growth of P. ureafaciens LY under specific pollutants and its concentrations, revealing a maximum specific growth rate (µmax ) of 0.33 h-1 . The isolation and characterization of P. ureafaciens LY, along with its ability to degrade chlorobenzene, provides valuable insights for the development of efficient and eco-friendly approaches to mitigate chlorobenzene contamination. Additionally, investigation of the degradation performance of the strain in the presence of other pollutants offers important information for understanding the complexities of co-metabolism in mixed-pollutant environments.


Assuntos
Clorobenzenos , Poluentes Ambientais , Micrococcaceae , Biodegradação Ambiental , Clorobenzenos/metabolismo , Fenol , Preparações Farmacêuticas
16.
Eur J Clin Invest ; 54(6): e14194, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38438337

RESUMO

BACKGROUND: Substantial focus has been placed on atrial fibrillation (AF) treatment and associated stroke prevention rather than preventing AF itself. We employed Mendelian randomization (MR) approach to examine the causal relationships between 50 modifiable risk factors (RFs) and AF. METHODS: Instrumental variables for genetically predicted exposures were derived from corresponding genome-wide association studies (GWASs). Summary-level statistical data for AF were obtained from a GWAS meta-analysis (discovery dataset, N = 1,030,836) and FinnGen (validation dataset, N = 208,594). Univariable and multivariable MR analyses were performed, primarily using inverse variance weighted method with a series of robust sensitivity analyses. RESULTS: Genetic predisposition to insomnia, daytime naps, apnea, smoking initiation, moderate to vigorous physical activity and obesity traits, including body mass index, waist-hip ratio, central and peripheral fat/fat-free mass, exhibited significant associations with an increased risk of AF. Coffee consumption and ApoB had suggestive increased risks. Hypertension (odds ratio (OR) 95% confidence interval (CI): 5.26 (4.42, 6.24)), heart failure (HF) (OR 95% CI, 4.77 (2.43, 9.37)) and coronary artery disease (CAD) (OR 95% CI: 1.20 (1.16, 1.24)) were strongly associated with AF, while college degree, higher education attachment and HDL levels were associated with a decreased AF risk. Reverse MR found a bidirectional relationship between genetically predicted AF and CAD, HF and ischemic stroke. Multivariable analysis further indicated that obesity-related traits, systolic blood pressure and lower HDL levels independently contributed to the development of AF. CONCLUSIONS: This study identified several lifestyles and cardiometabolic factors that might be causally related to AF, underscoring the importance of a holistic approach to AF management and prevention.


Assuntos
Fibrilação Atrial , Índice de Massa Corporal , Doença da Artéria Coronariana , Estudo de Associação Genômica Ampla , Insuficiência Cardíaca , Hipertensão , Análise da Randomização Mendeliana , Obesidade , Fumar , Fibrilação Atrial/genética , Fibrilação Atrial/epidemiologia , Humanos , Obesidade/genética , Obesidade/complicações , Fatores de Risco , Hipertensão/genética , Hipertensão/epidemiologia , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/epidemiologia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/epidemiologia , Fumar/genética , Relação Cintura-Quadril , Predisposição Genética para Doença , Exercício Físico , Apolipoproteínas B/genética , Apolipoproteína B-100/genética
17.
Heart Rhythm ; 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461922

RESUMO

BACKGROUND: Left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) are referred to as left bundle branch area pacing. OBJECTIVE: This study investigated whether long-term clinical outcomes differ in patients undergoing LBBP, LVSP, and biventricular pacing (BiVP) for cardiac resynchronization therapy (CRT). METHODS: Consecutive patients with reduced left ventricular ejection fraction (LVEF <50%) undergoing CRT were prospectively enrolled if they underwent successful LBBP, LVSP, or BiVP. The primary composite end point was all-cause mortality or heart failure hospitalization. Secondary end points included all-cause mortality, heart failure hospitalization, and echocardiographic measures of reverse remodeling. RESULTS: A total of 259 patients (68 LBBP, 38 LVSP, and 153 BiVP) were observed for a mean duration of 28.8 ± 15.8 months. LBBP was associated with a significantly reduced risk of the primary end point by 78% compared with both BiVP (7.4% vs 41.2%; adjusted hazard ratio [aHR], 0.22 [0.08-0.57]; P = .002) and LVSP (7.4% vs 47.4%; aHR, 0.22 [0.08-0.63]; P = .004]. The adjusted risk of all-cause mortality was significantly higher in LVSP than in BiVP (31.6% vs 7.2%; aHR, 3.19 [1.38-7.39]; P = .007) but comparable between LBBP and BiVP (2.9% vs 7.2%; aHR, 0.33 [0.07-1.52], P = .155). Propensity score adjustment also obtained similar results. LBBP showed a higher rate of echocardiographic response (ΔLVEF ≥10%: 60.0% vs 36.2% vs 16.1%; P < .001) than BiVP or LVSP. CONCLUSION: LBBP yielded long-term clinical outcomes superior to those of BiVP and LVSP. The role of LVSP for CRT needs to be reevaluated because of its high mortality risk.

18.
ACS Appl Mater Interfaces ; 16(13): 16132-16144, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38511296

RESUMO

The main impediment to the development of zinc-air batteries is the sluggish kinetics of the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER). Transition metal N-doped carbon catalysts offer a promising alternative to noble metal catalysts, with metal-organic framework (MOF)-derived carbon material catalysts being particularly noteworthy. Here, we synthesized MxP-Z-C carbon catalysts by combining two-dimensional (2D) metal porphyrin-based MOFs (MxPMFs, x = Fe, Co, Ni, Mn) and three-dimensional zeolitic imidazole framework-8 (ZIF-8) through electrostatic interaction, followed by carbonization. ZIF-8 was inserted between the layers of MxPMFs to prevent its Π-Π stacking, allowing the active sites to become fully exposed. MxP-Z-C demonstrated an impressive catalytic activity for both the ORR and the OER reactions. Among them, FeP-Z-C showed the best catalytic activity. The half-wave potential for ORR was 0.92 V (vs the reversible hydrogen electrode (RHE)), while the overpotential for the OER was 290 mV. In addition, the zinc-air battery assembled by FeP-Z-C exhibited high power density (133.14 mW cm-2) and significant specific capacity (816 mAh gZn-1), indicating considerable potential as a bifunctional catalyst for electronic devices.

19.
J Pharmacol Exp Ther ; 389(2): 163-173, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38453527

RESUMO

Hepatocellular carcinoma (HCC) is the predominant pathologic type of primary liver cancer. It is a malignant tumor of liver epithelial cells. There are many ways to treat HCC, but the survival rate for HCC patients remains low. Therefore, understanding the underlying mechanisms by which HCC occurs and develops is critical to explore new therapeutic targets. Aldehyde dehydrogenase 2 (ALDH2) is an important player in the redox reaction of ethanol with endogenous aldehyde products released by lipid peroxidation. Increasing evidence suggests that ALDH2 is a crucial regulator of human tumor development, including HCC. Therefore, clarifying the relationship between ALDH2 and HCC is helpful for formulating rational treatment strategies. This review highlights the regulatory roles of ALDH2 in the development of HCC, elucidates the multiple potential mechanisms by which ALDH2 regulates the development of HCC, and summarizes the progress of research on ALDH2 gene polymorphisms and HCC susceptibility. Meanwhile, we envision viable strategies for targeting ALDH2 in the treatment of HCC SIGNIFICANCE STATEMENT: Numerous studies have aimed to explore novel therapeutic targets for HCC, and ALDH2 has been reported to be a critical regulator of HCC progression. This review discusses the functions, molecular mechanisms, and clinical significance of ALDH2 in the development of HCC and examines the prospects of ALDH2-based therapy for HCC.


Assuntos
Aldeído Oxirredutases , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Aldeído Desidrogenase , Aldeído-Desidrogenase Mitocondrial/genética
20.
Biomark Med ; 18(5): 181-190, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38440887

RESUMO

Objective: This study aimed to investigate the prognostic potency of LRG1 in acute ischemic stroke (AIS) patients. Methods: Plasma LRG1 levels were detected at admission and on days 3, 7 and 30 in 150 AIS patients. Results: LRG1 positively correlated with total cholesterol (p = 0.016), triglycerides (p = 0.046), C-reactive protein (p < 0.001), TNF-α (p = 0.001) and IL-6 (p = 0.004). After admission, LRG1 showed a decreasing trend (p < 0.001). Interestingly, LRG1 levels at admission (p = 0.014), day 3 (p = 0.027), day 7 (p = 0.008) and day 30 (p = 0.002) were higher in patients with modified Rankin scale score ≥2 versus those with scores <2. The LRG1 levels at day 7 (p = 0.032) and day 30 (p = 0.023) were higher in patients with recurrence versus no recurrence. Conclusion: LRG1 correlates with blood lipids, inflammation and short-term prognosis of AIS.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Prognóstico , Glicoproteínas/metabolismo , Inflamação , Proteína C-Reativa , Acidente Vascular Cerebral/diagnóstico
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