RESUMEN
BACKGROUND: Proton pump inhibitors (PPIs) are frequently prescribed to patients with coronary heart disease (CHD) under antiplatelet therapy to prevent gastrointestinal (GI) bleeding. However, its clinical impact is still under debate, especially in Asian population. This study was undertaken to explore the effects of concurrent use of clopidogrel and PPIs on the clinical outcomes in Chinese patients with CHD in secondary prevention. METHODS: A single-center retrospective study was conducted in 638 patients with CHD on consecutive clopidogrel therapy for at least 1 year. After 18-month follow-up, adverse clinical events were collected. Cox regression was used to calculate hazard ratios (HR) and 95% confidence interval (CI) for the effect of PPI use on the outcomes. A total of 638 patients were recruited from 2014 to 2015 in this study, among whom 201 were sustained PPI users, 188 were intermittent PPI users and the remaining 249 were non-PPI users. RESULTS: Compared with sustained PPI users, intermittent use of PPIs was associated with a lower risk of stroke, major adverse cardiac events (MACE) and net adverse clinical event (NACE) (stroke: adjusted HR: 0.109, 95% CI 0.014-0.878, p = 0.037; MACE: adjusted HR: 0.293, 95% CI 0.119-0.722; p = 0.008; NACE: adjusted HR: 0.357, 95% CI 0.162-0.786, p = 0.011). Subgroup analysis further revealed the benefit of intermittent PPI use was significant in male CHD patients over 60 years old, with hypertension or chronic kidney disease, and undergoing percutaneous coronary intervention during hospitalization. CONCLUSION: The current findings suggest that the intermittent concurrent use of PPIs and clopidogrel is not associated with an increased risk of 18-month adverse clinical outcomes, and intermittent use of PPIs is associated with a lower rate of MACE and NACE.
Asunto(s)
Clopidogrel/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Hemorragia Gastrointestinal/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , China , Clopidogrel/efectos adversos , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/mortalidad , Femenino , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de la Bomba de Protones/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
C1orf112/FIRRM is a recently identified DNA damage repair factor that regulates RAD51 in homologous recombination through interacting with the anti-recombinase FIGNL1. Here, we describe steps for purifying C1orf112/FIRRM, FIGNL1, miBRCA2, and RAD51 proteins from Escherichia coli or Saccharomyces cerevisiae cells. We then detail procedures for reconstituting the disassembly of RAD51 filament by C1orf112/FIRRM-FIGNL1 in vitro and the antagonistic effect between C1orf112/FIRRM-FIGNL1 and miBRCA2 on RAD51 filament stabilization. For complete details on the use and execution of this protocol, please refer to Zhou et al. (2023).1.
Asunto(s)
Proteínas , Recombinasa Rad51 , Proteínas/genética , Recombinasa Rad51/genética , Reparación del ADN , Recombinación HomólogaRESUMEN
Applications for polylactic acid (PLA) are significantly impacted by its poor mechanical properties and lack of thermal stability. The goal of this work is to bridge the gap of poor compatibility among the components and enhance their interface interlocking capability to improve the toughness and thermal stability. Ultrafine bamboo charcoal (UFBC) was treated through deep eutectic solvent (DES) method to deposit sodium lignosulfonate (LS) on its surface. LS was used with PLA as a bio-coupling agent to create an eco-friendly PLA composite film with a wide range of characteristics. Benefiting from the penetration of PLA to the internal pores in UFBC, the resultant L-UFBC/PLA film has a good mechanical interlocking structure. Ls can increase the compatibility and strengthen the interface interlocking capability through DES method, which greatly improves the mechanical properties of the system. In comparison to pure PLA one, the elongation at break was 136.24 % greater, and the crystallinity (Xc) increased from 1.09 % to 3.33 %. Furthermore, the thermal stability of the system was also improved, and the residual at 600 °C rose by 4.83 %. These characteristics offer the prepared L-UFBC/PLA film a wide range of potential applications in the packaging, medical, agricultural, and other sectors.
Asunto(s)
Agricultura , Carbón Orgánico , Análisis por Conglomerados , PoliésteresRESUMEN
The recombinase RAD51 plays a core role in DNA repair by homologous recombination (HR). The assembly and disassembly of RAD51 filament need to be orderly regulated by mediators such as BRCA2 and anti-recombinases. To screen for potential regulators of RAD51, we perform RAD51 proximity proteomics and identify factor C1orf112. We further find that C1orf112 complexed with FIGNL1 facilitates RAD51 filament disassembly in the HR step of Fanconi anemia (FA) pathway. Specifically, C1orf112 physically interacts with FIGNL1 and enhances its protein stability. Meanwhile, the RAD51 filament disassembly activity of FIGNL1 is directly stimulated by C1orf112. BRCA2 directly interacts with C1orf112-FIGNL1 complex and functions upstream of this complex to protect RAD51 filament from premature disassembly. C1orf112- and FIGNL1-deficient cells are primarily sensitive to DNA interstrand cross-link (ICL) agents. Thus, these findings suggest an important function of C1orf112 in RAD51 regulation in the HR step of ICL repair by FA pathway.
Asunto(s)
Proteínas , Recombinasa Rad51 , Recombinasa Rad51/metabolismo , Proteínas/metabolismo , Proteína BRCA2/genética , Reparación del ADN , ADN/metabolismo , Daño del ADNRESUMEN
Brain-computer interfaces (BCIs) have garnered significant attention in recent years due to their potential applications in medical, assistive, and communication technologies. Building on this, noninvasive BCIs stand out as they provide a safe and user-friendly method for interacting with the human brain. In this work, we provide a comprehensive overview of the latest developments and advancements in material, design, and application of noninvasive BCIs electrode technology. We also explore the challenges and limitations currently faced by noninvasive BCI electrode technology and sketch out the technological roadmap from three dimensions: Materials and Design; Performances; Mode and Function. We aim to unite research efforts within the field of noninvasive BCI electrode technology, focusing on the consolidation of shared goals and fostering integrated development strategies among a diverse array of multidisciplinary researchers.
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Interfaces Cerebro-Computador , Humanos , Electroencefalografía/métodos , Encéfalo , ElectrodosRESUMEN
A P-/N-containing bamboo-activated carbon (BACm) was successfully synthesized by steam activation of bamboo charcoal and chemical grafting to as-prepared activated carbon using the reaction of phosphoric acid and urea. Characterizations of BACm presented a synergistic grafting of P and N elements to the BAC surface. The BACm was further loaded in a polylactic acid (PLA) matrix to prepare BACm/PLA composites. Mechanical strength study showed tensile strength dropped from 75.19 MPa to 61.30 MPa, and tensile modulus from 602.49 MPa to 375.56 MPa, suggesting a rigidity reduction and deformation resistance enhancement owing to the roughened surface of BACm that interlocked with the polymer. The thermogravimetric analysis showed that the carbon residue rate of BACm dramatically fell to 49.25 wt.% in contrast to 88.28% for the control BAC, and cone calorimeter measurements confirmed the enhancement of flame retardancy of the composites with BACm loading, and the carbon residue rate increased progressively with BACm loading in the composites, notably up to 8.60 wt.% for the BAC/PLA9 composite, which outweighed the theoretical residue rate by more than 50%. The elemental analysis also confirmed rich P/N levels of the dense carbon residue layer that could perform synergistically and effectively in fire suppression. The BACm tended to stimulate the earlier decomposition of the composites and formed a continuous residual carbon layer which functioned as an effective barrier hindering the mass and heat transfer between the combustion zone and the underlying matrix. Moreover, 9 wt.% of BACm loading could attain a V-0 rating (UL94) for the composite with an improved limiting oxygen index up to 31.7%. The biomass-based modified activated carbon in this work could be considered as an alternative flame retardant in polymer applications.
RESUMEN
In this work, nitrogen-doped bamboo-based activated carbon (NBAC) was in situ synthesized from simply blending bamboo charcoal (BC) with sodamide (SA, NaNH2) powders and heating with a protection of nitrogen flow at a medium temperature. The elemental analysis and X-ray photoelectron spectra of as-synthesized NBAC showed quite a high nitrogen level of the simultaneously activated and doped samples; an abundant pore structure had also been determined from the NBACs which has a narrow size distribution of micropores (<2 nm) and favorable specific surface area that presented superb adsorption performance. The fcarbon dioxide (CO2) adsorption of the NBACs was measured at 0 °C and 25 °C at a pressure of 1 bar, whose capture capacities reached 3.68-4.95 mmol/g and 2.49-3.52 mmol/g, respectively, and the maximum adsorption could be observed for NBACs fabricated with an SA/BC ratio of 3:1 and activated at 500 °C. Further, adsorption selectivity of CO2 over N2 was deduced with the ideal adsorbed solution theory ((IAST), the selectivity was finally calculated which ranged from 15 to 17 for the NBACs fabricated at 500 °C). The initial isosteric heat of adsorption (Qst) of NBACs was also determined at 30-40 kJ/mol, which suggested that CO2 adsorption was a physical process. The results of ten-cycle adsorption-desorption experimentally confirmed the regenerated NBACs of a steady CO2 adsorption performance, that is, the as-synthesized versatile NBAC with superb reproducibility makes it a perspective candidate in CO2 capture and separation application.
RESUMEN
To improve on the poor strength and flame retardancy of a chitosan (CS)-based functional film, cellulose nanofiber (CNF) was taken as the reinforced material and both ammonium polyphosphate (APP) and branched polyethyleneimine (BPEI) as the flame-retardant additives in the CS matrix to prepare the CS/CNF/APP/BPEI composite film by simple drying. The resulting composite film showed good mechanical strength, with a tensile strength reaching 71.84 Mpa due to the high flexibility of CNF and the combination of CS, CNF and BPEI through strong hydrogen bonding interactions. The flame retardant-performance of the composite film greatly enhanced the limit oxygen index (LOI), up to 32.7% from 27.6% for the pure film, and the PHRR intensity decreased to 28.87 W/g from 39.38% in the micro-scale combustion calorimetry (MCC) test due to the ability of BPEI to stimulate the decomposition of APP, releasing non-flammable gases such as CO2, N2, NH3, etc., and forming a protective phosphating layer to block the entry of O2. Based on the good flame retardancy, mechanical strength and transparency, the CS/CNF/APP/BPEI composite film has a great potential for future applications.
RESUMEN
DNA end resection is delicately regulated through various types of post-translational modifications to initiate homologous recombination, but the involvement of SUMOylation in this process remains incompletely understood. Here, we show that MRE11 requires SUMOylation to shield it from ubiquitin-mediated degradation when resecting damaged chromatin. Upon DSB induction, PIAS1 promotes MRE11 SUMOylation on chromatin to initiate DNA end resection. Then, MRE11 is deSUMOylated by SENP3 mainly after it has moved away from DSB sites. SENP3 deficiency results in MRE11 degradation failure and accumulation on chromatin, causing genome instability. We further show that cancer-related MRE11 mutants with impaired SUMOylation exhibit compromised DNA repair ability. Thus, we demonstrate that MRE11 SUMOylation in coordination with ubiquitylation is dynamically controlled by PIAS1 and SENP3 to facilitate DNA end resection and maintain genome stability.
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Cromatina , Proteína Homóloga de MRE11 , Sumoilación , Ubiquitinación , Cisteína Endopeptidasas/metabolismo , ADN/metabolismo , Roturas del ADN de Doble Cadena , Reparación del ADN , Inestabilidad Genómica , Homeostasis , Humanos , Proteína Homóloga de MRE11/genética , Proteína Homóloga de MRE11/metabolismo , Proteínas Inhibidoras de STAT Activados/metabolismo , Sumoilación/genética , Sumoilación/fisiología , Ubiquitinación/genética , Ubiquitinación/fisiologíaRESUMEN
We report on the development, validation, and utility of a measure assessing individual differences in activation of the parental care motivational system: The Parental Care and Tenderness (PCAT) questionnaire. Results from 1,608 adults (including parents and nonparents) show that the 25-item PCAT measure has high internal consistency, high test-retest reliability, high construct validity, and unique predictive utility. Among parents, it predicted self-child identity overlap and caring child-rearing attitudes; among nonparents, it predicted desire to have children. PCAT scores predicted the intensity of tender emotions aroused by infants, and also predicted the amount of time individuals chose look at infant (but not adult) faces. PCAT scores uniquely predicted additional outcomes in the realm of social perception, including mate preferences, moral judgments, and trait inferences about baby-faced adults. Practical and conceptual implications are discussed.