RESUMEN
Background: To investigate the correlation between inflammasomes and coronary artery calcification (CAC), and develop and validating a nomogram for predicting the risk of CAC in patients with coronary artery disease (CAD). Methods: A total of 626 patients with CAD at the Affiliated Hospital of Xuzhou Medical University were enrolled in this study. The patients were divided into the calcification group and the non-calcification group based on the assessment of coronary calcification. We constructed a training set and a validation set through random assignment. The least absolute shrinkage and selection operator (LASSO) regression and multivariate analysis were performed to identify independent risk factors of CAC in patients with CAD. Based on these independent predictors, we developed a web-based dynamic nomogram prediction model. The area under the receiver operating characteristic curve (AUC-ROC), calibration curves, and decision curve analysis (DCA) were used to evaluate this nomogram. Results: Age, smoking, diabetes mellitus (DM), hyperlipidemia, the serum level of nucleotide-binding oligomerization domain (NOD)-like receptor protein 1 (NLRP1), alkaline phosphatase (ALP) and triglycerides (TG) were identified as independent risk factors of CAC. The AUC-ROC of the nomogram is 0.881 (95% confidence interval (CI): 0.850-0.912) in the training set and 0.825 (95% CI: 0.760-0.876) in the validation set, implying high discriminative ability. Satisfactory performance of this model was confirmed using calibration curves and DCA. Conclusions: The serum NLRP1 level is an independent predictor of CAC. We established a web-based dynamic nomogram, providing a more accurate estimation and comprehensive perspective for predicting the risk of CAC in patients with CAD.
RESUMEN
Objective: To investigate the Levels of Nucleotide-binding, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) and Adiponectin (APN) and their relationship with the severity of coronary artery disease in patients with Unstable Angina (UA) and Type 2 Diabetes (T2D). Methods: Two hundred and thirty-one patients with UA were diagnosed by CAG in the Department of Cardiology of the Affiliated Hospital of Xuzhou Medical University from July 2022 to May 2023 were included, and 74 healthy subjects were included as the control group. The levels of NLRP3 and APN in each group were detected by ELISA and the Gensini score in each patient according to the results of CAG. The correlations between NLRP3, APN, and Gensini score were analyzed. According to whether complicated with T2D or not, we further analyze the effect of NLRP3 and APN levels of patients with UA and T2D on the severity of coronary artery stenosis. Results: The levels of NLRP3 in UA with T2D group were the highest, followed by simple UA group, and the lowest in the control group, and the level of APN was the opposite. Spearman Correlation analysis showed that the level of NLRP3 was positively correlated with Gensini score (ρ1=0.688, P<0.05) and the level of APN was negatively associated with Gensini score (ρ2= -0.515, P<0.05). There was a negative correlation between NLRP3 and the level of APN (ρ3= -0.366, P<0.05). High NLRP3 and low APN levels are the risk factors for atherosclerosis. Conclusion: The NLRP3 and APN were abnormally expressed in patients with UA complicated with T2D. With the aggravation of atherosclerosis, the level of NLRP3 increased and the level of APN decreased.
Asunto(s)
Adiponectina , Angina Inestable , Diabetes Mellitus Tipo 2 , Proteína con Dominio Pirina 3 de la Familia NLR , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Femenino , Adiponectina/sangre , Persona de Mediana Edad , Angina Inestable/sangre , Anciano , Enfermedad de la Arteria Coronaria/sangre , Estudios de Casos y Controles , Índice de Severidad de la EnfermedadRESUMEN
Biodegradable poly(butylene succinate-co-2-methyl succinate) (PBSMS)/cellulose nanocrystals (CNC) composites were successfully prepared at low CNC loadings with the aims of improving crystallization and mechanical properties and extending the practical application of PBSMS. CNC is finely dispersed in the PBSMS matrix without obvious aggregations. The low content of CNC obviously promoted the crystallization behavior of PBSMS under different conditions. The spherulitic morphology study revealed that CNC, as an effective heterogeneous nucleating agent, provided more nucleation sites during the melt crystallization process. In addition, the nucleation effect of CNC was quantitatively evaluated by the following two parameters, i.e., nucleation activity and nucleation efficiency. The crystal structure and crystallization mechanism of PBSMS remained unchanged in the composites. In addition, as a reinforcing nanofiller, CNC significantly increased Young's modulus and the yield strength of PBSMS. The crystallization behavior and mechanical properties of PBSMS were significantly improved by the low content of CNC, which should be interesting and essential from the perspective of biodegradable polymer composites.
RESUMEN
Photochromic hydrogels have promising prospects in areas such as wearable device, information encryption technology, optoelectronic display technology, and electronic skin. However, there are strict requirements for the properties of photochromic hydrogels in practical engineering applications, especially in some extreme application environments. The preparation of photochromic hydrogels with high transparency, high toughness, fast response, colour reversibility, excellent electrical conductivity, and anti-freezing property remains a challenge. In this study, a novel photochromic hydrogel (PAAm/SA/NaCl-Mo7) was prepared by loading ammonium molybdate (Mo7) and sodium chloride (NaCl) into a dual-network hydrogel of polyacrylamide (PAAm) and sodium alginate (SA) using a simple one-pot method. PAAm/SA/NaCl-Mo7 hydrogel has excellent conductivity (175.9 S/cm), water retention capacity and anti-freezing properties, which can work normally at a low temperature of -28.4 °C. In addition, the prepared PAAm/SA/NaCl-Mo7 hydrogel exhibits fast response (<15 s), high transparency (>70 %), good toughness (maximum elongation up to 1500 %), good cyclic compression properties at high compressive strains (60 %), good biocompatibility (78.5 %), stable reversible discolouration and excellent sensing properties, which can be used for photoelectric display, information storage and motion monitoring. This work provides a new inspiration for the development of flexible electronic skin devices.
Asunto(s)
Resinas Acrílicas , Alginatos , Conductividad Eléctrica , Hidrogeles , Cloruro de Sodio , Alginatos/química , Resinas Acrílicas/química , Hidrogeles/química , Cloruro de Sodio/química , Dispositivos Electrónicos Vestibles , Congelación , Materiales Biocompatibles/química , HumanosRESUMEN
Methylation quantitative trait loci (mQTLs) are essential for understanding the role of DNA methylation changes in genetic predisposition, yet they have not been fully characterized in East Asians (EAs). Here we identified mQTLs in whole blood from 3,523 Chinese individuals and replicated them in additional 1,858 Chinese individuals from two cohorts. Over 9% of mQTLs displayed specificity to EAs, facilitating the fine-mapping of EA-specific genetic associations, as shown for variants associated with height. Trans-mQTL hotspots revealed biological pathways contributing to EA-specific genetic associations, including an ERG-mediated 233 trans-mCpG network, implicated in hematopoietic cell differentiation, which likely reflects binding efficiency modulation of the ERG protein complex. More than 90% of mQTLs were shared between different blood cell lineages, with a smaller fraction of lineage-specific mQTLs displaying preferential hypomethylation in the respective lineages. Our study provides new insights into the mQTL landscape across genetic ancestries and their downstream effects on cellular processes and diseases/traits.
Asunto(s)
Metilación de ADN , Pueblos del Este de Asia , Sitios de Carácter Cuantitativo , Femenino , Humanos , Masculino , Pueblos del Este de Asia/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo/métodos , Herencia Multifactorial , Polimorfismo de Nucleótido SimpleRESUMEN
Ensuring the homeostatic integrity of pulmonary artery endothelial cells (PAECs) is essential for combatting pulmonary arterial hypertension (PAH), as it equips the cells to withstand microenvironmental challenges. Spermidine (SPD), a potent facilitator of autophagy, has been identified as a significant contributor to PAECs function and survival. Despite SPD's observed benefits, a comprehensive understanding of its protective mechanisms has remained elusive. Through an integrated approach combining metabolomics and molecular biology, this study uncovers the molecular pathways employed by SPD in mitigating PAH induced by monocrotaline (MCT) in a Sprague-Dawley rat model. The study demonstrates that SPD administration (5 mg/kg/day) significantly corrects right ventricular impairment and pathological changes in pulmonary tissues following MCT exposure (60 mg/kg). Metabolomic profiling identified a purine metabolism disorder in MCT-treated rats, which SPD effectively normalized, conferring a protective effect against PAH progression. Subsequent in vitro analysis showed that SPD (0.8 mM) reduces oxidative stress and apoptosis in PAECs challenged with Dehydromonocrotaline (MCTP, 50 µM), likely by downregulating purine nucleoside phosphorylase (PNP) and modulating polyamine biosynthesis through alterations in S-adenosylmethionine decarboxylase (AMD1) expression and the subsequent production of decarboxylated S-adenosylmethionine (dcSAM). These findings advocate SPD's dual inhibitory effect on PNP and AMD1 as a novel strategy to conserve cellular ATP and alleviate oxidative injuries, thus providing a foundation for SPD's potential therapeutic application in PAH treatment.
Asunto(s)
Células Endoteliales , Monocrotalina , Poliaminas , Hipertensión Arterial Pulmonar , Arteria Pulmonar , Purinas , Ratas Sprague-Dawley , Espermidina , Remodelación Vascular , Animales , Espermidina/farmacología , Espermidina/uso terapéutico , Purinas/farmacología , Poliaminas/metabolismo , Masculino , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Remodelación Vascular/efectos de los fármacos , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Ratas , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Hipertensión Arterial Pulmonar/inducido químicamente , Hipertensión Arterial Pulmonar/metabolismo , Células Cultivadas , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Purina-Nucleósido Fosforilasa/metabolismo , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/metabolismo , Adenosilmetionina Descarboxilasa/metabolismo , Modelos Animales de Enfermedad , HumanosRESUMEN
OBJECTIVE: Local vibration can cause microcirculatory abnormalities such as blood stasis and symmetrical intermittent digital artery vasospasm. Finger SBP (FSBP) measurement is a potential way of assessing vascular components. This study aims to comprehensively investigate the relationship between the occurrence of the vibration-induced white finger (VWF) and changes in FSBP and then set the application value of FSBP measurements in the early diagnosis of VWF. METHODS: All samples were judgmental sampling from one factory. Totally 50 patients with VWF were the case group, while 50 without occupational hand-transmitted vibration exposure were the control group. FSBP measurements and epidemiological feature investigations were taken. RESULTS: There were significant reductions in FSBP level and %FSBP index at both 10 °C and 30 °C in fingers reported VWF ( P â <â 0.05). The %FSBP abnormal rate of the index, ring and little finger in the VWF group was higher than the control (44.00% vs. 18.00%, 78.00% vs. 26.00%, 64.00% vs. 8.00%). The %FSBP of the ring and little finger had a relatively high application value (area under curveâ =â 0.902, 0.737), while their standard regression coefficients were -0.23 and -0.412. The diagnostic cutoff value of the ring finger was 77.60%, while the sensitivity and specificity were 86.67%. CONCLUSION: FSBP measurements were proven helpful in monitoring and diagnosing VWF prospectively and proved to have great application value in our study. %FSBP of the ring finger was the appropriate diagnostic index in FSBP measurements, while its abnormal value could be set as 80.00%.
Asunto(s)
Presión Sanguínea , Dedos , Vibración , Humanos , Dedos/irrigación sanguínea , Masculino , Femenino , Estudios Transversales , Adulto , China , Vibración/efectos adversos , Persona de Mediana Edad , MicrocirculaciónRESUMEN
Purpose: The underlying causes of pulmonary arterial hypertension (PAH) often remain obscure. Addressing PAH with effective treatments presents a formidable challenge. Studies have shown that Hydroxysafflor yellow A (HSYA) has a potential role in PAH, While the mechanism underlies its protective role is still unclear. The study was conducted to investigate the potential mechanisms of the protective effects of HSYA. Methods: Using databases such as PharmMapper and GeneCards, we identified active components of HSYA and associated PAH targets, pinpointed intersecting genes, and constructed a protein-protein interaction (PPI) network. Core targets were singled out using Cytoscape for the development of a model illustrating drug-component-target-disease interactions. Intersection targets underwent analysis for Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Selected components were then modeled for target interaction using Autodock and Pymol. In vivo validation in a monocrotaline-induced PAH (MCT-PAH) animal model was utilized to substantiate the predictions made by network pharmacology. Results: We associated HSYA with 113 targets, and PAH with 1737 targets, identifying 34 mutual targets for treatment by HSYA. HSYA predominantly affects 9 core targets. Molecular docking unveiled hydrogen bond interactions between HSYA and several PAH-related proteins such as ANXA5, EGFR, SRC, PPARG, PGR, and ESR1. Conclusion: Utilizing network pharmacology and molecular docking approaches, we investigated potential targets and relevant human disease pathways implicating HSYA in PAH therapy, such as the chemical carcinogenesis receptor activation pathway and the cancer pathway. Our findings were corroborated by the efficacious use of HSYA in an MCT-induced rat PAH model, confirming its therapeutic potential.
Asunto(s)
Chalcona , Chalcona/análogos & derivados , Medicamentos Herbarios Chinos , Hipertensión Arterial Pulmonar , Quinonas , Humanos , Animales , Ratas , Hipertensión Arterial Pulmonar/inducido químicamente , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Remodelación Vascular , Simulación del Acoplamiento Molecular , Chalcona/farmacologíaRESUMEN
Introduction: It was common for brands to use different numbers of endorsers in marketing practice. Nevertheless, research on brand endorsers' quantity has not yielded a uniform consensus. The previous research about brand endorsers mainly focuses on the appeal of endorsement, brand category, and endorser characteristics, paying less attention to the impact of cultural factors, particularly self-construal. This study delves into selecting brand endorsers across diverse cultural regions for the same brand. Methods: Drawing on the principles of self-consistency theory and self-construal theory, our research, conducted through three distinct experiments, reveals that consumers tend to hold more favorable opinions about brands endorsed by a single individual. Furthermore, self-consistency emerges as a crucial mediating factor in this phenomenon. Additionally, self-construal is an essential factor among consumers from various cultural backgrounds. Results: Consumers with an independent self-construal exhibit more favorable brand perceptions when it comes to single-endorser brands compared to their counterparts with an interdependent self-construal. Conversely, individuals with an interdependent self-construal demonstrate a more positive disposition towards brands with multiple endorsers than those with an independent self-construal. Discussion: This research not only enriches and extends our theoretical understanding of the impact of the number of brand endorsers on consumer brand attitudes but also provides valuable practical insights for optimizing the selection of brand endorsers for companies.
RESUMEN
Annotating genetic variants to their target genes is of great importance in unraveling the causal variants and genetic mechanisms that underlie complex diseases. However, disease-associated genetic variants are often located in non-coding regions and manifest context-specific effects, making it challenging to accurately identify the target genes and regulatory mechanisms. Here, we present TargetGene (https://ngdc.cncb.ac.cn/targetgene/), a comprehensive database reporting target genes for human genetic variants from various aspects. Specifically, we collected a comprehensive catalog of multi-omics data at the single-cell and bulk levels and from various human tissues, cell types and developmental stages. To facilitate the identification of Single Nucleotide Polymorphism (SNP)-to-gene connections, we have implemented multiple analytical tools based on chromatin co-accessibility, 3D interaction, enhancer activities and quantitative trait loci, among others. We applied the pipeline to evaluate variants from nearly 1300 Genome-wide association studies (GWAS) and assembled a comprehensive atlas of multiscale regulation of genetic variants. TargetGene is equipped with user-friendly web interfaces that enable intuitive searching, navigation and browsing through the results. Overall, TargetGene provides a unique resource to empower researchers to study the regulatory mechanisms of genetic variants in complex human traits.
Asunto(s)
Bases de Datos Genéticas , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Humanos , Cromatina/genética , Estudio de Asociación del Genoma Completo/métodos , Polimorfismo de Nucleótido SimpleRESUMEN
Leveraging genetics insights to promote drug repurposing has become a promising and active strategy in pharmacology. Indeed, among the 50 drugs approved by FDA in 2021, two-thirds have genetically supported evidence. In this regard, the increasing amount of widely available genome-wide association studies (GWAS) datasets have provided substantial opportunities for drug repurposing based on genetics discoveries. Here, we developed PharmGWAS, a comprehensive knowledgebase designed to identify candidate drugs through the integration of GWAS data. PharmGWAS focuses on novel connections between diseases and small-molecule compounds derived using a reverse relationship between the genetically-regulated expression signature and the drug-induced signature. Specifically, we collected and processed 1929 GWAS datasets across a diverse spectrum of diseases and 724 485 perturbation signatures pertaining to a substantial 33609 molecular compounds. To obtain reliable and robust predictions for the reverse connections, we implemented six distinct connectivity methods. In the current version, PharmGWAS deposits a total of 740 227 genetically-informed disease-drug pairs derived from drug-perturbation signatures, presenting a valuable and comprehensive catalog. Further equipped with its user-friendly web design, PharmGWAS is expected to greatly aid the discovery of novel drugs, the exploration of drug combination therapies and the identification of drug resistance or side effects. PharmGWAS is available at https://ngdc.cncb.ac.cn/pharmgwas.
Asunto(s)
Bases de Datos Farmacéuticas , Reposicionamiento de Medicamentos , Estudio de Asociación del Genoma Completo , Reposicionamiento de Medicamentos/métodos , Estudio de Asociación del Genoma Completo/métodosRESUMEN
Large-scale genome-wide association studies (GWAS) have provided profound insights into complex traits and diseases. Yet, deciphering the fine-scale molecular mechanisms of how genetic variants manifest to cause the phenotypes remains a daunting task. Here, we present COLOCdb (https://ngdc.cncb.ac.cn/colocdb), a comprehensive genetic colocalization database by integrating more than 3000 GWAS summary statistics and 13 types of xQTL to date. By employing two representative approaches for the colocalization analysis, COLOCdb deposits results from three key components: (i) GWAS-xQTL, pair-wise colocalization between GWAS loci and different types of xQTL, (ii) GWAS-GWAS, pair-wise colocalization between the trait-associated genetic loci from GWASs and (iii) xQTL-xQTL, pair-wise colocalization between the genetic loci associated with molecular phenotypes in xQTLs. These results together represent the most comprehensive colocalization analysis, which also greatly expands the list of shared variants with genetic pleiotropy. We expect that COLOCdb can serve as a unique and useful resource in advancing the discovery of new biological mechanisms and benefit future functional studies.
Asunto(s)
Estudio de Asociación del Genoma Completo , Herencia Multifactorial , Estudio de Asociación del Genoma Completo/métodos , Herencia Multifactorial/genética , Sitios de Carácter Cuantitativo , Fenotipo , Pleiotropía Genética , Polimorfismo de Nucleótido SimpleRESUMEN
Biocompatible self-healing hydrogels are new-generation smart soft materials that hold great promise in biomedical fields. Chitosan-based self-healing hydrogels, mainly prepared via dynamic imine bonds, have attracted broad attention due to their mild preparation conditions, excellent biocompatibility, and self-recovery ability under a physiological environment. In this review, we present a comprehensive overview of the design and fabrication of chitosan-based self-healing hydrogels, and summarize their biomedical applications in tissue regeneration, customized drug delivery, smart biosensors, and three/four dimensional (3D/4D) printing. Finally, we will discuss the challenges and future perspectives for the development of chitosan-based self-healing hydrogels in the biomedical field.
RESUMEN
PURPOSE: To investigate genetic loci associated with ocular axial length (AL) in the Chinese population. METHODS: A genome-wide association study meta-analysis was conducted in totalling 2644 Chinese individuals from 3 cohorts: the Guangzhou cohort (GZ, 537 high myopes and 151 hyperopes), Wenzhou cohort (334 high myopes and 6 hyperopes) and Guangzhou Twin Eye Study (1051 participants with normally distributed AL). Functional mapping was performed to annotate the significant signals, possible tissues and cell types by integrating available multiomics data. Logistic regression models using AL-associated SNPs were constructed to predict three AL status in GZ. RESULTS: Two novel loci (1q25.2 FAM163A and 7p22.2 SDK1) showed genome-wide significant associations with AL, together explaining 29.63% of AL variance in GZ. The two lead SNPs improved the prediction accuracy for AL status, especially for hyperopes. The frequencies of AL decreasing (less myopic) alleles of the two SNPs were lowest in East Asians as compared with other populations (rs17370084: f EAS=0.03, f EUR=0.24, f AFR=0.05; rs73046501: f EAS=0.06, f EUR=0.07, f AFR=0.20), which was in line with the global distribution of myopia. The cerebral cortex and gamma-aminobutyric acidergic interneurons showed possible functional involvement in myopia development, and the galactose metabolic pathways were significantly enriched. CONCLUSION: Our study identified two population-specific novel loci for AL, expanding our understanding of the genetic basis of AL and providing evidence for a role of the nervous system and glucose metabolism in myopia pathogenesis.
RESUMEN
Local vibration can induce vascular injuries, one example is the hand-arm vibration syndrome (HAVS) caused by hand-transmitted vibration (HTV). Little is known about the molecular mechanism of HAVS-induced vascular injuries. Herein, the iTRAQ (isobaric tags for relative and absolute quantitation) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics approach was applied to conduct the quantitative proteomic analysis of plasma from specimens with HTV exposure or HAVS diagnosis. Overall, 726 proteins were identified in iTRAQ. 37 proteins upregulated and 43 downregulated in HAVS. Moreover, 37 upregulated and 40 downregulated when comparing severe HAVS and mild HAVS. Among them, Vinculin (VCL) was found to be downregulated in the whole process of HAVS. The concentration of vinculin was further verified by ELISA, and the results suggested that the proteomics data was reliable. Bioinformative analyses were used, and those proteins mainly engaged in specific biological processes like binding, focal adhesion, and integrins. The potential of vinculin application in HAVS diagnosis was validated by the receiver operating characteristic curve.
Asunto(s)
Síndrome por Vibración de la Mano y el Brazo , Enfermedades Profesionales , Lesiones del Sistema Vascular , Humanos , Síndrome por Vibración de la Mano y el Brazo/diagnóstico , Síndrome por Vibración de la Mano y el Brazo/etiología , Enfermedades Profesionales/complicaciones , Enfermedades Profesionales/diagnóstico , Lesiones del Sistema Vascular/complicaciones , Vinculina , Cromatografía Liquida , Proteómica , Espectrometría de Masas en TándemRESUMEN
Efficient routes for the preparation of functional self-healing hydrogels from functional polymers are needed. In this study, we developed a strategy to effectively produce a vanillin-modified poly(vinyl alcohol) (PVA-vanillin) through the Hantzsch reaction. This polymer was cross-linked with a phenylboronic acid-containing polymer (PB) that was also prepared using the Hantzsch reaction to fabricate a hydrogel through borate ester linkages under mild conditions (25 °C, pH â¼ 7.4). This hydrogel had excellent antioxidant abilities due to the 1,4-dihydropyridine (DHP) rings and the vanillin moieties in the hydrogel structures; it was also self-healable and injectable owing to the dynamic borate ester linkages. Furthermore, the antioxidant self-healing hydrogel had low cytotoxicity and exhibited favorable safety in animal experiments, indicating its potential as a safe implantable cell or drug carrier. This study developed a method for preparing functional polymers and related self-healing hydrogels in a facile manner; it demonstrated the value of the Hantzsch reaction in exploiting antioxidant self-healing hydrogels for biomedical applications, which may provide insight into the design of other functional self-healing hydrogels through different multicomponent reactions.
Asunto(s)
Antioxidantes , Alcohol Polivinílico , Animales , Alcohol Polivinílico/química , Hidrogeles/química , Boratos , Polímeros/química , Ésteres/químicaRESUMEN
Background: The pathogenesis of coronary artery disease is complex, and inflammation is one of the regulatory factors. The nucleotide-binding oligomerization domain (NOD)-like receptor protein 1 (NLRP1) plays an important role in the cellular inflammatory response, cell apoptosis, cell death, and autoimmune diseases. Whether the level of NLRP1 is related to the severity of coronary artery stenosis in patients with coronary artery disease (CAD) has not been reported. Objective: To test the serum level of NLRP1 in unstable angina (UA) patients and investigate the effect of NLRP1 on coronary stenosis severity of the coronary artery disease (CAD). Methods: 307 patients hospitalized in the Department of Cardiology of the Affiliated Hospital of Xuzhou Medical University for coronary angiography from January 1, 2021, to December 31, 2022 were included. We detect the level of NLRP1 in the serum of the included patients. Patients were divided into UA group and control group according to coronary angiography results and other clinical data. We use logistic regression to screen the influencing factors of UA. Then, subgroups were divided according to the Gensini score and the number of coronary artery lesions, and the difference of serum NLRP1 level between the groups was compared. Spearman correlation analysis was used to explore the correlation between the serum NLRP1 level and Gensini score. We analyze the diagnostic value of NLRP1 for UA by drawing ROC curve. Results: The median level of serum NLRP1 in patients with UA (n = 257) was 49.71 pg/ml, IQR 30.15, 80.21, and that in patients without UA (n = 50) was 24.75 pg/ml, IQR 13.49, 41.95. Serum NLRP1 levels were significantly different among different subgroups. The patient's Gensini score was correlated with the patient's serum NLRP1 level. Conclusion: The serum NLRP1 level is increased in patients with UA, which is increased with the increasing severity of coronary lesions.
Asunto(s)
Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Humanos , Angina Inestable , Corazón , Angiografía Coronaria , Índice de Severidad de la Enfermedad , Proteínas NLRRESUMEN
Herein, we present a practical strategy for the direct construction of structurally diverse trifluoromethyl carbinol-containing compounds, especially CF3-substituted tertiary alcohol with chromone derivatives from easily available o-hydroxyaryl enaminones and trifluoroacetaldehyde/ketone derivatives under metal-free conditions. This reaction features a broad substrate scope with good yields and is easily scaled up. Notably, a one-pot in two-steps reaction of obtained products with amidines is also developed to provide a series of multi-substituted pyrimidine derivatives bearing two unique hydroxyls and one trifluoromethyl containing functional units.
RESUMEN
A broad range of complex phenotypes are related to dysfunctions in brain (hereafter referred to as brain-related traits), including various mental and behavioral disorders and diseases of the nervous system. These traits in general share overlapping symptoms, pathogenesis, and genetic components. Here, we present Brain Catalog (https://ngdc.cncb.ac.cn/braincatalog), a comprehensive database aiming to delineate the genetic components of more than 500 GWAS summary statistics datasets for brain-related traits from multiple aspects. First, Brain Catalog provides results of candidate causal variants, causal genes, and functional tissues and cell types for each trait identified by multiple methods using comprehensive annotation datasets (58 QTL datasets spanning 6 types of QTLs). Second, Brain Catalog estimates the SNP-based heritability, the partitioning heritability based on functional annotations, and genetic correlations among traits. Finally, through bidirectional Mendelian randomization analyses, Brain Catalog presents inference of risk factors that are likely causal to each trait. In conclusion, Brain Catalog presents a one-stop shop for the genetic components of brain-related traits, potentially serving as a valuable resource for worldwide researchers to advance the understanding of how GWAS signals may contribute to the biological etiology of brain-related traits.
Asunto(s)
Encéfalo , Bases de Datos Genéticas , Trastornos Mentales , Encéfalo/fisiopatología , Fenotipo , Sitios de Carácter Cuantitativo , Trastornos Mentales/genéticaRESUMEN
Standard genome-wide association studies (GWASs) rely on analyzing a single trait at a time. However, many human phenotypes are complex and composed by multiple correlated traits. Here we introduce C-GWAS, a method for combining GWAS summary statistics of multiple potentially correlated traits. Extensive computer simulations demonstrated increased statistical power of C-GWAS compared to the minimal p-values of multiple single-trait GWASs (MinGWAS) and the current state-of-the-art method for combining single-trait GWASs (MTAG). Applying C-GWAS to a meta-analysis dataset of 78 single trait facial GWASs from 10,115 Europeans identified 56 study-wide suggestively significant loci with multi-trait effects on facial morphology of which 17 are novel loci. Using data from additional 13,622 European and Asian samples, 46 (82%) loci, including 9 (53%) novel loci, were replicated at nominal significance with consistent allele effects. Functional analyses further strengthen the reliability of our C-GWAS findings. Our study introduces the C-GWAS method and makes it available as computationally efficient open-source R package for widespread future use. Our work also provides insights into the genetic architecture of human facial appearance.