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Functional studies of long noncoding RNAs (lncRNAs) have been hindered by the lack of methods to assess their evolution. Here we present lncRNA Homology Explorer (lncHOME), a computational pipeline that identifies a unique class of long noncoding RNAs (lncRNAs) with conserved genomic locations and patterns of RNA-binding protein (RBP) binding sites (coPARSE-lncRNAs). Remarkably, several hundred human coPARSE-lncRNAs can be evolutionarily traced to zebrafish. Using CRISPR-Cas12a knockout and rescue assays, we found that knocking out many human coPARSE-lncRNAs led to cell proliferation defects, which were subsequently rescued by predicted zebrafish homologs. Knocking down coPARSE-lncRNAs in zebrafish embryos caused severe developmental delays that were rescued by human homologs. Furthermore, we verified that human, mouse and zebrafish coPARSE-lncRNA homologs tend to bind similar RBPs with their conserved functions relying on specific RBP-binding sites. Overall, our study demonstrates a comprehensive approach for studying the functional conservation of lncRNAs and implicates numerous lncRNAs in regulating vertebrate physiology.
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ARN Largo no Codificante , Humanos , Animales , Ratones , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Pez Cebra/genética , Genómica , GenomaRESUMEN
Enhancing electrocatalytic performance through structural and compositional engineering attracts considerable attention. However, most materials only function as pre-catalysts and convert into "real catalysts" during electrochemical reactions. Such transition involves dramatic structural and compositional changes and disrupts their designed properties. Herein, for the first time, a laser-ironing (LI) approach capable of in-situ forming a laser-ironing capping layer (LICL) on the Co-ZIF-L flakes is developed. During the oxygen evolution reaction (OER) process, the LICL sustains the leaf-like morphology and promotes the formation of OER-active Co3 O4 nanoclusters with the highest activity and stability. In contrast, the pristine and conventional heat-treated Co-ZIF-Ls both collapse and transform to less active CoOOH. The density functional theory (DFT) calculations pinpoint the importance of the high spin (HS) states of Co ions and the narrowed band gap in Co3 O4 nanoclusters. They enhance the OER activity by promoting spin-selected electron transport, effectively lowering the energy barrier and realizing a spontaneous O2 -releasing step that is the potential determining step (pds) in CoOOH. This study presents an innovative approach for modulating both structural and compositional evolutions of electrocatalysts during the reaction, sustaining stability with high performance during dynamic electrochemical reactions, and providing new pathways for facile and high-precision surface microstructure control.
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Lipid droplets (LDs) are a neutral lipid storage organelle that is conserved in almost all species. Excessive storage of neutral lipids in LDs is directly associated with many metabolic syndromes. Zebrafish is a better model animal for the study of LD biology due to its transparent embryonic stage compared to other organisms. However, the study of LDs in fish has been difficult due to the lack of specific LD marker proteins and the limitation of purification technology. In this paper, the purification and proteomic analysis of liver LDs of fish including zebrafish and Carassius auratus were performed for the first time. 259 and 267 proteins were identified respectively. Besides most of the identified proteins were reported in previous LD proteomes of mammals, indicating the similarity between mammal and fish LDs. We also identified many unique proteins of liver LDs in fish that are involved in the regulation of LD dynamics. Through morphological and biochemical analysis, we found that the marker protein Plin2 of zebrafish LD was located on LDs in Huh7 cells. These results will facilitate further study of LDs in fish and liver metabolic diseases using fish as a model animal.
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During vertebrate embryogenesis, hematopoietic stem and progenitor cell (HSPC) production through endothelial-to-hematopoietic transition requires suitable developmental signals, but how these signals are accurately regulated remains incompletely understood. Cytoplasmic polyadenylation, which is one of the posttranscriptional regulations, plays a crucial role in RNA metabolism. Here, we report that Cpeb1b-mediated cytoplasmic polyadenylation is important for HSPC specification by translational control of Hedgehog (Hh) signaling during zebrafish early development. Cpeb1b is highly expressed in notochord and its deficiency results in defective HSPC production. Mechanistically, Cpeb1b regulates hemogenic endothelium specification by the Hedgehog-Vegf-Notch axis. We demonstrate that the cytoplasmic polyadenylation element motif-dependent interaction between Cpeb1b and shha messenger RNA (mRNA) in the liquid-like condensates, which are induced by Pabpc1b phase separation, is required for cytoplasmic polyadenylation of shha mRNA. Intriguingly, the cytoplasmic polyadenylation regulates translation but not stability of shha mRNA, which further enhances the Shha protein level and Hh signal transduction. Taken together, our findings uncover the role of Cpeb1b-mediated cytoplasmic polyadenylation in HSPC development and provide insights into how posttranscriptional regulation can direct developmental signals with high fidelity to translate them into cell fate transition.
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Poliadenilación , Pez Cebra , Animales , Pez Cebra/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Hedgehog/metabolismo , Hematopoyesis/genéticaRESUMEN
An increasing amount of evidence emphasizes the role of metabolic reprogramming in immune cells to fight infections. However, little is known about the regulation of metabolite transporters that facilitate and support metabolic demands. In this study, we found that the expression of equilibrative nucleoside transporter 3 (ENT3, encoded by solute carrier family 29 member 3, Slc29a3) is part of the innate immune response, which is rapidly upregulated upon pathogen invasion. The transcription of Slc29a3 is directly regulated by type I interferon-induced signaling, demonstrating that this metabolite transporter is an interferon-stimulated gene (ISG). Suprisingly, we unveil that several viruses, including SARS-CoV-2, require ENT3 to facilitate their entry into the cytoplasm. The removal or suppression of Slc29a3 expression is sufficient to significantly decrease viral replication in vitro and in vivo. Our study reveals that ENT3 is a pro-viral ISG co-opted by some viruses to gain a survival advantage.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Interferones/metabolismo , Proteínas de Transporte de Membrana/genética , Inmunidad Innata , Genoma Viral , Proteínas de Transporte de Nucleósidos/genética , Proteínas de Transporte de Nucleósidos/metabolismoRESUMEN
BACKGROUND: Oculomotor nerve palsy (OMNP) is a known risk in surgical management of intracranial aneurysms. The aim of this study was to determine the risk factors for surgery-induced OMNP. METHODS: This retrospective study examined 585 patients with posterior communicating artery aneurysms treated surgically between January 2000 and July 2019. The patients were categorized into 2 groups according to whether they experienced OMNP. Multiple factors, including sex, age, history of subarachnoid hemorrhage, Hunt and Hess grade, Fisher grade, preoperative time, sizes, sides, number, orientation, intraoperative rupture, and morphology, were analyzed to identify factors associated with surgery-induced OMNP. RESULTS: The overall OMNP rate was 4.4%. In univariate analysis, large size (P < 0.001), posterior infratentorial projection (P = 0.003), number of subarachnoid hemorrhages (P = 0.005), and late preoperative time (P < 0.001) were associated with increased risk of OMNP. Overall, multivariate logistic regression analysis showed that size (10.1-25 mm: odds ratio [OR] 30.083, P = 0.001, 95% confidence interval [CI], 3.703-244.419; >25 mm: OR 62.179, P = 0.012, 95% CI, 2.402-1609.418), intraoperative rupture (OR 3.018, P = 0.035, 95% CI, 1.083-8.412), and preoperative time (>14 days: OR 10.985, P < 0.001, 95% CI, 3.840-31.428) were independent risk factors of surgery-induced OMNP. CONCLUSIONS: This study showed that size, intraoperative rupture, and preoperative time were independent predictors of surgery-induced OMNP. Use of advanced technologies during the operation can assist in avoiding this complication.
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Aneurisma Intracraneal , Enfermedades del Nervio Oculomotor , Hemorragia Subaracnoidea , Humanos , Estudios Retrospectivos , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/cirugía , Enfermedades del Nervio Oculomotor/epidemiología , Enfermedades del Nervio Oculomotor/etiología , Enfermedades del Nervio Oculomotor/cirugía , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/cirugía , Factores de Riesgo , Resultado del TratamientoRESUMEN
Vertebrate embryogenesis involves a conserved and fundamental process, called the maternal-to-zygotic transition (MZT), which marks the switch from a maternal factors-dominated state to a zygotic factors-driven state. Yet the precise mechanism underlying MZT remains largely unknown. Here we report that the RNA helicase Ddx3xb in zebrafish undergoes liquid-liquid phase separation (LLPS) via its N-terminal intrinsically disordered region (IDR), and an increase in ATP content promotes the condensation of Ddx3xb during MZT. Mutant form of Ddx3xb losing LLPS ability fails to rescue the developmental defect of Ddx3xb-deficient embryos. Interestingly, the IDR of either FUS or hnRNPA1 can functionally replace the N-terminal IDR in Ddx3xb. Phase separation of Ddx3xb facilitates the unwinding of 5' UTR structures of maternal mRNAs to enhance their translation. Our study reveals an unprecedent mechanism whereby the Ddx3xb phase separation regulates MZT by promoting maternal mRNA translation.
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Pez Cebra , Cigoto , Animales , ADN Helicasas , Desarrollo Embrionario/genética , Regulación del Desarrollo de la Expresión Génica , ARN Mensajero Almacenado/genética , Pez Cebra/genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Cigoto/metabolismoRESUMEN
Background: Previous studies, using autopsy and angiography, have shown that 3.6-6% of the population have intracranial aneurysms, and the rupture of aneurysm can lead to brain dysfunction or even death in patients. Methods: To explore potential preventional target genes for the ruptured of aneurysm, we analyze three gene expression datasets (GSE13353, GSE15629 and GSE54083) derived from the GEO database. We confirm DEGs associated with the unrupture of aneurysms by R package. DAVID version provides functional classification and annotation analyses of associated genes, including GO and KEGG pathway. PPI of these DEGs is analyzed based on the string database and visualized by Cytoscape software. DEGs are verified by qRT-PCR using samples isolated from the patients. Results: 249 overlapping DEGs, including 96 up-regulated genes and 153 down-regulated genes are screened using the Venn diagram webtool. The GO term and KEGG pathways analysis results indicate that these DEGs are mainly enriched in protein phosphorylation, apoptotic process and inflammatory response in the BP term and focal adhesion, thyroid hormone signaling pathway, ErbB signaling pathway, cytokine-cytokine receptor interaction and some disease processes in the KEGG pathways. 6 candidates are confirmed by Cytoscape software and qRT-PCR, including APP, JUN, GSK3B, ErbB2, PPBP and THBS1. Conclusions: Our data and previous studies show that ErbB2 and THBS1 are crucial to prevent aneurysm rupture, while APP, JUN, GSK3B and PPBP performs the opposite role, and further experiments are needed to verify these findings.
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OBJECTIVE: To explore the clinical application of lockedge suspension combined with three steel wires vertical fixation in comminuted fracture of inferior pole of patella. METHODS: From August 2016 to May 2019, 23 patients with comminuted fracture of the lower pole of the patella, including 14 males and 9 females, were treated with lockedge suspension combined with three steel wires vertical fixation. The age ranged from 34 to 68 (55.0±1.2) years. One year after operation, the pain and function were evaluated by pain visual analogue scale(VAS) and knee flexion and extension range of motion, and the clinical efficacy was evaluated by Lysholm knee score standard. RESULTS: All 23 patients were followed up for 12 to 14, with a mean of(13.0±0.5) months. One patient had skin irritation by the tail of the steel wire, and the rest had no postoperative complications such as incision infection, internal fixation loosening and fracture displacement. The fractures of 23 patients were healed, and the healing time was 10 to 14 weeks with a mean of(12.0±1.1) weeks. The VAS score decreased from 7.96±0.93 before operation to 0.83±0.65 one year after operation. The range of knee flexion and extension activities increased from(20.30±8.69) ° before operation to 1 year after operation(127.39±6.55) °. Lysholm knee score increased from 18.48±4.00 before operation to 96.09±4.91 one year after operation(P<0.05). CONCLUSION: The treatment of comminuted fracture of the lower pole of patella by lockedge suspension combined with three steel wires vertical fixation has reliable fixation and high fracture healing rate. It can meet the requirements of rapid rehabilitation and functional exercise, and the early clinical effect is satisfactory.
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Fracturas Óseas , Fracturas Conminutas , Adulto , Anciano , Hilos Ortopédicos , Femenino , Fijación Interna de Fracturas , Fracturas Óseas/cirugía , Fracturas Conminutas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Rótula/cirugía , Acero , Resultado del TratamientoRESUMEN
The microvascular decompression procedure (MVD) is widely utilized on patients with neurovascular compression syndromes, such as trigeminal neuralgia, hemifacial spasm and glossopharyngeal neuralgia, which have failed medical therapy. However, surgical complications are an ongoing problem. We retrospectively reviewed a total of 596 patients undergoing MVD in the Affiliated Hospital of Qingdao University from January 2008 to December 2018. Furthermore, we discussed the cases with life-threatening complications to determine the potential causes, aiming to achieve the goal of safer microvascular decompression. There were seven cases with life-threatening complications. Of those complications, one was cerebellar infarction with acute hydrocephalus, one was infarction of the cerebellum and the brain stem with acute hydrocephalus and serious intracranial infection, two were cerebellar haematoma, one was multiple haemorrhage with acute hydrocephalus, one was supratentorial subdural haematoma, and one was cerebellar swelling with acute hydrocephalus. After therapy, one patient died, one was in a persistent vegetative state, and five were discharged from the hospital upon recovery. In brief, MVD is a safe operation, and life-threatening complications accompanying MVD are rare, but require attention. The causes of some life-threatening complications are still not completely clear. Surgeons should continuously improve surgical techniques and perioperative care to reduce potential risks.
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Enfermedades del Nervio Glosofaríngeo/cirugía , Espasmo Hemifacial/cirugía , Cirugía para Descompresión Microvascular/efectos adversos , Complicaciones Posoperatorias/etiología , Neuralgia del Trigémino/cirugía , Adulto , Anciano , Femenino , Enfermedades del Nervio Glosofaríngeo/etiología , Espasmo Hemifacial/etiología , Humanos , Masculino , Cirugía para Descompresión Microvascular/métodos , Persona de Mediana Edad , Síndromes de Compresión Nerviosa/complicaciones , Síndromes de Compresión Nerviosa/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Neuralgia del Trigémino/etiologíaRESUMEN
Nascent hematopoietic stem and progenitor cells (HSPCs) acquire definitive hematopoietic characteristics only when they develop into fetal HSPCs; however, the mechanisms underlying fetal HSPC development are poorly understood. Here, we profiled the chromatin accessibility and transcriptional features of zebrafish nascent and fetal HSPCs using ATAC-seq and RNA-seq and revealed dynamic changes during HSPC transition. Functional assays demonstrated that chromatin remodeler-mediated epigenetic programming facilitates fetal HSPC development in vertebrates. Systematical screening of chromatin remodeler-related genes identified that smarca5 is responsible for the maintenance of chromatin accessibility at promoters of hematopoiesis-related genes in fetal HSPCs. Mechanistically, Smarca5 interacts with nucleolin to promote chromatin remodeling, thereby facilitating genomic binding of transcription factors to regulate expression of hematopoietic regulators such as bcl11ab. Our results unravel a new role of epigenetic regulation and reveal that Smarca5-mediated epigenetic programming is responsible for fetal HSPC development, which will provide new insights into the generation of functional HSPCs both in vivo and in vitro.
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Adenosina Trifosfatasas/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Epigénesis Genética/genética , Hematopoyesis/genética , Células Madre Hematopoyéticas/citología , Proteínas de Pez Cebra/metabolismo , Adenosina Trifosfatasas/genética , Animales , Proteínas Cromosómicas no Histona/genética , Ratones , Ratones Endogámicos C57BL , Pez Cebra , Proteínas de Pez Cebra/genéticaRESUMEN
BACKGROUND: Vertebrate early embryogenesis is initially directed by a set of maternal RNAs and proteins, yet the mechanisms controlling this program remain largely unknown. Recent transcriptome-wide studies on RNA structure have revealed its pervasive and crucial roles in RNA processing and functions, but whether and how RNA structure regulates the fate of the maternal transcriptome have yet to be determined. RESULTS: Here we establish the global map of four nucleotide-based mRNA structures by icSHAPE during zebrafish early embryogenesis. Strikingly, we observe that RNA structurally variable regions are enriched in the 3' UTR and contain cis-regulatory elements important for maternal-to-zygotic transition (MZT). We find that the RNA-binding protein Elavl1a stabilizes maternal mRNAs by binding to the cis-elements. Conversely, RNA structure formation suppresses Elavl1a's binding leading to the decay of its maternal targets. CONCLUSIONS: Our study finds that RNA structurally variable regions are enriched in mRNA 3' UTRs and contain cis-regulatory elements during zebrafish early embryogenesis. We reveal that Elavl1a regulates maternal RNA stability in an RNA structure-dependent fashion. Overall, our findings reveal a broad and fundamental role of RNA structure-based regulation in vertebrate early embryogenesis.
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Embrión no Mamífero/metabolismo , Procesamiento Postranscripcional del ARN , ARN/metabolismo , Transcriptoma , Pez Cebra/embriología , Regiones no Traducidas 3' , Animales , Proteínas ELAV/metabolismo , Estructura Molecular , ARN/química , Estabilidad del ARN , Pez Cebra/metabolismo , Proteínas de Pez Cebra/metabolismoRESUMEN
It is well known that various developmental signals play diverse roles in hematopoietic stem and progenitor cell (HSPC) production; however, how these signaling pathways are orchestrated remains incompletely understood. Here, we report that Rab5c is essential for HSPC specification by endocytic trafficking of Notch and AKT signaling in zebrafish embryos. Rab5c deficiency leads to defects in HSPC production. Mechanistically, Rab5c regulates hemogenic endothelium (HE) specification by endocytic trafficking of Notch ligands and receptor. We further show that the interaction between Rab5c and Appl1 in the endosome is required for the survival of HE in the ventral wall of the dorsal aorta through AKT signaling. Interestingly, Rab5c overactivation can also lead to defects in HSPC production, which is attributed to excessive endolysosomal trafficking inducing Notch signaling defect. Taken together, our findings establish a previously unrecognized role of Rab5c-mediated endocytic trafficking in HSPC development and provide new insights into how spatiotemporal signals are orchestrated to accurately execute cell fate transition.
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Células Madre Hematopoyéticas/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Notch/metabolismo , Proteínas de Unión al GTP rab5/metabolismo , Animales , Animales Modificados Genéticamente , Embrión no Mamífero , Endocitosis , Endotelio/fisiología , Regulación del Desarrollo de la Expresión Génica , Células HEK293 , Humanos , Receptores Notch/genética , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Factores de Transcripción/genética , Pez Cebra/embriología , Pez Cebra/genética , Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Proteínas de Unión al GTP rab5/química , Proteínas de Unión al GTP rab5/genéticaRESUMEN
BACKGROUND Rupture of intracranial aneurysms (IA) is associated with high rates of mortality around the world. Use of intestinal probiotics can regulate the pathophysiology of aneurysms, but the details of the mechanism involved have been unclear. MATERIAL AND METHODS The GEO2R analysis website was used to detect the DEGs between IAs, AAAs, samples after supplementation with probiotics, and normal samples. The online tool DAVID provides functional classification and annotation analyses of associated genes, including GO and KEGG pathway. PPI of these DEGs was analyzed based on the STRING database, followed by analysis using Cytoscape software. RESULTS We found 170 intersecting DEGs (contained in GSE75240 and more than 2 of the 4 aneurysms datasets), 5 intersecting DEGs (contained in all datasets) and 1 intersecting DEG (contained in GSE75240 and all IAs datasets). GO analysis results suggested that the DEGs primarily participate in signal transduction, cell adhesion, immune response, response to drug, extracellular matrix organization, cell-cell signaling, and inflammatory response in the BP terms, and the KEGG pathways are mainly enriched in focal adhesion, cytokine-cytokine receptor interaction, ECM-receptor interaction, amoebiasis, chemokine signaling pathway, proteoglycans, and PI3K-Akt signaling pathway in cancer pathways. Through PPI network analysis, we confirmed 2 candidates for further study: CAV1 and MYH11. These downregulated DEGs are associated with the formation of aneurysms, and the change of these DEGs is the opposite in probiotics-treated animals. CONCLUSIONS Our study suggests that MYH11 and CAV1 are potential target genes for prevention of aneurysms. Further experiments are needed to verify these findings.
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Biología Computacional , Aneurisma Intracraneal/genética , Probióticos , Caveolina 1/genética , Regulación hacia Abajo , Regulación de la Expresión Génica , Ontología de Genes , Humanos , Cadenas Pesadas de Miosina/genética , Programas InformáticosRESUMEN
The maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment is converted to an environment of embryonic-driven development through dramatic reprogramming. However, how maternally supplied transcripts are dynamically regulated during MZT remains largely unknown. Herein, through genome-wide profiling of RNA 5-methylcytosine (m5C) modification in zebrafish early embryos, we found that m5C-modified maternal mRNAs display higher stability than non-m5C-modified mRNAs during MZT. We discovered that Y-box binding protein 1 (Ybx1) preferentially recognizes m5C-modified mRNAs through π-π interactions with a key residue, Trp45, in Ybx1's cold shock domain (CSD), which plays essential roles in maternal mRNA stability and early embryogenesis of zebrafish. Together with the mRNA stabilizer Pabpc1a, Ybx1 promotes the stability of its target mRNAs in an m5C-dependent manner. Our study demonstrates an unexpected mechanism of RNA m5C-regulated maternal mRNA stabilization during zebrafish MZT, highlighting the critical role of m5C mRNA modification in early development.
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5-Metilcitosina/metabolismo , Embrión no Mamífero/embriología , Desarrollo Embrionario/fisiología , Estabilidad del ARN/fisiología , ARN Mensajero Almacenado/metabolismo , Pez Cebra/embriología , Animales , Células HeLa , Humanos , Ratones , ARN Mensajero Almacenado/genética , Pez Cebra/genéticaRESUMEN
There are some controversies about the surgical treatment strategy of mirror aneurysms. Whether to choose 1-stage or 2-stage surgery, bilateral or unilateral craniotomy, or surgical or interventional treatment are the main points in dispute. In this review, the different surgery strategies faced by patients are discussed. Different surgical methods are adopted based on the patient's individual state and the location and size of the aneurysm. A new imaging method is introduced using 3D Slicer, which clearly recognizes the relationship among aneurysm, brain tissue, skull, and nerve. The 3D Slicer can help surgeons undertake adequate preoperative preparation. In addition, we also introduce some ruptured factors (e.g., age, gender, hypertension, morphologic, and hemodynamic) concerning mirror aneurysm. Systematic discussion of the controversies and methods in surgical treatment of mirror aneurysms may provide new perspectives in future research for the prevention and treatment of mirror aneurysms.
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Aneurisma Roto/epidemiología , Aneurisma Roto/cirugía , Manejo de la Enfermedad , Aneurisma Intracraneal/epidemiología , Aneurisma Intracraneal/cirugía , Aneurisma Roto/diagnóstico por imagen , Humanos , Imagenología Tridimensional/métodos , Aneurisma Intracraneal/diagnóstico por imagen , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Several reports have suggested a possible association between the interleukin (IL)-8-251A/T single-nucleotide polymorphism (SNP) and the susceptibility to coronary artery disease (CAD). Due to inconclusive results of the studies so far, we conducted a meta-analysis to systematically summarize the studies on the association between this SNP and CAD risk. A systematic literature search identified 9 case-control studies (3752 cases and 4219 controls) on the IL-8-251A/T polymorphism. We observed a significant association between different genetic forms of -251A/T SNP and CAD risk, like the allele model (A vs T: odds ratio [OR] 1.14, 95% confidence interval [CI] 1.02-1.27, Pâ=â.02), dominant model (AA + AT vs TT: OR 1.20, 95% CI 1.01-1.43, Pâ=â.042), recessive model (AA vs AT + TT: OR 1.15, 95% CI 1.03-1.27, Pâ=â.01), and homozygous model (AA vs TT: OR 1.26, 95% CI 1.01-1.56, Pâ=â.037), whereas the heterozygote model did not show any significant association (AT vs TT: OR 1.16, 95% CI 0.98-1.38, Pâ=â.091). Furthermore, significant heterogeneity was observed among studies in terms of all genetic models, except the recessive model. Analysis of the ethnic subgroups revealed a significantly higher risk of CAD in the East Asian population carrying this SNP, and the heterogeneity among the studies regarding the East Asian population was decreased after subgroup analysis. The results of this meta-analysis suggest that the IL-8-251A/T SNP may increase the risk of CAD, especially in people of East Asian ethnicity. Further large-scale, multicenter epidemiological studies are warranted to validate this finding.
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Enfermedad de la Arteria Coronaria/genética , Interleucina-8/genética , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/etnología , Etnicidad , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
The existence of Wigner crystallization, one of the most significant hallmarks of strong electron correlations, has to date only been definitively observed in two-dimensional systems. In one-dimensional (1D) quantum wires Wigner crystals correspond to regularly spaced electrons; however, weakening the confinement and allowing the electrons to relax in a second dimension is predicted to lead to the formation of a new ground state constituting a zigzag chain with nontrivial spin phases and properties. Here we report the observation of such zigzag Wigner crystals by use of on-chip charge and spin detectors employing electron focusing to image the charge density distribution and probe their spin properties. This experiment demonstrates both the structural and spin phase diagrams of the 1D Wigner crystallization. The existence of zigzag spin chains and phases which can be electrically controlled in semiconductor systems may open avenues for experimental studies of Wigner crystals and their technological applications in spintronics and quantum information.
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OBJECTIVE: To determine the correlation between serum uric acid (SUA) and insulin secretion function in patients with pre-diabetes and type-2 diabetes mellitus (T2DM). METHODS: A total of 4 112 adult people participated in this study. They were divided into three groups according to the results of oral glucose tolerance test (OGTT): 493 with normal glucose regulation (NGR),1 251 with impaired glucose regulation (IGR),and 2 368 with T2DM. Their levels of SUA,fasting insulin (FIns),2 h post-meal insulin (2 h-Ins),and insulin resistance index (HOMA-IR) were determined. Correlations between SUA and insulin secretion and HOMA-IR were estimated. RESULTS: IGR patients had higher levels of SUA and 2 h-Ins compared with those with NGR and T2DM ( P<0.000 1). T2DM patients had higher levels of FIns,glucosylated hemoglobin (HbA1c) and HOMA-IR compared with those with NGR and IGR ( P<0.000 1). In both male and female participants,the highest level of 2 h-Ins appeared in those with IGR,while T2DM had the highest level of HOMA-IA and HbA1c. FIns,2 h-Ins and HOMA-IR increased with SUA in both patients with IGR and T2DM. HbA1c decreased with SUA in T2DM patients. CONCLUSION: High serum SUA is correlated with islet ß-cell dysfunction. It may become an indicator of progression from pre-diabetes to T2DM.