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1.
Nature ; 604(7907): 647-652, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35478239

RESUMEN

Quantum phases can be classified by topological invariants, which take on discrete values capturing global information about the quantum state1-13. Over the past decades, these invariants have come to play a central role in describing matter, providing the foundation for understanding superfluids5, magnets6,7, the quantum Hall effect3,8, topological insulators9,10, Weyl semimetals11-13 and other phenomena. Here we report an unusual linking-number (knot theory) invariant associated with loops of electronic band crossings in a mirror-symmetric ferromagnet14-20. Using state-of-the-art spectroscopic methods, we directly observe three intertwined degeneracy loops in the material's three-torus, T3, bulk Brillouin zone. We find that each loop links each other loop twice. Through systematic spectroscopic investigation of this linked-loop quantum state, we explicitly draw its link diagram and conclude, in analogy with knot theory, that it exhibits the linking number (2, 2, 2), providing a direct determination of the invariant structure from the experimental data. We further predict and observe, on the surface of our samples, Seifert boundary states protected by the bulk linked loops, suggestive of a remarkable Seifert bulk-boundary correspondence. Our observation of a quantum loop link motivates the application of knot theory to the exploration of magnetic and superconducting quantum matter.

2.
Nature ; 583(7817): 533-536, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32699400

RESUMEN

The quantum-level interplay between geometry, topology and correlation is at the forefront of fundamental physics1-15. Kagome magnets are predicted to support intrinsic Chern quantum phases owing to their unusual lattice geometry and breaking of time-reversal symmetry14,15. However, quantum materials hosting ideal spin-orbit-coupled kagome lattices with strong out-of-plane magnetization are lacking16-21. Here, using scanning tunnelling microscopy, we identify a new topological kagome magnet, TbMn6Sn6, that is close to satisfying these criteria. We visualize its effectively defect-free, purely manganese-based ferromagnetic kagome lattice with atomic resolution. Remarkably, its electronic state shows distinct Landau quantization on application of a magnetic field, and the quantized Landau fan structure features spin-polarized Dirac dispersion with a large Chern gap. We further demonstrate the bulk-boundary correspondence between the Chern gap and the topological edge state, as well as the Berry curvature field correspondence of Chern gapped Dirac fermions. Our results point to the realization of a quantum-limit Chern phase in TbMn6Sn6, and may enable the observation of topological quantum phenomena in the RMn6Sn6 (where R is a rare earth element) family with a variety of magnetic structures. Our visualization of the magnetic bulk-boundary-Berry correspondence covering real space and momentum space demonstrates a proof-of-principle method for revealing topological magnets.

3.
Proc Natl Acad Sci U S A ; 120(1): e2215484119, 2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36574683

RESUMEN

We report the discovery of a dodecagonal quasicrystal Mn72.3Si15.6Cr9.7Al1.8Ni0.6-composed of a periodic stacking of atomic planes with quasiperiodic translational order and 12-fold symmetry along the two directions perpendicular to the planes-accidentally formed by an electrical discharge event in an eolian dune in the Sand Hills near Hyannis, Nebraska, United States. The quasicrystal, coexisting with a cubic crystalline phase with composition Mn68.9Si19.9Ni7.6Cr2.2Al1.4, was found in a fulgurite consisting predominantly of fused and melted sand along with traces of melted conductor metal from a nearby downed power line. The fulgurite may have been created by a lightning strike that combined sand with material from downed power line or from electrical discharges from the downed power line alone. Extreme temperatures of at least 1,710 °C were reached, as indicated by the presence of SiO2 glass in the sample. The dodecagonal quasicrystal is an example of a quasicrystal of any kind formed by electrical discharge, suggesting other places to search for quasicrystals on Earth or in space and for synthesizing them in the laboratory.

4.
J Biol Chem ; 300(3): 105765, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38367667

RESUMEN

CLEC12A, a member of the C-type lectin receptor family involved in immune homeostasis, recognizes MSU crystals released from dying cells. However, the molecular mechanism underlying the CLEC12A-mediated recognition of MSU crystals remains unclear. Herein, we reported the crystal structure of the human CLEC12A-C-type lectin-like domain (CTLD) and identified a unique "basic patch" site on CLEC12A-CTLD that is necessary for the binding of MSU crystals. Meanwhile, we determined the interaction strength between CLEC12A-CTLD and MSU crystals using single-molecule force spectroscopy. Furthermore, we found that CLEC12A clusters at the cell membrane and seems to serve as an internalizing receptor of MSU crystals. Altogether, these findings provide mechanistic insights for understanding the molecular mechanisms underlying the interplay between CLEC12A and MSU crystals.


Asunto(s)
Lectinas Tipo C , Receptores Mitogénicos , Ácido Úrico , Humanos , Gota/metabolismo , Lectinas Tipo C/química , Lectinas Tipo C/inmunología , Receptores Mitogénicos/química , Receptores Mitogénicos/inmunología , Ácido Úrico/química , Ácido Úrico/inmunología , Dominios Proteicos , Cristalografía por Rayos X , Imagen Individual de Molécula , Línea Celular
5.
Plant Cell ; 34(2): 889-909, 2022 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-34850198

RESUMEN

Phosphatidic acid (PA) is an important lipid essential for several aspects of plant development and biotic and abiotic stress responses. We previously suggested that submergence induces PA accumulation in Arabidopsis thaliana; however, the molecular mechanism underlying PA-mediated regulation of submergence-induced hypoxia signaling remains unknown. Here, we showed that in Arabidopsis, loss of the phospholipase D (PLD) proteins PLDα1 and PLDδ leads to hypersensitivity to hypoxia, but increased tolerance to submergence. This enhanced tolerance is likely due to improvement of PA-mediated membrane integrity. PA bound to the mitogen-activated protein kinase 3 (MPK3) and MPK6 in vitro and contributed to hypoxia-induced phosphorylation of MPK3 and MPK6 in vivo. Moreover, mpk3 and mpk6 mutants were more sensitive to hypoxia and submergence stress compared with wild type, and fully suppressed the submergence-tolerant phenotypes of pldα1 and pldδ mutants. MPK3 and MPK6 interacted with and phosphorylated RELATED TO AP2.12, a master transcription factor in the hypoxia signaling pathway, and modulated its activity. In addition, MPK3 and MPK6 formed a regulatory feedback loop with PLDα1 and/or PLDδ to regulate PLD stability and submergence-induced PA production. Thus, our findings demonstrate that PA modulates plant tolerance to submergence via both membrane integrity and MPK3/6-mediated hypoxia signaling in Arabidopsis.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiología , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Ácidos Fosfatidicos/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Hipoxia , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/genética , Mutación , Fenotipo , Fosfolipasa D/genética , Fosfolipasa D/metabolismo , Plantas Modificadas Genéticamente , Estabilidad Proteica , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
6.
Proc Natl Acad Sci U S A ; 119(51): e2204050119, 2022 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-36508665

RESUMEN

De novo proteins constructed from novel amino acid sequences are distinct from proteins that evolved in nature. Construct K (ConK) is a binary-patterned de novo designed protein that rescues Escherichia coli from otherwise toxic concentrations of copper. ConK was recently found to bind the cofactor PLP (pyridoxal phosphate, the active form of vitamin B6). Here, we show that ConK catalyzes the desulfurization of cysteine to H2S, which can be used to synthesize CdS nanocrystals in solution. The CdS nanocrystals are approximately 3 nm, as measured by transmission electron microscope, with optical properties similar to those seen in chemically synthesized quantum dots. The CdS nanocrystals synthesized using ConK have slower growth rates and a different growth mechanism than those synthesized using natural biomineralization pathways. The slower growth rate yields CdS nanocrystals with two desirable properties not observed during biomineralization using natural proteins. First, CdS nanocrystals are predominantly of the zinc blende crystal phase; this is in stark contrast to natural biomineralization routes that produce a mixture of zinc blende and wurtzite phase CdS. Second, in contrast to the growth and eventual precipitation observed in natural biomineralization systems, the CdS nanocrystals produced by ConK stabilize at a final size. Future optimization of CdS nanocrystal growth using ConK-or other de novo proteins-may help to overcome the limits on nanocrystal quality typically observed from natural biomineralization by enabling the synthesis of more stable, high-quality quantum dots at room temperature.


Asunto(s)
Puntos Cuánticos , Sulfuros , Sulfuros/química , Semiconductores , Proteínas , Zinc
7.
Proc Natl Acad Sci U S A ; 119(43): e2210617119, 2022 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-36252022

RESUMEN

Carbonate mud represents one of the most important geochemical archives for reconstructing ancient climatic, environmental, and evolutionary change from the rock record. Mud also represents a major sink in the global carbon cycle. Yet, there remains no consensus about how and where carbonate mud is formed. Here, we present stable isotope and trace-element data from carbonate constituents in the Bahamas, including ooids, corals, foraminifera, and algae. We use geochemical fingerprinting to demonstrate that carbonate mud cannot be sourced from the abrasion and mixture of any combination of these macroscopic grains. Instead, an inverse Bayesian mixing model requires the presence of an additional aragonite source. We posit that this source represents a direct seawater precipitate. We use geological and geochemical data to show that "whitings" are unlikely to be the dominant source of this precipitate and, instead, present a model for mud precipitation on the bank margins that can explain the geographical distribution, clumped-isotope thermometry, and stable isotope signature of carbonate mud. Next, we address the enigma of why mud and ooids are so abundant in the Bahamas, yet so rare in the rest of the world: Mediterranean outflow feeds the Bahamas with the most alkaline waters in the modern ocean (>99.7th-percentile). Such high alkalinity appears to be a prerequisite for the nonskeletal carbonate factory because, when Mediterranean outflow was reduced in the Miocene, Bahamian carbonate export ceased for 3-million-years. Finally, we show how shutting off and turning on the shallow carbonate factory can send ripples through the global climate system.


Asunto(s)
Carbonatos , Sedimentos Geológicos , Teorema de Bayes , Carbonato de Calcio , Carbonatos/análisis , Agua de Mar
8.
J Cell Physiol ; 239(5): e31237, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38468464

RESUMEN

GINS1 regulates DNA replication in the initiation and elongation phases and plays an important role in the progression of various malignant tumors. However, the role of GINS1 in hepatocellular carcinoma (HCC) remains largely unclear. In this study, we investigated the role and underlying mechanisms of GINS1 in contributing to HCC metastasis. We found that GINS1 was significantly upregulated in HCC tissues and cell lines, especially in HCC tissues with vascular invasion and HCC cell lines with highly metastatic properties. Additionally, high expression of GINS1 was positively correlated with the progressive clinical features of HCC patients, including tumor number (multiple), tumor size (>5 cm), advanced tumor stage, vascular invasion and early recurrence, suggesting that GINS1 upregulation was greatly involved in HCC metastasis. Moreover, Kaplan-Meier survival analysis revealed that high GINS1 expression predicted a poor prognosis. Both in vitro and in vivo, silencing of GINS1 inhibited proliferation, migration, invasion and metastasis, while overexpression of GINS1 induced opposite effects. Mechanistically, we found that ZEB1 was a crucial regulator of GINS1-induced epithelial-mesenchymal transition (EMT), and GINS1 promoted EMT and tumor metastasis through ß-catenin signaling. Overall, the present study demonstrated that GINS1 promoted ZEB1-mediated EMT and tumor metastasis via ß-catenin signaling in HCC.


Asunto(s)
Carcinoma Hepatocelular , Movimiento Celular , Proteínas Cromosómicas no Histona , Proteínas de Unión al ADN , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , Homeobox 1 de Unión a la E-Box con Dedos de Zinc , beta Catenina , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , beta Catenina/metabolismo , beta Catenina/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Metástasis de la Neoplasia , Transducción de Señal , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo
9.
Trends Genet ; 37(8): 699-710, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34016450

RESUMEN

Stochastic gains and losses of DNA methylation at CG dinucleotides are a frequent occurrence in plants. These spontaneous 'epimutations' occur at a rate that is 100 000 times higher than the genetic mutation rate, are effectively neutral at the genome-wide scale, and are stably inherited across mitotic and meiotic cell divisions. Mathematical models have been extraordinarily successful at describing how epimutations accumulate in plant genomes over time, making this process one of the most predictable epigenetic phenomena to date. Here, we propose that their high rate and effective neutrality make epimutations a powerful new molecular clock for timing evolutionary events of the recent past and for age dating of long-lived perennials such as trees.


Asunto(s)
Metilación de ADN/genética , Epigénesis Genética/genética , Genoma de Planta/genética , Selección Genética/genética , Modelos Teóricos , Tasa de Mutación , Plantas/genética
10.
Clin Immunol ; 263: 110219, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38631594

RESUMEN

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two common subtypes of autoimmune bullous disease (AIBD). The key role of circulating autoreactive immune cells contributing to skin damage of AIBD has been widely recognized. Nevertheless, the immune characteristics in cutaneous lesions remain unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell VDJ sequencing (scRNA-seq) to generate transcriptional profiles for cells and T/B cell clonetype in skin lesions of BP and PV. We found that the proportions of NK&T, macrophages/ dendritic cells, B cells, and mast cells increased in BP and PV lesions. Then, BP and PV cells constituted over 75% of all myeloid cell subtypes, CD4+ T cell subtypes and CD8+ T cell subtypes. Strikingly, CD8+ Trm was identified to be expanded in PV, and located in the intermediate state of the pseudotime trajectory from CD8+ Tm to CD8+ Tem. Interestingly, CD8+ Tem and CD4+ Treg highly expressed exhaustion-related genes, especially in BP lesions. Moreover, the enhanced cell communication between stromal cells and immune cells like B cells and macrophages/ dendritic cells was also identified in BP and PV lesions. Finally, clone expansion was observed in T cells of BP and PV compared with HC, while CD8+ Trm represented the highest ratio of hyperexpanded TCR clones among all T cell subtypes. Our study generally depicts a large and comprehensive single-cell landscape of cutaneous lesions and highlights immune cell features in BP and PV. This offers potential research targets for further investigation.


Asunto(s)
Penfigoide Ampolloso , Pénfigo , Análisis de la Célula Individual , Humanos , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/genética , Penfigoide Ampolloso/patología , Pénfigo/inmunología , Pénfigo/genética , Pénfigo/patología , Análisis de la Célula Individual/métodos , Piel/inmunología , Piel/patología , Linfocitos T CD8-positivos/inmunología , Femenino , Masculino , Análisis de Secuencia de ARN , Linfocitos T CD4-Positivos/inmunología , Macrófagos/inmunología , Linfocitos B/inmunología , Anciano , Células Dendríticas/inmunología , Persona de Mediana Edad
11.
J Exp Bot ; 75(5): 1314-1330, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38069660

RESUMEN

Sphingolipids are membrane lipids and play critical roles in signal transduction. Ceramides are central components of sphingolipid metabolism that are involved in cell death. However, the mechanism of ceramides regulating cell death in plants remains unclear. Here, we found that ceramides accumulated in mitochondria of accelerated cell death 5 mutant (acd5), and expression of mitochondrion-localized ceramide kinase (ACD5) suppressed mitochondrial ceramide accumulation and the acd5 cell death phenotype. Using immuno-electron microscopy, we observed hyperaccumulation of ceramides in acer acd5 double mutants, which are characterized by mutations in both ACER (alkaline ceramidase) and ACD5 genes. The results confirmed that plants with specific ceramide accumulation exhibited localization of ceramides to mitochondria, resulting in an increase in mitochondrial reactive oxygen species production. Interestingly, when compared with the wild type, autophagy-deficient mutants showed stronger resistance to ceramide-induced cell death. Lipid profiling analysis demonstrated that plants with ceramide accumulation exhibited a significant increase in phosphatidylethanolamine levels. Furthermore, exogenous ceramide treatment or endogenous ceramide accumulation induces autophagy. When exposed to exogenous ceramides, an increase in the level of the autophagy-specific ubiquitin-like protein, ATG8e, associated with mitochondria, where it directly bound to ceramides. Taken together, we propose that the accumulation of ceramides in mitochondria can induce cell death by regulating autophagy.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Ceramidas/metabolismo , Ceramidas/farmacología , Arabidopsis/metabolismo , Mitocondrias/metabolismo , Autofagia , Muerte Celular , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo
12.
J Sleep Res ; : e14166, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38414320

RESUMEN

Despite the high prevalence and significant health burden of obstructive sleep apnea (OSA), its underlying pathophysiology remains incompletely understood. This comprehensive review explores the emerging connection between vitamin D deficiency and OSA, discusses potential mechanisms underlying this association, and explores the therapeutic implications of these findings. Recent research has consistently highlighted the high incidence of vitamin D deficiency among patients with OSA, which often occurs independently of geographical location. This suggests that factors beyond lack of sunlight exposure may be involved. This review also discusses how reduced vitamin D may be associated with more severe manifestations of OSA. In addition, it explores the potentiality of using vitamin D supplements as a therapeutic strategy for OSA, noting that some studies have found improvements in sleep quality and a reduction in OSA severity. Potential mechanisms are proposed, including the role of vitamin D deficiency in promoting inflammation, oxidative stress, hypoxia, impairing immune function, muscle function, and gene polymorphism of vitamin D receptors, all of which could contribute to the pathogenesis of obstructive sleep apnea. The paper underscores the need for future research to validate these observations, to determine optimal vitamin D supplementation dosage and duration, to explore potential side effects and risks, and to investigate potential interactions with other treatments.

13.
Chem Rev ; 122(12): 10970-11021, 2022 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-35576674

RESUMEN

Rechargeable batteries have become indispensable implements in our daily life and are considered a promising technology to construct sustainable energy systems in the future. The liquid electrolyte is one of the most important parts of a battery and is extremely critical in stabilizing the electrode-electrolyte interfaces and constructing safe and long-life-span batteries. Tremendous efforts have been devoted to developing new electrolyte solvents, salts, additives, and recipes, where molecular dynamics (MD) simulations play an increasingly important role in exploring electrolyte structures, physicochemical properties such as ionic conductivity, and interfacial reaction mechanisms. This review affords an overview of applying MD simulations in the study of liquid electrolytes for rechargeable batteries. First, the fundamentals and recent theoretical progress in three-class MD simulations are summarized, including classical, ab initio, and machine-learning MD simulations (section 2). Next, the application of MD simulations to the exploration of liquid electrolytes, including probing bulk and interfacial structures (section 3), deriving macroscopic properties such as ionic conductivity and dielectric constant of electrolytes (section 4), and revealing the electrode-electrolyte interfacial reaction mechanisms (section 5), are sequentially presented. Finally, a general conclusion and an insightful perspective on current challenges and future directions in applying MD simulations to liquid electrolytes are provided. Machine-learning technologies are highlighted to figure out these challenging issues facing MD simulations and electrolyte research and promote the rational design of advanced electrolytes for next-generation rechargeable batteries.

14.
BMC Public Health ; 24(1): 57, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166928

RESUMEN

BACKGROUND: Gastric cancer has attracted widespread attention on social media due to its high incidence and severity. The Bilibili, TikTok, and YouTube video-sharing platforms have received considerable interest among general health consumers. Nevertheless, it remains unclear whether the information in videos on these platforms is of satisfactory content and quality. METHODS: A total of 300 eligible videos related to gastric cancer were screened from three video-sharing platforms, Bilibili, TikTok, and YouTube, for assessment and analysis. First, the basic information presented in the videos was recorded. Next, we identified the source and content type of each video. Then, the Global Quality Scale (GQS), Journal of the American Medical Association (JAMA), and Modified DISCERN were used to assess the educational content and quality of each video. A comparative analysis was undertaken of the videos procured from these three sources. RESULTS: We identified six categories of uploaders of the 300 videos: 159 videos (53%) were uploaded by health professionals, 21 videos (7%) by users in science communications, 29 videos (9.67%) by general users, 27 videos (9%) from news agencies, 63 videos (12%) by nonprofit organizations, and one video (0.33%) by a for-profit organization. In terms of the content types of the 300 videos, we identified five distinct categories. There were 48 videos (16%) on early signals, 12 videos (4%) on late symptoms, 40 videos (13.33%) on etiologies and causations, 160 videos (53.33%) on scientific introductions, and 40 videos (13.33%) on treatment methods. The overall quality of the videos was evaluated by the GQS, JAMA, and Modified DISCERN and was found to be medium, with scores of 2.6/5, 2.41/4, and 2.71/5 points, respectively. CONCLUSIONS: This innovative study demonstrates that videos on social media platforms can help the public learn about early signals, late symptoms, treatment methods, etiologies and causations, and scientific introductions of gastric cancer. However, both the content and quality of uploaded recordings are inadequate currently. More efforts should be made to enhance the content and quality of videos on gastric cancer and to increase public awareness.


Asunto(s)
Medios de Comunicación Sociales , Neoplasias Gástricas , Estados Unidos , Humanos , Neoplasias Gástricas/diagnóstico , Comunicación , Escolaridad , Personal de Salud , Reproducibilidad de los Resultados , Grabación en Video , Difusión de la Información
15.
BMC Public Health ; 24(1): 114, 2024 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-38191356

RESUMEN

BACKGROUND: This study aimed to explore the association between ideal cardiovascular health metrics (ICVHM) and arthritis (AR), as well as the interactions of various indicators in ICVHM on AR in US adults. METHODS: We involved 17,041 participants who were interviewed by NHANES from 2011 to 2018. AR included osteoarthritis or degenerative arthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis and other arthritis (Other AR). Logistic regression was applied to analyze the association between AR and ICVHM. Mixed graphical model (MGM) was used to explore the interaction between variables in ICVHM. RESULTS: Higher ICVHM scores had a protective effect on AR. Compared to "≤1" score, the ORs of AR in participants with 2, 3, 4, and ≥5 were 0.586, 0.472, 0.259, and 0.130, respectively. Similar results were also found in different types of AR. ICVHM has a maximum area under the curve value of 0.765 and the interaction between blood pressure and total cholesterol was 0.43. CONCLUSIONS: ICVHM correlates significantly with AR and is better at identifying AR than individual indicators. ICVHM can be better improved by controlling the indicators with stronger interactions. Our findings provide guidance for promoting health factors, which have important implications for identification and prevention of AR.


Asunto(s)
Artritis , Sistema Cardiovascular , Adulto , Humanos , Encuestas Nutricionales , Indicadores de Calidad de la Atención de Salud , Presión Sanguínea
16.
J Appl Toxicol ; 44(2): 175-183, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37605992

RESUMEN

Clozapine (CLZ) is the most prescribed medication for treating refractory schizophrenia but is associated with significant cardiovascular toxicity. This study aimed to investigate the cardiovascular toxicity induced by CLZ using zebrafish as a model animal. For this purpose, zebrafish developed to 80-h post-fertilization were exposed to different CLZ concentration solutions for 24 h followed by cardiac morphological observations in yolk sac edema, pericardial edema, and blood coagulation, in addition to increased SV-BA distance, functionally manifested as bradycardia, and decreased cardiac ejection fraction using the untreated embryos as control. At the same time, RNA sequencing was used to study the possible molecular mechanism of CLZ-induced cardiovascular toxicity. The results indicated that compared to the control group, the experimental groups possessed a total of 5888 differentially expressed genes (DEGs), where gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment of analysis indicated that DEGs were mainly enriched in the pathways related to ion channels. These findings may provide new insights and directions for the subsequent in-depth study of the molecular mechanism of CLZ-induced cardiovascular toxicity.


Asunto(s)
Clozapina , Pez Cebra , Animales , Clozapina/toxicidad , Clozapina/metabolismo , Transcriptoma , Análisis de Secuencia de ARN , Perfilación de la Expresión Génica , Edema
17.
Proc Natl Acad Sci U S A ; 118(14)2021 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-33782126

RESUMEN

microRNA-218 (miR-218) has been linked to several cognition related neurodegenerative and neuropsychiatric disorders. However, whether miR-218 plays a direct role in cognitive functions remains unknown. Here, using the miR-218 knockout (KO) mouse model and the sponge/overexpression approaches, we showed that miR-218-2 but not miR-218-1 could bidirectionally regulate the contextual and spatial memory in the mice. Furthermore, miR-218-2 deficiency induced deficits in the morphology and presynaptic neurotransmitter release in the hippocampus to impair the long term potentiation. Combining the RNA sequencing analysis and luciferase reporter assay, we identified complement component 3 (C3) as a main target gene of miR-218 in the hippocampus to regulate the presynaptic functions. Finally, we showed that restoring the C3 activity in the miR-218-2 KO mice could rescue the synaptic and learning deficits. Therefore, miR-218-2 played an important role in the cognitive functions of mice through C3, which can be a mechanism for the defective cognition of miR-218 related neuronal disorders.


Asunto(s)
Complemento C3/genética , Hipocampo/metabolismo , Potenciación a Largo Plazo , MicroARNs/metabolismo , Vesículas Sinápticas/metabolismo , Regiones no Traducidas 3' , Animales , Células Cultivadas , Complemento C3/metabolismo , Exocitosis , Hipocampo/citología , Hipocampo/fisiología , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Neuronas/metabolismo , Neuronas/fisiología
18.
Eur Arch Otorhinolaryngol ; 281(6): 3071-3082, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38584217

RESUMEN

PURPOSE: To establish two nomograms to quantify the risk of lung metastasis (LM) in laryngeal carcinoma (LC) and predict the overall survival of LC patients with LM. METHODS: Totally 9515 LC patients diagnosed histologically from 2000 to 2019 were collected from the Surveillance, Epidemiology, and End Results database. The independent diagnostic factors for LM in LC patients and prognostic factors for LC patients with LM were identified by logistic and Cox regression analysis, respectively. Nomograms were established based on regression coefficients and evaluated by receiver operating characteristic curve, calibration curves, and decision curve analysis. RESULTS: Patients with supraglottis, higher pathological grade, higher N stage, and distant metastasis (bone, brain, or liver) were more likely to have LM (P < 0.05). Chemotherapy, surgery and radiotherapy were independent factors of the overall survival of LC patients with LM (P < 0.05). The area under curve of diagnostic nomogram were 0.834 and 0.816 in the training and validation cohort respectively. For the prognostic nomogram, the area under curves of 1-, 2-, and 3-years were 0.735, 0.734, and 0.709 in the training cohort and 0.705, 0.803, and 0.809 in the validation cohort. The calibration curves and decision curve analysis indicated good performance of the nomograms. CONCLUSION: Distant metastasis (bone, brain, or liver) and N stage should be considered for prediction of LM in LC patients. Chemotherapy is the most significant influencing prognostic factor improving the survival of LC patients with LM. Two nomograms may benefit for providing better precautionary measures and treatment decision.


Asunto(s)
Neoplasias Laríngeas , Neoplasias Pulmonares , Nomogramas , Programa de VERF , Humanos , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/terapia , Neoplasias Laríngeas/mortalidad , Neoplasias Laríngeas/diagnóstico , Masculino , Femenino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/diagnóstico , Persona de Mediana Edad , Pronóstico , Anciano , Estadificación de Neoplasias , Curva ROC , Adulto , Tasa de Supervivencia
19.
J Craniofac Surg ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949256

RESUMEN

OBJECTIVE: To compare the clinical application effect and safety of polyetheretherketone (PEEK) and titanium mesh (TM) in cranioplasty. METHODS: Four-year retrospective comparison of patients (96 cases) undergoing synthetic cranioplasty with PEEK or TM. The patients were divided into the PEEK group (24 cases) and the TM group (72 cases) according to the implants, and the patient demographics, general conditions before the operation, postoperative complications, length of postoperative hospital stay, total costs, satisfaction with shaping and long-term complications were compared between the 2 groups. RESULTS: Patients in the PEEK group were younger than those in the TM group (P=0.019). Hospitalization costs were significantly higher in the PEEK group than in the TM group (P<0.001). The incidence of postoperative subcutaneous effusion was 33% in the PEEK group and 6.9% in the TM group, which suggests that patients in the PEEK group had a higher risk of postoperative subcutaneous effusion (P=0.001). There was no significant difference in the incidence of long-term complications and cosmetic satisfaction between the 2 groups at 4 years postoperatively. CONCLUSIONS: In this study, both titanium mesh and PEEK are reliable implants for cranioplasty. Titanium mesh is widely used in cranioplasty due to its cost-effective performance. PEEK has gradually gained recognition due to the characteristics of the material and surgical procedure, but the price needs to be further reduced, and attention should be paid to the occurrence and treatment of early postoperative subcutaneous effusion.

20.
Nano Lett ; 23(15): 6868-6874, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37477415

RESUMEN

Bulk Td-WTe2 is a semimetal, while its monolayer counterpart is a two-dimensional (2D) topological insulator. Recently, electronic transport resembling a Luttinger liquid state was found in twisted-bilayer WTe2 (tWTe2) with a twist angle of ∼5°. Despite the strong interest in 2D WTe2 systems, little experimental information is available about their intrinsic microstructure, leaving obstacles in modeling their physical properties. The monolayer, and consequently tWTe2, are highly air-sensitive, and therefore, probing their atomic structures is difficult. In this study, we develop a robust method for atomic-resolution visualization of monolayers and tWTe2 obtained through mechanical exfoliation and fabrication. We confirm the high crystalline quality of mechanically exfoliated WTe2 samples and observe that tWTe2 with twist angles of ∼5 and ∼2° retains its pristine moiré structure without substantial deformations or reconstructions. The results provide a structural foundation for future electronic modeling of monolayer and tWTe2 moiré lattices.

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