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1.
Proc Natl Acad Sci U S A ; 120(20): e2217096120, 2023 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-37155902

RESUMEN

Diverse extracellular proteins negatively regulate WNT signaling. One such regulator is adenomatosis polyposis coli down-regulated 1 (APCDD1), a conserved single-span transmembrane protein. In response to WNT signaling in a variety of tissues, APCDD1 transcripts are highly up-regulated. We have determined the three-dimensional structure of the extracellular domain of APCDD1, and this structure reveals an unusual architecture consisting of two closely apposed ß-barrel domains (ABD1 and ABD2). ABD2, but not ABD1, has a large hydrophobic pocket that accommodates a bound lipid. The APCDD1 ECD can also bind to WNT7A, presumably via its covalently bound palmitoleate, a modification that is common to all WNTs and is essential for signaling. This work suggests that APCDD1 functions as a negative feedback regulator by titrating WNT ligands at the surface of responding cells.


Asunto(s)
Poliposis Adenomatosa del Colon , Proteínas de la Membrana , Humanos , Proteínas de la Membrana/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Vía de Señalización Wnt , Lípidos , beta Catenina/genética , beta Catenina/metabolismo
2.
Proc Natl Acad Sci U S A ; 120(14): e2221103120, 2023 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-36996108

RESUMEN

In many organs, small openings across capillary endothelial cells (ECs) allow the diffusion of low-molecular weight compounds and small proteins between the blood and tissue spaces. These openings contain a diaphragm composed of radially arranged fibers, and current evidence suggests that a single-span type II transmembrane protein, plasmalemma vesicle-associated protein-1 (PLVAP), constitutes these fibers. Here, we present the three-dimensional crystal structure of an 89-amino acid segment of the PLVAP extracellular domain (ECD) and show that it adopts a parallel dimeric alpha-helical coiled-coil configuration with five interchain disulfide bonds. The structure was solved using single-wavelength anomalous diffraction from sulfur-containing residues (sulfur SAD) to generate phase information. Biochemical and circular dichroism (CD) experiments show that a second PLVAP ECD segment also has a parallel dimeric alpha-helical configuration-presumably a coiled coil-held together with interchain disulfide bonds. Overall, ~2/3 of the ~390 amino acids within the PLVAP ECD adopt a helical configuration, as determined by CD. We also determined the sequence and epitope of MECA-32, an anti-PLVAP antibody. Taken together, these data lend strong support to the model of capillary diaphragms formulated by Tse and Stan in which approximately ten PLVAP dimers are arranged within each 60- to 80-nm-diameter opening like the spokes of a bicycle wheel. Passage of molecules through the wedge-shaped pores is presumably determined both by the length of PLVAP-i.e., the long dimension of the pore-and by the chemical properties of amino acid side chains and N-linked glycans on the solvent-accessible faces of PLVAP.


Asunto(s)
Diafragma , Células Endoteliales , Diafragma/metabolismo , Células Endoteliales/metabolismo , Proteínas Portadoras/metabolismo , Endotelio Vascular/metabolismo , Disulfuros/metabolismo , Dicroismo Circular
3.
J Biol Chem ; 300(5): 107283, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38608728

RESUMEN

Over the past 3 decades, a diverse collection of small protein domains have been used as scaffolds to generate general purpose protein-binding reagents using a variety of protein display and enrichment technologies. To expand the repertoire of scaffolds and protein surfaces that might serve this purpose, we have explored the utility of (i) a pair of anti-parallel alpha-helices in a small highly disulfide-bonded 4-helix bundle, the CC4 domain from reversion-inducing Cysteine-rich Protein with Kazal Motifs and (ii) a concave beta-sheet surface and two adjacent loops in the human FN3 domain, the scaffold for the widely used monobody platform. Using M13 phage display and next generation sequencing, we observe that, in both systems, libraries of ∼30 million variants contain binding proteins with affinities in the low µM range for baits corresponding to the extracellular domains of multiple mammalian proteins. CC4- and FN3-based binding proteins were fused to the N- and/or C-termini of Fc domains and used for immunostaining of transfected cells. Additionally, FN3-based binding proteins were inserted into VP1 of AAV to direct AAV infection to cells expressing a defined surface receptor. Finally, FN3-based binding proteins were inserted into the Pvc13 tail fiber protein of an extracellular contractile injection system particle to direct protein cargo delivery to cells expressing a defined surface receptor. These experiments support the utility of CC4 helices B and C and of FN3 beta-strands C, D, and F together with adjacent loops CD and FG as surfaces for engineering general purpose protein-binding reagents.


Asunto(s)
Biblioteca de Péptidos , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Animales , Humanos , Bacteriófago M13 , Técnicas de Visualización de Superficie Celular , Células HEK293 , Unión Proteica
4.
Hum Genomics ; 18(1): 74, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956740

RESUMEN

BACKGROUND: Evidence has revealed a connection between cuproptosis and the inhibition of tumor angiogenesis. While the efficacy of a model based on cuproptosis-related genes (CRGs) in predicting the prognosis of peripheral organ tumors has been demonstrated, the impact of CRGs on the prognosis and the immunological landscape of gliomas remains unexplored. METHODS: We screened CRGs to construct a novel scoring tool and developed a prognostic model for gliomas within the various cohorts. Afterward, a comprehensive exploration of the relationship between the CRG risk signature and the immunological landscape of gliomas was undertaken from multiple perspectives. RESULTS: Five genes (NLRP3, ATP7B, SLC31A1, FDX1, and GCSH) were identified to build a CRG scoring system. The nomogram, based on CRG risk and other signatures, demonstrated a superior predictive performance (AUC of 0.89, 0.92, and 0.93 at 1, 2, and 3 years, respectively) in the training cohort. Furthermore, the CRG score was closely associated with various aspects of the immune landscape in gliomas, including immune cell infiltration, tumor mutations, tumor immune dysfunction and exclusion, immune checkpoints, cytotoxic T lymphocyte and immune exhaustion-related markers, as well as cancer signaling pathway biomarkers and cytokines. CONCLUSION: The CRG risk signature may serve as a robust biomarker for predicting the prognosis and the potential viability of immunotherapy responses. Moreover, the key candidate CRGs might be promising targets to explore the underlying biological background and novel therapeutic interventions in gliomas.


Asunto(s)
Biomarcadores de Tumor , Glioma , Microambiente Tumoral , Humanos , Glioma/genética , Glioma/inmunología , Glioma/patología , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Pronóstico , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica/genética , Nomogramas , Femenino , Masculino , Perfilación de la Expresión Génica , Persona de Mediana Edad
5.
Int J Med Sci ; 21(8): 1438-1446, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903927

RESUMEN

Background: Exploring potential biomarkers for predicting clinical outcomes and developing targeted therapies for acute myeloid leukemia (AML) is of utmost importance. This study aimed to investigate the expression pattern of the thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) pathway and its role in the prognosis of AML patients. Methods: In this study, we examined the prognostic value of TXNIP/NLRP3 pathway in AML patients using microarray data from Gene Expression Omnibus (GEO) and transcriptome data from the Cancer Genome Atlas (TCGA) to develop a prognostic model and validated the results by quantitative real-time PCR (qRT-PCR) in a validation cohort of 26 AML patients and 18 healthy individuals from Jinan University (JNU) database. Results: Analysis of the GSE13159 database revealed that TXNIP, interleukin 1 beta (IL1B) within the TXNIP/NLRP3 pathway were significantly upregulated and caspase1 (CASP1) was downregulated in AML patients (TXNIP, P = 0.031; IL1B, P = 0.042; CASP1, P = 0.038). Compared to high NLRP3 expression, AML patients with low NLRP3 expression had a longer overall survival (OS) in the GSE12417 dataset (P = 0.004). Moreover, both the training and validation results indicated that lower TXNIP, NLRP3, and IL1B expression were associated with favorable prognosis (GSE12417, P = 0.009; TCGA, P = 0.050; JNU, P = 0.026). According to the receiver operating characteristic curve analysis, this model demonstrated a sensitivity of 84% for predicting three-year survival. These data might provide novel predictors for AML outcome and direction for further investigation of the possibility of using TXNIP/NLRP3/IL1B genes in novel targeted therapies for AML.


Asunto(s)
Biomarcadores de Tumor , Proteínas Portadoras , Inflamasomas , Interleucina-1beta , Leucemia Mieloide Aguda , Proteína con Dominio Pirina 3 de la Familia NLR , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Femenino , Masculino , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Persona de Mediana Edad , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Inflamasomas/metabolismo , Inflamasomas/genética , Transducción de Señal/genética , Adulto , Anciano , Regulación Leucémica de la Expresión Génica , Tiorredoxinas/genética , Tiorredoxinas/metabolismo
6.
Proc Natl Acad Sci U S A ; 117(26): 15104-15111, 2020 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-32541044

RESUMEN

Five small protein domains, the CC-domains, at the N terminus of the RECK protein, play essential roles in signaling by WNT7A and WNT7B in the context of central nervous system angiogenesis and blood-brain barrier formation and maintenance. We have determined the structure of CC domain 4 (CC4) at 1.65-Å resolution and find that it folds into a compact four-helix bundle with three disulfide bonds. The CC4 structure, together with homology modeling of CC1, reveals the surface locations of critical residues that were shown in previous mutagenesis studies to mediate GPR124 binding and WNT7A/WNT7B recognition and signaling. Surprisingly, sequence and structural homology searches reveal no other cell-surface or secreted domains in vertebrates that resemble the CC domain, a pattern that is in striking contrast to other ancient and similarly sized domains, such as Epidermal Growth Factor, Fibronectin Type 3, Immunoglobulin, and Thrombospondin type 1 domains, which are collectively present in hundreds of proteins.


Asunto(s)
Evolución Molecular , Proteínas Ligadas a GPI/química , Proteínas Ligadas a GPI/metabolismo , Secuencia de Aminoácidos , Animales , Caenorhabditis elegans , Proteínas Ligadas a GPI/genética , Humanos , Ratones , Dominios Proteicos , Alineación de Secuencia
7.
Int J Mol Sci ; 24(7)2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-37047249

RESUMEN

A high oleic acid content is considered an essential characteristic in the breeding of high-quality rapeseed in China. Long-chain non-coding RNA (lncRNA) molecules play an important role in the plant's growth and its response to stress. To better understand the role of lncRNAs in regulating plant reproductive development, we analyzed whole-transcriptome and physiological data to characterize the dynamic changes in lncRNA expression during the four representative times of seed development of high- and low-oleic-acid rapeseed in three regions. We identified 21 and 14 lncRNA and mRNA modules, respectively. These modules were divided into three types related to region, development stages, and material. Next, we analyzed the key modules related to the oil content and the oleic acid, linoleic acid, and linolenic acid contents with physiological data and constructed the key functional network analysis on this basis. Genes related to lipid metabolism, such as 3-ketoacyl-CoA synthase 16 (KCS16) and acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), were present in the co-expression network, suggesting that the effect of these genes on lipid metabolism might be embodied by the expression of these lncRNAs. Our results provide a fresh insight into region-, development-stage-, and material-biased changes in lncRNA expression in the seeds of Brassica napus. Some of these lncRNAs may participate in the regulatory network of lipid accumulation and metabolism, together with regulated genes. These results may help elucidate the regulatory system of lncRNAs in the lipid metabolism of high-oleic-acid rapeseed seeds.


Asunto(s)
Brassica napus , Brassica rapa , ARN Largo no Codificante , Brassica napus/genética , Brassica napus/metabolismo , Ácido Oléico/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Aceites de Plantas/metabolismo , Metabolismo de los Lípidos/genética , Fitomejoramiento , Brassica rapa/genética , Brassica rapa/metabolismo , Semillas/metabolismo
8.
Int J Mol Sci ; 24(7)2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-37047446

RESUMEN

The color of rapeseed (Brassica napus L.) petal is usually yellow but can be milky-white to orange or pink. Thus, the petal color is a popular target in rapeseed breeding programs. In his study, metabolites and RNA were extracted from the yellow (Y), yellow/purple (YP), light purple (LP), and purple (P) rapeseed petals. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), RNA-Seq, and quantitative real-time (qRT-PCR) analyses were performed to analyze the expression correlation of differential metabolites and differential genes. A total of 223 metabolites were identified in the petals of the three purple and yellow rapeseed varieties by UPLC-MS/MS. A total of 20511 differentially expressed genes (DEGs) between P, LP, YP, versus Y plant petals were detected. This study focused on the co-regulation of 4898 differential genes in the three comparison groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation and quantitative RT-PCR analysis showed that the expression of BnaA10g23330D (BnF3'H) affects the synthesis of downstream peonidin and delphinidin and is a key gene regulating the purple color of petals in B. napus. L. The gene may play a key role in regulating rapeseed flower color; however, further studies are needed to verify this. These results deepen our understanding of the molecular mechanisms underlying petal color and provide the theoretical and practical basis for flower breeding targeting petal color.


Asunto(s)
Brassica napus , Brassica napus/metabolismo , Cromatografía Liquida , Espectrometría de Masas en Tándem , Fitomejoramiento , Flores/metabolismo , Regulación de la Expresión Génica de las Plantas , Color
9.
Entropy (Basel) ; 25(9)2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37761602

RESUMEN

Recently, many password guessing algorithms have been proposed, seriously threatening cyber security. In this paper, we systematically review over thirty methods for password guessing published between 2016 and 2023. First, we introduce a taxonomy for classifying the existing methods into trawling guessing and targeted guessing. Second, we present an extensive benchmark dataset that can assist researchers and practitioners in successive works. Third, we conduct a bibliometric analysis to present trends in this field and cross-citation between reviewed papers. Further, we discuss the open challenges of password guessing in terms of diverse application scenarios, guessing efficiency, and the combination of traditional and deep learning methods. Finally, this review presents future research directions to guide successive research and development of password guessing.

10.
Molecules ; 27(15)2022 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-35897889

RESUMEN

Plant-parasitic nematodes infect a diversity of crops, resulting in severe economic losses in agriculture. Microbial volatile organic compounds (VOCs) are potential agents to control plant-parasitic nematodes and other pests. In this study, VOCs emitted by a dozen bacterial strains were analyzed using solid-phase microextraction followed by gas chromatography-mass spectrometry. Fumigant toxicity of selected VOCs, including dimethyl disulfide (DMDS), 2-butanone, 2-pentanone, 2-nonanone, 2-undecanone, anisole, 2,5-dimethylfuran, glyoxylic acid, and S-methyl thioacetate (MTA) was then tested against Caenorhabditis elegans. DMDS and MTA exhibited much stronger fumigant toxicity than the others. Probit analysis suggested that the values of LC50 were 8.57 and 1.43 µg/cm3 air for DMDS and MTA, respectively. MTA also showed stronger fumigant toxicity than DMDS against the root-knot nematode Meloidogyne incognita, suggesting the application potential of MTA.


Asunto(s)
Plaguicidas , Tylenchoidea , Compuestos Orgánicos Volátiles , Animales , Bacterias , Caenorhabditis elegans , Productos Agrícolas , Compuestos Orgánicos Volátiles/química , Compuestos Orgánicos Volátiles/farmacología
11.
Nature ; 519(7542): 187-192, 2015 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-25731175

RESUMEN

Signalling by Wnt proteins is finely balanced to ensure normal development and tissue homeostasis while avoiding diseases such as cancer. This is achieved in part by Notum, a highly conserved secreted feedback antagonist. Notum has been thought to act as a phospholipase, shedding glypicans and associated Wnt proteins from the cell surface. However, this view fails to explain specificity, as glypicans bind many extracellular ligands. Here we provide genetic evidence in Drosophila that Notum requires glypicans to suppress Wnt signalling, but does not cleave their glycophosphatidylinositol anchor. Structural analyses reveal glycosaminoglycan binding sites on Notum, which probably help Notum to co-localize with Wnt proteins. They also identify, at the active site of human and Drosophila Notum, a large hydrophobic pocket that accommodates palmitoleate. Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase.


Asunto(s)
Carboxilesterasa/metabolismo , Proteínas de Drosophila/metabolismo , Esterasas/metabolismo , Proteínas Wnt/química , Proteínas Wnt/metabolismo , Vía de Señalización Wnt , Acilación , Animales , Sitios de Unión , Carboxilesterasa/química , Proteínas de Drosophila/química , Esterasas/química , Esterasas/genética , Ácidos Grasos Monoinsaturados/metabolismo , Glicosilfosfatidilinositoles/metabolismo , Glipicanos/metabolismo , Humanos , Cinética , Ligandos , Espectrometría de Masas , Modelos Moleculares , Unión Proteica
12.
Immunopharmacol Immunotoxicol ; 43(3): 380-385, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34028330

RESUMEN

BACKGROUND: Allergic dermatitis (AD) is a chronic inflammatory skin disease that a variety of immune cells are involved in the progression of AD. Among them, T cells are one of major players of AD pathogenesis. The V-domain Ig suppressor of T cell activation (VISTA) has been reported that it has a potential immunomodulatory for T cell response. OBJECTIVE: This study aimed to investigate immunomodulatory of recombinant VISTA-Ig fusion protein in AD mice model. METHODS: The model of AD was built with oxazolone (OXA) in BALB/c mice, then VISTA-Ig was used to treat AD by intraperitoneal (IP) injection. The ear thickness was measured by a digital thickness gauge. The ears tissues were collected and subjected to hematoxylin-eosin (H&E) and toluidine blue (TB) staining. The secretion levels of IL-4 and IgE in the serum were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of inflammatory cytokines (IL-1ß, IL-6, IL-12, and INF-γ) in ear tissues were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Treatment with VISTA-Ig successfully alleviated the symptoms of AD, such as erythema, horny substance, and swelling. The infiltration of inflammatory cells was significantly reduced following VISTA-Ig therapy. The secretion levels of IL-4 and IgE in the serum were significantly attenuated following treatment with VISTA-Ig. Additionally, VISTA-Ig observably down-regulated inflammatory cytokines expression in ear tissues. CONCLUSIONS & CLINICAL RELEVANCE: Taken together, our results showed that VISTA-Ig possessed the potential to be a novel immunomodulatory candidate drug against AD.


Asunto(s)
Dermatitis Alérgica por Contacto , Proteínas de la Membrana/farmacología , Oxazolona/efectos adversos , Proteínas Recombinantes de Fusión/farmacología , Animales , Dermatitis Alérgica por Contacto/tratamiento farmacológico , Dermatitis Alérgica por Contacto/inmunología , Proteínas de la Membrana/inmunología , Ratones , Ratones Endogámicos BALB C , Oxazolona/farmacología , Proteínas Recombinantes de Fusión/inmunología
13.
Acta Pharmacol Sin ; 41(1): 47-55, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31607752

RESUMEN

T cell metabolic activation plays a crucial role in inflammation of atherosclerosis. Shikonin (SKN), a natural naphthoquinone with anti-inflammatory activity, has shown to exert cardioprotective effects, but the effect of SKN on atherosclerosis is unclear. In addition, SKN was found to inhibit glycolysis via targeting pyruvate kinase muscle isozyme 2 (PKM2). In the present study, we investigated the effects of SKN on hyperhomocysteinemia (HHcy)-accelerated atherosclerosis and T cell inflammatory activation in ApoE-/- mice and the metabolic mechanisms in this process. Drinking water supplemented with Hcy (1.8 g/L) was administered to ApoE-/- mice for 2 weeks and the mice were injected with SKN (1.2 mg/kg, i.p.) or vehicle every 3 days. We showed that SKN treatment markedly attenuated HHcy-accelerated atherosclerosis in ApoE-/- mice and significantly decreased inflammatory activated CD4+ T cells and proinflammatory macrophages in plaques. In splenic CD4+ T cells isolated from HHcy-ApoE-/- mice, SKN treatment significantly inhibited HHcy-stimulated PKM2 activity, interferon-γ secretion and the capacity of these T cells to promote macrophage proinflammatory polarization. SKN treatment significantly inhibited HHcy-stimulated CD4+ T cell glycolysis and oxidative phosphorylation. Metabolic profiling analysis of CD4+ T cells revealed that Hcy administration significantly increased various glucose metabolites as well as lipids and acetyl-CoA carboxylase 1, which were reversed by SKN treatment. In conclusion, our results suggest that SKN is effective to ameliorate atherosclerosis in HHcy-ApoE-/- mice and this is at least partly associated with the inhibition of SKN on CD4+ T cell inflammatory activation via PKM2-dependent metabolic suppression.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Apolipoproteínas E/deficiencia , Aterosclerosis/tratamiento farmacológico , Hiperhomocisteinemia/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Naftoquinonas/farmacología , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerosis/metabolismo , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Hiperhomocisteinemia/metabolismo , Inflamación/metabolismo , Inyecciones Intraperitoneales , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Naftoquinonas/administración & dosificación
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(9): 942-947, 2020 Sep.
Artículo en Zh | MEDLINE | ID: mdl-32933623

RESUMEN

OBJECTIVE: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China. METHODS: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017. RESULTS: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66). CONCLUSIONS: Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.


Asunto(s)
Síndrome de Dificultad Respiratoria del Recién Nacido , China , Femenino , Humanos , Recién Nacido , Síndrome de Aspiración de Meconio , Embarazo , Estudios Retrospectivos
15.
Behav Res Methods ; 51(5): 2310-2336, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31429062

RESUMEN

The application of word associations has become increasingly widespread. However, the association norms produced by traditional free association tests tend not to exceed 10,000 stimulus words, making the number of associated words too small to be representative of the overall language. In this study we used text corpora totaling over 400 million Chinese words, along with a multitude of association measures, to automatically construct a Chinese Lexical Association Database (CLAD) comprising the lexical association of over 80,000 words. Comparison of the CLAD with a database of traditional Chinese word association norms shows that word associations extracted from large text corpora are similar in strength to those elicited from free association tests but contain a much greater number of associative word pairs. Additionally, the relatively small numbers of participants involved in the creation of traditional norms result in relatively coarse scales of association measurement, whereas the differentiation of association strengths is greatly enhanced in the CLAD. The CLAD provides researchers with a great supplement to traditional word association norms. A query website at www.chinesereadability.net/LexicalAssociation/CLAD/ affords access to the database.


Asunto(s)
Bases de Datos Factuales , Adulto , Pueblo Asiatico , Femenino , Asociación Libre , Humanos , Lenguaje , Masculino , Adulto Joven
16.
Angew Chem Int Ed Engl ; 58(38): 13360-13364, 2019 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-31353768

RESUMEN

Metallosupramolecular poly-NHC-metal assemblies were prepared from trigonal hexakis (H6 -1 a(PF6 )6 and H6 -1 b(PF6 )6 ) or nonakis (H9 -3(BF4 )9 ) imidazolium salts and Ag2 O. Complexes [Ag6 (1 a)2 ](PF6 )6 and [Ag6 (1 b)2 ](PF6 )6 are built from six Ag+ ions sandwiched between two trigonal hexacarbene ligands with an inner and an outer NHC donor in each of the three ligand arms. The metal atoms are arranged in two triangles. The hexakis-NHC ligands bear cinnamic ester groups at the outlying NHC donors, used in postsynthetic [2+2] cycloaddition reactions linking two hexakis-NHC ligands by three cyclobutane units to give complexes [Ag6 (2 a)](PF6 )6 and [Ag6 (2 b)](PF6 )6 bearing a dodecacarbene ligand. From the related nonakisimidazolium salt H9 -3(BF4 )9 , complex [Ag9 (4)](BF4 )9 bearing an octadecacarbene ligand was obtained. Removal of the template metals yielded very large, stable, polyimidazolium cations with 12 or 18 internal imidazolium groups.

17.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(1): 6-10, 2019 Jan.
Artículo en Zh | MEDLINE | ID: mdl-30675856

RESUMEN

OBJECTIVE: To investigate the incidence of neonatal asphyxia and possible contributing factors for the development of severe asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture, China. METHODS: A total of 16 hospitals in Hubei Enshi Tujia and Miao Autonomous Prefecture were selected as research centers. A retrospective analysis was performed for the clinical data of 22 294 live births in these 16 hospitals from January to December, 2016 to investigate the incidence rate of neonatal asphyxia and possible contributing factors for the development of severe asphyxia. RESULTS: Of the 22 294 neonates born alive, 733 (3.29%) were diagnosed with neonatal asphyxia, among whom 627 had mild asphyxia and 106 had severe asphyxia. The neonates with low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight had a higher incidence of severe asphyxia (P<0.05). CONCLUSIONS: The incidence rate of neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture is higher. Low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight may be related to the development of severe neonatal asphyxia.


Asunto(s)
Asfixia Neonatal , Asfixia Neonatal/epidemiología , China , Humanos , Incidencia , Recién Nacido , Estudios Retrospectivos
18.
BMC Plant Biol ; 18(1): 259, 2018 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-30367612

RESUMEN

BACKGROUND: Heat stress is a severe environmental stress that affects plant growth and reduces yield. Bax inhibitor-1 (BI-1) is a cytoprotective protein that is involved in the response to biotic and abiotic stresses. The Arabidopsis (Arabidopsis thaliana) BI-1 mutants atbi1-1 and atbi1-2 are hypersensitive to heat stress, and AtBI-1 overexpression rescues thermotolerance deficiency in atbi1 plants. Nevertheless, the mechanism of BI-1 in plant thermotolerance is still unclear. RESULTS: We identified a wheat (Triticum aestivum L.) BI-1 gene, TaBI-1.1, which was highly upregulated in an RNA sequencing (RNA-seq) analysis of heat-treated wheat. The upregulation of TaBI-1.1 under heat stress was further demonstrated by real time quantitative PCR (qRT-PCR) and ß-glucuronidase (GUS) staining. Compared with the wild type Col-0, the atbi1-2 mutant is hypersensitive to heat stress, and constitutive expression of TaBI-1.1 in atbi1-2 (35S::TaBI-1.1/ atbi1-2) rescued the deficiency of atbi1-2 under heat stress. Furthermore, we identified TaFKBP62 as a TaBI-1.1-interacting protein that co-localized with TaBI-1.1 on the endoplasmic reticulum (ER) membrane and enhanced heat stress tolerance. Additionally, HSFA2, HSFB1, ROF1, HSP17.4B, HSP17.6A, HSP17.8, HSP70B, and HSP90.1 expression levels were suppressed in atbi1-2 plants under heat stress. In contrast, 35S::TaBI-1.1/atbi1-2 relieved the inhibitory effect of AtBI-1 loss of function. CONCLUSIONS: TaBI-1.1 interacted with TaFKBP62 and co-localized with TaFKBP62 on the ER membrane. Both TaBI-1.1 and AtBI-1 regulated the expression of heat-responsive genes and were conserved in plant thermotolerance.


Asunto(s)
Respuesta al Choque Térmico/fisiología , Proteínas de Plantas/genética , Triticum/fisiología , Arabidopsis/genética , Arabidopsis/fisiología , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Retículo Endoplásmico/metabolismo , Regulación de la Expresión Génica de las Plantas , Respuesta al Choque Térmico/genética , Membranas Intracelulares/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Mutación , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Dominios y Motivos de Interacción de Proteínas , Triticum/genética , Regulación hacia Arriba
19.
BMC Plant Biol ; 18(1): 93, 2018 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-29801463

RESUMEN

BACKGROUND: The calcineurin B-like protein (CBL)-interacting protein kinase (CIPK) signaling pathway responds to various abiotic stresses in plants. RESULTS: Wheat CIPK23, isolated from wheat drought transcriptome data set, was induced by multiple abiotic stresses, including drought, salt, and abscisic acid (ABA). Compared with wild-type plants, TaCIPK23-overexpression wheat and Arabidopsis showed an higher survival rate under drought conditions with enhanced germination rate, developed root system, increased accumulation of osmolytes, and reduced water loss rate. Over-expression of TaCIPK23 rendered transgenic plants ABA sensitivity, as evidenced by delayed seed germination and the induction of stomatal closure. Consistent with the ABA-sensitive phenotype, the expression level of drought- and ABA-responsive genes were increased under drought conditions in the transgenic plants. In addition, using yeast two-hybrid system, pull-down and bimolecular fluorescence complementation (BiFc) assays, TaCIPK23 was found to interact with TaCBL1 on the plasma membrane. CONCLUSIONS: These results suggest that TaCIPK23 plays important roles in ABA and drought stress responses, and mediates crosstalk between the ABA signaling pathway and drought stress responses in wheat.


Asunto(s)
Ácido Abscísico/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas Quinasas/metabolismo , Transducción de Señal , Triticum/enzimología , Arabidopsis/genética , Arabidopsis/fisiología , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Sequías , Genes Reporteros , Germinación , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/enzimología , Raíces de Plantas/genética , Raíces de Plantas/fisiología , Plantas Modificadas Genéticamente , Proteínas Quinasas/genética , Plantones/enzimología , Plantones/genética , Plantones/fisiología , Semillas/enzimología , Semillas/genética , Semillas/fisiología , Cloruro de Sodio/metabolismo , Estrés Fisiológico , Triticum/genética , Triticum/fisiología , Técnicas del Sistema de Dos Híbridos
20.
BMC Plant Biol ; 18(1): 320, 2018 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-30509166

RESUMEN

BACKGROUND: Abiotic stress severely influences plant growth and development. MYB transcription factors (TFs), which compose one of the largest TF families, play an important role in abiotic stress responses. RESULT: We identified 139 soybean MYB-related genes; these genes were divided into six groups based on their conserved domain and were distributed among 20 chromosomes (Chrs). Quantitative real-time PCR (qRT-PCR) indicated that GmMYB118 highly responsive to drought, salt and high temperature stress; thus, this gene was selected for further analysis. Subcellular localization revealed that the GmMYB118 protein located in the nucleus. Ectopic expression (EX) of GmMYB118 increased tolerance to drought and salt stress and regulated the expression of several stress-associated genes in transgenic Arabidopsis plants. Similarly, GmMYB118-overexpressing (OE) soybean plants generated via Agrobacterium rhizogenes (A. rhizogenes)-mediated transformation of the hairy roots showed improved drought and salt tolerance. Furthermore, compared with the control (CK) plants, the clustered, regularly interspaced, short palindromic repeat (CRISPR)-transformed plants exhibited reduced drought and salt tolerance. The contents of proline and chlorophyll in the OE plants were significantly greater than those in the CK plants, whose contents were greater than those in the CRISPR plants under drought and salt stress conditions. In contrast, the reactive oxygen species (ROS) and malondialdehyde (MDA) contents were significantly lower in the OE plants than in the CK plants, whose contents were lower than those in the CRISPR plants under stress conditions. CONCLUSIONS: These results indicated that GmMYB118 could improve tolerance to drought and salt stress by promoting expression of stress-associated genes and regulating osmotic and oxidizing substances to maintain cell homeostasis.


Asunto(s)
Proteínas de Plantas/metabolismo , Factores de Transcripción/metabolismo , Agrobacterium/metabolismo , Arabidopsis/metabolismo , Arabidopsis/fisiología , Deshidratación , Regulación de la Expresión Génica de las Plantas , Genes de Plantas/genética , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/fisiología , Raíces de Plantas/microbiología , Plantas Modificadas Genéticamente , Reacción en Cadena en Tiempo Real de la Polimerasa , Estrés Salino , Glycine max/genética , Glycine max/metabolismo , Glycine max/fisiología , Factores de Transcripción/genética , Factores de Transcripción/fisiología
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