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1.
Nature ; 617(7960): 417-425, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37138078

RESUMEN

The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorders1. However, the development of KOR analgesics has been hindered by the associated hallucinogenic side effects2. The initiation of KOR signalling requires the Gi/o-family proteins including the conventional (Gi1, Gi2, Gi3, GoA and GoB) and nonconventional (Gz and Gg) subtypes. How hallucinogens exert their actions through KOR and how KOR determines G-protein subtype selectivity are not well understood. Here we determined the active-state structures of KOR in a complex with multiple G-protein heterotrimers-Gi1, GoA, Gz and Gg-using cryo-electron microscopy. The KOR-G-protein complexes are bound to hallucinogenic salvinorins or highly selective KOR agonists. Comparisons of these structures reveal molecular determinants critical for KOR-G-protein interactions as well as key elements governing Gi/o-family subtype selectivity and KOR ligand selectivity. Furthermore, the four G-protein subtypes display an intrinsically different binding affinity and allosteric activity on agonist binding at KOR. These results provide insights into the actions of opioids and G-protein-coupling specificity at KOR and establish a foundation to examine the therapeutic potential of pathway-selective agonists of KOR.


Asunto(s)
Microscopía por Crioelectrón , Proteínas de Unión al GTP Heterotriméricas , Ligandos , Receptores Opioides kappa , Analgésicos Opioides/metabolismo , Analgésicos Opioides/farmacología , Receptores Opioides kappa/química , Receptores Opioides kappa/metabolismo , Receptores Opioides kappa/ultraestructura , Transducción de Señal , Proteínas de Unión al GTP Heterotriméricas/química , Proteínas de Unión al GTP Heterotriméricas/metabolismo , Proteínas de Unión al GTP Heterotriméricas/ultraestructura , Especificidad por Sustrato , Regulación Alostérica/efectos de los fármacos , Alucinógenos/metabolismo , Alucinógenos/farmacología
2.
Plant Cell Physiol ; 64(8): 893-905, 2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37233621

RESUMEN

Phosphorus (P) is a growth-limiting nutrient for plants, which is taken up by root tissue from the environment as inorganic phosphate (Pi). To maintain an appropriate status of cellular Pi, plants have developed sophisticated strategies to sense the Pi level and modulate their root system architecture (RSA) under the ever-changing growth conditions. However, the molecular basis underlying the mechanism remains elusive. Inositol polyphosphate kinase (IPK2) is a key enzyme in the inositol phosphate metabolism pathway, which catalyzes the phosphorylation of IP3 into IP5 by consuming ATP. In this study, the functions of a rice inositol polyphosphate kinase gene (OsIPK2) in plant Pi homeostasis and thus physiological response to Pi signal were characterized. As a biosynthetic gene for phytic acid in rice, overexpression of OsIPK2 led to distinct changes in inositol polyphosphate profiles and an excessive accumulation of Pi levels in transgenic rice under Pi-sufficient conditions. The inhibitory effects of OsIPK2 on root growth were alleviated by Pi-deficient treatment compared with wild-type plants, suggesting the involvement of OsIPK2 in the Pi-regulated reconstruction of RSA. In OsIPK2-overexpressing plants, the altered acid phosphatase (APase) activities and misregulation of Pi-starvation-induced (PSI) genes were observed in roots under different Pi supply conditions. Notably, the expression of OsIPK2 also altered the Pi homeostasis and RSA in transgenic Arabidopsis. Taken together, our findings demonstrate that OsIPK2 plays an important role in Pi homeostasis and RSA adjustment in response to different environmental Pi levels in plants.


Asunto(s)
Arabidopsis , Oryza , Polifosfatos/metabolismo , Oryza/metabolismo , Inositol/metabolismo , Fosfatos/metabolismo , Arabidopsis/genética , Homeostasis , Raíces de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
3.
Nature ; 530(7591): 447-52, 2016 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-26886794

RESUMEN

The mixed lineage leukaemia (MLL) family of proteins (including MLL1-MLL4, SET1A and SET1B) specifically methylate histone 3 Lys4, and have pivotal roles in the transcriptional regulation of genes involved in haematopoiesis and development. The methyltransferase activity of MLL1, by itself severely compromised, is stimulated by the three conserved factors WDR5, RBBP5 and ASH2L, which are shared by all MLL family complexes. However, the molecular mechanism of how these factors regulate the activity of MLL proteins still remains poorly understood. Here we show that a minimized human RBBP5-ASH2L heterodimer is the structural unit that interacts with and activates all MLL family histone methyltransferases. Our structural, biochemical and computational analyses reveal a two-step activation mechanism of MLL family proteins. These findings provide unprecedented insights into the common theme and functional plasticity in complex assembly and activity regulation of MLL family methyltransferases, and also suggest a universal regulation mechanism for most histone methyltransferases.


Asunto(s)
Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , N-Metiltransferasa de Histona-Lisina/química , N-Metiltransferasa de Histona-Lisina/metabolismo , Proteína de la Leucemia Mieloide-Linfoide/química , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Secuencia de Aminoácidos , Cristalografía por Rayos X , Activación Enzimática , N-Metiltransferasa de Histona-Lisina/genética , Histonas/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular , Modelos Moleculares , Datos de Secuencia Molecular , Complejos Multiproteicos , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Unión Proteica , Estructura Cuaternaria de Proteína , Estructura Terciaria de Proteína , Factores de Transcripción/química , Factores de Transcripción/metabolismo
4.
Nucleic Acids Res ; 47(19): 10426-10438, 2019 11 04.
Artículo en Inglés | MEDLINE | ID: mdl-31544921

RESUMEN

The Mixed Lineage Leukemia protein 1 (MLL1) plays an essential role in the maintenance of the histone H3 lysine 4 (H3K4) methylation status for gene expression during differentiation and development. The methyltransferase activity of MLL1 is regulated by three conserved core subunits, WDR5, RBBP5 and ASH2L. Here, we determined the structure of human RBBP5 and demonstrated its role in the assembly and regulation of the MLL1 complex. We identified an internal interaction between the WD40 propeller and the C-terminal distal region in RBBP5, which assisted the maintenance of the compact conformation of the MLL1 complex. We also discovered a vertebrate-specific motif in the C-terminal distal region of RBBP5 that contributed to nucleosome recognition and methylation of nucleosomes by the MLL1 complex. Our results provide new insights into functional conservation and evolutionary plasticity of the scaffold protein RBBP5 in the regulation of KMT2-family methyltransferase complexes.


Asunto(s)
Proteínas de Unión al ADN/ultraestructura , N-Metiltransferasa de Histona-Lisina/ultraestructura , Complejos Multiproteicos/ultraestructura , Proteína de la Leucemia Mieloide-Linfoide/ultraestructura , Factores de Transcripción/genética , Diferenciación Celular/genética , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , N-Metiltransferasa de Histona-Lisina/química , N-Metiltransferasa de Histona-Lisina/genética , Histonas/genética , Humanos , Péptidos y Proteínas de Señalización Intracelular , Conformación Molecular , Complejos Multiproteicos/química , Complejos Multiproteicos/genética , Proteína de la Leucemia Mieloide-Linfoide/química , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteínas Nucleares/genética , Unión Proteica/genética , Conformación Proteica , Dominios y Motivos de Interacción de Proteínas/genética , Factores de Transcripción/química
5.
BMC Plant Biol ; 20(1): 211, 2020 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-32398153

RESUMEN

BACKGROUND: The tree peony (Paeonia suffruticosa Andr.) cultivar 'Er Qiao' is appreciated for its unstable variegated flower coloration, with cyanic and acyanic flowers appearing on different branches of the same plant and occasionally in a single flower or petal. However, the variegation mechanism is still unclear. RESULTS: In this study, we found significantly higher contents and more diverse sets of anthocyanins in the cyanic petals than in the acyanic petals. Comparative transcriptome analysis between the two flower types revealed 477 differentially expressed genes (DEGs). Quantitative real-time PCR results verified that the transcript levels of the flavonol synthase (FLS) gene were significantly increased in the acyanic petals. Furthermore, we found that a GCGGCG insertion at 246 bp in the flavonoid 3'-hydroxylase (F3'H) gene-coding region constitutes a duplication of the 241-245 bp section and was consistently found only in acyanic flowers. Sequence alignment of the F3'H gene from different plant species indicated that only the acyanic petals of 'Er Qiao' contained the GCGGCG insertion. The transformation of Arabidopsis tt7-1 lines demonstrated that the ectopic expression of F3'H-cyanic, but not F3'H-acyanic, could complement the colors in the hypocotyl and seed coat. CONCLUSION: In summary, we found that an indel in F3'H and the upregulation of FLS drastically reduced the anthocyanin content in acyanic petals. Our results provide molecular candidates for a better understanding of the variegation mechanisms in tree peony.


Asunto(s)
Antocianinas/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Flores/genética , Oxidorreductasas/genética , Paeonia/genética , Proteínas de Plantas/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Flores/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Mutación INDEL , Oxidorreductasas/metabolismo , Paeonia/crecimiento & desarrollo , Proteínas de Plantas/metabolismo , Alineación de Secuencia , Árboles , Regulación hacia Arriba
6.
BMC Genet ; 21(1): 124, 2020 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-33198624

RESUMEN

BACKGROUND: R2R3 myeloblastosis (MYB) genes are widely distributed in plants and comprise one of the largest transcription factor gene families. They play important roles in the regulatory networks controlling development, metabolism, and stress responses. Researches on functional genes in tree peony are still in its infancy. To date, few MYB genes have thus far been reported. RESULTS: In this study, we constructed a comprehensive reference gene set by transcriptome sequencing to obtain R2R3 MYB genes. The transcriptomes of eight different tissues were sequenced, and 92,837 unigenes were obtained with an N50 of 1662 nt. A total of 48,435 unigenes (77.98%) were functionally annotated in public databases. Based on the assembly, we identified 57 R2R3 MYB genes containing full-length open reading frames, which clustered into 35 clades by phylogenetic analysis. PsMYB57 clustered with anthocyanin regulation genes in Arabidopsis and was mainly transcribed in the buds and young leaves. The overexpression of PsMYB57 induced anthocyanin accumulation in tobacco, and four detected anthocyanin structural genes, including NtCHS, NtF3'H, NtDFR, and NtANS, were upregulated. The two endogenous bHLH genes NtAn1a and NtAn1b were also upregulated and may work in combination with PsMYB57 in regulating anthocyanin structural genes. CONCLUSIONS: Our study offers a useful reference to the selection of candidate MYB genes for further functional studies in tree peony. Function analysis of PsMYB57 is helpful to understand the color accumulation in vegetative organs of tree peony. PsMYB57 is also a promising resource to improve plant color in molecular breeding.


Asunto(s)
Antocianinas/metabolismo , Regulación de la Expresión Génica de las Plantas , Paeonia/genética , Proteínas de Plantas/genética , Factores de Transcripción/genética , Arabidopsis , Genes de Plantas , Familia de Multigenes , Filogenia , Plantas Modificadas Genéticamente , Nicotiana , Transcriptoma
7.
Plant J ; 95(3): 444-457, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29752755

RESUMEN

Hydroxycinnamic acid amides (HCAAs) are a class of antimicrobial metabolites involved in plant defense against necrotrophic pathogens, including Alternaria brassicicola and Botrytis cinerea. The agmatine coumaryl transferase (AtACT) is the key enzyme that catalyzes the last reaction in the biosynthesis of HCAAs, including p-coumaroylagmatine (CouAgm) and feruloylagmatine in Arabidopsis thaliana. However, the regulatory mechanism of AtACT gene expression is currently unknown. Yeast one-hybrid screening using the AtACT promoter as bait isolated the key positive regulator ORA59 that is involved in jasmonic acid/ethylene (JA/ET)-mediated plant defense responses. AtACT gene expression and HCAAs biosynthesis were synergistically induced by a combination of JA and ET. In the AtACT promoter, two GCC-boxes function equivalently for trans-activation by ORA59 in Arabidopsis protoplasts, and mutation of either GCC-box abolished AtACT mRNA accumulation in transgenic plants. Site-directed mutation analysis demonstrated that the specific Leu residue at position 228 of the ORA59 EDLL motif mainly contributed to its transcriptional activity on AtACT gene expression. Importantly, MEDIATOR25 (MED25) and ORA59 homodimer are also required for ORA59-dependent activation of the AtACT gene. These results suggest that ORA59 and two functionally equivalent GCC-boxes form the regulatory module together with MED25 that enables AtACT gene expression and HCAAs biosynthesis to respond to simultaneous activation of the JA/ET signaling pathways.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Ácidos Cumáricos/metabolismo , Ciclopentanos/metabolismo , Etilenos/metabolismo , Oxilipinas/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Factores de Transcripción/metabolismo , Aciltransferasas/metabolismo , Agmatina/análogos & derivados , Agmatina/metabolismo , Arabidopsis/metabolismo , Transducción de Señal , Técnicas del Sistema de Dos Híbridos
8.
FEBS J ; 291(13): 2784-2791, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38151714

RESUMEN

Receptor-G protein promiscuity is frequently observed in class A G protein-coupled receptors (GPCRs). In particular, GPCRs can couple with G proteins from different families (Gαs, Gαq/11, Gαi/o, and Gα12/13) or the same family subtypes. The molecular basis underlying the selectivity/promiscuity is not fully revealed. We recently reported the structures of kappa opioid receptor (KOR) in complex with the Gi/o family subtypes [Gαi1, GαoA, Gαz, and Gustducin (Gαg)] determined by cryo-electron microscopy (cryo-EM). The structural analysis, in combination with pharmacological studies, provides insights into Gi/o subtype selectivity. Given the conserved sequence identity and activation mechanism between different G protein families, the findings within Gi/o subtypes could be likely extended to other families. Understanding the KOR-Gi/o or GPCR-G protein selectivity will facilitate the development of more precise therapeutics targeting a specific G protein subtype.


Asunto(s)
Microscopía por Crioelectrón , Receptores Acoplados a Proteínas G , Receptores Opioides kappa , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/química , Receptores Opioides kappa/metabolismo , Receptores Opioides kappa/química , Receptores Opioides kappa/agonistas , Receptores Opioides kappa/genética , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/química , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/genética , Proteínas de Unión al GTP/metabolismo , Proteínas de Unión al GTP/química , Proteínas de Unión al GTP/genética , Unión Proteica , Animales , Conformación Proteica , Modelos Moleculares
9.
Bioorg Med Chem ; 21(11): 2843-55, 2013 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-23628470

RESUMEN

A series of novel 4-(2-fluorophenoxy)quinoline derivatives containing 4-oxo-1,4-dihydrocinnoline-3-carboxamide moiety were designed, synthesized and evaluated for their in vitro biological activities against c-Met kinase and six typical cancer cell lines (A549, H460, HT-29, MKN-45, U87MG and SMMC-7721). All the prepared compounds showed moderate to excellent antiproliferative activity, and the analysis of their structure-activity relationships indicated that 2-chloro or 2-trifluoromethyl substituted phenyl group on the 1-position of cinnoline ring was more favorable for antitumor activity. In this study, a promising compound 33, with a c-Met IC50 value of 0.59 nM, was identified as a multitargeted receptor tyrosine kinase inhibitor.


Asunto(s)
Anilidas/síntesis química , Antineoplásicos/síntesis química , Inhibidores de Proteínas Quinasas/síntesis química , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Quinolinas/síntesis química , Anilidas/química , Anilidas/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Concentración 50 Inhibidora , Simulación del Acoplamiento Molecular , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-met/química , Quinolinas/química , Quinolinas/farmacología , Espectrometría de Fluorescencia , Relación Estructura-Actividad
10.
Hepatogastroenterology ; 60(126): 1274-9, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23933917

RESUMEN

BACKGROUND/AIMS: The aim of this study was to evaluate the effects of obstructive jaundice on Infectious Complications of the patients who underwent pancreaticoduodenectomy. METHODOLOGY: One-hundred and sixteen consecutive patients without preoperative biliary drainage underwent pancreaticoduodenectomy from January 2006 to April 2010 and their data of post-operative complication were analyzed. Different level of bilirubin and different times of jaundice on infectious complications of the patients underwent pancreaticoduodenectomy were analysis. RESULTS: Patients with severe jaundice (Total bilirubin ≥5 mg/dL; n = 55), had a higher incidence in subsequent infectious complications than the patients with total bilirubin level of less than 5 mg/dL (n = 61) (36.06% vs. 56.36%, p <0.05). The patients with preoperative TB level of 5 or more sub classified according to the duration of jaundice. However, two groups without statistical significance in terms of post-operative complications. There were no significant differences in post-operative mortality rate among the different groups. CONCLUSIONS: The elevated serum bilirubin increases the rate of infectious complications of the patients underwent pancreaticoduodeneotomy.


Asunto(s)
Infecciones Bacterianas/etiología , Ictericia Obstructiva/complicaciones , Pancreaticoduodenectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Bilirrubina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreaticoduodenectomía/mortalidad
11.
Zhonghua Wai Ke Za Zhi ; 51(2): 131-4, 2013 Feb 01.
Artículo en Zh | MEDLINE | ID: mdl-23711005

RESUMEN

OBJECTIVE: To determine the outcome of hepatic venousaplasty and transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of the Budd-Chiari syndrome with occlusion of the hepatic veins. METHODS: Fifty patients of the Budd-Chiari syndrome with occlusion of the hepatic veins (23 males and 27 females, with a mean age of (39 ± 11) years) were elected for venousaplasty or TIPS. The average of Child-Pugh scores was 9.6 ± 2.6. Three patients had a acute course of the disease, while 47 patients had a subacute or a chronic course of the disease. The clinical presentation was ascites in all 50 cases, with concomitant upper gastrointestinal bleeding in 10 patients, hepatorenal syndrome in 4 patients and impaired liver function in all patients. Hepatic venousplasty was performed for 12 patients with occlusion of hepatic venous. Hepatic and inferior caval venousplasty were performed for 6 patients with occlusion of hepatic and inferior caval vein. TIPS was performed for 13 patients with occlusion of small hepatic vein. Modified TIPS was performed for 19 patients with extensive occlusion of hepatic vein. RESULTS: The procedure of treatment was successfully performed in all patients. The shunt reduced the portosystemic pressure gradient from (41 ± 10) to (27 ± 6) cmH2O (1 cmH2O = 0.098 kPa, t = 20.20, P = 0.001) and improved the portal flow velocity from (14 ± 10) to (52 ± 14) cm/s (t = 15.02, P = 0.001) after TIPS or modified TIPS. Clinical symptoms and the biochemical test results improved significantly during 3 weeks after hepatic venousplasty and shunt treatment. During the hospitalization, the death occurred in 1 case due to hepatic failure and the acute occlusion of shunt was treated with secondary intervention in another case. The mean follow-up was (82 ± 46) months. The revisions of shunt with TIPS were needed in 2 patients and the inflation of stenosised hepatic vein in another 2 patients during the follow-up. All patients were still observed. CONCLUSION: Hepatic venousaplasty and TIPS provide an excellent outcome in patients of Budd-Chiari syndrome with occlusion of the hepatic veins.


Asunto(s)
Angioplastia , Síndrome de Budd-Chiari/cirugía , Derivación Portosistémica Intrahepática Transyugular/métodos , Adulto , Femenino , Venas Hepáticas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
12.
Nat Commun ; 14(1): 1978, 2023 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-37031211

RESUMEN

Dysregulation of polyamine homeostasis strongly associates with human diseases. ATP13A2, which is mutated in juvenile-onset Parkinson's disease and autosomal recessive spastic paraplegia 78, is a transporter with a critical role in balancing the polyamine concentration between the lysosome and the cytosol. Here, to better understand human ATP13A2-mediated polyamine transport, we use single-particle cryo-electron microscopy to solve high-resolution structures of human ATP13A2 in six intermediate states, including the putative E2 structure for the P5 subfamily of the P-type ATPases. These structures comprise a nearly complete conformational cycle spanning the polyamine transport process and capture multiple substrate binding sites distributed along the transmembrane regions, suggesting a potential polyamine transport pathway. Integration of high-resolution structures, biochemical assays, and molecular dynamics simulations allows us to obtain a better understanding of the structural basis of how hATP13A2 transports polyamines, providing a mechanistic framework for ATP13A2-related diseases.


Asunto(s)
Trastornos Parkinsonianos , Poliaminas , Humanos , ATPasas de Translocación de Protón/metabolismo , Microscopía por Crioelectrón , Trastornos Parkinsonianos/metabolismo , Proteínas de Transporte de Membrana
13.
Nat Commun ; 14(1): 8064, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38052802

RESUMEN

Despite the increasing number of GPCR structures and recent advances in peptide design, the development of efficient technologies allowing rational design of high-affinity peptide ligands for single GPCRs remains an unmet challenge. Here, we develop a computational approach for designing conjugates of lariat-shaped macrocyclized peptides and a small molecule opioid ligand. We demonstrate its feasibility by discovering chemical scaffolds for the kappa-opioid receptor (KOR) with desired pharmacological activities. The designed De Novo Cyclic Peptide (DNCP)-ß-naloxamine (NalA) exhibit in vitro potent mixed KOR agonism/mu-opioid receptor (MOR) antagonism, nanomolar binding affinity, selectivity, and efficacy bias at KOR. Proof-of-concept in vivo efficacy studies demonstrate that DNCP-ß-NalA(1) induces a potent KOR-mediated antinociception in male mice. The high-resolution cryo-EM structure (2.6 Å) of the DNCP-ß-NalA-KOR-Gi1 complex and molecular dynamics simulations are harnessed to validate the computational design model. This reveals a network of residues in ECL2/3 and TM6/7 controlling the intrinsic efficacy of KOR. In general, our computational de novo platform overcomes extensive lead optimization encountered in ultra-large library docking and virtual small molecule screening campaigns and offers innovation for GPCR ligand discovery. This may drive the development of next-generation therapeutics for medical applications such as pain conditions.


Asunto(s)
Analgésicos Opioides , Receptores Opioides kappa , Masculino , Ratones , Animales , Receptores Opioides kappa/metabolismo , Ligandos , Analgésicos Opioides/química , Receptores Opioides mu/metabolismo , Péptidos Cíclicos/química
14.
Front Chem ; 10: 1111435, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36590279

RESUMEN

We report a facile and effective inorganic polycondensation combined with aerosol-spray strategy towards high-performance photocatalyst by fabricating mesoporous Ti1-xSnxO2 (0 < x < 1) solid solution. Such Ti1-xSnxO2 nanocrystals with high Sn-doped contents are self-assembled into mesoporous spheres can effectively promote visible-light harvest and high quantum yield, leading a longer lifetime of the photoelectron-hole pairs and less recombination. Such the photocatalysts enhanced photocatalytic activity for the degradation of Rhodamine B (RhB). The representative Ti0.9Sn0.1O2 and Ti0.8Sn0.2O2 compounds reach an optimum degradation of ≈50% and 70%, respectively, after 120 min irradiation under visible irradiation. The mesoporous Ti1-xSnxO2 solid solution could inhibit the recombination of electron-hole pairs, which promote reaction thermodynamics and kinetics for RhB degradation.

15.
Sci Total Environ ; 840: 156537, 2022 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-35679936

RESUMEN

Plant carbon (C) assimilation is expected to nonlinearly increase with continuously increasing nitrogen (N) deposition, causing a N saturation threshold for productivity. However, the response of plant productivity to N deposition rates and further the N saturation threshold still await comprehensive quantization for forest ecosystem. Here, we tested the effect of N addition on aboveground net primary productivity (ANPP) of three-year old Chinese fir (Cunninghamia lanceolata) trees by adding N at 0, 5.6, 11.2, 22.4, and 44.8 g N m-2 yr-1 for 2.5 years. The N saturation threshold was estimated based on a quadratic-plus-plateau model. Results showed that ANPP transitioned from an increasing stage with increasing N addition rate to a plateaued stage at an N rate of 16.3 g N m-2 yr-1. The response of ANPP to N addition rates was well explained by the net photosynthetic rates of needles. Results from the dual isotope measurement [simultaneous determination of needle stable carbon (δ13C) and oxygen (δ18O) isotopes] indicated that the photosynthetic capacity, rather than the stomatal conductance, mediated the response of photosynthesis and ANPP of the young Chinese fir trees to N addition. Accordingly, the amount of needle N partitioning to water-soluble fraction, which is associated with the photosynthetic capacity, also responded to N enrichment with a nonlinear increase. Our study will contribute to a more accurate prediction on the influence of N deposition on C cycles in Chinese fir plantations.


Asunto(s)
Abies , Cunninghamia , Carbono , Ecosistema , Agujas , Nitrógeno , Fotosíntesis/fisiología , Hojas de la Planta/fisiología , Plantas , Árboles
16.
J Clin Ultrasound ; 38(7): 353-60, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20533444

RESUMEN

OBJECTIVE: This prospectively randomized controlled study aimed to assess with Doppler ultrasound (US) the shunt function of expanded polytetrafluoroethylene (ePTFE)-covered transjugular intrahepatic portosystemic shunt (TIPS) stent versus bare stent and to evaluate the usefulness of routine TIPS follow-up of ePTFE-covered stents. METHODS: Sixty consecutive patients were randomized for bare or covered transjugular TIPS stenting in our institution between April 2007 and April 2009. Data of follow-up Doppler US, angiography, and portosystemic pressure gradient measurements were collected and analyzed. RESULTS: The follow-up period was 8.34 + or - 4.42 months in the bare-stent group and 6.16 + or - 3.89 months in the covered-stent group. Baseline clinical characteristics were similar in both groups. Two hundred three US studies were performed in 60 patients, with a mean of 3.4 per patient, and demonstrated abnormalities in 28 patients (21 bare stents, 7 ePTFE-covered stents), 19 of them (13 in bare-stent group, 6 in covered-stent group) showing no clinical evidence of recurrence. Ten of 13 patients in the bare-stent group underwent balloon angioplasty or additional stent placement, whereas only one of six patients in the covered-stent group needed reintervention for intimal hyperplasia. The average peak velocity in the midshunt of ePTFE-covered stent was 139 + or - 26 cm/s after TIPS creation and 125 + or - 20 cm/s during follow-up, which was significantly higher than the bare-stent group (p < 0.05). The main portal vein and hepatic artery showed higher flow velocities in the ePTFE-covered stent group than in the bare-stent group. ePTFE-covered stents maintained lower portosystemic pressure gradient than bare stents (9.5 + or - 2.9 versus 13.2 + or - 1.5 mmHg, p < 0.05). CONCLUSIONS: ePTFE-covered stents resulted in higher patency rates and better hemodynamics than bare stents. Routine US surveillance may not be necessary in patients with ePTFE-covered TIPS stent.


Asunto(s)
Venas Hepáticas/diagnóstico por imagen , Vena Porta/diagnóstico por imagen , Derivación Portosistémica Intrahepática Transyugular/instrumentación , Stents , Ultrasonografía Doppler/métodos , Femenino , Estudios de Seguimiento , Venas Hepáticas/cirugía , Humanos , Circulación Hepática , Masculino , Persona de Mediana Edad , Politetrafluoroetileno , Vena Porta/cirugía , Derivación Portosistémica Intrahepática Transyugular/métodos , Estudios Prospectivos , Diseño de Prótesis , Resultado del Tratamiento , Grado de Desobstrucción Vascular
17.
Zhonghua Wai Ke Za Zhi ; 48(2): 83-7, 2010 Jan 15.
Artículo en Zh | MEDLINE | ID: mdl-20302722

RESUMEN

OBJECTIVE: To retrospectively compare the clinical outcome in patients with portal hypertension treated with transjugular intrahepatic portosystemic shunt (TIPS) using Fluency stent-graft (PTFE-covered stents) or bare stents. METHODS: Approval of study and treatment protocol and waiver of informed consent for the retrospective study were obtained from institutional review board. Informed consent was obtained from each patient before procedure. Sixty consecutive patients with portal hypertension treated with TIPS from April 2007 to April 2009 were included. TIPS creation was performed with Fluency stent-graft in 30 patients (group A) and with bare stents in 30 patients (group B). Liver function, TIPS patency and clinical outcome were evaluated every 3 months. RESULTS: During hospitalization, there was no hepatic encephalopathy and recurrency of variceal bleeding.Acute shunt occlusion was observed in one patient with group A and another patient with group B.Follow-up was performed with average time of (6.2 +/- 3.9) months in group A and (8.3 +/- 4.4) months in group B. The rates of recurrent bleeding, acute shunt occlusion, hepatic encephalopathy and death were 3.3% and 20.0%, 0 and 30.0%, 16.7% and 20.0%, 0 and 13.3% in group A and B. The rates of recurrent bleeding, acute shunt occlusion and death in group A was lower than those in group B. There was no difference of hepatic encephalopathy between group A and B. The decrease of portal pressure and portosystemic pressure gradient, and the increase of portal flow and shunt flow in group A were higher than those in group B. There were no difference of liver function, ammonia and MELD between group A and B. CONCLUSIONS: Fluency stent-graft is safe and effective in TIPS creation, with high patency rate. Covered-stent can improve the clinical outcome of portal hypertension.


Asunto(s)
Hipertensión Portal/cirugía , Derivación Portosistémica Intrahepática Transyugular/instrumentación , Stents , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
18.
Dent Mater J ; 39(5): 855-861, 2020 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-32461510

RESUMEN

This study was evaluating how three desensitizing toothpastes used at home influence the effect associated with desensitizing agents after application in the clinic. Fifty dentine disks measure it permeability and 32 dentine disks with similar permeability levels were selected. Following Dental desensitizer treatment, dentine disks were randomly divided into three subgroups (n=10) that received applications of three toothpastes, respectively. The permeability (Lp) of each specimen was measured after each treatment. One specimen was selected from each group for scanning electron microscopy (SEM) observation. After each treatment, the Lp values decreased significantly for each group (p<0.05) and either completely or partially blocked the dentine tubules upon SEM observation. However, no significant differences in Lp values were observed amongst subgroups (p>0.05). After using the Dental desensitizer, Sensodyne, Crest and Colgate desensitizing toothpastes both can continued to reduce the permeability of the dentine disk, and no significant differences were found amongst them.


Asunto(s)
Desensibilizantes Dentinarios/farmacología , Sensibilidad de la Dentina/tratamiento farmacológico , Sensibilidad de la Dentina/prevención & control , Dentina , Permeabilidad de la Dentina/efectos de los fármacos , Microscopía Electrónica de Rastreo , Fluoruro de Sodio/farmacología , Pastas de Dientes/farmacología
19.
Zhonghua Wai Ke Za Zhi ; 47(6): 446-9, 2009 Mar 15.
Artículo en Zh | MEDLINE | ID: mdl-19595233

RESUMEN

OBJECTIVE: To analyze the long-term results of TIPS, TIPS with coronary vein occlusion (CVO) and combined TIPS and portal azygous disconnection for the treatment of portal hypertension and variceal bleedings. METHODS: Three hundreds and fifty-eight patients with portal hypertension were admitted because of variceal bleeding from July 1993 to May 2008. All patients were divided into 3 groups: 227 cases in group TIPS, 36 cases in TIPS and CVO group, 95 cases in combined TIPS and portal azygous disconnection group. The rates of successful operation, shunt patency, rebleeding, encephalopathy and survival were observed and compared by statistics methods. RESULTS: There were 349 cases (97.5%) underwent successful surgery and 9 cases with failure surgery. The rates of occluded shunts, encephalopathy, rebleeding, and death in early periods were 2.5%, 31.8%, 4.7% and 9.0% respectively. The rate of encephalopathy and death in group with TIPS were higher than in group with combined TIPS and portal azygous disconnection (P < 0.01). The rate of encephalopathy and death were 41.2% and 24.7% in 85 cases with emergency TIPS. During the follow-up 1 - 15 years, the rate of patency shunts in 12 and 24 months after operation was 74.0% and 48.1% respectively. The rate of 1-year patency shunts in group with combined TIPS and portal azygous disconnection was higher than in group with TIPS, TIPS and CVO (P < 0.01 and P < 0.05). The rebleeding in group with TIPS was higher than in group with combined TIPS and portal azygous disconnection (P < 0.01), and the survival rate in group with TIPS was lower than in group with TIPS and CVO, combined TIPS and portal azygous disconnection (P < 0.01 and P < 0.01). CONCLUSIONS: TIPS is an efficient therapy for portal hypertension with CVO, combined TIPS and portal azygous disconnection can improve the results of TIPS for portal hypertension.


Asunto(s)
Hipertensión Portal/cirugía , Derivación Portosistémica Intrahepática Transyugular , Adulto , Anciano , Vena Ácigos/cirugía , Vasos Coronarios , Embolización Terapéutica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
20.
Microsc Res Tech ; 82(9): 1557-1565, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31206921

RESUMEN

Triblemma Ching is a genus proposed by Ching Ren-Chang in 1978, and it is composed of two species, Triblemma lancea (Thunb.) Ching and Triblemma zeylanica (Hook.) Ching. There has been much debate on the systematic position of Triblemma, and this genus has always been included in Diplazium. Here, we have described new features of tracheary elements, epidermis, spore, scale, and rachis of Triblemma revealed using light and scanning electron microscopy and proposed that Triblemma is closely related to Athyriopsis, which conflicts with the traditional viewpoint.


Asunto(s)
Microscopía Electrónica de Rastreo , Microscopía , Tracheophyta/anatomía & histología , Tracheophyta/clasificación , Animales
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