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1.
Nature ; 616(7956): 275-279, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37045918

RESUMEN

Singlet fission1-13 may boost photovoltaic efficiency14-16 by transforming a singlet exciton into two triplet excitons and thereby doubling the number of excited charge carriers. The primary step of singlet fission is the ultrafast creation of the correlated triplet pair17. Whereas several mechanisms have been proposed to explain this step, none has emerged as a consensus. The challenge lies in tracking the transient excitonic states. Here we use time- and angle-resolved photoemission spectroscopy to observe the primary step of singlet fission in crystalline pentacene. Our results indicate a charge-transfer mediated mechanism with a hybridization of Frenkel and charge-transfer states in the lowest bright singlet exciton. We gained intimate knowledge about the localization and the orbital character of the exciton wave functions recorded in momentum maps. This allowed us to directly compare the localization of singlet and bitriplet excitons and decompose energetically overlapping states on the basis of their orbital character. Orbital- and localization-resolved many-body dynamics promise deep insights into the mechanics governing molecular systems18-20 and topological materials21-23.

2.
J Environ Sci (China) ; 138: 439-449, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38135409

RESUMEN

The booming development of rare earth industry and the extensive utilization of its products accompanied by urban development have led to the accelerated accumulation of rare earth elements (REEs) as emerging pollutants in atmospheric environment. In this study, the variation of REEs in PM2.5 with urban (a non-mining city) transformation was investigated through five consecutive years of sample collection. The compositional variability and provenance contribution of REEs in PM2.5 were characterized, and the REEs exposure risks of children and adults via inhalation, ingestion and dermal absorption were also evaluated. The results showed an increase in the total REEs concentration from 46.46 ± 35.16 mg/kg (2017) to 81.22 ± 38.98 mg/kg (2021) over the five-year period, with Ce and La making the largest contribution. The actual increment of industrial and traffic emission source among the three pollution sources was 1.34 ng/m3. Coal combustion source displayed a downward trend. Ingestion was the main exposure pathway for REEs in PM2.5 for both children and adults. Ce contributed the most to the total intake of REEs in PM2.5 among the population, followed by La and Nd. The exposure risks of REEs in PM2.5 in the region were relatively low, but the trend of change was of great concern. It was strongly recommended to strengthen the concern about traffic-related non-exhaust emissions of particulate matter.


Asunto(s)
Contaminantes Atmosféricos , Metales de Tierras Raras , Adulto , Niño , Humanos , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Ciudades , Monitoreo del Ambiente/métodos , Metales de Tierras Raras/análisis , China
3.
Phys Rev Lett ; 131(6): 066402, 2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37625042

RESUMEN

We performed spin-, time- and angle-resolved extreme ultraviolet photoemission spectroscopy of excitons prepared by photoexcitation of inversion-symmetric 2H-WSe_{2} with circularly polarized light. The very short probing depth of XUV photoemission permits selective measurement of photoelectrons originating from the top-most WSe_{2} layer, allowing for direct measurement of hidden spin polarization of bright and momentum-forbidden dark excitons. Our results reveal efficient chiroptical control of bright excitons' hidden spin polarization. Following optical photoexcitation, intervalley scattering between nonequivalent K-K^{'} valleys leads to a decay of bright excitons' hidden spin polarization. Conversely, the ultrafast formation of momentum-forbidden dark excitons acts as a local spin polarization reservoir, which could be used for spin injection in van der Waals heterostructures involving multilayer transition metal dichalcogenides.

4.
Mol Pharm ; 20(10): 4971-4983, 2023 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-37699256

RESUMEN

mRNA vaccines encoding a single spike protein effectively prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the emergence of SARS-CoV-2 variants leads to a wide range of immune evasion. Herein, a unique trivalent mRNA vaccine based on ancestral SARS-CoV-2, Delta, and Omicron variant spike receptor-binding domain (RBD) mRNAs was developed to tackle the immune evasion of the variants. First, three RBD mRNAs of SARS-CoV-2, Delta, and Omicron were coencapsulated into lipid nanoparticles (LNPs) by using microfluidic technology. After that, the physicochemical properties and time-dependent storage stability of the trivalent mRNA vaccine nanoformulation were tested by using dynamic light scattering (DLS). In vitro, the trivalent mRNA vaccine exhibited better lysosomal escape ability, transfection efficiency, and biocompatibility than did the commercial transfection reagent Lipo3000. In addition, Western blot analyses confirmed that the three RBD proteins can be detected in cells transfected with the trivalent mRNA vaccine. Furthermore, ex vivo imaging analysis indicated that the livers of BALB/c mice had the strongest protein expression levels after intramuscular (IM) injection. Using a prime-boost strategy, this trivalent vaccine elicited robust humoral and T-cell immune responses in both the high-dose and low-dose groups and showed no toxicity in BALB/c mice. Three specific IgG antibodies in the high-dose group against SARS-CoV-2, Delta, and Omicron variants approached ∼1/1,833,333, ∼1/1,866,667, and ∼1/925,000, respectively. Taken together, two doses of inoculation with the trivalent mRNA vaccine may provide broad and effective immunization responses against SARS-CoV-2 and variants.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Ratones , Humanos , SARS-CoV-2/genética , Vacunas contra la COVID-19 , COVID-19/prevención & control , Inmunización , Vacunas de ARNm , Anticuerpos Neutralizantes
5.
Bioorg Med Chem ; 78: 117135, 2023 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-36577327

RESUMEN

Vascular endothelial growth factor A (VEGFA) plays an important role in the healing of skin wound. However, the application of VEGFA protein in clinic is limited because of its high cost manufacturing, complicated purification and poor pharmacokinetic profile. Herein, we developed nucleoside-modified mRNA encoding VEGFA encapsulated ionizable lipid nanoparticles (LNP) to improve angiogenesis and increase wound healing rate. First, VEGFA mRNA was synthesized by an in vitro transcription (IVT) method. After that, VEGFA mRNA-LNP was prepared by encapsulating mRNA in ionizable lipid based nanoparticles via a microfluidic mixer. The physicochemical properties of VEGFA mRNA-LNP were investigated via dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results showed that the VEGFA mRNA-LNP possessed regular spherical morphology with an average size of 112.67 nm and a negative Zeta potential of -3.43 mV. The LNP delivery system had excellent lysosome escape capability and high transfection efficiency. ELISA and Western Blot analysis indicated that the mRNA-LNP could express VEGFA protein in Human umbilical vein endothelial cells (HUVECs). Besides, endothelial tube formation, cell proliferation and scratch assays were performed. The results revealed VEGFA mRNA-LNP boosted angiogenesis, cell proliferation and cell migration by expressing VEGFA protein. Finally, C57BL/6 mouse model of skin wound was established and intradermally treated with VEGFA mRNA-LNP. The VEGFA mRNA-LNP treated wounds were almost healed with an average wound size of 1.56 mm2 compared with the blank of 18.66 mm2 after 9 days. The results indicated that the VEGFA mRNA-LNP was able to significantly expedite wound healing. Histological analysis further demonstrated tissue epithelialization, collagen deposition and enhancement of vascular density after treatment. Taken together, VEGFA mRNA-LNP can be uptaken by cells to express protein effectively and promote wound healing, which may provide a promising strategy for clinical remedy.


Asunto(s)
Nanopartículas , Factor A de Crecimiento Endotelial Vascular , Ratones , Animales , Humanos , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , ARN Mensajero/genética , Ratones Endogámicos C57BL , Cicatrización de Heridas , Nanopartículas/química , Células Endoteliales de la Vena Umbilical Humana/metabolismo
6.
Perfusion ; : 2676591231163014, 2023 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-36959776

RESUMEN

OBJECTIVE: To verify the administration of a new nano delivery system coated with Tirofiban on preventing early thrombosis in vein graft. METHODS: Forty New Zealand white rabbits were randomly divided into five groups with eight rabbits in each group. The rabbits of all groups underwent jugular vein transplantation, except group I with only neck opening and closing operation. Vein grafts of group II were preprocessed by intravenous injection of normal saline; group III were preprocessed by tirofiban alone; group IV were preprocessed by unloaded nanoparticles of PLGA-PEG; group V were preprocessed by PLGA-PEG coated with tirofiban. Coagulation and platelet function of peripheral and vein graft blood were detected at 1, 2, 4, 12 h and 1, 3, 7, 10, 14 days after operation. Patency rate of vein graft and blood flow index were measured by vascular ultrasound at third, seventh, 10th, and 14th days after operation; two rabbits in each group were randomly sacrificed at the corresponding time of detection. Pathological differences of vein grafts were observed by HE stainin. RESULTS: The patency rate of vein grafts in group V was significantly higher than that in group II to IV. The platelet and platelet aggregation rate in group V were inhibited in vein graft blood significantly. The post-operative PT and APTT in vein graft blood in group V were increased obviously while the FBG, D-dimer and FDP were significantly inhibited. Except group I, the lumen loss rate of vein grafts in group V was significantly lower than that in other groups, and vein graft blood in group V had a significant lower expression of platelet P-selectin and GP IIb/IIIa receptor than that in other groups. CONCLUSION: This study proves that PEG-PLGA coated with tirofiban can effectively prevent early vein graft stenosis from thrombosis by inhibition of platelet function, coagulation function.

7.
Nano Lett ; 22(13): 5420-5426, 2022 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-35709372

RESUMEN

Two-dimensional quantum spin Hall (QSH) insulators are a promising material class for spintronic applications based on topologically protected spin currents in their edges. Yet, they have not lived up to their technological potential, as experimental realizations are scarce and limited to cryogenic temperatures. These constraints have also severely restricted characterization of their dynamical properties. Here, we report on the electron dynamics of the novel room-temperature QSH candidate bismuthene after photoexcitation using time- and angle-resolved photoemission spectroscopy. We map the transiently occupied conduction band and track the full relaxation pathway of hot photocarriers. Intriguingly, we observe photocarrier lifetimes much shorter than those in conventional semiconductors. This is ascribed to the presence of topological in-gap states already established by local probes. Indeed, we find spectral signatures consistent with these earlier findings. Demonstration of the large band gap and the view into photoelectron dynamics mark a critical step toward optical control of QSH functionalities.

8.
Int J Mol Sci ; 24(18)2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37762432

RESUMEN

Soybean (Glycine max (L.) Merr.) is an important source of plant protein, the nutritional quality of which is considerably affected by the content of the sulfur-containing amino acid, methionine (Met). To improve the quality of soybean protein and increase the Met content in seeds, soybean cystathionine γ-synthase 2 (GmCGS2), the first unique enzyme in Met biosynthesis, was overexpressed in the soybean cultivar "Jack", producing three transgenic lines (OE3, OE4, and OE10). We detected a considerable increase in the content of free Met and other free amino acids in the developing seeds of the three transgenic lines at the 15th and 75th days after flowering (15D and 75D). In addition, transcriptome analysis showed that the expression of genes related to Met biosynthesis from the aspartate-family pathway and S-methyl Met cycle was promoted in developing green seeds of OE10. Ultimately, the accumulation of total amino acids and soluble proteins in transgenic mature seeds was promoted. Altogether, these results indicated that GmCGS2 plays an important role in Met biosynthesis, by providing a basis for improving the nutritional quality of soybean seeds.


Asunto(s)
Aminoácidos , Glycine max , Glycine max/metabolismo , Aminoácidos/metabolismo , Proteínas de Soja/genética , Proteínas de Soja/metabolismo , Proteínas de Plantas/metabolismo , Semillas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Regulación de la Expresión Génica de las Plantas
9.
Mol Pharm ; 19(12): 4588-4600, 2022 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-35731922

RESUMEN

Protein kinase N3 (PKN3), by virtue of its abnormal expression in prostate cells, has been widely used as a target of RNAi (shRNA, siRNA, miRNA) therapy. The major challenges of PKN3 RNAi therapy lie in how to design effective interference sequences and delivery systems. Herein, new PKN3 shRNA sequences (shPKN3-2459 and shPKN3-3357) were designed, and bioreducible, biodegradable, ionizable lipid-based nanoparticles were developed for shPKN3 delivery. First, an ionizable lipid (DDA-SS-DMA) bridged with disulfide bond and ester bonds was synthesized by a three-step reaction and confirmed by MS, 1H NMR, and 13C NMR. The ionizable lipid was mixed with cholesterol, DSPC, PEG-lipid, and shPKN3 by a microfluidic mixer to prepare lipid nanoparticles (LNP-shPKN3) which were characterized by DLS and TEM. Afterward, the pH and glutathione (GSH)-responsiveness of the DDA-SS-DMA based LNP delivery system were investigated by lysosome escape and gel electrophoresis assays. Compared with the commercial transfection reagent Lipo2000, the DDA-SS-DMA based delivery system showed higher transfection efficiency and lower toxicity. Western blot analysis, invasion tests, and migration assays were performed to evaluate the silencing effect of shPKN3 in vitro. In in vivo studies, high tumor suppression (65.8%) and treatment safety were evident in the LNP-shPKN3-2459 treatment group. Taken together, the DDA-SS-DMA based delivery system encapsulating shPKN3-2459 showed significant antitumor efficacy and might be a promising formulation for the treatment of prostate cancer.


Asunto(s)
Nanopartículas , Neoplasias de la Próstata , Humanos , Masculino , Lípidos/química , Nanopartículas/química , Próstata , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapia , ARN Interferente Pequeño
10.
Bioorg Med Chem ; 69: 116884, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35752145

RESUMEN

Protein kinase N3 (PKN3), an AGC-family member, is often overexpressed in breast tumor cells. RNAi therapy is a promising approach to inhibit tumor growth by reducing the expression of PKN3. In this report, lipid nanoparticles encapsulated with new shRNA PKN3 (SS-LNP/shPKN3) with redox-responsiveness were developed in order to specifically down-regulate the expression of PKN3 for breast cancer treatment. The SS-LNP/shPKN3 was prepared by microfluidic method using disulfide bonds based ionizable lipid as main component. The as-prepared SS-LNP/shPKN3 lipid nanoparticles were characterized via using dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results indicated that the obtained SS-LNP/shPKN3 exhibited uniform particle size and regular spherical morphology. Moreover, glutathione (GSH) triggered release of shPKN3 confirmed the redox-responsiveness of the SS-LNP/shPKN3. Finally, the anti-tumor effect of SS-LNP/shPKN3 was evaluated against MDA-MB-231 cells and derived xenograft tumor bearing mice. It was found that the SS-LNP/shPKN3-2 had the highest PKN3 protein inhibition rate of 60.8% and tumor inhibition rate of 62.3%. Taken together, the SS-LNP/shPKN3 might be a potential therapeutic strategy for breast cancer.


Asunto(s)
Neoplasias de la Mama , Nanopartículas , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Liposomas , Ratones , Nanopartículas/química , Proteína Quinasa C , ARN Interferente Pequeño/química
11.
Artículo en Inglés | MEDLINE | ID: mdl-34491893

RESUMEN

Cells of bacterial strains G9T and 7MK23T, isolated from forest soil samples collected from the Dinghushan Biosphere Reserve, Guangdong Province, PR China, were Gram-stain-negative, aerobic and rod-shaped. Strain G9T was motile with single polar flagellum and grew at 12-37 °C (optimum, 28 °C), pH 4.5-8.0 (optimum, pH 6.0-7.5) and in the presence of 0-3.5 % NaCl (optimum, 1.5%, w/v); while strain 7MK23T was non-motile and grew at 12-42 °C (optimum, 28-33 °C), pH 2.5-8.5 (optimum, pH 4.5-6.5) and NaCl levels of 0-1.0 % (optimum, 0-0.5 %, w/v). Phylogenetic analysis based on 16S rRNA gene sequences revealed that both isolates fell within the cluster of the genus Dyella. The closely related species (with a 16S rRNA gene sequence similarity >98.65%) of strain G9T were Dyella terrae JS14-6T (99.0 %), D. kyungheensis THG-B117T (98.8 %) and D. amyloliquefaciens DHC06T (98.7 %) while that of strain 7MK23T were D. mobilis DHON07T (99.2 %) and D. flava DHOC52T (99.1 %), but the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strains G9T, 7MK23T and the closely related Dyella species listed above were in the ranges of 77.5-83.8 % and 22.0-27.0 %, much lower than the species demarcation lines of 95.5 and 70 %, respectively. Phylogenomic analyses using UBCG and Phylophlan also supported that these two strains represent two novel species of Dyella. The major fatty acids of strain G9T were iso-C15 : 0, iso-C17 : 1 ω9c and iso-C17 : 0 while that of strain 7MK23T were iso-C15 : 0 and anteiso-C15 : 0. Ubiquinone-8 was the only respiratory quinone detected in both strains. The polar lipids of strain G9T consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, and several unknown phospholipids, aminophospholipids, aminolipids and lipid while strain 7MK23T contained phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine and several unknown phospholipids and aminophospholipids. The DNA G+C contents of strains G9T and 7MK23T were 64.7 and 63.4 mol%, respectively. On the basis of 16S rRNA gene sequence phylogenetic and phylogenomic analyses as well as phenotypic data obtained, we propose that strains G9T and 7MK23T represent two novel species of the genus Dyella, for which the names Dyella telluris sp. nov. (type strain G9T=KACC 21725T=GDMCC 1.2132T) and Dyella acidiphila sp. nov. (type strain 7MK23T=KCTC 62739T=GDMCC 1.1446T) are proposed.


Asunto(s)
Bosques , Gammaproteobacteria/clasificación , Filogenia , Microbiología del Suelo , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Gammaproteobacteria/aislamiento & purificación , Hibridación de Ácido Nucleico , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
12.
Phys Rev Lett ; 125(9): 096401, 2020 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-32915590

RESUMEN

Time-resolved soft-x-ray photoemission spectroscopy is used to simultaneously measure the ultrafast dynamics of core-level spectral functions and excited states upon excitation of excitons in WSe_{2}. We present a many-body approximation for the Green's function, which excellently describes the transient core-hole spectral function. The relative dynamics of excited-state signal and core levels clearly show a delayed core-hole renormalization due to screening by excited quasifree carriers resulting from an excitonic Mott transition. These findings establish time-resolved core-level photoelectron spectroscopy as a sensitive probe of subtle electronic many-body interactions and ultrafast electronic phase transitions.

13.
Molecules ; 24(24)2019 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-31888183

RESUMEN

3-Alkyl-2-methoxypyrazines (MPs) contribute to the herbaceous flavor characteristics of wine and are generally considered associated with poor-quality wine. To control the MPs in grapes and wine, an accurate understanding of MP metabolism is needed. This review covers factors affecting people in the perception of MPs. Also, the history of O-methyltransferases is revisited, and the present review discusses the MP biosynthesis, degradation, and biochemical regulation. We propose the existence of a cycle between MPs and 3-alkyl-2-hydropyrazines (HPs), which proceeds via O-(de)methylation steps. This cycle governs the MP contents of wines, which make the cycle the key participant in MP regulation by genes, environmental stimuli, and microbes. In conclusion, a comprehensive metabolic pathway on which the HP-MP cycle is centered is proposed after gaining insight into their metabolism and regulation. Some directions for future studies on MPs are also proposed in this paper.


Asunto(s)
Pirazinas/química , Pirazinas/metabolismo , Vitis/química , Vitis/metabolismo , Vino/análisis , Catálisis , Fermentación , Regulación de la Expresión Génica , Redes y Vías Metabólicas , Metilación , Estructura Molecular , Odorantes , Percepción Olfatoria , Pirazinas/análisis , Olfato , Vitis/genética
14.
Nano Lett ; 17(5): 3312-3319, 2017 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-28437116

RESUMEN

Femtosecond optical pump-probe spectroscopy resolves hitherto unobserved coherent acoustic phonons in colloidal CdSe/CdS core/shell nanoplatelets (NPLs). With increasing pump fluence, the frequency of the in-plane acoustic mode increases from 5.2 to 10.7 cm-1, whereas the frequency of the out-of-plane mode remains at ∼20 cm-1. Analysis of the oscillation phases suggests that the coherent acoustic phonon generation mechanism transitions from displacive excitation to subpicosecond Auger hole trapping with increasing pump fluence. The measurements yield Huang-Rhys parameters of ∼10-2 for both acoustic modes. The weak electron-phonon coupling strengths favor the application of NPLs in optoelectronics.

15.
Nano Lett ; 15(10): 6875-82, 2015 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-26359970

RESUMEN

Recent observations of excitonic coherences within photosynthetic complexes suggest that quantum coherences could enhance biological light harvesting efficiencies. Here, we employ optical pump-probe spectroscopy with few-femtosecond pulses to observe an excitonic quantum coherence in CdSe nanocrystals, a prototypical artificial light harvesting system. This coherence, which encodes the high-speed migration of charge over nanometer length scales, is also found to markedly alter the displacement amplitudes of phonons, signaling dynamics in the non-Born-Oppenheimer regime.

16.
Tumour Biol ; 36(8): 6559-68, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25820701

RESUMEN

The deregulation of claudin-3 has been reported to correlate with the invasion and metastasis of various cancers, but little is known about its expression level and the prognostic value in squamous cell lung carcinoma (SqCC). The purpose of this study is to determine the expression levels and the prognostic value of claudin-3 in completely resected SqCC tissues, and the potential underlying mechanism. The protein expression of claudin-3, E-cadherin, ß-catenin, and vimentin in the tumor tissues from 103 patients with surgically resected SqCC was examined using immunohistochemistry, western blots, as well as semi-quantitative estimation. The claudin-3 protein level was significantly associated with E-cadherin, ß-catenin, and vimentin protein expression. A decreased claudin-3 protein level was significantly correlated with TNM stage, lymph node metastasis, and disease recurrence. Similarly, downregulation of E-cadherin was significantly correlated with lymph node metastasis and disease recurrence. Decreased ß-catenin expression also had a significant correlation with disease recurrence. Univariate analyses indicated that the T stage, lymph node metastasis, the TNM stage, and the expression of claudin-3, ß-catenin, and vimentin were significant predictors for overall survival (OS). Moreover, multivariate analyses demonstrated that the TNM stage and protein levels of claudin-3, ß-catenin, and vimentin were independent predictors for OS of SqCC patients. Claudin-3 plays an important role in the epithelial-mesenchymal transition of SqCC and might be used as a potential prognostic factor for SqCC.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Carcinoma de Pulmón de Células no Pequeñas/genética , Claudina-3/biosíntesis , Vimentina/biosíntesis , beta Catenina/biosíntesis , Adulto , Anciano , Biomarcadores de Tumor/genética , Cadherinas/biosíntesis , Cadherinas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Claudina-3/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Pronóstico , Vimentina/genética , beta Catenina/genética
17.
Cancer Cell ; 12(1): 36-51, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17613435

RESUMEN

While formation of higher-order oncogenic transcriptional complexes is critical for RARalpha fusion proteins in acute promyelocytic leukemia, the essential components and their roles in mediating transformation are still largely unknown. To this end, the present study demonstrates that homodimerization is not sufficient for RARalpha fusion-mediated transformation, which requires higher-order homotetramerization. Surprisingly, intrinsic homo-oligomeric DNA binding by the fusion proteins is also dispensable. Importantly, higher-order RXR/RARalpha fusion hetero-oligomeric complexes that aberrantly recruit transcriptional corepressors to downstream targets are essential for transformation. Intervention of RXR-dependent pathways by panRXR-agonists or RXRalpha shRNAs suppresses RARalpha fusion-mediated transformation. Taken together, these results define the oncogenic threshold for self-association and reveal the pathological significance of higher-order RARalpha fusion/RXR hetero-oligomeric complexes and their potential value as a therapeutic target.


Asunto(s)
Transformación Celular Neoplásica , Receptores de Ácido Retinoico/fisiología , Proteínas Recombinantes de Fusión/metabolismo , Receptor alfa X Retinoide/fisiología , Biopolímeros , Receptores de Ácido Retinoico/química , Receptor alfa de Ácido Retinoico , Factor de Transcripción STAT5/fisiología
18.
Cancer Cell ; 9(2): 95-108, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16473277

RESUMEN

Almost 100% of APL patients carry chimeric transcripts encoding truncated RARalpha fused to homo-oligomerization domains from partner proteins. To gain further insights into the cellular transformation mechanisms mediated by RARalpha fusion proteins, thorough structure/function analyses have been performed and identified the POZ homo-oligomerization domain as the minimal transformation domain that is necessary and sufficient for PLZF-RARalpha-mediated in vitro transformation of primary hematopoietic cells. A transformation-incompetent PLZF-RARalpha mutant defective in homo-oligomerization but not corepressor interaction could be rescued by synthetic FKBP-oligomerization domains. Furthermore, an artificial FKBP-RARalpha construct not only mimicked various biochemical properties of bona fide RARalpha fusion proteins but also mediated an ATRA-dependent transformation. Taken together, these findings endorse an oligomerization-dependent mechanism for RARalpha-mediated transformation and suggest a potential avenue for molecular therapy.


Asunto(s)
Transformación Celular Neoplásica , Sistema Hematopoyético/metabolismo , Sistema Hematopoyético/patología , Receptores de Ácido Retinoico/química , Receptores de Ácido Retinoico/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Animales , Biopolímeros/química , Biopolímeros/metabolismo , Proteínas de Unión al ADN/metabolismo , Ratones , Ratones Endogámicos C57BL , Imitación Molecular , Peso Molecular , Complejos Multiproteicos/química , Complejos Multiproteicos/metabolismo , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Co-Represor 2 de Receptor Nuclear , Proteínas de Fusión Oncogénica/química , Proteínas de Fusión Oncogénica/metabolismo , Fenotipo , Mutación Puntual/genética , Unión Proteica , Estructura Terciaria de Proteína , Receptores de Ácido Retinoico/genética , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Represoras/metabolismo , Receptor alfa de Ácido Retinoico
19.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 39(8): 849-54, 2014 Aug.
Artículo en Zh | MEDLINE | ID: mdl-25202955

RESUMEN

OBJECTIVE: To evaluate the influence of perioperative intravenous administration of ambroxol on pulmonary function, postoperative complications, postoperative hospital stay, and cost after video-assisted thoracic surgery lobectomy for lung cancer. METHODS: Sixty patients who underwent video-assisted thoracic surgery lobectomy for lung cancer in Xiangya Hospital, Central South University between May 2011 and May 2012 were randomly assigned into 2 groups: An ambroxol group (n=30) and a control group (n=30). In the ambroxol group, patients were given ambroxol (1 000 mg/d) on the day of operation and on the first 3 postoperative days. In control group, placebo was given. The pulmonary function tests, arterial blood gases, incidence of perioperative morbidity, postoperative mechanical ventilation time, duration of ICU stay, length and costs of postoperative hospital stay were compared between the 2 groups. RESULTS: The 2 groups were well matched for demographics and operative variables. The ambroxol group showed better the percent predicted forced expiratory volume in 1 second (FEV1%), the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC%), the percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) and arterial oxygen pressure than the control group. The postoperative pulmonary complications was significantly reduced, the duration of mechanical ventilation and the length of ICU stay were shortened, and the length and costs of postoperative hospital stay were significantly decreased in the ambroxol group compared with the control group (all P<0.05). CONCLUSION: Perioperative intravenous administration of ambroxol can improve the postoperative lung function, reduce the incidence of pulmonary complications, shorten the length of postoperative hospital stay, and lower the total cost of hospitalization after video-assisted thoracic surgery lobectomy for lung cancer.


Asunto(s)
Ambroxol/uso terapéutico , Neoplasias Pulmonares/cirugía , Pulmón/efectos de los fármacos , Cirugía Torácica Asistida por Video , Humanos , Tiempo de Internación , Oxígeno , Periodo Perioperatorio , Complicaciones Posoperatorias , Pruebas de Función Respiratoria , Volumen de Ventilación Pulmonar , Capacidad Vital
20.
Polymers (Basel) ; 16(2)2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38276693

RESUMEN

Water scarcity and water pollution have become increasingly severe, and therefore, the purification of water resources has recently garnered increasing attention. Given its position as a major water resource, the efficient purification of drinking water is of crucial importance. In this study, we adopted a phase transition method to prepare ZrO2/BCM (bamboo cellulose membranes), after which we developed IP-ZrO2/BC-NFM (bamboo cellulose nanofiltration membranes) through interfacial polymerization using piperazine (PIP) and tricarbonyl chloride (TMC). Subsequently, we integrated these two membranes to create a combined "ultrafiltration + nanofiltration" membrane process for the treatment of drinking water. The membrane combination process was conducted at 25 °C, with ultrafiltration at 0.1 MPa and nanofiltration at 0.5 MPa. This membrane combination, featuring "ultrafiltration + nanofiltration," had a significant impact on reducing turbidity, consistently maintaining the post-filtration turbidity of drinking water at or below 0.1 NTU. Furthermore, the removal rates for CODMN and ammonia nitrogen reached 75% and 88.6%, respectively, aligning with the standards for high-quality drinking water. In a continuous 3 h experiment, the nanofiltration unit exhibited consistent retention rates for Na2SO4 and bovine serum protein (BSA), with variations of less than 5%, indicating exceptional separation performance. After 9 h of operation, the water flux of the nanofiltration unit began to stabilize, with a decrease rate of approximately 25%, demonstrating that the "ultrafiltration + nanofiltration" membrane combination can maintain consistent performance during extended use. In conclusion, the "ultrafiltration + nanofiltration" membrane combination exhibited remarkable performance in the treatment of drinking water, offering a viable solution to address issues related to water scarcity and water pollution.

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