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1.
Opt Express ; 32(7): 11296-11306, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38570980

RESUMEN

Tabletop three-dimensional light field display is a kind of compelling display technology that can simultaneously provide stereoscopic vision for multiple viewers surrounding the lateral side of the device. However, if the flat panel light field display device is simply placed horizontally and displayed directly above, the visual frustum will be tilted and the 3D content outside the display panel will be invisible, the large oblique viewing angle will also lead to serious aberrations. In this paper, we demonstrate what we believe to be a new vertical spliced light field cave display system with an extended depth content. A separate optimization of different compound lens array attenuates the aberration from different oblique viewing angles, and a local heating fitting method is implemented to ensure the accuracy of fabrication process. The image coding method and the correction of the multiple viewpoints realize the correct construction of spliced voxels. In the experiment, a high-definition and precisely spliced 3D city terrain scene is demonstrated on the prototype with a correct oblique perspective in 100-degree horizontal viewing range. We envision that our research will provide more inspiration for future immersive large-scale glass-free virtual reality display technologies.

2.
Crit Rev Food Sci Nutr ; : 1-25, 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38556920

RESUMEN

The global aging population has brought about a pressing health concern: dysphagia. To effectively address this issue, we must develop specialized diets, such as thickened fluids made with polysaccharide-dextrin (e.g., water, milk, juices, and soups), which are crucial for managing swallowing-related problems like aspiration and choking for people with dysphagia. Understanding the flow behaviors of these thickened fluids is paramount, and it enables us to establish methods for evaluating their suitability for individuals with dysphagia. This review focuses on the shear and extensional flow properties (e.g., viscosity, yield stress, and viscoelasticity) and tribology (e.g., coefficient of friction) of polysaccharide-dextrin-based thickened fluids and highlights how dextrin inclusion influences fluid flow behaviors considering molecular interactions and chain dynamics. The flow behaviors can be integrated into the development of diverse evaluation methods that assess aspects such as flow velocity, risk of aspiration, and remaining fluid volume. In this context, the key in-vivo (e.g., clinical examination and animal model), in-vitro (e.g., the Cambridge Throat), and in-silico (e.g., Hamiltonian moving particles semi-implicit) evaluation methods are summarized. In addition, we explore the potential for establishing realistic assessment methods to evaluate the swallowing performance of thickened fluids, offering promising prospects for the future.

3.
Proc Natl Acad Sci U S A ; 118(15)2021 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-33876771

RESUMEN

Uterine leiomyosarcomas (uLMS) are aggressive tumors arising from the smooth muscle layer of the uterus. We analyzed 83 uLMS sample genetics, including 56 from Yale and 27 from The Cancer Genome Atlas (TCGA). Among them, a total of 55 Yale samples including two patient-derived xenografts (PDXs) and 27 TCGA samples have whole-exome sequencing (WES) data; 10 Yale and 27 TCGA samples have RNA-sequencing (RNA-Seq) data; and 11 Yale and 10 TCGA samples have whole-genome sequencing (WGS) data. We found recurrent somatic mutations in TP53, MED12, and PTEN genes. Top somatic mutated genes included TP53, ATRX, PTEN, and MEN1 genes. Somatic copy number variation (CNV) analysis identified 8 copy-number gains, including 5p15.33 (TERT), 8q24.21 (C-MYC), and 17p11.2 (MYOCD, MAP2K4) amplifications and 29 copy-number losses. Fusions involving tumor suppressors or oncogenes were deetected, with most fusions disrupting RB1, TP53, and ATRX/DAXX, and one fusion (ACTG2-ALK) being potentially targetable. WGS results demonstrated that 76% (16 of 21) of the samples harbored chromoplexy and/or chromothripsis. Clinically actionable mutational signatures of homologous-recombination DNA-repair deficiency (HRD) and microsatellite instability (MSI) were identified in 25% (12 of 48) and 2% (1 of 48) of fresh frozen uLMS, respectively. Finally, we found olaparib (PARPi; P = 0.002), GS-626510 (C-MYC/BETi; P < 0.000001 and P = 0.0005), and copanlisib (PIK3CAi; P = 0.0001) monotherapy to significantly inhibit uLMS-PDXs harboring derangements in C-MYC and PTEN/PIK3CA/AKT genes (LEY11) and/or HRD signatures (LEY16) compared to vehicle-treated mice. These findings define the genetic landscape of uLMS and suggest that a subset of uLMS may benefit from existing PARP-, PIK3CA-, and C-MYC/BET-targeted drugs.


Asunto(s)
Genotipo , Leiomiosarcoma/genética , Mutación , Fusión de Oncogenes , Neoplasias Uterinas/genética , Animales , Antineoplásicos/uso terapéutico , Femenino , Humanos , Leiomiosarcoma/tratamiento farmacológico , Redes y Vías Metabólicas , Ratones , Ratones Endogámicos C57BL , Terapia Molecular Dirigida/métodos , Ftalazinas/administración & dosificación , Ftalazinas/uso terapéutico , Piperazinas/administración & dosificación , Piperazinas/uso terapéutico , Pirimidinas/administración & dosificación , Pirimidinas/uso terapéutico , Quinazolinas/administración & dosificación , Quinazolinas/uso terapéutico , Neoplasias Uterinas/tratamiento farmacológico
4.
Nano Lett ; 23(2): 523-532, 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36622363

RESUMEN

Ultralong carbon nanotubes (CNTs) are in huge demand in many cutting-edge fields due to their macroscale lengths, perfect structures, and extraordinary properties, while their practical application is limited by the difficulties in their mass production. Herein, we report the synthesis of ultralong CNTs with a dramatically increased yield by a simple but efficient substrate interception and direction strategy (SIDS), which couples the advantages of floating-catalyst chemical vapor deposition with the flying-kite-like growth mechanism of ultralong CNTs. The SIDS-assisted approach prominently improves the catalyst utilization and significantly increases the yield. The areal density of the ultralong CNT arrays with length of over 1 cm reached a record-breaking value of ∼6700 CNTs mm-1, which is 2-3 orders of magnitude higher than the previously reported values obtained by traditional methods. The SIDS provides a solution for synthesizing high-quality ultralong CNTs with high yields, laying the foundation for their mass production.

5.
J Sci Food Agric ; 104(7): 4371-4382, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38459765

RESUMEN

BACKGROUND: Whole-grain rice noodles are a kind of healthy food with rich nutritional value, and their product quality has a notable impact on consumer acceptability. The quality evaluation model is of great significance to the optimization of product quality. However, there are few methods that can establish a product quality prediction model with multiple preparation conditions as inputs and various quality evaluation indexes as outputs. In this study, an artificial neural network (ANN) model based on a backpropagation (BP) algorithm was used to predict the comprehensive quality changes of whole-grain rice noodles under different preparation conditions, which provided a new way to improve the quality of extrusion rice products. RESULTS: The results showed that the BP-ANN using the Levenberg-Marquardt algorithm and the optimal topology (4-11-8) gave the best performance. The correlation coefficients (R2) for the training, validation, testing, and global data sets of the BP neural network were 0.927, 0.873, 0.817, and 0.903, respectively. In the validation test, the percentage error in the quality prediction of whole-grain rice noodles was within 10%, indicating that the BP-ANN could accurately predict the quality of whole-grain rice noodles prepared under different conditions. CONCLUSION: This study showed that the quality prediction model of whole-grain rice noodles based on the BP-ANN algorithm was effective, and suitable for predicting the quality of whole-grain rice noodles prepared under different conditions. © 2024 Society of Chemical Industry.


Asunto(s)
Oryza , Redes Neurales de la Computación , Algoritmos , Granos Enteros , Valor Nutritivo
6.
Opt Express ; 31(20): 32273-32286, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37859034

RESUMEN

Tabletop light field displays are compelling display technologies that offer stereoscopic vision and can present annular viewpoint distributions to multiple viewers around the display device. When employing the lens array to realize the of integral imaging tabletop light field display, there is a critical trade-off between the increase of the angular resolution and the spatial resolution. Moreover, as the viewers are around the device, the central viewing range of the reconstructed 3D images are wasteful. In this paper, we explore what we believe to be a new method for realizing tabletop flat-panel light field displays to improve the efficiency of the pixel utilization and the angular resolution of the tabletop 3D display. A 360-degree directional micro prism array is newly designed to refract the collimated light rays to different viewing positions and form viewpoints, then a uniform 360-degree annular viewpoint distribution can be accurately formed. In the experiment, a micro prism array sample is fabricated to verify the performance of the proposed tabletop flat-panel light field display system. One hundred viewpoints are uniformly distributed in the 360-degree viewing area, providing a full-color, smooth parallax 3D scene.

7.
Nano Lett ; 22(9): 3713-3720, 2022 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-35471846

RESUMEN

Transition metal oxides (TMOs) are promising inorganic electrochromic materials (ECMs) that can be widely used in electronic displays and adaptive camouflage. However, there are still huge challenges for TMOs to simultaneously achieve multicolor transformation capability and good cycling stability. Herein, we assemble Au-modified (0.01 wt %) VxO2x+1 (x > 2) nanoflowers (Au@VxO2x+1 NFs) composed of two-dimensional porous nanosheets containing two valences states of vanadium (V4+ and V5+). The Au@VxO2x+1 NFs exhibits outstanding electrochromic performance with five reversible color transformations (orange, yellow, green, gray, and blue) at a voltage less than 1.5 V and excellent cycling stability (2000 cycles without significant decay). To the best of our knowledge, this is the first time that a single vanadium oxide ECM, rather than a device, realizes five color changes. This work provides a feasible way for the efficient preparation of multicolor electrochromic TMOs. The newly developed Au@VxO2x+1 NFs demonstrate the potential application in adaptive camouflage.

8.
J Am Chem Soc ; 144(6): 2694-2704, 2022 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-35104401

RESUMEN

The development of high-efficiency and durable bifunctional electrocatalysts for both the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is critical for the widespread application of rechargeable zinc-air (Zn-air) batteries. This calls for rational screening of targeted ORR/OER components and precise control of their atomic and electronic structures to produce synergistic effects. Here, we report a Mn-doped RuO2 (Mn-RuO2) bimetallic oxide with atomic-scale dispersion of Mn atoms into the RuO2 lattice, which exhibits remarkable activity and super durability for both the ORR and OER, with a very low potential difference (ΔE) of 0.64 V between the half-wave potential of ORR (E1/2) and the OER potential at 10 mA cm-2 (Ej10) and a negligible decay of E1/2 and Ej10 after 250 000 and 30 000 CV cycles for ORR and OER, respectively. Moreover, Zn-air batteries using the Mn-RuO2 catalysts exhibit a high power density of 181 mW cm-2, low charge/discharge voltage gaps of 0.69/0.96/1.38 V, and ultralong lifespans of 15 000/2800/1800 cycles (corresponding to 2500/467/300 h operation time) at a current density of 10/50/100 mA cm-2, respectively. Theoretical calculations reveal that the excellent performances of Mn-RuO2 is mainly due to the precise optimization of valence state and d-band center for appropriate adsorption energy of the oxygenated intermediates.

9.
Proc Natl Acad Sci U S A ; 116(45): 22730-22736, 2019 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-31624127

RESUMEN

The prognosis of advanced/recurrent cervical cancer patients remains poor. We analyzed 54 fresh-frozen and 15 primary cervical cancer cell lines, along with matched-normal DNA, by whole-exome sequencing (WES), most of which harboring Human-Papillomavirus-type-16/18. We found recurrent somatic missense mutations in 22 genes (including PIK3CA, ERBB2, and GNAS) and a widespread APOBEC cytidine deaminase mutagenesis pattern (TCW motif) in both adenocarcinoma (ACC) and squamous cell carcinomas (SCCs). Somatic copy number variants (CNVs) identified 12 copy number gains and 40 losses, occurring more often than expected by chance, with the most frequent events in pathways similar to those found from analysis of single nucleotide variants (SNVs), including the ERBB2/PI3K/AKT/mTOR, apoptosis, chromatin remodeling, and cell cycle. To validate specific SNVs as targets, we took advantage of primary cervical tumor cell lines and xenografts to preclinically evaluate the activity of pan-HER (afatinib and neratinib) and PIK3CA (copanlisib) inhibitors, alone and in combination, against tumors harboring alterations in the ERBB2/PI3K/AKT/mTOR pathway (71%). Tumors harboring ERBB2 (5.8%) domain mutations were significantly more sensitive to single agents afatinib or neratinib when compared to wild-type tumors in preclinical in vitro and in vivo models (P = 0.001). In contrast, pan-HER and PIK3CA inhibitors demonstrated limited in vitro activity and were only transiently effective in controlling in vivo growth of PIK3CA-mutated cervical cancer xenografts. Importantly, combinations of copanlisib and neratinib were highly synergistic, inducing long-lasting regression of tumors harboring alterations in the ERBB2/PI3K/AKT/mTOR pathway. These findings define the genetic landscape of cervical cancer, suggesting that a large subset of cervical tumors might benefit from existing ERBB2/PIK3CA/AKT/mTOR-targeted drugs.


Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I/genética , Secuenciación del Exoma , Mutación , Receptor ErbB-2/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/terapia , Animales , Línea Celular Tumoral , Terapia Combinada , Variaciones en el Número de Copia de ADN , Femenino , Xenoinjertos , Humanos , Polimorfismo de Nucleótido Simple , Neoplasias del Cuello Uterino/patología
10.
Nano Lett ; 21(22): 9633-9641, 2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-34761938

RESUMEN

Designing high-performance trifunctional electrocatalysts for ORR/OER/HER with outstanding activity and stability for each reaction is quite significant yet challenging for renewable energy technologies. Herein, a highly efficient and durable trifunctional electrocatalyst RuCoOx is prepared by a unique one-pot glucose-blowing approach. Remarkably, RuCoOx catalyst exhibits a small potential difference (ΔE) of 0.65 V and low HER overpotential of 37 mV (10 mA cm-2), as well as a negligible decay of overpotential after 200 000/10 000/10 000 CV cycles for ORR/OER/HER, all of which show overwhelming superiorities among the advanced trifunctional electrocatalysts. When used in liquid rechargeable Zn-air batteries and water splitting electrolyzer, RuCoOx exhibits high efficiency and outstanding durability even at quite large current density. Such excellent performance can be attributed to the rational combination of targeted ORR/OER/HER active sites into one electrocatalyst based on the double-phase coupling strategy, which induces sufficient electronic structure modulation and synergistic effect for enhanced trifunctional properties.

11.
Compr Rev Food Sci Food Saf ; 21(4): 3244-3273, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35686475

RESUMEN

Nowadays, resulting from disordered glucose and lipid metabolism, metabolic diseases (e.g., hyperglycemia, type 2 diabetes, and obesity) are among the most serious health issues facing humans worldwide. Increasing evidence has confirmed that dietary intervention (with healthy foods) is effective at regulating the metabolic syndrome. Whole grain rice (WGR) rich in dietary fiber and many bioactive compounds (e.g., γ-amino butyric acid, γ-oryzanol, and polyphenols) can not only inhibit starch digestion and prevent rapid increase in the blood glucose level, but also reduce oxidative stress and damage to the liver, thereby regulating glucose and lipid metabolism. The rate of starch digestion is directly related to the blood glucose level in the organism after WGR intake. Therefore, the effects of different factors (e.g., additives, cooking, germination, and physical treatments) on WGR starch digestibility are examined in this review. In addition, the mechanisms from human and animal experiments regarding the correlation between the intake of WGR or its products and the lowered blood glucose and lipid levels and the reduced incidence of diabetes and obesity are discussed. Moreover, information on developing WGR products with the health benefits is provided.


Asunto(s)
Diabetes Mellitus Tipo 2 , Oryza , Glucemia/metabolismo , Glucosa , Humanos , Metabolismo de los Lípidos , Obesidad , Oryza/metabolismo , Almidón , Granos Enteros
12.
Angew Chem Int Ed Engl ; 61(21): e202116059, 2022 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-35261133

RESUMEN

Achieving efficient catalytic conversion over a heterogeneous catalyst with excellent resistance against leaching is still a grand challenge for sustainable chemical synthesis in aqueous solution. Herein, we devised a single-atom Pt1 /hydroxyapatite (HAP) catalyst via a simple hydrothermal strategy. Gratifyingly, this robust Pt1 /HAP catalyst exhibits remarkable catalytic selectivity and catalyst stability for the selective oxidation of C2 -C4 polyols to corresponding primary hydroxy acids. It is found that the Pt-(O-P) linkages with strong electron-withdrawing function of PO4 3- (Pt1 -OPO4 3- pair active site) not only realize the activation of the C-H bond, but also destabilize the transition state from adsorbed hydroxy acids toward the C-C cleavage, resulting in the sharply increased selectivity of hydroxy acids. Moreover, the strong PO4 3- -coordination effect provides electrostatic stabilization for single-atom Pt, ensuring the highly efficient catalysis of Pt1 /HAP for over 160 hours with superior leaching resistance.

13.
Am J Hum Genet ; 102(6): 1031-1047, 2018 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-29754769

RESUMEN

Analysis of de novo mutations (DNMs) from sequencing data of nuclear families has identified risk genes for many complex diseases, including multiple neurodevelopmental and psychiatric disorders. Most of these efforts have focused on mutations in protein-coding sequences. Evidence from genome-wide association studies (GWASs) strongly suggests that variants important to human diseases often lie in non-coding regions. Extending DNM-based approaches to non-coding sequences is challenging, however, because the functional significance of non-coding mutations is difficult to predict. We propose a statistical framework for analyzing DNMs from whole-genome sequencing (WGS) data. This method, TADA-Annotations (TADA-A), is a major advance of the TADA method we developed earlier for DNM analysis in coding regions. TADA-A is able to incorporate many functional annotations such as conservation and enhancer marks, to learn from data which annotations are informative of pathogenic mutations, and to combine both coding and non-coding mutations at the gene level to detect risk genes. It also supports meta-analysis of multiple DNM studies, while adjusting for study-specific technical effects. We applied TADA-A to WGS data of ∼300 autism-affected family trios across five studies and discovered several autism risk genes. The software is freely available for all research uses.


Asunto(s)
Mapeo Cromosómico , Predisposición Genética a la Enfermedad , Mutación/genética , Estadística como Asunto , Secuenciación Completa del Genoma , Trastorno Autístico/genética , Calibración , Elementos de Facilitación Genéticos/genética , Humanos , Anotación de Secuencia Molecular , Tasa de Mutación , Empalme del ARN/genética , Factores de Riesgo , Secuenciación del Exoma
14.
Chem Rec ; 21(7): 1792-1810, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33973696

RESUMEN

Catalytic transfer hydrogenolysis, using liquid H-donors in the absence of pressurized H2 under mild temperatures, is regarded as the most important technology to substitute traditional hydrogenation processes in industry. Despite decade development with several breakthroughs in catalyst design, the reaction mechanism involved in H2 generation and subsequent hydrogenolysis reactions is still under debate. In this review, transfer hydrogenolysis of glycerol, as a representative example, on metallic catalysts is revised critically with respect to surface reaction mechanism and catalyst design. The detailed reaction pathways for propanol, methanol, formic acid and ethanol for H2 generation have been discussed systematically. In particular, reaction mechanism for catalytic C-H cleavage, H spillover/transfer and C-O cleavage reaction steps will be critically revised with experimental and theoretical results in literature. Insights into reaction pathways, mechanism and H2 transfer efficiency and structure-performance relation for Pd, Cu and Ni catalysts will be provided for future development of catalyst manufacture and process development. The outcome of this work is useful for successful implementation of bio-refinery.

15.
Proc Natl Acad Sci U S A ; 113(8): 2170-5, 2016 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-26864202

RESUMEN

The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10(-4)), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10(-17)); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers.


Asunto(s)
Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Mutación , Anciano , Carcinoma de Células Renales/clasificación , Desdiferenciación Celular/genética , Reparación de la Incompatibilidad de ADN/genética , Proteínas de Unión al ADN , Exoma , Femenino , Genes p53 , Humanos , Neoplasias Renales/clasificación , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Proteínas Nucleares/genética , Oncogenes , Polimorfismo de Nucleótido Simple , Pronóstico , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética
16.
Proc Natl Acad Sci U S A ; 113(43): 12238-12243, 2016 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-27791010

RESUMEN

Carcinosarcomas (CSs) of the uterus and ovary are highly aggressive neoplasms containing both carcinomatous and sarcomatous elements. We analyzed the mutational landscape of 68 uterine and ovarian CSs by whole-exome sequencing. We also performed multiregion whole-exome sequencing comprising two carcinoma and sarcoma samples from six tumors to resolve their evolutionary histories. The results demonstrated that carcinomatous and sarcomatous elements derive from a common precursor having mutations typical of carcinomas. In addition to mutations in cancer genes previously identified in uterine and ovarian carcinomas such as TP53, PIK3CA, PPP2R1A, KRAS, PTEN, CHD4, and BCOR, we found an excess of mutations in genes encoding histone H2A and H2B, as well as significant amplification of the segment of chromosome 6p harboring the histone gene cluster containing these genes. We also found frequent deletions of the genes TP53 and MBD3 (a member with CHD4 of the nucleosome remodeling deacetylase complex) and frequent amplification of chromosome segments containing the genes PIK3CA, TERT, and MYC Stable transgenic expression of H2A and H2B in a uterine serous carcinoma cell line demonstrated that mutant, but not wild-type, histones increased expression of markers of epithelial-mesenchymal transition (EMT) as well as tumor migratory and invasive properties, suggesting a role in sarcomatous transformation. Comparison of the phylogenetic relationships of carcinomatous and sarcomatous elements of the same tumors demonstrated separate lineages leading to these two components. These findings define the genetic landscape of CSs and suggest therapeutic targets for these highly aggressive neoplasms.


Asunto(s)
Histonas/genética , Neoplasias Ováricas/genética , Proteína p53 Supresora de Tumor/genética , Neoplasias Uterinas/genética , Anciano , Anciano de 80 o más Años , Carcinosarcoma/genética , Carcinosarcoma/patología , Fosfatidilinositol 3-Quinasa Clase I/genética , Proteínas de Unión al ADN/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Mutación , Neoplasias Ováricas/patología , Fosfohidrolasa PTEN/genética , Telomerasa/genética , Neoplasias Uterinas/patología
17.
Br J Cancer ; 115(3): 303-11, 2016 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-27351214

RESUMEN

BACKGROUND: Clinical options for patients harbouring advanced/recurrent uterine serous carcinoma (USC), an aggressive variant of endometrial tumour, are very limited. Next-generation sequencing (NGS) data recently demonstrated that cyclin E1 (CCNE1) gene amplification and pik3ca driver mutations are common in USC and may therefore represent ideal therapeutic targets. METHODS: Cyclin E1 expression was evaluated by immunohistochemistry (IHC) on 95 USCs. The efficacy of the cyclin-dependent kinase 2/9 inhibitor CYC065 was assessed on multiple primary USC cell lines with or without CCNE1 amplification. Cell-cycle analyses and knockdown experiments were performed to assess CYC065 targeting specificity. Finally, the in vitro and in vivo activity of CYC065, Taselisib (a PIK3CA inhibitor) and their combinations was tested on USC xenografts derived from CCNE1-amplified/pik3ca-mutated USCs. RESULTS: We found that 89.5% of the USCs expressed CCNE1. CYC065 blocked cells in the G1 phase of the cell cycle and inhibited cell growth specifically in CCNE1-overexpressing USCs. Cyclin E1 knockdown conferred increased resistance to CYC065, whereas CYC065 treatment of xenografts derived from CCNE1-amplified USCs significantly reduced tumour growth. The combination of CYC065 and Taselisib demonstrated synergistic effect in vitro and was significantly more effective than single-agent treatment in decreasing tumour growth in xenografts of CCNE1-amplified/pik3ca-mutated USCs. CONCLUSIONS: Dual CCNE1/PIK3CA blockade may represent a novel therapeutic option for USC patients harbouring recurrent CCNE1-amplified/pi3kca-mutated tumours.


Asunto(s)
Ciclina E/genética , Mutación , Proteínas Oncogénicas/genética , Fosfatidilinositol 3-Quinasas/genética , Neoplasias Uterinas/tratamiento farmacológico , Animales , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasa Clase I , Ciclina E/metabolismo , Variaciones en el Número de Copia de ADN , Femenino , Técnicas de Silenciamiento del Gen , Xenoinjertos , Humanos , Hibridación Fluorescente in Situ , Técnicas In Vitro , Ratones , ARN Mensajero/genética , Análisis de Matrices Tisulares , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismo
18.
Proc Natl Acad Sci U S A ; 110(8): 2916-21, 2013 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-23359684

RESUMEN

Uterine serous carcinoma (USC) is a biologically aggressive subtype of endometrial cancer. We analyzed the mutational landscape of USC by whole-exome sequencing of 57 cancers, most of which were matched to normal DNA from the same patients. The distribution of the number of protein-altering somatic mutations revealed that 52 USC tumors had fewer than 100 (median 36), whereas 5 had more than 3,000 somatic mutations. The mutations in these latter tumors showed hallmarks of defects in DNA mismatch repair. Among the remainder, we found a significantly increased burden of mutation in 14 genes. In addition to well-known cancer genes (i.e., TP53, PIK3CA, PPP2R1A, KRAS, FBXW7), there were frequent mutations in CHD4/Mi2b, a member of the NuRD-chromatin-remodeling complex, and TAF1, an element of the core TFIID transcriptional machinery. Additionally, somatic copy-number variation was found to play an important role in USC, with 13 copy-number gains and 12 copy-number losses that occurred more often than expected by chance. In addition to loss of TP53, we found frequent deletion of a small segment of chromosome 19 containing MBD3, also a member of the NuRD-chromatin-modification complex, and frequent amplification of chromosome segments containing PIK3CA, ERBB2 (an upstream activator of PIK3CA), and CCNE1 (a target of FBXW7-mediated ubiquitination). These findings identify frequent mutation of DNA damage, chromatin remodeling, cell cycle, and cell proliferation pathways in USC and suggest potential targets for treatment of this lethal variant of endometrial cancer.


Asunto(s)
Variaciones en el Número de Copia de ADN , Mutación , Neoplasias Uterinas/genética , Secuencia de Aminoácidos , Animales , Disparidad de Par Base , Femenino , Humanos , Datos de Secuencia Molecular , Homología de Secuencia de Aminoácido
19.
Nat Genet ; 56(2): 336-347, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38279041

RESUMEN

Many methods have been developed to leverage expression quantitative trait loci (eQTL) data to nominate candidate genes from genome-wide association studies. These methods, including colocalization, transcriptome-wide association studies (TWAS) and Mendelian randomization-based methods; however, all suffer from a key problem-when assessing the role of a gene in a trait using its eQTLs, nearby variants and genetic components of other genes' expression may be correlated with these eQTLs and have direct effects on the trait, acting as potential confounders. Our extensive simulations showed that existing methods fail to account for these 'genetic confounders', resulting in severe inflation of false positives. Our new method, causal-TWAS (cTWAS), borrows ideas from statistical fine-mapping and allows us to adjust all genetic confounders. cTWAS showed calibrated false discovery rates in simulations, and its application on several common traits discovered new candidate genes. In conclusion, cTWAS provides a robust statistical framework for gene discovery.


Asunto(s)
Estudio de Asociación del Genoma Completo , Transcriptoma , Humanos , Transcriptoma/genética , Estudio de Asociación del Genoma Completo/métodos , Herencia Multifactorial/genética , Sitios de Carácter Cuantitativo/genética , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Predisposición Genética a la Enfermedad
20.
Food Res Int ; 184: 114274, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38609251

RESUMEN

Thermal processing with salt ions is widely used for the production of food products (such as whole grain food) containing protein and anthocyanin. To date, it is largely unexplored how salt ion presence during thermal processing regulates the practical performance of protein/anthocyanin binary system. Here, rice albumin (RA) and black rice anthocyanins (BRA) were used to prepare RA/BRA composite systems as a function of temperature (60-100 °C) and NaCl concentration (10-40 mM) or CaCl2 concentration (20 mM). It was revealed that the spontaneous complexing reaction between RA and BRA was driven by hydrophobic interactions and hydrogen bonds and becomes easier and more favorable at a higher temperature (≤90 °C), excessive temperature (100 °C), however, may result in the degradation of BRA. Moreover, the salt ion presence during thermal processing may bind with RA and BRA, respectively, which could restrict the interaction between BRA and RA. Additionally, the inclusion of Na+ or Ca2+ at 20 mM endowed the binary system with strengthened DPPH radical scavenging capacity (0.95 for Na+ and 0.99 for Ca2+). Notably, Ca2+ performed a greater impact on the stability of the system than Na+.


Asunto(s)
Oryza , Antocianinas , Albúminas , Cloruro de Sodio , Cloruro de Sodio Dietético , Grano Comestible , Iones
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