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1.
Artículo en Inglés | MEDLINE | ID: mdl-38700975

RESUMEN

Recently, Large Language Model based Autonomous System (LLMAS) has gained great popularity for its potential to simulate complicated behaviors of human societies. One of its main challenges is to present and analyze the dynamic events evolution of LLMAS. In this work, we present a visualization approach to explore the detailed statuses and agents' behavior within LLMAS. Our approach outlines a general pipeline that organizes raw execution events from LLMAS into a structured behavior model. We leverage a behavior summarization algorithm to create a hierarchical summary of these behaviors, arranged according to their sequence over time. Additionally, we design a cause trace method to mine the causal relationship between agent behaviors. We then develop AgentLens, a visual analysis system that leverages a hierarchical temporal visualization for illustrating the evolution of LLMAS, and supports users to interactively investigate details and causes of agents' behaviors. Two usage scenarios and a user study demonstrate the effectiveness and usability of our AgentLens.

2.
Curr Med Imaging ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38693743

RESUMEN

BACKGROUND: Congenital ileal atresia is a rare neonatal disease, the most common type of intestinal malformation in newborns, and one of the most common causes of congenital intestinal obstruction. It can cause various digestive system symptoms, including abdominal distension, vomiting, abnormal bowel movements, etc. In severe cases, it can be life-threatening. A prenatal ultrasound examination can assist clinical diagnosis of congenital ileal atresia, and those with a clear prenatal diagnosis should undergo surgical treatment after birth. CASE PRESENTATION: We have, herein, reported two cases of congenital ileal atresia, both of which showed fetal intestinal dilation (>7mm) and excessive amniotic fluid on prenatal ultrasound. Both newborns underwent surgical treatment after delivery and were confirmed to have congenital ileal atresia during surgery. Due to the different prenatal ultrasound manifestations of the two patients, they were divided into two different subtypes based on intraoperative manifestations. We observed significant differences in the prognosis of the two patients after surgery. CONCLUSION: Accurately locating and classifying ileal atresia using prenatal ultrasound is challenging; however, it plays an effective role in disease progression, gestational assessment, and prognosis. Accurately identifying intestinal diseases and/or the location of lesion sites through direct and indirect ultrasound findings in the fetal abdominal cavity is an important research direction for prenatal ultrasound.

3.
J Matern Fetal Neonatal Med ; 36(1): 2203792, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37121902

RESUMEN

Background: Ultrasound is key to evaluating placental function. However, traditional ultrasound examinations cannot evaluate the changes in the biomechanical properties of the placenta in vivo. As a non-invasive technique, shear wave elastography (SWE) can be used analyze the physiological and biomechanical properties of the placenta. Moreover, it can evaluate the pathological changes in early placental insufficiency in a more direct and sensitive manner.Objective: This study aimed to systematically introduce SWE in placental function evaluations.Materials and methods: The terms 'placenta', 'ultrasound', and 'elastography' were searched on Pubmed, Embase, and CNKI databases (Apr 2023); this review was limited to results including placental sonoelastography.Results: Twenty-six studies satisfied the inclusion criteria and were included in this review. Herein, we introduce the basic principle of SWE, analyze the factors affecting placental measurements, and summarize the prospects of clinical applications of SWE in the field of obstetrical diseases.Conclusion: The SWE technology demonstrates excellent clinical application value and research prospects in obstetrics, particularly in placental function evaluation, owing to its objective and repeatable quantitative operation.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Embarazo , Humanos , Femenino , Diagnóstico por Imagen de Elasticidad/métodos , Placenta/diagnóstico por imagen , Ultrasonografía/métodos
4.
Polymers (Basel) ; 15(2)2023 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-36679329

RESUMEN

To overcome the high flammability and brittleness of epoxy resins without sacrificing their glass transition temperature (Tg) and mechanical properties, three epoxy-terminated hyperbranched flame retardants (EHBFRs) with a rigid central core and different branches, named EHBFR-HB, EHBFR-HCM, and EHBFR-HBM, were synthesized. After chemical structure characterization, the synthesized EHBFRs were introduced into the diglycidyl ether of bisphenol A (DGEBA) and cured with 4, 4-diaminodiphenylmethane (DDM). The compatibility, thermal stability, mechanical properties, and flame retardancy of the resultant resins were evaluated. Results showed that all three EHBFRs could significantly improve the fire safety of cured resins, and 30 wt. % of EHBFRs (less than 1.0 wt. % phosphorus content) endowed cured DGEBA with a UL-94 V-0 rating. In addition, the increased rigidity of branches in EHBFRs could increase the flexural strength and modulus of cured resins, and the branches with appropriate rigidity were also beneficial for improving their room temperature impact strength and Tg.

5.
Cancer Res ; 82(12): 2281-2297, 2022 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-35442423

RESUMEN

Immunosuppressive elements within the tumor microenvironment, such as tumor-associated macrophages (TAM), can present a barrier to successful antitumor responses by cytolytic T cells. Here we employed preclinical syngeneic p53 null mouse models of triple-negative breast cancer (TNBC) to develop a treatment regimen that harnessed the immunostimulatory effects of low-dose cyclophosphamide coupled with the pharmacologic inhibition of TAMs using either a small-molecule CSF1R inhibitor or an anti-CSF1R antibody. This therapeutic combination was effective in treating several highly aggressive TNBC murine mammary tumor and lung metastasis models. Single-cell RNA sequencing characterized tumor-infiltrating lymphocytes including Th cells and antigen-presenting B cells that were highly enriched in responders to combination therapy. In one model that exhibited long-term posttreatment tumor regression, high-dimensional imaging techniques identified the close spatial localization of B220+/CD86+-activated B cells and CD4+ T cells in tertiary lymphoid structures that were present up to 6 weeks posttreatment. The transcriptional and metabolic heterogeneity of TAMs was also characterized in two closely related claudin-low/mesenchymal subtype tumor models with differential treatment responses. A murine TAM signature derived from the T12 model was highly conserved in human claudin-low breast cancers, and high expression of the TAM signature correlated with reduced overall survival in patients with breast cancer. This TAM signature may help identify human patients with claudin-low breast cancer that will benefit from the combination of cyclophosphamide and anti-CSF1R therapy. These studies illustrate the complexity of the tumor immune microenvironment and highlight different immune responses that result from rational immunotherapy combinations. SIGNIFICANCE: Immunostimulatory chemotherapy combined with pharmacologic inhibition of TAMs results in durable treatment responses elicited by Th cells and B cells in claudin-low TNBC models.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Animales , Linfocitos B , Claudinas/metabolismo , Claudinas/uso terapéutico , Ciclofosfamida/farmacología , Ciclofosfamida/uso terapéutico , Humanos , Macrófagos/metabolismo , Ratones , Linfocitos T Citotóxicos/patología , Neoplasias de la Mama Triple Negativas/patología , Microambiente Tumoral
6.
Cell Syst ; 12(8): 810-826.e4, 2021 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-34146472

RESUMEN

The recent advent of CRISPR and other molecular tools enabled the reconstruction of cell lineages based on induced DNA mutations and promises to solve the ones of more complex organisms. To date, no lineage reconstruction algorithms have been rigorously examined for their performance and robustness across dataset types and number of cells. To benchmark such methods, we decided to organize a DREAM challenge using in vitro experimental intMEMOIR recordings and in silico data for a C. elegans lineage tree of about 1,000 cells and a Mus musculus tree of 10,000 cells. Some of the 22 approaches submitted had excellent performance, but structural features of the trees prevented optimal reconstructions. Using smaller sub-trees as training sets proved to be a good approach for tuning algorithms to reconstruct larger trees. The simulation and reconstruction methods here generated delineate a potential way forward for solving larger cell lineage trees such as in mouse.


Asunto(s)
Benchmarking , Caenorhabditis elegans , Algoritmos , Animales , Caenorhabditis elegans/genética , Linaje de la Célula/genética , Simulación por Computador , Ratones
7.
Front Immunol ; 12: 653356, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33796116

RESUMEN

Background: Pemphigus is a rare but life-threatening autoimmune skin disease characterized by blistering on skin and/or mucous membranes. The physiological process of blister formation involves IgG antibodies against the desmogleins (Dsgs) and desmocollins (Dscs). Additional autoAbs have also been suggested to mediate the disease heterogeneity, such as anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies, the essential culprits of the immune system in autoimmune thyroid diseases. Purpose: To investigate the levels and antibody positivity of anti-TPO and anti-Tg antibodies in pemphigus patients. Methods: Antibody positivity and levels of anti-TPO and anti-Tg antibodies in pemphigus patients as compared to healthy controls were examined. A meta-analysis was conducted by reviewing six similar studies. Results: 98 Chinese pemphigus patients and 65 healthy controls were enrolled in the study. Our meta-analysis revealed a significant correlation between increased presence of positive anti-TPO and anti-Tg antibodies and pemphigus, particularly for pemphigus vulgaris (PV). Such correlation was also observed in our own hospitalized PV patients, but not in pemphigus foliaceus (PF) patients. In addition, the status of anti-TPO and anti-Tg antibodies were also compared between females and males within PV patients, PF patients or controls, as well as compared for females or males between pemphigus patients and controls. In the analysis of T cell counts, we found abnormal low CD3 + T cell counts (< 690 n/µl) were only detected in patients whose thyroid antibody levels were less than 20 IU/ml. Conclusion: Pemphigus patients showed higher levels and antibody positivity of anti-TPO and anti-Tg antibodies than healthy controls. Further investigations are needed to identify the pathogenic functions of these antibodies in pemphigus, as well as to identify the potential shared susceptibility genes.


Asunto(s)
Autoanticuerpos/sangre , Autoantígenos/inmunología , Yoduro Peroxidasa/inmunología , Proteínas de Unión a Hierro/inmunología , Pénfigo/inmunología , Tiroglobulina/inmunología , Adulto , Anciano , Autoanticuerpos/inmunología , Estudios de Casos y Controles , China , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Pénfigo/sangre , Estudios Retrospectivos , Adulto Joven
8.
Cell ; 184(9): 2471-2486.e20, 2021 04 29.
Artículo en Inglés | MEDLINE | ID: mdl-33878291

RESUMEN

Metastasis has been considered as the terminal step of tumor progression. However, recent genomic studies suggest that many metastases are initiated by further spread of other metastases. Nevertheless, the corresponding pre-clinical models are lacking, and underlying mechanisms are elusive. Using several approaches, including parabiosis and an evolving barcode system, we demonstrated that the bone microenvironment facilitates breast and prostate cancer cells to further metastasize and establish multi-organ secondary metastases. We uncovered that this metastasis-promoting effect is driven by epigenetic reprogramming that confers stem cell-like properties on cancer cells disseminated from bone lesions. Furthermore, we discovered that enhanced EZH2 activity mediates the increased stemness and metastasis capacity. The same findings also apply to single cell-derived populations, indicating mechanisms distinct from clonal selection. Taken together, our work revealed an unappreciated role of the bone microenvironment in metastasis evolution and elucidated an epigenomic reprogramming process driving terminal-stage, multi-organ metastases.


Asunto(s)
Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Metástasis de la Neoplasia , Neoplasias de la Próstata/patología , Microambiente Tumoral , Animales , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Proliferación Celular , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones Desnudos , Ratones SCID , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
9.
Dev Cell ; 56(8): 1100-1117.e9, 2021 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-33878299

RESUMEN

Estrogen receptor-positive (ER+) breast cancer exhibits a strong bone tropism in metastasis. How the bone microenvironment (BME) impacts ER signaling and endocrine therapy remains poorly understood. Here, we discover that the osteogenic niche transiently and reversibly reduces ER expression and activities specifically in bone micrometastases (BMMs), leading to endocrine resistance. As BMMs progress, the ER reduction and endocrine resistance may partially recover in cancer cells away from the osteogenic niche, creating phenotypic heterogeneity in macrometastases. Using multiple approaches, including an evolving barcoding strategy, we demonstrated that this process is independent of clonal selection, and represents an EZH2-mediated epigenomic reprogramming. EZH2 drives ER+ BMMs toward a basal and stem-like state. EZH2 inhibition reverses endocrine resistance. These data exemplify how epigenomic adaptation to BME promotes phenotypic plasticity of metastatic seeds, fosters intra-metastatic heterogeneity, and alters therapeutic responses. Our study provides insights into the clinical enigma of ER+ metastatic recurrences despite endocrine therapies.


Asunto(s)
Adaptación Fisiológica , Huesos/patología , Neoplasias de la Mama/patología , Receptores de Estrógenos/metabolismo , Microambiente Tumoral , Animales , Neoplasias Óseas/secundario , Neoplasias de la Mama/metabolismo , Comunicación Celular , Evolución Clonal , Modelos Animales de Enfermedad , Regulación hacia Abajo , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Femenino , Uniones Comunicantes/metabolismo , Genes Reporteros , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Células MCF-7 , Ratones , Micrometástasis de Neoplasia , Osteogénesis , Transducción de Señal
10.
Environ Technol ; 42(2): 306-317, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31169458

RESUMEN

The fly ash from a coal-fired power plants was modified with non-thermal plasma in air to improve the elemental mercury (Hg0) removal performance. The Hg0 adsorption experiments were implemented via a bench-scale fixed-bed reactor system. Brunauer-Emmett-Teller (BET), X-ray photoelectron spectroscopy (XPS), ultimate, X-ray diffraction (XRD) and XRF analysis were employed to characterize the fly ash. The effect of non-thermal plasma voltage and time on Hg0 removal efficiency was investigated. The results showed that fly ash had better Hg0 removal performance when treatment voltage was 3.0 kV and treatment time was 7 min. Furthermore, the results showed that non-thermal plasma treatment had little influence on the specific surface area. However, non-thermal plasma treatment increased the relative content of oxygen. XPS and temperature programmed desorption results indicated that Hg0 removal process included adsorption and oxidation of Hg0. Moreover, ester and carbonyl groups played extremely vital roles in the improvement of Hg0 removal performance, and their temperature programmed desorption peak occurred at around 250°C and 320°C, respectively.


Asunto(s)
Contaminantes Atmosféricos , Mercurio , Contaminantes Atmosféricos/análisis , Carbón Mineral , Ceniza del Carbón , Mercurio/análisis , Plasma/química , Centrales Eléctricas
11.
J Am Chem Soc ; 141(17): 6843-6847, 2019 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-30995028

RESUMEN

Converting elemental white phosphorus directly into organophosphorus or polyphosphorus is meaningful, challenging and attractive. The ate-complexes of aluminacyclopentadienes 1a,b react with P4 to afford selectively the cyclotetraphosphanes 2a,b featuring four newly formed P-C bonds and a planar square cyclo-P4 ring. Density functional theory calculations show that the conversion of tetrahedral P4 to planar cyclo-P4 moiety undergoes through an unexpected 1,1- P-insertion/Diels-Alder reaction/isomerization cascade process. The reaction of 2a with iodomethane or p-benzoquinone afforded the P-methylation product 3 and the metal-free cyclotetraphosphane 4, respectively. Interestingly, reduction of 4 generated the phospholyl anions 5 and 6 while treatment of 4 with iodomethane afforded the phospholyl cation 7.

12.
Chem Commun (Camb) ; 52(68): 10396-9, 2016 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-27481503

RESUMEN

A novel copper-catalyzed difluoromethylation of 2- or 3-propargylamide-substituted indoles with ICF2CO2Et via a radical cascade cyclization process is described. A wide substrate scope is compatible with the reaction conditions to synthesize mono- and bis-difluoromethylated indoloazepinone derivatives, which contain a seven-membered ring.

13.
Org Lett ; 18(11): 2664-7, 2016 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-27191858

RESUMEN

A novel, four-component synthetic strategy to synthesize a series of ß-difluoroalkyl unsaturated esters/amides with high regioslectivity is described. This Pd-catalyzed difluoroalkylation and carbonylation reaction can be carried out with simple starting materials. Through this protocol, two new C-C bonds (including one C-CF2 bond) and one C-O(N) bond are constructed simultaneously in a single step. The synthetic utility of this reaction system has been certified by the applicability to a wide scope of alkynes and nucleophiles. Preliminary mechanistic studies suggest that the difluoroalkyl radical pathway is involved in this reaction.

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