Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 409
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Cell ; 185(23): 4428-4447.e28, 2022 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-36318921

RESUMEN

Human brain development is underpinned by cellular and molecular reconfigurations continuing into the third decade of life. To reveal cell dynamics orchestrating neural maturation, we profiled human prefrontal cortex gene expression and chromatin accessibility at single-cell resolution from gestation to adulthood. Integrative analyses define the dynamic trajectories of each cell type, revealing major gene expression reconfiguration at the prenatal-to-postnatal transition in all cell types followed by continuous reconfiguration into adulthood and identifying regulatory networks guiding cellular developmental programs, states, and functions. We uncover links between expression dynamics and developmental milestones, characterize the diverse timing of when cells acquire adult-like states, and identify molecular convergence from distinct developmental origins. We further reveal cellular dynamics and their regulators implicated in neurological disorders. Finally, using this reference, we benchmark cell identities and maturation states in organoid models. Together, this captures the dynamic regulatory landscape of human cortical development.


Asunto(s)
Neurogénesis , Organoides , Embarazo , Femenino , Humanos , Adulto , Cromatina , Corteza Prefrontal , Análisis de la Célula Individual , Redes Reguladoras de Genes
2.
Cell ; 172(5): 1122-1131.e9, 2018 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-29474911

RESUMEN

The implementation of clinical-decision support algorithms for medical imaging faces challenges with reliability and interpretability. Here, we establish a diagnostic tool based on a deep-learning framework for the screening of patients with common treatable blinding retinal diseases. Our framework utilizes transfer learning, which trains a neural network with a fraction of the data of conventional approaches. Applying this approach to a dataset of optical coherence tomography images, we demonstrate performance comparable to that of human experts in classifying age-related macular degeneration and diabetic macular edema. We also provide a more transparent and interpretable diagnosis by highlighting the regions recognized by the neural network. We further demonstrate the general applicability of our AI system for diagnosis of pediatric pneumonia using chest X-ray images. This tool may ultimately aid in expediting the diagnosis and referral of these treatable conditions, thereby facilitating earlier treatment, resulting in improved clinical outcomes. VIDEO ABSTRACT.


Asunto(s)
Aprendizaje Profundo , Diagnóstico por Imagen , Neumonía/diagnóstico , Niño , Humanos , Redes Neurales de la Computación , Neumonía/diagnóstico por imagen , Curva ROC , Reproducibilidad de los Resultados , Tomografía de Coherencia Óptica
3.
Nucleic Acids Res ; 52(D1): D929-D937, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-37831137

RESUMEN

DNA methylation acts as a vital epigenetic regulatory mechanism involved in controlling gene expression. Advances in sequencing technologies have enabled characterization of methylation patterns at single-base resolution using bisulfite sequencing approaches. However, existing methylation databases have primarily focused on mean methylation levels, overlooking phased methylation patterns. The methylation status of CpGs on individual sequencing reads represents discrete DNA methylation haplotypes (mHaps). Here, we present mHapBrowser, a comprehensive database for visualizing and analyzing mHaps. We systematically processed data of diverse tissues in human, mouse and rat from public repositories, generating mHap format files for 6366 samples. mHapBrowser enables users to visualize eight mHap metrics across the genome through an integrated WashU Epigenome Browser. It also provides an online server for comparing mHap patterns across samples. Additionally, mHap files for all samples can be downloaded to facilitate local processing using downstream analysis toolkits. The utilities of mHapBrowser were demonstrated through three case studies: (i) mHap patterns are associated with gene expression; (ii) changes in mHap patterns independent of mean methylation correlate with differential expression between lung cancer subtypes; and (iii) the mHap metric MHL outperforms mean methylation for classifying tumor and normal samples from cell-free DNA. The database is freely accessible at http://mhap.sibcb.ac.cn/.


Asunto(s)
Metilación de ADN , Bases de Datos Genéticas , Animales , Humanos , Ratones , Ratas , Epigénesis Genética , Haplotipos , Análisis de Secuencia de ADN
4.
Plant J ; 118(5): 1413-1422, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38341804

RESUMEN

Mung bean (Vigna radiata) stands as a crucial legume crop in Asia, contributing to food security. However, our understanding of the underlying genetic foundation governing domesticated agronomic traits, especially those linked to pod architecture, remains largely unexplored. In this study, we delved into the genomic divergence between wild and domesticated mung bean varieties, leveraging germplasm obtained from diverse sources. Our findings unveiled pronounced variation in promoter regions (35%) between the two mung bean subpopulations, suggesting substantial changes in gene expression patterns during domestication. Leveraging transcriptome analysis using distinct reproductive stage pods and subpopulations, we identified candidate genes responsible for pod and seed architecture development, along with Genome-Wide Association Studies (GWAS) and Quantitative Trait Locus (QTL) analysis. Notably, our research conclusively confirmed PDH1 as a parallel domesticated gene governing pod dehiscence in legumes. This study imparts valuable insights into the genetic underpinnings of domesticated agronomic traits in mung bean, and simultaneously highlighting the parallel domestication of pivotal traits within the realm of legume crops.


Asunto(s)
Productos Agrícolas , Domesticación , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Vigna , Vigna/genética , Sitios de Carácter Cuantitativo/genética , Productos Agrícolas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Semillas/genética , Genoma de Planta/genética , Regulación de la Expresión Génica de las Plantas , Genómica , Fenotipo
5.
Cancer Metastasis Rev ; 43(3): 1075-1093, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38592427

RESUMEN

The current CAR-T cell therapy products have been hampered in their druggability due to the personalized preparation required, unclear pharmacokinetic characteristics, and unpredictable adverse reactions. Enabling standardized manufacturing and having clear efficacy and pharmacokinetic characteristics are prerequisites for ensuring the effective practicality of CAR-T cell therapy drugs. This review provides a broad overview of the different approaches for controlling behaviors of CAR-T cells in vivo. The utilization of genetically modified vectors enables in vivo production of CAR-T cells, thereby abbreviating or skipping the lengthy in vitro expansion process. By equipping CAR-T cells with intricately designed control elements, using molecule switches or small-molecule inhibitors, the control of CAR-T cell activity can be achieved. Moreover, the on-off control of CAR-T cell activity would yield potential gains in phenotypic remodeling. These methods provide beneficial references for the future development of safe, controllable, convenient, and suitable for standardized production of CAR-T cell therapy products.


Asunto(s)
Inmunoterapia Adoptiva , Neoplasias , Receptores Quiméricos de Antígenos , Humanos , Inmunoterapia Adoptiva/métodos , Animales , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Linfocitos T/inmunología
6.
Methods ; 226: 151-160, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38670416

RESUMEN

Chromatin loop is of crucial importance for the regulation of gene transcription. Cohesin is a type of chromatin-associated protein that mediates the interaction of chromatin through the loop extrusion. Cohesin-mediated chromatin interactions have strong cell-type specificity, posing a challenge for predicting chromatin loops. Existing computational methods perform poorly in predicting cell-type-specific chromatin loops. To address this issue, we propose a random forest model to predict cell-type-specific cohesin-mediated chromatin loops based on chromatin states identified by ChromHMM and the occupancy of related factors. Our results show that chromatin state is responsible for cell-type-specificity of loops. Using only chromatin states as features, the model achieved high accuracy in predicting cell-type-specific loops between two cell types and can be applied to different cell types. Furthermore, when chromatin states are combined with the occurrence frequency of CTCF, RAD21, YY1, and H3K27ac ChIP-seq peaks, more accurate prediction can be achieved. Our feature extraction method provides novel insights into predicting cell-type-specific chromatin loops and reveals the relationship between chromatin state and chromatin loop formation.


Asunto(s)
Factor de Unión a CCCTC , Proteínas de Ciclo Celular , Cromatina , Proteínas Cromosómicas no Histona , Cohesinas , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Cromatina/metabolismo , Cromatina/genética , Humanos , Factor de Unión a CCCTC/metabolismo , Factor de Unión a CCCTC/genética , Factor de Transcripción YY1/metabolismo , Factor de Transcripción YY1/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Biología Computacional/métodos , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Histonas/metabolismo , Histonas/genética , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Secuenciación de Inmunoprecipitación de Cromatina/métodos
7.
J Am Chem Soc ; 146(35): 24638-24653, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39171830

RESUMEN

Identifying biologically active ligands for membrane proteins is an important task in chemical biology. We report an approach to directly identify small molecule agonists against membrane proteins by selecting DNA-encoded libraries (DELs) on live cells. This method connects extracellular ligand binding with intracellular biochemical transformation, thereby biasing the selection toward agonist identification. We have demonstrated the methodology with three membrane proteins: epidermal growth factor receptor (EGFR), thrombopoietin receptor (TPOR), and insulin receptor (INSR). A ∼30 million and a 1.033 billion-compound DEL were selected against these targets, and novel agonists with subnanomolar affinity and low micromolar cellular activities have been discovered. The INSR agonists activated the receptor by possibly binding to an allosteric site, exhibited clear synergistic effects with insulin, and activated the downstream signaling pathways. Notably, the agonists did not activate the insulin-like growth factor 1 receptor (IGF-1R), a highly homologous receptor whose activation may lead to tumor progression. Collectively, this work has developed an approach toward "functional" DEL selections on the cell surface and may provide a widely applicable method for agonist discovery for membrane proteins.


Asunto(s)
ADN , Receptores ErbB , Receptor de Insulina , Bibliotecas de Moléculas Pequeñas , Humanos , Receptor de Insulina/agonistas , Receptor de Insulina/metabolismo , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/síntesis química , ADN/química , ADN/metabolismo , Receptores ErbB/metabolismo , Receptores ErbB/agonistas , Proteínas de la Membrana/agonistas , Proteínas de la Membrana/metabolismo , Descubrimiento de Drogas , Células HEK293 , Ligandos , Antígenos CD
8.
Lab Invest ; 104(6): 102059, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38615731

RESUMEN

High-grade serous ovarian cancer (HGSOC) remains the most lethal female cancer by far. Herein, clinical HGSOC samples had higher N6-methyladenosine (m6A) modification than normal ovarian tissue, and its dysregulation had been reported to drive aberrant transcription and translation programs. However, Kringle-containing transmembrane protein 2 (KREMEN2) and its m6A modification have not been fully elucidated in HGSOC. In this study, the data from the high-throughput messenger RNA (mRNA) sequencing of clinical samples were processed using the weighted correlation network analysis and functional enrichment analysis. Results revealed that KREMEN2 was a driver gene in the tumorigenesis of HGSOC and a potential target of m6A demethylase fat-mass and obesity-associated protein (FTO). KREMEN2 and FTO levels were upregulated and downregulated, respectively, and correlation analysis showed a significant negative correlation in HGSOC samples. Importantly, upregulated KREMEN2 was remarkably associated with lymph node metastasis, distant metastasis, peritoneal metastasis, and high International Federation of Gynecology and Obstetrics stage (Ⅲ/Ⅳ), independent of the age of patients. KREMEN2 promoted the growth of HGSOC in vitro and in vivo, which was dependent on FTO. The methylated RNA immunoprecipitation qPCR and RNA immunoprecipitation assays were performed to verify the m6A level and sites of KREMEN2. FTO overexpression significantly decreased m6A modification in the 3' and 5' untranslated regions of KREMEN2 mRNA and downregulated its expression. In addition, we found that FTO-mediated m6A modification of KREMEN2 mRNA was recognized and stabilized by the m6A reader IGF2BP1 rather than by IGF2BP2 or IGF2BP3. This study highlights the m6A modification of KREMEN2 and extends the importance of RNA epigenetics in HGSOC.


Asunto(s)
Adenosina , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Neoplasias Ováricas , Receptores de Superficie Celular , Animales , Femenino , Humanos , Ratones , Persona de Mediana Edad , Adenosina/análogos & derivados , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Carcinogénesis/genética , Línea Celular Tumoral , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/secundario , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Ratones Desnudos , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Receptores de Superficie Celular/genética
9.
EMBO J ; 39(19): e104063, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32790115

RESUMEN

The tumour stroma regulates nearly all stages of carcinogenesis. Stromal heterogeneity in human triple-negative breast cancers (TNBCs) remains poorly understood, limiting the development of stromal-targeted therapies. Single-cell RNA sequencing of five TNBCs revealed two cancer-associated fibroblast (CAF) and two perivascular-like (PVL) subpopulations. CAFs clustered into two states: the first with features of myofibroblasts and the second characterised by high expression of growth factors and immunomodulatory molecules. PVL cells clustered into two states consistent with a differentiated and immature phenotype. We showed that these stromal states have distinct morphologies, spatial relationships and functional properties in regulating the extracellular matrix. Using cell signalling predictions, we provide evidence that stromal-immune crosstalk acts via a diverse array of immunoregulatory molecules. Importantly, the investigation of gene signatures from inflammatory-CAFs and differentiated-PVL cells in independent TNBC patient cohorts revealed strong associations with cytotoxic T-cell dysfunction and exclusion, respectively. Such insights present promising candidates to further investigate for new therapeutic strategies in the treatment of TNBCs.


Asunto(s)
Neoplasias de la Mama Triple Negativas/inmunología , Escape del Tumor , Matriz Extracelular/inmunología , Matriz Extracelular/patología , Femenino , Humanos , RNA-Seq , Células del Estroma/inmunología , Células del Estroma/patología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/patología , Neoplasias de la Mama Triple Negativas/patología
10.
Diabetes Metab Res Rev ; 40(5): e3832, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39031573

RESUMEN

INTRODUCTION: Due to the high cost and complexity, the oral glucose tolerance test is not adopted as the screening method for identifying diabetes patients, which leads to the misdiagnosis of patients with isolated post-challenge hyperglycemia (IPH), that is., patients with normal fasting plasma glucose (<7.0 mmoL/L) and abnormal 2-h postprandial blood glucose (≥11.1 mmoL/L). We aimed to develop a model to differentiate individuals with IPH from the normal population. METHODS: Data from 54301 eligible participants were obtained from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study in China. Data from 37740 participants were used to develop the diagnostic system. External validation was performed among 16561 participants. Three machine learning algorithms were used to create the predictive models, which were further evaluated by various classification algorithms to establish the best predictive model. RESULTS: Ten features were selected to develop an IPH diagnosis system (IPHDS) based on an artificial neural network. In external validation, the AUC of the IPHDS was 0.823 (95% CI 0.811-0.836), which was significantly higher than the AUC of the Taiwan model [0.799 (0.786-0.813)] and that of the Chinese Diabetes Risk Score model [0.648 (0.635-0.662)]. The IPHDS model had a sensitivity of 75.6% and a specificity of 74.6%. This model outperformed the Taiwan and CDRS models in subgroup analyses. An online site with instant predictions was deployed at https://app-iphds-e1fc405c8a69.herokuapp.com/. CONCLUSIONS: The proposed IPHDS could be a convenient and user-friendly screening tool for diabetes during health examinations in a large general population.


Asunto(s)
Glucemia , Prueba de Tolerancia a la Glucosa , Hiperglucemia , Aprendizaje Automático , Humanos , Hiperglucemia/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Glucemia/análisis , China/epidemiología , Pronóstico , Estudios Longitudinales , Estudios de Seguimiento , Biomarcadores/análisis , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Algoritmos
11.
BMC Cancer ; 24(1): 119, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38263004

RESUMEN

BACKGROUND: Adoptive cell therapy has achieved great success in treating hematological malignancies. However, the production of chimeric antigen receptor T (CAR-T) cell therapy still faces various difficulties. Natural killer (NK)-92 is a continuously expandable cell line and provides a promising alternative for patient's own immune cells. METHODS: We established CAR-NK cells by co-expressing natural killer group 2 member D (NKG2D) and IL-21, and evaluated the efficacy of NKG2D-IL-21 CAR-NK cells in treating lung cancer in vitro and in vivo. RESULTS: Our data suggested that the expression of IL-21 effectively increased the cytotoxicity of NKG2D CAR-NK cells against lung cancer cells in a dose-dependent manner and suppressed tumor growth in vitro and in vivo. In addition, the proliferation of NKG2D-IL-21 CAR-NK cells were enhanced while the apoptosis and exhaustion of these cells were suppressed. Mechanistically, IL-21-mediated NKG2D CAR-NK cells function by activating AKT signaling pathway. CONCLUSION: Our findings provide a novel option for treating lung cancer using NKG2D-IL-21 CAR-NK cell therapy.


Asunto(s)
Interleucinas , Neoplasias Pulmonares , Subfamilia K de Receptores Similares a Lectina de Células NK , Humanos , Inmunoterapia Adoptiva , Tratamiento Basado en Trasplante de Células y Tejidos
12.
Arch Microbiol ; 206(5): 235, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38722413

RESUMEN

In recent years, blueberry root rot has been caused mainly by Fusarium commune, and there is an urgent need for a green and efficient method to control this disease. To date, research on Schizophyllum commune has focused on antioxidant mechanisms, reactive dye degradation, etc., but the mechanism underlying the inhibition of pathogenic microorganisms is still unclear. Here, the control effects of S. commune on F. commune and blueberry root rot were studied using adversarial culture, tissue culture, and greenhouse pot experiments. The results showed that S. commune can dissolve insoluble phosphorus and secrete various extracellular hydrolases. The results of hyphal confrontation and fermentation broth antagonism experiments showed that S. commune had a significant inhibitory effect on F. commune, with inhibition rates of 70.30% and 22.86%, respectively. Microscopy results showed distortion of F. commune hyphae, indicating that S. commune is strongly parasitic. S. commune had a significant growth-promoting effect on blueberry tissue-cultured seedlings. After inoculation with S. commune, inoculation with the pathogenic fungus, or inoculation at a later time, the strain significantly reduced the root rot disease index in the potted blueberry seedlings, with relative control effects of 79.14% and 62.57%, respectively. In addition, S. commune G18 significantly increased the antioxidant enzyme contents in the aboveground and underground parts of potted blueberry seedlings. We can conclude that S. commune is a potential biocontrol agent that can be used to effectively control blueberry root rot caused by F. commune in the field.


Asunto(s)
Arándanos Azules (Planta) , Fusarium , Enfermedades de las Plantas , Raíces de Plantas , Schizophyllum , Arándanos Azules (Planta)/microbiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Raíces de Plantas/microbiología , Fusarium/fisiología , Schizophyllum/metabolismo , Schizophyllum/crecimiento & desarrollo , Antibiosis , Hifa/crecimiento & desarrollo , Agentes de Control Biológico , Plantones/microbiología , Plantones/crecimiento & desarrollo
13.
Arch Microbiol ; 206(2): 86, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38302781

RESUMEN

Dark septate endophytes (DSEs) inhabit plant roots and soil in ecosystems and host plants worldwide. DSE colonization is influenced by cultivars, soil factors, and specific habitat conditions. The regular diversity of DSEs in blueberries in Guizhou, China, is still unclear. In this study, four cultivars (Gardenblue, Powderblue, O'Neal, and Legacy) in three areas (Gaopo, Majiang, and Fenggang) in Guizhou were used to identify DSEs by morphological and molecular biological methods and to clarify the relationship between DSE diversity and DSE colonization and soil factors of cultivated blueberries in Guizhou. The DSEs isolated from cultivated blueberry roots in 3 areas in Guizhou Province were different, belonging to 17 genera, and the dominant genera were Penicillium, Phialocephala, and Thozetella. DSEs isolated from Majiang belonged to 12 genera and 16 species, those from Gaopo belonged to 7 genera and 15 species, and those from Fenggang belonged to 5 genera and 7 species. Among the different blueberry varieties, 11 genera were isolated from O'Neal, 12 genera were isolated from Powderblue, 11 genera were isolated from Legacy and 13 genera were isolated from Gardenblue. Coniochaeta is endemic to O'Neal, Chaetomium and Curvularia are endemic to Powderblue, and Thielavia is endemic to Legacy. Correlation analysis showed that DSE diversity was significantly correlated with DSE colonization and soil factors.


Asunto(s)
Ascomicetos , Arándanos Azules (Planta) , Micorrizas , Ecosistema , Suelo , Raíces de Plantas/microbiología , Endófitos/genética
14.
Pharmacol Res ; 204: 107221, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38768669

RESUMEN

Based on the concept of "Evolutionary Traps", targeting survival essential genes obtained during tumor drug resistance can effectively eliminate resistant cells. While, it still faces limitations. In this study, lapatinib-resistant cells were used to test the concept of "Evolutionary Traps" and no suitable target stand out because of the identified genes without accessible drug. However, a membrane protein PDPN, which is low or non-expressed in normal tissues, is identified as highly expressed in lapatinib-resistant tumor cells. PDPN CAR-T cells were developed and showed high cytotoxicity against lapatinib-resistant tumor cells in vitro and in vivo, suggesting that CAR-T may be a feasible route for overcoming drug resistance of tumor based on "Evolutionary Trap". To test whether this concept is cell line or drug dependent, we analyzed 21 drug-resistant tumor cell expression profiles reveal that JAG1, GPC3, and L1CAM, which are suitable targets for CAR-T treatment, are significantly upregulated in various drug-resistant tumor cells. Our findings shed light on the feasibility of utilizing CAR-T therapy to treat drug-resistant tumors and broaden the concept of the "Evolutionary Trap".


Asunto(s)
Antineoplásicos , Resistencia a Antineoplásicos , Inmunoterapia Adoptiva , Humanos , Animales , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Inmunoterapia Adoptiva/métodos , Lapatinib/farmacología , Lapatinib/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/terapia , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/inmunología , Ratones Desnudos , Ratones Endogámicos BALB C , Ratones , Femenino
15.
Faraday Discuss ; 249(0): 181-194, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-37791622

RESUMEN

The nanoconfinement of water can result in dramatic differences in its physical and chemical properties compared to bulk water. However, a detailed molecular-level understanding of these properties is still lacking. Vibrational spectroscopy, such as Raman and infrared, is a popular experimental tool for studying the structure and dynamics of water, and is often complemented by atomistic simulations to interpret experimental spectra, but there have been few theoretical spectroscopy studies of nanoconfined water using first-principles methods at ambient conditions, let alone under extreme pressure-temperature conditions. Here, we compute the Raman and IR spectra of water nanoconfined by graphene at ambient and extreme pressure-temperature conditions using ab initio simulations. Our results revealed alterations in the Raman stretching and low-frequency bands due to the graphene confinement. We also found spectroscopic evidence indicating that nanoconfinement considerably changes the tetrahedral hydrogen bond network, which is typically found in bulk water. Furthermore, we observed an unusual bending band in the Raman spectrum at ∼10 GPa and 1000 K, which is attributed to the unique molecular structure of confined ionic water. Additionally, we found that at ∼20 GPa and 1000 K, confined water transformed into a superionic fluid, making it challenging to identify the IR stretching band. Finally, we computed the ionic conductivity of confined water in the ionic and superionic phases. Our results highlight the efficacy of Raman and IR spectroscopy in studying the structure and dynamics of nanoconfined water in a large pressure-temperature range. Our predicted Raman and IR spectra can serve as a valuable guide for future experiments.

16.
Bioorg Med Chem Lett ; 99: 129613, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38224754

RESUMEN

A series of bis-isatin conjugates with lysine linker were synthesized with the aim of probing their antiproliferative potential. All the newly synthesized derivatives (0-100 µM) were first screened against liver cancer cell lines(Huh1, H22, Huh7, Hepa1-6, HepG2, Huh6 and 97H) using CCK-8 assay. Results indicated that the derivative 4d exhibited the most potent activity against Huh1 (IC50 = 17.13 µM) and Huh7(IC50 = 8.265 µM). In vivo anti-tumor study showed that compound 4d effectively inhibited tumor growth in Huh1-induced xenograft mouse model; the anti-tumor effect of compound 4d (15 mg/kg) was comparable with sorafenib (20 mg/kg). H&E staining analysis and routine blood test and blood serum biochemistry examination was performed to confirm the safety of compound 4d in xenograft models. The mechanism of action of 4d on tumor growth inhibition was further investigated by RNA-Seq analysis, which indicates a positive regulation of autophagy signaling pathway, which was further confirmed with key biomarker expression of autophagy after 4d treatment. Our results suggest that the bis-isatin conjugate compound 4d is a promising tumor inhibitory agent for some liver cancer.


Asunto(s)
Antineoplásicos , Isatina , Neoplasias Hepáticas , Humanos , Animales , Ratones , Línea Celular Tumoral , Isatina/química , Ensayos de Selección de Medicamentos Antitumorales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Proliferación Celular , Relación Estructura-Actividad , Estructura Molecular
17.
Environ Sci Technol ; 58(14): 6370-6380, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38497719

RESUMEN

The discovery of the significant lethal impacts of the tire additive transformation product N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) on coho salmon has garnered global attention. However, the bioaccumulation and trophic transfer of tire additives and their transformation products (TATPs) within food webs remain obscure. This study first characterized the levels and compositions of 15 TATPs in the Pearl River Estuary, estimated their bioaccumulation and trophic transfer potential in 21 estuarine species, and identified priority contaminants. Our observations indicated that TATPs were prevalent in the estuarine environment. Eight, six, seven, and 10 TATPs were first quantified in the shrimp, sea cucumber, snail, and fish samples, with total mean levels of 45, 56, 64, and 67 ng/g (wet weight), respectively. N,N'-Diphenyl-p-phenylenediamine (DPPD) and N,N'-bis(2-methylphenyl)-1,4-benzenediamine (DTPD) exhibited high bioaccumulation. Significant biodilution was only identified for benzothiazole, while DPPD and DTPD displayed biomagnification trends based on Monte Carlo simulations. The mechanisms of bioaccumulation and trophodynamics of TATPs could be explained by their chemical hydrophobicity, molecular mass, and metabolic rates. Based on a multicriteria scoring technique, DPPD, DTPD, and 6PPD-Q were characterized as priority contaminants. This work emphasizes the importance of biomonitoring, particularly for specific hydrophobic tire additives.


Asunto(s)
Cadena Alimentaria , Fenilendiaminas , Contaminantes Químicos del Agua , Animales , Bioacumulación , Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisis
18.
Acta Pharmacol Sin ; 45(8): 1673-1685, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38641746

RESUMEN

Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 µM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg-1·d-1, i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI.


Asunto(s)
Lesión Renal Aguda , Ferroptosis , Ratones Endogámicos C57BL , Fenilendiaminas , Animales , Ferroptosis/efectos de los fármacos , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Ratones , Masculino , Fenilendiaminas/farmacología , Fenilendiaminas/uso terapéutico , Ciclohexilaminas/farmacología , Ciclohexilaminas/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo
19.
BMC Palliat Care ; 23(1): 24, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38273273

RESUMEN

OBJECTIVE: This study aims to investigate the experiences of parents who have experienced bereavement in their efforts to preserve memories of their deceased child. METHODS: Employing a qualitative meta-synthesis approach, this study systematically sought relevant qualitative literature by conducting searches across various electronic databases, including PubMed, Embase, CINAHL, PsycINFO, Web of Science, Cochrane Library, and Wiley, up until July 2023. RESULTS: Nine studies are eligible for inclusion and included in the meta-synthesis. Three overarching categories are identified: (1) Affirming the Significance of Memory Making. (2) Best Practices in Memory Making. (3) Barriers to Effective Memory Making. CONCLUSION: Bereaved parents highly value the act of creating lasting memories, emphasizing its profound significance. While forming these memories, it is imperative to offer family-centered care and honor diverse preferences and needs. It is essential to offer effective support to parents, offering them a range of choices. Furthermore, a more comprehensive examination of memory-making practices is required to better understand their influence on parents' recollections of their deceased child.


Asunto(s)
Aflicción , Niño , Humanos , Pesar , Padres , Investigación Cualitativa
20.
BMC Oral Health ; 24(1): 179, 2024 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-38311720

RESUMEN

OBJECTIVE: To clarify whether the 3D printing model has auxiliary functions in toto extraction of donor tooth in autotransplantation cases. METHODS: Two hundred and sixty patients who would have operation of ATT were divided into two groups. In group 1, determination of the tooth extraction in toto was predicted only according to the clinical and imaging examination. In group 2, the prediction was performed according to the clinical and imaging examination as well as the 3D model of donor tooth pre-extraction. A prespctive clinical study was designed on intra-group comparison between the predicted and actual donor teeth situation when extraction in cases of ATT. The consistent rate for the predicted results and the actual results were compared with the two groups. RESULTS: A remarkable difference was observed between the predicted results and the actual results of tooth positions and root numbers in group without model (p < 0,05). The consistency rate of the model group (94.62%) was significantly higher than that of non 3D model group (86.15%) (p = 0.034). CONCLUSION: The 3D printing model for the donor tooth is helpful for dentists to predict the accuracy of toto extraction of donor teeth in autotransplantation cases.


Asunto(s)
Compuestos de Quinolinio , Cirugía Asistida por Computador , Tiazoles , Diente , Humanos , Trasplante Autólogo/métodos , Cirugía Asistida por Computador/métodos , Extracción Dental , Impresión Tridimensional
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA