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Hemi-methylated cytosine dyads widely occur on mammalian genomic DNA, and can be stably inherited across cell divisions, serving as potential epigenetic marks. Previous identification of hemi-methylation relied on harsh bisulfite treatment, leading to extensive DNA degradation and loss of methylation information. Here we introduce Mhemi-seq, a bisulfite-free strategy, to efficiently resolve methylation status of cytosine dyads into unmethylation, strand-specific hemi-methylation, or full-methylation. Mhemi-seq reproduces methylomes from bisulfite-based sequencing (BS-seq & hpBS-seq), including the asymmetric hemi-methylation enrichment flanking CTCF motifs. By avoiding base conversion, Mhemi-seq resolves allele-specific methylation and associated imprinted gene expression more efficiently than BS-seq. Furthermore, we reveal an inhibitory role of hemi-methylation in gene expression and transcription factor (TF)-DNA binding, and some displays a similar extent of inhibition as full-methylation. Finally, we uncover new hemi-methylation patterns within Alu retrotransposon elements. Collectively, Mhemi-seq can accelerate the identification of DNA hemi-methylation and facilitate its integration into the chromatin environment for future studies.
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Metilación de ADN , Análisis de Secuencia de ADN , Animales , Citosina/metabolismo , Metilación de ADN/genética , Mamíferos/genética , Retroelementos , Análisis de Secuencia de ADN/métodos , Sulfitos , Regulación de la Expresión GénicaRESUMEN
Transcription factor (TF) residence on chromatin translates into quantitative transcriptional or structural outcomes on genome. Commonly used formaldehyde crosslinking fixes TF-DNA interactions cumulatively and compromises the measured occupancy level. Here we mapped the occupancy level of global or individual zinc finger TFs like CTCF and MAZ, in the form of highly resolved footprints, on native chromatin. By incorporating reinforcing perturbation conditions, we established S-score, a quantitative metric to proxy the continuum of CTCF or MAZ retention across different motifs on native chromatin. The native chromatin-retained CTCF sites harbor sequence features within CTCF motifs better explained by S-score than the metrics obtained from other crosslinking or native assays. CTCF retention on native chromatin correlates with local SUMOylation level, and anti-correlates with transcriptional activity. The S-score successfully delineates the otherwise-masked differential stability of chromatin structures mediated by CTCF, or by MAZ independent of CTCF. Overall, our study established a paradigm continuum of TF retention across binding sites on native chromatin, explaining the dynamic genome organization.
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Factor de Unión a CCCTC , Cromatina , Factores de Transcripción , Dedos de Zinc , Cromatina/metabolismo , Cromatina/genética , Factor de Unión a CCCTC/metabolismo , Factor de Unión a CCCTC/genética , Sitios de Unión , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Humanos , Unión Proteica , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Sumoilación , GenomaRESUMEN
Regulatory T (Treg) cells that infiltrate human tumors exhibit stronger immunosuppressive activity compared to peripheral blood Treg cells (PBTRs), thus hindering the induction of effective antitumor immunity. Previous transcriptome studies have identified a set of genes that are conserved in tumor-infiltrating Treg cells (TITRs). However, epigenetic profiles of TITRs have not yet been completely deciphered. Here, we employed ATAC-seq and CUT&Tag assays to integrate transcriptome profiles and identify functional regulatory elements in TITRs. We observed a global difference in chromatin accessibility and enhancer landscapes between TITRs and PBTRs. We identified two types of active enhancer formation in TITRs. The H3K4me1-predetermined enhancers are poised to be activated in response to tumor microenvironmental stimuli. We found that AP-1 family motifs are enriched at the enhancer regions of TITRs. Finally, we validated that c-Jun binds at regulatory regions to regulate signature genes of TITRs and AP-1 is required for Treg cells activation in vitro. High c-Jun expression is correlated with poor survival in human HCC. Overall, our results provide insights into the mechanism of AP-1-mediated activation of TITRs and can hopefully be used to develop new therapeutic strategies targeting TITRs in liver cancer treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Factor de Transcripción AP-1 , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Elementos de Facilitación Genéticos/genética , Epigénesis Genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Linfocitos T Reguladores , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismoRESUMEN
Language models have been increasingly popular for automatic creativity assessment, generating semantic distances to objectively measure the quality of creative ideas. However, there is currently a lack of an automatic assessment system for evaluating creative ideas in the Chinese language. To address this gap, we developed TransDis, a scoring system using transformer-based language models, capable of providing valid originality (novelty) and flexibility (variety) scores for Alternative Uses Task (AUT) responses in Chinese. Study 1 demonstrated that the latent model-rated originality factor, comprised of three transformer-based models, strongly predicted human originality ratings, and the model-rated flexibility strongly correlated with human flexibility ratings as well. Criterion validity analyses indicated that model-rated originality and flexibility positively correlated to other creativity measures, demonstrating similar validity to human ratings. Study 2 and 3 showed that TransDis effectively distinguished participants instructed to provide creative vs. common uses (Study 2) and participants instructed to generate ideas in a flexible vs. persistent way (Study 3). Our findings suggest that TransDis can be a reliable and low-cost tool for measuring idea originality and flexibility in Chinese language, potentially paving the way for automatic creativity assessment in other languages. We offer an open platform to compute originality and flexibility for AUT responses in Chinese and over 50 other languages ( https://osf.io/59jv2/ ).
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Creatividad , Lenguaje , Humanos , Femenino , Masculino , Adulto Joven , China , Adulto , Pensamiento/fisiología , Reproducibilidad de los Resultados , Pueblos del Este de AsiaRESUMEN
Ovarian cancer (OC) poses significant oncological challenges, notably impaired wound healing in the context of cisplatin (DDP) resistance. This study investigates the role of miR-200b in OC, emphasizing its impact on wound healing processes through DNMT3A/TGF-ß1 pathway. The primary aim was to explore how miR-200b regulates autophagy and its consequential effects on wound healing in OC, alongside its influence on cisplatin resistance. Utilizing DDP-sensitive (A2780) and resistant (A2780/DDP) OC cell lines, along with human fibroblast cultures, the study employed an array of in vitro techniques. These included cell transfection with miR-200b mimic or inhibitor, chromatin immunoprecipitation (ChIP), dual-luciferase reporter (DLR) assays, quantitative PCR, Western blotting, MTT and particularly, wound healing assays. The research highlighted the role of miR-200b in wound healing within OC. Inhibition of miR-200b in A2780 cells and its mimic in A2780/DDP cells affected cell viability, indicating the link with DDP resistance. Crucially, miR-200b mimic significantly delayed fibroblast-mediated wound closure in assays, underscoring its impact on wound healing. Bioinformatics analysis and subsequent DLR assays confirmed miR-200b's interaction with DNMT3A, affecting TGF-ß1 expression, the key factor in wound repair. Further, ChIP, quantitative PCR and Western blot analyses validated the interaction and expression changes in DNMT3A and TGF-ß1. The study demonstrated that miR-200b played a pivotal role in OC by modulating autophagy, which in turn significantly affected wound healing through the DNMT3A/TGF-ß1 pathway.
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MicroARNs , Neoplasias Ováricas , Humanos , Femenino , Cisplatino/farmacología , Cisplatino/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Factor de Crecimiento Transformador beta1 , Línea Celular Tumoral , MicroARNs/genética , Resistencia a Antineoplásicos , Proliferación CelularRESUMEN
We propose the coupling of multiple quantum wells and surface plasmons can improve coherence of light emitted from LED wafers, as evidenced herein by a shallow-etched conic pit array with evaporated Ag (V-Ag) on a GaN-based LED wafer. The improvement in spatial coherence is critically verified by angle-resolved spectra. The temporal coherence length of the V-Ag wafer is 1.4 times larger than that of the plain wafer. The coherence-enhanced wafer achieves anisotropic and deflective emission in micro area and at far field by diffraction. This research provides a novel perspective on research of plasmonic LEDs and a new straightforward architecture to acquire partially coherent light from LEDs.
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Realistic fluid models play an important role in computer graphics applications. However, efficiently reconstructing volumetric fluid flows from monocular videos remains challenging. In this work, we present a novel approach for reconstructing 3D flows from monocular inputs through a physics-based differentiable renderer coupled with joint density and velocity estimation. Our primary contributions include the proposed efficient differentiable rendering framework and improved coupled density and velocity estimation strategy. Rather than relying on automatic differentiation, we derive the differential form of the radiance transfer equation under single scattering. This allows the direct computation of the radiance gradient with respect to density, yielding higher efficiency compared to prior works. To improve temporal coherence in the reconstructed flows, subsequent fluid densities are estimated via a coupled strategy that enables smooth and realistic fluid motions suitable for applications that require high efficiency. Experiments on synthetic and real-world data demonstrated our method's capacity to reconstruct plausible volumetric flows with smooth dynamics efficiently. Comparisons to prior work on fluid motion reconstruction from monocular video revealed over 50-170x speedups across multiple resolutions.
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Catalytic combustion of ubiquitous chlorinated volatile organic compounds (CVOCs) encounters bottlenecks regarding catalyst deactivation by chlorine poisoning and generation of toxic polychlorinated byproducts. Herein, Ru, Pd, and Rh were loaded on {001}-TiO2 for thermal catalytic oxidation of chlorobenzene (CB), with Ru/{001}-TiO2 representing superior reactivity, CO2 selectivity, and stability in the 1000 min on-stream test. Interestingly, both acid sites and reactive active oxygen species (ROS) were remarkably promoted via adding NaBH4. But merely enhancing these active sites of the catalyst in CVOC treatment is insufficient. Continuous deep oxidation of CB with effective Cl desorption is also a core issue successfully tackled through the steady Ru0âRu4+ circulation. This circulation was facilitated by the observed higher subnanometer Ru dispersion on {001}-TiO2 than the other two noble metals that was supported by single atom stability DFT calculation. Nearly 88 degradation products in off-gas were detected, with Ru/{001}-TiO2 producing the lowest polychlorinated benzene byproducts. An effective and sustainable CB degradation mechanism boosted by the cooperation of NaBH4 enhanced active sites and Ru circulation was proposed accordingly. Insights gained from this study open a new avenue to the rational design of promising catalysts for the treatment of CVOCs.
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OBJECTIVES: One of the major challenges in treating patients with coronavirus disease 2019 (COVID-19) is predicting the severity of disease. We aimed to develop a new score for predicting progression from mild/moderate to severe COVID-19. METHODS: A total of 239 hospitalized patients with COVID-19 from two medical centers in China between February 6 and April 6, 2020 were retrospectively included. The prognostic abilities of variables, including clinical data and laboratory findings from the electronic medical records of each hospital, were analysed using the Cox proportional hazards model and Kaplan-Meier methods. A prognostic score was developed to predict progression from mild/moderate to severe COVID-19. RESULTS: Among the 239 patients, 216 (90.38%) patients had mild/moderate disease, and 23 (9.62%) progressed to severe disease. After adjusting for multiple confounding factors, pulmonary disease, age > 75, IgM, CD16+/CD56+ NK cells and aspartate aminotransferase were independent predictors of progression to severe COVID-19. Based on these five factors, a new predictive score (the 'PAINT score') was established and showed a high predictive value (C-index = 0.91, 0.902 ± 0.021, p < 0.001). The PAINT score was validated using a nomogram, bootstrap analysis, calibration curves, decision curves and clinical impact curves, all of which confirmed its high predictive value. CONCLUSIONS: The PAINT score for progression from mild/moderate to severe COVID-19 may be helpful in identifying patients at high risk of progression.
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COVID-19 , COVID-19/diagnóstico , Humanos , Nomogramas , Pronóstico , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
Polycyclic aromatic hydrocarbons (PAHs) are widely present in the environment. The coking industry is an important industrial source of PAHs. Coke production in China accounts for 67.44% of total global coke production. Tangshan, a coastal city on the Bohai Rim, contains the largest cluster of coking plants in China. Extremely high PAH emissions in Tangshan may cause long-distance cross-border pollution problems. In this study, the concentrations and sources of 16 priority PAHs in soil at a coking plant in Tangshan were determined and the risks posed by the PAHs were assessed. The PAH concentrations were generally higher in surface soil than subsurface soil, particularly near the coke oven, crude benzol, and coal blending areas. The dibenz[a,h]anthracene (DBA) concentrations were higher than the risk screening value (1500 ngg-1) but lower than the control value (15,000 ngg-1) for type II land defined in Chinese standard (GB36600-2018). The main sources of PAHs were coal combustion, the coke oven, and traffic. The PAH concentrations were higher in the ammonium sulfate, boiler room, coal blending, and coke oven areas than in the other areas. Toxic equivalent concentrations were calculated to assess the toxic and carcinogenic risks posed by PAHs. The toxic equivalent concentrations were relatively high in the boiler, crude benzol, and coal blending areas, where the toxic equivalent concentrations for the sums of seven highly carcinogenic PAHs contributed 95% of the toxic equivalent concentrations for the sums of the 16 PAHs that were analyzed. The carcinogenic risks posed to humans were therefore assessed using the concentrations of the seven highly carcinogenic PAHs. Dermal contact was found to be an important exposure pathway leading to carcinogenic risks. The carcinogenic risk posed by DBA was > 1 × 10-6 but < 5 × 10-6, indicating that DBA concentrations at the study site monitored closely.
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Coque , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , China , Coque/análisis , Monitoreo del Ambiente , Humanos , Hidrocarburos Policíclicos Aromáticos/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisisRESUMEN
BACKGROUND: The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. METHODS: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4+ T cells and CD19+ B cells. RESULTS: We observed that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared to that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, positive correlations were observed between the frequencies of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5)+CD4+ T cells and CXCR5+CD8+ T cells. Notably, in vitro experimental results demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4+ T cells and promoted the proliferation of autologous intrasplenic CD19+ B cells. CONCLUSIONS: Expanded FDCs in patients with chronic HBV infection may favor host immune responses against HBV. The identification of this unique population of cell may contribute to a better understanding of the immune regulatory mechanisms associated with chronic HBV infection and provide a potential immunotherapeutic target for this disease.
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Hepatitis B Crónica , Linfocitos T CD8-positivos , Células Dendríticas , Células Dendríticas Foliculares , Virus de la Hepatitis B , Humanos , InmunidadRESUMEN
PURPOSE: Emerging evidences have raised concerns about electrolyte disorders caused by restrictive fluid management in the enhanced recovery after surgery (ERAS) protocol. This study aims to investigate the morbidity and treatment of electrolyte disorders associated with ERAS in patients undergoing hepato-pancreato-biliary (HPB) surgery. METHODS: Clinical data from 157 patients under the ERAS program and 166 patients under the traditional (Non-ERAS) program after HPB surgery were retrospectively analyzed. Risk factors and predictive factors of postoperative electrolyte disorders were analyzed by logistic regression analysis and receiver operator characteristic (ROC) curve analysis, respectively. RESULTS: The average of intravenous fluid, sodium, chloride, and potassium supplementation after surgery were significantly lower in the ERAS group. Hypokalemia was the most common type of electrolyte disorders in the ERAS group, whose incidence was substantially increased compared to that in the Non-ERAS group [28.77% vs. 8.97%, p < 0.001, on postoperative (POD) 5]. Logistic regression analysis identified the ERAS program and age as independent risk factors of hypokalemia. ROC curve analysis identified serum potassium levels below 3.76 mmol/L on POD 3 (area under curve 0.731, sensitivity 58.54%, specificity 82.69%) as a predictive factor for postoperative hypokalemia in ERAS patients. Oral supplementation at an average of 35.41 mmol potassium per day was effective in restoring the ERAS-associated hypokalemia. CONCLUSIONS: ERAS procedures were particularly associated with a lower supplementation of potassium and a higher incidence of hypokalemia in patients after HPB surgery. Oral potassium supplementation could be an adopted ERAS program for the elderly undergoing HPB surgery.
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Procedimientos Quirúrgicos del Sistema Digestivo , Recuperación Mejorada Después de la Cirugía , Fluidoterapia/efectos adversos , Hipopotasemia/etiología , Complicaciones Posoperatorias/etiología , Desequilibrio Hidroelectrolítico/etiología , Enfermedades de las Vías Biliares/cirugía , China , Femenino , Humanos , Hipopotasemia/prevención & control , Hepatopatías/cirugía , Masculino , Persona de Mediana Edad , Enfermedades Pancreáticas/cirugía , Complicaciones Posoperatorias/prevención & control , Potasio/administración & dosificación , Estudios Retrospectivos , Factores de Riesgo , Desequilibrio Hidroelectrolítico/prevención & controlRESUMEN
Interfacial bioconjugation methods are developed for intact liquid emulsion droplets. Complex emulsion droplets having internal hydrocarbon and fluorocarbon immiscible structured phases maintain a dynamic interface for controlled interfacial reactivity. The internal morphological change after binding to biomolecules is readily visualized and detected by light transmission, which provides a platform for the formation of inexpensive and portable bio-sensing assays for enzymes, antibodies, nucleic acids and carbohydrates.
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Técnicas Biosensibles/métodos , Emulsiones/química , Aminas/química , Anticuerpos/análisis , Enzimas/análisis , Fluorocarburos/química , Hidrocarburos/química , Ácidos Nucleicos/análisis , Compuestos de Sulfhidrilo/química , Tensoactivos/químicaRESUMEN
BACKGROUND Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic protein cloned from activated macrophages in human and rat allografts. AIF-1 has been identified as a modulator of inflammatory response, and recently published studies have shown its increased expression in carcinogenesis. However, there are still limited data on the potential functional role of AIF-1 in hepatocellular carcinoma (HCC). MATERIAL AND METHODS We evaluated the expression of AIF-1 in 104 cases of paired HCC and adjacent non-cancerous liver tissues using immunohistochemistry, Western blotting, and qPCR analysis, and sought to determine whether its expression was correlated with clinicopathological features. In vitro assays, including cell proliferation and migration assays, were used to study the effects of AIF-1 knockdown in L02 human hepatocyte, and Huh7 and SMMC7721 liver cancer cell lines. RESULTS Expression of AIF-1 was increased in HCC compared to adjacent normal liver tissues and was positively correlated with median tumor size (p=0.046), number of tumor deposits (p=0.009), the Barcelona Clinic Liver Cancer (BCLC) stage (p=0.004), and portal vein tumor thrombus (PVTT) (p<0.001). Huh7 and SMMC7721 human HCC cells demonstrated upregulated AIF-1 expression compared to normal hepatocytes. Small interfering RNA (siRNA)-mediated silencing of AIF-1 expression resulted in a reduction in cell proliferation and migration in human HCC cells. CONCLUSIONS These findings suggest AIF-1 may have roles as a diagnostic or prognostic biomarker and a promising therapeutic target in HCC.
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Carcinoma Hepatocelular/metabolismo , Proteínas de Unión al ADN/biosíntesis , Neoplasias Hepáticas/metabolismo , Anciano , Anciano de 80 o más Años , Aloinjertos/metabolismo , Animales , Apoptosis/genética , Proteínas de Unión al Calcio , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Proteínas de Unión al ADN/genética , Femenino , Células Hep G2 , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/genética , Masculino , Proteínas de Microfilamentos , Persona de Mediana Edad , Pronóstico , RatasRESUMEN
Increasing evidence suggests that the glutathione peroxidase 2 may actually play important roles in tumorigenesis and progression in various human cancers such as colorectal carcinomas and lung adenocarcinomas. However, the role of glutathione peroxidase 2 in gastric carcinoma remains to be determined. In this study, the expression and prognostic significance of glutathione peroxidase 2 in gastric carcinoma were investigated and the well-known prognostic factor Ki-67 labeling index was also assessed as positive control. Glutathione peroxidase 2 expression levels in the tumor tissue specimens, the matched adjacent normal tissue specimens, and the lymph node metastases of 176 patients with gastric carcinoma were evaluated by quantitative polymerase chain reaction, western blotting, and immunohistochemical staining. The associations between glutathione peroxidase 2 expression levels, as determined by immunohistochemical staining, and multiple clinicopathological characteristics were determined by Pearson's chi-square test and Spearman's correlation analysis. The relationships between glutathione peroxidase 2 expression and other clinicopathological variables and patient prognoses were analyzed further by the Kaplan-Meier method, the log-rank test, and Cox multivariate regression. The quantitative polymerase chain reaction, western blotting, and immunohistochemical staining results showed that glutathione peroxidase 2 expression levels were upregulated in both the primary tumor foci and the lymph node metastases of patients with gastric carcinoma (all p values < 0.05). Furthermore, Pearson's chi-square tests, as well as Spearman's correlation analysis, revealed that glutathione peroxidase 2 expression levels were strongly correlated with the Ki-67 labeling index, differentiation, histological patterns, Lauren classifications, lymph node metastasis, vascular invasion, tumor-node-metastasis stages, Helicobacter pylori infection, and overall survival (all p values < 0.05). Kaplan-Meier analysis, as well as the log-rank test and multivariate Cox regression analysis, showed that multiple clinicopathological risk factors and glutathione peroxidase 2 expression were novel independent prognostic factors for gastric carcinoma (all p values < 0.05). Glutathione peroxidase 2 expression is a novel independent prognostic biomarker for gastric carcinoma that may be used to devise personalized therapeutic regimens and precision treatments for this disease.
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Biomarcadores de Tumor/genética , Carcinoma/genética , Glutatión Peroxidasa/genética , Infecciones por Helicobacter/genética , Neoplasias Gástricas/genética , Adulto , Anciano , Biomarcadores de Tumor/biosíntesis , Carcinoma/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Glutatión Peroxidasa/biosíntesis , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Neoplasias Gástricas/patologíaRESUMEN
Epithelial-mesenchymal transition (EMT) occurs during the progression of liver fibrosis in response to chronic liver injury. However, the molecular mechanism underlying the regulation of hepatocyte EMT remains unclear. The aim of this study was to determine whether advanced oxidation protein products (AOPP) had an effect on hepatocyte EMT. The human L02 hepatocyte cell line and hepatocytes from normal Sprague-Dawley rats were challenged with AOPP treatment in both in vitro and in vivo studies. The expression of cell and molecular markers of EMT in L02 hepatocytes were studied using Western blotting, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays. Hepatocyte migratory potential was analyzed using a wound healing assay. Intracellular reactive oxygen species (ROS) were detected using the dichlorofluorescein (DCF) assay. In liver tissue sections, expression of EMT markers was evaluated using immunohistochemistry, and collagen was assessed using histochemical staining with Masson's trichrome. The findings were that AOPP treatment resulted in EMT in hepatocytes, which was associated with reduced expression of E-cadherin, increased expression of vimentin, increased deposition of collagen protein, and enhanced cell migration in vivo and in vitro. AOPP was also found to promote migration in L02 cells, and to promote the production of ROS and the activation of TGF-ßR and Smad signaling. Inhibition of the generation of intracellular ROS and TGF-ß receptor blocking could reverse AOPP-induced EMT in hepatocytes. This study has identified a novel mechanism in the regulation of hepatocyte EMT, and the findings may have implications for the control of liver fibrosis.
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Productos Avanzados de Oxidación de Proteínas/metabolismo , Hepatocitos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Animales , Cadherinas/metabolismo , Línea Celular , Movimiento Celular , Colágeno/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Humanos , Hígado/metabolismo , Oxidación-Reducción , Ratas , Ratas Sprague-Dawley , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Transducción de Señal , Vimentina/metabolismoRESUMEN
Sperm-associated antigen 9 (SPAG9) has been reported to express in several cancers and have clinical significance. Using immunohistochemistry, we found that there was a strong association among SPAG9 expression and tumor size, TNM stage, histological grade, lymph node metastasis, and recurrence. It suggested that SPAG9-elevated expression was an independently prognostic indicator for both OS and DFS. Furthermore, the selected treatment of chemotherapy with Taxol/non-Taxol significantly affects OS and DFS. To sum up, SPAG9-elevated expression contributes to malignant behavior and poor prognosis of breast cancer and may support a potential indicator in treatment selection.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Antineoplásicos Fitogénicos/farmacología , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Paclitaxel/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Femenino , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Persona de Mediana Edad , Análisis Multivariante , Paclitaxel/uso terapéutico , PronósticoRESUMEN
We aimed to assess the efficacy and safety of S-1 combined with cisplatin (SC) over cisplatin alone (C) for the treatment of advanced gastric cancer in China. Between July 2009 and June 2011, 72 eligible patients with advanced gastric cancer were selected and divided randomly into two groups. Thirty-six patients received SC, with S-1 on days 1 through 14 of a 21-day cycle and cisplatin (60 mg/m on day 1) every 4 weeks for two cycles. The other 36 patients were administered only cisplatin (in the same manner as SC). The primary outcome was overall survival. The secondary outcomes were progression-free survival and adverse events. The 2-year overall response rate was 51.5 and 42.3% for the SC and C groups, respectively, and the difference was statistically significant, whereas the median overall survival was 9.4 months (range, 1.9-24.4 months) and 7.6 months (range, 1.7-21.4 months), respectively (P=0.039). The median progression-free survival was 7.7 months for SC (range, 1.8-19.4 months), whereas it was 6.5 months (range, 1.5-16.4 months) for C (P=0.047). The toxicity profile was similar in both groups. In summary, we have shown that S-1 combined with cisplatin is more effective, with acceptable toxicity in comparison with cisplatin alone in Chinese patients with advanced gastric cancer. Chinese Clinical Trials Register: ChiCTR-TRC-13003993.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Cisplatino/administración & dosificación , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Proyectos Piloto , Neoplasias Gástricas/patología , Tegafur/administración & dosificaciónRESUMEN
A cross-reactive colorimetric sensor array composed of solvatochromic dyes in semi-liquid matrices was used to successfully discriminate among eleven common solvents. The multidimensional array response is attributed to both chemical (i.e., analyte-dye interactions) and physical (i.e., spot blooming and refractive index alteration) changes in the sensor spot.
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Colorimetría/instrumentación , Compuestos Orgánicos/análisis , Solventes/análisis , Colorantes/análisisRESUMEN
We present a novel framework for reconstructing fluid dynamics in real-life scenarios. Our approach leverages sparse view images and incorporates physical priors across long series of frames, resulting in reconstructed fluids with enhanced physical consistency. Unlike previous methods, we utilize a differentiable fluid simulator (DFS) and a differentiable renderer (DR) to exploit global physical priors, reducing reconstruction errors without the need for manual regularization coefficients. We introduce divergence-free Laplacian eigenfunctions (div-free LE) as velocity bases, improving computational efficiency and memory usage. By employing gradient-related strategies, we achieve better convergence and superior results. Extensive experiments demonstrate the effectiveness of our method, showcasing improved reconstruction quality and computational efficiency compared to existing approaches. We validate our approach using both synthetic and real data, highlighting its practical potential.