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BACKGROUND: Excessive pericyte coverage promotes tumor growth, and a downregulation may solve this dilemma. Due to the double-edged sword role of vascular pericytes in tumor microenvironment (TME), indiscriminately decreasing pericyte coverage by imatinib causes poor treatment outcomes. Here, we optimized the use of imatinib in a colorectal cancer (CRC) model in high pericyte-coverage status, and revealed the value of multiparametric magnetic resonance imaging (mpMRI) at 9.4T in monitoring treatment-related changes in pericyte coverage and the TME. METHODS: CRC xenograft models were evaluated by histological vascular characterizations and mpMRI. Mice with the highest pericyte coverage were treated with imatinib or saline; then, vascular characterizations, tumor apoptosis and HIF-1α level were analyzed histologically, and alterations in the expression of Bcl-2/bax pathway were assessed through qPCR. The effects of imatinib were monitored by dynamic contrast-enhanced (DCE)-, diffusion-weighted imaging (DWI)- and amide proton transfer chemical exchange saturation transfer (APT CEST)-MRI at 9.4T. RESULTS: The DCE- parameters provided a good histologic match the tumor vascular characterizations. In the high pericyte coverage status, imatinib exhibited significant tumor growth inhibition, necrosis increase and pericyte coverage downregulation, and these changes were accompanied by increased vessel permeability, decreased microvessel density (MVD), increased tumor apoptosis and altered gene expression of apoptosis-related Bcl-2/bax pathway. Strategically, a 4-day imatinib effectively decreased pericyte coverage and HIF-1α level, and continuous treatment led to a less marked decrease in pericyte coverage and re-elevated HIF-1α level. Correlation analysis confirmed the feasibility of using mpMRI parameters to monitor imatinib treatment, with DCE-derived Ve and Ktrans being most correlated with pericyte coverage, Ve with vessel permeability, AUC with microvessel density (MVD), DWI-derived ADC with tumor apoptosis, and APT CEST-derived MTRasym at 1 µT with HIF-1α. CONCLUSIONS: These results provided an optimized imatinib regimen to achieve decreasing pericyte coverage and HIF-1α level in the high pericyte-coverage CRC model, and offered an ultrahigh-field multiparametric MRI approach for monitoring pericyte coverage and dynamics response of the TME to treatment.
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Apoptosis , Neoplasias Colorrectales , Subunidad alfa del Factor 1 Inducible por Hipoxia , Mesilato de Imatinib , Imágenes de Resonancia Magnética Multiparamétrica , Pericitos , Mesilato de Imatinib/farmacología , Mesilato de Imatinib/uso terapéutico , Animales , Pericitos/metabolismo , Pericitos/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/diagnóstico por imagen , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Humanos , Ratones Desnudos , Microambiente Tumoral/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We aimed to evaluate the relationship between imaging features, therapeutic responses (comparative cross-product and volumetric measurements), and overall survival (OS) in pediatric diffuse intrinsic pontine glioma (DIPG). A total of 134 patients (≤ 18 years) diagnosed with DIPG were included. Univariate and multivariate analyses were performed to evaluate correlations of clinical and imaging features and therapeutic responses with OS. The correlation between cross-product (CP) and volume thresholds in partial response (PR) was evaluated by linear regression. The log-rank test was used to compare OS patients with discordant therapeutic response classifications and those with concordant classifications. In univariate analysis, characteristics related to worse OS included lower Karnofsky, larger extrapontine extension, ring-enhancement, necrosis, non-PR, and increased ring enhancement post-radiotherapy. In the multivariate analysis, Karnofsky, necrosis, extrapontine extension, and therapeutic response can predict OS. A 25% CP reduction (PR) correlated with a 32% volume reduction (R2 = 0.888). Eight patients had discordant therapeutic response classifications according to CP (25%) and volume (32%). This eight patients' median survival time was 13.0 months, significantly higher than that in the non-PR group (8.9 months), in which responses were consistently classified as non-PR based on CP (25%) and volume (32%). We identified correlations between imaging features, therapeutic responses, and OS; this information is crucial for future clinical trials. Tumor volume may represent the DIPG growth pattern more accurately than CP measurement and can be used to evaluate therapeutic response.
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Neoplasias del Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Humanos , Neoplasias del Tronco Encefálico/diagnóstico por imagen , Neoplasias del Tronco Encefálico/terapia , Neoplasias del Tronco Encefálico/mortalidad , Neoplasias del Tronco Encefálico/patología , Masculino , Niño , Femenino , Adolescente , Glioma Pontino Intrínseco Difuso/terapia , Preescolar , Resultado del Tratamiento , Imagen por Resonancia Magnética , Lactante , Estudios Retrospectivos , Glioma/terapia , Glioma/patología , Glioma/diagnóstico por imagen , Glioma/mortalidadRESUMEN
This study aimed to investigate the link between COL1A1 production and colorectal carcinoma and assess the value of prognosis and immunotherapy. For this purpose, the transcriptional level of COL1A1 was analyzed. The clinicopathological information and gene expression profile were analyzed to reveal the link between COL1A1 and clinicopathological characteristics. For bioinformatics examination, GSEA and GSVA were utilized. Correlation analysis was implemented to study the causal relationship between COL1A1 and immune checkpoint molecules and inflammation immune cell infiltration. Results showed that in colorectal cancer, COL1A1 was highly expressed and linked with a few clinicopathological characteristics, inflammation and immunological response, tumor immune cell infiltration, and immune checkpoint markers. COL1A1 might likely indicate a bad prognosis and serve as a target of immunotherapy for colon cancer.
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Neoplasias del Colon , Humanos , Neoplasias del Colon/genética , Neoplasias del Colon/terapia , Biología Computacional , Inmunoterapia , Inflamación , PronósticoRESUMEN
Coal is one of the primary energy sources in China and is widely used for electricity generation. Crops growing in overlapped areas of farmland and coal resources (OAFCR) suffer from coal fly ash stress, especially during stem elongation, which is a key stage that impacts wheat yield and is sensitive to environmental stress. As a primary food crop of China, wheat is essential for food security. However, the characteristics of wheat under the combined stress of fly ash and various heavy metals have not been sufficiently investigated. In this study, we explored the response of stem elongation in wheat to different levels of coal fly ash stress and determined the content of heavy metals (HMs) in wheat leaves. We found that with an increase in fly ash content, the Cu content in the shoots increased, while that in the roots decreased. Coal fly ash exposure reduced the proportions of Pb and Zn in the cytoderm, and the proportion of Cu in the soluble constituents decreased from 58.3% to 45.7%. Total chlorophyll, chlorophyll a, and chlorophyll b levels decreased significantly, whereas peroxidase (POD) and catalase (CAT) activities generally increased with increasing fly ash dose. Meanwhile, chloroplasts, mitochondria, and their internal structures were damaged, and the cell structures of leaves, such as the internal membrane structure, were damaged.
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Ceniza del Carbón , Metales Pesados , Fotosíntesis , Triticum , Fotosíntesis/efectos de los fármacos , Carbón Mineral , Hojas de la Planta , Tallos de la Planta/efectos de los fármacos , Clorofila , China , Estrés FisiológicoRESUMEN
It is certainly one of the most feasible ways to extract fresh water from seawater in the face of the current depletion of fresh water resources. Although solar energy as a heat source for desalination is the cleanest and most abundant way, its intermittent and seasonal also poses an obstacle to its practical application. In order to solve the above-mentioned issues, we prepared a series of phase change composites (PCCs) with excellent light-absorbing and magnetic properties by growing MIL-101(Fe) in situ on cotton fabric. All-day desalination through the synergistic action of phase change material (PCM) and magnetic particles. The evaporation rate of PCC can reach 2.76 kg m-2h-1 with an evaporation efficiency of 90.19 % under one sunlight condition. The evaporation rate of sea water under the synergistic effect of magnetic particles and PCM reached 4.53 kg m-2h-1 in the absence of sunlight. This paper provides a new approach to all-day desalination without contact heating.
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The severe dependence of traditional phase change materials (PCMs) on the temperature-response and lattice deficiencies in versatility cannot satisfy demand for using such materials in complex application scenarios. Here, we introduced metal ions to induce the self-assembly of MXene nanosheets and achieve their ordered arrangement by combining suction filtration and rapid freezing. Subsequently, a series of MXene/ K+/paraffin wax (PW) phase change composites (PCCs) were obtained via vacuum impregnation in molten PW. The prepared MXene-based PCCs showed versatile applications from macroscale technologies, successfully transforming solar, electric, and magnetic energy into thermal energy stored as latent heat in the PCCs. Moreover, due to the absence of binder in the MXene-based aerogel, MK3@PW exhibits a prime solar-thermal conversion efficiency (98.4%). Notably, MK3@PW can further convert the collected heat energy into electric energy through thermoelectric equipment and realize favorable solar-thermal-electric conversion (producing 206 mV of voltage with light radiation intensity of 200 mw cm-2). An excellent Joule heat performance (reaching 105 °C with an input voltage of 2.5 V) and responsive magnetic-thermal conversion behavior (a charging time of 11.8 s can achieve a thermal insulation effect of 285 s) for contactless thermotherapy were also demonstrated by the MK3@PW. Specifically, as a result of the ordered arrangement of MXene nanosheet self-assembly induced by potassium ions, MK3@PW PCC exhibits a higher electromagnetic shielding efficiency value (57.7 dB) than pure MXene aerogel/PW PCC (29.8 dB) with the same MXene mass. This work presents an opportunity for the multi-scene response and practical application of PCMs that satisfy demand of next-generation multifunctional PCCs.