RESUMEN
Photodynamic therapy has been regarded as a noninvasive treatment for cancer with spatiotemporal control over drug activation. Bis-terpyridyl Ru(II) complexes exhibit a promising achiral structure but suffer from low photoreactivity due to deviation from the ideal octahedral geometry. Herein, we introduce the donor-acceptor-donor motif to construct a dinuclear bis-terpyridyl Ru(II) complex (Ru2). Ru2 exhibits superior light absorption properties compared with mononuclear complex Ru1. Importantly, upon 595 nm light excitation, Ru2 shows promising synergetic type I/II photosensitization and photocatalytic activity, while Ru1 is inactive. Anticancer mechanistic studies reflect that Ru2 induces intracellular redox imbalance and affects the biosynthetic and metabolic processes, leading to cell apoptosis. Overall, this work provides a simple strategy to rouse the PDT efficiency of bis-terpyridyl Ru(II) complexes.
Asunto(s)
Antineoplásicos , Complejos de Coordinación , Fotoquimioterapia , Fármacos Fotosensibilizantes , Rutenio , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Rutenio/química , Rutenio/farmacología , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/síntesis química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Piridinas/farmacología , Piridinas/química , Piridinas/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Relación Estructura-ActividadRESUMEN
Landscape changes resulting from anthropogenic activities and climate changes severely impact surface water quality. A global perspective on understanding their relationship is a prerequisite for pursuing equity in water security and sustainable development. A sequent meta-analysis synthesizing 625 regional studies from 63 countries worldwide was conducted to analyze the impacts on water quality from changing landscape compositions in the catchment and explore the moderating factors and temporal evolution. Results exhibit that total nitrogen (TN), total phosphorus (TP), and chemical oxygen demand (COD) in water are mostly concerned and highly responsive to landscape changes. Expansion of urban lands fundamentally degraded worldwide water quality over the past 20 years, of which the arid areas tended to suffer more harsh deterioration. Increasing forest cover, particularly low-latitude forests, significantly decreased the risk of water pollution, especially biological and heavy metal contamination, suggesting the importance of forest restoration in global urbanization. The effect size of agricultural land changes on water quality was spatially scale-dependent, decreasing and then increasing with the buffer radius expanding. Wetland coverage positively correlated with organic matter in water typified by COD, and the correlation coefficient peaked in the boreal areas (r=0.82, p<0.01). Overall, the global impacts of landscape changes on water quality have been intensifying since the 1990s. Nevertheless, knowledge gaps still exist in developing areas, especially in Africa and South America, where the water quality is sensitive to landscape changes and is expected to experience dramatic shifts in foreseeable future development. Our study revealed the worldwide consistency and heterogeneity between regions, thus serving as a research roadmap to address the quality-induced global water scarcity under landscape changes and to direct the management of land and water.
Asunto(s)
Calidad del Agua , Fósforo/análisis , Nitrógeno/análisis , Humedales , Monitoreo del Ambiente , Cambio ClimáticoRESUMEN
OBJECTIVE: CT and MRI are synergistic in the information provided for neurosurgical planning. While obtaining both types of images lends unique data from each, doing so adds to cost and exposes patients to additional ionizing radiation after MRI has been performed. Cross-modal synthesis of high-resolution CT images from MRI sequences offers an appealing solution. The authors therefore sought to develop a deep learning conditional generative adversarial network (cGAN) which performs this synthesis. METHODS: Preoperative paired CT and contrast-enhanced MR images were collected for patients with meningioma, pituitary tumor, vestibular schwannoma, and cerebrovascular disease. CT and MR images were denoised, field corrected, and coregistered. MR images were fed to a cGAN that exported a "synthetic" CT scan. The accuracy of synthetic CT images was assessed objectively using the quantitative similarity metrics as well as by clinical features such as sella and internal auditory canal (IAC) dimensions and mastoid/clinoid/sphenoid aeration. RESULTS: A total of 92,981 paired CT/MR images obtained in 80 patients were used for training/testing, and 10,068 paired images from 10 patients were used for external validation. Synthetic CT images reconstructed the bony skull base and convexity with relatively high accuracy. Measurements of the sella and IAC showed a median relative error between synthetic CT scans and ground truth images of 6%, with greater variability in IAC reconstruction compared with the sella. Aerations in the mastoid, clinoid, and sphenoid regions were generally captured, although there was heterogeneity in finer air cell septations. Performance varied based on pathology studied, with the highest limitation observed in evaluating meningiomas with intratumoral calcifications or calvarial invasion. CONCLUSIONS: The generation of high-resolution CT scans from MR images through cGAN offers promise for a wide range of applications in cranial and spinal neurosurgery, especially as an adjunct for preoperative evaluation. Optimizing cGAN performance on specific anatomical regions may increase its clinical viability.
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BACKGROUND: We assessed the value of positron emission tomography/computed tomography (PET/CT) with [13N]N-ammonia ([13N]N-NH3) and [11C]C-methionine ([11C]C-MET) for the evaluation and management of recurrent secreting pituitary adenoma, which could not be detected by magnetic resonance imaging (MRI) or fluorine-18 fluorodeoxyglucose ([18F]F-FDG) PET. METHODS: Nine consecutive patients with biochemical and clinical evidence of active recurrent tumor not detected by MRI and [18F]F-FDG PET were enrolled in this study. All of the patients underwent [13N]N-NH3 and [11C]C-MET PET/CT, after which the pattern of tracer uptake was studied, the tumor position was located, and a clinical decision was made. RESULTS: In general, [11C]C-MET had a higher uptake in pituitary adenomas (PAs) than that in pituitary tissues, while [13N]N-NH3 had a higher uptake in pituitary tissue than in pituitary adenomas. Increased [11C]C-MET uptake was observed in all nine PAs and three pituitary tissues, while all pituitary tissues and only one pituitary adenoma showed increased [13N]N-NH3 uptake. Four patients had concordant imaging and surgical findings indicative of biochemical remission without hypopituitarism after treatment. Radiotherapy was adopted in two patients, medication in another two, and follow-up observation in one case. CONCLUSION: Combined [11C]C-MET and [13N]N-NH3 PET/CT is effective in the differentiation of PAs from pituitary tissue in recurrent functional PAs with negative MRI or [18F]F-FDG PET. These results provide a valuable reference for further disease management.