Background: Despite studies on positron emission tomography/magnetic resonance imaging (PET/MRI) in oncological imaging with high soft-tissue contrast resolution, PET/MRI has not been studied in ophthalmology. 89 Zr-bevacizumab, designed as a probe for PET, targets vascular endothelial growth factor, which is highly expressed in ocular angiogenesis. Intravitreal injections of bevacizumab agents have curative effects on ocular disease. Objectives: To study the ocular biodistribution of 89 Zr-bevacizumab in New Zealand rabbits using PET/MRI. Materials and Methods: 89 Zr-bevacizumab, synthesized from conjugated bevacizumab and 89 Zr-oxalate, and the purity of radiolabeled antibodies were determined using radio high-performance liquid chromatography (radio-HPLC). Instant thin-layer chromatography (ITLC) was utilized to differentiate the labeled product from aggregates and unlabeled 89 Zr. 89 Zr-bevacizumab was injected 2 mm from the left limbus into the vitreous humor of six normal New Zealand white rabbits. Micro-PET was utilized for dynamic imaging from 5 minutes to 60 minutes postinjection and for static imaging at 4 hours, 24 hours, 48 hours, 120 hours, and 144 hours (10-minutes scans) postinjection. PET/MRI scans were fused using PMOD software. Results: 89 Zr-bevacizumab with a radiochemical purity of 93.21% was monitored via PET imaging. Radioactivity levels in the eyes plateaued approximately 5 minutes after administration of 89 Zr-bevacizumab, and the measured vitreous values decreased from 340.52 ± 41.6% injected dose (ID)/g to 21.53 ± 3.39%ID/g by 144 hours. The half-life of the drug in the eye was calculated for 84.25 hours. Conclusion:89 Zr-bevacizumab could be monitored in animals by PET imaging, and the radiolabel exhibited high sensitivity in the vitreous body. Radioactivity levels in the eyes plateaued approximately 5 minutes after administration. This study clearly demonstrates the biodistribution of 89 Zr-bevacizumab.
Recently, biomimetic nanoparticles for tumor−targeted therapy have attracted intensifying interest. Although exosomes are an excellent biomimetic material, numerous challenges are still hindering its clinical applications, such as low yield, insufficient targeting efficiency, and high cost. In this work, urinary exosomes (UEs) with high expression of CD9 and CD47 were extracted from breast cancer patients by a non−invasive method. Here, a nanotechnology approach is reported for tumor homologous targeting via CD9 and phagocytosis escape via CD47 through UE−coated poly (2−ethyl−2−oxazoline)−poly (D, L−lactide) (PEOz−PLA) nanoparticles (UEPP NPs). The cytotoxic agent doxorubicin (DOX)−loaded UEPP (UEPP−D) NPs with an initial particle size of 61.5 nm showed a burst release under acidic condition mimicking the tumor microenvironment. In vitro experiments revealed that UEPP−D NPs exhibited significantly improved cellular uptake, cytotoxicity, and apoptosis in MCF−7 cell lines as compared to DOX−loaded PEOz−PLA nanoparticles (PP−D NPs) and free DOX. More importantly, anti−phagocytosis and pharmacokinetic studies confirmed that UEPP−D NPs had superior immune escape ability and significantly prolonged the drug’s bloodstream circulation in vivo. Finally, UEPP−D NPs showed a markedly higher antitumor efficacy and lower side−toxicity in MCF−7 tumor bearing nude mice model. Thus, this versatile nano−system with immune escape, homologous targeting, and rapid response release characteristics could be a promising tool for breast cancer treatment.
Grapes are one of the world's largest fruit crops, which are rich in nutrients and taste. Summer Black, Gui Fei, Kyoho Grape, Giant Rose, Shine Muscat, and Rosario Bianco are the six most popular table grapes in Wuxi city, Jiangsu province. Owing to the lack of comprehensive investigations of metabolites in table grapes, the metabolic causes of differences in their taste are unknown. In this study, metabolites of six table grapes were profiled using ultrahigh-performance liquid chromatography-Q-Exactive Orbitrap tandem mass spectrometry combined with multivariate analysis. Orthogonal partial least squares discriminant analysis discriminated among the metabolites of these varieties. Metabolic pathway analysis revealed that carbohydrate and amino acid metabolisms were highly conserved among these varieties. Our results suggest that the taste differences in the six table grape varieties can be explained by variations in composition and abundance of carbohydrates, organic acids, amino acids, and polyphenols. This study provides comprehensive insights into the underlying metabolic causes of taste variation in table grapes.
Discourse markers (DMs for short hereafter) are used widely by native speakers and L2 learners. Previous studies are mostly about the acquisition and application of DMs, but studies on the potential factors that might affect the use of DMs are rare. Under the Relevance Theory, the present corpus-based study aims to reveal the influence of gender and oral proficiency on the use of DMs by Chinese English majors. It found that: (1) generally speaking, the variety of DMs employed by Chinese learners of English is rather limited; (2) male Chinese learners of English use more DMs than female learners; (3) high proficiency Chinese learners of English employ more DMs than the low proficiency group; moreover, the variety of DMs used by the former group is much larger than that of the latter. These findings reveal that the learner factors of gender and oral proficiency do influence the use of DMs in L2 learners' conversations and they should be taken into consideration when we are learning or researching.
Background: It is important to assess the nutritional status of patients who have experienced adverse drug reactions (ADRs) after chemotherapy. We aimed to explore the nutritional status of patients who developed ADRs after chemotherapy, using the Nutritional Risk Screening 2002 (NRS 2002) tool, the Onodera Prognostic Nutrition Index (OPNI), and their combined application.Methods: NRS2002 screening and OPNI calculation for patients before chemotherapy. Patients with ADRs after chemotherapy were grouped according to the NRS 2002, OPNI, and combined scores from both assessments. The types of ADRs were classified according to the National adverse drug reaction monitoring system (http://www.adrs.org.cn/).The impact of nutritional risk on the classification and types of ADRs in cancer chemotherapy patients was analyzed. Logistic regression was used to analyze the key influencing factors of gastrointestinal damage and bone marrow suppression. the consistency between the NRS 2002, OPNI, and their combined application analyzed. Results:The difference in body mass index (BMI) scores between the OPNI (P=0.041) and NRS 2002 groups was statistically significant (P=0.051). The difference in ADR type in the OPNI subgroups (P=0.04) was statistically significant. It showed that the proportion of new and severe ADRs in the low OPNI group (47.14%) was significantly higher than that in the high OPNI group (27.13%). The differences in digestive tract-associated ADRs were statistically significant among the OPNI groups (P=0.004), NRS 2002 groups (P=0.012), and combined measures groups (P=0.000), as were the differences in myelosuppressive-type ADRs in the OPNI groups (P=0.035), NRS 2002 groups (P=0.000), and combined measures groups (P=0.000).Logistic regression analysis showed that BMI was the key influencing factor for digestive tract-associated ADRs (95% CI: 1.267, 95% CI: 1.022-1.570, P=0.031) and myelosuppressive-type ADRs (95% CI: 1.213, 95% CI: 1.020-1.443, P=0.029). It had good consistency with the combined measures of nutritional risk (Kappa value =0.675).Conclusions: Patients with severe ADRs after chemotherapy showed low OPNI values, high NRS 2002 scores, and malnutrition. These patients also had a significantly increased incidence of digestive tract and myelosuppressive-type ADRs with BMI as the key influencing factor. The combined assessments showed good consistency with the NRS 2002 scores.
A novel optimal multilevel thresholding algorithm for image segmentation is presented to deal with RAPD Fingerprint of acinetobacter calcoaceticus-baumannii. The proposed algorithm is an artificial immune network used to optimize multilevel thresholds of image segmentation. In addition, a fast fuzzy clustering technique is used to improve efficiency of the algorithm. Experimental results show that the algorithm can effectively extract fingerprint from the images to facilitate genotyping analysis of RAPD fingerprinting of acinetobacter calcoaceticus-baumannii.
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