Purpose: We evaluated the activity of AZD8205, a B7-H4–directed antibody–drug conjugate (ADC) bearing a novel topoisomerase I inhibitor (TOP1i) payload, alone and in combination with the PARP1-selective inhibitor AZD5305, in preclinical models. Experimental Design: IHC and deep-learning–based image analysis algorithms were used to assess prevalence and intratumoral heterogeneity of B7-H4 expression in human tumors. Several TOP1i-ADCs, prepared with Val-Ala or Gly–Gly–Phe–Gly peptide linkers, with or without a PEG8 spacer, were compared in biophysical, in vivo efficacy, and rat toxicology studies. AZD8205 mechanism of action and efficacy studies were conducted in human cancer cell line and patient-derived xenograft (PDX) models. Results: Evaluation of IHC-staining density on a per-cell basis revealed a range of heterogeneous B7-H4 expression across patient tumors. This informed selection of bystander-capable Val-Ala–PEG8–TOP1i payload AZ14170133 and development of AZD8205, which demonstrated improved stability, efficacy, and safety compared with other linker–payload ADCs. In a study of 26 PDX tumors, single administration of 3.5 mg/kg AZD8205 provided a 69% overall response rate, according to modified RECIST criteria, which correlated with homologous recombination repair (HRR) deficiency (HRD) and elevated levels of B7-H4 in HRR-proficient models. Addition of AZD5305 sensitized very low B7-H4–expressing tumors to AZD8205 treatment, independent of HRD status and in models representing clinically relevant mechanisms of PARPi resistance. Conclusions: These data provide evidence for the potential utility of AZD8205 for treatment of B7-H4–expressing tumors and support the rationale for an ongoing phase 1 clinical study (NCT05123482). See related commentary by Pommier and Thomas, p. 991
The purpose of this study was to determine the effect of postharvest ripening on the concentration of phenolic compounds and antioxidant activity in fruits of ten plum cultivars. The degree of ripeness was defined as the CIRG index, based on the CIE Lab color values and ranging from 1.05 to 10.04, soluble solids (12.9 to 20.7%), and firmness (4.47 to 13.64 N). Fruits were analyzed directly after harvest and after 3 and 6 days of storage at 18 °C. The CIRG index increased by 2% to 23% after 3 days of storage, and by as much as 64% after 6 days, depending on the cultivar. Ripening resulted in increased concentration of phenolic compounds and in higher antioxidant activity. The predominant compounds in the majority of the cultivars were proanthocyanidins, which constituted over 50% of the total polyphenols, at concentrations between 30 and 453 mg 100 g−1 FW. Additionally, postharvest ripening caused the proanthocyanidins to increase up to 76%. The polymerization of proanthocyanidins ranged from 6.6 to 20.0. For some cultivars, the concentration of anthocyanins approximately doubled after 6 days of fruit storage. Fruits of ‘Čačanska Najbolja’ and ‘Čačanska Lepotica’ were characterized by the highest concentration of bioactive compounds and the highest antioxidant activity.
The strawberry is the most widely consumed berry in Europe, with a high content of minerals and bioactive compounds. During drying, the bioactive compounds are concentrated, but also partially degraded due to the interaction of high temperature and oxygen, among other factors. In this study, the effect of ultrasound support during the drying of strawberry slices of two cultivars, ‘Florence’ and ‘Alba’, was investigated. The effect of ultrasound application on the rate of drying, the retention of phenolic compounds and ascorbic acid, as well as the total colour difference, was measured. The time of ultrasonic-assisted drying was shorter than unassisted drying for the ‘Florence’ and ‘Alba’ cultivars, respectively, 35.7% and 34.6%. In addition, the dried product obtained with ultrasound had comparable antioxidant activity and polyphenol content. It was also shown that ultrasound can be successfully used in convective dryers without major equipment modifications.
Berries are a valuable source of health-promoting substances, including vitamins, microelements, and polyphenols. Optimising the extraction efficiency of these compounds during processing is crucial to minimise their loss into the waste stream. Ultrasound technology is recognised as a sustainable and promising tool for improving extraction; however, previous literature has not sufficiently addressed the optimal point of its application in fruit puree processing, and its impact on the sensory properties of the final product has only occasionally been explored. As one of the first reports, this study aimed to determine the optimal moment for ultrasound application within a puree production scheme. In the second stage of the experiment, four recipes based on strawberry and haskap berry were tested. The results demonstrated the potential for enhancing sensory quality of puree by using an ultrasound treatment. It was found that the ultrasound-treated purees showed significantly higher pectin levels and improved rheological properties, while the content of anthocyanins and L-ascorbic acid remained mainly unchanged. This indicates that the non-thermal nature of ultrasound treatment can induce positive changes from a sensory and rheological point of view without causing the degradation of health-promoting compounds, offering a viable strategy for improving berry puree quality.
This study aimed at determining the relationships between the selected quality properties of four new apple clones: ‘Free Redstar’ × ‘Melfree’, ‘Free Redstar’ × ‘Ariwa’, ‘Free Redstar’ × ‘Rajka’, and ‘Free Redstar’ × ‘Rubinola’. Significant differences between the selected clones in terms of quality properties were revealed. For example, the ‘Free Redstar’ × ‘Ariwa’ clone had the highest total sugar content (132.7 g kg−1) and total polyphenol content (TPC) (260.7 mg 100 g−1 GAE), while ‘Free Redstar’ × ‘Rajka’ was characterized by the highest total acid level of 739.0 mg 100 g−1 and the lowest a* value of −0.62, which were significantly different from all other clones. Correlations between image textures and chemical and color characteristics were observed. Among the sugars, sucrose showed the strongest positive correlation with the selected texture parameters of images in color channel Y, obtaining a Pearson correlation coefficient (R) of 0.946, while sorbitol had the strongest negative correlation (R = −0.946) with the selected texture of images in color channel b. In terms of acids, the Pearson correlation coefficient was up to 0.953 for the relationship between the content of citric acid and the selected texture of images in color channel G, and for TPC, the value of Pearson’s correlation coefficient reached 0.921 for the selected texture feature of images in color channel X. Regarding color parameters, the correlations were also strong, reaching 0.945 between parameter a* and the selected texture of the images in color channel a. These findings provide insights into the potential use of image texture analysis in combination with chemical profiling for evaluating apple quality and clone differentiation.
The aim of this study was to evaluate the effects of protein-based (zein) and polysaccharide-based (carboxymethylcellulose, CMC) edible coatings and citric acid (CA) applied prior to freeze-drying on the quality parameters of Jerusalem artichoke (Helianthus tuberosus L.) slices from ‘Albik’ and ‘Rubik’ cultivars. Freeze-drying increased inulin extraction efficiency (57–61 g 100 g−1 vs. 44–45 g 100 g−1 in fresh samples). In the ‘Albik’ cv., CMC and CA coatings significantly minimized L-ascorbic acid losses, with a 10–20% reduction vs. control. For the same cultivar, enhanced polyphenol retention was observed (up to 13%) when CA coating was applied, while the use of zein reduced vitamin C content in both cultivars. Sensory analysis (PCA, 92.4% variance) revealed that CMC improved appearance, texture, and overall acceptability, while zein imparted an off-taste, odor, and fragility. Image texture analysis showed elevated parameters (e.g., HMean) post freeze-drying, with CA inducing the greatest structural changes and zein yielding samples most similar to raw material. Machine learning classification (quadratic/linear SVM, 10-fold CV) achieved 91.5% (‘Albik’) and 81.9% (‘Rubik’) accuracy, perfectly distinguishing raw slices (100%). These findings demonstrate that CMC and CA coatings optimize bioactive retention, sensory quality, and textural differentiation in freeze-dried Jerusalem artichoke, supporting their application in functional food production.