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Carotenoids constitute a large group of natural pigments widely distributed in nature. These compounds not only provide fruits and flowers with distinctive colors, but also have significant health benefits for humans. Lutein and zeaxanthin, both oxygen-containing carotenoids, are considered to play vital roles in promoting ocular development and maintaining eye health. However, humans and mammals cannot synthesize these carotenoid derivatives, which can only be taken from certain fruits or vegetables. Here, by introducing four endogenous synthetic genes, SlLCYE, SlLCYB, SlHYDB, and SlHYDE under fruit-specific promoters, we report the metabolic engineering of lutein/zeaxanthin biosynthesis in tomato fruit. Transgenic lines overexpression of one (SlLCYE), two (SlLCYE and SlLCYB; SlLCYB and SlHYDB), and all these four synthetic genes re-established the lutein/zeaxanthin biosynthetic pathways in the ripe tomato fruit and thus resulted in various types of carotenoid riched lines. Metabolic analyses of these engineered tomato fruits showed the strategy involved expression of SlLCYE tends to produce α-carotene and lutein, as well as a higher content of β-carotene and zeaxanthin was detected in lines overexpressing SlLCYB. In addition, the different combinations of engineered tomatoes with riched carotenoids showed higher antioxidant capacity and were associated with a significantly extended shelf life during postharvest storage. This work provides a successful example of accurate metabolic engineering in tomato fruit, suggesting the potential utility for synthetic biology to improve agronomic traits in crops. These biofortified tomato fruits could be also exploited as new research subjects for studying the health benefits of carotenoid derivatives.

Abstract At present, radiotherapy (RT) still acquires limited success in clinical due to the lessened DNA damage under hypoxia and acquired immune tolerance owing to the amplified programmed death ligand‐1 (PD‐L1) expression. Incredibly, intracellular PD‐L1 expression depression is proven to better sensitize RT by inhibiting DNA damage repair. However, the disability of the clinically used antibodies in disrupting the extracellular PD‐L1function still limits the effectiveness of radio‐immunotherapy. Therefore, better PD‐L1 regulation strategies are still urgently needed to better sensitize radio‐immunotherapy. Hence, for this purpose, TPP‐LND is synthesized by linking mitochondrial‐targeted triphenylphosphine cations (TPP+) to the antineoplastic agent lonidamine (LND), which significantly reduces the dose needed for LND to induce effective oxidative phosphorylation inhibition (2 vs 300 µM). Then, TPP‐LND is wrapped with liposomes to form TPP‐LND@Lip nanoparticles. By doing this, TPP‐LND@Lip nanoparticles can sensitize RT by reversing the hypoxic microenvironment of tumors to generate more DNA damage and reducing the expression of PD‐L1 via enhancing the adenosine 5′‐monophosphate‐activated protein kinase activation. As expected, these well‐designed economical TPP‐LND@Lip nanoparticles are more effective than conventional anti‐PD‐L1 antibodies to some extent.

BackgroundRadiation proctitis is a common complication after radiotherapy for cervical cancer. Unlike simple radiation damage to other organs, radiation proctitis is a complex disease closely related to the microbiota. However, analysis of the gut microbiota is time-consuming and expensive. This study aims to mine rectal information using radiomics and incorporate it into a nomogram model for cheap and fast prediction of severe radiation proctitis prediction in postoperative cervical cancer patients.MethodsThe severity of the patient’s radiation proctitis was graded according to the RTOG/EORTC criteria. The toxicity grade of radiation proctitis over or equal to grade 2 was set as the model’s target. A total of 178 patients with cervical cancer were divided into a training set (n = 124) and a validation set (n = 54). Multivariate logistic regression was used to build the radiomic and non-raidomic models.ResultsThe radiomics model [AUC=0.6855(0.5174-0.8535)] showed better performance and more net benefit in the validation set than the non-radiomic model [AUC=0.6641(0.4904-0.8378)]. In particular, we applied SHapley Additive exPlanation (SHAP) method for the first time to a radiomics-based logistic regression model to further interpret the radiomic features from case-based and feature-based perspectives. The integrated radiomic model enables the first accurate quantitative assessment of the probability of radiation proctitis in postoperative cervical cancer patients, addressing the limitations of the current qualitative assessment of the plan through dose-volume parameters only.ConclusionWe successfully developed and validated an integrated radiomic model containing rectal information. SHAP analysis of the model suggests that radiomic features have a supporting role in the quantitative assessment of the probability of radiation proctitis in postoperative cervical cancer patients.