Abstract

We investigated the combined effects of ataxia telangiectasia and Rad3-related (ATR) inhibition, ablative radiotherapy, and immune checkpoint inhibitor (ICI) therapy against lung cancer. ATR inhibitor was administered combined with ablative radiotherapy to assess its radiosensitizing effect on lung cancer cells. Treatment response and survival were evaluated in vivo using A549 xenograft flank tumor and synchronous LLC lung and flank tumor mouse models. Mice received ablative radiotherapy (12 Gy/d for 2 d), ATR inhibitor, and ICI. The tumor microenvironment was assessed in irradiated flank and non-irradiated lung tumors. Programmed death-ligand 1 expression was upregulated after irradiation. ATR inhibition attenuated this upregulation. ATR inhibitor pretreatment decreased cell survival after irradiation by inhibiting DNA double-strand break repair, inducing mitotic cell death, and altering cell cycle progression. ATR inhibition enhanced radiation-induced damage-associated molecular patterns determined by high mobility group box 1 quantification and activated the cyclic GMP-AMP synthase-stimulator of interferon genes pathway. Combined ATR inhibition and ablative radiotherapy inhibited tumor growth and improved survival in mice. Adding ICI therapy further enhanced local antitumor effects, reducing the metastatic lung tumor burden and remodeling the tumor microenvironment through immunogenic cell death induction and enhanced immune cell infiltration. Triple therapy increased immune cell infiltration in distant non-irradiated lung tumors and stimulated the generation of protective T-cell immunity in splenocytes. Safety analysis showed minimal toxicity. ATR inhibition enhanced the efficacy of ablative radiotherapy and immunotherapy in lung cancer. These findings underscore the importance of combination therapies for enhancing systemic antitumor immune responses and outcomes.

• Book : 74(1)
• Pub. Date : 2025
• Page : pp.8
• Keyword :

Abstract

Burning plasma performance, transport, and the effect of hydrogen isotope (H, D, D-T fuel mix) on confinement has been predicted for ITER baseline scenario (IBS) conditions using nonlinear gyrokinetic profile predictions. Accelerated by surrogate modeling (Rodriguez-Fernandez et al 2022 Nucl. Fusion62 076036), high fidelity, nonlinear gyrokinetic simulations performed with the CGYRO code (Candy et al 2016 J. Comput. Phys.324 73), were used to predict profiles of Ti, Te, and ne while including the effects of alpha heating, auxiliary power (NBI + ECH), collisional energy exchange, and radiation losses inside of $ r / a $ = 0.9. Predicted profiles and resulting energy confinement are found to produce fusion power and gain that are approximately consistent with mission goals ($ P_{\text{fusion}} = 500 $ MW at Q = 10) for the baseline scenario and exhibit energy confinement that is within 1σ of the H-mode energy confinement scaling. The power of the surrogate modeling technique is demonstrated through the prediction of alternative ITER scenarios with reduced computational cost. These scenarios include conditions with maximized fusion gain and an investigation of potential resonant magnetic perturbation (RMP) effects on performance with a minimal number of gyrokinetic profile iterations required (3-6). These predictions highlight the stiff ITG nature of the core turbulence predicted in the ITER baseline and demonstrate that $ Q @@\symbol{'3E} @@ $ 17 conditions may be accessible by reducing auxiliary input power while operating in IBS conditions. Prediction of full kinetic profiles allowed for the projection of hydrogen isotope effects around ITER baseline conditions. The gyrokinetic fuel ion species was varied from H, D, and 50/50 D-T and kinetic profiles were predicted. Results indicate that a weak or negligible isotope effect will be observed to arise from core turbulence in IBS conditions. The resulting energy confinement, turbulence, and density peaking, and the implications for ITER operations will be discussed.

• Book : 65(1)
• Pub. Date : 2025
• Page : pp.016002
• Keyword :

• Book : 603()
• Pub. Date : 2025
• Page : pp.155477
• Keyword :

ABSTRACT Nuclear magnetic resonance (NMR) is a spectroscopy technique widely used by chemists and physicists to determine the chemical structure of molecules that was adapted to generate imaging, known as nuclear magnetic resonance imaging (MRI), which is widely used in medical diagnosis. The importance of NMR in chemistry, physics, medicine, materials, and agriculture has been recognized with several Nobel Prizes in Physics, 1952, Chemistry, 1991 and 2002, and Medicine in 2003. Therefore, NMR can be applied to obtain: i) imaging of the human body, animal and materials; ii) high-resolution spectra to obtain structural and dynamical information of chemicals, materials etc.; and iii) quantitative and qualitative information of chemical composition of products such as food and agricultural products, using low-resolution relaxometry. High-resolution NMR and MRI have been applied in agri-food products, mostly as a research tool as they typically rely on expensive and bulk instruments, which restrict their uses in routine applications. The NMR sensors that have been more frequently used in agri-food products are based on low-resolution or low-field or time-domain NMR (TD-NMR) instruments. These low-cost instruments have been used for qualitative and quantitative analysis of agri-food products such as intact seeds and grains, intact fruits, meat, oils, and processed foods. In this paper, an overview of the NMR techniques and its main instrumentation aspects are presented, and some applications of TD-NMR and MRI in the non-invasive analysis of food, seeds, and others agricultural products are discussed.

• Book : 29(3)
• Pub. Date : 2025
• Page : pp.e280966
• Keyword :

Abstract

Immunostimulant phytogenic feed additives are given great concern for improving fish health, growth, immune responses, and resistance to diseases. This research investigated the impact of dietary propolis (PRO), turmeric (TUR), and their combination on the growth, hematology, antioxidant-immune responses, and their regulating genes in Nile tilapia (Oreochromis niloticus) during Edwardsiella tarda challenge. For 8 weeks, a total number of 320 fish (20.70 ± 0.14 g) were allocated into four groups at random, each with eight replicates (10 fish each). The first group (1st) was given the basal diet (control) without any supplements. The 2nd, 3rd, and 4th groups were supplemented with 1% PRO, 1% TUR, and the mixture (1%PRO + 1%TUR), respectively. The experimental groups were challenged intraperitoneally with E. tarda at a dose of 0.1 mL (1 × 10⁵ CFU) at the termination of the feeding trial, and the fish survival was estimated for an additional 7 days. The results demonstrated that fish-fed diets supplemented with PRO and/or TUR showed higher body weight, condition factor, specific growth rate, feed intake, and feed efficiency utilization than the control group (P < 0.05). The hematological, protein profile, and antioxidant-immune (total antioxidant capacity, lysozymes, and IgM) parameters were substantially improved in the challenged fish fed on PRO and/or TUR diets compared to the challenged non-fed fish. The lipid profile and malondialdehyde were substantially decreased in the challenged fish fed on PRO and/or TUR diets compared to the challenged non-fed group. Notably, a down-turning of nuclear factor kappa B (NFκB) and tumor necrosis factor-alpha (TNF-α) expression with up-turning of nuclear factor erythroid 2-related factor 2 (Nrf2) and transforming growth factor-beta (TGF-β) expression was noticed in the challenged fish fed on PRO and/or TUR diets compared to the challenged non-fed fish. Noteworthy, dietary PRO and/or TUR improved the fish survival during E. tarda challenge. The mixture of PRO and TUR can be added to Nile tilapia diets to enhance their growth, immune response, and resistance to E. tarda. These outcomes help in the sustainable development of the Nile tilapia culture industry.

Graphical Abstract

• Book : 33(1)
• Pub. Date : 2025
• Page : pp.46
• Keyword :

• Book : 226()
• Pub. Date : 2025
• Page : pp.112257
• Keyword :

• Book : 226()
• Pub. Date : 2025
• Page : pp.112166
• Keyword :

• Book : 226()
• Pub. Date : 2025
• Page : pp.112245
• Keyword :

• Book : 226()
• Pub. Date : 2025
• Page : pp.112274
• Keyword :

• Book : 211()
• Pub. Date : 2025
• Page : pp.111027
• Keyword :