Sharma, R. A. | bioRxiv Science

bioRxiv2026

Reprogramming of Lipid Metabolism by FLASH Radiotherapy Selectively Protects Radiosensitive Normal Tissues

FLASH radiotherapy, delivered at ultra-high dose rates exceeding 100 Gy/s, spares normal tissues while maintaining tumor control, yet the molecular mechanisms underlying this differential response remain poorly understood. Here we employed spatial and bulk multi-omics to investigate lipid and protein remodeling in tongue tissue and Mouse oral carcinoma 2 (MOC2) tumors at two weeks post-irradiation with FLASH or conventional dose-rate (CONV) proton radiotherapy. Bulk lipidomics revealed that CONV irradiation induced marked triglyceride (TG) depletion in tongue tissue, whereas FLASH attenuated this depletion. Spatial lipidomics using MALDI-MSI demonstrated that this TG loss was spatially restricted to minor salivary glands, identifying these radiosensitive structures as focal points of radiation-induced lipid damage. Additionally, FLASH irradiation uniquely promoted increases in membrane phospholipids and their lysophospholipid intermediates, consistent with active phospholipid turnover rather than passive damage avoidance. Proteomics revealed divergent metabolic programs: CONV activated a destructive cascade characterized by Ces1d depletion, Acox1-mediated peroxisomal {beta}-oxidation, and Acot7-driven fatty acid overflow, collectively defining a lipid droplet collapse; whereas FLASH engaged a protective program featuring Mgll suppression, Apoe-mediated triglyceride redistribution, and Lypla2-mediated lysophospholipid clearance. We propose a lipid metabolic reprogramming hypothesis in which FLASH not only minimizes acute oxidative damage but actively reprograms lipid metabolism to preserve lipid droplet stores and promote membrane remodeling. These findings provide a putative molecular foundation for the FLASH effect and support published data on the protection of normal tissues.

cancer biology↗

bioRxiv2025

Transcriptomic profiling of desert tree Prosopis cineraria under heat stress reveals potential role of multiple gene families in its high thermotolerance

The static nature of plants restrains their potential to evade heat stress and requires them to withstand stress through inherent defence abilities. Prosopis cineraria is a leguminous phreatophyte distributed across arid and semi-arid regions of India and can tolerate very high temperatures due to its adaptive physiological and biochemical mechanisms. Therefore, P. cineraria represents a repository of genes for abiotic stress tolerance. Two-months-old P. cineraria plants were subjected to heat stress at two different temperature regimes and transcriptome sequencing was performed to identify differentially expressed genes (DEGs). A total of 1151 and 1562 DEGs were observed in response to 45 and 55 heat stress compared to control, respectively, indicating that 55 treatment has a pronounced effect on P. cineraria. The transcriptomic data highlighted the potential role of multiple gene families and their interactions for high thermotolerance of P. cineraria. The expression of a few representative heat stress-responsive genes was validated with real-time qPCR. The in-depth bioinformatic analysis provided the detailed transcriptome profiling, supported by its validation, and new insights for important abiotic stress-related genes from thermotolerant P. cineraria, which can be used for crop improvement.

plant biology↗