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In India, amphidiploid (AABB, 2n=36) is a significant oilseed crop, but its small gene pool limits its ability to develop traits of higher breeding and economic value. Through interspecific hybridization from various lines of the progenitor species, resynthesized (RBJ) can provide breeders with additional resources for creating genetically diverse stress-tolerant and high-yielding cultivars. Three accessions and eight accessions were crossed in this study to develop 33 synthetic lines. A total of 28 crosses were attempted, including the three-way crosses, but only the cross combinations with cytoplasm led to successful embryonic development. Molecular diversity analysis of these lines in S generation revealed significant genetic diversity with higher levels of heterozygosity and allelic richness, along with significant variations for the yield-related traits. These results suggest that the synthesized lines could effectively enrich the genetic base of and generate variability for agronomically important traits in a shorter time duration. The characterized variability in the synthetic lines needs to be utilized in hybridization, with already evolved genotypes, in early generations before it is lost due to chromosomal rearrangements, recombination and natural selection.
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http://dx.doi.org/10.3389/fpls.2025.1493618 | DOI Listing |
J Med Chem
September 2025
Repare Therapeutics, 7171 Frederick-Banting, Building 2, H4S 1Z9 Montréal, Québec, Canada.
DNA polymerase theta (Polθ) plays a critical role in repairing DNA double-strand breaks through microhomology-mediated end joining (MMEJ) and has emerged as a key synthetic lethal drug target in cancers with homologous recombination (HR) deficiencies. Its inhibition has shown a strong potential to synergize with PARP inhibitors, particularly in tumors with deleterious or mutations. Here, we describe the discovery and preclinical development of RP-2119, a selective, potent, and bioavailable Polθ ATPase inhibitor.
View Article and Find Full Text PDFToxicon
September 2025
Research and Innovation Hub, Innovation Aesthetics, London UK.
Botulinum Neurotoxin Type A (BoNT-A) remains the cornerstone of glabellar frown line treatment, yet conventional low-dose, high-volume protocols often result in limited durability and imprecise diffusion. This study presents multiscale, in silico framework specifically designed to evaluate high-dose (60-80 Units), low-volume (≤0.045 mL/site) BoNT-A glabellar injection strategies across anatomically realistic conditions.
View Article and Find Full Text PDFCell Stem Cell
August 2025
Centre for Oncology and Immunology, Hong Kong Science Park, Pak Shek Kok, Hong Kong SAR, China; Laboratory of Combinatorial Genetics and Synthetic Biology, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. Electronic address:
The discrepancy between organoid and immortalized cell line cultures for cancer target discovery remains unclear. Here, our multi-tiered clustered regularly interspaced short palindromic repeats (CRISPR) screens reveal in vivo-relevant metabolic dependencies and synthetic lethal pairs that can be uncovered with tumor organoids but not cell lines or even three-dimensional (3D) spheroids. These screens identify lanosterol synthase and acetyl-coenzyme A (CoA) carboxylase inhibitors as effective treatments that impede xenografted tumor growth in mice.
View Article and Find Full Text PDFBioconjug Chem
September 2025
Lobachevsky State University of Nizhny Novgorod, Gagarina av. 23, Nizhny Novgorod 603950, Russian Federation.
Latest studies highlight boron-dipyrromethene (BODIPY) with a -methyl moiety as a promising photoremovable protecting group due to its activation within the phototherapeutic window. While BODIPYs inherently generate ROS and act as photosensitizers, few studies have explored combining their photouncaging capability with photodynamic therapy (PDT). Herein, we developed novel -methyl-BODIPY conjugates of the DNA alkylator Boc--CBI and the multikinase inhibitor cabozantinib derivative activated by green or red light.
View Article and Find Full Text PDFMath Biosci Eng
July 2025
Department of Applied Mathematics, University of Waterloo, Waterloo, ON, N2L 3G1, Canada.
Understanding the metabolic adaptations of cancer cells is crucial for uncovering potential therapeutic targets and improving treatment strategies. In this study, we present a hybrid modeling framework that combines Physics-Informed Neural Networks (PINNs) and Universal PINNs (UPINNs) to investigate glucose-lactate metabolism in glioblastoma cell lines. We first employed PINNs to infer critical model parameters governing glucose uptake and phenotypic switching in tumor cells, demonstrating high accuracy using synthetic data.
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