Exosomes are a class of naturally occurring nanoparticles that are secreted endogenously by mammalian cells. Clinical applications for exosomes remain a challenge because of their unsuitable donors, low scalability, and insufficient targeting ability. In this study, we developed a dual-functional exosome-based superparamagnetic nanoparticle cluster as a targeted drug delivery vehicle for cancer therapy. The resulting exosome-based drug delivery vehicle exhibits superparamagnetic behavior at room temperature, with a stronger response to an external magnetic field than individual superparamagnetic nanoparticles. These properties enable exosomes to be separated from the blood and to target diseased cells. In vivo studies using murine hepatoma 22 subcutaneous cancer cells showed that drug-loaded exosome-based vehicle delivery enhanced cancer targeting under an external magnetic field and suppressed tumor growth. Our developments overcome major barriers to the utility of exosomes for cancer application.
Osmotic stresses such as drought, salinity, and cold are major environmental factors that limit agricultural productivity worldwide. Protein phosphorylation/dephosphorylation are major signalling events induced by osmotic stress in higher plants. Sucrose non-fermenting 1-related protein kinase2 family members play essential roles in response to hyperosmotic stresses in Arabidopsis, rice, and maize. In this study, the function of TaSnRK2.4 in drought, salt, and freezing stresses in Arabidopsis was characterized. A translational fusion protein of TaSnRK2.4 with green fluorescent protein showed subcellular localization in the cell membrane, cytoplasm, and nucleus. To examine the role of TaSnRK2.4 under various environmental stresses, transgenic Arabidopsis plants overexpressing wheat TaSnRK2.4 under control of the cauliflower mosaic virus 35S promoter were generated. Overexpression of TaSnRK2.4 resulted in delayed seedling establishment, longer primary roots, and higher yield under normal growing conditions. Transgenic Arabidopsis overexpressing TaSnRK2.4 had enhanced tolerance to drought, salt, and freezing stresses, which were simultaneously supported by physiological results, including decreased rate of water loss, enhanced higher relative water content, strengthened cell membrane stability, improved photosynthesis potential, and significantly increased osmotic potential. The results show that TaSnRK2.4 is involved in the regulation of enhanced osmotic potential, growth, and development under both normal and stress conditions, and imply that TaSnRK2.4 is a multifunctional regulatory factor in Arabidopsis. Since the overexpression of TaSnRK2.4 can significantly strengthen tolerance to drought, salt, and freezing stresses and does not retard the growth of transgenic Arabidopsis plants under well-watered conditions, TaSnRK2.4 could be utilized in transgenic breeding to improve abiotic stresses in crops.
Genetic analyses of nine traits associated with stem water-soluble carbohydrate (SWSC) accumulation and remobilization at grain-filling period under drought stress (DS) and well-watered (WW) conditions were undertaken using doubled haploid lines (DHLs) derived from two Chinese common wheat cultivars. Some significantly and very significantly positive correlation was observed among nine traits associated with SWSC. Higher phenotypic values for most traits were detected under DS. Broad sense heritabilities (h 2 B ) of the traits showed wide fluctuations between two water treatments. A total of 48 additive and 62 pairs of epistatic QTL for nine traits were identified as distributing on all 21 chromosomes. A majority of QTL involved significant additive and epistatic effects with interactions of QTL and environments (QEIs). Two additive and two pairs of epistatic loci involved only QEIs without corresponding significant additive or epistatic effects. The contributions of the additive QEIs were two-to fourfolds higher than those of their corresponding additive QTL. Most of the additive QEIs for traits associated with SWSC interacted with DS. In addition, some QTL for the grain-filling efficiencies and thousand-grain weight were colocated in the same or adjacent chromosome intervals with QTL for accumulation and remobilization efficiency of SWSC before 14 days after flowering.
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