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Radiotherapy (RT) is a local control of tumors using radiation, including external irradiation (EBRT) and internal irradiation (RIT). Cancer radiotherapy based on external beams is a major clinical treatment for...

The current experiments were designed to determine the diurnal carbon partitioning among sorbitol, sucrose, and starch in mature apple (Malus domestica Borhk. cv. Gala) leaves and to determine whether photoperiod altered photosynthate partitioning among carbohydrates. Sorbitol accounted for > 80% of newly fixed 14C-labelled carbohydrate during the light period. Forty-seven percent of sorbitol that had accumulated at the end of the light period disappeared during the dark period. As photoperiod increased from 1 to 10 h, sorbitol, glucose, fructose, and starch concentrations in mature apple leaves increased, but were stable from 10 to 14 h. Sucrose concentration, on the other hand, decreased slightly as photoperiod increased. As a result, sorbitol to sucrose ratios increased from 2 in the 1-h photoperiod to 5 in the 10-h photoperiod. The relative partitioning of 14C into sorbitol increased, whereas the partitioning into sucrose, glucose, and fructose decreased as photoperiod increased from 1 to 10 h. Our results suggest that longer photoperiods favoured sorbitol over sucrose accumulation while shorter photoperiods favoured sucrose over sorbitol synthesis. The observed changes in sorbitol and sucrose concentrations with changes in photoperiod may result from different rates of synthesis and export.

Defective left–right (LR) organization involving abnormalities in cilia ultrastructure causes laterality disorders including situs inversus (SI) and heterotaxy (Htx) with the prevalence approximately 1/10,000 births. In this study, we describe two unrelated family trios with abnormal cardiac LR patterning. Through whole-exome sequencing (WES), we identified compound heterozygous mutations (c.805-1G >C; p. Ile269GlnfsTer8/c.1117dupA; p.Thr373AsnfsTer19) (c.29T>C; p.Ile10Thr/c.356A>G; p.His119Arg) of NEK3, encoding a NIMA (never in mitosis A)-related kinase, in two affected individuals, respectively. Protein levels of NEK3 were abrogated in Patient-1 with biallelic loss-of function (LoF) NEK3 mutations that causes premature stop codon. Subsequence transcriptome analysis revealed that NNMT (nicotinamide N-methyltransferase) and SIRT2 (sirtuin2) was upregulated by NEK3 knockdown in human retinal pigment epithelial (RPE) cells in vitro, which associates α-tubulin deacetylation by western blot and immunofluorescence. Transmission electron microscopy (TEM) analysis further identified defective ciliary ultrastructure in Patient-1. Furthermore, inner ring components of nuclear pore complex (NPC) including nucleoporin (NUP)205, NUP188, and NUP155 were significantly downregulated in NEK3-silenced cells. In conclusion, we identified biallelic mutations of NEK3 predispose individual to abnormal cardiac left–right patterning via SIRT2-mediated α-tubulin deacetylation and downregulation of inner ring nucleoporins. Our study suggested that NEK3 could be a candidate gene for human ciliopathies.

The main objective of the present article was to prepare stable and well-dispersible budesonide (BUD) nanosuspensions by microfluidizer method. The morphology, particle size, and zeta potential of formulation were investigated and in vitro release and in vivo lung distribution were evaluated. Characterizations showed that BUD nanosuspensions were spherical in shape with a smooth surface. The measured average particle size was 122.5 ± 6.3 nm, and ζ potential was - 13.6 ± 0.4 mV. In vitro release behavior of three batches BUD nanosuspensions had a good reproduction. The deposition distribution of BUD different formulations was measured using a modified multi-stage liquid collision method. The data showed that BUD nanosuspensions have the most outstanding deposition distribution with fine particle ratio 82.2%. Compared with normal particle and micronized particles, nanosuspensions were easier to be distributed in lung. After inhalation of 1 h, the drug concentration can reach 872.9 ng/g, which was extremely significantly different from normal particles (p < 0.01) and significantly different from micronized particles (p < 0.05).