Synthesis and evaluation of a 68Ga-labeled spermine derivative for tumor PET imaging.

BACKGROUND: The polyamine transporter system (PTS), which renders it a promising target for tumor therapy and imaging applications, facilitates the transmembrane transport of polyamines. We reported a novel derivative of spermine labeled with gallium-68 ([68Ga]Ga-NOTA-Spermine) for the imaging of the PTS in mouse models of tumor. RESULTS: The radiochemical yield of [68Ga]Ga-NOTA-Spermine was determined to be 64-69 %, demonstrating exceptional stability and radiochemical purity (>98 %). Cellular uptake experiments revealed that A549 cells exhibited peak uptake of [68Ga]Ga-NOTA-Spermine at 90 min (15.4 % ± 0.68 %). Biodistribution analysis demonstrated significant accumulation of [68Ga]Ga-NOTA-Spermine in kidneys and liver, while exhibiting low uptake levels in muscle, brain, and bones. Furthermore, Micro-PET/CT scans conducted on A549 tumor-bearing mouse models indicated substantial uptake of [68Ga]Ga-NOTA-Spermine, with maximum tumor/muscle (T/M) ratios reaching 3.71. CONCLUSION: These results suggest that [68Ga]Ga-NOTA-Spermine holds potential as a PET imaging agent for tumors with high levels of PTS.

A new 68Ga-labeled ornithine derivative for PET imaging of ornithine metabolism in tumors.

Ornithine metabolism plays a vital role in tumorigenesis. For cancer cells, ornithine is mainly used as a substrate for ornithine decarboxylase (ODC) for the synthesis of polyamines. The ODC as a key enzyme of polyamine metabolism has become an important target for cancer diagnosis and treatment. To non-invasively detect the levels of ODC expression in malignant tumors, we have synthesized a novel 68Ga-labeled ornithine derivative ([68Ga]Ga-NOTA-Orn). The synthesis time of [68Ga]Ga-NOTA-Orn was about 30 min with a radiochemical yield of 45-50% (uncorrected), and the radiochemical purity was > 98%. [68Ga]Ga-NOTA-Orn was stable in saline and rat serum. Cellular uptake and competitive inhibition assays using DU145 and AR42J cells demonstrated that the transport pathway of [68Ga]Ga-NOTA-Orn was similar to that of L-ornithine, and it could interact with the ODC after transporting into the cell. Biodistribution and micro-positron emission tomography (Micro-PET) imaging studies showed that [68Ga]Ga-NOTA-Orn exhibited rapid tumor uptake and was rapidly excreted through the urinary system. All above results suggested that [68Ga]Ga-NOTA-Orn is a novel amino acid metabolic imaging agent with great potential of tumor diagnosis.

Transcriptome changes of Apis mellifera female embryos with fem gene knockout by CRISPR/Cas9.

The sex of honey bees is decided by a regulatory cascade comprising of csd, fem and Amdsx. In order to further identify other genes involved in sex determination and differentiation of honey bees in the early stages of embryo development, the CRISPR/Cas9 method was used to knock out fem gene in the embryonic stage of diploid western honey bees, and RNA-seq was used to analyze gene expression changes in the embryo after fem knockout. Finally, we found that the bees had undergone gender changes due to fem knockout. A total of 155 differentially expressed genes (DEGs) were obtained, with 48 up-regulated and 107 down-regulated DEGs in the mutant group compared to the control group. Of them, many genes are related to sex development or differentiation. In addition, 1502 differentially expressed alternative splicing events (DEASEs) related to 1011 genes, including the main honey bee sex-determining genes csd, tra2, fem, and Amdsx, were identified between the mutant group and control group, indicating that fem regulates alternative splicing of a large number of downstream genes. Our results provide valuable clues for further investigating the molecular mechanism of sex determination and differentiation in honey bees.

Expression Profile of microRNAs during Development of the Hypopharyngeal Gland in Honey Bee, Apis mellifera.

The hypopharyngeal gland is an important organ for honey bees to secrete royal jelly, and its secretory activity varies with the age of workers. However, by now, the regulation mechanism of hypopharyngeal gland development is still unclear. Here, the expression profiles of miRNAs in the hypopharyngeal gland of newly emerged workers, nurses, and foragers were investigated via small RNA sequencing. From these three stages, 81 known miRNAs and 135 novel miRNAs have been identified. A total of 85 miRNAs showed expression differences between different development stages, and their target genes were predicted to range from 1 to more than 10. Many of the differentially expressed miRNAs and target genes are related to growth and development or apoptosis. Moreover, dual-luciferase-reporter assays verified that novel-miR-11 directly targets the 3'-untranslated regions of LOC410685 (inactive tyrosine-protein kinase 7) and LOC725318 (uncharacterized protein). These results suggested that miRNAs were widely involved in the developmental regulation of the hypopharyngeal gland in honey bees.

Evaluation of N-(6-[18F]Fluoropyridin-3-yl)glycine PET renography to detect renal function progression in a rat model of diabetic nephropathy.

OBJECTIVE: Given the limitation of biomarkers to predict the renal function progression in diabetic nephropathy, N-(6-[18F]Fluoropyridin-3-yl)glycine (6-[18F]FPyGly) was used to evaluate renal function progression in a rat model of diabetic nephropathy. METHODS: Twenty male Sprague-Dawley rats were randomly divided into four groups, including the healthy control group (HC group), diabetic nephropathy group (DNM group), routine diet treated diabetic nephropathy group (RDNM group), and high fat/high sucrose -diet-fed diabetic nephropathy group (HDNM group). All renal function parameters were determined from animal PET renograms. P and Tmax represent the curve peak counts and the time to the curve peak counts of 6-[18F]FPyGly in kidneys after injection, C1/2 and the 15 min/Peak ratio represent the time from peak to 1/2 peak in the clearance phase, and the ratio of the curve counts at 15 min to the curve peak counts. RESULTS: P, Tmax, C1/2, and 15 min/peak ratio of each rat were significantly correlated with S-Cr, BUN. There were significant differences in Tmax, P, serum creatinine (SCr), and blood urea nitrogen (BUN) levels between HC and DNM groups. P and the 15 min/Peak ratio were significantly different among DNM, RDNM, and HDNM groups, while Tmax and C1/2 were only significantly different between DNM and RDNM or HDNM groups. There only was a significant difference in BUN between the DNM and HDNM groups. CONCLUSION: The renal function parameters P, Tmax, C1/2 and 15 min/peak value obtained by dynamic renal imaging based on 6-[18F]FPyGly could reflect changes of renal function in rats, which had a good correlation with SCr and BUN, and showed more efficient in the diagnosis of diabetic nephropathy and renal function classification than SCr and BUN.

Natural Tendency towards Beauty in Humans: Evidence from Binocular Rivalry.

Although human preference for beauty is common and compelling in daily life, it remains unknown whether such preference is essentially subserved by social cognitive demands or natural tendency towards beauty encoded in the human mind intrinsically. Here we demonstrate experimentally that humans automatically exhibit preference for visual and moral beauty without explicit cognitive efforts. Using a binocular rivalry paradigm, we identified enhanced gender-independent perceptual dominance for physically attractive persons, and the results suggested universal preference for visual beauty based on perceivable forms. Moreover, we also identified perceptual dominance enhancement for characters associated with virtuous descriptions after controlling for facial attractiveness and vigilance-related attention effects, which suggested a similar implicit preference for moral beauty conveyed in prosocial behaviours. Our findings show that behavioural preference for beauty is driven by an inherent natural tendency towards beauty in humans rather than explicit social cognitive processes.