Ultrasmall Glutathione-Protected Gold Nanoclusters as Next Generation Radiotherapy Sensitizers with High Tumor Uptake and High Renal Clearance

Radiotherapy is often the most straightforward first line cancer treatment for solid tumors. While it is highly effective against tumors, there is also collateral damage to healthy proximal tissues especially with high doses. The use of radiosensitizers is an effective way to boost the killing efficacy of radiotherapy against the tumor while drastically limiting the received dose and reducing the possible damage to normal tissues. Here, we report the design and application of a good radiosensitizer by using ultrasmall gold nanoclusters with a naturally occurring peptide (e.g., glutathione or GSH) as the protecting shell. The GSH coated gold nanoclusters can escape the RES absorption, leading to a good tumor uptake (8.1% ID/g at 24 h post injection). As a result, the as-designed Au nanoclusters led to a strong enhancement for radiotherapy, as well as a negligible damage to normal tissues. After the treatment, the ultrasmall gold nanoclusters can be efficiently cleared by the kidney, thereby avoiding potential long term side effects caused by the accumulation of gold atoms in the body. Our data suggest that the ultrasmall peptide protected Au nanoclusters are a promising radiosensitizer for cancer radiotherapy.Comment: 15 Pages, 6 Figures, Scientific Reports 5, 201

Molecular identification and population differentiation of Aurelia spp. ephyrae in sea cucumber aquaculture ponds of northern China

Aurelia spp. ephyrae have been reported to form blooms in sea cucumber aquaculture ponds in the Bohai and Yellow Seas. To identify the species, we carried out a genetic analysis of Aurelia spp. ephyrae and medusae based on mitochondrial 16S rRNA gene. Samples of four Aurelia sp. ephyrae populations were collected in sea cucumber aquaculture ponds and samples of four Aurelia sp. medusae populations were collected in coastal waters. Using a BLASTn search, we found that both the ephyrae collected in the aquaculture ponds and medusae collected in coastal waters belong to Aurelia coerulea. Seventeen haplotypes were recovered from the 16S rRNA gene. The overall haplotype diversity and nucleotide diversity of the 166 A. coerulea individuals were 0.686 and 0.329%, respectively, indicating high haplotype diversity and low nucleotide diversity. Moreover, the haplotype diversity of ephyrae populations were generally lower than that of medusae populations with close sampling points. The genetic differentiation between ephyrae populations collected in the sea cucumber aquaculture ponds and A. coerulea medusae collected in coastal waters was not significant, suggesting the ephyrae populations in the sea cucumber culture ponds were part of the same genetic group as the medusae populations in the coastal waters. Phylogeographic analysis of the 16S rRNA region revealed that there was no significant correlation between the haplotypes and the geographic distribution of populations. Pairwise fixation index values showed significant genetic differentiation and limited gene flow between A. coerulea population of Weifang and other locations

Composition and Potential Functions of Bacterial Communities Associated With Aurelia Polyps

Jellyfish and their associated microbes form an ecological unit called the holobiont. Changes in the composition of dominant microbial assemblages may influence the environmental resilience and function of the holobionts. Differentiating the microbial communities from diverse jellyfish is essential for characterizing the functional contributions of microorganisms but has not been fully explored. In this study, based on 16S rRNA gene sequencing, we investigated the composition of microbial communities associated with two Aurelia polyp species (Aurelia coerulea and Aurelia solida) obtained from seven locations, which were maintained under the same environmental conditions. Sequence analysis showed that the genera Sphingomonas, Phyllobacterium, and Ralstonia were the most abundant members of the Aurelia-associated microbial communities and dominated the core microbiome of the Aurelia polyps in this study. Functional prediction revealed that chemoheterotrophy and aerobic chemoheterotrophy, based on the FAPROTAX dataset, were the primary functions of the associated microbes of Aurelia polyps. In addition, the comparison of microbial communities from different Aurelia polyp populations revealed interspecific instead of intraspecific variation, indicating a correlation between the composition of the symbiotic microbiota and genetic background of Aurelia polyps

Clinical analysis of acute postoperative pain after total laparoscopic hysterectomy for adenomyosis and uterine fibroids – a prospective observational study

AbstractObjective To investigate the outcome of total laparoscopic hysterectomy (TLH) and postoperative pain characteristics and compare the pain severity after TLH for adenomyosis or uterine fibroids.Methods This prospective observational study collected 101 patients received TLH for adenomyosis (AD group) including 41 patients were injected goserelin (3.6 mg) 28 days before TLH, while other adenomyosis patients received TLH without preoperative treatment, and 113 patients received TLH for uterine fibroids (UF group). Pain scores were evaluated at different time sites from operation day to postoperative 72 h using the numeric rating scale. Clinical data were collected from clinical record.Results Operative time and anaesthetic time were longer in the AD group than those in the UF group (66.88 ± 8.65 vs. 64.46 ± 7.21, p = 0.04; 83.95 ± 10.05 vs. 79.77 ± 6.88, p < 0.01), severe endometriosis was quite more common in AD group (23.76% vs. 2.65%, p < 0.01). Postoperative usage of Flurbiprofen in AD group were more than that of UF group (15.48 ± 38.00 vs. 4.79 ± 18.16, p = 0.02). Total pains and abdominal visceral pains of AD group were more severe compared with UF group in motion and rest pattern at several time sites, while incision pain and shoulder pain were similar. The total postoperative pains after goserelin preoperative treatment in AD group were less than that without goserelin preoperative treatment (p < 0.05). The levels of serum NPY, PGE2 and NGF after laparoscopic hysterectomy of adenomyosis reduced with GnRH agonist pretreatment.Conclusions Acute postoperative pain for adenomyosis and uterine fibroids showed considerably different severity, postoperative total pain and abdominal visceral pains of TLH for adenomyosis were more severe compared with uterine fibroids. While patients received goserelin before laparoscopic hysterectomy of adenomyosis suffered from less severity of postoperative total pain than that without goserelin preoperative treatment

Adakitic rocks associated with the Shilu copper–molybdenum deposit in the Yangchun Basin, South China, and their tectonic implications

South China is famous for the extensive magmatism and polymetallic mineralization that took place there in the Mesozoic. Shilu is a large porphyry–skarn Cu–Mo deposit in the Yangchun Basin, South China. The lithology of the Shilu intrusion is granodiorite and quartz diorite, both of which are high-K calc-alkaline series, with high Sr (>400 ppm) content along with low Y and Yb contents. Most of the samples have characteristics of adakite except for a few samples that have slightly higher Y and Yb contents, which may be plausibly explained by crustal contamination. Laser Ablation Inductively Coupled Plasma Mass Spectrometry zircon U–Pb dating revealed ages between 106.6 ± 1.3 and 103.9 ± 0.5 Ma, with multiple magmatic pulses. Molybdenite Re–Os isochron age of 102.2 ± 2.9 Ma (MSWD = 9.4) was determined, which is identical to the youngest zircon U–Pb age (103.9 ± 0.5 Ma) within error. The Shilu intrusion has high oxygen fugacity as indicated by high zircon Ce4+/Ce3+ and EuN/EuN* ratios. Considering the geochemical characteristics (high Sr, and low Y and Yb contents), high oxygen fugacity, and copper mineralization of the Shilu intrusion, it was most likely formed by partial melting of a subducted young oceanic slab. Whole-rock Sr–Nd isotope-, zircon Hf isotope-, and whole-rock trace element analyses show that Shilu adakitic magmas may have interacted with type II enriched mantle and/or crustal materials during ascent. South China was affected by the Pacific tectonic regime to the east and the Neo-Tethys tectonic regime to the south in the Cretaceous. Based on the Pacific Plate drifting and rotation history, it is hard to explain how the Pacific Plate would have subducted and melted, forming adakitic rocks in the Shilu region. Considering the tectonic history of Southeast Asia and the South China Sea, the Neo-Tethys trench should have been much closer to the South China Block in the Cretaceous, and thus have had a greater impact on the South China Block. Based on the subduction direction, time of subduction, and distance between the Neo-Tethys subduction zone and the Shilu deposit, subduction of the Neo-Tethys ridge is the best mechanism for explaining the Shilu adakitic rocks and Cu–Mo mineralization.This study was supported by the DREAM project of MOST China 2016YFC0600408, NSFC 91328204, 41421062, and China Geological Survey (12120114015801). GIGCAS contribution No. IS-000