SET8 is a member of the SET domain-containing family and the only known lysine methyltransferase (KMT) that monomethylates lysine 20 of histone H4 (H4K20me1). SET8 has been implicated in many ...essential cellular processes, including cell cycle regulation, DNA replication, DNA damage response, and carcinogenesis. There is no conclusive evidence, however, regarding the effect of SET8 on radiotherapy. In the current study we determined the efficacy of SET8 inhibition on radiotherapy of tumors and the underlying mechanism.
First, we explored the radiotherapy benefit of the SET8 expression signature by analyzing clinical data. Then, we measured a series of biological endpoints, including the xenograft tumor growth in mice and apoptosis, frequency of micronuclei, and foci of 53BP1 and γ-H2AX in cells to detect the SET8 effects on radiosensitivity. RNA sequencing and subsequent experiments were exploited to verify the mechanism underlying the SET8 effects on radiotherapy.
Low expression of SET8 predicted a better benefit to radiotherapy in lung adenocarcinoma (LUAD) and invasive breast carcinoma (BRCA) patients. Furthermore, genetic deletion of SET8 significantly enhanced radiation treatment efficacy in a murine tumor model, and A549 and MCF7 cells; SET8 overexpression decreased the radiosensitivity. SET8 inhibition induced more apoptosis, the frequency of micronuclei, and blocked the kinetics process of DNA damage repair as 53BP1 and γ-H2AX foci remained in cells. Moreover, RNF8 was positively correlated with the SET8 impact on DNA damage repair.
Our results demonstrated that SET8 inhibition enhanced radiosensitivity by suppressing DNA damage repair, thus suggesting that SET8 potentiated radiotherapy of carcinomas. As new inhibitors of SET8 are synthesized and tested in preclinical and clinical settings, combining SET8 inhibitors with radiation warrants consideration for precise radiotherapy.
Ferns and lycophytes have remarkably large genomes. However, little is known about how their genome size evolved in fern lineages. To explore the origins and evolution of chromosome numbers and ...genome size in ferns, we used flow cytometry to measure the genomes of 240 species (255 samples) of extant ferns and lycophytes comprising 27 families and 72 genera, of which 228 species (242 samples) represent new reports. We analyzed correlations among genome size, spore size, chromosomal features, phylogeny, and habitat type preference within a phylogenetic framework. We also applied ANOVA and multinomial logistic regression analysis to preference of habitat type and genome size. Using the phylogeny, we conducted ancestral character reconstruction for habitat types and tested whether genome size changes simultaneously with shifts in habitat preference. We found that 2C values had weak phylogenetic signal, whereas the base number of chromosomes (x) had a strong phylogenetic signal. Furthermore, our analyses revealed a positive correlation between genome size and chromosome traits, indicating that the base number of chromosomes (x), chromosome size, and polyploidization may be primary contributors to genome expansion in ferns and lycophytes. Genome sizes in different habitat types varied significantly and were significantly correlated with habitat types; specifically, multinomial logistic regression indicated that species with larger 2C values were more likely to be epiphytes. Terrestrial habitat is inferred to be ancestral for both extant ferns and lycophytes, whereas transitions to other habitat types occurred as the major clades emerged. Shifts in habitat types appear be followed by periods of genomic stability. Based on these results, we inferred that habitat type changes and multiple whole-genome duplications have contributed to the formation of large genomes of ferns and their allies during their evolutionary history.
•This is the first study to use big data to more comprehensively analyze the evolution of genome sizes of extant ferns and lycophytes.•We detected strong phylogenetic signal for the base number of chromosomes of ferns.•Genome size and chromosome traits (x and 2n) are significantly positive.•Species with larger 2C values are more likely to be epiphytes, and terrestrial habitat is inferred to be ancestral for extant ferns and lycophytes.•Transitions from terrestrial habitat to other habitat types occurred during the evolutionary history of ferns and lycophytes.
Understanding how simple molecules are pieced together in organisms may aid biotechnological manipulation and synthetic approaches to complex natural products. The mantis-associated fungus Daldinia ...eschscholzii IFB-TL01 produces the unusually structured immunosuppressants (±)-dalesconols A and B, along with their congener (±)-dalesconol C, with the (-)-enantiomers in excess. Here we report that these structural and stereochemical peculiarities of dalesconols A-C are a result of promiscuous and atropselective couplings of radicals derived from 1,3,6,8-tetrahydroxynaphthalene, 1,3,8-trihydroxynaphthalene and 1,8-dihydroxynaphthalene. The observed (-)-enantiomeric excess is found to depend on the dominance of particular conformers of naphthol dimer intermediates, which are ligands of laccase.
A position-sensitive CsI(Tl) crystal array coupled with the multi-anode position sensitive photomultiplier tube (PS-PMT), Hamamatsu H8500C, has been developed at the Institute of Modern Physics. An ...effective, fast, and economical readout circuit based on discretized positioning circuit (DPC) bridge was designed for the 64-channel multi-anode flat panel PSPMT. The horizontal and vertical position resolutions are 0.58 mm and 0.63 mm respectively for the 1.0 × 1.0 × 5.0 mm3 CsI(Tl) array, and the horizontal and vertical position resolutions are 0.86 mm and 0.80 mm respectively for the 2.0 × 2.0 × 10.0 mm3 CsI(Tl) array. These results show that the CsI(Tl) crystal array with low cost could be applied in the fields of medical imaging and high-resolution gamma camera.
Purpose
To develop a new nanobiosystem based on folate-functionalized silica-coated gold nanorods and to investigate its cellular uptake and intra-organ biodistribution
in vitro
and
in vivo
.
...Procedures
Ellipsoidal silica-coated gold nanorods (GNRs@SIO
2
) were prepared by seeded growth method using silicon dioxide (SIO
2
) as the shell material. Rhodamine-labeled GNRs@SiO
2
-folic acid (FA) were obtained by reacting the amino group located on GNRs@SiO
2
-FA with rhodamine isothiocyanate. The characteristics of the prepared GNRs@SiO
2
-FA were studied using transmission electron microscopy (TEM) and UV spectra. The 3-4, 5-dimethylthiazol-2-yl-2,5 diphenyltetrazolium bromide (MTT) colorimetric method was used to assess the biocompatibility of GNRs@SiO
2
-FA, and their uptake into cells was observed using TEM.
In vivo
experiments of cellular uptake and study of the intra-organ biodistribution of GNRs@SiO
2
-FA were detected using intrinsic two-photon luminescence.
Results
Analysis of UV spectra confirmed the successfu1 preparation of GNRs@SiO
2
-FA. Results of the MTT assay demonstrated that surface modification of GNRs@SiO
2
-FA resulted in excellent biocompatibility. TEM examination revealed that GNRs@SiO
2
-FA entered the cells via endocytosis, which could connect to cancer cells with high folic acid expression. We found that GNRs exhibit bright luminescence and could be visualized
in vivo
by direct imaging of these particles within the tissue. Additionally, GNRs@SiO
2
-FA could specifically bind to tumor cells. GNRs@SiO
2
-FA entered tumor cells within 24 h and had a heterogeneous distribution with higher accumulation at the tumor cytoplasm.
Conclusion
GNRs@SiO
2
-FA can bind to cells and were found to be internalized by targeted folate receptor-expressing cells via a ligand-receptor-mediated endocytosis pathway, which is very useful in diagnosing diseases as well as in treating neoplasm with I-125 particles.
The diffusion reaction of Mn2+ ions, the bidentate ligand dabco, and Mo(CN)83– units at different temperatures produced 2D layer MnII(dabco)MoV(CN)82·MnII(H2O)6·2H2O (1) and 3D network ...MnII(dabco)2MnII(CH3OH)4MoV(CN)82·2H2O (2). Structural analysis revealed that there are two independent central Mn atoms (Mn1 and Mn2) in the structure for each compound, which exhibit trigonal bipyramid and octahedral arrangement, respectively. Notably, the coordination mode of the Mn2 unit between layers in both compounds was responsible for the resulting structural dimensionalities. The crystal growth process of final products was dominantly controlled by the kinetics. The isolation of both compounds provides an insight into the effect of crystallization temperatures on the formation and structural conversion of manganese octacyanometalates.
The diffusion reaction of Mn
2+
ions, the bidentate ligand dabco, and Mo(CN)
8
3–
units at different temperatures produced 2D layer Mn
II
(dabco)Mo
V
(CN)
8
2
·
Mn
II
(H
2
O)
6
·
2H
2
O (
1
) and ...3D network Mn
II
(dabco)
2
Mn
II
(CH
3
OH)
4
Mo
V
(CN)
8
2
·
2H
2
O (
2
). Structural analysis revealed that there are two independent central Mn atoms (Mn1 and Mn2) in the structure for each compound, which exhibit trigonal bipyramid and octahedral arrangement, respectively. Notably, the coordination mode of the Mn2 unit between layers in both compounds was responsible for the resulting structural dimensionalities. The crystal growth process of final products was dominantly controlled by the kinetics. The isolation of both compounds provides an insight into the effect of crystallization temperatures on the formation and structural conversion of manganese octacyanometalates.
We aimed to compare the therapeutic effect of recombinant tissue plasminogen activator (rt-PA) administered at different time windows within the first 6 hours after onset of acute ischemic stroke ...(AIS). A retrospective analysis was performed of data collected from 194 patients who received rt-PA thrombolysis within 4.5 hours after AIS onset and from 29 patients who received rt-PA thrombolysis between 4.5-6 hours after AIS onset. The National Institutes of Health Stroke Scale (NIHSS) scores were statistically decreased in both groups (P < 0.05) at 24 hours and 7 days after onset. There was no statistical difference in the modified Rankin score or mortality at day 90 after treatment between the two groups (P > 0.05). In conclusion, AIS patients who received rt-PA treatment between 4.5-6 hours after onset were similar in therapeutic efficacy to those who received rt-PA within 4.5 hours after onset. Our results suggest that intravenous thrombolytic therapy for AIS within 4.5-6 hours after onset is effective and safe.
Heading date of rice is a key agronomic trait determining cultivated areas and seasons and affecting yield. In the present study, five primary single segment substitution lines with the same genetic ...background were used to detect quantitative trait loci (QTLs) for heading date in rice. Two QTLs, qHD3 and qHD6 on the short arm of chromosome 3 and the short arm of chromosome 6, respectively, were identified under natural long-day (NLD). Nineteen secondary single segment substitution lines (SSSLs) and seven double segments pyramiding lines were designed to map the two QTLs and to evaluate their epistatic interaction between them. By overlapping mapping, qHD3 was mapped in a 791-kb interval between SSR markers RM3894 and RM569 and qHD6 in a 1 125-kb interval between RM587 and RM225. Results revealed the existence of epistatic interaction between qHD3 and qHD6 under natural long-day (NLD). It was also found that qHD3 and qHD6 had significant effects on plant height and yield traits, indicating that both of the QTLs have pleiotropic effects.
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