2,311 research outputs found
Synergistic binding of actinomycin D and echinomycin to DNA mismatch sites and their combined anti-tumour effects
Combination cancer chemotherapy is one of the most useful treatment methods to achieve a synergistic effect and reduce the toxicity of dosing with a single drug. Here, we use a combination of two well-established anticancer DNA intercalators, actinomycin D (ActD) and echinomycin (Echi), to screen their binding capabilities with DNA duplexes containing different mismatches embedded within Watson-Crick base-pairs. We have found that combining ActD and Echi preferentially stabilised thymine-related T:T mismatches. The enhanced stability of the DNA duplex-drug complexes is mainly due to the cooperative binding of the two drugs to the mismatch duplex, with many stacking interactions between the two different drug molecules. Since the repair of thymine-related mismatches is less efficient in mismatch repair (MMR)-deficient cancer cells, we have also demonstrated that the combination of ActD and Echi exhibits enhanced synergistic effects against MMR-deficient HCT116 cells and synergy is maintained in a MMR-related MLH1 gene knockdown in SW620 cells. We further accessed the clinical potential of the two-drug combination approach with a xenograft mouse model of a colorectal MMR-deficient cancer, which has resulted in a significant synergistic anti-tumour effect. The current study provides a novel approach for the development of combination chemotherapy for the treatment of cancers related to DNA-mismatches
Zinc-Catalyzed Asymmetric Formal [4+3] Annulation of Isoxazoles with Enynol Ethers by 6π Electrocyclization: Stereoselective Access to 2H-Azepines.
6π electrocyclization has attracted interest in organic synthesis because of its high stereospecificity and atom economy in the construction of versatile 5-7-membered cycles. However, examples of asymmetric 6π electrocyclization are quite scarce, and have to rely on the use of chiral organocatalysts, and been limited to pentadienyl-anion- and triene-type 6π electrocyclizations. Described herein is a zinc-catalyzed formal [4+3] annulation of isoxazoles with 3-en-1-ynol ethers via 6π electrocyclization, leading to the site-selective synthesis of functionalized 2H-azepines and 4H-azepines in good to excellent yields with broad substrate scope. Moreover, this strategy has also been used to produce chiral 2H-azepines with high enantioselectivities (up to 97:3 e.r.). This protocol not only is the first asymmetric heptatrienyl-cation-type 6π electrocyclization, but also is the first asymmetric reaction of isoxazoles with alkynes and the first asymmetric catalysis based on ynol ethers
The LAMOST Complete Spectroscopic Survey of Pointing Area (LaCoSSPAr) in the Southern Galactic Cap I. The Spectroscopic Redshift Catalog
We present a spectroscopic redshift catalog from the LAMOST Complete
Spectroscopic Survey of Pointing Area (LaCoSSPAr) in the Southern Galactic Cap
(SGC), which is designed to observe all sources (Galactic and extra-galactic)
by using repeating observations with a limiting magnitude of in
two fields. The project is mainly focusing on the completeness of
LAMOST ExtraGAlactic Surveys (LEGAS) in the SGC, the deficiencies of source
selection methods and the basic performance parameters of LAMOST telescope. In
both fields, more than 95% of galaxies have been observed. A post-processing
has been applied to LAMOST 1D spectrum to remove the majority of remaining sky
background residuals. More than 10,000 spectra have been visually inspected to
measure the redshift by using combinations of different emission/absorption
features with uncertainty of . In total, there are 1528
redshifts (623 absorption and 905 emission line galaxies) in Field A and 1570
redshifts (569 absorption and 1001 emission line galaxies) in Field B have been
measured. The results show that it is possible to derive redshift from low SNR
galaxies with our post-processing and visual inspection. Our analysis also
indicates that up to 1/4 of the input targets for a typical extra-galactic
spectroscopic survey might be unreliable. The multi-wavelength data analysis
shows that the majority of mid-infrared-detected absorption (91.3%) and
emission line galaxies (93.3%) can be well separated by an empirical criterion
of . Meanwhile, a fainter sequence paralleled to the main population
of galaxies has been witnessed both in / and /
diagrams, which could be the population of luminous dwarf galaxies but
contaminated by the edge-on/highly inclined galaxies ().Comment: 19 pages, 14 figures, 2 MRT, accepted by ApJ
The application of radiomics in esophageal cancer: Predicting the response after neoadjuvant therapy
Esophageal cancer (EC) is one of the fatal malignant neoplasms worldwide. Neoadjuvant therapy (NAT) combined with surgery has become the standard treatment for locally advanced EC. However, the treatment efficacy for patients with EC who received NAT varies from patient to patient. Currently, the evaluation of efficacy after NAT for EC lacks accurate and uniform criteria. Radiomics is a multi-parameter quantitative approach for developing medical imaging in the era of precision medicine and has provided a novel view of medical images. As a non-invasive image analysis method, radiomics is an inevitable trend in NAT efficacy prediction and prognosis classification of EC by analyzing the high-throughput imaging features of lesions extracted from medical images. In this literature review, we discuss the definition and workflow of radiomics, the advances in efficacy prediction after NAT, and the current application of radiomics for predicting efficacy after NAT
JUNO Conceptual Design Report
The Jiangmen Underground Neutrino Observatory (JUNO) is proposed to determine
the neutrino mass hierarchy using an underground liquid scintillator detector.
It is located 53 km away from both Yangjiang and Taishan Nuclear Power Plants
in Guangdong, China. The experimental hall, spanning more than 50 meters, is
under a granite mountain of over 700 m overburden. Within six years of running,
the detection of reactor antineutrinos can resolve the neutrino mass hierarchy
at a confidence level of 3-4, and determine neutrino oscillation
parameters , , and to
an accuracy of better than 1%. The JUNO detector can be also used to study
terrestrial and extra-terrestrial neutrinos and new physics beyond the Standard
Model. The central detector contains 20,000 tons liquid scintillator with an
acrylic sphere of 35 m in diameter. 17,000 508-mm diameter PMTs with high
quantum efficiency provide 75% optical coverage. The current choice of
the liquid scintillator is: linear alkyl benzene (LAB) as the solvent, plus PPO
as the scintillation fluor and a wavelength-shifter (Bis-MSB). The number of
detected photoelectrons per MeV is larger than 1,100 and the energy resolution
is expected to be 3% at 1 MeV. The calibration system is designed to deploy
multiple sources to cover the entire energy range of reactor antineutrinos, and
to achieve a full-volume position coverage inside the detector. The veto system
is used for muon detection, muon induced background study and reduction. It
consists of a Water Cherenkov detector and a Top Tracker system. The readout
system, the detector control system and the offline system insure efficient and
stable data acquisition and processing.Comment: 328 pages, 211 figure
Search for the decay
We search for radiative decays into a weakly interacting neutral
particle, namely an invisible particle, using the produced through the
process in a data sample of
decays collected by the BESIII detector
at BEPCII. No significant signal is observed. Using a modified frequentist
method, upper limits on the branching fractions are set under different
assumptions of invisible particle masses up to 1.2 . The upper limit corresponding to an invisible particle with zero mass
is 7.0 at the 90\% confidence level
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