Temozolomide (TMZ) is an alkylating agent currently used as first-line therapy for gliomas treatment due to its DNA-damaging effect. However, drug resistance occurs, preventing multi-cycle use of ...this chemotherapeutic agent. One of the major mechanisms of cancer drug resistance is enhanced activity of a DNA repair enzyme, O(6)-methylguanine-DNA-methyltransferase (MGMT), which counteracts chemotherapy-induced DNA alkylation and is a key component of chemoresistance. MGMT repairs TMZ-induced DNA lesions, O(6)-meG, by transferring the alkyl group from guanine to a cysteine residue. This review provides an overview of recent advances in the field, with particular emphasis on the inhibitors of MGMT and underlying mechanisms. Literature search was performed through PubMed and all relevant articles were reviewed, with particular attention to MGMT, its role in TMZ-resistant gliomas, effects of MGMT inhibitors and the underlying mechanisms. Several strategies are currently being pursued to improve the therapeutic efficacy of TMZ via inhibition of MGMT to reduce chemoresistance and improve overall survival. MGMT may be a promising target for the treatment of TMZ-resistant gliomas.
Self-assembled monolayers are a unique class of nanostructured materials, with properties determined by their molecular lattice structures, as well as the interfaces with their substrates and ...environments. As with other nanostructured materials, defects and dimensionality play important roles in the physical, chemical, and biological properties of the monolayers. In this review, we discuss monolayer structures ranging from surfaces (two-dimensional) down to single molecules (zero-dimensional), with a focus on applications of each type of structure, and on techniques that enable characterization of monolayer physical properties down to the single-molecule scale.
ABSTRACT A sample of the Large Sky Area Multi-Object Fibre Spectroscopic Telescope spectra of early-type M0-M3 dwarfs is compared with Kepler observations. It is found that M dwarfs with strong ...chromospheric emission in have large flare activity in general. The rotational periods derived from the Kepler measurements have close correlations with the sizes of the flares, the power-law distribution index, and the equivalent widths of the emission. A clear trend exists for higher magnetic activities being detected in faster-rotating M dwarfs (rotation periods < 20 days).
Unlike the widely studied
Re
FeAsO series, the newly discovered iron-based superconductor ThFeAsN exhibits a remarkably high critical temperature of 30 K, without chemical doping or external ...pressure. Here we investigate in detail its magnetic and superconducting properties via muon-spin rotation/relaxation and nuclear magnetic resonance techniques and show that ThFeAsN exhibits strong magnetic fluctuations, suppressed below ~35 K, but no magnetic order. This contrasts strongly with the
Re
FeAsO series, where stoichiometric parent materials order antiferromagnetically and superconductivity appears only upon doping. The ThFeAsN case indicates that Fermi-surface modifications due to structural distortions and correlation effects are as important as doping in inducing superconductivity. The direct competition between antiferromagnetism and superconductivity, which in ThFeAsN (as in LiFeAs) occurs at already zero doping, may indicate a significant deviation of the
s
-wave superconducting gap in this compound from the standard
s
±
scenario.
Exploring the interplay between the superconducting gap and the antiferromagnetic phase in Fe-based superconductors remains an open issue. Here, the authors show that Fermi-surface modifications by means of structural distortions and correlation effects are as important as doping in inducing superconductivity in undoped ThFeAsN.
Deciphering the flow below the cloud‐level of Jupiter remains a critical milestone in understanding Jupiter's internal structure and dynamics. The expected high‐precision Juno measurements of both ...the gravity field and the magnetic field might help to reach this goal. Here we propose a method that combines both fields to constrain the depth‐dependent flow field inside Jupiter. This method is based on a mean‐field electrodynamic balance that relates the flow field to the anomalous magnetic field, and geostrophic balance that relates the flow field to the anomalous gravity field. We find that the flow field has two distinct regions of influence: an upper region in which the flow affects mostly the gravity field and a lower region in which the flow affects mostly the magnetic field. An optimization procedure allows to reach a unified flow structure that is consistent with both the gravity and the magnetic fields.
Key Points
Juno will provide high‐accuracy measurements of both the gravity and the magnetic fields of Jupiter
We propose a new method for using both measurements to estimate the flow structure below the cloud‐level
Two regions are found: an upper region where the flow affects the gravity field and a lower region where it affects the magnetic field
Energy consumption in machining contributes a significant part of manufacturing cost and produces a great environmental impact. This paper provides a critical assessment on energy consumption in a ...machining system. Energy consumption is classified at the process, machine, and system levels. Machine tool power demand at different machine states by different components is also discussed. Then predictive methods of energy consumption at different levels are summarized. Finally, energy consumption reduction strategies are discussed to achieve sustainable manufacturing.
•Energy consumption is classified at the process, machine, and system levels.•The concept of net cutting energy is established.•Empirical and analytical models of energy consumption are critically analyzed.•The strategies for reducing energy consumption are recommended.
Objective
The incidence of type 2 diabetes mellitus (T2DM) among children and adolescents has been rising. Accumulating evidences have noted the significant role of betatrophin in the regulation of ...lipid metabolism and glucose homeostasis. In our study, we tried to figure out the underlying mechanism of betatrophin in insulin resistance (IR) in type 2 diabetes mellitus (T2DM).
Methods
First, fasting serum betatrophin, fasting blood glucose (FBG), insulin, total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were detected in T2DM children. The homeostasis model assessment of insulin resistance (HOMA-IR), Gutt insulin sensitivity index (ISI
G
) and Matsuda insulin sensitivity index (ISI
M
) were calculated. A T2DM-IR mouse model was induced by high-fat diet, with the expression of GSK-3β and PGC-1α detected. Besides, HepG2 cells were induced by a high concentration of insulin to establish an IR cell model (HepG2-IR). The cell viability, glucose consumption, liver glycogen content, inflammation, and fluorescence level of GSK-3β and PGC-1α were analyzed.
Results
Betatrophin was highly expressed in serum of T2DM children and was positively correlated with FBG, insulin, TC, TG, LDL-C and HOMA-IR, while negatively correlated with ISI
G
and ISI
M
. Betatrophin and GSK-3β in the liver tissues of T2DM-IR mice were increased, while the PGC-1α expression was decreased. Betatrophin expression was negatively correlated with PGC-1α and positively correlated with GSK-3β. Silencing of betatrophin enhanced insulin sensitivity through the activation of GSK-3β/PGC-1α signaling pathway. In vitro experiments also found that silencing of betatrophin promoted glucose consumption and glycogen synthesis while inhibited inflammation.
Conclusion
Our findings concluded that silencing of betatrophin could enhance insulin sensitivity and improve histopathological morphology through the activation of GSK-3β/PGC-1α signaling pathway.
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