Arsenic trioxide targets Hsp60, triggering degradation of p53 and survivin

The mechanisms of action of arsenic trioxide (ATO), a clinically used drug for the treatment of acute promyelocytic leukemia (APL), have been actively studied mainly through characterization of individual putative protein targets. There appear to be no studies at a system level. Herein, we integrate metalloproteomics through a newly developed organoarsenic probe, As-AC (C₂₀H₁₇AsN₄O₃S₂) with quantitative proteomics, allowing 37 arsenic binding and 250 arsenic regulated proteins to be identified in NB4, a human APL cell line. Bioinformatics analysis reveals that ATO disrupts multiple physiological processes, in particular, chaperone-related protein folding and cellular response to stress. Furthermore, we discover heat shock protein 60 (Hsp60) as a vital target of ATO. Through biophysical and cell-based assays, we demonstrate that ATO binds to Hsp60, leading to abolishment of Hsp60 refolding capability. Significantly, the binding of ATO to Hsp60 disrupts the formation of Hsp60-p53 and Hsp60-survivin complexes, resulting in degradation of p53 and survivin. This study provides significant insights into the mechanism of action of ATO at a systemic perspective, and serves as guidance for the rational design of metal-based anticancer drugs.

A highly selective organoarsenic fluorescent probe As-AC and quantitative proteomics were employed to track arsenic-binding and regulating proteins in live leukemia cells. Hsp60 was validated as a new target of ATO.     

On the cumulative quantile regression process

Let (X, Y) be a bivariate random vector and F(x) the marginal distribution function of X. The quantile regression (QR) function of Y on X is defined as r(u) = E[Y | F(X) = u] and the cumulative QR function (CQR) M(u) as its integral over [0, u]. The empirical counterpart based on a sample of size n is M _n (u). In this paper, we construct strong Gaussian approximations of the associated CQR process under appropriate assumptions. The construction provides a firm basis for the study of functional statistics based on M _in (u). A law of the iterated logarithm for the CQR process follows from our result.     

Low Viscosity Poly(trimethylene carbonate) for Localized Drug Delivery: Rheological Properties and in vivo Degradation

The purpose of this study is to examine the potential of low‐molecular‐weight poly(trimethylene carbonate) for localized delivery for acid‐sensitive drugs. Poly(trimethylene carbonate) of various molecular weights is prepared by ring‐opening polymerization initiated by octan‐1‐ol and co‐initiated/catalyzed by tin 2‐ethylhexanoate. The resultant polymers are amorphous with low glass transition temperatures and viscosities at 37 °C that permit their injection through an G 1.5″ needle. Their biocompatibility and the influence of the molecular weight on the rate of degradation are assessed in vivo through subcutaneous implantation in rats over 40 weeks. The polymers are well tolerated in vivo, and degrade in a fashion dependent on their initial molecular weight. For very low initial molecular weight (620 Da) and for high initial molecular weight (2 400 Da), polymer mass loss is a result of dissolution of the soluble low molecular chains from the bulk. This is contrasted by the results obtained for an intermediate initial molecular weight (1 600 Da), for which polymer mass loss is a result of both dissolution and enzymatic hydrolysis or oxidation as a result of reactive species secreted by activated macrophages at the implant surface.

     

Adsorption and desorption characteristics of 3-dimensional networks of fused graphene

Here we explore the exceptional structural characteristics of a set of graphene-related materials prepared by a wet chemical approach. We present a comprehensive study of the effects of morphology, sonication, temperature, probe species, and stacking behaviour on the measurement of graphene surface area. Nitrogen gas was used in the solid state gas adsorption measurements and methylene blue dye for adsorption measurements on aqueous dispersions of graphene. The surface area values obtained are among the highest reported for synthetic graphenes: 1700 m² g^? 1 in aqueous dispersions and 612 m² g^? 1 in the solid state. Microscopy revealed the graphene used in the study was present in large part as free sheets and electron diffraction confirmed the successful synthesis of high quality graphene with a regular C–C bond length of 1.41 ± 0.02 Å.     

Identifying the Zn-Co binary as a robust bifunctional electrocatalyst in oxygen reduction and evolution reactions via shifting the apexes of the volcano plot

The performance of an electrocatalyst is closely correlated with the binding strength of key oxygencontaining intermediates,i.e.,*OOH,*O and*OH,in the oxygen reduction reaction(ORR)and oxygen evolution reaction(OER).Facile strategies to achieve favorable binding strength of these oxygen-containing species are urgently demanded,yet it still remains great challenges.Herein,the Zn-Co bimetallic isolation,which serves as an ideal model,is studied systematically by the density functional theory(DFT).Reaction activity volcano plots are built from 48 models,among them the ZnCoN6-gra(I)configuration is confirmed to be the most stable,featured of the strongest interaction with the oxygen-containing species.Optimal △G*O(free energy change of an atomic oxygen containing intermediate)is facilitated,which effectively drifts the volcano peaks of ORR and OER closer to each other,enabling promising bifunctional catalyst.Moreover,the small overpotential in the simulation of protonation and oxidation by hydroxy groups rationalizes the durability of the catalyst in both acid and alkaline media.     

Identification of Temperature Dependent Parameters in Radiative Heat Transfer

Laser-induced thermotherapy (LITT) is an established minimally invasive percutaneous technique of tumor ablation. Nevertheless, there is a need to predict the effect of laser applications and optimizing irradiation planning in LITT. Optical attributes (absorption, scattering) change due to thermal denaturation. The work presents the possibility to identify these temperature dependent parameters from given temperature measurements via an optimal control problem. The solvability of the optimal control problem is analyzed and results of successful implementations are shown. (© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Concerted and Selective Electrooxidation of Polyethylene-Terephthalate-Derived Alcohol to Glycolic Acid at an Industry-Level Current Density over a Pd−Ni(OH)2 Catalyst

Electro-reforming of Polyethylene-terephthalate-derived (PET-derived) ethylene glycol (EG) into fine chemicals and H₂ is an ideal solution to address severe plastic pollution. Here, we report the electrooxidation of EG to glycolic acid (GA) with a high Faraday efficiency and selectivity (>85 %) even at an industry-level current density (600 mA cm⁻² at 1.15 V vs. RHE) over a Pd−Ni(OH)₂ catalyst. Notably, stable electrolysis over 200 h can be achieved, outperforming all available Pd-based catalysts. Combined experimental and theoretical results reveal that 1) the OH* generation promoted by Ni(OH)₂ plays a critical role in facilitating EG-to-GA oxidation and removing poisonous carbonyl species, thereby achieving high activity and stability; 2) Pd with a downshifted d-band center and the oxophilic Ni can synergistically facilitate the rapid desorption and transfer of GA from the active Pd sites to the inactive Ni sites, avoiding over-oxidation and thus achieving high selectivity.