TRAF6 promotes chemoresistance to paclitaxel of triple negative breast cancer via regulating PKM2-mediated glycolysis.

Ample evidence reveals that glycolysis is crucial to tumor progression; however, the underlying mechanism of its drug resistance is still worth being further explored. TRAF6, an E3 ubiquitin ligase, is well recognized to overexpress in various types of cancer, which predicts a poor prognosis. In our study, we discovered that TRAF6 was expressed more significantly in the case of triple-negative breast cancer (TNBC) than in other of breast cancers, promoting chemoresistance to paclitaxel; that inhibited TRAF6 expression in the chemoresistant TNBC (TNBC-CR) cells enhanced the sensitivity by decreasing glucose uptake and lactate production; that TRAF6 regulated glycolysis and facilitated chemoresistance via binding directly to PKM2; and that overexpressing PKM2 in the TNBC-CR cells with TRAF6 knocked down regained significantly TRAF6-dependent drug resistance and glycolysis. Additionally, we verified that TRAF6 could facilitate PKM2-mediated glycolysis and chemoresistance in animal models and clinical tumor tissues. Thus, we identified the novel function of TRAF6 to promote glycolysis and drug resistance in TNBC with the regulation of PKM2, which could provide a potential molecular target for TNBC treatment.

Powder activated coke prepared from coal fast pyrolysis: fractal characteristics and SO2 adsorption.

The rapid and low-cost preparation of powder activated coke (PAC) is very important for the promotion of fluidized dry desulfurization technology of activated coke. In order to explore the effect of rapid pyrolysis process on SO2 adsorption capacity of PAC, the fractal analysis of PAC prepared under different atmospheres was carried out. The Frenkel-Halsey-Hill (FHH) method was used to determine two fractal dimensions D1 and D2, under relative pressures of 0-0.5 and 0.5-1, respectively. The results indicate that the fractal dimensions were influenced by the concentrations of activation agents with D1 ranging from 2.1838 to 2.8643 and D2 ranging from 2.7485 to 2.9257. The effect of steam on the fractal dimension of PAC sample is small, but oxygen has a great promotion effect on the fractal dimension. An n-shaped curve-based relationship between fractal dimensions and coke yields is observed with a peak values of fractal dimensions appearing around 64% yield. The SO2 adsorption capacity shows a consecutively positive linear correlation with D2, while it illustrates distinctly different linear rates with D1 in intervals of 2-2.6 and 2.6-3, respectively. Taking advantage of fractal analysis as research method, this paper clarified the influence of activation atmosphere and ablative degree on the SO2 adsorption capacity of PAC, and the research conclusion provided a basis for the PAC preparation with high SO2 capacity.

Application value of modified radical mastectomy in female patients with breast cancer of different molecular types: a prognosis study.

OBJECTIVE: This study aimed to explore the application values of modified radical mastectomy in female patients with mammary cancer of different molecular types and from this we conducted a prognosis study. METHODS: A total of 204 Breast Cancer (BC) patients who were admitted to our hospital from March 2015 to March 2017 were included and divided into Group A (Luminal A type, n = 68), Group B (Luminal B type, n = 48), Group C (ERBB2: Erb-B2 Receptor Tyrosine Kinase 2 + type, n = 42), and Group D (Basal-like type, n = 46) according to their molecular cancer types. Patients in Groups A and B demonstrated superior treatment efficacy and lower incidence of adverse reactions than those in Groups C and D (P < 0.05), while no statistical difference was observed among the 4 groups in terms of the total operation time, intraoperative blood loss, and postoperative 48-h drainage volume (P > 0.05). Before treatment, the 4 groups exhibited similar results from the EORTC breast cancer-specific quality of life questionnaire (EORTCQLQ-BR23) (P > 0.05). RESULTS: After treatment, Group A was superior to the other 3 groups in this regard (P < 0.05). Further, no significant difference was observed among the 4 groups in terms of the prognosis of 3-year survival (P > 0.05). CONCLUSION: The clinical application of modified radical mastectomy does not depend on the molecular typing of BC; however, the treatment was more effective in the treatment of Luminal A type BC.

Ni-Co bimetallic catalysts on coconut shell activated carbon prepared using solid-phase method for highly efficient dry reforming of methane.

Ni-Co bimetallic catalysts supported on coconut shell activated carbon are synthesized using solid-phase method and investigated for dry reforming of methane, to explore the impact of Ni:Co ratio on the catalyst activity and stability. The catalyst performances are evaluated under the temperature varying from 600 to 900 °C and gas hourly space velocity (GHSV) of 7200 mL/h·g-cat. The characterization results show that metal nanoparticles are produced on the support, and the bimetallic catalyst with an explicit Ni:Co ratio (2:1) is the most beneficial for metal particle dispersion and acquires the minimum particle size of 4.41 nm. The bimetallic catalysts with an explicit Ni:Co ratio of 1:2 and 1:1 exhibit a synergistic effect towards the conversions of CH4 and CO2, respectively. The experimental results reveal that the highest CH4 and CO2 conversions rise to 94.0% and 97.5% within 12 h at 900 °C on average, respectively, assisted with the two bimetallic catalysts. The intensity of disordered carbon and thermal stability are enhanced with the extension of reforming process, contributing to a long-term catalytic stability. Besides, no obvious carbon deposition is detected, leading to a highly catalytic stability for the bimetallic catalysts.

Highly stable halide perovskite with Na incorporation for efficient photocatalytic degradation of organic dyes in water solution.

To overcome water instability and low photocatalytic activity of lead-free halide perovskite for the degradation of organic dyes, we report a novel photocatalyst of lead-free halide perovskite with Na incorporation and employ it for the photocatalytic degradation of organic dyes in water solution under visible light irradiation. The main purpose of this work is to confirm the feasibility of lead-free halide perovskite with Na incorporation for improving the photocatalytic efficiency and recyclability in water solution and further to explore the mechanism behind the enhancement of photocatalytic performance after Na incorporation. The results show that Cs2Ag0.60Na0.40InCl6 can increase the dye degradation rate by at least 50% than the lead-free halide perovskite (Cs2AgInCl6) and the photocatalyst of Ag substituted by Na (Cs2NaInCl6). The degradation efficiency of rhodamine 6G catalyzed by Cs2Ag0.60Na0.40InCl6 reaches 94.94% over 60 min, which is 72% higher than that catalyzed by Cs2NaInCl6 and 27% higher than that catalyzed by Cs2AgInCl6. What's more, the degradation efficiency of methyl orange catalyzed by Cs2Ag0.60Na0.40InCl6 is 90.39% within 150 min, which is 66% higher than that catalyzed by Cs2NaInCl6 and 54% higher than that catalyzed by Cs2AgInCl6. Moreover, the photocatalyst of Cs2Ag0.60Na0.40InCl6 exhibits a desirable recyclability by water exposure, retaining the degradation efficiency over 90% after five cycles. The strengthened photocatalytic performance in the presence of Cs2Ag0.60Na0.40InCl6 is ascribed to an increase of radiative recombination rate and an improvement of average lifetime to 204 ns since an appropriate Na incorporation at the atomic ratio of Na/Ag=4:6 breaks the original crystal lattice and meanwhile increases the electron and hole overlap. The work proves a great potential of halide perovskite with Na incorporation for the highly efficient photocatalytic degradation of organic dyes in water solution.

Structure-based derivation and intramolecular cyclization of peptide inhibitors from PD-1/PD-L1 complex interface as immune checkpoint blockade for breast cancer immunotherapy.

The interaction event between programmed death receptor-1 (PD-1) and its ligand (PD-L1) functions as an essential immune checkpoint against cytotoxic T effector cell activation. Previously, a number of small-molecule inhibitors and antibody drugs have been successfully developed to block the PD1/PDL1 signaling axis for breast cancer immunotherapy. Here, we attempt to directly disrupt the formation of PD-1/PD-L1 complex by using a self-inhibitory peptide (SIP) strategy. In the procedure, the complex crystal structure is examined systematically with energetic analysis and alanine scanning. Two double-stranded segments I and II in PD-L1 active finger are identified as hotspot regions; they directly interact with the amphipathic pocket of PD-1 to form the complex system. The segments are derived from PD-L1 to define two SIP peptides, namely, DS-I and DS-II, which are thought to have capability of rebinding at the complex interface, thus disrupting PD-1/PD-L1 interaction as a new immune checkpoint blockade. A further analysis reveals that the free linear DS-I and DS-II peptides are highly flexible without protein context support, which would incur a large entropy penalty (unfavorable indirect readout effect) when rebinding to PD-1. Next, intramolecular cyclization is applied to constraining the intrinsically disordered conformation of free DS-II peptide into native ordered double-stranded configuration, which can be substantiated by molecular dynamics simulation and circular dichroism spectroscopy. Several cyclized counterparts of linear DS-II peptide are designed and their affinities to PD-1 are determined using fluorescence polarization assays. As might be expected, three designed cyclic peptides DS-II[c111-127], ΔDS-II[c111-127] and ΔDS-II[c110-128] exhibit considerably increased potency (Kd = 28.0 ±â€¯4.2, 17.5 ±â€¯3.1 and 11.6 ±â€¯2.3 µM, respectively) relative to linear DS-II peptide (Kd = 109 ±â€¯15 µM).

Fe-rich biomass derived char for microwave-assisted methane reforming with carbon dioxide.

Microwave-assisted methane reforming with carbon dioxide was dealt with in this work, using a Fe-rich biomass-derived char by one-step preparation. The main factors on the reforming reaction and stability of this catalyst were evaluated, together with a series of characterization on the produced gas and the used char. The char obtained from biomass pyrolysis with Fe2O3 addition of 10% exhibited the best performance on dry reforming reaction. A target CH4 conversion of 95% over this char was realized at 800 °C. Moreover, H2/CO ratio achieved with this char was prone to approach the stoichiometric value. Compared to CO2 conversion, CH4 conversion was more promoted with the increase of CO2/CH4 ratio. The variation of CO2/CH4 ratio also leaded to a noticeable changes on H2/CO ratio. More importantly, the selected char presented a satisfied stability, evidenced by the total decrease of 4.8% for CH4 conversion and 3.1% for CO2 conversion in the test of 160 min. This was contributed to a depressed in-situ carbon consumption and a moderate deterioration of porous structure. Gaseous products obtained with the appropriate char in a long run had a syngas content of 88.79% and H2/CO ratio of 0.92 on average.

A microwave reactor for characterization of pyrolyzed biomass.

A microwave reactor (MWR) was designed to investigate microwave-induced pyrolysis of biomass. Condensation of tars on the quartz reactor and the pipelines was prevented by an electric heating device, and a temperature control function allowed determination of product characteristics at constant temperatures. Temperature had an important influence on microwave pyrolysis; the yields of gas products increased from 17.69 wt.% to 22.27 wt.% and the ratio of combustible gas to total gas products increased from 67.21 vol.% to 77.14 vol.% as the temperature increased from 400 °C to 600 °C. A large number of volatiles was released as temperature increased, resulting in an increase in the number of pores of the coke and a uniform pore structure was obtained. The specific surface area of coke increased from 0.89 m(2)/g (400 °C) to 9.81m(2)/g (600 °C) and the pore volume increased from 0.006 cm(3)/g (400 °C) to 0.012 cm(3)/g (600 °C), but the average pore size decreased from 282.16 nm (400 °C) to 46.64 nm (600 °C).