Although new developments of surgery, chemotherapy, radiotherapy, and immunotherapy treatments for cancer have improved patient survival, the emergence of chemoresistance in cancer has significant ...impacts on treatment effects. The development of chemoresistance involves several polygenic, progressive mechanisms at the molecular and cellular levels, as well as both genetic and epigenetic heterogeneities. Chemotherapeutics induce epigenetic reprogramming in cancer cells, converting a transient transcriptional state into a stably resistant one. Super-enhancers (SEs) are central to the maintenance of identity of cancer cells and promote SE-driven-oncogenic transcriptions to which cancer cells become highly addicted. This dependence on SE-driven transcription to maintain chemoresistance offers an Achilles' heel for chemoresistance. Indeed, the inhibition of SE components dampens oncogenic transcription and inhibits tumor growth to ultimately achieve combined sensitization and reverse the effects of drug resistance. No reviews have been published on SE-related mechanisms in the cancer chemoresistance. In this review, we investigated the structure, function, and regulation of chemoresistance-related SEs and their contributions to the chemotherapy via regulation of the formation of cancer stem cells, cellular plasticity, the microenvironment, genes associated with chemoresistance, noncoding RNAs, and tumor immunity. The discovery of these mechanisms may aid in the development of new drugs to improve the sensitivity and specificity of cancer cells to chemotherapy drugs.
The interest for a wider range of usable materials for the technology of selective laser melting (SLM) is growing. In this work, the manufacturing of wrought Al–Cu–Mg parts using SLM technology was ...systematically investigated. The effect of processing parameters on the density of the deposited Al–Cu–Mg samples was studied. It shows that the laser energy density plays a significant role in the densification behavior of the Al–Cu–Mg powder during the SLM process. The laser energy density value of 340J/mm3 is found to be the threshold, above which high density samples (99.8%) without imperfections and microcracks can be obtained. The SLMed Al–Cu–Mg part presents a unique layer-wise feature which consisted of an extremely fine supersaturated cellular-dendrites structure. The ultimate tensile strength of 402MPa and the yield strength of 276MPa are achieved for the SLMed Al–Cu–Mg part. The combination of grain refinement and solid solution strengthening mechanisms during SLM process are proposed to explain the high mechanical strength.
A strategy for one‐pot and large‐scale synthesis of functionalized core–shell nanowires (NWs) to high‐efficiently construct single nanowire electrodes is proposed. Based on the polymerization ...reaction between 3,4‐ethylenedioxythiophene (EDOT) and noble metal cations, manifold noble metal nanoparticles‐polyEDOT (PEDOT) nanocomposites can be uniformly modified on the surface of any nonconductive NWs. This provides a facile and versatile approach to produce massive number of core–shell NWs with excellent conductivity, adjustable size, and well‐designed properties. Nanoelectrodes manufactured with such core–shell NWs exhibit excellent electrochemical performance and mechanical stability as well as favorable antifouling properties, which are demonstrated by in situ intracellular monitoring of biological molecules (nitric oxide) and unraveling its relevant unclear signaling pathway inside single living cells.
Versatile one‐pot synthesis of functionalized core–shell nanowires breaks through the limitation of nanoelectrode materials to facilely construct high‐performance single nanowire electrodes. Concurrently with excellent electrochemical, mechanical, and antifouling properties, the nanowire electrodes show great superiority in real‐time monitoring of biological molecules and unraveling the relevant signaling pathway inside single living cells.
Antarctic krill protein (AKP) was extracted from Antarctic krill by an alkali dissolution‐isoelectric precipitation method and then it was phosphorylated with sodium tripolyphosphate. The ...phosphorylated Antarctic krill protein (P‐AKP) powder was obtained by spray‐drying (SD), freeze‐drying (FD), and hot‐air drying (AD), and the effects of these drying methods on the structures and functional properties of proteins were investigated. The P‐AKP powder dried by SD had the best sensory performance, and its particle size was much smaller than that of FD and AD. Scanning electron microscope displayed a uniform particle size of SD powder and the particles were uniformly dispersed. X‐ray diffraction analysis showed a higher crystallinity of SD sample than AD and FD. Differential scanning calorimeter analysis revealed that SD sample had the best thermal stability and less protein denaturation (ΔH = 210.80 J/g), followed by FD (ΔH = 80.48 J/g) and AD (ΔH = 73.94 J/g; P < 0.05). Fourier transform infrared showed that SD sample contained more protein secondary structure. Compared with SD, the phosphorylated group‐related chemical bonds in FD and AD samples were partially destroyed. SD sample had the highest protein solubility, oil absorption capacity, emulsifying, and foaming activities than FD and AD (P < 0.05). Although FD had the highest water absorption capacity, sample prepared with AD had the worst functional performance. Therefore, different drying methods used for preparation of the P‐AKP can affect its physicochemical and associated functional properties, and SD could be an appropriate drying method for the industrial mass production of P‐AKP powders with better functionalities.
Practical Application
The optimal drying method for preparing the phosphorylated Antarctic krill protein (P‐AKP) powder was proved to be spray‐drying (SD), because the physicochemical and functional properties were better for P‐AKP dried by SD than the other drying methods. Hence, SD was recommended for the industrial mass production of P‐AKP powders with better functionalities. This research can provide theoretical guidance for the further processing and utilization of P‐AKP, and offer technical reference for food processing and preservation.
Existing ploughing mechanism and velocity-dependent mechanism, which were used for explaining the process damping in milling, did not consider the feedback influence of vibrations in normal ...direction, and thus, they cannot be used to reveal the underlying cause of process damping in milling process of thin-walled workpiece. This paper systematically studies the generation mechanism of process damping in thin-wall milling, and turns out that the relative vibration of cutter-workpiece system rather than the ploughing indentation is the main source of process damping in this kind of process. Theoretically, the actual cutting velocity and the relative vibrations in both feed and normal directions are combined to formulate the expression of instantaneous uncut chip thickness, which is then used to derive the equations of dynamic cutting forces. Taylor series expansions are carried out around harmonic response to linearize the equations of dynamic cutting forces. Derivations show that the dynamic cutting forces are composed of two items, i.e. the vibration displacements-induced force and the vibration velocities-induced force. The latter, which is actually an additional dissipative force being inversely proportional to the cutting velocity, constitutes a source of process damping. It is subsequently integrated into the process's governing equation to estimate the stability lobe diagrams (SLDs). Verification shows that the SLDs predicted by the proposed velocity-dependent mechanism reasonably agree with the experimentally observed results (among 672 sets of detailed comparisons, agreement rate is more than 95%.). Especially, thin-wall milling experiments with various values of spindle speeds show that the SLDs predicted using the proposed velocity-dependent mechanism are much closer to the experimental observations than those obtained by the ploughing mechanism (among 36 sets of detailed comparisons, agreement rate between the predictions and measurements is more than 94% for the proposed velocity-dependent mechanism, while the agreement rate is only 47% for the ploughing mechanism.).
•Underlying mechanism of process damping in milling process of thin-walled workpiece is studied deeply.•A velocity-dependent process damping model considering the relative vibrations of cutter-workpiece system in both feed and normal directions is established.•Instantaneous uncut chip thickness and dynamic cutting force are calculated based on the actual cutting velocity.•Validity of the proposed mechanism is verified by conducting thin-wall milling tests with relatively low radial immersion.
Catalytic hydrogenation of maleic anhydride (MA) into succinic anhydride (SA) is one of the most important transformations in synthetic organic chemistry. Herein, we firstly synthesized ...well‐dispersed nickel particles confined by mixed metal oxides (Ni/MMO) derived from in situ transformation of Ni‐Al hydrotalcite in a rotating packed bed (RPB) to catalyze this process. A series of Ni/MMO catalysts (63 wt%–89 wt% Ni) were effectively fabricated and the structure–activity relationship was established. Results showed that a Ni/MMO catalyst (82 wt% Ni) with substantial surface defect sites and the highest Ni surface area among the prepared Ni/MMO catalysts, demonstrates the highest activity with ~100% MA conversion and ~100% selectivity to SA under 25°C within 77 min. This is, to our knowledge, the highest conversion and selectivity under room temperature to date. Moreover, the Ni/MMO catalyst prepared by RPB has higher specific surface area and Ni surface area, therefore possessing a higher hydrogenation rate compared to that by stirred tank reactor (1.69 vs. 1.36, 10−3·molMA/gcat/min). These results will provide an attractive option of the catalysts for MA hydrogenation, and a novel strategy for synthesizing nickel catalyst derived from Ni‐Al hydrotalcite.
Based on the system dynamics theory, this paper establishes an environmental mass event evolution model and explores the evolution law of mass events caused by environmental problems. From a ...methodological point of view, the mixed-strategy evolutionary game principle and dynamic punishment measures are combined, and simulation analysis is carried out by Anylogic software, and the results show that there is no stable evolutionary equilibrium solution for the two sides of the game in the traditional asymmetric mixed-strategy game model, and after adjusting the game payoff matrix and incorporating the dynamic punishment strategy, stable evolutionary equilibrium solutions appear in the evolutionary game model, and the system begins to tend to be stabilized. The process and conclusions of the simulation experiment provide methodological reference and theoretical support for the analysis of the evolution of environmental mass events.
Nanocrystalline SmCo5 and SmCo3Cu2 alloys were prepared by using high pressure torsion (HPT) method. The effect of severe plastic deformation of HPT on the structure and magnetic properties of the ...samples were investigated systematically. The grain size of SmCo5 and SmCo3Cu2 alloys was refined to the nanocrystalline regime or even amorphous state by HPT, depending on the number of the HPT rotation. Lamellar microstructures of the grains were observed in the samples after HPT for 2 turns of rotation. With increasing number of HPT rotation, a further structural refinement and an increasing coercivity were observed. The coercivity of the as-cast SmCo5 and SmCo3Cu2 alloys after HPT reached up to 0.5 and 1.64 T, respectively. This work demonstrates that HPT is a high efficiency method in producing bulk nanocrystalline magnetic materials.
statistics from genome-wide association studies (GWAS) have facilitated the development of various summary data-based methods, which typically require a reference sample for linkage disequilibrium ...(LD) estimation. Analyses using these methods may be biased by errors in GWAS summary data or LD reference or heterogeneity between GWAS and LD reference. Here we propose a quality control method, DENTIST, that leverages LD among genetic variants to detect and eliminate errors in GWAS or LD reference and heterogeneity between the two. Through simulations, we demonstrate that DENTIST substantially reduces false-positive rate in detecting secondary signals in the summary-data-based conditional and joint association analysis, especially for imputed rare variants (false-positive rate reduced from >28% to <2% in the presence of heterogeneity between GWAS and LD reference). We further show that DENTIST can improve other summary-data-based analyses such as fine-mapping analysis.
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