The mechanisms of sorafenib resistance in hepatocellular carcinoma:theoretical basis and therapeutic aspects

Sorafenib is a multikinase inhibitor capable of facilitating apoptosis,mitigating angiogenesis and suppressing tumor cell proliferation.In late-stage hepatocellular carcinoma(HCC),sorafenib is currently an effective first-line therapy.Unfortunately,the development of drug resistance to sorafenib is becoming increasingly common.This study aims to identify factors contributing to resistance and ways to mitigate resistance.Recent studies have shown that epigenetics,transport processes,regulated cell death,and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC progression.This study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.

Emerging roles of activating transcription factor (ATF) family members in tumourigenesis and immunity: Implications in cancer immunotherapy

Activating transcription factors, ATFs, are a group of bZIP transcription factors that act as homodimers or heterodimers with a range of other bZIP factors. In general, ATFs respond to extracellular signals, indicating their important roles in maintaining homeostasis. The ATF family includes ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, and ATF7. Consistent with the diversity of cellular processes reported to be regulated by ATFs, the functions of ATFs are also diverse. ATFs play an important role in cell proliferation, apoptosis, differentiation and inflammation-related pathological processes. The expression and phosphorylation status of ATFs are also related to neurodegenerative diseases and polycystic kidney disease. Various miRNAs target ATFs to regulate cancer proliferation, apoptosis, autophagy, sensitivity and resistance to radiotherapy and chemotherapy. Moreover, ATFs are necessary to maintain cell redox homeostasis. Therefore, deepening our understanding of the regulation and function of ATFs will provide insights into the basic regulatory mechanisms that influence how cells integrate extracellular and intracellular signals into genomic responses through transcription factors. Under pathological conditions, especially in cancer biology and response to treatment, the characterization of ATF dysfunction is important for understanding how to therapeutically utilize ATF2 or other pathways controlled by transcription factors. In this review, we will demonstrate how ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, and ATF7 function in promoting or suppressing cancer development and identify their roles in tumour immunotherapy.

Ionic liquids on uncharged and charged surfaces: In situ microstructures and nanofriction

In situ changes in the nanofriction and microstructures of ionic liquids(ILs)on uncharged and charged surfaces have been investigated using colloid probe atomic force microscopy(AFM)and molecular dynamic(MD)simulations.Two representative ILs,[BMIM][BF_(4)](BB)and[BMIM][PF_(6)](BP),containing a common cation,were selected for this study.The torsional resonance frequency was captured simultaneously when the nanoscale friction force was measured at a specified normal load;and it was regarded as a measure of the contact stiffness,reflecting in situ changes in the IL microstructures.A higher nanoscale friction force was observed on uncharged mica and highly oriented pyrolytic graphite(HOPG)surfaces when the normal load increased;additionally,a higher torsional resonance frequency was detected,revealing a higher contact stiffness and a more ordered IL layer.The nanofriction of ILs increased at charged HOPG surfaces as the bias voltage varied from 0 to 8 V or from 0 to−8 V.The simultaneously recorded torsional resonance frequency in the ILs increased with the positive or negative bias voltage,implying a stiffer IL layer and possibly more ordered ILs under these conditions.MD simulation reveals that the[BMIM]+imidazolium ring lies parallel to the uncharged surfaces preferentially,resulting in a compact and ordered IL layer.This parallel“sleeping”structure is more pronounced with the surface charging of either sign,indicating more ordered ILs,thereby substantiating the AFM-detected stiffer IL layering on the charged surfaces.Our in situ observations of the changes in nanofriction and microstructures near the uncharged and charged surfaces may facilitate the development of IL-based applications,such as lubrication and electrochemical energy storage devices,including supercapacitors and batteries.

Delivering quantum dots to lubricants: Current status and prospect

Very recently,two-dimensional quantum dots(2D QDs)have been pioneeringly investigated as lubricant additives,which exhibit superior friction-reducing and wear resistance.Compared with 2D nanoparticles,2D QDs possess small size(~10 nm)and abundant active groups.These distinguished advantages enable them to quickly disperse into common lube mediums and maintain long-term storage stability.The good dispersion stability of 2D QDs not only effectively improves their embedding capacity,but also enables continuous supplements of lubricants during the sliding process.Therefore,2D QDs are attracting increasing research interest as efficient lubricants with desirable service life.In this review,we focus on the latest studies of 2D QDs as liquid lubricant additives(both in polar and nonpolar mediums),self-lubricating solid coatings and gels,etc.Various advanced strategies for synthesis and modification of 2D QDs are summarized.A comprehensive insight into the tribological behavior of a variety of 2D QDs together with the associated mechanism is reviewed in detail.The superior lubricating performances of 2D QDs are attributed to various mechanisms,including rolling effect,self-mending performance,polishing effect,tribofilm formation,nanostructure transfer and synergistic effects,etc.Strategies for friction modulation of 2D QDs,including internal factors(surface modification,elemental doping)and extrinsic factors(counter surfaces,test conditions)are discussed,special attentions for achieving intelligent tribology toward superlubricity and bio-engineering,are also included.Finally,the future challenges and research directions regarding QDs as lubricants conforming to the concept of“green tribology”toward a sustainable society are discussed.

Probing the nanofriction of non-halogenated phosphonium-based ionic liquid additives in glycol ether oil on titanium surface

The nanofrictional behavior of non-halogentated phosphonium-based ionic liquids(ILs)mixed with diethylene glycol dibutyl ether in the molar ratios of 1:10 and 1:70 was investigated on the titanium(Ti)substrate using atomic force microscopy(AFM).A significant reduction is observed in the friction coefficientμfor the IL-oil mixtures with a higher IL concentration(1:10,μ~0.05),compared to that for the lower concentration 1:70(μ~0.1).AFM approaching force–distance curves and number density profiles for IL-oil mixtures with a higher concentration revealed that the IL preferred to accumulate at the surface forming IL-rich layered structures.The ordered IL-rich layers formed on the titanium surface facilitated the reduction of the nanoscale friction by preventing direct surface-to-surface contact.However,the ordered IL layers disappeared in the case of lower concentration,resulting in an incomplete boundary layers,because the ions were displaced by molecules of the oil during sliding and revealed to be less efficient in friction reduction.