The P53-P21-RB1 pathway promotes BRD4 degradation in liver cancer through USP1.

Liver cancer is notoriously refractory to conventional therapeutics. Tumor progression is governed by the interplay between tumor-promoting genes and tumor-suppressor genes. BRD4, an acetyl lysine-binding protein, is overexpressed in many cancer types, which promotes activation of a pro-tumor gene network. But the underlying mechanism for BRD4 overexpression remains incompletely understood. In addition, understanding the regulatory mechanism of BRD4 protein level will shed insight into BRD4-targeting therapeutics. In this study, we investigated the potential relation between BRD4 protein level and P53, the most frequently dysregulated tumor suppressor. By analyzing the TCGA datasets, we first identify a strong negative correlation between protein levels of P53 and BRD4 in liver cancer. Further investigation shows that P53 promotes BRD4 protein degradation. Mechanistically, P53 indirectly represses the transcription of USP1, a deubiquitinase, through the P21-RB1 axis. USP1 itself is also overexpressed in liver cancer and we show USP1 deubiquitinates BRD4 in vivo and in vitro, which increases BRD4 stability. With cell proliferation assays and xenograft model, we show the pro-tumor role of USP1 is partially mediated by BRD4. With functional transcriptomic analysis, we find the USP1-BRD4 axis upholds expression of a group of cancer-related genes. In summary, we identify a functional P53-P21-RB1-USP1-BRD4 axis in liver cancer.

Hydronium Intercalation Enables High Rate in Hexagonal Molybdate Single Crystals.

Rapid proton transport in solid-hosts promotes a new chemistry in achieving high-rate Faradaic electrodes. Exploring the possibility of hydronium intercalation is essential for advancing proton-based charge storage. Nevertheless, this is yet to be revealed. Herein, a new host is reported of hexagonal molybdates, (A2 O)x ·MoO3 ·(H2 O)y (A = Na+ , NH4 + ), and hydronium (de)intercalation is demonstrated with experiments. Hexagonal molybdates show a battery-type initial reduction followed by intercalation pseudocapacitance. Fast rate of 200 C (40 A g-1 ) and long lifespan of 30 000 cycles are achieved in electrodes of monocrystals even over 200 µm. Solid-state nuclear magnetic resonance confirms hydronium intercalations, and operando measurements using electrochemical quartz crystal microbalance and synchrotron X-ray diffraction disclose distinct intercalation behaviours in different electrolyte concentrations. Remarkably, characterizations of the cycled electrodes show nearly identical structures and suggest equilibrium products are minimally influenced by the extent of proton solvation. These results offer new insights into proton electrochemistry and will advance correlated high-power batteries and beyond.

An Emerging Chemistry Revives Proton Batteries.

Developing new energy techniques that simultaneously integrate the fast rate capabilities of supercapacitors and high capacities of batteries represents an ultimate goal in the field of electrochemical energy storage. A new possibility arises with an emerging battery chemistry that relies on proton-ions as the ion-charge-carrier and benefits from the fast transportation kinetics. Proton-based battery chemistry starts with the recent discoveries of materials for proton redox reactions and leads to a renaissance of proton batteries. In this article, the historical developments of proton batteries are outlined and key aspects of battery chemistry are reviewed. First, the fundamental knowledge of proton-ions and their transportation characteristics is introduced; second, Faradaic electrodes for proton storage are categorized and highlighted in detail; then, reported electrolytes and different designs of proton batteries are summarized; last, perspectives of developments for proton batteries are proposed. It is hoped that this review will provide guidance on the rational designs of proton batteries and benefit future developments.

Rational Design of Electrode-Electrolyte Interphase and Electrolytes for Rechargeable Proton Batteries.

Rechargeable proton batteries have been regarded as a promising technology for next-generation energy storage devices, due to the smallest size, lightest weight, ultrafast diffusion kinetics and negligible cost of proton as charge carriers. Nevertheless, a proton battery possessing both high energy and power density is yet achieved. In addition, poor cycling stability is another major challenge making the lifespan of proton batteries unsatisfactory. These issues have motivated extensive research into electrode materials. Nonetheless, the design of electrode-electrolyte interphase and electrolytes is underdeveloped for solving the challenges. In this review, we summarize the development of interphase and electrolytes for proton batteries and elaborate on their importance in enhancing the energy density, power density and battery lifespan. The fundamental understanding of interphase is reviewed with respect to the desolvation process, interfacial reaction kinetics, solvent-electrode interactions, and analysis techniques. We categorize the currently used electrolytes according to their physicochemical properties and analyze their electrochemical potential window, solvent (e.g., water) activities, ionic conductivity, thermal stability, and safety. Finally, we offer our views on the challenges and opportunities toward the future research for both interphase and electrolytes for achieving high-performance proton batteries for energy storage.

Fabrication of multifunctional materials based on chitosan/gelatin incorporating curcumin-clove oil emulsion for meat freshness monitoring and shelf-life extension.

A new multifunctional film with active and intelligent effects was developed by incorporating curcumin-clove oil emulsion into natural materials. The basic properties, functional characteristics, and pH/NH3-sensitivity of films were investigated, and then these films were applied to extend shelf-life and monitor freshness of meat. Curcumin solution and emulsion illustrated significant color variations at different pH values. The incorporation of emulsion improved the UV-vis barrier and water resistance properties of films, which blocked most of UV-light and its water contact angle reached 100.03°. Meanwhile, the films had stronger mechanical strength and higher thermal stability, with elongation at break reaching 79.18 % and the maximum degradation temperature rising to 316 °C. Moreover, emulsion made films have a slow-release effect on clove oil, which not only enhanced the antioxidant property but also significantly improved their antibacterial activity. Additionally, the multifunctional films presented a significant color response to acidic/alkaline environments over a short time interval and could be easily identified by naked eyes. Finally, the films effectively extended the shelf-life of fresh meat by 3 days at 4 °C and visually monitored freshness through color changes in real-time. This knowledge provides insights and ideas for the development of novel food packaging with both active and intelligent functions.

Molecular Crowding Electrolytes for Stable Proton Batteries.

Proton electrochemistry is promising for developing post-lithium energy storage devices with high capacity and rate capability. However, some electrode materials are vulnerable because of the co-intercalation of free water molecules in traditional acid electrolytes, resulting in rapid capacity fading. Here, the authors report a molecular crowding electrolyte with the usage of poly(ethylene glycol) (PEG) as a crowding agent, achieving fast and stable electrochemical proton storage and expanded working potential window (3.2 V). Spectroscopic characterisations reveal the formation of hydrogen bonds between water and PEG molecules, which is beneficial for confining the activity of water molecules. Molecular dynamics simulations confirm a significant decrease of free water fraction in the molecular crowding electrolyte. Dynamic structural evolution of the MoO3 anode is studied by in-situ synchrotron X-ray diffraction (XRD), revealing a reversible multi-step naked proton (de)intercalation mechanism. Surficial adsorption of PEG molecules on MoO3 anode works in synergy to alleviate the destructive effect of concurrent water desolvation, thereby achieving enhanced cycling stability. This strategy offers possibilities of practical applications of proton electrochemistry thanks to the low-cost and eco-friendly nature of PEG additives.

"Water-in-Sugar" Electrolytes Enable Ultrafast and Stable Electrochemical Naked Proton Storage.

Proton is an ideal charge carrier for rechargeable batteries due to its small ionic radius, ultrafast diffusion kinetics and wide availability. However, in commonly used acid electrolytes, the co-interaction of polarized water and proton (namely hydronium) with electrode materials often causes electrode structural distortions. The hydronium adsorption on electrode surfaces also facilitates hydrogen evolution as an unwanted side reaction. Here, a "water-in-sugar" electrolyte with high concentration of glucose dissolved in acid to enable the naked proton intercalation, as well as an extended 3.9 V working potential window, is shown. A glucose-derived organic thin film is formed on electrode surface upon cycling. Molecular dynamics simulations reveal the significant decrease of free water in bulk electrolytes, while density functional theory calculations indicate that glucose preferentially binds to the electrode surface which can inhibit water adsorption. The scarcity of free water and the protective organic film work in synergy to suppress water interactions with the electrode surface, which enables the naked proton (de)intercalation. The "water-in-sugar" electrolyte significantly enhances a MoO3 electrode for stable cycling over 100 000 times. This facile electrolyte approach opens new avenues to aqueous electrochemistry and energy storage devices.

Vanadium hexacyanoferrate as high-capacity cathode for fast proton storage.

Proton electrochemistry is promising for developing future energy storage devices with both high capacity and good rate capability. However, the development of this technology is now hindered by the limited choice of accessible electrodes, especially for cathodes. Herein, we report vanadium hexacyanoferrate (VHCF) as a candidate cathode for proton batteries. Exploiting dual redox-centers of vanadium and iron, VHCF delivers a high specific capacity of 108 mA h g-1. Furthermore, an outstanding rate capability (∼60% of initial value at 100C) and stable cycling for tens of thousands of cycles are also demonstrated. These results are anticipated to inspire searches for more accessible materials and accelerate advances in energy storage devices.

Understanding the Discrepancy of Defect Kinetics on Anionic Redox in Lithium-Rich Cathode Oxides.

Reversible anionic (oxygen) redox in lithium-rich cathode oxides has been becoming a blooming research topic to further boost the energy density in lithium-ion batteries. There are numerous experimental observations and theoretical calculations to illustrate the importance of defects on anionic redox activity, but how the defects on the surface and bulk control the kinetics of anionic redox is not well understood. Here, we uncover this intriguing ambiguity on the correlation among defects states, Li-ion diffusion, and oxygen redox reaction. It is found that the surface-defective microstructure has fast Li-ion diffusion to achieve superior cationic redox activities/kinetics, whereas the bulk-defective microstructure corresponds to a slow Li-ion diffusion to result in poor cationic redox activities/kinetics. By contrast, both surface and bulk defects can be of benefit to the enhancement of oxygen redox activities/kinetics. Moreover, a positive correlation is also established among charge-transfer resistance, interface reaction charge-transfer activation energy, and oxygen redox activity in these electrode materials. This study on defect-anionic activity provides a new insight for controlling anionic redox reaction in lithium-rich cathode materials for real-world application.

Confining Al-Li alloys between pre-constructed conductive buffers for advanced aluminum anodes.

An aluminum anode with pre-constructed two-layer conductive buffers was prepared to restrict the expanding Al-Li alloy inside, and provide continuous electron pathways for promising electrical contact. The full cell demonstrates superior cycling stability (0.0352% capacity decay per cycle for 400 cycles at 0.2C) and outstanding rate capability.

Facile Preparation of Cu/Ag Core/Shell Electrospun Nanofibers as Highly Stable and Flexible Transparent Conductive Electrodes for Optoelectronic Devices.

Novel transparent conductive electrodes (TCEs) with copper (Cu)/silver (Ag) core/shell nanofibers (NFs) containing random, aligned, and crossed structures were prepared using a combination of electrospinning (ES) and chemical reduction. The ES process was used to prepare continuous copper nanofibers (Cu-NFs), which were used as core materials and were then immersed in silver ink (Ag ink) to form a protective layer of Ag to protect the Cu-NFs from oxidation. The Ag shell layer protected the Cu-NFs against oxidation and enhanced their conductivity. Such Cu/Ag core/shell webs can be easily transferred on the flexible matrix and can be applied in TCEs. The metal NF webs of different structures exhibited various degrees of conductivity and followed the order random type > crossed type > aligned type; however, the order with respect to transmittance ( T) was inverse. The aligned nanowire networks exhibited a high T of over 80%, and the random ones exhibited a low sheet resistance of less than 102 Ω/sq (the best value is 7.85 Ω/sq). The present study demonstrated that TCEs based on Cu/Ag core/shell NF webs have considerable flexibility, transparency, and conductivity and can be applied in novel flexible light-emitting diode devices and solar cells in the future.

Ion-responsive Intramolecular Charge-transfer Absorption Using a Pyridinium Benzocrown Ether Conjugate.

A pyridinium benzocrown ether conjugated compound, 1, and its analogue with a non-crown ether unit, 2, have been prepared. Both compounds showed similar absorption spectra with two absorption bands at around 260 and 330 nm in acetonitrile. The bands at the longer wavelength side are associated with intramolecular charge transfer (ICT) absorption, in which the dialkoxyphenyl unit in benzocrown ether and the pyridinium unit act as the donor and acceptor, respectively. The addition of a guest, such as Li(+) or Mg(2+), caused a blue shift in the ICT absorption band for 1, but not for 2. This is explained by the formation of a 1:1 host-guest inclusion complex of 1 with the guest. The guest-induced absorption variation of 1 can be used for alkali and alkaline metal ion sensing. Compound 1 could detect divalent cations, especially for Mg(2+), rather than univalent ones (Li(+), Na(+), K(+), Rb(+), and Cs(+)), although Li(+) was detected with high sensitivity among the alkali metal ions. Compound 3, which has a pyridyl unit at the para position on the pyridinium of 1, showed a similar trend to that of 1 with lower sensitivity than that of 1. The fact that the Mg(2+)/Li(+) sensitivity ratio of 1 and 3 was estimated to be 8.63 and 5.08, respectively, suggests a higher Mg(2+)-preference of 1 rather than 3, while the Ca(2+)/Na(+) ones were 4.98 and 4.85, respectively, when compared ions with similar ionic radii. The sensitivity values of 1 were roughly proportional to their binding constants, as shown by the binding constants with Li(+), Na(+), Mg(2+), and Ca(2+) with values of 2100, 910, 11500, and 2000 M(-1) for 1, respectively. The binding constants of 3 were estimated to be 1710, 650, 3000, and 1400 M(-1) for Li(+), Na(+), Mg(2+), and Ca(2+), respectively, but could not be obtained for alkaline metal ions. The limit concentration for the detection of 1 for Mg(2+) was estimated to be 0.0156 mM, which was the smallest value in this system.

Ion sensing by charge transfer absorption variations of benzocrown-bipyridinium conjugates with an alkyl chain.

Two benzocrown ether-bipyridinium conjugates, 1 and 2, each having a different length of alkyl chains with butyl and dodecyl groups, respectively, have been synthesized for the purpose of developing a new guest-responsive color-change chemosensor. Both 1 and 2 showed yellow colors with broad absorption bands around 400 nm in acetonitrile. These are associated with the intramolecular charge transfer (CT) absorption, in which the benzocrown ether and bipyridinium units act as the donor and acceptor, respectively. Upon addition of the guest; such as Na(+), they faded in color due to the blue shift in their intramolecular charge transfer absorption bands. These are associated with the formation of 1:1 host-guest inclusion complex. Analogues, 3 and 4, both being similar in structure to 1 and 2 with non-crown ether unit, also showed intramolecular CT absorptions around 400 nm, but did not change their absorption spectra upon addition of the guest because of the lack of guest-binding abilities. The guest-induced color change of 1 and 2 can be used for alkali and alkaline metal ion sensing. Both 1 and 2 could detect divalent cations such as Mg(2+) and Ca(2+) rather than univalent ones, Li(+), Na(+), K(+), Rb(+), and Cs(+). Although a marked difference between 1 and 2 was not observed in their guest sensing abilities, the remarkable recognition of 1 and 2 for Mg(2+) and Ca(2+) was found compared with that of 5, which has benzyl unit instead of alkyl chains of 1 and 2. The sensitivity values of 1 and 2 were roughly proportional to their binding constants, as shown by the binding constants with Li(+), Na(+), Mg(2+), and Ca(2+) with the values of 910, 260, 820, and 2300 M(-1) for 1 and 930, 290, 1270, and 2790 M(-1) for 2, while the binding constants of 5 were estimated to be 930, 440, 210, and 1200 M(-1) for Li(+), Na(+), Mg(2+), and Ca(2+), respectively. The limit concentration of detection of 2 for Ca(2+) was estimated to be 0.016 mM, which was the smallest value in this system.