Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their ...sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very longchain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.
For catalysing dioxygen reduction, iron–nitrogen–carbon (Fe–N–C) materials are today the best candidates to replace platinum in proton-exchange membrane fuel cell (PEMFC) cathodes. Despite tremendous ...progress in their activity and site-structure understanding, improved durability is critically needed but challenged by insufficient understanding of their degradation mechanisms during operation. Here, we show that FeN x C y moieties in a representative Fe–N–C catalyst are structurally stable but electrochemically unstable when exposed in an acidic medium to H 2 O 2 , the main oxygen reduction reaction (ORR) byproduct. We reveal that exposure to H 2 O 2 leaves iron-based catalytic sites untouched but decreases their turnover frequency (TOF) via oxidation of the carbon surface, leading to weakened O 2 -binding on iron-based sites. Their TOF is recovered upon electrochemical reduction of the carbon surface, demonstrating the proposed deactivation mechanism. Our results reveal for the first time a hitherto unsuspected key deactivation mechanism during the ORR in an acidic medium. This study identifies the N-doped carbon surface as the Achilles' heel during ORR catalysis in PEMFCs. Observed in acidic but not in alkaline electrolytes, these insights suggest that durable Fe–N–C catalysts are within reach for PEMFCs if rational strategies minimizing the amount of H 2 O 2 or reactive oxygen species (ROS) produced during the ORR are developed.
Catalysis is a key technology for the synthesis of renewable fuels through electrochemical reduction of CO2. However, successful CO2 reduction still suffers from the lack of affordable catalyst ...design and understanding the factors governing catalysis. Herein, we demonstrate that the CO2 conversion selectivity on Sn (or SnOx/Sn) electrodes is correlated to the native oxygen content at the subsurface. Electrochemical analyses show that the reduced Sn electrode with abundant oxygen species effectively stabilizes a CO2.− intermediate rather than the clean Sn surface, and consequently results in enhanced formate production in the CO2 reduction. Based on this design strategy, a hierarchical Sn dendrite electrode with high oxygen content, consisting of a multi‐branched conifer‐like structure with an enlarged surface area, was synthesized. The electrode exhibits a superior formate production rate (228.6 μmol h−1 cm−2) at −1.36 VRHE without any considerable catalytic degradation over 18 h of operation.
Not exactly what it says on the tin: Rational design principles for tin electrodes to be used in selective CO2 reduction to formate are suggested using hierarchical tin dendrite electrodes (multi‐branched conifer‐like structure) that show remarkable activity and stability. The initial oxygen content of the tin electrode is set as “selectivity descriptor” and the architecture is manipulated to maximize the number of active sites.
Abstract
Ultra-thin two-dimensional semiconducting crystals in their monolayer and few-layer forms show promising aspects in nanoelectronic applications. However, the ultra-thin nature of ...two-dimensional crystals inevitably results in high contact resistance from limited channel/contact volume as well as device-to-device variability, which seriously limit reliable applications using two-dimensional semiconductors. Here, we incorporate rather thick two-dimensional layered semiconducting crystals for reliable vertical diodes showing excellent Ohmic and Schottky contacts. Using the vertical transport of WSe
2
, we demonstrate devices which are functional at various frequency ranges from megahertz AM demodulation of audio signals, to gigahertz rectification for fifth-generation wireless electronics, to ultraviolet–visible photodetection. The WSe
2
exhibits an excellent Ohmic contact to bottom platinum electrode with record-low contact resistance (~50 Ω) and an exemplary Schottky junction to top transparent conducting oxide electrode. Our semitransparent vertical WSe
2
Schottky diodes could be a key component of future high frequency electronics in the era of fifth-generation wireless communication.
Flexible thermoelectrics that enable conformal contact with heat sources of arbitrary shape are indispensable for self‐powered wearable electronics. Scalable integration of flexible thermoelectric ...(TE) materials into functional devices has improved over the past few years, however, the practical applications of flexible TE materials are still hindered by low performance. Herein, highly aligned carbon‐nanotube yarns (CNTYs) are proposed, combined with selective doping via picoliter scale inkjet printing. Coagulation assisted by van der Waals forces ensures a highly aligned structure of the CNTY, thus achieving the ultrahigh power factors of 4091 and 4739 µW m−1 K−2 for the p‐ and n‐type, respectively. The proposed TE materials can be effortlessly up‐scaled into highly integrated modules via inkjet printing. A highly integrated, flexible CNTY‐based TE generator (TEG) with 600 PN pairs generates unparalleled milliwatt‐scale power at ΔT = 25 K, which is a few orders of magnitude higher than those of previously reported flexible material‐based TEGs. This TEG successfully powers a red light‐emitting diode using body heat alone, requiring no external power sources. For the seamless operation of practical applications requiring high power, this work explores the key design parameters for flexible TEGs with high performance and manufacturability and presents new platforms for self‐powered wearable electronics.
Flexible thermoelectrics (TE) that enable conformal contact with heat sources of arbitrary shape are indispensable for self‐powered wearable electronics. The authors propose highly aligned carbon‐nanotube yarns combined with selective doping via picoliter scale inkjet printing, offering effortless scale‐up into highly integrated modules. The TE module with 600 PN pairs generates unparalleled milliwatt‐scale power at ΔT = 25 K.
PIK3CA is a frequently mutated gene in cancer, including about ~15 to 20% of colorectal cancers (CRC). PIK3CA mutations lead to activation of the PI3K/AKT/mTOR signaling pathway, which plays pivotal ...roles in tumorigenesis. Here, we investigated the mechanism of resistance of PIK3CA‐mutant CRC cell lines to gedatolisib, a dual PI3K/mTOR inhibitor. Out of a panel of 29 CRC cell lines, we identified 7 harboring one or more PIK3CA mutations; of these, 5 and 2 were found to be sensitive and resistant to gedatolisib, respectively. Both of the gedatolisib‐resistant cell lines expressed high levels of active glycogen synthase kinase 3‐beta (GSK3β) and harbored the same frameshift mutation (c.465_466insC; H155fs*) in TCF7, which encodes a positive transcriptional regulator of the WNT/β‐catenin signaling pathway. Inhibition of GSK3β activity in gedatolisib‐resistant cells by siRNA‐mediated knockdown or treatment with a GSK3β‐specific inhibitor effectively reduced the activity of molecules downstream of mTOR and also decreased signaling through the WNT/β‐catenin pathway. Notably, GSK3β inhibition rendered the resistant cell lines sensitive to gedatolisib cytotoxicity, both in vitro and in a mouse xenograft model. Taken together, these data demonstrate that aberrant regulation of WNT/β‐catenin signaling and active GSK3β induced by the TCF7 frameshift mutation cause resistance to the dual PI3K/mTOR inhibitor gedatolisib. Cotreatment with GSK3β inhibitors may be a strategy to overcome the resistance of PIK3CA‐ and TCF7‐mutant CRC to PI3K/mTOR‐targeted therapies.
What's new?
Mutations in the PI3K/mTOR and WNT/β‐catenin pathways are common in colorectal cancer. Here, in colorectal cancer cells, the authors show that the frameshift mutation H155fs* in transcription factor TCF7 serves a critical role in mediating resistance to the PI3K/mTOR dual inhibitor gedatolisib. TCF7 H155fs* maintained mTOR signaling by inducing the active form of glycogen synthase kinase 3‐beta (GSK3β) and aberrant WNT/β‐catenin signaling. The latter conferred resistance to gedatolisib. Co‐treatment with a GSK3β inhibitor increased sensitivity to gedatolisib, a combination that synergistically inhibited colorectal tumor growth in mice. The findings shed light on gedatolisib resistance mechanisms and potential resistance biomarkers.
Top‐gate ferroelectric memory transistors with single‐ to triple‐layered MoS2 nanosheets adopting poly(vinylidenefluoride‐trifluoroethylene) P(VDF‐TrFE) are demonstrated. The nonvolatile memory ...transistor with a single‐layer MoS2 channel exhibits excellent retention properties for more than 1000 s, maintaining ~5 × 103 for the program/erase ratio and displaying a high mobility of ~220 cm2/(V·s).
Simultaneous monitoring of electrophysiology and magnetic resonance imaging (MRI) could guide the innovative diagnosis and treatment of various neurodegenerative diseases that are previously ...impossible. However, this technique is difficult because the existing metal‐based implantable neural interface for electrophysiology is not free from signal distortions from its intrinsic magnetic susceptibility while performing an MRI of the implanted area of the neural interface. Moreover, brain tissue heating from neural implants generated by the radiofrequency field from MRI poses potential hazards for patients. Previous studies with soft polymer‐based electrode arrays provide relatively suitable MRI compatibility but does not guarantee high‐resolution electrophysiological signal acquisition and stimulation performance. Here, MRI compatible, optically transparent flexible implantable device capable of electrophysiological multichannel mapping and electrical stimulation is introduced. Using the device, neuropathic pain (NP) relief with a 30‐channel electrophysiological mapping of the somatosensory area before and after motor cortex stimulation (MCS) in allodynia rats after noxious stimulation is confirmed. Additionally, artifact‐free manganese‐enhanced MRI of dramatic relief of pain‐related region activity by MCS is demonstrated. Furthermore, artifact‐free optogenetics with transgenic mice is also investigated by recording light‐evoked potentials. These results suggest a promising neuro‐prosthetic for analyzing and modulating spatiotemporal neurodynamic without MRI or optical modality resolution constraints.
Integration of electrophysiology with magnetic resonance imaging (MRI) is achieved by MRI compatible, transparent Poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) neural implantable device. The neuropathic pain alleviation is demonstrated by this MRI compatible electrode array, simultaneously recording/stimulating the brain with manganese‐enhanced MRI. This work highlights a future technology that eliminates the potential risks and inconveniences of medical imaging of patients with conventional neural implants.
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MR performance of carbonyl iron based MR fluid with four different additive concentration of γ-Fe2O3 nanoparticles were examined. Their magnetorheological behavior was observed using ...a rotational rheometer along with the dispersion stability test of the MR fluids using a Turbiscan.
γ-Fe2O3 nanoparticle additive system was adopted to enhance both the dispersion stability and MR behavior of CI microsphere based MR fluid.Dispersion stability of the MR fluid composed of CI and γ-Fe2O3 particles was confirmed by Turbiscan.Dynamic yield stresses of the MR fluids were well correlated with universal yield stress equation.
Magneto-responsive magnetorheological (MR) characteristics of soft-magnetic carbonyl iron (CI) based MR fluid were examined at four different additive concentrations of hard magnetic γ-Fe2O3 nanoparticles to improve both the dispersion stability and the MR performance. The magnetic stimuli-response of their rheological behavior was determined by examining the flow and dynamic oscillation properties at each additive concentration under a magnetic field using a rotational rheometer. Enhanced yield stresses due to the addition of hard magnetic nanoparticles correlated well using the universal yield stress scaling equation and the parameter critical magnetic field strength. Sedimentation properties of the MR fluid with and without the hard magnetic nanoparticle additive were further tested using a Turbiscan, and showed improved dispersion stability with the additive.
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