Tumour lineage plasticity is an emerging hallmark of aggressive tumours. Tumour cells usually hijack developmental signalling pathways to gain cellular plasticity and evade therapeutic targeting. In ...the present study, the secreted protein growth and differentiation factor 1 (GDF1) is found to be closely associated with poor tumour differentiation. Overexpression of GDF1 suppresses cell proliferation but strongly enhances tumour dissemination and metastasis. Ectopic expression of GDF1 can induce the dedifferentiation of hepatocellular carcinoma (HCC) cells into their ancestral lineages and reactivate a broad panel of cancer testis antigens (CTAs), which further stimulate the immunogenicity of HCC cells to immune-based therapies. Mechanistic studies reveal that GDF1 functions through the Activin receptor-like kinase 7 (ALK7)-Mothers against decapentaplegic homolog 2/3 (SMAD2/3) signalling cascade and suppresses the epigenetic regulator Lysine specific demethylase 1 (LSD1) to boost CTA expression. GDF1-induced tumour lineage plasticity might be an Achilles heel for HCC immunotherapy. Inhibition of LSD1 based on GDF1 biomarker prescreening might widen the therapeutic window for immune checkpoint inhibitors in the clinic.
Alloyed PdmAu nanoparticles (m refers to the atomic Pd/Au ratio), prepared through the co-reduction of K2PdCl4 and HAuCl4 precursors in aqueous solutions, are employed as the catalysts for ethanol ...electro-oxidation reaction (EOR) in alkaline electrolyte. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) are used to characterize the morphology and confirm the alloy structure of the samples. Cyclic voltammetry (CV) and chronoamperometry (CA) results indicate that the addition of Au to Pd can significantly improve the catalytic activity of Pd toward EOR and the improvement is strongly dependent on the composition of the catalysts. Pd1.0Au/C is identified as the most efficient catalyst since it produces the highest catalytic activity and long-term stability. The mass-specific activity (MSA) and intrinsic activity (IA) data of Pd1.0Au/C is 1.45 mA μg−1Pd+Au and 80.2 A m−2Pd, which is found to be 2.3 and 11.3 times that of the Pd/C catalyst, respectively. These findings clearly suggest that the proximity and relative amount of Au and Pd on the surface of the nanoparticles (NPs) are crucial for the improvement of Pd catalysis, which would have important implications for designed preparation of bimetallic catalysts for the direct alcohol fuel cells.
► Alloyed PdmAu NPs are prepared through the co-reduction of K2PdCl4 and HAuCl4 precursors. ► The addition of Au into Pd catalysts improves the catalytic activity and stability of Pd for EOR. ► Proper proximity and relative amount of Au and Pd are crucial for the promotion effect of Au.
•Physiological changes in the brain under different vibration frequencies were measured using a custom-built vibration instrument.•Cerebral blood flow was modulated with vibration and decreased with ...increased frequency.•The regions with a significant cerebral blood flow decrease coincided with the default mode network.
Human brain experiences vibration of certain magnitude and frequency during various physical activities such as vehicle transportation and machine operation, which may cause traumatic brain injury or other brain diseases. However, the mechanisms of brain pathogenesis due to vibration are not fully elucidated due to the lack of techniques to study brain functions while applying vibration to the brain at a specific magnitude and frequency. Here, this study reported a custom-built head-worn electromagnetic actuator that applied vibration to the brain in vivo at an accurate frequency inside a magnetic resonance imaging scanner while cerebral blood flow (CBF) was acquired. Using this technique, CBF values from 45 healthy volunteers were quantitatively measured immediately following vibration at 20, 30, 40 Hz, respectively. Results showed increasingly reduced CBF with increasing frequency at multiple regions of the brain, while the size of the regions expanded. Importantly, the vibration-induced CBF reduction regions largely fell inside the brain's default mode network (DMN), with about 58 or 46% overlap at 30 or 40 Hz, respectively. These findings demonstrate that vibration as a mechanical stimulus can change strain conditions, which may induce CBF reduction in the brain with regional differences in a frequency-dependent manner. Furthermore, the overlap between vibration-induced CBF reduction regions and DMN suggested a potential relationship between external mechanical stimuli and cognitive functions.
In the present work, CeO2 nanocrystals with three well-defined morphologies including nanooctahedra, nanosphere and nanocube are synthesized and used as the promoter to Pt catalyst toward methanol ...electrooxidation reaction (MOR). The promotion effects of the CeO2 nanocrystals are investigated through electrochemical techniques including cyclic voltammetry (CV), linear sweep voltammetry (LSV), electrochemical impedance spectroscopy (EIS) and chronoamperometry (CA). Results indicate that the promotion effects are closely related to the nanostructure of CeO2 nanocrystals. Among the Pt-CeO2/C catalysts, Pt-CeO2/C-S catalyst with CeO2 nanosphere as the promoter shows the highest catalytic performance for MOR, which arises from both physical interaction and electronic effects between CeO2 and Pt. The loosened nanosphere structure with rough surface allows the Pt nanoparticles (NPs) to highly disperse onto the surface and thereby produce a strong physical interaction between Pt and CeO2. In addition, the change in the valence state from Ce4+ to Ce3+ generates abundant oxygen vacancies (VO) into the crystal lattice, and the increased vacancies lead to surplus electrons which would transfer from CeO2 to Pt. The increased electron density lowers the d-band center and thus improves the intrinsic activities (IA) of Pt. These data are used to discuss the role of physical interaction and electronic effects between the promoter and Pt and would be promising in designing the nanostructure of the Pt-based catalysts for DMFCs and other applications.
•CeO2 nanooctahedron, nanosphere and nanocube are prepared.•The CeO2 nanocrystals are used as the promoter to Pt electrocatalyst for MOR.•Morphology effects of CeO2 on the catalytic properties of Pt are investigated.•CeO2 nanospheres show the highest promotion effects.
The advancement of an affordable and highly effective catalyst for the oxygen evolution reaction (OER) is essential to enhance the performance of overall water splitting (OWS). Here, we report a ...highly efficient nickel foam (NF)-supported CoFe(OH)x-Co3O4/NF heterostructure catalyst for OER. The CoFe(OH)x-Co3O4/NF heterostructure catalyst contain amorphous phase CoFe(OH)x and crystalline Co3O4, and the synergistic interaction between the two different phases reduces the charge transfer resistance, accelerates the kinetic processes of electrocatalysis and makes the catalysts exhibit excellent catalytic performance. In 1.0 M KOH solution, an overpotential (η) of merely 262 mV is needed to attain a current density of 100 mA cm−2. Even at high current densities demanded for commercial applications, the overpotentials remain very low (η500 = 291 mV, η1000 = 319 mV). The catalytic activity of CoFe(OH)x-Co3O4/NF has exceeded that of most non-noble metal OER catalysts documented in the literature. Furthermore, the CoFe(OH)x-Co3O4/NF catalyst demonstrates superior catalytic stability to OER, with only a 23 mV potential increase after 24 h of stability testing at a high current density of 500 mA cm−2. Owing to the heterostructure, the CoFe(OH)x-Co3O4/NF catalyst also exhibits excellent catalytic performance for the urea oxidation reaction (UOR), and the use of UOR instead of OER at the anode of OWS significantly reduces the cell voltage, thereby reducing the electrolytic energy consumption. The findings in this work offer precious insights into the design of OWS anode catalysts and their important applications in industrial water electrolysis. These insights are crucial for advancing the development of highly efficient and sustainable water electrolysis processes, which is essential for the production of green hydrogen and other valuable chemicals.
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•Nickel foam supported CoFe(OH)x-Co3O4 heterostructure catalyst is synthesized.•CoFe(OH)x-Co3O4/NF exhibits excellent activity for OER at high current densities.•CoFe(OH)x-Co3O4/NF can maintain excellent catalytic stability for more than 24 h.•UOR can replace OER in combination with HER for energy-efficient H2 production.
Reduced graphene oxide (RGO) supported PtmAu electrocatalysts with different atomic Pt/Au ratios (m = 0.5–2.0) are prepared via co-reduction of H2PtCl6 and HAuCl4. The catalysts are comprehensively ...characterized through TEM, XRD and XPS. The catalytic behaviors of the PtmAu catalysts toward methanol oxidation reaction (MOR) in alkaline electrolyte are investigated via cyclic voltammetry (CV) and chronoamperometry (CA) techniques. Results show that methanol oxidation currents on the PtmAu catalysts are higher than that on pure Pt catalyst, suggesting that the introduction of Au in Pt catalyst can significantly promote the catalytic properties of Pt. Among the PtmAu catalysts, Pt1.0Au/RGO shows the highest mass-specific activity (MSA) and intrinsic activity (IA). The MSA and IA of Pt1.0Au/RGO is 0.72 A mg−1Pt+Au and 105.4 A m−2Pt, which are ca. 2.40 and 3.56 times those of Pt/RGO (0.30 A mg−1Pt+Au and 29.6 A m−2Pt), respectively. CO stripping voltammograms and CV curves suggest that the improved electrocatalytic properties of the PtmAu/RGO catalysts are especially attributed to the decreased CO formation rather than the facile removal of CO on the surface of Pt. The findings of this work have potential applications in understanding the mechanism of MOR and designing highly effective Pt-based anodic catalysts of direct methanol fuel cells.
•Reduced graphene oxide supported bimetallic PtmAu electrocatalysts are prepared.•The catalytic properties for methanol oxidation reaction (MOR) are investigated.•The introduction of Au exhibits significant promoting effect to Pt for MOR.•Decreased CO formation on Pt is the key reason for the enhanced catalytic activity.
The sluggish kinetics of the oxygen evolution reaction (OER) always results in a high overpotential at the anode of water electrolysis and an excessive electric energy consumption, which has been a ...major obstacle for hydrogen production through water electrolysis. In this study, we present a CoNi-LDH/Fe MOF/NF heterostructure catalyst with nanoneedle array morphology for the OER. In 1.0 M KOH solution, the heterostructure catalyst only required overpotentials of 275 and 305 mV to achieve high current densities of 500 and 1000 mA/cm2 for OER, respectively. The catalytic activities are much higher than those of the reference single-component CoNi-LDH/NF and Fe MOF/NF catalysts. The improved catalytic performance of the heterostructure catalyst can be ascribed to the synergistic effect of CoNi-LDH and Fe MOF. In particular, when the anodic OER is replaced with the urea oxidation reaction (UOR), which has a relatively lower thermodynamic equilibrium potential and is expected to reduce the cell voltage, the overpotentials required to achieve the same current densities can be reduced by 80 and 40 mV, respectively. The cell voltage required to drive overall urea splitting (OUS) is only 1.55 V at 100 mA/cm2 in the Pt/C/NF||CoNi-LDH/Fe MOF/NF two-electrode electrolytic cell. This value is 60 mV lower compared with that required for overall water splitting (OWS). Our results indicate that a reasonable construction of a heterostructure catalyst can significantly give rise to higher electrocatalytic performance, and using UOR to replace the anodic OER of the OWS can greatly reduce the electrolytic energy consumption.
Clinical observation of the association between cancer aggressiveness and embryonic development stage implies the importance of developmental signals in cancer initiation and therapeutic resistance. ...However, the dynamic gene expression during organogenesis and the master oncofetal drivers are still unclear, which impeded the efficient elimination of poor prognostic tumors, including human hepatocellular carcinoma (HCC). In this study, human embryonic stem cells were induced to differentiate into adult hepatocytes along hepatic lineages to mimic liver development in vitro. Combining transcriptomic data from liver cancer patients with the hepatocyte differentiation model, the active genes derived from different hepatic developmental stages and the tumor tissues were selected. Bioinformatic analysis followed by experimental assays was used to validate the tumor subtypespecific oncofetal signatures and potential therapeutic values. Hierarchical clustering analysis revealed the existence of two subtypes of liver cancer with different oncofetal properties. The gene signatures and their clinical significance were further validated in an independent clinical cohort and The Cancer Genome Atlas database. Upstream activator analysis and functional screening further identified E2F1 and SMAD3 as master transcriptional regulators. Small-molecule inhibitors specifically targeting the oncofetal drivers extensively down-regulated subtype-specific developmental signaling and inhibited tumorigenicity. Liver cancer cells and primary HCC tumors with different oncofetal properties also showed selective vulnerability to their specific inhibitors. Further precise targeting of the tumor initiating steps and driving events according to subtype-specific biomarkers might eliminate tumor progression and provide novel therapeutic strategy.
Operational amplifiers (op-amps) are generally used for actualizing simple and complex electronic circuits in the subject of analogue electronics. In an effort to improve the teaching of op-amps in ...electronics engineering curricula, op-amp circuits in various configurations are often used for experiments in laboratory sessions so that students can acquire certain psychomotor and cognitive skills by constructing circuit connections and analyzing input–output waveforms. As a result, multiple configurations of operational amplifier circuits are often needed, requiring multiple sets of experimental boards or circuits for each experiment. This is usually not cost effective, requires more consumable electronic components, requires more maintenance and storage space in facilities, and is less user friendly for the students. Therefore, the aim of this research is to design a single, compact, and easy-to-replicate experimental board that can be converted into multiple configurations of the LM741 operational amplifier, comprising an inverting amplifier, a noninverting amplifier, a voltage follower, a summing amplifier, a differential amplifier, a differentiator, and an integrator, with minimal electronic components at a cost lower than EUR 10. The experimental board was tested with a constant input voltage of 1.0 V AC and a switching frequency of 1.0 kHz. It is capable of producing an output voltage corresponding to the individual operational amplifier configurations and can thus be used as a facilitating module for teaching and learning activities in the field of analogue electronics.
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