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Single-atom catalysts with maximal atom-utilization have emerged as promising alternatives for chlorine evolution reaction (CER) toward valuable Cl2 production. However, understanding their intrinsic CER activity has so far been plagued due to the lack of well-defined atomic structure controlling. Herein, we prepare and identify a series of atomically dispersed noble metals (e.g., Pt, Ir, Ru) in nitrogen-doped nanocarbons (M1-N-C) with an identical M-N4 moiety, which allows objective activity evaluation. Electrochemical experiments, operando Raman spectroscopy, and quasi-in situ electron paramagnetic resonance spectroscopy analyses collectively reveal that all the three M1-N-C proceed the CER via a direct Cl-mediated Vomer-Heyrovský mechanism with reactivity following the trend of Pt1-N-C>Ir1-N-C>Ru1-N-C. Density functional theory (DFT) calculations reveal that this activity trend is governed by the binding strength of Cl*-Cl intermediate (ΔGCl*-Cl) on M-N4 sites (Pt
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Mitophagy influences the progression and prognosis of ischemic stroke (IS). However, whether DNA methylation in the brain is associated with altered mitophagy in hypoxia-injured neurons remains unclear. Here, miR-138-5p was found to be highly expressed in exosomes secreted by astrocytes stimulated with oxygen and glucose deprivation/re-oxygenation (OGD/R), which could influence the recovery of OGD/R-injured neurons through autophagy. Mechanistically, miR-138-5p promotes the stable expression of Ras homolog enriched in brain like 1(Rhebl1) through DNA-methyltransferase-3a (DNMT3A), thereby enhancing ubiquitin-dependent mitophagy to maintain mitochondrial homeostasis. Furthermore, we employed glycosylation engineering and bioorthogonal click reactions to load mirna onto the surface of microglia and deliver them to injured region utilising the inflammatory chemotactic properties of microglia to achieve drug-targeted delivery to the central nervous system (CNS). Our findings demonstrate miR-138-5p improves mitochondrial function in neurons through the miR-138-5p/DNMT3A/Rhebl1 axis. Additionally, our engineered cell vector-targeted delivery system could be promising for treating IS. STATEMENT OF SIGNIFICANCE: In this study, we demonstrated that miR-138-5p in exosomes secreted by astrocytes under hypoxia plays a critical role in the treatment of hypoxia-injured neurons. And we find a new target of miR-138-5p, DNMT3A, which affects neuronal mitophagy and thus exerts a protective effect by regulating the methylation of Rbebl1. Furthermore, we have developed a carrier delivery system by combining miR-138-5p with the cell membrane of microglia and utilized the inflammatory chemotactic properties of microglia to deliver this system to the brain via intravenous injection. This groundbreaking study not only provides a novel therapeutic approach for ischemia-reperfusion treatment but also establishes a solid theoretical foundation for further research on targeted drug delivery for central nervous system diseases with promising clinical applications.
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DNA Metiltransferase 3A , MicroRNAs , Mitofagia , Neurônios , Mitofagia/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Animais , Hipóxia Celular/efeitos dos fármacos , Humanos , DNA (Citosina-5-)-Metiltransferases/metabolismo , Exossomos/metabolismo , Camundongos , Astrócitos/metabolismo , Astrócitos/efeitos dos fármacosRESUMO
Sorafenib, an anticancer drug, has been shown to induce ferroptosis in cancer cells. However, resistance to sorafenib greatly limits its therapeutic efficacy, and the exact mechanism of resistance is not fully understood. This study investigated the role of N-Acetyltransferase 10 (NAT10) in influencing the anticancer activity of sorafenib in nasopharyngeal carcinoma (NPC) and its molecular mechanism. NAT10 expression was significantly upregulated in NPC. Mechanistically, NAT10 promotes proteins of solute carrier family 7 member 11 (SLC7A11) expression through ac4C acetylation, inhibiting sorafenib-induced ferroptosis in NPC cells. The combined application of sorafenib and the NAT10 inhibitor remodelin significantly inhibits SLC7A11 expression and promotes ferroptosis in NPC cells. In vivo knockout of NAT10 inhibited the growth of sorafenib-resistant NPC. Our findings suggest that NAT10 inhibition might be a promising therapeutic approach to enhance the anticancer activity of sorafenib.
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Sistema y+ de Transporte de Aminoácidos , Resistencia a Medicamentos Antineoplásicos , Ferroptose , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Sorafenibe , Sorafenibe/farmacologia , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/genética , Animais , Camundongos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/antagonistas & inibidores , Antineoplásicos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Acetiltransferases/metabolismo , Acetiltransferases/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos Nus , Masculino , Acetilação/efeitos dos fármacos , FemininoRESUMO
The inherent large number of hydroxyl groups of silica poses strong hydrophilicity, resulting in poor dispersibility in the natural rubber matrix. Here, the silica's surface was hydrophobically modified with [3-(triethoxysiliconyl) propyl] tetrasulfide (Si69) to improve the dispersibility and reinforce the mechanical properties of silica/natural rubber composites. The structure and morphology of modified silica were characterized by Fourier infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray electron spectroscopy (XPS), nuclear magnetic resonance spectroscopy and the contact angle. Further, the mechanical properties, dynamic mechanical properties and morphology of silica/natural rubber composites were studied with a universal electronic tension machine, dynamic thermal mechanical properties analyzer (DMA) and scanning electron microscope (SEM). The experimental results show that the Si69 was successfully grafted onto the surface of silica, thereby significantly improving the water contact angle (a 158.6% increase) and enhancing the mechanical properties of modified silica/natural rubber composites.
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Iron-nitrogen-carbon (Fe-N-C) catalysts, although the most active platinum-free option for the cathodic oxygen reduction reaction (ORR), suffer from poor durability due to the Fe leaching and consequent Fenton effect, limiting their practical application in low-temperature fuel cells. This work demonstrates an integrated catalyst of a platinum-iron (PtFe) alloy planted in an Fe-N-C matrix (PtFe/Fe-N-C) to address this challenge. This novel catalyst exhibits both high-efficiency activity and stability, as evidenced by its impressive half-wave potential (E1/2) of 0.93 V versus reversible hydrogen electrode (vs RHE) and minimal 7 mV decay even after 50,000 potential cycles. Remarkably, it exhibits a very low hydrogen peroxide (H2O2) yield (0.07%) at 0.6 V and maintains this performance with negligible change after 10,000 potential cycles. Fuel cells assembled with this cathode PtFe/Fe-N-C catalyst show exceptional durability, with only 8 mV voltage loss at 0.8 A cm-2 after 30,000 cycles and ignorable current degradation at a voltage of 0.6 V over 85 h. Comprehensive in situ experiments and theoretical calculations reveal that oxygen species spillover from Fe-N-C to PtFe alloy not only inhibits H2O2 production but also eliminates harmful oxygenated radicals. This work paves the way for the design of highly efficient and stable ORR catalysts and has significant implications for the development of next-generation fuel cells.
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The electrochemical reduction reaction of carbon dioxide (CO2RR) into valuable products offers notable economic benefits and contributes to environmental sustainability. However, precisely controlling the reaction pathways and selectively converting key intermediates pose considerable challenges. In this study, our theoretical calculations reveal that the active sites with different states of copper atoms (1-3-5-7-9) play a pivotal role in the adsorption behavior of the *CHO critical intermediate. This behavior dictates the subsequent hydrogenation and coupling steps, ultimately influencing the formation of the desired products. Consequently, we designed two model electrocatalysts comprising Cu single atoms and particles supported on CeO2. This design enables controlled *CHO intermediate transformation through either hydrogenation with *H or coupling with *CO, leading to a highly selective CO2RR. Notably, our selective control strategy tunes the Faradaic efficiency from 61.1% for ethylene (C2H4) to 61.2% for methane (CH4). Additionally, the catalyst demonstrated a high current density and remarkable stability, exceeding 500 h of operation. This work not only provides efficient catalysts for selective CO2RR but also offers valuable insights into tailoring surface chemistry and designing catalysts for precise control over catalytic processes to achieve targeted product generation in CO2RR technology.
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Due to the heavy burden on human drivers when remotely controlling hexapod robots in complex terrain environments, there is a critical need for robot intelligence to assist in generating control commands. Therefore, this study proposes a mapping process framework that generates a combination of human-robot commands based on decision target values, focusing on the task of robot intelligence assisting drivers in generating human-robot command combinations. Furthermore, human-robot state constraints are quantified as geometric constraints on robot motion and driver fatigue constraints. By optimizing and filtering the feasible set of human-robot commands based on human-robot state constraints, instruction combinations are formed and recommended to the driver in real-time, thereby enhancing the efficiency and safety of human-machine coordination. To validate the effectiveness of the proposed method, a remote human-robot collaborative driving control system based on wearable devices is designed and implemented. Experimental results demonstrate that drivers utilizing the human-robot command recommendation system exhibit significantly improved robot walking stability and reduced collision rates compared to individual driving.
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BACKGROUND: Regorafenib, a multi-targeted kinase inhibitor, has been used in the treatment of Hepatocellular carcinoma (HCC). The purpose of this study is to investigate the mechanism of Regorafenib in HCC. METHODS: Regorafenib's impact on the sensitivity of HCC cells was assessed using CCK8. Differential gene expression analysis was performed by conducting mRNA sequencing after treatment with Regorafenib. The m6A methylation status of CHOP and differential expression of m6A methylation-related proteins were assessed by RIP and Western Blot. To explore the molecular mechanisms involved in the therapeutic effects of Regorafenib in HCC and the impact of METTL14 and CHOP on Regorafenib treatment, we employed shRNA/overexpression approaches to transfect METTL14 and CHOP genes, as well as conducted in vivo experiments. RESULTS: Treatment with Regorafenib led to a notable decrease in viability and proliferation of SK-Hep-1 and HCC-LM3 cells. The expression level of CHOP was upregulated after Regorafenib intervention, and CHOP underwent m6A methylation. Among the m6A methylation-related proteins, METTL14 exhibited the most significant downregulation. Mechanistic studies revealed that Regorafenib regulated the cell cycle arrest in HCC through METTL14-mediated modulation of CHOP, and the METTL14/CHOP axis affected the sensitivity of HCC to Regorafenib. In vivo, CHOP enhanced the anticancer effect of Regorafenib. CONCLUSION: The inhibition of HCC development by Regorafenib is attributed to its modulation of m6A expression of CHOP, mediated by METTL14, and the METTL14/CHOP axis enhances the sensitivity of HCC to Regorafenib. These findings provide insights into the treatment of HCC and the issue of drug resistance to Regorafenib.
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Adenosina/análogos & derivados , Carcinoma Hepatocelular , Pontos de Checagem do Ciclo Celular , Neoplasias Hepáticas , Metiltransferases , Compostos de Fenilureia , Piridinas , Fator de Transcrição CHOP , Humanos , Piridinas/farmacologia , Piridinas/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Camundongos , Animais , Linhagem Celular Tumoral , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Metiltransferases/metabolismo , Metiltransferases/genética , Fator de Transcrição CHOP/metabolismo , Fator de Transcrição CHOP/genética , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos NusRESUMO
Water-soluble organic aerosol (WSOA) plays a crucial role in altering radiative forcing and impacting human health. However, our understanding of the seasonal variations of WSOA in Chinese megacities after the three-year clean air action plan is limited. In this study, we analyzed PM2.5 filter samples collected over one year (2020-2021) in Beijing to characterize the seasonal changes in the chemical and optical properties of WSOA using an offline aerosol mass spectrometer along with spectroscopy techniques. The mean mass concentration of WSOA during the observation period was 8.84 ± 7.12 µg m-3, constituting approximately 64-67 % of OA. Our results indicate the contribution of secondary OA (SOA) increased by 13-28 % due to a substantial reduction in primary emissions after the clean air action plan. The composition of WSOA exhibited pronounced seasonal variations, with a predominant contribution from less oxidized SOA in summer (61 %) and primary OA originating from coal combustion and biomass burning during the heating season (34 %). The mass absorption efficiency of WSOA at 365 nm in winter was nearly twice that in summer, suggesting that WSOA from primary emissions possesses a stronger light-absorbing capability than SOA. On average, water-soluble brown carbon accounted for 33-48 % of total brown carbon absorption. Fluorescence analysis revealed humic-like substances as the most significant fluorescence component of WSOA, constituting 82 %. Furthermore, both absorption and fluorescence chromophores were associated with nitrogen-containing compounds, highlighting the role of nitrogen-containing species in influencing the optical properties of WSOA. The results are important for chemical transport models to accurately simulate the WSOA and its climate effects.
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Modern miniaturized intelligent electronics call for smart switchable and flexible electromagnetic interference (EMI) shielding material for highly precise applications. However, most switchable EMI shielding materials are based on an explicit structural change. Herein, we report a succulent-inspired smart switchable MXene (WR-MXene) coating film realized by inner implicit structural change, which benefits from the insertion of our reversible large-cavity yolk-shell biomicrospheres. The novel switchable yolk-shell biomicrospheres contain a soft N-isopropylacrylamide (PNIPAM) hydrogel core, an "ON/OFF" switchable cavity (over 30% volume fraction), and a porous polydopamine (p-PDA) shell. The yolk-shell biomicrospheres can be obtained by a facile two-step polymerization and a simple drying-dehydration treatment. Because of the "ON/OFF" switchable void space brought by the smart biomicrospheres and conductive framework of MXene, an optimized ultralight and flexible WR-MXene coating film (vWR-coating film) showed both large switchable change (over 60 dB) and extraordinary EMI shielding effectiveness, reaching 95 and over 50 dB in the whole X band (8.2-12.4 GHz). These novel reversible yolk-shell biomicrospheres and the succulent-inspired switchable coating films are promising for smart flexible wearable devices and many advanced multifunctional systems needing dynamic real-time response.
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Electrocatalytic water splitting driven by renewable electricity has been recognized as a promising approach for green hydrogen production. Different from conventional strategies in developing electrocatalysts for the two half-reactions of water splitting (e.g., the hydrogen and oxygen evolution reactions, HER and OER) separately, there has been a growing interest in designing and developing bifunctional electrocatalysts, which are able to catalyze both the HER and OER. In addition, considering the high overpotentials required for OER while limited value of the produced oxygen, there is another rapidly growing interest in exploring alternative oxidation reactions to replace OER for hybrid water splitting toward energy-efficient hydrogen generation. This Review begins with an introduction on the fundamental aspects of water splitting, followed by a thorough discussion on various physicochemical characterization techniques that are frequently employed in probing the active sites, with an emphasis on the reconstruction of bifunctional electrocatalysts during redox electrolysis. The design, synthesis, and performance of diverse bifunctional electrocatalysts based on noble metals, nonprecious metals, and metal-free nanocarbons, for overall water splitting in acidic and alkaline electrolytes, are thoroughly summarized and compared. Next, their application toward hybrid water splitting is also presented, wherein the alternative anodic reactions include sacrificing agents oxidation, pollutants oxidative degradation, and organics oxidative upgrading. Finally, a concise statement on the current challenges and future opportunities of bifunctional electrocatalysts for both overall and hybrid water splitting is presented in the hope of guiding future endeavors in the quest for energy-efficient and sustainable green hydrogen production.
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Revealing the dynamic reconstruction process and tailoring advanced copper (Cu) catalysts is of paramount significance for promoting the conversion of CO2 into ethylene (C2H4), paving the way for carbon neutralization and facilitating renewable energy storage. In this study, we initially employed density functional theory (DFT) and molecular dynamics (MD) simulations to elucidate the restructuring behavior of a catalyst under electrochemical conditions and delineated its restructuring patterns. Leveraging insights into this restructuring behavior, we devised an efficient, low-coordination copper-based catalyst. The resulting synthesized catalyst demonstrated an impressive Faradaic efficiency (FE) exceeding 70 % for ethylene generation at a current density of 800â mA cm-2. Furthermore, it showed robust stability, maintaining consistent performance for 230â hours at a cell voltage of 3.5â V in a full-cell system. Our research not only deepens the understanding of the active sites involved in designing efficient carbon dioxide reduction reaction (CO2RR) catalysts but also advances CO2 electrolysis technologies for industrial application.
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N6-methyladenosine (m6A) is an RNA modification that can be removed by demethylases [fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5)], which regulate gene expression and cell function. We show that m6A levels and m6A demethylase levels are altered in nasopharyngeal carcinoma (NPC) tissues vs. normal tissues. High FTO and ALKBH5 predict a poor prognosis in NPC patients. Silencing FTO and ALKBH5 inhibited the malignant behavior of patient-derived NPC cells in a short time. However, as time progressed, the inhibitory effect of FTO or ALKBH5 was weakened, and the cosilencing of FTO and ALKBH5 maintained a better inhibitory effect. Combined transcriptome and m6A-seq analysis revealed a downstream target gene that was jointly regulated by FTO and ALKBH5 in NPC, and ARHGAP35 was chosen to do further study. The synergistic silencing of FTO and ALKBH5 increased the methylation level on the mRNA CDS of a new transcription factor (ARHGAP35) and positively regulate the protein coding capacity and mRNA stability of ARHGAP35, thus leading to increased expression of ARHGAP35 and inhibition of the malignant phenotype of tumor cells. Our study revealed that the growth and metastasis of NPC can be stably inhibited through synergistic silencing of the demethylases FTO and ALKBH5, which play a positive role in the treatment of NPC by regulating the downstream transcript ARHGAP35 and increasing its m6A level.
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Recently, many efforts have been made to address the rapid spread of newly identified COVID-19 virus variants. Wastewater-based epidemiology (WBE) is considered a potential early warning tool for identifying the rapid spread of this virus. This study investigated the occurrence of SARS-CoV-2 in eight wastewater treatment plants (WWTPs) and their sewerage systems which serve most of the population in Taoyuan City, Taiwan. Across the entire study period, the wastewater viral concentrations were correlated with the number of COVID-19 cases in each WWTP (Spearman's r = 0.23-0.76). In addition, it is confirmed that several treatment technologies could effectively eliminate the virus RNA from WWTP influent (> 90%). On the other hand, further results revealed that an inverse distance weighted (IDW) interpolation and hotspot model combined with the geographic information system (GIS) method could be applied to analyze the spatiotemporal variations of SARS-CoV-2 in wastewater from the sewer system. In addition, socio-economic factors, namely, population density, land use, and income tax were successfully identified as the potential drivers which substantially affected the onset of the COVID-19 outbreak in Taiwan. Finally, the data obtained from this study can provide a powerful tool in public health decision-making not only in response to the current epidemic situation but also to other epidemic issues in the future.
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COVID-19 , RNA Viral , Humanos , Águas Residuárias , SARS-CoV-2 , Vigilância Epidemiológica Baseada em Águas Residuárias , COVID-19/epidemiologiaRESUMO
Matrix stiffness potently promotes the malignant phenotype in various biological contexts. Therefore, identification of gene expression to participate in mechanical force signals transduced into downstream biochemical signaling will contribute substantially to the advances in nasopharyngeal carcinoma (NPC) treatment. In the present study, we detected that cortactin (CTTN) played an indispensable role in matrix stiffness-induced cell migration, invasion, and invadopodia formation. Advances in cancer research have highlighted that dysregulated alternative splicing contributes to cancer progression as an oncogenic driver. However, whether WT-CTTN or splice variants (SV1-CTTN or SV2-CTTN) regulate matrix stiffness-induced malignant phenotype is largely unknown. We proved that alteration of WT-CTTN expression modulated matrix stiffness-induced cell migration, invasion, and invadopodia formation. Considering that splicing factors might drive cancer progression through positive feedback loops, we analyzed and showed how the splicing factor PTBP2 and TIA1 modulated the production of WT-CTTN. Moreover, we determined that high stiffness activated PTBP2 expression. Taken together, our findings showed that the PTBP2-WT-CTTN level increases upon stiffening and then promotes cell migration, invasion, and invadopodia formation in NPC.
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Neoplasias Nasofaríngeas , Podossomos , Humanos , Cortactina/genética , Cortactina/metabolismo , Carcinoma Nasofaríngeo/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Nasofaríngeas/genética , Invasividade NeoplásicaRESUMO
Electrolysis that reduces carbon dioxide (CO2) to useful chemicals can, in principle, contribute to a more sustainable and carbon-neutral future1-6. However, it remains challenging to develop this into a robust process because efficient conversion typically requires alkaline conditions in which CO2 precipitates as carbonate, and this limits carbon utilization and the stability of the system7-12. Strategies such as physical washing, pulsed operation and the use of dipolar membranes can partially alleviate these problems but do not fully resolve them11,13-15. CO2 electrolysis in acid electrolyte, where carbonate does not form, has therefore been explored as an ultimately more workable solution16-18. Herein we develop a proton-exchange membrane system that reduces CO2 to formic acid at a catalyst that is derived from waste lead-acid batteries and in which a lattice carbon activation mechanism contributes. When coupling CO2 reduction with hydrogen oxidation, formic acid is produced with over 93% Faradaic efficiency. The system is compatible with start-up/shut-down processes, achieves nearly 91% single-pass conversion efficiency for CO2 at a current density of 600 mA cm-2 and cell voltage of 2.2 V and is shown to operate continuously for more than 5,200 h. We expect that this exceptional performance, enabled by the use of a robust and efficient catalyst, stable three-phase interface and durable membrane, will help advance the development of carbon-neutral technologies.
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Solar driven proton exchange membrane water electrolysis (PEMWE) is of great promise for stable and high-purity H2 production, but often limited by the serious partial loading issue due to the intermittent nature of solar energy, the kinetically sluggish oxygen evolution reaction (OER) and the usage of noble metal-based anodes (e. g., Pt, Ir, and Ru). Herein, we report an efficient integrated water electrolysis by replacing OER with favorable pyrrole electrooxidation polymerization for H2 generation in acidic solutions, wherein nonprecious Co2P and carbon cloth (CC) served as cathode and anode, respectively. A voltage of only 1.0â V was needed to afford 10â mA cm-2, 590â mV smaller than that in traditional PEMWE based on noble Pt/C@RuO2 benchmark couple. Moreover, simple carbonization of the resulting polypyrrole/CC at anode yielded a supercapacitor electrode with a high specific capacitance of 290â F g-1 at 1â A g-1 and robust stability, which then functioned as energy reservoir to alleviate the partial loading issue for coproduction of solar H2 and supercapacitor electrode.
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PURPOSE: Nasopharyngeal carcinoma (NPC) has characteristics of high invasion and early metastasis. Most NPC patients present with locoregionally advanced illness when first diagnosed. Therefore, it is urgent to discover NPC biomarkers. Fibroblast growth Factor 19 (FGF19) plays a role in various physiological or pathological processes, including cancer. In this research, we discovered the importance of FGF19 in NPC, and clarified its role in tumour angiogenesis. METHODS: Western blotting, immunohistochemistry and ELISA were used to investigate FGF19 expression in NPC. Then we took CCK8, colony formation, Transwell and wound healing assays to identify the influence of FGF19 on NPC malignant behaviours. The proliferative and metastatic capacity of FGF19 were evaluated in nude mice and zebrafish. The role of FGF19 in angiogenesis was investigated by tube formation and Matrigel plug angiogenesis assays. We then evaluated the variation in Annexin A2(ANXA2) levels with the treatment of FGF19. Lastly, co-immunoprecipitation and ubiquitination assays were performed to identify the mechanisms involved. RESULTS: FGF19 levels were elevated in tissues and serum of NPC patients and were associated with poor clinical stages. High expression of FGF19 promoted NPC malignant behaviours. In particular, FGF19 expression was correlated with microvessel density in tissues and NPC-derived FGF19 could accelerate angiogenesis in vitro and in vivo. Mechanistically, FGF19 influenced ANXA2 expression to promote angiogenesis. Moreover, tripartite motif-containing 21(TRIM21) interacted with ANXA2 and was responsible for ANXA2 ubiquitination. CONCLUSION: FGF19 promoted NPC angiogenesis by inhibiting TRIM21-mediated ANXA2 ubiquitination. It may serve as a noninvasive biomarker for NPC and provides new insights for therapy.
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Anexina A2 , Fatores de Crescimento de Fibroblastos , Neoplasias Nasofaríngeas , Ribonucleoproteínas , Animais , Humanos , Camundongos , Angiogênese , Anexina A2/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Fatores de Crescimento de Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Peixe-Zebra/metabolismo , Ribonucleoproteínas/metabolismoRESUMO
Direct CO2 electroreduction to valuable chemicals is critical for carbon neutrality, while its main products are limited to simple C1 /C2 compounds, and traditionally, the anodic O2 byproduct is not utilized. We herein report a tandem electrothermo-catalytic system that fully utilizes both cathodic (i.e., CO) and anodic (i.e., O2 ) products during overall CO2 electrolysis to produce valuable organic amides from arylboronic acids and amines in a separate chemical reactor, following the Pd(II)-catalyzed oxidative aminocarbonylation mechanism. Hexamethylenetetramine (HMT)-incorporated silver and nickel hydroxide carbonate electrocatalysts were prepared for efficient coproduction of CO and O2 with Faradaic efficiencies of 99.3 % and 100 %, respectively. Systematic experiments, operando attenuated total reflection surface-enhanced Fourier transform infrared spectroscopy characterizations and theoretical studies reveal that HMT promotes *CO2 hydrogenation/*CO desorption for accelerated CO2 -to-CO conversion, and O2 inhibits reductive deactivation of the Pd(II) catalyst for enhanced oxidative aminocarbonylation, collectively leading to efficient synthesis of 10 organic amides with high yields of above 81 %. This work demonstrates the effectiveness of a tandem electrothermo-catalytic strategy for economically attractive CO2 conversion and amide synthesis, representing a new avenue to explore the full potential of CO2 utilization.