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OBJECTIVES: To assess the efficacy and tolerability of iGlarLixi-a novel, fixed-ratio, soluble combination of insulin glargine and lixisenatide-for the treatment of type 2 diabetes (T2D). METHODS: The PubMed, Embase, Cochrane Library and ClinicalTrials.gov databases were searched from inception to November 15, 2023 to identify randomized controlled trials (RCTs) comparing iGlarLixi with a placebo or any other antidiabetic agent in adults with T2D. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated to evaluate the outcomes. RESULTS: A total of 10 trials enrolling 6071 T2D patients were included. Compared with placebos or other antidiabetic agents, iGlarLixi exerted beneficial effects on changes in HbA1c, the percentage of patients who achieved an HbA1c < 7%, the percentage of patients who achieved an HbA1c < 6.5%, the percentage of patients who achieved an HbA1c < 7.0% without weight gain and/or without severe or blood glucose-confirmed hypoglycemic episodes, changes in fasting plasma glucose, and changes in self-measured plasma glucose. Regarding safety, iGlarLixi did not increase the incidence of severe hypoglycemia or serious adverse events but did increase the incidence of gastrointestinal adverse events, symptomatic hypoglycemia, and adverse events (e.g., nausea, vomiting, diarrhea). CONCLUSIONS: iGlarLixi showed improved efficacy and safety in patients with T2D. Additional large, multicenter RCTs are warranted to obtain deeper insights into the efficacy and safety of iGlarLixi, thereby providing guidance for clinical treatment decisions.
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This study proposes a novel inferior vena cava filter (IVCF) design, "Lotus," aiming to enhance release stability and endothelialization. A catheter-filter-vessel model was established for IVCF property analysis, validated by comparing numerical simulations and in vitro tests. Lotus's mechanical properties were analyzed, and optimization suggestions are provided. Compared to existing clinical filters, Lotus demonstrates improved release stability and thrombus capture ability. This work suggests Lotus as a potential technical reference for improved IVCF treatment.
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Gleditsia sinensis, commonly known as Chinese Zaojiao, has important economic value and medicinal compounds in its fruits and thorns, making it widely cultivated artificially in China. However, the available literature on the impact of waterlogging on the growth of G. sinensis seedlings and the accumulation of metabolite compounds in its thorns is limited. To address this knowledge gap, G. sinensis seedlings were planted in soil supplemented with pindstrup substrate, which enhances the water-holding capacity of the soil. The analyses of morphological traits and nutrient elements in one-year-old G. sinensis seedlings grown naturally under ambient conditions and metabolite accumulation in its thorns were conducted. The results showed that the waterlogged soil significantly diminished the height, fresh weight, and dry weight of seedling roots and stems (P < 0.05). Furthermore, waterlogging hindered the uptake of iron (Fe) and manganese (Mn), as well as the transport of potassium (K). The identified metabolites within the thorns were categorized into 16 distinct groups. Relative to the control soil, fatty acids and derivatives were the most down-regulated metabolites in the waterlogged soil, accounting for 40.58% of the total metabolites, followed by lignans (38.71%), phenolic acids (34.48%), saccharides and alcohols (34.15%), steroids (16.67%), alkaloids (12.24%), flavonoids (9.28%), and glycerophospholipids (7.41%). Conversely, nucleotides and derivatives experienced the greatest up-regulation in the waterlogged soil, accounting for 50.00% of the total metabolites. In conclusion, waterlogging negatively impacted the growth of G. sinensis seedlings and inhibited the accumulation of metabolites. Hence, when considering the accumulation of secondary metabolites such as lignans and phenolic acids, appropriate management of soil moisture levels should be taken into account.
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Gleditsia , Lignanas , Plântula , Lignanas/metabolismo , Gleditsia/química , Extratos Vegetais/metabolismo , Raízes de PlantasRESUMO
OBJECTIVES: IDegLira is a novel fixed-ratio soluble combination of insulin degludec and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide approved for type 2 diabetes (T2D) patients. Individual trials have assessed the clinical profile of IDegLira vs different comparators. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of IDegLira for T2D. METHODS: PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched from inception to August 15, 2023. The primary outcomes included change from baseline in haemoglobin A1c (HbA1c) and body weight. Risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) were calculated to evaluate the outcomes. RESULTS: This meta-analysis identified 1044 citations, and included 13 eligible trials, enroling 7773 patients. Compared with the control groups, IDegLira was optimal in change in HbA1c, percentage of patients achieving HbA1c < 7%, percentage of patients achieving HbA1c < 6.5%, HbA1c < 7.0% without weight gain and without severe or blood glucose (BG)-confirmed hypoglycaemia episodes, HbA1c < 6.5% without weight gain and without severe or BG-confirmed hypoglycaemia episodes, change in fasting plasma glucose, change in self-measured plasma glucose, change in systolic pressure, and total daily insulin dose. No difference was found between the IDegLira and control groups in terms of change in body weight, change in diastolic pressure, severe or BG-confirmed symptomatic hypoglycaemia, nocturnal severe or BG-confirmed symptomatic hypoglycaemia, adverse events or serious adverse events. CONCLUSIONS: In patients with T2D, IDegLira improved glycaemic control whilst balancing out risk for hypoglycaemia and gastrointestinal side effects.
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Diabetes Mellitus Tipo 2 , Hipoglicemia , Insulina de Ação Prolongada , Humanos , Liraglutida/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Glicemia , Hemoglobinas Glicadas , Hipoglicemia/induzido quimicamente , Hipoglicemia/tratamento farmacológico , Aumento de Peso , Combinação de MedicamentosRESUMO
Designing an efficient catalyst for acidic oxygen evolution reaction (OER) is of critical importance in manipulating proton exchange membrane water electrolyzer (PEMWE) for hydrogen production. Here, we report a fast, nonequilibrium strategy to synthesize quinary high-entropy ruthenium iridium-based oxide (M-RuIrFeCoNiO2) with abundant grain boundaries (GB), which exhibits a low overpotential of 189 millivolts at 10 milliamperes per square centimeter for OER in 0.5 M H2SO4. Microstructural analyses, density functional calculations, and isotope-labeled differential electrochemical mass spectroscopy measurements collectively reveal that the integration of foreign metal elements and GB is responsible for the enhancement of activity and stability of RuO2 toward OER. A PEMWE using M-RuIrFeCoNiO2 catalyst can steadily operate at a large current density of 1 ampere per square centimeter for over 500 hours. This work demonstrates a pathway to design high-performance OER electrocatalysts by integrating the advantages of various components and GB, which breaks the limits of thermodynamic solubility for different metal elements.
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Crystalline/amorphous phase engineering is demonstrated as a powerful strategy for electrochemical performance optimization. However, it is still a considerable challenge to prepare transition metal-based crystalline/amorphous heterostructures because of the low redox potential of transition metal ions. Herein, a facile H2 -assisted method is developed to prepare ternary Ni2 P/MoNiP2 /MoP crystalline/amorphous heterostructure nanowires on the conductive substrate. The characterization results show that the content of the MoNiP2 phase and the crystallinity of the MoP phase can be tuned by simply controlling the H2 concentration. The obtained electrocatalyst exhibits a superior alkaline hydrogen evolution reaction performance, delivering overpotentials of 20 and 76 mV to reach current densities of 10 and 100 mA cm-2 with a Tafel slope of 30.6 mV dec-1 , respectively. The catalysts also reveal excellent stability under a constant 100 h operation, higher than most previously reported electrocatalysts. These striking performances are ascribed to the optimized hydrogen binding energy and favorable hydrogen adsorption/desorption kinetics. This work not only exhibits the potential application of ternary Ni2 P/MoNiP2 /MoP crystalline/amorphous heterostructure nanowires catalysts for practical electrochemical water splitting, but also paves the way to prepare non-noble transition metal-based electrocatalysts with optimized crystalline/amorphous heterostructures.
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The development of low-cost and high-durability bifunctional electrocatalysts is of considerable importance for overall water splitting (OWS). This work reports the controlled synthesis of nickel-iridium alloy derivative nanochain array electrodes (NiIrx NCs) with fully exposed active sites that facilitated mass transfer for efficient OWS. The nanochains have a self-supported three-dimensional core-shell structure, composed of a metallic NiIrx core and a thin (5-10 nm) amorphous (hydr)oxide film as the shell (e.g., IrO2/NiIrx and Ni(OH)2/NiIrx). Interestingly, NiIrx NCs have bifunctional properties. Particularly, the oxygen evolution reaction (OER) current density (electrode geometrical area) of NiIr1 NCs is four times higher than that of IrO2 at 1.6 V vs. RHE. Meanwhile, its hydrogen evolution reaction (HER) overpotential at 10 mA cm-2 (η10 = 63 mV) is comparable to that of 10 wt% Pt/C. These performances may originate from the interfacial effect between the surface (hydr)oxide shell and metallic NiIrx core, which facilitates the charge transfer, along with the synergistic effect between Ni2+ and Ir4+ in the (hydr)oxide shell. Furthermore, NiIr1 NCs exhibits excellent OER durability (100 h @ 200 mA cm-2) and OWS durability (100 h @ 500 mA cm-2) with the nanochain array structure well preserved. This work provides a promising route for developing effective bifunctional electrocatalysts for OWS applications.
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Cardiac troponin I (cTnI) is an extremely sensitive biomarker for early indication of acute myocardial infarction (AMI). However, it still remains a tough challenge for many newly developed cTnI biosensors to achieve superior sensing performance including high sensitivity, rapid detection, and resistance to interference in clinical serum samples. Herein, a novel photocathodic immunosensor toward cTnI sensing has been successfully developed by designing a unique S-scheme heterojunction based on the porphyrin-based covalent organic frameworks (p-COFs) and p-type silicon nanowire arrays (p-SiNWs). In the novel heterojunction, the p-SiNWs are employed as the photocathode platform to acquire a strong photocurrent response. The in situ-grown p-COFs can accelerate the spatial migration rate of charge carriers by forming proper band alignment with the p-SiNWs. The crystalline π-conjugated network of p-COFs with abundant amino groups also promotes the electron transfer and anti-cTnI immobilizing process. The developed photocathodic immunosensor demonstrates a broad detection range of 5 pg/mL-10 ng/mL and a low limit of detection (LOD) of 1.36 pg/mL in clinical serum samples. Besides, the PEC sensor owns several advantages including good stability and superior anti-interference ability. By comparing our results with that of the commercial ELISA method, the relative deviations range from 0.06 to 0.18% (n = 3), and the recovery rates range from 95.4 to 109.5%. This work displays a novel strategy to design efficient and stable PEC sensing platforms for cTnI detection in real-life serums and provides guidance in future clinical diagnosis.
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Técnicas Biossensoriais , Estruturas Metalorgânicas , Infarto do Miocárdio , Porfirinas , Humanos , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Infarto do Miocárdio/diagnósticoRESUMO
Sunitinib (SNT)-induced cardiotoxicity is associated with abnormal calcium regulation caused by phosphoinositide 3 kinase inhibition in the heart. Berberine (BBR) is a natural compound that exhibits cardioprotective effects and regulates calcium homeostasis. We hypothesized that BBR ameliorates SNT-induced cardiotoxicity by normalizing the calcium regulation disorder via serum and glucocorticoid-regulated kinase 1 (SGK1) activation. Mice, neonatal rat cardiomyocytes (NRVMs), and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to study the effects of BBR-mediated SGK1 activity on the calcium regulation disorder caused by SNT as well as the underlying mechanism. BBR offered prevention against SNT-induced cardiac systolic dysfunction, QT interval prolongation, and histopathological changes in mice. After the oral administration of SNT, the Ca2+ transient and contraction of cardiomyocytes was significantly inhibited, whereas BBR exhibited an antagonistic effect. In NRVMs, BBR was significantly preventive against the SNT-induced reduction of calcium transient amplitude, prolongation of calcium transient recovery, and decrease in SERCA2a protein expression; however, SGK1 inhibitors resisted the preventive effects of BBR. In hiPSC-CMs, BBR pretreatment significantly prevented SNT from inhibiting the contraction, whereas coincubation with SGK1 inhibitors antagonized the effects of BBR. These findings indicate that BBR attenuates SNT-induced cardiac dysfunction by normalizing the calcium regulation disorder via SGK1 activation.
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Berberina , Cardiopatias , Ratos , Camundongos , Humanos , Animais , Sunitinibe/metabolismo , Sunitinibe/farmacologia , Cálcio/metabolismo , Berberina/farmacologia , Cardiotoxicidade/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Cardiopatias/induzido quimicamente , Cardiopatias/prevenção & controle , Cardiopatias/metabolismo , Miócitos CardíacosRESUMO
An efficient NiSx -modified ß-Ni(OH)2 electrode is reported for the selective oxidation reaction of 5-hydroxymethylfurfural (HMFOR) with excellent electrocatalytic 5-hydroxymethylfurfural (HMF) selectivity (99.4%), conversion (97.7%), and Faradaic efficiency (98.3%). The decoration of NiSx will evoke high-valence Ni2+ δ species in the reconstructed ß-Ni(OH)2 electrode, which are the real active species for HMFOR. The generated NiSx /Ni(OH)O modulates the proton-coupled electron-transfer (PCET) process of HMFOR, where the electrocatalytically generated Ni(OH)O can effectively trap the protons from the CHO end in HMF to realize electron transfer. The oxygen evolution reaction (OER) competes with the HMFOR when NiSx /Ni(OH)O continues to accumulate, to generate the NiSx /NiOx (OH)y intermediate. Density functional theory (DFT) calculations and experimental results verify that the adsorption energy of HMF can be optimized through the increased NiSx composition for more efficient capture of protons and electrons in the HMFOR.
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Herein, we report a multiple regulation strategy towards an all-in-one NiCuMo/MoOx heterostructure for the HOR, which exhibits ultrahigh HOR activity (j@0.05V = 4.63 mA cm-2) and excellent durability for almost 24 h for the synergistic regulation of Mo and Cu on the Ni electrode. This study provides a new strategy for designing efficient non-noble metal-based HOR catalysts.
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The work aims to elucidate the importance of hybrid microwave annealing technology (HMA) in ultrafast fabrication of deficient cadmium stannate (Cd2SnO4) photoanodes with a worm-like porous structure and significant enhancement of solar water oxidation performance and stability. Comparison of three synthetic routes and experimental characterization revealed that relative to conventional thermal annealing (CTA) or even with extra HMA for 5 min (optimal), direct HMA for only 8 min can form cubic Cd2SnO4 thin films of unique worm-like and highly porous nanostrucures with a large interfacial surface area, high degree of phase crystallinity and high-concentration defects. The obtained results from the photoluminescence spectra and the charge efficiency measurements collaboratively verified that compared to using CTA treatment solely, the HMA treatment is effective in significantly improving charge separation, recombination and transfer processes, mainly by an over 13.5-fold increase in the bulk charge separation efficiency. Benefiting from these merits, under optimized conditions the HMA treated Cd2SnO4 film exhibited a remarkable 6-fold and 2-fold solar photocurrent enhancement compared with those of the CTA treated one and the combined CTA-HMA treated one, respectively, and an IPCE of 39% at 300 nm and 18% at 350 nm at 1.7 V versus RHE. Despite a high external bias required in this case, the study provides a simple route for synthesis of ideal Cd2SnO4 photoanodes which can be further extended to doping engineering and non-noble metal cocatalyst deposition.
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Based on the necessity and urgency of cardiac troponin I (cTnI) detection for the diagnosis of myocardial infarction, a novel unlabeled photoelectrochemical (PEC) immunosensor has been developed to detect cTnI rapidly and sensitively. Silicon nanowire arrays (SiNWs) were prepared via metal-assisted chemical etching. To improve the stability and sensitivity towards cTnI sensing, the surface of silicon nanowire arrays were coated with polydopamine by an in situ growth method. PDA was uniformly modified on the nanowire surface to provide a reliable active site for antibody binding. The linear dynamic range of the cTnI detection method was 0.005-10 ng mL-1, and the detection limit was 1.47 pg mL-1. The designed PEC immunosensor exhibited good sensitivity, selectivity, stability and reproducibility. The electrode enabled label-free detection and provided a new route to realize point-of-care testing of cTnI.
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Técnicas Biossensoriais , Infarto do Miocárdio , Nanofios , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas , Humanos , Imunoensaio/métodos , Infarto do Miocárdio/diagnóstico , Nanofios/química , Reprodutibilidade dos Testes , Silício , Troponina IRESUMO
Nickel-iron-based layered double hydroxides (NiFe LDHs) have attracted tremendous research and industrial interests for oxygen evolution reaction (OER) electrocatalysis. However, methodologies on simultaneous regulation of performance-influencing factors remain scarce and their real synergistic effects are not clear enough. Herein, a versatile polyoxometallic acids (POMs) etching approach is reported to ingeniously reconstruct NiFe LDH, including 3D morphological nanotailoring, Fe3+ and α-Ni(OH)2 active species reconfiguration, creation of multiple Ni, Fe, and O vacancies, and intercalation of POM polyanionic clusters. The experimental and theoretical data collaboratively unveil that control of the key performance-influencing factors and their multiple synergistic mechanisms dominantly contribute to the step-like OER performance enhancement. The reinforced electrocatalyst is further produced with low cost and high performance up to Ф180 mm in diameter, showing its feasibility and advancement of the promising configuration of NiFe LDH-PMo12(+) II Ni@NiFe LDH(-) for alkaline anion-exchange-membrane electrode stack cells. Furthermore, to mathematically evaluate the evolution, a novel empirical formula is proposed for quantitative identification of structure-activity correlations, which offers an opportunity for first and fast reliability on materials screening.
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Rapid and accurate detection of myocardial infarction (MI) can boost the patient's chance of survival. Surface enhanced Raman scattering (SERS) is an outstanding diagnostic technique because of its strong light stability, high resolution, and qualitative and quantitative analysis based on the characteristic fingerprint. However, its reliability, stability and specificity remain to be improved, especially in the quantitative analysis of serum samples. In this study, we developed in situ silver nanoparticles (Ag NPs) on the surface of polydopamine (PDA) as a SERS substrate and found that PDA could act as a reducing agent to support the nucleation and growth of Ag NPs and control the distance and aggregation of Ag NPs to stabilize the Raman signal. In a standard phosphate buffered saline (PBS) environment, PDA@Ag could reach a low detection limit of 0.01 ng mL-1 cardiac troponin I (cTn I) with a good linear relationship. At the same time, the PDA@Ag substrate also possessed excellent stability, specificity and biocompatibility for cTn I detection. In addition, we verified the application potentiality of PDA@Ag in real serum samples and found that the performance of SERS was almost the same as that in PBS. This excellent detection performance of PDA@Ag could be attributed to both the enhanced electromagnetic field and the increased Raman cross-section, dominated by the gap distance between Ag NPs, reaction force between the antigen and the antibody and excellent biocompatibility and reducibility of PDA. In conclusion, this work may provide a new perspective for the in situ synthesis and growth of a uniform SERS substrate on the carrier to achieve the stability and specificity of SERS-based biological detection of MI.
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Nanopartículas Metálicas , Infarto do Miocárdio , Humanos , Indóis , Infarto do Miocárdio/diagnóstico , Polímeros , Reprodutibilidade dos Testes , Prata , Análise Espectral Raman/métodos , Troponina IRESUMO
Two-dimensional (2D) ZnSnO3 is a promising candidate for future gas sensors due to its high chemical response and excellent electronic properties. However, the preparation of 2D ZnSnO3 nanosheets by utilizing soluble inorganic salts and nonorganic solvents remains a challenge. In this work, 2D ZnSnO3 was synthesized via a facile graphene oxide (GO)-assisted co-precipitation method, in which inorganic salts in the aqueous phase replaced metal organic salts in a non-aqueous system. Meanwhile, a "dissolution and recrystallization" mechanism was proposed to explain the transformation from 3D nanocubes to 2D nanosheets. In comparison, the 2D ZnSnO3 nanosheets showed a higher response to formaldehyde (HCHO) at low operating temperature (100 °C). The response (Ra/Rg) of the 2D ZnSnO3 sensor to 10 ppm HCHO was as high as 57, which was approximately 5 times the response of the ZnSnO3 nanocubes sensor. However, the ZnSnO3 nanocubes sensor showed better gas sensing performance to ethanol at high temperature (200 °C). Different gas-sensitive properties were attributed to the different gas diffusion and adsorption processes caused by the morphology and nanostructure. Moreover, both sensors could detect either 0.1 ppm HCHO or ethanol at their optimum operating temperature. This work presents a relatively economical method to prepare 2D compound metal oxides, provides a novel "dissolution and recrystallization" mechanism for 2D multi-metal oxide preparation, and sheds light on the great potential of high-efficiency HCHO and/or ethanol gas sensors.
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Nanoestruturas , Formaldeído , Metais , Óxidos , TemperaturaRESUMO
The growth differentiation factor-15 (GDF-15) may be involved in atherosclerosis. However, the role of GDF-15 in atherosclerosis remains unclear. The main goal of this study was to verify the role and mechanism of GDF-15 in atherogenesis. We first compared the serum GDF-15 level between patients with coronary atherosclerosis and healthy people. And then one ApoE-/- mouse model of atherosclerosis was used to explore the effects of GDF-15 on oxidized low-density lipoprotein (oxLDL) accumulation, atherosclerosis-related gene expression, and lipid accumulation-related protein expression in mouse macrophages. As a result, the level of serum GDF-15 in patients with coronary atherosclerosis was significantly higher than that in healthy people. In the mouse model, GDF-15 expression was elevated in the core of plaque, and it was secreted mainly by the macrophages. In addition, GDF-15 decreased oxLDL-induced lipid accumulation and inflammation activation in macrophages. GDF-15 decreased the mRNA expressions of CD36, LOX1, and TLR4 that are associated with lipoprotein accumulation in macrophages. Further study showed that GDF-15 might suppress oxLDL-induced lipoprotein accumulation via inhibiting CD36 and LOX1 and decrease inflammation in macrophages by inhibiting TLR4. Thus, GDF-15 may suppress atherosclerosis and plaque formation by inhibiting lipoprotein accumulation and inflammation activation.
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The development of highly efficient non-precious metal catalysts for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is key for large-scale hydrogen evolution through water splitting technology. Here, we report an air-stable Cu-based nanostructure consisting of Mn doped CuCl and CuO (CuCl/CuO(Mn)-NF) as a dual functional electrocatalyst for water splitting. CuCl is identified as the main active component, together with Mn doping and the synergistic effect between CuCl and CuO are found to make responsibility for the excellent OER and HER catalytic activity and stability. The assembled electrolyzes also exhibit decent water splitting performance. This work not only provides a simple method for preparing Cu-based composite catalyst, but also demonstrates the great potential of Cu-based non-noble metal electrocatalysts for water splitting and other renewable energy conversion technologies.
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Oxygen electrocatalysts are of great importance for the air electrode in zinc-air batteries (ZABs). Owing to the high specific surface area, controllable pore size and unsaturated metal active sites, metal-organic frameworks (MOFs) derivatives have been widely studied as oxygen electrocatalysts in ZABs. To date, many strategies have been developed to generate efficient oxygen electrocatalysts from MOFs for improving the performance of ZABs. In this review, the latest progress of the MOF-derived non-noble metal-oxygen electrocatalysts in ZABs is reviewed. The performance of these MOF-derived catalysts toward oxygen reduction, and oxygen evolution reactions is discussed based on the categories of metal-free carbon materials, single-atom catalysts, metal cluster/carbon composites and metal compound/carbon composites. Moreover, we provide a comprehensive overview on the design strategies of various MOF-derived non-noble metal-oxygen electrocatalysts and their structure-performance relationship. Finally, the challenges and perspectives are provided for further advancing the MOF-derived oxygen electrocatalysts in ZABs.