Publications by authors named "Jianbo Wu"

266 Publications

An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope.

Protein Cell 2021 Sep 23. Epub 2021 Sep 23.

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences; Shanghai Institute of Infectious Disease and Biosecurity; the Fifth People's Hospital of Shanghai; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology); Institutes of Biomedical Sciences; Biosafety Level 3 Laboratory, Shanghai Medical College, Fudan University, Shanghai, 200032, China.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
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http://dx.doi.org/10.1007/s13238-021-00871-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458794PMC
September 2021

Defect Width Assessment Based on the Near-Field Magnetic Flux Leakage Method.

Sensors (Basel) 2021 Aug 11;21(16). Epub 2021 Aug 11.

School of Mechanical Engineering, Sichuan University, Chengdu 610065, China.

Magnetic flux leakage (MFL) testing has been widely used as a non-destructive testing method for various materials. However, it is difficult to separate the influences of the defect geometrical parameters such as depth, width, and length on the received leakage signals. In this paper, a "near-field" MFL method is proposed to quantify defect widths. Both the finite element modelling (FEM) and experimental studies are carried out to investigate the performance of the proposed method. It is found that that the distance between two peaks of the "near-field" MFL is strongly related to the defect width and lift-off value, whereas it is slightly affected by the defect depth. Based on this phenomenon, a defect width assessment relying on the "near-field" MFL method is proposed. Results show that relative judging errors are less than 5%. In addition, the analytical expression of the "near-field" MFL is also developed.
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http://dx.doi.org/10.3390/s21165424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399627PMC
August 2021

Deletion of SDF-1 or CXCR4 regulates platelet activation linked to glucose metabolism and mitochondrial respiratory reserve.

Platelets 2021 Aug 4:1-7. Epub 2021 Aug 4.

Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Drug Discovery Research Center, Southwest Medical University, Luzhou, China.

Stromal cell-derived factor 1 (SDF-1, also known as CXCL12) and its receptor CXCR4 have shown to play a role in the homing and engraftment of hematopoietic stem and progenitor cells. SDF-1 is highly expressed in platelets and involved in thrombosis formation. However, the exact roles of platelet-derived SDF-1 and CXCR4 in platelet activation and mitochondrial function have not been revealed yet. Deletion of Sdf-1 and Cxcr4 specifically in platelets decreased agonist-induced platelet aggregation and dramatically impaired thrombin-induced glucose uptake. In SDF-1-deficient and CXCR4-deficient platelets, intracellular ATP secretions were reduced when activated by the addition of thrombin. SDF-1 deficiency in platelets can impair the routine respiration during resting state and maximal capacity of the electron transfer system (ETS) during activated state. Mitochondrial respiration measurements in permeabilized platelets indicated an impaired function of the oxidative phosphorylation system in -SDF-1 or CXCR4-deficient platelets. These results suggested a novel role of the SDF-1/CXCR4 axis in modulating platelet energy metabolism and activation by regulating mitochondrial respiration, glucose uptake, and ATP production.
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http://dx.doi.org/10.1080/09537104.2021.1961713DOI Listing
August 2021

Design of Highly Durable Core-Shell Catalysts by Controlling Shell Distribution Guided by In-Situ Corrosion Study.

Adv Mater 2021 Sep 4;33(38):e2101511. Epub 2021 Aug 4.

State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai, 200240, P. R. China.

Most degradations in electrocatalysis are caused by corrosion in operation, for example the corrosion of the core in a core-shell electrocatalyst during the oxygen reduction reaction (ORR). Herein, according to the in-situ study on nanoscale corrosion kinetics via liquid cell transmission electron microscopy (LC-TEM) in the authors' previous work, they sequentially designed an optimized nanocube with the protection of more layers on the corners by adjusting the Pt atom distribution on corners and terraces. This modified nanocube (MNC) is much more corrosion resistant in the in-situ observation. Furthermore, in the practical electrochemical stability testing, the MNC catalyst also showed the best stability performance with the 0.37% and 9.01% loss in specific and mass activity after 30 000 cycles accelerated durability test (ADT). This work also demonstrates that how an in-situ study can guide the design of desired materials with improved properties and build a bridge between in-situ study and practical application.
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http://dx.doi.org/10.1002/adma.202101511DOI Listing
September 2021

A Large-Scalable, Surfactant-Free, and Ultrastable Ru-Doped PtCo Oxygen Reduction Catalyst.

Nano Lett 2021 Aug 28;21(15):6625-6632. Epub 2021 Jul 28.

State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Developing a large-scale method to produce platinum (Pt)-based electrocatalysts for the oxygen reduction reaction (ORR) is highly desirable to propel the commercialization of the membrane electrode assembly (MEA). Here, we successfully report the large-scale production of surfactant-free ruthenium-doped Pt-cobalt octahedra grown on carbon (Ru-PtCo/C), which display a much higher ORR activity and stability and MEA stability than PtCo/C and Pt/C. Significantly, the in-situ X-ray absorption fine structure result reveals that Ru can drive the reduced Pt atoms to reverse to their initial state after the ORR by transferring a redundant electron from Pt to Ru, preventing the over-reduction of Pt active sites and boosting the chemical stability. Theory investigations further confirm that the doped Ru can accelerate the breach and desorption of oxygen intermediates, making it active and durable for the ORR. The present work sheds light on the exploration of a large-scale strategy for producing advanced Pt-based nanocatalysts, which may offer significant advantages for practical fuel cell applications in the future.
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http://dx.doi.org/10.1021/acs.nanolett.1c02064DOI Listing
August 2021

In situ transplantation of adipose-derived stem cells via photoactivation improves glucose metabolism in obese mice.

Stem Cell Res Ther 2021 07 15;12(1):408. Epub 2021 Jul 15.

Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.

Background: Accumulating evidence suggests that enhanced adipose tissue macrophages (ATMs) are associated with metabolic disorders in obesity and type 2 diabetes. However, therapeutic persistence and reduced homing stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches.

Methods: We demonstrate that the effect of a combined application of photoactivation and adipose-derived stem cells (ASCs) using transplantation into visceral epididymal adipose tissue (EAT) in obesity. Cultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND).

Results: In diet-induced obesity, implantation of light-treated ASCs improved glucose tolerance and ameliorated systemic insulin resistance. Intriguingly, compared with non-light-treated ASCs, light-treated ASCs reduced monocyte infiltration and the levels of ATMs in EAT. Moreover, implantation of light-treated ASCs exerts more anti-inflammatory effects by suppressing M1 polarization and enhancing macrophage M2 polarization in EAT. Mass spectrometry revealed that light-treated human obese ASCs conditioned medium retained a more complete secretome with significant downregulation of pro-inflammatory cytokines and chemokines.

Conclusions: These data suggest that the combined application of photoactivation and ASCs using transplantation into dysfunctional adipose tissue contribute to selective suppression of inflammatory responses and protection from insulin resistance in obesity and type 2 diabetes.
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http://dx.doi.org/10.1186/s13287-021-02494-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281693PMC
July 2021

The molecular mechanism of LRP1 in physiological vascular homeostasis and signal transduction pathways.

Biomed Pharmacother 2021 Jul 7;139:111667. Epub 2021 May 7.

Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Drug Discovery Reseach Center, Southwest Medical University, 319 Zhongshan Road, Luzhou, Sichuan 646000, China; Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, the School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China. Electronic address:

Interactions between vascular smooth muscle cells (VSMCs), endothelial cells (ECs), pericytes (PCs) and macrophages (MФ), the major components of blood vessels, play a crucial role in maintaining vascular structural and functional homeostasis. Low-density lipoprotein (LDL) receptor-related protein-1 (LRP1), a transmembrane receptor protein belonging to the LDL receptor family, plays multifunctional roles in maintaining endocytosis, homeostasis, and signal transduction. Accumulating evidence suggests that LRP1 modulates vascular homeostasis mainly by regulating vasoactive substances and specific intracellular signaling pathways, including the plasminogen activator inhibitor 1 (PAI-1) signaling pathway, platelet-derived growth factor (PDGF) signaling pathway, transforming growth factor-β (TGF-β) signaling pathway and vascular endothelial growth factor (VEGF) signaling pathway. The aim of the present review is to focus on recent advances in the discovery and mechanism of vascular homeostasis regulated by LRP1-dependent signaling pathways. These recent discoveries expand our understanding of the mechanisms controlling LRP1 as a target for studies on vascular complications.
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http://dx.doi.org/10.1016/j.biopha.2021.111667DOI Listing
July 2021

MG53 inhibits angiogenesis through regulating focal adhesion kinase signalling.

J Cell Mol Med 2021 Aug 9;25(15):7462-7471. Epub 2021 Jul 9.

Drug Discovery Research Center, Southwest Medical University, Luzhou, China.

Mitsugumin 53 (MG53), which is expressed predominantly in striated muscle, has been demonstrated to be a myokine/cardiokine secreted from striated muscle under specific conditions. The important roles of MG53 in non-striated muscle tissues have also been examined in multiple disease models. However, no previous study has implicated MG53 in the control of endothelial cell function. In order to explore the effects of MG53 on endothelial cells, human umbilical vein endothelial cells (HUVECs) were stimulated with recombinant human MG53 (rhMG53). Then, rhMG53 uptake, focal adhesion kinase (FAK)/Src/Akt/ERK1/2 signalling pathway activation, cell migration and tube formation were determined in vitro. The efficacy of rhMG53 in regulating angiogenesis was also detected in postnatal mouse retinas. The results demonstrated that rhMG53 directly entered into endothelial cells in a cholesterol-dependent manner. The uptake of rhMG53 directly bound to FAK in endothelial cells, which resulted in a significant decrease in FAK phosphorylation at Y397. Accompanied by the dephosphorylation of FAK, rhMG53 uncoupled FAK-Src interaction and reduced the phosphorylation of Src at Y416. Consequently, the activation of FAK/Src downstream signalling pathways, such as Akt and ERK1/2, was also significantly inhibited by rhMG53. Furthermore, rhMG53 remarkably decreased HUVEC migration and tube formation in vitro and postnatal mouse retinal angiogenesis in vivo. Taken together, these data indicate that rhMG53 inhibits angiogenesis through regulating FAK/Src/Akt/ERK1/2 signalling pathways. This may provide a novel molecular mechanism for the impaired angiogenesis in ischaemic diseases.
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http://dx.doi.org/10.1111/jcmm.16777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335693PMC
August 2021

Understanding of Strain-Induced Electronic Structure Changes in Metal-Based Electrocatalysts: Using [email protected] Core-Shell Nanocrystals as an Ideal Platform.

Small 2021 07 29;17(30):e2100559. Epub 2021 Jun 29.

Laboratory of Advanced Materials, Shanghai Key Lab of Molecular Catalysis and Innovative Materials, Department of Materials Science, Fudan University, Shanghai, 200438, P. R. China.

While metal-based electrocatalysts have garnered extensive attention owing to the large variety of enzyme-mimic properties, the search for such highly-efficient catalysts still relies on empirical explorations, owing to the lack of predictive indicators as well as the ambiguity of structure-activity relationships. Notably, surface electronic structures play a crucial role in metal-based catalysts yet remain unexplored in enzyme-mimics. Herein, the authors investigate the electronic structure as a possible indicator of electrocatalytic activities of H O decomposition and glucose oxidation using [email protected] core-shell nanocrystals as a well-defined platform. The electron densities of the [email protected] are modulated with the correlation of strain through precise control of surface orientation and the number of atomic layers. The close relationships between the electrocatalytic activities and the surface charge accumulation are found, in which the increase of the electron accumulation can enhance both the enzyme-mimic activities. As a result, the [email protected] icosahedra with compressive strain in Pt shells exhibit the highest electrocatalytic activities for H O decomposition and glucose oxidation. Such systematic and comprehensive study provides the structure-activity relationships and paves a new way for the rational design of metal-based electrocatalysts. Especially, the charge accumulation degrees may serve as a general performance indicator for metal-based catalysts.
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http://dx.doi.org/10.1002/smll.202100559DOI Listing
July 2021

Correction to: High-Index-Faceted NiS Branch Arrays as Bifunctional Electrocatalysts for Efficient Water Splitting.

Nanomicro Lett 2020 Oct 31;13(1):16. Epub 2020 Oct 31.

State Key Laboratory of Silicon Materials, Key Laboratory of Advanced Materials and Applications for Batteries of Zhejiang Province, and Department of Materials Science and Engineering, Zhejiang University, Hangzhou, 310027, People's Republic of China.

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http://dx.doi.org/10.1007/s40820-020-00530-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187692PMC
October 2020

Gold nanoclusters treat intracellular bacterial infections: Eliminating phagocytic pathogens and regulating cellular immune response.

Colloids Surf B Biointerfaces 2021 Sep 2;205:111899. Epub 2021 Jun 2.

Drug Discovery Research Center, Key Laboratory of Ministry of Education for Medical Electrophysiology and the Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, China; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China. Electronic address:

Intracellular bacterial infection is underlying many serious human disorders, leading to high morbidity and mortality. The development of safe and efficient therapeutic agents is the most effective solutions to combat intracellular bacterial infections. Recently, ultrasmall gold nanoclusters (AuNCs) have emerged as an innovative nanoantibiotics against multidrug-resistant bacterial infections due to their inherent antibacterial activity. However, the therapeutic effects of AuNCs on intracellular bacterial infections and their effects on host cells still remain unvisited. Here, we demonstrate the therapeutic potential of 4,6-diamino-2-mercaptopyrimidine-functionalized AuNCs (AuDAMP) for intracellular multidrug-resistant infections in a co-culture model of macrophages and methicillin-resistant Staphylococcus aureus (MRSA). The AuNCs were found to show a superior intracellular antibacterial capability, which can eliminate most of the MRSA phagocytosed by macrophages, and without exhibiting obvious cytotoxicity on host RAW 264.7 macrophages at tested concentrations. More importantly, treatment of AuDAMP exerts critical roles on enhancing the innate immune response to defend against pathogens invading inside the host cells and alleviating the bacterial infection-induced inflammatory response to avoid pyroptosis by up-regulating significantly xenophagy level in macrophages. Taken together, our results suggest that AuNCs hold great potential for the treatment of intracellular bacterial infections.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111899DOI Listing
September 2021

Analysis of the Possibility of Plastic Deformation Characterisation in X2CrNi18-9 Steel Using Measurements of Electromagnetic Parameters.

Materials (Basel) 2021 May 28;14(11). Epub 2021 May 28.

Faculty of Civil Engineering, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.

An analysis was conducted on the possibility of making an assessment of the degree of plastic deformation ε in X2CrNi18-9 steel by measuring three electromagnetic diagnostic signals: the Barkhausen noise features, the impedance components in in-series LCR circuits, and the residual magnetic field components. The impact of ε on a series of different extracted features of diagnostic signals was investigated. The occurrence of two regions of sensitivity was found for all the features of the analysed signals. The two regions were separated by the following critical deformation value: ε ~ 10% for the components of the residual magnetic field and ε ~ 15% for the normalised components of impedance. As for the Barkhausen noise signal, the values were as follows: ε ~ 20% for the mean value, ε ~ 20% for the peak value of the signal envelope, and ε ~ 5% for the total number of the signal events. Metallographic tests were performed, which revealed essential changes in the microstructure of the tested material for the established critical values. The martensite transformation occurring during the plastic deformation process of X2CrNi18-9 austenitic steel process generated a magnetic phase. This magnetic phase was strong enough to relate the strain state to the values of diagnostic signals. The changes in the material electromagnetic properties due to martensitic transformation (γ → α') began much earlier than indicated by the metallographic testing results.
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http://dx.doi.org/10.3390/ma14112904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198741PMC
May 2021

Highly Surface-Distorted Pt Superstructures for Multifunctional Electrocatalysis.

Nano Lett 2021 Jun 1;21(12):5075-5082. Epub 2021 Jun 1.

State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, People's Republic of China.

Platinum (Pt) catalysts play a key role in energy conversion and storage processes, but the realization of further performance enhancement remains challenging. Herein, we report a new class of Pt superstructures (SSs) with surface distortion engineering by electrochemical leaching of PtTe SSs that can largely boost the oxygen reduction reaction (ORR), the methanol oxidation reaction (MOR), and the hydrogen evolution reaction (HER). In particular, the high-distortion (H)-Pt SSs achieve a mass activity of 2.24 A mg at 0.90 V for the ORR and 2.89 A mg for the MOR as well as a low overpotential of 25.3 mV at 10 mA cm for the HER. Moreover, the distorted surface features of Pt SSs can be preserved by mitigating the detrimental effects of agglomeration/degradation during long-time electrocatalysis. A multiscale modeling demonstrates that surface compressions, defects, and nanopores act in synergy for the enhanced ORR performance. This work highlights the advances of stable superstructure and distortion engineering for realizing high-performance Pt nanostructures.
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http://dx.doi.org/10.1021/acs.nanolett.1c00902DOI Listing
June 2021

Diaryl Ureas as an Antiprotozoal Chemotype.

ACS Infect Dis 2021 06 10;7(6):1578-1583. Epub 2021 May 10.

College of Pharmacy, University of Nebraska Medical Center, 986125 Nebraska Medical Center, Omaha, Nebraska 68198-6125, United States.

We now describe the physicochemical profiling, ADME, and antiparasitic activity of eight ,-diarylureas to assess their potential as a broad-spectrum antiprotozoal chemotype. Chromatographic LogD values ranged from 2.5 to 4.5; kinetic aq. solubilities were ≤6.3 μg/mL, and plasma protein binding ranged from 95 to 99%. All of the compounds had low intrinsic clearance values in human, but not mouse, liver microsomes. Although no ,-diarylurea had submicromolar potency against , two had submicromolar potencies against and , and five had submicromolar potencies against . appeared to be the most susceptible to growth inhibition by this compound series. Most of the ,-diarylureas had antiprotozoal selectivities ≥10. One ,-diarylurea had demonstrable activity in mouse models of malaria and toxoplasmosis.
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http://dx.doi.org/10.1021/acsinfecdis.1c00135DOI Listing
June 2021

RNA kinase CLP1/Cbc regulates meiosis initiation in spermatogenesis.

Hum Mol Genet 2021 Aug;30(17):1569-1578

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, BeiChenXiLu#1, Beijing 100101, P.R. China.

CLP1, TSEN complex, and VCP are evolutionarily conserved proteins whose mutations are associated with neurodegenerative diseases. In this study, we have found that they are also involved in germline differentiation. To optimize both quantity and quality in gametes production, germ cells expand themselves through limited mitotic cycles prior to meiosis. Stemming from our previous findings on the correlation between mRNA 3'-processing and meiosis entry, here we identify that the RNA kinase Cbc, the Drosophila member of the highly conserved CLP1 family, is a component of the program regulating the transition from mitosis to meiosis. Using genetic manipulations in Drosophila testis, we demonstrate that nuclear Cbc is required to promote meiosis entry. Combining biochemical and genetic methods, we reveal that Cbc physically and/or genetically intersects with Tsen54 and TER94 (VCP ortholog) in this process. The C-terminal half of Tsen54 is both necessary and sufficient for its binding with Cbc. Further, we illustrate the functional conservation between Cbc and mammalian CLP1 in the assays of subcellular localization and Drosophila fertility. As CLP1, TSEN complex, and VCP have also been identified in neurodegenerations of animal models, a mechanism involving these factors seems to be shared in gametogenesis and neurogenesis.
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http://dx.doi.org/10.1093/hmg/ddab107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369837PMC
August 2021

Deposition of Atomically Thin Pt Shells on Amorphous Palladium Phosphide Cores for Enhancing the Electrocatalytic Durability.

ACS Nano 2021 Apr 23;15(4):7348-7356. Epub 2021 Mar 23.

Frontier Institute of Science and Technology and State Key Laboratory of Multiphase Flow in Power Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China.

As an excellent electrocatalyst, platinum (Pt) is often deposited as a thin layer on a nanoscale substrate to achieve high utilization efficiency. However, the practical application of the as-designed catalysts has been substantially restricted by the poor durability arising from the leaching of cores. Herein, by employing amorphous palladium phosphide (a-Pd-P) as substrates, we develop a class of leaching-free, ultrastable core-shell Pt catalysts with well-controlled shell thicknesses and surface structures for fuel cell electrocatalysis. When a submonolayer of Pt is deposited on the 6 nm nanocubes, the resulting [email protected]@Pt core-shell catalyst can deliver a mass activity as high as 4.08 A/mg and 1.37 A/mg toward the oxygen reduction reaction at 0.9 V the reversible hydrogen electrode and undergoes 50 000 potential cycles with only ∼9% activity loss and negligible structural deformation. As elucidated by the DFT calculations, the superior durability of the catalysts originates from the high corrosion resistance of the disordered a-Pd-P substrates and the strong interfacial Pt-P interactions between the Pt shell and amorphous Pd-P layer.
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http://dx.doi.org/10.1021/acsnano.1c00602DOI Listing
April 2021

Combination Effect of Outdoor Activity and Screen Exposure on Risk of Preschool Myopia: Findings From Longhua Child Cohort Study.

Front Public Health 2021 5;9:607911. Epub 2021 Mar 5.

Department of Medical Statistics and Epidemiology, Guangzhou Key Laboratory of Environmental Pollution and Health Assessment, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Evidence regarding screen use and outdoor activity during very early childhood (i. e., from aged 1 to 3 years) and their potential combined links to the later preschool myopia is limited. This information is needed to release effective public health messages and propose intervention strategies against preschool myopia. We collected information regarding very early childhood screen use, outdoor activity and the kindergartens vision screenings of 26,611 preschoolers from Longhua Child Cohort Study by questionnaires. Logistic regression models were used to examine the associations between reported outdoor activity, screen use from 1 to 3 years of age, and preschool myopia. Throughout very early childhood, from 1 to 3 years, the proportion of children exposed to screens increased (from 35.8 to 68.4%, < 0.001), whereas the proportion of children who went outdoors ≥7 times/week (67.4-62.1%, < 0.001) and who went outdoors for ≥60 min/time (53.3-38.0%, < 0.001) declined. Exposure to fixed screen devices [adjusted odds ratio (AOR) = 2.66, 95% confidence interval (CI) = 2.09-3.44], mobile screen devices (AOR = 2.76, 95% CI = 2.15-3.58), and limited outdoor activity (AOR = 1.87, 95% CI = 1.42-2.51) during early childhood were associated with preschool myopia. Among children whose parents were myopic, the interactions between outdoor activity and fixed or mobile screen use on later preschool myopia were significant; the ORs and 95% CI were 3.34 (1.19-9.98) and 3.04 (1.06-9.21), respectively. Our findings suggest the possibility that the impact of screen exposure during early childhood on preschool myopia could be diminished by outdoor activity for children whose parents have myopia.
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http://dx.doi.org/10.3389/fpubh.2021.607911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973103PMC
May 2021

Antagonizing αvβ3 Integrin Improves Ischemia-Mediated Vascular Normalization and Blood Perfusion by Altering Macrophages.

Front Pharmacol 2021 24;12:585778. Epub 2021 Feb 24.

Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Drug Discovery Research Center, Southwest Medical University, Luzhou, China.

: αVβ3 integrin has been implicated in the physiological processes and pathophysiology of important angiogenesis-related disorders; however, the preclinical and clinical data on integrin αVβ3 antagonists have not demonstrated improved outcomes. Our goal was to test the hypothesis that inhibition of αVβ3 integrin improves blood flow in a mouse hindlimb ischemia model. : In this study, we examined the effect of cilengitide, an αVβ3/αVβ5 integrin-specific RGD-mimetic cyclic peptide, on blood perfusion and angiogenesis after hindlimb ischemia. Blood flow was measured using Laser Doppler Scanner. Vascular density, and macrophages infiltration were examined by immunofluorescence. Macrophage polarization was measured by quantitative real time PCR. : We found that low-dose, not high-dose, cilengitide increased blood flow perfusion, capillary formation, and pericyte coverage, accompanied by an accumulation of macrophages and increased expression of the chemokine (C-C motif) ligand 2 (CCL2) in ischemic muscles. Macrophage depletion using clodronate liposomes resulted in a reduction in low-dose cilengitide-induced blood flow perfusion, macrophage accumulation, pericyte coverage, and CCL2 expression. Finally, assays showed that low-dose, not high-dose, cilengitide increased macrophage migration. : These studies identified a novel role of the inhibition of αVβ3 integrin in modulating ischemia-induced angiogenesis, possibly through effects on macrophage infiltration and polarization, and revealed αVβ3 integrin inhibition to be a promising therapeutic strategy for peripheral artery disease.
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http://dx.doi.org/10.3389/fphar.2021.585778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944575PMC
February 2021

Association between greater residential greenness and decreased risk of preschool myopia and astigmatism.

Environ Res 2021 05 6;196:110976. Epub 2021 Mar 6.

Department of Epidemiology, Guangzhou Key Laboratory of Environmental Pollution and Health Assessment, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, 510080, Guangzhou, China; Department of Information Management, Xinhua College of Sun Yat-sen University, 510080, Guangzhou, China. Electronic address:

Objective: Rapid urbanization has led to reduced greenness in many areas, this has been linked to adverse health outcomes. The aim was to determine the association between residential greenness experienced during very early childhood with preschool myopia and astigmatism and to explore the potential mediating role of screen time on any associations.

Method: Information regarding socio-demographic characteristics, home address, screen time during early childhood, and refraction data from vision screenings of 53,575 preschoolers from Longhua Child Cohort Study were collected via questionnaires. Residential greenness was calculated as the average of satellite-derived Normalized Difference Vegetation Index in buffers of 100, 250, and 500 m around each child's home address. Logistic and linear regression models were used to examine the relationships between residential greenness, screen time, and preschool myopia and astigmatism.

Result: The mean (SD) age of the 53,575 preschoolers was 5.0 (0.7) years, and 24,849 (46.4%) were girls. A total of 1236 (2.3%) preschoolers had myopia and 5347 (10.0%) had astigmatism. In the adjusted model, a higher neighborhood greenness level within 100 m buffers around the home address was associated with decreased risk of myopia (adjusted odds ratios (AOR): 0.62, 95% confidence interval (CI): 0.38-0.99), and higher neighborhood greenness levels within 100, 250, and 500 m decreased the risk of astigmatism, and their AORs (95% CIs) were 0.55 (0.43-0.70) for 100 m, 0.59 (0.41-0.83) for 250 m, 0.61 (0.42-0.90) for 500 m, respectively. Greater screen time during early childhood increased the risk of myopia (AOR = 1.33) and astigmatism (AOR = 1.23). Reduction in screen time fully mediated the benefits of greater residential greenness on preschool myopia, but partially mediated that on preschool astigmatism (p < 0.05).

Conclusion: Higher residential greenness reduces the risk of preschool myopia and astigmatism; the benefits of residential greenness were mediated through reduced daily screen time.
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http://dx.doi.org/10.1016/j.envres.2021.110976DOI Listing
May 2021

Heterostructure of ZnO Nanosheets/Zn with a Highly Enhanced Edge Surface for Efficient CO Electrochemical Reduction to CO.

ACS Appl Mater Interfaces 2021 Mar 23;13(9):10837-10844. Epub 2021 Feb 23.

State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.

Electrochemical reduction of CO to valuable chemicals or fuels is critical for closing the carbon cycle and preventing further deterioration of the environment. Here, we discover that by adopting the Zn foil as the substrate, a ZnO two-dimensional sheet array is in situ synthesized on the Zn foil by a facile hydrothermal method. The obtained ZnO sheet array/Zn foil exhibited an outstanding CO reduction performance to CO, which showed the highest Faraday efficiency of 85% for CO at -2.0 V (vs Ag/AgCl) with a current density of 11.5 mA/cm compared with the freestanding ZnO sheets and particles and excellent stability in the 0.1 M KHCO electrolyte. The in situ vertical ZnO sheet array exposed with abundant exposed (11̅00) edge facets can accelerate the electron transfer and improve the number of active sites, which leads to the enhanced reduction performance. Alongside, the density functional theory simulation indicated that the vertical-grown ZnO sheet array possesses lower Gibbs free energy for the CO activation, with a more exposed (11̅00) edge surface of ZnO.
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http://dx.doi.org/10.1021/acsami.0c20302DOI Listing
March 2021

Atomistic Imaging of Competition between Surface Diffusion and Phase Transition during the Intermetallic Formation of Faceted Particles.

ACS Nano 2021 Mar 19;15(3):5284-5293. Epub 2021 Feb 19.

State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

To explore the ordering mechanism of facet alloy nanocrystals with randomly distributed atoms, we investigate kinetic and thermodynamic behaviors of the ordering phase transition from face-centered cubic PtCo nanocrystals to L1-PtCo intermetallic nanocrystals. It is observed that the ordering occurs from the surface and then gradually into the interior in a layer-by-layer mode, involving the competition between two kinds of phase transition modes: long-range surface diffusion-induced phase transition (SDIPT) and short-range reconstruction-induced body phase transition (RIBPT). The density functional theory calculations demonstrate that the surface status acts as a pivotal part in the thermodynamics and kinetics of the nanoscale ordering transition. With the development of the controllable heating process, both SDIPT and RIBPT modes can be manipulated as well as the morphology of the final product. This work lays the foundations for potentially realizing shape-controlled intermetallic nanostructures by utilizing the thermal annealing method and makes preparations for the rational design of the surface and near-surface atomic configurations at the atomic scale.
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http://dx.doi.org/10.1021/acsnano.0c10775DOI Listing
March 2021

Atomically Dispersed Indium Sites for Selective CO Electroreduction to Formic Acid.

ACS Nano 2021 Mar 15;15(3):5671-5678. Epub 2021 Feb 15.

Research School of Chemistry, College of Science, Australian National University, Canberra, ATC 2601, Australia.

An atomically dispersed structure is attractive for electrochemically converting carbon dioxide (CO) to fuels and feedstock due to its unique properties and activity. Most single-atom electrocatalysts are reported to reduce CO to carbon monoxide (CO). Herein, we develop atomically dispersed indium (In) on a nitrogen-doped carbon skeleton (In-N-C) as an efficient catalyst to produce formic acid/formate in aqueous media, reaching a turnover frequency as high as 26771 h at -0.99 V relative to a reversible hydrogen electrode (RHE). Electrochemical measurements show that trace amounts of In loaded on the carbon matrix significantly improve the electrocatalytic behavior for the CO reduction reaction, outperforming conventional metallic In catalysts. Further experiments and density functional theory (DFT) calculations reveal that the formation of intermediate *OCHO on isolated In sites plays a pivotal role in the efficiency of the CO-to-formate process, which has a lower energy barrier than that on metallic In.
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http://dx.doi.org/10.1021/acsnano.1c00858DOI Listing
March 2021

Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD.

Cell Rep 2021 02 12;34(5):108699. Epub 2021 Jan 12.

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Biosafety Level 3 Laboratory, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address:

Several potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been identified. However, antibody-dependent enhancement (ADE) has not been comprehensively studied for SARS-CoV-2, and the relationship between enhancing versus neutralizing activities and antibody epitopes remains unknown. Here, we select a convalescent individual with potent IgG neutralizing activity and characterize his antibody response. Monoclonal antibodies isolated from memory B cells target four groups of five non-overlapping receptor-binding domain (RBD) epitopes. Antibodies to one group of these RBD epitopes mediate ADE of entry in Raji cells via an Fcγ receptor-dependent mechanism. In contrast, antibodies targeting two other distinct epitope groups neutralize SARS-CoV-2 without ADE, while antibodies against the fourth epitope group are poorly neutralizing. One antibody, XG014, potently cross-neutralizes SARS-CoV-2 variants, as well as SARS-CoV-1, with respective IC (50% inhibitory concentration) values as low as 5.1 and 23.7 ng/mL, while not exhibiting ADE. Therefore, neutralization and ADE of human SARS-CoV-2 antibodies correlate with non-overlapping RBD epitopes.
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http://dx.doi.org/10.1016/j.celrep.2021.108699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802522PMC
February 2021

Mechanisms of action of metformin and its regulatory effect on microRNAs related to angiogenesis.

Pharmacol Res 2021 02 19;164:105390. Epub 2020 Dec 19.

Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China; Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, the School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China. Electronic address:

Angiogenesis is rapidly initiated in response to pathological conditions and is a key target for pharmaceutical intervention in various malignancies. Anti-angiogenic therapy has emerged as a potential and effective therapeutic strategy for treating cancer and cardiovascular-related diseases. Metformin, a first-line oral antidiabetic agent for type 2 diabetes mellitus (T2DM), not only reduces blood glucose levels and improves insulin sensitivity and exerts cardioprotective effects but also shows benefits against cancers, cardiovascular diseases, and other diverse diseases and regulates angiogenesis. MicroRNAs (miRNAs) are endogenous noncoding RNA molecules with a length of approximately 19-25 bases that are widely involved in controlling various human biological processes. A large number of miRNAs are involved in the regulation of cardiovascular cell function and angiogenesis, of which miR-21 not only regulates vascular cell proliferation, migration and apoptosis but also plays an important role in angiogenesis. The relationship between metformin and abnormal miRNA expression has gradually been revealed in the context of numerous diseases and has received increasing attention. This paper reviews the drug-target interactions and drug repositioning events of metformin that influences vascular cells and has benefits on angiogenesis-mediated effects. Furthermore, we use miR-21 as an example to explain the specific molecular mechanism underlying metformin-mediated regulation of the miRNA signaling pathway controlling angiogenesis and vascular protective effects. These findings may provide a new therapeutic target and theoretical basis for the clinical prevention and treatment of cardiovascular diseases.
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http://dx.doi.org/10.1016/j.phrs.2020.105390DOI Listing
February 2021

Linagliptin Regulates the Mitochondrial Respiratory Reserve to Alter Platelet Activation and Arterial Thrombosis.

Front Pharmacol 2020 30;11:585612. Epub 2020 Nov 30.

Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Drug Discovery Research Center, Southwest Medical University, Luzhou, China.

The pharmacological inhibition of dipeptidyl peptidase-4 (DPP-4) potentiates incretin action, and DPP-4 is a drug target for type 2 diabetes and reducing cardiovascular risk. However, little is known about the non-enteroendocrine pathways by which DPP-4 might contribute to ischaemic cardiovascular events. We tested the hypothesis that inhibition of DPP-4 can inhibit platelet activation and arterial thrombosis by preventing platelet mitochondrial dysfunction and release. The effects of pharmacological DPP-4 inhibition on carotid artery thrombosis, platelet aggregation, and platelet mitochondrial respiration signaling pathways were studied in mice. Platelet-dependent arterial thrombosis was significantly delayed in mice treated with high dose of linagliptin, a potent DPP-4 inhibitor, and fed normal chow diet compared to vehicle-treated mice. Thrombin induced DPP-4 expression and activity, and platelets pretreated with linagliptin exhibited reduced thrombin-induced aggregation. Linagliptin blocked phosphodiesterase activity and contrained cyclic AMP reduction when thrombin stimulates platelets. Linagliptin increases the inhibition of platelet aggregation by nitric oxide. The bioenergetics profile revealed that platelets pretreated with linagliptin exhibited decreased oxygen consumption rates in response to thrombin. In transmission electron microscopy, platelets pretreated with linagliptin showed markedly reversed morphological changes in thrombin-activated platelets, including the secretion of -granules and fewer mitochondria. Collectively, these findings identify distinct roles for DPP-4 in platelet function and arterial thrombosis.
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http://dx.doi.org/10.3389/fphar.2020.585612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734318PMC
November 2020

PM2.5 promotes apoptosis of human epidermal melanocytes through promoting oxidative damage and autophagy.

Gen Physiol Biophys 2020 Nov;39(6):569-577

Department of Dermatology, Zhongnan Hospital of Wuhan University, Wuchang District, Wuhan, Hubei, P.R. China.

Pollutants such as PM2.5 are polluting the environment seriously, causing numerous health problems. However, the skin toxicity caused by PM2.5 has been little reported so far. CCK-8 was used to test the effects of PM2.5 on melanin cell proliferation. The effect of PM2.5 on melanocyte apoptosis was detected by flow cytometry. ELISA was used to detect the expression of oxidative stress-related factors, including reactive oxygen species (ROS). The expression of autophagosomes was detected by MDC immunohistochemical staining, and Western blot was used to detect the expression of autophagy marker LC3II/I. With the increasing concentrations of PM2.5, the proliferation rate and apoptosis rate of melanocytes decreased significantly, meanwhile the expression of oxidative stress-related factors ROS, was obviously increased. The expression of LC3II/I induced by PM2.5 venom was higher than that of the control group in a concentration-dependent manner. However, there was no statistically significant difference between the water-soluble components of PM2.5 and the water-insoluble ones. PM2.5 can inhibit the proliferation of melanocytes and induce their apoptosis, which may be related to the oxidative damage of PM2.5. PM2.5 also induced autophagy in melanocytes, which is obviously correlated with its concentration. The mechanism may be a self-protective response of cells to oxidative stress injury and apoptosis.
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http://dx.doi.org/10.4149/gpb_2020018DOI Listing
November 2020

SARS-CoV-2 microbiome dysbiosis linked disorders and possible probiotics role.

Biomed Pharmacother 2021 Jan 11;133:110947. Epub 2020 Nov 11.

Drug Discovery Research Center, Southwest Medical University, Luzhou, 646000, Sichuan, China. Electronic address:

In December 2019, a pneumonia outbreak of unknown etiology was reported which caused panic in Wuhan city of central China, which was later identified as Coronavirus disease (COVID-19) caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by the Chinese Centre for Disease Control and Prevention (CDC) and WHO. To date, the SARS-CoV-2 spread has already become a global pandemic with a considerable death toll. The associated symptoms of the COVID-19 infection varied with increased inflammation as an everyday pathological basis. Among various other symptoms such as fever, cough, lethargy, gastrointestinal (GI) symptoms included diarrhea and IBD with colitis, have been reported. Currently, there is no sole cure for COVID-19, and researchers are actively engaged to search out appropriate treatment and develop a vaccine for its prevention. Antiviral for controlling viral load and corticosteroid therapy for reducing inflammation seems to be inadequate to control the fatality rate. Based on the available related literature, which documented GI symptoms with diarrhea, inflammatory bowel diseases (IBD) with colitis, and increased deaths in the intensive care unit (ICU), conclude that dysbiosis occurs during SARS-COV-2 infection as the gut-lung axis cannot be ignored. As probiotics play a therapeutic role for GI, IBD, colitis, and even in viral infection. So, we assume that the inclusion of studies to investigate gut microbiome and subsequent therapies such as probiotics might help decrease the inflammatory response of viral pathogenesis and respiratory symptoms by strengthening the host immune system, amelioration of gut microbiome, and improvement of gut barrier function.
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http://dx.doi.org/10.1016/j.biopha.2020.110947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657099PMC
January 2021

The lncRNA H19 alleviates muscular dystrophy by stabilizing dystrophin.

Nat Cell Biol 2020 11 26;22(11):1332-1345. Epub 2020 Oct 26.

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Dystrophin proteomic regulation in muscular dystrophies (MDs) remains unclear. We report that a long noncoding RNA (lncRNA), H19, associates with dystrophin and inhibits E3-ligase-dependent polyubiquitination at Lys 3584 (referred to as Ub-DMD) and its subsequent protein degradation. In-frame deletions in BMD and a DMD non-silent mutation (C3340Y) resulted in defects in the ability of the protein to interact with H19, which caused elevated Ub-DMD levels and dystrophin degradation. Dmd C3333Y mice exhibited progressive MD, elevated serum creatine kinase, heart dilation, blood vessel irregularity and respiratory failure with concurrently reduced dystrophin and increased Ub-DMD status. H19 RNA oligonucleotides conjugated with agrin (AGR-H19) and nifenazone competed with or inhibited TRIM63. Dmd C3333Y animals, induced-pluripotent-stem-cell-derived skeletal muscle cells from patients with Becker MD and mdx mice subjected to exon skipping exhibited inhibited dystrophin degradation, preserved skeletal and cardiac muscle histology, and improved strength and heart function following AGR-H19 or nifenazone treatment. Our study paves the way for meaningful targeted therapeutics for Becker MD and for certain patients with Duchenne MD.
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http://dx.doi.org/10.1038/s41556-020-00595-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951180PMC
November 2020

Reconsidering the Benchmarking Evaluation of Catalytic Activity in Oxygen Reduction Reaction.

iScience 2020 Oct 5;23(10):101532. Epub 2020 Sep 5.

State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, 200240 Shanghai, China.

The sluggish kinetics of the oxygen reduction reaction (ORR) on electrocatalysts represents a major obstacle in the development of fuel cell technology. A tremendous amount of work has reported the increasing ORR activity for catalysts. Nevertheless, when applied to practical Membrane Electrode Assembly (MEA, an assembled stack of a proton exchange membrane fuel cell) configuration, the high-performance catalysts on the rotating disk electrode (RDE) may not display the same high activity as in the lab-scale tests. This led us to reexamine the ORR evaluation based on the RDE technique. With the development of high active electrocatalysts, it may become significant to determine the reasonable kinetic current at a conventional fixed potential approaching the limited current by using the Koutecky-Levich (K-L) technique on RDE for the evaluation of ORR activity. Here we describe such a challenging situation and systematically discuss the proper kinetic region when comparing the ORR activity with the unsuitable potential or Pt loading based on the K-L technique. Furthermore, the rational benchmarking guidelines are given for the evaluation of the ORR electrocatalysts.
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http://dx.doi.org/10.1016/j.isci.2020.101532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516295PMC
October 2020
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