| 1. |
- Beal, Jacob, et al.
(author)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Lin, Qing, et al.
(author)
-
Mechanistic and therapeutic study of novel anti-tumor function of natural compound imperialine for treating non-small cell lung cancer
- 2020
-
In: Journal of Ethnopharmacology. - : Elsevier. - 0378-8741 .- 1872-7573. ; 247
-
Journal article (peer-reviewed)abstract
- Ethnopharmacological relevance: Bulbus Fritillaria cirrhosa D. Don (BFC) is a Chinese traditional herbal medicine that has long been used as an indispensable component in herbal prescriptions for bronchopulmonary diseases due to its well-established strong anti-inflammation and pulmonary harmonizing effects. Interestingly, there are few case reports in traditional Chinese medicine available where they found it to contribute in anti-tumor therapies. Imperialine is one of the most favored active substances extracted from BFC and has been widely recognized as an anti-inflammatory agent. Aim of the study: The aim of the current work is to provide first-hand evidences both in vitro and in vivo showing that imperialine exerts anti-cancer effects against non-small cell lung cancer (NSCLC), and to explore the molecular mechanism of this anti-tumor activity. It is also necessary to examine its systemic toxicity, and to investigate how to develop strategies for feasible clinical translation of imperialine. Materials and methods: To investigate anti-NSCLC efficacy of imperialine using both in vitro and in vivo methods where A549 cell line were chosen as in vitro model NSCLC cells and A549 tumor-bearing mouse model was constructed for in vivo study. The detailed underlying anti-cancer mechanism has been systematically explored for the first time through a comprehensive set of molecular biology methods mainly including immunohistochemistry, western blot and enzyme-linked immunosorbent assays. The toxicity profile of imperialine treatments were evaluated using healthy nude mice by examining hemogram and histopathology. An imperialine-loaded liposomal drug delivery system was developed using thin film hydration method to evaluate target specific delivery. Results: The results showed that imperialine could suppress both NSCLC tumor and associated inflammation through an inflammation-cancer feedback loop in which NF-kappa B activity was dramatically inhibited by imperialine. The NSCLC-targeting liposomal system was successfully developed for targeted drug delivery. The developed platform could favorably enhance imperialine cellular uptake and in vivo accumulation at tumor sites, thus improving overall anti-tumor effect. The toxicity assays revealed imperialine treatments did not significantly disturb blood cell counts in mice or exert any significant damage to the main organs. Conclusions: Imperialine exerts anti-cancer effects against NSCLC both in vitro and in vivo, and this previously unknown function is related to NF-kappa B centered inflammation-cancer feedback loop. Imperialine mediated anticancer activity is not through cytotoxicity and exhibit robust systemic safety. Furthermore, the liposome-based system we commenced would dramatically enhance therapeutic effects of imperialine while exhibiting extremely low side effects both on cellular and in NSCLC model. This work has identified imperialine as a promising novel anti-cancer compound and offered an efficient target-delivery solution that greatly facilitate practical use of imperialine.
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| 3. |
- Xu, Ke-Jun, et al.
(author)
-
Bogoliubov quasiparticle on the gossamer Fermi surface in electron-doped cuprates
- 2023
-
In: Nature Physics. - 1745-2473 .- 1745-2481. ; 19:12, s. 1834-1840
-
Journal article (peer-reviewed)abstract
- Electron-doped cuprates consistently exhibit strong antiferromagnetic correlations, leading to the prevalent belief that antiferromagnetic spin fluctuations mediate Cooper pairing in these unconventional superconductors. However, early investigations showed that although antiferromagnetic spin fluctuations create the largest pseudogap at hot spots in momentum space, the superconducting gap is also maximized at these locations. This presented a paradox for spin-fluctuation-mediated pairing: Cooper pairing is strongest at momenta where the normal-state low-energy spectral weight is most suppressed. Here we investigate this paradox and find evidence that a gossamer—meaning very faint—Fermi surface can provide an explanation for these observations. We study Nd2–xCexCuO4 using angle-resolved photoemission spectroscopy and directly observe the Bogoliubov quasiparticles. First, we resolve the previously observed reconstructed main band and the states gapped by the antiferromagnetic pseudogap around the hot spots. Within the antiferromagnetic pseudogap, we also observe gossamer states with distinct dispersion, from which coherence peaks of Bogoliubov quasiparticles emerge below the superconducting critical temperature. Moreover, the direct observation of a Bogoliubov quasiparticle permits an accurate determination of the superconducting gap, yielding a maximum value an order of magnitude smaller than the pseudogap, establishing the distinct nature of these two gaps. We propose that orientation fluctuations in the antiferromagnetic order parameter are responsible for the gossamer states.
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| 4. |
- Xu, Ke Jun, et al.
(author)
-
Bogoliubov quasiparticle on the gossamer Fermi surface in electron-doped cuprates
- 2023
-
In: Nature Physics. - : Springer Nature. - 1745-2473 .- 1745-2481. ; 19:12, s. 1834-1840
-
Journal article (peer-reviewed)abstract
- Electron-doped cuprates consistently exhibit strong antiferromagnetic correlations, leading to the prevalent belief that antiferromagnetic spin fluctuations mediate Cooper pairing in these unconventional superconductors. However, early investigations showed that although antiferromagnetic spin fluctuations create the largest pseudogap at hot spots in momentum space, the superconducting gap is also maximized at these locations. This presented a paradox for spin-fluctuation-mediated pairing: Cooper pairing is strongest at momenta where the normal-state low-energy spectral weight is most suppressed. Here we investigate this paradox and find evidence that a gossamer—meaning very faint—Fermi surface can provide an explanation for these observations. We study Nd2–xCexCuO4 using angle-resolved photoemission spectroscopy and directly observe the Bogoliubov quasiparticles. First, we resolve the previously observed reconstructed main band and the states gapped by the antiferromagnetic pseudogap around the hot spots. Within the antiferromagnetic pseudogap, we also observe gossamer states with distinct dispersion, from which coherence peaks of Bogoliubov quasiparticles emerge below the superconducting critical temperature. Moreover, the direct observation of a Bogoliubov quasiparticle permits an accurate determination of the superconducting gap, yielding a maximum value an order of magnitude smaller than the pseudogap, establishing the distinct nature of these two gaps. We propose that orientation fluctuations in the antiferromagnetic order parameter are responsible for the gossamer states.
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| 5. |
- Bentham, James, et al.
(author)
-
A century of trends in adult human height
- 2016
-
In: eLIFE. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 6. |
- Bentham, James, et al.
(author)
-
A century of trends in adult human height
- 2016
-
In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 7. |
- Czeszumski, Artur, et al.
(author)
-
#EEGManyLabs: Investigating the Replicability of Influential EEG Experiments
- 2024
-
Other publication (other academic/artistic)abstract
- There is growing awareness across the neuroscience community that the replicability of findings on the relationship between brain activity and cognitive phenomena can be improved by conducting studies with high statistical power that adhere to well-defined and standardized analysis pipelines. Inspired by efforts from the psychological sciences, and with the desire to examine some of the foundational findings using electroencephalography (EEG), we have launched #EEGManyLabs, a large-scale international collaborative replication effort. Since its discovery in the early 20th century, EEG has had a profound influence on our understanding of human cognition, but there is limited evidence on the replicability of some of the most highly cited discoveries. After a systematic search and selection process, we have identified 27 of the most influential and continually cited studies in the field. We plan to directly test the replicability of key findings from 20 of these studies in teams of at least three independent laboratories. The design and protocol of each replication effort will be submitted as a Registered Report and peer-reviewed prior to data collection. Prediction markets, open to all EEG researchers, will be used as a forecasting tool to examine which findings the community expects to replicate. This project will update our confidence in some of the most influential EEG findings and generate a large open access database that can be used to inform future research practices. Finally, through this international effort, we hope to create a cultural shift towards inclusive, high-powered multi-laboratory collaborations.
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| 8. |
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| 9. |
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| 10. |
- He, Haoran, et al.
(author)
-
Deciphering microbiomes dozens of meters under our feet and their edaphoclimatic and spatial drivers
- 2024
-
In: Global Change Biology. - 1354-1013. ; 30:1
-
Journal article (peer-reviewed)abstract
- Microbes inhabiting deep soil layers are known to be different from their counterpart in topsoil yet remain under investigation in terms of their structure, function, and how their diversity is shaped. The microbiome of deep soils (>1 m) is expected to be relatively stable and highly independent from climatic conditions. Much less is known, however, on how these microbial communities vary along climate gradients. Here, we used amplicon sequencing to investigate bacteria, archaea, and fungi along fifteen 18-m depth profiles at 20–50-cm intervals across contrasting aridity conditions in semi-arid forest ecosystems of China's Loess Plateau. Our results showed that bacterial and fungal α diversity and bacterial and archaeal community similarity declined dramatically in topsoil and remained relatively stable in deep soil. Nevertheless, deep soil microbiome still showed the functional potential of N cycling, plant-derived organic matter degradation, resource exchange, and water coordination. The deep soil microbiome had closer taxa–taxa and bacteria–fungi associations and more influence of dispersal limitation than topsoil microbiome. Geographic distance was more influential in deep soil bacteria and archaea than in topsoil. We further showed that aridity was negatively correlated with deep-soil archaeal and fungal richness, archaeal community similarity, relative abundance of plant saprotroph, and bacteria–fungi associations, but increased the relative abundance of aerobic ammonia oxidation, manganese oxidation, and arbuscular mycorrhizal in the deep soils. Root depth, complexity, soil volumetric moisture, and clay play bridging roles in the indirect effects of aridity on microbes in deep soils. Our work indicates that, even microbial communities and nutrient cycling in deep soil are susceptible to changes in water availability, with consequences for understanding the sustainability of dryland ecosystems and the whole-soil in response to aridification. Moreover, we propose that neglecting soil depth may underestimate the role of soil moisture in dryland ecosystems under future climate scenarios.
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| 11. |
- Klionsky, Daniel J., et al.
(author)
-
Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
-
In: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
-
Research review (peer-reviewed)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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| 12. |
- Lamichhaney, Sangeet, 1984-, et al.
(author)
-
Structural genomic changes underlie alternative reproductive strategies in the ruff (Philomachus pugnax)
- 2016
-
In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 48:1, s. 84-88
-
Journal article (peer-reviewed)abstract
- The ruff is a Palearctic wader with a spectacular lekking behavior where highly ornamented males compete for females1,2,3,4. This bird has one of the most remarkable mating systems in the animal kingdom, comprising three different male morphs (independents, satellites and faeders) that differ in behavior, plumage color and body size. Remarkably, the satellite and faeder morphs are controlled by dominant alleles5,6. Here we have used whole-genome sequencing and resolved the enigma of how such complex phenotypic differences can have a simple genetic basis. The Satellite and Faeder alleles are both associated with a 4.5-Mb inversion that occurred about 3.8 million years ago. We propose an evolutionary scenario where the Satellite chromosome arose by a rare recombination event about 500,000 years ago. The ruff mating system is the result of an evolutionary process in which multiple genetic changes contributing to phenotypic differences between morphs have accumulated within the inverted region.
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| 13. |
- Lin, Qing, et al.
(author)
-
Exosome-like nanoplatform modified with targeting ligand improves anti-cancer and anti-inflammation effects of imperialine
- 2019
-
In: Journal of Controlled Release. - : ELSEVIER. - 0168-3659 .- 1873-4995. ; 311, s. 104-116
-
Journal article (peer-reviewed)abstract
- Currently, most anti-cancer therapies are still haunted by serious and deleterious adverse effects. Here, we report a highly biocompatible tumor cell-targeting delivery systems utilizing exosome-like vesicles (ELVs) that delivers a low-toxicity anti-cancer agent imperialine against non-small cell lung cancer (NSCLC). First, we introduced a novel micelle-aided method to efficiently load imperialine into intact ELVs. Then, integrin alpha 3 beta 1-binding octapeptide cNGQGEQc was modified onto ELV platform for tumor targeting as integrin alpha 3 beta 1 is overexpressed on NSCLC cells. This system not only significantly improved imperialine tumor accumulation and retention, but also had extremely low systemic toxicity both in vitro and in vivo. Our discoveries offer new ways to utilize ELV more efficiently for both drug loading and targeting. The solid pharmacokinetics improvement and extraordinary safety of this system also highlight possibilities of alternative long course cancer therapies using similar strategies.
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| 14. |
- Martínez Barrio, Álvaro, et al.
(author)
-
The genetic basis for ecological adaptation of the Atlantic herring revealed by genome sequencing
- 2016
-
In: eLIFE. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Ecological adaptation is of major relevance to speciation and sustainable population management, but the underlying genetic factors are typically hard to study in natural populations due to genetic differentiation caused by natural selection being confounded with genetic drift in subdivided populations. Here, we use whole genome population sequencing of Atlantic and Baltic herring to reveal the underlying genetic architecture at an unprecedented detailed resolution for both adaptation to a new niche environment and timing of reproduction. We identify almost 500 independent loci associated with a recent niche expansion from marine (Atlantic Ocean) to brackish waters (Baltic Sea), and more than 100 independent loci showing genetic differentiation between spring- and autumn-spawning populations irrespective of geographic origin. Our results show that both coding and non-coding changes contribute to adaptation. Haplotype blocks, often spanning multiple genes and maintained by selection, are associated with genetic differentiation.
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| 15. |
- Snyder, Joel S., et al.
(author)
-
#EEGManyLabs: Investigating the replicability of influential EEG experiments
- 2021
-
In: Cortex. - : Elsevier. - 1973-8102 .- 0010-9452. ; 144, s. 213-229
-
Journal article (peer-reviewed)abstract
- There is growing awareness across the neuroscience community that the replicability of findings about the relationship between brain activity and cognitive phenomena can be improved by conducting studies with high statistical power that adhere to well-defined and standardised analysis pipelines. Inspired by recent efforts from the psychological sciences, and with the desire to examine some of the foundational findings using electroencephalog-raphy (EEG), we have launched #EEGManyLabs, a large-scale international collaborative replication effort. Since its discovery in the early 20th century, EEG has had a profound in-fluence on our understanding of human cognition, but there is limited evidence on the replicability of some of the most highly cited discoveries. After a systematic search and se-lection process, we have identified 27 of the most influential and continually cited studies in the field. We plan to directly test the replicability of key findings from 20 of these studies in teams of at least three independent laboratories. The design and protocol of each replication effort will be submitted as a Registered Report and peer-reviewed prior to data collection. Prediction markets, open to all EEG researchers, will be used as a forecasting tool to examine which findings the community expects to replicate. This project will update our confidence in some of the most influential EEG findings and generate a large open access database that can be used to inform future research practices. Finally, through this international effort, we hope to create a cultural shift towards inclusive, high-powered multi-laboratory collaborations. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 16. |
- Xie, Haotian, et al.
(author)
-
A Low-Complexity Gradient Descent Solution with Backtracking Iteration Approach for Finite Control Set Predictive Current Control
- 2022
-
In: IEEE Transactions on Industrial Electronics. - 0278-0046 .- 1557-9948. ; 69:5, s. 4522-4533
-
Journal article (peer-reviewed)abstract
- Finite control set model predictive control (FCS-MPC) has been widely recognized in the field of electrical drive control during the past decades, due to its merits of quick dynamic response and low switching frequency. However, it is inherently penalized by the high tracking deviations in the steady state as well as exhaustive search among the switching sequences. To cope with this issue, a low-complexity gradient descent based finite control set predictive current control (GD-FCSPCC) combined with backtracking optimized iteration approach is proposed in this paper, aiming to improve the control performance by effectively tracking the reference value. Firstly, FCS-PCC is reformulated as a quadratic programming (QP) problem from a geometric perspective. Consequently, the convexity of QP problem is proved to underlying the gradient descent to minimize the tracking error in an effective manner. Thus, the control objectives are determined by optimizing the deviation between the gradient descent and the stator current derivative in a cascade structure, to reduce the number of enumerated sequences. The procedures are repeated in the iteration periods optimized via a backtracking search method, until the stopping criterion is satisfied. The effectiveness of the proposed GD-FCSPCC is experimentally validated on a 2.2 kW induction machine testbench.
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| 17. |
- Xie, Haotian, et al.
(author)
-
Iterative Gradient Descent Based Finite Control Set Predictive Current Control with Least Squares Optimized Duty Cycles
- 2022
-
In: IEEE Journal of Emerging and Selected Topics in Power Electronics. - 2168-6777 .- 2168-6785. ; 10:2, s. 1422-1433
-
Journal article (peer-reviewed)abstract
- Finite Control Set Predictive Current Control (FCS-PCC) is widely recognized as a competitive control strategy in the field of electrical drives, due to its superiority of fast dynamic response and low switching frequency. However, FCS-PCC is penalized by its inherent drawback that the discrete nature of switching states leads to relatively high torque and current deviations. In this paper, an iterative gradient descent method combined with least squares optimized duty cycles is presented to improve the steady-state performance of FCS-PCC. Unlike the cost function optimization in the conventional FCS-PCC, the quadratic programming problem is solved from a geometric perspective, by obtaining the gradient descent which minimizes the tracking deviation in the fastest manner. To synthesize the gradient descent, the optimal stator current derivatives in the current and previous iteration are employed, and their duty cycles are determined by the least squares method. The abovementioned procedures are iteratively repeated in the dichotomy-based periods. The experimental performance of the proposed gradient descent based FCS-PCC is verified at a 8 kHz sampling frequency, which is compared with that of conventional and dichotomy-based FCS-PCC. It is validated that the proposed algorithm outperforms the conventional and dichotomy-based FCS-PCC at both the steady-state and transient state.
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| 18. |
- Yu, Xianbin, et al.
(author)
-
Preface
- 2024
-
In: Journal of Physics. - : IOP Publishing.
-
Conference paper (peer-reviewed)
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| 19. |
- Zhao, Xue, et al.
(author)
-
Simultaneous anchoring of Ni nanoparticles and single-atom Ni on BCN matrix promotes efficient conversion of nitrate in water into high-value-added ammonia
- 2022
-
In: Chemical Engineering Journal. - : Elsevier. - 1385-8947 .- 1873-3212. ; 433:Part 2
-
Journal article (peer-reviewed)abstract
- Electrochemical synthesis of ammonia driven by clean energy is expected to realize the supply of ammonia for distributed production of industry and agriculture. Here, nickel nanoparticles and nickel in the form of single atoms were simultaneously anchored on the electrochemically active carrier BCN matrix through a structured domain strategy, which realized a high-efficiency, high-value-added, conversion of nitrate in sewage. Specifically, the electrochemical nitrate reduction reaction (NIRR) driven by BCN@Ni in alkaline media achieves an ammonia yield rate as high as 2320.2 μg h−1 cm−2 (at −0.5 V vs RHE), and Faraday efficiency as high as 91.15% (at −0.3 V vs RHE). Even in neutral and acidic media, the ammonia yield rates of NIRR driven by BCN@Ni are as high as 1904.2 μg h−1 cm−2 and 2057.4 μg h−1 cm−2, respectively (at −0.4 V vs RHE). The 15NO3- isotope labeling experiment verified that the recorded ammonia all came from the electrochemical reduction of NO3– on BCN@Ni. Density functional theory (DFT) calculations show that both nano-Ni and single-atom Ni in BCN@Ni have the ability to electrochemically convert NO3– into NH3, and that the addition of BCN can further promote the NIRR on Ni.
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| 20. |
- Zhao, Xue, et al.
(author)
-
Two-dimensional BCN matrix inlaid with single-atom-Cu driven electrochemical nitrate reduction reaction to achieve sustainable industrial-grade production of ammonia
- 2021
-
In: APPLIED MATERIALS TODAY. - : Elsevier. - 2352-9407. ; 25
-
Journal article (peer-reviewed)abstract
- Electrochemical methods have been proven to effectively eliminate nitrates in sewage and convert them into high value-added ammonia products. Here, after annealing treatment of metal boron cluster organic polymers formed by the combination of 1,10-phenanthroline, Cu2+ and closo-[B12H12](2)(-), a Cu single-atom doped BCN (B-doped CN) with a diamond-shaped nanosheet structure was obtained. In the electrochem-ical reduction reaction of nitrate, BCN-Cu exhibits excellent catalytic activity, specifically: 1) the ammonia yield rate reached as high as 498.85 mu g h(-1) cm(-2), 1047.14 mu g h(-1) cm(-2), 1900.07 mu g h(-1) cm(-2) and 3358.74 mu g h(-1) cm(-2) at -0.3 V, -0.4 V, -0.5 V and -0.6 V vs reversible hydrogen electrode, respectively, and Faradaic efficiency is 95.90%, 97.28%, 98.23% and 97.37%; 2) after repeated use of BCN-Cu 10 times or continuous operation for 16 h, the activity against electrochemical reduction reaction of nitrate anions is almost unchanged. The (NO3-)-N-15 isotopic labeling experiment proved that the detected NH3 comes from the reduction of NO3- on BCN-Cu. Control experiments show that the presence of Cu determines whether BCN-Cu has the possibility of catalyzing electrochemical reduction reactions of nitrate, and the presence of the B element enhances the catalytic activity of BCN-Cu. Density functional calculations indicate that in the water phase the process of reducing NO3- to NH3 on Cu-0 is an exothermic reaction, and that the adsorption process of NO3- on Cu-0 is the rate-determining step.
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| 21. |
- Zhou, Weibin, et al.
(author)
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Targeting VEGF-A/VEGFR2 Y949 Signaling-Mediated Vascular Permeability Alleviates Hypoxic Pulmonary Hypertension
- 2022
-
In: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 146:24, s. 1855-1881
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Journal article (peer-reviewed)abstract
- Background:Pulmonary hypertension (PH) is associated with increased expression of VEGF-A (vascular endothelial growth factor A) and its receptor, VEGFR2 (vascular endothelial growth factor 2), but whether and how activation of VEGF-A signal participates in the pathogenesis of PH is unclear. Methods:VEGF-A/VEGFR2 signal activation and VEGFR2 Y949-dependent vascular leak were investigated in lung samples from patients with PH and mice exposed to hypoxia. To study their mechanistic roles in hypoxic PH, we examined right ventricle systolic pressure, right ventricular hypertrophy, and pulmonary vasculopathy in mutant mice carrying knock-in of phenylalanine that replaced the tyrosine at residual 949 of VEGFR2 (Vefgr2(Y949F)) and mice with conditional endothelial deletion of Vegfr2 after chronic hypoxia exposure. Results:We show that PH leads to excessive pulmonary vascular leak in both patients and hypoxic mice, and this is because of an overactivated VEGF-A/VEGFR2 Y949 signaling axis. In the context of hypoxic PH, activation of Yes1 and c-Src and subsequent VE-cadherin phosphorylation in endothelial cells are involved in VEGFR2 Y949-induced vascular permeability. Abolishing VEGFR2 Y949 signaling by Vefgr2(Y949F) point mutation was sufficient to prevent pulmonary vascular permeability and inhibit macrophage infiltration and Rac1 activation in smooth muscle cells under hypoxia exposure, thereby leading to alleviated PH manifestations, including muscularization of distal pulmonary arterioles, elevated right ventricle systolic pressure, and right ventricular hypertrophy. It is important that we found that VEGFR2 Y949 signaling in myeloid cells including macrophages was trivial and dispensable for hypoxia-induced vascular abnormalities and PH. In contrast with selective blockage of VEGFR2 Y949 signaling, disruption of the entire VEGFR2 signaling by conditional endothelial deletion of Vegfr2 promotes the development of PH. Conclusions:Our results support the notion that VEGF-A/VEGFR2 Y949-dependent vascular permeability is an important determinant in the pathogenesis of PH and might serve as an attractive therapeutic target pathway for this disease.
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