Publications by authors named "Qi Hu"

249 Publications

3D Acoustic Tweezers Using a 2D Matrix Array with Time-multiplexed Traps.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Jul 19;PP. Epub 2021 Jul 19.

The use of acoustic tweezers for precise manipulation of microparticles in the aqueous environment is essential and challenging for biomechanical applications in vivo. A 3D acoustic tweezer is developed in this study for three-dimensional manipulation by using a 2D phased array consisting of 256 elements operating at 1.04 MHz. The emission phases of each element are iteratively determined by a backpropagation algorithm to generate multiple acoustic traps. Different traps are multiplexed in time, thus forming synthesized acoustic fields. We demonstrate the three-dimensional levitation and translation of positive acoustic contrast particles, a major class of bioparticles, in water by different acoustic traps, and compare the positional deviation along the intended path via experimentally measured trajectories. Improved manipulating stability was achieved by multiplexed acoustic traps. The 3D acoustic tweezers proposed in this study provide a versatile approach of contactless bioparticle trapping and translation, paving the way towards future application of nanodroplet and microbubble manipulations.
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http://dx.doi.org/10.1109/TUFFC.2021.3098191DOI Listing
July 2021

A Nomogram for Predicting Survival in Patients With Breast Cancer Liver Metastasis: A Population-Based Study.

Front Oncol 2021 2;11:600768. Epub 2021 Jun 2.

Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Objective: The prognosis of patients with breast cancer liver metastasis (BCLM) was poor. We aimed at constructing a nomogram to predict overall survival (OS) for BCLM patients using the SEER (Surveillance Epidemiology and End Results) database, thus choosing an optimized therapeutic regimen to treat.

Methods: We identified 1173 patients with BCLM from the SEER database and randomly divided them into training (n=824) and testing (n=349) cohorts. The Cox proportional hazards model was applied to identify independent prognostic factors for BCLM, based on which a nomogram was constructed to predict 1-, 2-, and 3-year OS. Its discrimination and calibration were evaluated by the Concordance index (C-index) and calibration plots, while the accuracy and benefits were assessed by comparing it to AJCC-TNM staging system using the decision curve analysis (DCA). Kaplan-Meier survival analyses were applied to test the clinical utility of the risk stratification system.

Results: Grade, marital status, surgery, radiation therapy, chemotherapy, CS tumor size, tumor subtypes, bone metastatic, brain metastatic, and lung metastatic were identified to be independent prognostic factors of OS. In comparison with the AJCC-TNM staging system, an improved C-index was obtained (training group: 0.701 0.557, validation group: 0.634 0.557). The calibration curves were consistent between nomogram-predicted survival probability and actual survival probability. Additionally, the DCA curves yielded larger net benefits than the AJCC-TNM staging system. Finally, the risk stratification system can significantly distinguish the ones with different survival risk based on the different molecular subtypes.

Conclusion: We have successfully built an effective nomogram and risk stratification system to predict OS in BCLM patients, which can assist clinicians in choosing the appropriate treatment strategies for individual BCLM patients.
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http://dx.doi.org/10.3389/fonc.2021.600768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206538PMC
June 2021

Floquet wave theory-based time-corrected ultrasonic total focusing method for fiber-reinforced composite laminate.

Ultrasonics 2021 May 21;116:106467. Epub 2021 May 21.

School of Mechanical Engineering and Automation, Harbin Institute of Technology, Shenzhen 518055, PR China.

Fiber reinforced polymers (FRPs) are increasingly used in thick primary load-bearing structures. Nevertheless, manufacturing and in-service defects occur with a higher chance as the FRP thickness increases and thus the potential structure defects should be detected and evaluated. To image defects in thick FRP over 10 mm thick, this study proposes a frequency-and-structure dependent time-corrected ultrasonic total focusing method (FS-TFM) based on Floquet wave theory, which differs from conventional TFM that the wave velocity correction along different propagation direction bases on not only the structural anisotropy and inhomogeneity of FRP, but also on the probing frequency. First an analytical Floquet-wave-based dynamic homogenization for a crossply FRP laminate is performed, to obtain the homogenization region and then the wave anisotropy and dispersion therein. Then numerical finite element analysis follows, to further interrogate the time domain feature of wave signals. With the understanding of wave propagation, by accurately correcting the wave velocity anisotropy related to both the inspected crossply FPR and wave frequency, the FS-TFM imaging technique is proposed to focus the defect-scattered wave energy on the defect location. In addition, the signal-to-noise ratio (SNR) analysis of side-drilled-hole (Ø2 mm) imaging via different imaging algorithms shows that the proposed FS-TFM achieves the highest SNR at the frequency approaching the upper limit of the homogenization region. Finally, the experimental validation further indicates the potential of the proposed FS-TFM for accurate defect imaging in thick FRP.
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http://dx.doi.org/10.1016/j.ultras.2021.106467DOI Listing
May 2021

Extraction and identification methods of microplastics and nanoplastics in agricultural soil: A review.

J Environ Manage 2021 Sep 7;294:112997. Epub 2021 Jun 7.

The UWA Institute of Agriculture and School of Agriculture & Environment, The University of Western Australia, Perth, WA, 6001, Australia.

As the abundance of microplastics and nanoplastics (MPs/NPs) increases in the environment, their presence in agricultural soil has become of interest. MPs/NPs can affect soil physical and chemical properties and be absorbed by plants and soil animals, causing physical and chemical damage. Soil MPs exceeding a certain concentration cause significant harm. Therefore, the extraction and identification of MPs in soil are vital for determining soil pollution. However, soils contain many other particles of similar size to MPs/NPs, making it more difficult to distinguish them than in water bodies. No standardized extraction and identification method is available to quantify MPs/NPs in soil. Various methods have been described in the literature, but they involve many different procedures for sampling, purification, digestion, and identification. This paper reviews extraction and identification methods for MPs/NPs in soil, sediment, and water and summarizes agricultural soil sampling and preservation, MPs/NPs separation, organic matter removal, and MPs/NPs identification. We also compare the advantages and disadvantages of existing methods and propose future research topics.
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http://dx.doi.org/10.1016/j.jenvman.2021.112997DOI Listing
September 2021

Quad-channel independent wavefront encoding with dual-band multitasking metasurface.

Opt Express 2021 May;29(10):15678-15688

Achieving multiple electromagnetic (EM) functionalities on a shared aperture in dual frequency bands is crucial for many applications; however, existing dual-band metasurfaces are affected by limited channels or narrow bandwidths. Herein, we propose a reflective coding metasurface that empowers four independent EM functionalities in quad-polarization channels in two wide frequency bands. By integrating quasi-I-shaped and cross-shaped metastructures, the meta-atom can feature independent phase modulation for two orthogonally linear and two decoupled circular polarizations at low and high frequencies, respectively. To validate the proposed metasurface, a multifunctional metadevice is designed that integrates beam deflection, diffuse scattering, and vortex beam generation. Both experimental and simulation results indicate distinct wavefront tailoring in each channel. The proposed multi-functional metasurface with low cross-talk and independent phase modulation depending on frequencies and polarizations may unlock the metasurfaces' potentials for complete wavefront control in EM function integration, multiple channel communication, polarization optics, etc.
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http://dx.doi.org/10.1364/OE.419212DOI Listing
May 2021

Contribution of trace element exposure to gestational diabetes mellitus through disturbing the gut microbiome.

Environ Int 2021 08 25;153:106520. Epub 2021 Mar 25.

State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address:

Background: A healthy gut microbiome is critical for glucose metabolism during pregnancy. In vivo studies indicate that trace element affects the composition and function of the gut microbiome and potentially leads to metabolic disorders but their relationships are largely unknown. We aimed to investigate whether the gut microbiome plays a role in the relationship between trace element exposure and gestational diabetes mellitus (GDM).

Methods: In a prospective cohort study, serum levels of 22 trace elements and the fecal gut microbiome composition were assessed in 837 pregnant women in the second trimester between 22 and 24 weeks of pregnancy prior to GDM diagnosis. Regression and mediation analysis were used to explore the link between element exposure, the gut microbiome, and GDM.

Results: 128 pregnant women (15.3%) were diagnosed with GDM. No individual trace elements were found significantly associated with GDM. In contrast, the composition of the gut microbiome was dramatically altered in women later diagnosed with GDM and characterized by lower alpha diversity and lower abundance of co-abundance groups (CAGs) composed of genera belonging to Ruminococcaceae, Coriobacteriales, and Lachnospiraceae. Rubidium (Rb) was positively associated with alpha diversity indices while mercury (Hg) and vanadium (V) showed negative associations. Elements including rubidium (Rb), thallium (Tl), arsenic (As), and antimony (Sb) were significantly correlated with GDM-related CAGs and mediation analysis revealed that Rb and Sb were inversely related to GDM risk by altering abundance levels of CAGs enriched for Lachnospiraceae, Coriobacteriales, and Ruminococcaceae.

Conclusion: Our study indicates that trace element exposure is associated with specific gut microbiome features that may contribute to GDM development, which could provide a new avenue for intervening in environmental exposure-related GDM.
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http://dx.doi.org/10.1016/j.envint.2021.106520DOI Listing
August 2021

Exosomal miR-512-3p derived from mesenchymal stem cells inhibits oxidized low-density lipoprotein-induced vascular endothelial cells dysfunction via regulating Keap1.

J Biochem Mol Toxicol 2021 Jun 24;35(6):1-11. Epub 2021 Mar 24.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.

Atherosclerosis (AS) is a prevalent chronic inflammatory vascular disease. Upregulated oxidized low-density lipoprotein (ox-LDL) in the serum has been found to induce endothelial cells (ECs) apoptosis by increasing oxidative stress and promoting inflammatory response, which are essential mechanisms of AS development. Mesenchymal stem cells (MSCs), which secrete exosomes to transport microRNAs (miRNAs) and regulate cell functions, have become a research focus in recent years. The results of this study manifested that MSCs-derived exosomes were phagocytosed by EC. In addition, miR-512-3p enriched by MSCs- derived exosomes markedly inhibited ox-LDL-mediated EC damage, namely, accelerated EC proliferation, inhibited Caspase-3 activation and cell apoptosis, inhibited the levels of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, and IL-6) and oxidative factor MDA, and increased the contents of SOD and GSH-PX. Mechanistically, Keleh-like ECH-associated protein 1 (Keap1) was proved to be a functional target of miR-512-3p. Furthermore, silencing Keap1 limited ox-LDL-mediated EC cell dysfunction, while over-expressing Keap1 mitigated the exosomal miR-512-3p-mediated protective effect in Ox-LDL-induced EC. The above results confirmed that miR-512-3p shuttled by MSCs-derived exosomes protected EC against ox-LDL by targeting Keap1.
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http://dx.doi.org/10.1002/jbt.22767DOI Listing
June 2021

Detection of Urinary Albumin Using a "Turn-on" Fluorescent Probe with Aggregation-Induced Emission Characteristics.

Chem Asian J 2021 May 1;16(10):1245-1252. Epub 2021 Apr 1.

Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Victoria, 3086, Australia.

Human serum albumin (HSA) is a broadly used biomarker for the diagnosis of various diseases such as chronic kidney disease. Here, a fluorescent probe TC426 with aggregation-induced emission (AIE) characteristics is reported as a sensitive and specific probe for HSA. This probe is non-emissive in aqueous solution, meanwhile it shows bright fluorescence upon interacting with HSA, which makes it applicable in detecting HSA with a high signal to noise ratio. Besides, the fluorescence of TC426 exhibits a high linear correlation with the concentration of albumin in the range of microalbumin (20-200 mg/L), which has a significant importance for the early diagnosis of glomerulus related diseases. Compared with previously reported HSA probes TPE-4TA and BSPOTPE, TC426 shows comparable anti-interference ability towards creatinine and other major components in urine but is excited by a longer excitation wavelength at the visible light range. Finally, with the established assay, TC426 shows excellent performance in detecting HSA in real human urine, indicating its great potential in practical urinalysis.
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http://dx.doi.org/10.1002/asia.202100180DOI Listing
May 2021

Using culturomics and social media data to characterize wildlife consumption.

Authors:
Juan Li Qi Hu

Conserv Biol 2021 04 22;35(2):452-459. Epub 2021 Mar 22.

School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou, Zhejiang Province, 310024, China.

Wildlife provides food, medicine, clothing, and other necessities for humans, but overexploitation can disrupt the sustainability of wildlife resources and severely threaten global biodiversity. Understanding the characteristics of consumer behavior is helpful for wildlife managers and policy makers, but the traditional survey methods are laborious and time-consuming. In contrast, culturomics may more efficiently identify the features of wildlife consumption. As a case study of the culturomics approach, we examined tiger bone wine consumption in China based on social media and Baidu search engine data. Tiger bone wine is one of the most purchased tiger products; its consumption is closely related to tiger poaching, which greatly threatens wild tiger survival. We searched a popular social media website for the term "tiger bone wine" and focused on posts that were originally created from 1 January 2012 to 31 December 2018. We filtered and classified posts related to the purchase, sale, or consumption of tiger bone wine and extracted information on providers, consumption motivations, year of production, and place of origin of the tiger bone wines based on the texts and photos of these posts. We found 756 posts related to tiger bone wine consumption, 113 of which mentioned providers of tiger bone wine, including friends (53%), elder relatives (37%), peer relatives (7%), and others (3%). Out of the 756 posts, 266 indicated the motivations of tiger bone wine consumption. Tiger bone wines were consumed as a tonic (34%), medicine (23%), game product (30%), and a symbol of wealth (28%). Some posts indicated ≥2 consumption motivations. These findings were consistent with the search queries from Baidu index. Such information could help develop targeted strategies for tiger conservation. The culturomics approach illustrated by our study is a rapid and cost-efficient way to characterize wildlife consumption.
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http://dx.doi.org/10.1111/cobi.13703DOI Listing
April 2021

Effects of exposure to urban particulate matter SRM 1648a during pregnancy on the neurobehavioral development of offspring mice.

Ecotoxicol Environ Saf 2021 Jun 17;215:112142. Epub 2021 Mar 17.

State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address:

The development of the nervous system is crucial to a child's health. However, the nervous system is also susceptible to a variety of factors during development. To date, epidemiological studies have reported controversial results on the relationship between prenatal exposure to particulate matter (PM) and neurobehavioral development. Thus, we investigated the effect of PM exposure during pregnancy on the neurobehavioral development of offsprings. Adult C57BL/6 mice were exposed to PM from gestation day (GD) 0.5-21 by the intratracheal instillation. The daily exposure doses were 250 µg/kg.b.w and 2500 µg/kg.b.w respectively. The offspring mice began behavioral tests at the 5th week. We assessed neurobehavioral development, and the gene expression level changes in the mouse hippocampus using RNA-seq. In the open field test, the movement distance in the central area was significantly decreased in the high-dose group. Serum free triiodothyronine (FT3) levels were significantly increased in male offspring mice with prenatal high-dose PM exposure. The RNA-seq results suggested that the Prkca, Med12l, Ep300, and Slc16a10 in the thyroid hormone signaling pathway were significantly decreased in offspring mice in the high-dose group. Our data showed that prenatal PM exposure caused the offspring mice's anxiety-like behaviors and increased serum FT3 levels. The changes in thyroid hormone pathway-related genes might be the causes of the above series of changes.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112142DOI Listing
June 2021

Effect of biodegradable film mulching on crop yield, soil microbial and enzymatic activities, and optimal levels of irrigation and nitrogen fertilizer for the Zea mays crops in arid region.

Sci Total Environ 2021 Jul 19;776:145970. Epub 2021 Feb 19.

College of Water Conservancy and Civil Engineering, Inner Mongolia Agricultural University, Huhhot 010018, China.

Biodegradable film mulching (BM) is considered as the best alternative to plastic film mulching (PM) since it can prevent pollution caused due to plastic residues. However, the differences in soil microbial biomass and enzymatic activities between BM and PM, especially for different soil water and nitrogen contents remain ambiguous. In this study, the effects of BM, PM, and no film mulching (NM) on soil microbial biomass C (C), N (N), soil enzymes, and soil C/N ratio in a cornfield were evaluated using experimental data from 2018 and 2019. Additionally, different irrigation depths (30 mm, 22.5 mm, and 15 mm) and N-fertilizer application levels (280 kg ha and 210 kg ha) were used in BM. The experimental results demonstrated no apparent differences between the C, N, and soil enzymes between BM and PM in the early stage (elongation stage), but these values under BM were significantly lower than that of PM in the middle stage of crop growth (tasseling and filling stages). Soil sucrase, catalase, and urease under PM were increased by 20.2%, 0.6%, and 12.0%, respectively, compared to BM. The analysis of C, N, soil enzymes, and crop yield under different irrigation and N-fertilizer application levels demonstrated the preponderance of BM showing the highest yield of 14,110.1 kg ha and NUE of 61.7.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145970DOI Listing
July 2021

Association between mercury exposure and thyroid hormones levels: A meta-analysis.

Environ Res 2021 05 26;196:110928. Epub 2021 Feb 26.

State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. Electronic address:

Background: The relationship between mercury (Hg) exposure and thyroid hormones (THs) levels in the general population has been inconclusive. We conducted a random effects model meta-analysis to identify the association between Hg exposure and THs levels in the general population.

Methods: This meta-analysis were performed based on the PECO questions (P = general population; E =1ug/L Hg in blood and urine; C =1ug/L incremental increase on; and O = variation of THs levels). We searched four electronic databases including PubMed, Web of Science, Embase, and Cochrane Library for studies published on or before 20th July 2020. Prospective and cross-sectional studies that evaluated the association between Hg exposure and the levels of thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), and free thyroxine (FT4) were included. We also assessed aggregate risks for the reliability of the included studies.

Results: Initially, we retrieved 4889 articles. 18 studies met our inclusion criteria after screening and 13 articles were eligible to be included in the meta-analysis. The meta-analysis results suggest that blood Hg may be significantly associated with THs levels. The presence of Hg in blood may significantly increase the levels of TSH (β=0.55; 95%CI: 0.20,0.90; p < 0.001) and FT4 (β=0.47; 95%CI: 0.11,0.82; p < 0.001), with the opposite association in T4 (β=-0.02; 95%CI: 0.02, -0.01; p < 0.001). For the subgroup analysis, blood Hg was positively correlated with TSH levels in children and adolescents (β=0.62; 95%CI: 0.09, 1.15; p < 0.001) and FT4 levels in pregnant women (β=1.00; 95%CI: 0.99, 1.00; p < 0.001) respectively.

Conclusions: This meta-analysis indicates that exposure to Hg in blood could significantly corrrelate with the levels of TSH, T4, and FT4 in the general population. Therefore, it is crucial to control the use of Hg and strengthen protection of the thyroid.
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http://dx.doi.org/10.1016/j.envres.2021.110928DOI Listing
May 2021

A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia.

J Hematol Oncol 2021 Feb 25;14(1):37. Epub 2021 Feb 25.

Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients.

Methods: Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 10/L) after 8 weeks of treatment.

Results: The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83-68.63; p < 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39-86.87; p < 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment.

Conclusions: In ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile. Trial registration Clinical trials.gov NCT03222843 , registered July 19, 2017, retrospectively registered.
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http://dx.doi.org/10.1186/s13045-021-01047-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905908PMC
February 2021

Enantioselective Hydrogenation of Tetrasubstituted α,β-Unsaturated Carboxylic Acids Enabled by Cobalt(II) Catalysis: Scope and Mechanistic Insights.

Angew Chem Int Ed Engl 2021 05 7;60(20):11384-11390. Epub 2021 Apr 7.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, 518000, China.

Chiral carboxylic acids are important compounds because of their prevalence in pharmaceuticals, natural products and agrochemicals. Asymmetric hydrogenation of α,β-unsaturated carboxylic acids has been widely recognized as one of the most efficient synthetic approaches to afford such compounds. Although related asymmetric hydrogenation of di- and trisubstituted unsaturated acids with noble metals is well established, asymmetric hydrogenation of challenging tetrasubstituted α,β-unsaturated carboxylic acids is rarely reported. We demonstrate enantioselective hydrogenation of cyclic and acyclic tetrasubstituted α,β-unsaturated carboxylic acids via cobalt(II) catalysis. This protocol showed broad substrate scope and gave chiral carboxylic acids in good yields with excellent enantiocontrol (up to 98 % yield and 99 % ee). Combined experimental and computational mechanistic studies support a Co catalytic cycle involving migratory insertion and σ-bond metathesis processes. DFT calculations reveal that enantioselectivity may originate from the steric effect between the phenyl groups of the ligand and the substrate.
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http://dx.doi.org/10.1002/anie.202016705DOI Listing
May 2021

Ultrathin h-BN/BiMoO heterojunction with synergetic effect for visible-light photocatalytic tetracycline degradation.

J Colloid Interface Sci 2021 May 13;589:545-555. Epub 2021 Jan 13.

School of Materials Science and Engineering, Hebei University of Technology, Tianjin 300130, China; Hebei Key Laboratory of Boron Nitride Micro and Nano Materials, Hebei University of Technology, Tianjin 300130, China. Electronic address:

Herein, a series of ultrathin h-BN/BiMoO heterojunction with excellent photocatalytic activity has been firstly prepared via a feasible solvothermal method. Our results suggest that the optimized photocatalyst possesses a high degradation ratio of tetracycline (TC), oxytetracycline (OTC) and doxycycline (DC) up to 99.19%, 95.28% and 91.04% under visible-light irradiation, respectively. We highlight that the outstanding photocatalytic activity is mainly attributed to the prominent performance of tetracycline adsorption on h-BN and the dominant visible-light absorption by BiMoO as well as the effective photogenerated carrier separation induced by the synergetic effect between h-BN and BiMoO. Moreover, DFT calculations reveal that the built-in electric field formed between h-BN and BiMoO gives rise to the separation of carriers and the polarization of tetracycline molecules. Last but not the least, the specific process and micro-mechanism of the photocatalytic tetracycline degradation under visible-light driven have also been illuminated. The present work pioneers the application of ultrathin h-BN/BiMoO heterojunction as a novel tetracycline degradation photocatalyst and further guides the design of more visible-light photocatalysts.
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http://dx.doi.org/10.1016/j.jcis.2021.01.027DOI Listing
May 2021

Clinical characteristics and follow-up analysis of 324 discharged COVID-19 patients in Shenzhen during the recovery period.

Int J Med Sci 2021 1;18(2):347-355. Epub 2021 Jan 1.

Central Laboratory, Shenzhen Samii Medical Center, Shenzhen 518118, China.

Research on recovering COVID-19 patients could be helpful for containing the pandemic and developing vaccines, but we still do not know much about the clinical features, recovery process, and antibody reactions during the recovery period. We retrospectively analysed the epidemiological information, discharge summaries, and laboratory results of 324 patients. In all, 15 (8.62%) patients experienced chest distress/breath shortness, where 8 of the 15 were severely ill. This means severely ill patients need an extended amount of time to recover after discharge; next, 20 (11.49%) patients experienced anxiety and 21 (12.07%) had headache/insomnia and a small fraction of them complained of anosmia/ageusia, indicating that these patients need treatment for mental and psychological health issues. Regarding the re-positive patients, their CT and laboratory test results showed no obvious evidence of illness progress or infectivity but a high anti-SARS-CoV-2 antibody expression. Recovered COVID-19 patients need psychological and physiological care and treatment, re-positivity can occur in any person, but juveniles, females, and patients with mild/moderate existing symptoms have higher rates of re-positivity, While there is no evidence that turning re-positive has an impact on their infectivity, but it still alerted us that we need differentiate them in the following managements.
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http://dx.doi.org/10.7150/ijms.50873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757147PMC
January 2021

Pathway engineering in yeast for synthesizing the complex polyketide bikaverin.

Nat Commun 2020 12 3;11(1):6197. Epub 2020 Dec 3.

Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY, 10016, USA.

Fungal polyketides display remarkable structural diversity and bioactivity, and therefore the biosynthesis and engineering of this large class of molecules is therapeutically significant. Here, we successfully recode, construct and characterize the biosynthetic pathway of bikaverin, a tetracyclic polyketide with antibiotic, antifungal and anticancer properties, in S. cerevisiae. We use a green fluorescent protein (GFP) mapping strategy to identify the low expression of Bik1 (polyketide synthase) as a major bottleneck step in the pathway, and a promoter exchange strategy is used to increase expression of Bik1 and bikaverin titer. Then, we use an enzyme-fusion strategy to directly couple the monooxygenase (Bik2) and methyltransferase (Bik3) to efficiently channel intermediates between modifying enzymes, leading to an improved titer of bikaverin at 202.75 mg/L with flask fermentation (273-fold higher than the initial titer). This study demonstrates that the biosynthesis of complex fungal polyketides can be established and efficiently engineered in S. cerevisiae, highlighting the potential for natural product synthesis and large-scale fermentation in yeast.
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http://dx.doi.org/10.1038/s41467-020-19984-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713123PMC
December 2020

Respiratory Syncytial Virus Infection Reduces Kynurenic Acid Production and Reverses Th17/Treg Balance by Modulating Indoleamine 2,3-Dioxygenase (IDO) Molecules in Plasmacytoid Dendritic Cells.

Med Sci Monit 2020 Dec 2;26:e926763. Epub 2020 Dec 2.

Department of Pediatrics, The First Affiliated Hospital (Southwest Hospital) of Army Medical University, Chongqing, China (mainland).

BACKGROUND Respiratory syncytial virus (RSV) infection causes a world-wide medical and economic burden. This study analyzed the effects of RSV infection on plasmacytoid dendritic cells (pDCs) and evaluated the immunopathogenesis of RSV infection by measuring relative numbers of FoxP3+ Treg cells and Th17 cells. MATERIAL AND METHODS pDCs were isolated from human blood samples, purified using magnetic microbeads, and treated with RSV, IFN-g, or vehicle. These cells were mixed with purified CD4+ T cells to yield preparations of pDCs+T cells+vehicle, pDCs+T cells+RSV, and pDCs+T cells+IFN-g. Preparations of pDCs+T cells+RSV were also incubated with an inducer or an inhibitor of indoleamine 2,3-dioxygenase (IDO). Kynurenic acid concentration was measured by high-pressure liquid chromatography (HPLC). The differentiation of Foxp3+ Treg and Th17 cells from CD4+ T cells was determined by flow cytometry. RESULTS pDCs were successfully isolated and purified using the magnetic microbeads. Compared with preparations of pDCs+T cells+vehicle, RSV infection (pDCs+T cells+RSV) significantly reduced and IFN-g treatment (pDC+T cells+IFN-g) increased kynurenic acid concentrations and the proportions of Foxp3+ Tregs (p<0.05 each). Conversely, RSV infection increased and IFN-g treatment decreased the proportions of Th17 cells (p<0.05 each). RSV infection reduced kynurenic acid concentrations and inhibited the transformation from Th17 to Foxp3+ Tregs by modulating IDO molecules. CONCLUSIONS RSV infection reduced the production of kynurenic acid and inhibited transformation from Th17 to Foxp3+ Tregs (Th17/Treg balance) by modulating IDO molecules in pDCs.
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http://dx.doi.org/10.12659/MSM.926763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720431PMC
December 2020

Tetracycline Removal by Activating Persulfate with Diatomite Loading of Fe and Ce.

Molecules 2020 Nov 25;25(23). Epub 2020 Nov 25.

School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Shenyang 110016, China.

Persulfate (PS)-based oxidation technology is efficient in removing refractory organics from water. A novel diatomite (DIA) support Fe and Ce composite (Fe-Ce/DIA) was prepared for activating persulfate to degrade tetracycline in water. The Fe and Ce were uniformly loaded on DIA, and the total pore size of Fe-Ce/DIA was 6.99 × 10 cm/g, and the average pore size was 12.06 nm. Fe-Ce/DIA presented a good catalytic activity and 80% tetracycline was removed under the persulfate system. The Fe-Ce/DIA also had photocatalytic activity, and the corresponding tetracycline removal efficiency was 86% under UV irradiation. Fe-Ce/DIA exhibited less iron dissolution rate compared with Fe-DIA. The tetracycline degradation rate was enhanced when the temperature increased. The optimal tetracycline removal efficiency was obtained when the conditions were of persulfate 10 mM, Fe-Ce/DIA dosage 0.02 g/L, and tetracycline concentration 50 mg/L. In addition, Fe-Ce/DIA showed a wide pH application and good reusability and stability.
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http://dx.doi.org/10.3390/molecules25235531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728345PMC
November 2020

Enhanced phosphate scavenging with effective recovery by magnetic porous biochar supported La(OH): Kinetics, isotherms, mechanisms and applications for water and real wastewater.

Bioresour Technol 2021 Jan 7;319:124232. Epub 2020 Oct 7.

School of Resources and Environment, Northeast Agricultural University, Harbin 150030, China. Electronic address:

Herein, La(OH) decorated magnetic porous biochar (MPBC) was synthesized via KHCO activation and hydrothermal processes. The La-to-MPBC mass ratio of 3:1 described as La-MPBC possessed a monolayer phosphate adsorption capacity of 116.08 mg/g across a pH range of 3.0-6.0 with fast attainment of adsorption equilibrium in 150 min. Moreover, the phosphate adsorption was substantially stable during the interference of various co-existing ions with over 92% of phosphate removal and 77% of desorption efficiency maintained after four recycles. And La-MPBC was easily separated by magnet force with negligible La and Fe leakages within the pH range of 3.0-10.0. Furthermore, La-MPBC was supported to achieve phosphate binding through the synergistic actions of electrostatic attraction, ligand exchange, inner-sphere complexation and weak precipitation. Significantly, La-MPBC exhibited a high performance for decontaminating low-concentration phosphate to meet regulatory requirements. All these results suggested La-MPBC to be an ideal candidate for phosphate removal in real applications.
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http://dx.doi.org/10.1016/j.biortech.2020.124232DOI Listing
January 2021

GTP-State-Selective Cyclic Peptide Ligands of K-Ras(G12D) Block Its Interaction with Raf.

ACS Cent Sci 2020 Oct 23;6(10):1753-1761. Epub 2020 Sep 23.

Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

We report the identification of three cyclic peptide ligands of K-Ras(G12D) using an integrated translation-mRNA display selection platform. These cyclic peptides show preferential binding to the GTP-bound state of K-Ras(G12D) over the GDP-bound state and block Ras-Raf interaction. A co-crystal structure of peptide KD2 with K-Ras(G12D)·GppNHp reveals that this peptide binds in the Switch II groove region with concomitant opening of the Switch II loop and a 40° rotation of the α2 helix, and that a threonine residue (Thr10) on KD2 has direct access to the mutant aspartate (Asp12) on K-Ras. Replacing this threonine with non-natural amino acids afforded peptides with improved potency at inhibiting the interaction between Raf1-RBD and K-Ras(G12D) but not wildtype K-Ras. The union of G12D over wildtype selectivity and GTP state/GDP state selectivity is particularly desirable, considering that oncogenic K-Ras(G12D) exists predominantly in the GTP state in cancer cells, and wildtype K-Ras signaling is important for the maintenance of healthy cells.
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http://dx.doi.org/10.1021/acscentsci.0c00514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596874PMC
October 2020

Practical sensorless aberration estimation for 3D microscopy with deep learning.

Opt Express 2020 Sep;28(20):29044-29053

Estimation of optical aberrations from volumetric intensity images is a key step in sensorless adaptive optics for 3D microscopy. Recent approaches based on deep learning promise accurate results at fast processing speeds. However, collecting ground truth microscopy data for training the network is typically very difficult or even impossible thereby limiting this approach in practice. Here, we demonstrate that neural networks trained only on simulated data yield accurate predictions for real experimental images. We validate our approach on simulated and experimental datasets acquired with two different microscopy modalities and also compare the results to non-learned methods. Additionally, we study the predictability of individual aberrations with respect to their data requirements and find that the symmetry of the wavefront plays a crucial role. Finally, we make our implementation freely available as open source software in Python.
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http://dx.doi.org/10.1364/OE.401933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679184PMC
September 2020

Study on Pyrolysis Characteristics of SF in a Trace-Oxygen (O) Environment: ReaxFF Force Field Optimization and Reactive Molecular Dynamics Simulation.

ACS Omega 2020 Oct 6;5(41):26518-26526. Epub 2020 Oct 6.

Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources, North China Electric Power University, Beijing 102206, China.

The ReaxFF force field for a SF-O system is developed based on the density functional theory (DFT) calculation data. Then, a series of molecular dynamics (MD) simulations were performed. The results show that the main oxygen-containing compounds that appeared in the MD simulation include SOF, SOF, and SOF. The relative quantitative relationship between SOF and SOF can be used to determine the fault temperature. Besides, under overheating conditions, O rarely undergoes a self-cracking process to generate free O atoms. Instead, the basic route for O to participate in the SF pyrolysis process is X + Y + O = XO + YO. Furthermore, the reactivity order of various groups to O is (SF)* > (SF)* > (SF)* > F*, so O is more likely to participate in the reaction by attacking (SF)* or (SF)* groups. This study laid the foundation for the application of ReaxFF MD simulations to study the microscopic dynamic mechanism of SF pyrolysis in more complex systems.
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http://dx.doi.org/10.1021/acsomega.0c03214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581245PMC
October 2020

A longitudinal study reveals the alterations of the Microtus fortis colonic microbiota during the natural resistance to Schistosoma japonicum infection.

Exp Parasitol 2020 Dec 17;219:108030. Epub 2020 Oct 17.

Department of Laboratory Animal Science, Xiangya Medical College, Central South University, Changsha, China; Hunan Key Laboratory of Animal Models for Human Diseases, Changsha, China. Electronic address:

The gut microbiota has been demonstrated to associate with protection against helminth infection and mediate via microbial effects on the host humoral immunity. As a non-permissive host of Schistosoma japonicum, the Microtus fortis provides an ideal animal model to be investigated, because of its natural self-healing capability. Although researches on the systemic immunological responses have revealed that the host immune system contributes a lot to the resistance, the role of gut microbiome remains unclear. In this study, we exposed the M. fortis to the S.japonicum infection, carried out a longitudinal research (uninfected control, infected for 7 days, 14 days, 21 days, and 31 days) on their colonic microbiota based on the 16S rRNA gene amplicon sequencing. The bacterial composition disclosed a disturbance-recovery alteration followed by the resistance to S. japonicum. The alpha diversity of colon microbiota was reduced after the infection, but it gradually recovered along with self-healing process. Further LEfSe analysis revealed that phyla shifted from Firmicutes to Bacteroidetes, which were mainly driven by an increase of Ruminococcaceae and a depletion of Muribaculaceae in the family level along the Control-Infection-Recovery (CIR) process. We identified a temporary blooming of Lactobacillaceae and Lactobacillus in the mid infection stage (D14). As a recognized probiotics repository, we speculate the increased abundance of Lactobacillaceae in M. fortis colonic microbiota might relate to the natural resistance to the schistosome. Besides, potential microbial functions were also significantly changed in the resistance process. These results demonstrate the remarkable alterations of reed vole colonic microbiota in both community structure and potential functions along with the resistance to S. japonicum infection. The identified microbial biomarkers might offer new ways for drug development to conquer human schistosomiasis.
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http://dx.doi.org/10.1016/j.exppara.2020.108030DOI Listing
December 2020

Microwave-assisted one pot synthesis of β-cyclodextrin modified biochar for concurrent removal of Pb(II) and bisphenol a in water.

Carbohydr Polym 2020 Dec 29;250:117003. Epub 2020 Aug 29.

School of Resources and Environment, Northeast Agricultural University, Harbin 150030, China. Electronic address:

Herein, β-cyclodextrin (β-CD) functionalized rice husk-derived biochar (BC) was conveniently and fast synthesized via microwave (MW)-assisted one pot process, and employed for simultaneous elimination of bisphenol A (BPA) and plumbum (Pb). Profiting by microwave irradiation, the surface modification was implemented in 15 min and the prepared BC-β-CD presented an excellent adsorption performance with a heterogeneous adsorption capacity of 209.20 mg/g for BPA and a theoretical monolayer uptake of 240.13 mg/g for Pb(II) in the mono-component system. Furthermore, the BC-β-CD could simultaneously achieve efficient cleanup of BPA and Pb(II) through avoiding the competitive behaviors between them, which were due to the different adsorption mechanisms for Pb(II) (i.e. electrostatic attraction and complexation) and BPA (i.e. host-guest supramolecular and π-π interactions). Moreover, the adsorbed BPA and Pb(II) could be sequentially desorbed with mild decrease in the adsorption performance of BC-β-CD even after five cycles in the Pb(II)-BPA multi-component system.
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http://dx.doi.org/10.1016/j.carbpol.2020.117003DOI Listing
December 2020

Giant African snail genomes provide insights into molluscan whole-genome duplication and aquatic-terrestrial transition.

Mol Ecol Resour 2021 Feb 21;21(2):478-494. Epub 2020 Oct 21.

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.

Whole-genome duplication (WGD), contributing to evolutionary diversity and environmental adaptability, has been observed across a wide variety of eukaryotic groups, but not in molluscs. Molluscs are the second largest animal phylum in terms of species numbers, and among the organisms that have successfully adapted to the nonmarine realm through aquatic-terrestrial (A-T) transition. We assembled a chromosome-level reference genome for Achatina immaculata, a globally invasive species, and compared the genomes of two giant African snails (A. immaculata and Achatina fulica) to other available mollusc genomes. Macrosynteny, colinearity blocks, Ks peak and Hox gene clusters collectively suggested a WGD event in the two snails. The estimated WGD timing (~70 million years ago) was close to the speciation age of the Sigmurethra-Orthurethra (within Stylommatophora) lineage and the Cretaceous-Tertiary (K-T) mass extinction, indicating that the WGD may have been a common event shared by all Sigmurethra-Orthurethra species and conferred ecological adaptability allowing survival after the K-T extinction event. Furthermore, the adaptive mechanism of WGD in terrestrial ecosystems was confirmed by the presence of gene families related to the respiration, aestivation and immune defence. Several mucus-related gene families expanded early in the Stylommatophora lineage, and the haemocyanin and phosphoenolpyruvate carboxykinase families doubled during WGD, and zinc metalloproteinase genes were highly tandemly duplicated after WGD. This evidence suggests that although WGD may not have been the direct driver of the A-T transition, it played an important part in the terrestrial adaptation of giant African snails.
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http://dx.doi.org/10.1111/1755-0998.13261DOI Listing
February 2021

Multi-omics profiling highlights lipid metabolism alterations in pigs fed low-dose antibiotics.

BMC Genet 2020 09 21;21(1):112. Epub 2020 Sep 21.

Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518120, China.

Background: In order to study the relations of hepatocellular functions, weight gain and metabolic imbalance caused by low-dose antibiotics (LDA) via epigenetic regulation of gene transcription, 32 weaned piglets were employed as animal models and randomly allocated into two groups with diets supplemented with 0 or LDA (chlorotetracycline and virginiamycin).

Results: During the 4 weeks of the experiment, LDA showed a clear growth-promoting effect, which was exemplified by the significantly elevated body weight and average daily gain. Promoter methylome profiling using liquid hybridization capture-based bisulfite sequencing (LHC-BS) indicated that most of the 745 differential methylation regions (DMRs) were hypermethylated in the LDA group. Several DMRs were significantly enriched in genes related with fatty acids metabolic pathways, such as FABP1 and PCK1. In addition, 71 differentially expressed genes (DEGs) were obtained by strand-specific transcriptome analysis of liver tissues, including ALOX15, CXCL10 and NNMT, which are three key DEGs that function in lipid metabolism and immunity and which had highly elevated expression in the LDA group. In accordance with these molecular changes, the lipidome analyses of serum by LC-MS identified 38 significantly differential lipids, most of which were downregulated in the LDA group.

Conclusions: Our results indicate that LDA could induce epigenetic and transcriptional changes of key genes and lead to enhanced efficiency of lipid metabolism in the liver.
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http://dx.doi.org/10.1186/s12863-020-00918-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507292PMC
September 2020

Engineering biomimetic graphene nanodecoys camouflaged with the EGFR/HEK293 cell membrane for targeted capture of drug leads.

Biomater Sci 2020 Oct 14;8(20):5690-5697. Epub 2020 Sep 14.

School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.

Advanced graphene (G)-based nanomaterials have risen as emerging stars for biomedical applications over the past decade due to their unique physicochemical properties. However, the preparation of G-based nanomaterials with satisfactory bioactivity to meet the growing demands of multitasking applications in biocomplexity systems remains a challenge. Herein, we presented a biomimetic route to modify graphene oxide (GO) using high expression epidermal growth factor receptor cell membrane (CM). Owing to the inherent properties of the CM for multifaceted interaction with active ligands, the well camouflaged GO could capture the drug leads with targeting properties. The as-prepared CM-coated magnetic GO exhibited excellent binding properties, including good selectivity, high adsorption capacity, and suitable adsorption rates. In addition, by coupling this assay with mass spectrometry, two potential bioactive compounds, luteolin and caffeic acid, were screened from Taraxacum mongolicum Hand.-Mazz. It is anticipated that this biomimetic approach can open new possibilities for the rational design of improved G-based biocomposites and extend their bioapplications.
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http://dx.doi.org/10.1039/d0bm00841aDOI Listing
October 2020

Microwave-assisted synthesis of β-cyclodextrin functionalized celluloses for enhanced removal of Pb(II) from water: Adsorptive performance and mechanism exploration.

Sci Total Environ 2021 Jan 21;752:141854. Epub 2020 Aug 21.

School of Resources and Environment, Northeast Agricultural University, Harbin 150030, China. Electronic address:

Herein, β-cyclodextrin (β-CD) was efficiently grafted onto rice husk-based celluloses using different cross-linking agents of epichlorohydrin (EPI) and glutaraldehyde (GA). By feat of microwave irradiation, the functionalization procedure was completed in 17 min, and the synthesized RHEPIMWβ-CD and RHGAMWβ-CD exhibited fast adsorption equilibrium for Pb(II) within 20 min, excellent monolayer adsorption capacities of 216.06 and 279.08 mg g across an extensive pH scope of 3.0-6.0, unaffected affinity to Pb(II) during the existence of co-existing ions, superior reusability with over 81% and 87% of Pb(II) uptake sustained for four adsorption-desorption cycles. Thermodynamic parameters implied that the uptake process of Pb(II) occurred spontaneously (-ΔG) with an endothermic characteristic (+ΔH). Furthermore, electrostatic attraction and complexation were demonstrated to enhance the Pb(II) uptake onto the RHEPIMWβ-CD and RHGAMWβ-CD. In fix-bed columns, these two adsorbents also efficiently eliminated Pb(II) under various flow rates with experimental breakthrough curves well simulated by Thomas and Yoon-Nelson models. Significantly, the RHEPIMWβ-CD and RHGAMWβ-CD could effectively purify acid battery effluent containing Pb(II) for meeting regulatory requirement. Overall, the fast fabrication, excellent adsorption and recycling performance facilitate the development of tailored adsorbents for Pb(II) elimination in wastewater.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141854DOI Listing
January 2021

Achieving delafossite analog by in situ electrochemical self-reconstruction as an oxygen-evolving catalyst.

Proc Natl Acad Sci U S A 2020 Sep 26;117(36):21906-21913. Epub 2020 Aug 26.

School of Chemistry, Beijing Advanced Innovation Center for Biomedical Engineering, Key Laboratory of Bio-Inspired Smart Interfacial Science and Technology, Beihang University, 100191 Beijing, China;

Development of novel and robust oxygen evolution reaction (OER) catalysts with well-modulated atomic and electronic structure remains a challenge. Compared to the well-known metal hydroxides or (oxyhydr)oxides with lamellar structure, delafossites (ABO) are characterized by alternating layers of A cations and edge-sharing BO octahedra, but are rarely used in OER due to their poor electron conductivity and intrinsic activity. Here, we propose a delafossite analog by mutation of metal oxyhydroxide and delafossite based on first-principles calculations. Modulation on the electronic structure due to distortion of the original crystal field of the BO layers is calculated to enhance electron conductivity and catalytic activity. Inspired by the theoretical design, we have experimentally realized the delafossite analog by electrochemical self-reconstruction (ECSR). X-ray absorption spectroscopy and other experimental techniques reveal the formation of delafossite analog with Ag intercalated into bimetallic cobalt-iron (oxyhydr)oxide layers from a metastable precursor through amorphization. Benefitting from the featured local electronic and geometric structures, the delafossite analog shows superior OER activity, affording a current density of 10 mA⋅cm at an overpotential of 187 mV and an excellent stability (300 h) in alkaline conditions.
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http://dx.doi.org/10.1073/pnas.2009180117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486770PMC
September 2020