Publications by authors named "Lu Yang"

2,886 Publications

  • Page 1 of 1

Ferrimagnetic mPEG--PHEP copolymer micelles loaded with iron oxide nanocubes and emodin for enhanced magnetic hyperthermia-chemotherapy.

Natl Sci Rev 2020 Apr 17;7(4):723-736. Epub 2020 Jan 17.

Division of Nanomaterials & Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, CAS Center for Excellence in Nanoscience, Hefei Science Center of CAS, Department of Chemistry, Institute of Biomimetic Materials & Chemistry, University of Science and Technology of China, Hefei 230026, China.

As a non-invasive therapeutic method without penetration-depth limitation, magnetic hyperthermia therapy (MHT) under alternating magnetic field (AMF) is a clinically promising thermal therapy. However, the poor heating conversion efficiency and lack of stimulus-response obstruct the clinical application of magnetofluid-mediated MHT. Here, we develop a ferrimagnetic polyethylene glycol-poly(2-hexoxy-2-oxo-1,3,2-dioxaphospholane) (mPEG--PHEP) copolymer micelle loaded with hydrophobic iron oxide nanocubes and emodin (denoted as EMM). Besides an enhanced magnetic resonance (MR) contrast ability (  = 271 mM s) due to the high magnetization, the specific absorption rate (2518 W/g at 35 kA/m) and intrinsic loss power (6.5 nHm/kg) of EMM are dozens of times higher than the clinically available iron oxide nanoagents (Feridex and Resovist), indicating the high heating conversion efficiency. Furthermore, this composite micelle with a flowable core exhibits a rapid response to magnetic hyperthermia, leading to an AMF-activated supersensitive drug release. With the high magnetic response, thermal sensitivity and magnetic targeting, this supersensitive ferrimagnetic nanocomposite realizes an above 70% tumor cell killing effect at an extremely low dosage (10 μg Fe/mL), and the tumors on mice are completely eliminated after the combined MHT-chemotherapy.
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http://dx.doi.org/10.1093/nsr/nwz201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289054PMC
April 2020

Lipid-oligonucleotide conjugates for bioapplications.

Natl Sci Rev 2020 Dec 9;7(12):1933-1953. Epub 2020 Jul 9.

Center for Research at Bio/Nano Interface, Department of Chemistry and Department of Physiology and Functional Genomics, Health Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, FL 32611-7200, USA.

Lipid-oligonucleotide conjugates (LONs) are powerful molecular-engineering materials for various applications ranging from biosensors to biomedicine. Their unique amphiphilic structures enable the self-assembly and the conveyance of information with high fidelity. In particular, LONs present remarkable potential in measuring cellular mechanical forces and monitoring cell behaviors. LONs are also essential sensing tools for intracellular imaging and have been employed in developing cell-surface-anchored DNA nanostructures for biomimetic-engineering studies. When incorporating therapeutic oligonucleotides or small-molecule drugs, LONs hold promise for targeted therapy. Moreover, LONs mediate the controllable assembly and fusion of vesicles based on DNA-strand displacements, contributing to nanoreactor construction and macromolecule delivery. In this review, we will summarize the general synthesis strategies of LONs, provide some characterization analysis and emphasize recent advances in bioanalytical and biomedical applications. We will also consider the relevant challenges and suggest future directions for building better functional LONs in nanotechnology and materials-science applications.
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http://dx.doi.org/10.1093/nsr/nwaa161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290939PMC
December 2020

The removal of uranium (VI) from aqueous solution by the anaerobically digested sewage sludge with hydrothermal pretreatment.

Chemosphere 2021 Oct 21:132644. Epub 2021 Oct 21.

MOE Key Laboratory of Resources and Environmental Systems Optimization, College of Environmental Science and Engineering, North China Electric Power University, Beijing, 102206, China.

Anaerobic digestion (AD) with hydrothermal (HT) pretreatment (sequential HT-AD treatment) is a novel technology for sludge management. HT-AD sludge is rich in functional groups and its applications as pollutant sorbents might be a win-win strategy. This study investigated the removal of uranium (VI) from water using HT-AD sludge as affected by solution pH, temperature, and ion strength. The reusability and heavy metal risk of HT-AD sludge were also assessed. The batch sorption experiments demonstrated that even at an acidic initial pH of 3.2, the maximum adsorption of HT-AD sludge for uranium (VI) reached 117.13 mg/g, higher than that of most carbon-based materials. The inner-sphere and out-sphere complexation between uranium (VI) and the HT-AD sludge dominated the adsorption when pH was in the range of 2-6 and 6-11, respectively. The FTIR and XPS analysis indicated that the primary mechanisms of uranium (VI) adsorption by the HT-AD sludge were the surface complexation and the electric attraction between uranium (VI) and the functional groups (e.g. -COO-) on HT-AD sludge. The removal rate of uranium (VI) by HT-AD sludge only decreased by ∼7% after 3 consecutive adsorption cycles. Leaching experiment showed that less than 5% of the total heavy metal were released from HT-AD sludge. Our research proved that HT-AD sludge can be used as an efficient uranium (VI) adsorbent with good reusability and environmental safety.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132644DOI Listing
October 2021

Circulating Fluidized Bed Fly Ash Mixed Functional Cementitious Materials: Shrinkage Compensation of f-CaO, Autoclaved Hydration Characteristics and Environmental Performance.

Materials (Basel) 2021 Oct 12;14(20). Epub 2021 Oct 12.

School of Metallurgical and Ecological Engineering, University of Science and Technology Beijing, Beijing 100083, China.

Circulating fluidized bed (CFB) fly ash is a by-product from CFB power generation, which is hard to utilize in cement because it contains f-CaO and SO. This work aims to explore the mechanism of the shrinkage compensation of free-CaO (f-CaO) and the autoclaved hydration characteristics and environmental performance of CFB fly ash mixed cementitious materials (CMM). In this work, long-term volume stability of CMM is improved with the addition of CFBFA. These findings suggest that the compressive strength of sample CMM0.5 is the highest under both standard condition (67.21 MPa) and autoclaved condition (89.56 MPa). Meanwhile, the expansion rate (0.0207%) of sample CMM0.5 is the lowest, which proves the shrinkage compensation effect of f-CaO in CFBFA. The main hydration products of CMM0.5 are CaSiO•HO (C-S-H) gel, CaAlSiO(OH)•HO (C-A-S-H) gel and Ca(OH). In addition, the high polymerization degree of [Si(Al)O] and the densified microstructure are presented at the sample CMM0.5. The leaching results indicates that the heavy metals in CMM0.5 satisfies the WHO standards for drinking water due to physical encapsulation and charge balance. Therefore, this investigation provides a novel method of using CFB fly ash in cement.
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http://dx.doi.org/10.3390/ma14206004DOI Listing
October 2021

Selection of Specific Nanobodies against Lupine Allergen Lup an 1 for Immunoassay Development.

Foods 2021 Oct 13;10(10). Epub 2021 Oct 13.

Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China.

The declaration of lupine supplements is mandatory to avoid lupine allergy for sensitive individuals. However, reliable detection methods against lupine allergen remain critical to prevent the unintended consumption of allergen contaminated food. In this study, we have immunized an alpaca with lupine protein extracts and retrieved nanobodies (Nbs). Nevertheless, the target antigen has been recognized as Lup an 1, which has been classified as β-conglutin, and confirmed to connect with lupine allergy. After selection of the best Nb-pair, a sandwich enzyme-linked immunosorbent assay (ELISA) has been developed providing a linear range of 0.036-4.4 μg/mL with detection limit of 1.15 ng/mL. This immunoassay was confirmed by detecting the samples with spiked allergen, and a recovery from 86.25% to 108.45% with coefficient of variation (CV) less than 4.0% has been determined. Generally, this study demonstrated the selection of Nbs against allergen with crude protein content to develop the immunoassay for lupine surveillance in foods.
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http://dx.doi.org/10.3390/foods10102428DOI Listing
October 2021

Simultaneous Determination of Albendazole and Its Three Metabolites in Pig and Poultry Muscle by Ultrahigh-Performance Liquid Chromatography-Fluorescence Detection.

Foods 2021 Oct 2;10(10). Epub 2021 Oct 2.

College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.

A fast, simple and efficient ultrahigh-performance liquid chromatography-fluorescence detection (UPLC-FLD) method for the determination of residues of albendazole (ABZ) and its three metabolites, albendazole sulfone (ABZ-SO), albendazole sulfoxide (ABZ-SO), and albendazole-2-aminosulfone (ABZ-2NH-SO), in pig and poultry muscle (chicken, duck and goose) was established. The samples were extracted with ethyl acetate, and the extracts were further subjected to cleanup by utilizing a series of liquid-liquid extraction (LLE) steps. Then, extracts were purified by OASIS PRiME hydrophilic-lipophilic balance (HLB) solid-phase extraction (SPE) cartridges (60 mg/3 mL). The target compounds were separated on an ACQUITY UPLC BEH C (2.1 mm × 100 mm, 1.7 μm) chromatographic column, using a mobile phase composed of 31% acetonitrile and 69% aqueous solution (containing 0.2% formic acid and 0.05% triethylamine). The limits of detection (LODs) and limits of quantification (LOQs) of the four target compounds in pig and poultry muscle were 0.2-3.8 µg/kg and 1.0-10.9 µg/kg, respectively. The recoveries were all above 80.37% when the muscle samples were spiked with the four target compounds at the LOQ, 0.5 maximum residue limit (MRL), 1.0 MRL, and 2.0 MRL levels. The intraday relative standard deviations (RSDs) were less than 5.11%, and the interday RSDs were less than 6.29%.
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http://dx.doi.org/10.3390/foods10102350DOI Listing
October 2021

Bile Duct Ligation Upregulates Expression and Function of L-Amino Acid Transporter 1 at Blood-Brain Barrier of Rats via Activation of Aryl Hydrocarbon Receptor by Bilirubin.

Biomedicines 2021 Sep 26;9(10). Epub 2021 Sep 26.

Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.

Liver failure is associated with increased levels of brain aromatic amino acids (AAAs), whose transport across the blood-brain barrier (BBB) is mainly mediated by L-amino acid transporter 1 (LAT1). We aimed to investigate whether liver failure induced by bile duct ligation (BDL) increases levels of brain AAAs by affecting the expression and function of LAT1. The LAT1 function was assessed using the brain distribution of gabapentin. It was found that BDL significantly increased levels of gabapentin, phenylalanine, and tryptophan in the cortex, hippocampus, and striatum of rats, and upregulated the expression of total LAT1 protein in hippocampus and striatum as well as cortex membrane LAT1 protein. HCMEC/D3 served as in vitro BBB model, and the data showed that both the serum of BDL rats and bilirubin induced LAT1 expression and function, while bilirubin oxidase almost abolished the upregulation of LAT1 protein by bilirubin and the serum of BDL rats. The enhanced function and expression of LAT1 were also observed in the hippocampus and striatum of hyperbilirubinemia rats. Both aryl hydrocarbon receptor (AhR) antagonist α-naphthoflavone and AhR silencing obviously attenuated the upregulation of LAT1 protein by bilirubin or omeprazole. This study provides the first evidence that BDL upregulates LAT1 at the rat BBB, attributed to the activation of AhR by the increased plasma bilirubin. The results highlight the mechanisms causing BDL-increased levels of brain AAAs and their physiological significance.
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http://dx.doi.org/10.3390/biomedicines9101320DOI Listing
September 2021

The imbalance of PGD2-DPs pathway is involved in the type 2 diabetes brain injury by regulating autophagy.

Int J Biol Sci 2021 21;17(14):3993-4004. Epub 2021 Sep 21.

Department of Pharmacology, Chongqing Medical University, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.

Prostaglandin D2 (PGD2) is the most abundant prostaglandin in the brain, but its involvement in brain damage caused by type 2 diabetes (T2D) has not been reported. In the present study, we found that increased PGD2 content is related to the inhibition of autophagy, which aggravates brain damage in T2D, and may be involved in the imbalanced expression of the corresponding PGD2 receptors DP1 and DP2. We demonstrated that DP2 inhibited autophagy and promotedT2D-induced brain damage by activating the PI3K/AKT/mTOR pathway, whereas DP1enhanced autophagy and amelioratedT2D brain damage by activating the cAMP/PKA pathway. In a T2D rat model, DP1 expression was decreased, and DP2 expression was increased; therefore, the imbalance in PGD2-DPs may be involved in T2D brain damage through the regulation of autophagy. However, there have been no reports on whether PKA can directly inhibit mTOR. The PKA catalytic subunit (PKA-C) has three subtypes (α, β and γ), and γ is not expressed in the brain. Subsequently, we suggested that PKA could directly interact with mTOR through PKA-C(α) and PKA-C(β). Our results suggest that the imbalance in PGD2-DPs is related to changes in autophagy levels in T2D brain damage, and PGD2 is involved in T2D brain damage by promoting autophagy via DP1-PKA/mTOR and inhibiting autophagy via DP2-PI3K/AKT/mTOR.
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http://dx.doi.org/10.7150/ijbs.60149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495389PMC
September 2021

Catalytic Asymmetric Inverse-Electron-Demand Diels-Alder Reactions of 2-Pyrones with Indenes: Total Syntheses of Cephanolides A and B.

Angew Chem Int Ed Engl 2021 Oct 20. Epub 2021 Oct 20.

Fudan University, Department of Chemistry, CHINA.

An inverse-electron-demand Diels-Alder (IEDDA) reaction could complement the conventional normal-electron-demand Diels-Alder reaction in the synthesis of six-membered carbocycles. However, catalytic asymmetric all-carbon-based IEDDA reactions are underdeveloped. Herein, we disclosed a copper-catalyzed asymmetric IEDDA reaction using electron-deficient 3-carboalkoxyl-2-pyrones and electronically unbiased indenes as reactants. This method enables the rapid and enantioselective construction of a wide range of hexahydrofluorenyl bridged-lactone scaffolds. Using this method, the asymmetric total syntheses of cephanolides A and B were accomplished.
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http://dx.doi.org/10.1002/anie.202112223DOI Listing
October 2021

Genetic spectrum and clinical features in a cohort of Chinese patients with autosomal recessive cerebellar ataxias.

Transl Neurodegener 2021 Oct 18;10(1):40. Epub 2021 Oct 18.

Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, 310000, China.

Background: Although many causative genes have been uncovered in recent years, genetic diagnosis is still missing for approximately 50% of autosomal recessive cerebellar ataxia (ARCA) patients. Few studies have been performed to determine the genetic spectrum and clinical profile of ARCA patients in the Chinese population.

Methods: Fifty-four Chinese index patients with unexplained autosomal recessive or sporadic ataxia were investigated by whole-exome sequencing (WES) and copy number variation (CNV) calling with ExomeDepth. Likely causal CNV predictions were validated by CNVseq.

Results: Thirty-eight mutations including 29 novel ones were identified in 25 out of the 54 patients, providing a 46.3% positive molecular diagnostic rate. Ten different genes were involved, of which four most common genes were SACS, SYNE1, ADCK3 and SETX, which accounted for 76.0% (19/25) of the positive cases. The de novo microdeletion in SACS was reported for the first time in China and the uniparental disomy of ADCK3 was reported for the first time worldwide. Clinical features of the patients carrying SACS, SYNE1 and ADCK3 mutations were summarized.

Conclusions: Our results expand the genetic spectrum and clinical profiles of ARCA patients, demonstrate the high efficiency and reliability of WES combined with CNV analysis in the diagnosis of suspected ARCA, and emphasize the importance of complete bioinformatics analysis of WES data for accurate diagnosis.
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http://dx.doi.org/10.1186/s40035-021-00264-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522248PMC
October 2021

Functional Hybrid Micro/Nanoentities Promote Agro-Food Safety Inspection.

J Agric Food Chem 2021 Oct 18. Epub 2021 Oct 18.

Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.

The rapid development of nanomaterials has provided a good theoretical basis and technical support to solve the problems of food safety inspection. The combination of functionalized composite nanomaterials and well-known detection methods is gradually applied to detect hazardous substances, such as chemical residues and toxins, in agricultural food products. This review concentrates on the latest agro-food safety inspection techniques and methodologies constructed with the assistance of new hybrid micro/nanoentities, such as molecular imprinting polymers integrated with quantum dots ([email protected]), molecular imprinting polymers integrated with upconversion luminescent nanoparticles ([email protected]), upconversion luminescent nanoparticles combined with metal-organic frameworks ([email protected]), magnetic metal-organic frameworks ([email protected]), magnetic covalent-organic frameworks ([email protected]), covalent-organic frameworks doped with quantum dots ([email protected]), nanobody-involved immunoassay for fast inspection, etc. The presented summary and discussion favor a relevant outlook for further integrating various disciplines, like material science, nanotechnology, and analytical methodology, for addressing new challenges that emerge in agro-food research fields.
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http://dx.doi.org/10.1021/acs.jafc.1c05185DOI Listing
October 2021

A 15-Year-Old Adolescent With Obstructive Shock and Emerging Thrombus.

JACC Cardiovasc Interv 2021 Oct 8. Epub 2021 Oct 8.

Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. Electronic address:

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http://dx.doi.org/10.1016/j.jcin.2021.08.030DOI Listing
October 2021

Clinical Molecular and Genomic Epidemiology of in China.

Front Microbiol 2021 28;12:744291. Epub 2021 Sep 28.

Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Ongoing acquisition of antimicrobial resistance genes has made a new clinical treatment challenge. Understanding the molecular epidemiology of will contribute to clinical treatment and prevention. We undertook a 6-year clinical molecular epidemiological investigation of from three tertiary hospitals in China since 2014. Antimicrobial susceptibility testing was performed using a VITEK-2 system. All isolates were screened for β-lactam and plasmid-mediated quinolone resistance genes by PCR. Isolates carrying carbapenem-resistant genes were subjected to whole-genome sequencing (WGS). The variation and evolution of these mobile genetic elements (MGEs) were then systematically analyzed. Among all isolates ( = 335), forty (11.9%) were recognized as multidrug resistant strains. , , , and were the top four most prevalent resistance genes. Notably, phylogenomic and population structure analysis suggested clade 1 (rhierBAPS SC3 and SC5) associated with multiple resistance genes seemed to be widely spread. WGS showed a -carrying IncX3 plasmid and a genomic island 2 variant carrying , coexisted in the same multidrug resistant strain zy_m28. Additionally, a -carrying IncP-1β type plasmid was found in the strain nx_m63. This study indicates a clade of is prone to acquire resistance genes, and multidrug resistant are increasing by harboring a variety of MGEs including two newly discovered ones in the species. We should be vigilant that may bring more extensive and challenging antimicrobial resistance issue.
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http://dx.doi.org/10.3389/fmicb.2021.744291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507844PMC
September 2021

Smoking behavior and circulating vitamin D levels in adults: A meta-analysis.

Food Sci Nutr 2021 Oct 5;9(10):5820-5832. Epub 2021 Aug 5.

Hebei General Hospital Shijiazhuang China.

To determine the effect of smoking on circulating vitamin D in adults, we performed a meta-analysis. Literature before 9 May 2021 was retrieved from electronic literature databases such as EMBASE, PubMed, and Cochrane. The quality of the included studies was assessed by two researchers against the Newcastle-Ottawa scale and JBI Evidence-based Health Care Centre criteria. All eligible studies and statistical analyses were performed using STATA 14. Twenty-four studies with 11,340 participants meeting the criteria were included in the meta-analysis. The results of meta-analysis showed that the level of circulating 25(OH)D in smokers was lower than that in nonsmokers. A subgroup analysis based on vitamin D supplement use showed that both smokers who used vitamin D supplements and smokers who did not use vitamin D supplements had lower blood 25(OH)D levels compared with the control group. In addition, subjects were divided into different subgroups according to age for meta-analysis, and the results showed that the serum 25(OH)D level in each subgroup of smokers was lower than that in the control group. This meta-analysis revealed differences in circulating vitamin D levels between smokers and nonsmokers, with smokers likely to have lower circulating vitamin D levels.
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http://dx.doi.org/10.1002/fsn3.2488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497833PMC
October 2021

Glycoproteome remodeling in MLL-rearranged B-cell precursor acute lymphoblastic leukemia.

Theranostics 2021 21;11(19):9519-9537. Epub 2021 Sep 21.

Institute for Glycomics, Griffith University, Gold Coast Campus, QLD, Australia.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with mixed-lineage leukemia gene rearrangement (MLL-r) is a poor-prognosis subtype for which additional therapeutic targets are urgently needed. Currently no multi- data set for primary MLL r patient cells exists that integrates transcriptomics, proteomics and glycomics to gain an inclusive picture of theranostic targets. We have integrated transcriptomics, proteomics and glycomics to i) obtain the first inclusive picture of primary patient BCP-ALL cells and identify molecular signatures that distinguish leukemic from normal precursor B-cells and ii) better understand the benefits and limitations of the applied technologies to deliver deep molecular sequence data across major cellular biopolymers. MLL-r cells feature an extensive remodeling of their glycocalyx, with increased levels of Core 2-type O-glycans and complex N-glycans as well as significant changes in sialylation and fucosylation. Notably, glycosaminoglycan remodeling from chondroitin sulfate to heparan sulfate was observed. A survival screen, to determine if glycan remodeling enzymes are redundant, identified MGAT1 and NGLY1, essential components of the N-glycosylation/degradation pathway, as highly relevant within this screening. OGT and OGA, unique enzymes that regulate intracellular O-GlcNAcylation, were also indispensable. Transcriptomics and proteomics further identified Fes and GALNT7-mediated glycosylation as possible therapeutic targets. While there is overall good correlation between transcriptomics and proteomics data, we demonstrate that a systematic combined multi- approach delivers important diagnostic information that is missed when applying a single omics technology. Apart from confirming well-known MLL-r BCP-ALL glycoprotein markers, our integrated multi- workflow discovered previously unidentified diagnostic/therapeutic protein targets.
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http://dx.doi.org/10.7150/thno.65398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490503PMC
September 2021

Study of Pavement Micro- and Macro-Texture Evolution Due to Traffic Polishing Using 3D Areal Parameters.

Materials (Basel) 2021 Oct 2;14(19). Epub 2021 Oct 2.

School of Civil and Environmental Engineering, Oklahoma State University, Stillwater, OK 74078, USA.

Pavement micro- and macro-texture have significant effects on roadway friction and driving safety. The influence of traffic polish on pavement texture has been investigated in many laboratory studies. This paper conducts field evaluation of pavement micro- and macro-texture under actual traffic polishing using three-dimensional (3D) areal parameters. A portable high-resolution 3D laser scanner measured pavement texture from a field site in 2018, 2019, and 2020. Then, the 3D texture data was decomposed to micro- and macro-texture using Fourier transform and Butterworth filter methods. Twenty 3D areal parameters from five categories, including height, spatial, hybrid, function, and feature parameters, were calculated to characterize pavement micro- and macro-texture. The results demonstrate that the 3D areal parameters provide an alternative to comprehensively characterize the evolution of pavement texture under traffic polish from different aspects.
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http://dx.doi.org/10.3390/ma14195769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510056PMC
October 2021

Colonic expression of , the SARS-CoV-2 entry receptor, is suppressed by commensal human microbiota.

Gut Microbes 2021 Jan-Dec;13(1):1984105

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.

Infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Angiotensin-converting enzyme 2 () is expressed in the gastrointestinal (GI) tract and a receptor for SARS-CoV-2, making the GI tract a potential infection site. This study investigated the effects of commensal intestinal microbiota on colonic expression using a humanized mouse model. We found that colonic expression decreased significantly upon microbial colonization. Humanization with healthy volunteer or dysbiotic microbiota from irritable bowel syndrome (IBS) patients resulted in similar expression. Despite the differences in microbiota, no associations between α-diversity, β-diversity or individual taxa, and were noted post-humanization. These results highlight that commensal microbiota play a key role in regulating intestinal expression and the need to further examine the underlying mechanisms of this regulation.
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http://dx.doi.org/10.1080/19490976.2021.1984105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510562PMC
October 2021

Highly Selective and Sensitive Detection of Volatile Sulfur Compounds by Ionically Conductive Metal-Organic Frameworks.

Adv Mater 2021 Oct 11:e2104120. Epub 2021 Oct 11.

Interdisciplinary Materials Research Center, School of Materials Science and Engineering, Frontiers Science Center for Intelligent Autonomous Systems, Tongji University, Shanghai, 201804, P. R. China.

High selectivity to specific analyte is essential for chemical sensors but difficult to achieve. For most chemical sensors, although the response to the target analyte can be more significant than interference analytes, they still show obvious responses to the interference analytes. Here, highly selective chemical sensors are developed with negligible responses to other interference vapors. Instead of the widely investigated electronically conductive metal-organic frameworks (EC-MOFs), ionically conductive MOFs (IC-MOFs) are used as the sensing materials, and the unique interaction between the ion charge carrier and the analyte is utilized to achieve high sensing selectivity. Through the modulation of the metal nodes (Cu, Co, Ni, Zn, Mg) and organic ligands (H TCPP, H THPP, H BTEC), sensor arrays based on a set of IC-MOFs are fabricated and achieve highly selective detection toward volatile sulfur compounds (VSCs). H S and CH SH can be selectively detected at concentrations down to 1 ppb and 1 ppm, respectively. The facile preparation and low cost endow the device with disposability. These results suggest new approaches for the development of highly selective chemical sensors.
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http://dx.doi.org/10.1002/adma.202104120DOI Listing
October 2021

Activation of transient receptor potential vanilloid 4 exacerbates myocardial ischemia-reperfusion injury via JNK-CaMKII phosphorylation pathway in isolated mice hearts.

Cell Calcium 2021 Oct 5;100:102483. Epub 2021 Oct 5.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Previous studies, including our own, have demonstrated that transient receptor potential vanilloid 4 (TRPV4) is involved in myocardial ischemia-reperfusion (IR) injury, yet its underlying molecular mechanism remains unclear. In this study, we isolated mice hearts for a Langendorff perfusion test and used HL-1 myocytes for in vitro assessments. We first confirmed that TRPV4 agonist (GSK101) enhanced myocardial IR injury, as demonstrated by the reduced recovery of cardiac function, larger myocardial infarct size, and more apoptotic cells. We also found that GSK101 could further increase the phosphorylation of JNK and CaMKII in isolated hearts during IR. Notably, GSK101 dose-dependently evoked the phosphorylation of JNK and CaMKII in isolated normal hearts. All above GSK101-induced effects could be significantly blocked by the pharmacological inhibition or genetic ablation of TRPV4. More importantly, JNK inhibition (with SP600125) or CaMKII inhibition (with KN93 or in transgenic AC3-I mice) could prevent GSK101-induced myocardial injury during IR. In HL-1 myocytes, GSK101 triggered Ca influx and evoked the phosphorylation of JNK and CaMKII but these effects were abolished by removing extracellular Ca or in the presence of a TRPV4 antagonist. Finally, we showed that in HL-1 myocytes and isolated hearts during IR, JNK inhibition significantly inhibited the phosphorylation of CaMKII induced by GSK101 but CaMKII inhibition had no effect on JNK activation induced by GSK101. Our data suggest that TRPV4 activation exacerbates myocardial IR injury via the JNK-CaMKII phosphorylation pathway.
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http://dx.doi.org/10.1016/j.ceca.2021.102483DOI Listing
October 2021

Cancer immunogenic cell death via photo-pyroptosis with light-sensitive Indoleamine 2,3-dioxygenase inhibitor conjugate.

Biomaterials 2021 Sep 30;278:121167. Epub 2021 Sep 30.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, PR China; State Key Laboratory of Fine Chemicals, Shenzhen Research Institute, Dalian University of Technology, Nanshan District, Shenzhen, 518057, PR China. Electronic address:

Immune checkpoint blockade (ICB) therapy currently considered as to be effective way to cure cancer in clinic. However, the insufficient tumor immunogenicity and the immunosuppressive tumor microenvironment always result in diminished efficacy of immunotherapy. Herein, we report the synthesis of an organic photo-immune activator NBS-1MT, the combination of photosensitizer and Indoleamine 2,3-dioxygenase (IDO) inhibitor effectively stimulates lysosomes oxidative stress the releases inflammatory cytokines. This process triggers pyroptosis for the considerable immunogenic cell death (ICD) while reversing suppressive tumor microenvironment. The photo-immune drug shows outstanding potential to activate caspase-1and then remove gasdermin-D (GSDMD), which could stimulate pyroptosis and also inhibit the tumor growth successfully in both primary and distant tumor. Furthermore, pyroptosis activated by photodynamic therapy (PDT) promotes the immune related factors release, and enhance the intratumoral infiltration of cytotoxic T lymphocytes (CTLs) with the induction of ICD of tumor cells and the cascaded synergize with IDO inhibitor, so the general antitumor immune response could be strengthened effectively. Our research confirms that the use of NBS-1MT is a promising strategy to boost the immune response and eventually to inhibit tumor growth.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121167DOI Listing
September 2021

[Preparation and Release Properties of Recombinant Protein PLGA Microspheres and PLGA-Chitosan Microspheres].

Sichuan Da Xue Xue Bao Yi Xue Ban 2021 Sep;52(5):794-798

Department of Pathogenic Biology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610041, China.

Objective: To preparethe poly lactic-co-glycolic acid (PLGA) microspheres and PLGA-chitosan microspheres containing recombinant protein, namely the BIB protein, and to explore their optimal preparation parameters and release performance in gastric and intestinal fluids.

Methods: Double emulsions (water-in-oil-in-water, or W1/O/W2) solvent evaporation method was used to prepare the BIB-PLGA microspheres and the BIB-PLGA-chitosan microspheres. Univariate analysis was done to study the impact of the water-to-oil ratio (W1/O), PLGA mass fraction and PVA concentration on the morphology, particle size, polydispersity index (PDI), encapsulation efficiency (EE), and drug loading (DL) so as to identify the optimal parameters. Bicinchoninic acid (BCA) assay was used to determine the protein concentration and the release efficiency of BIB.

Results: The optimal preparation parameters identified in the study were as follows: W1/O at 1∶2, PLGA mass fraction at 5%, and PVA mass fraction at 0.2%. The BIB-PLGA microspheres were found to be (2.11±0.08) μm in particle size, 0.35±0.18 in PDI, (78.20±1.73)% in EE and (10.58±0.23)% in DL. The BIB-PLGA-chitosan microspheres were (2.28±0.52) μm in particle size, 0.39±0.54 in PDI, and (78.87±1.30)% and (15.50±0.25)% in EE and DL, respectively. Both BIB-PLGA microspheres and BIB-PLGA-chitosan microspheres showed slow-release property in gastric and intestinal fluids , with BIB-PLGA-chitosan microspheres showing better slow-release performance.

Conclusion: The BIB-PLGA microspheres and BIB-PLGA-chitosan microspheres prepared with the double emulsions solvent evaporation method showed high DL and EE, controllable particle sizes, dispersive appearance, and slow-release property in gastric and intestinal fluids .
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http://dx.doi.org/10.12182/20210960208DOI Listing
September 2021

Multifunctional Macroassembled Graphene Nanofilms with High Crystallinity.

Adv Mater 2021 Oct 8:e2104195. Epub 2021 Oct 8.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, 38 Zheda Road, Hangzhou, 310027, P. R. China.

A "cooling-contraction" method to separate large-area (up to 4.2 cm in lateral size) graphene oxide (GO)-assembled films (of nanoscale thickness) from substrates is reported. Heat treatment at 3000 °C of such free-standing macroscale films yields highly crystalline "macroassembled graphene nanofilms" (nMAGs) with 16-48 nm thickness. These nMAGs present tensile strength of 5.5-11.3 GPa (with ≈3 µm gauge length), electrical conductivity of 1.8-2.1 MS m , thermal conductivity of 2027-2820 W m K , and carrier relaxation time up to ≈23 ps. As a demonstration application, an nMAG-based sound-generator shows a 30 µs response and sound pressure level of 89 dB at 1 W cm . A THz metasurface fabricated from nMAG has a light response of 8.2% for 0.159 W mm and can detect down to 0.01 ppm of glucose. The approach provides a straightforward way to form highly crystallized graphene nanofilms from low-cost GO sheets.
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http://dx.doi.org/10.1002/adma.202104195DOI Listing
October 2021

Non-Invasive Electrochemical Biosensors for TNF-α Cytokines Detection in Body Fluids.

Front Bioeng Biotechnol 2021 21;9:701045. Epub 2021 Sep 21.

State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun, China.

The measurement of pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-α), which is an important indicator of the inflammatory process, has received increasing attention recently because it is easy to extract from body fluid and serves as an early sign of a serious systemic inflammatory disease. Developing fast and simple detection methods to quantify the concentration of TNF-α is essential. Saliva, tears, and urine, which can easily be sampled in a non-invasive way, are considered to be important matrices for monitoring and assessing the physiological status of humans; importantly, they also provide an ideal window for monitoring the concentration of TNF-α. As a fast, accurate, inexpensive, portable, and scalable method, electrochemical biosensors are very promising for biomarker detection in matrices obtained in a non-invasive manner. This review summarises and compares the electrochemical biosensors for the detection of TNF-α in a non-invasive manner and highlights recent advances and future prospects in developing high-performance electrochemical platforms for noninvasive measurement of TNF-α.
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http://dx.doi.org/10.3389/fbioe.2021.701045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490748PMC
September 2021

Cardiac ectopic lymphoid follicle formation in viral myocarditis involving the regulation of podoplanin in Th17 cell differentiation.

FASEB J 2021 Nov;35(11):e21975

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Autoimmunity contributes to the pathogenesis of viral myocarditis (VMC), which is characterized by the production of anti-heart autoantibodies (AHA) from lymphoid follicles. Recently, the formation of ectopic lymphoid follicles (ELFs) was reported in heart grafts. However, the existence and role of ELFs in myocardial tissues of VMC remain unclear. This study aimed to explore whether and how cardiac ELFs with germinal centers (GCs) could be generated during the development of VMC. We identified the existence of ELFs and explored the underlying mechanism. In a BALB/c mouse model of VMC, the dynamic myocardial infiltrations of lymphocytic aggregates and expressions of associated lymphorganogenic factors were investigated, accompanied by the detection of the production and location of myocardial AHA. The data indicated ELFs formation in myocardial tissues of VMC, and the number of ELFs was in accordance with the severity of VMC. Moreover, the functional ELFs with GCs were capable of facilitating the production of local AHA. Blocking IL-17 or podoplanin (PDPN) could inhibit cardiac ELFs generation, perhaps due to the negative regulation of PDPN neutralization in Th17 cell proliferation and differentiation. The presence of cardiac ELFs and AHA might offer new opportunities for stratification and early identification of VMC patients.
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http://dx.doi.org/10.1096/fj.202101050RRDOI Listing
November 2021

Magnetic field and temperature two-parameter sensor based on optical microfiber coupler interference (OMCI) wrapped with magnetic fluid and PDMS.

Opt Express 2021 Aug;29(18):29492-29504

In this paper, an optical fiber magnetic field and temperature sensor based on an optical microfiber coupler (OMC), Polydimethylsiloxane (PDMS), and magnetic fluid (MF) is proposed, and its magnetic field and temperature sensing characteristics are analyzed theoretically and verified experimentally. Based on the OMC and using MF as the sensing medium, the sensor can respond to the magnetic field and temperature respectively after encapsulated by PDMS. The experimental results show that the maximum magnetic field sensitivity is 96.8 pm/Oe, and the maximum temperature sensitivity is 919.1 pm/°C. To overcome the cross-sensitivity of the magnetic field and temperature of the sensor, the sensitivity matrix is established and demodulated. In addition, we discuss the optimization of the sensitivity demodulation matrix by the size design of the PDMS package and the OMC structure. The proposed two-parameter sensor in this article has the advantages of high sensitivity, low cost, small volume and high integration, which is of great significance for the multi-parameter sensing of basic physical parameters such as magnetic field and temperature.
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http://dx.doi.org/10.1364/OE.435864DOI Listing
August 2021

Stability and bioavailability of protein matrix-encapsulated astaxanthin ester microcapsules.

J Sci Food Agric 2021 Oct 6. Epub 2021 Oct 6.

College of Food Science and Engineering, Ocean University of China, Qingdao, China.

Background: Astaxanthin ester derived from Haematococcus pluvialis is often used as a functional and nutritional ingredient in foods. However, its utilization is currently limited as a result of its chemical instability and low bioavailability. Food matrix microcapsules are becoming increasingly popular because of their safety and high encapsulation efficiency. In the present study, the effect of protein matrixes on the properties of microcapsules was evaluated.

Results: We investigated the effects of storage on astaxanthin ester microcapsules and the corresponding rehydration solution at 40 °C under a nitrogen atmosphere, as well as in darkness. The results showed that the stability of products prepared based on whey protein (WP) and corn-gluten was superior to that of products prepared based on lactoferrin, soy protein and sodium caseinate. The bioavailability of astaxanthin ester microcapsules encapsulated with different proteins and examined by means of astaxanthin concentrations in the serum and liver after oral administration was compared. All five protein wall materials could significantly improve the bioavailability of astaxanthin ester. The microcapsules prepared based on WP had the highest bioavailability, with a value of 10.69 ± 0.75 μg·h mL , which was 3.15 times higher compared to that of the control group.

Conclusion: The results of the present study showed that protein encapsulation, especially WP encapsulation, could effectively improve the stability, water solubility and bioavailability of astaxanthin esters. Thus, WP can be used as the main wall material in delivery systems. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11556DOI Listing
October 2021

Possibility of brigatinib-based therapy, or chemotherapy plus anti-angiogenic treatment after resistance of osimertinib harboring EGFR T790M-cis-C797S mutations in lung adenocarcinoma patients.

Cancer Med 2021 Oct 6. Epub 2021 Oct 6.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: There was no standard treatment for patients who acquired resistance to osimertinib mediated by epidermal growth factor receptor (EGFR) T790M-cis-C797S. The aim of this study was to investigate the association between different therapeutic strategies and survival outcomes among these patients.

Methods: This retrospective cohort study analyzed 46 patients with metastatic lung adenocarcinoma and EGFR T790M-cis-C797S after osimertinib progression from January 1, 2017 to October 31, 2020. Among them, 13 patients received brigatinib-based therapy, 23 patients received chemotherapy in combination of anti-angiogenics or not, and 10 patients received other targeted treatments like dacomtinib, bevacizumab, or a combined therapy of osimertinib and other targeted drugs.

Results: Compared to other targeted therapy, brigatinib-based therapy (median progression-free survival [mPFS]: 4.40 vs. 1.63 months, hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.21-0.73, p = 0.001) and chemotherapy-based treatment (mPFS: 4.70 vs. 1.63 months, HR = 0.18, 95% CI: 0.06-0.50, p < 0.001) presented a better survival outcome and there was no significant difference between brigatinib-based therapy and chemotherapy-based treatment (mPFS: 4.40 vs. 4.70 months, HR = 1.24, 95% CI: 0.57-2.67, p = 0.58). Chemotherapy combined with anti-angiogenics achieved a better efficacy than only chemotherapy (mPFS: 5.50 vs. 1.03 months, HR = 0.30, 95% CI: 0.11-0.83, p = 0.02). Patients carrying EGFR exon 19 deletion mutation had a longer PFS than those who harboring EGFR exon 21 p.L858R mutation (4.57 vs. 1.03 months, HR = 0.18, 95% CI: 0.06-0.54, p = 0.001), no matter they received brigatinib-based therapy (mPFS: 5.00 vs. 3.23 months, HR = 0.19, 95% CI: 0.01-0.96, p = 0.05) or chemotherapy-based treatment (mPFS: 7.23 vs. 1.03 months, HR = 0.05, 95% CI 0.01-0.49, p < 0.001).

Conclusion: Brigatinib-based therapy and chemotherapy plus anti-angiogenics could be considered beyond progression from osimertinib therapy. For patients harboring EGFR exon 19 deletion/T790M/cis-C797S mutation, the clinical efficacy was superior to patients harboring EGFR exon 21 p.L858R/T790M/cis-C797S mutation.
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http://dx.doi.org/10.1002/cam4.4336DOI Listing
October 2021

Intensified antiplatelet therapy in patients after percutaneous coronary intervention with high on-treatment platelet reactivity: the OPTImal Management of Antithrombotic Agents (OPTIMA)-2 Trial.

Br J Haematol 2021 Oct 5. Epub 2021 Oct 5.

Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

High on-treatment platelet reactivity (HOPR) is associated with increased risk of cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). We randomised post-PCI patients with HOPR after 5 days of standard dual antiplatelet therapy (DAPT) to intensified therapy with aspirin 100 mg once daily in combination with either clopidogrel 150 mg once daily, clopidogrel 75 mg once daily plus cilostazol 100 mg twice daily, ticagrelor 90 mg twice daily, or standard therapy with clopidogrel 75 mg once daily (STD) for 1 month, after which all patients were switched to standard DAPT for a further 11 months. The primary outcome was residual HOPR rate at 1 month. We screened 1724 patients with light transmission aggregation studies and randomised 434 with HOPR. At 1 month the proportion of patients with persistent HOPR was significantly lower in the intensified therapy groups compared with STD group. Compared to the group receiving STD therapy, those receiving intensified therapy had significantly lower rate of major adverse cardiovascular events (MACE) at both 1 month and 12 months with no significant increase in bleeding. In patients with post-PCI HOPR, 1 month of intensified antiplatelet therapy provides greater platelet inhibition and improves outcomes without increasing bleeding. Clinical Trial Registration URL: http://www.clinicaltrials.gov; Unique Identifier: NCT01955200.
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http://dx.doi.org/10.1111/bjh.17847DOI Listing
October 2021

A wider field of view to predict expression.

Nat Methods 2021 Oct;18(10):1155-1156

Department of Genome Sciences, University of Washington, Seattle, WA, USA.

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http://dx.doi.org/10.1038/s41592-021-01259-4DOI Listing
October 2021

Inhibitory Effect on Acrolein by Cyanidin-3--glucoside and Its Acrolein Adducts from the Pigment of Mynica Red.

J Agric Food Chem 2021 Oct 4;69(40):11937-11946. Epub 2021 Oct 4.

Department of Food Science and Technology, School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, 2 Xuelin Road, Nanjing, Jiangsu 210023, People's Republic of China.

Acrolein (ACR), the simplest α,β-unsaturated aldehyde, possesses high reactivity and toxicity both and and results in various chronic diseases. This has attracted increasing interest from researchers to screen various bioactive compounds to control it. In this article, we attempted to discover a new attribute of cyanidin-3--glucoside (C3G), including its ACR-scavenging capacity, reaction pathway, and possible application. Our findings revealed that C3G could capture ACR to form mono- and diadducts at room temperature by using liquid chromatography-mass spectrometry, and we further synthesized and elucidated the structures of C3G-ACR and C3G-2ACR using HRMS and 2D NMR. The structural data validated that there were two active sites of C3G for trapping ACR: at C-6 in the A-ring and C-5' in the B-ring. In addition, we found that C3G-ACR exhibited a more remarkable clearing ability than C3G within a short time. More than 65.9% of ACR was eliminated by C3G-ACR within 5 min further formation of C3G-2ACR, but there was no obvious effect of C3G on ACR. When the incubation time was extended to 120 min, C3G could remove up to 83.2% of ACR. Subsequently, we also observed that mynica red (>5% C3G), as a pigmented food additive, could efficiently eliminate ACR generated in the Chinese liquor model and real red bayberry wine products to form C3G-ACR and C3G-2ACR. Both adducts increased significantly, by 10 times to a 100 times, after adding mynica red to red bayberry wine products for 24 h; they also increased rapidly with prolonged incubation time in the liquor-mynica red model system. Therefore, our findings suggest that C3G or mynica red may be developed as a promising novel ACR inhibitor in fruit wine and assembled alcoholic drinks or as a health food.
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http://dx.doi.org/10.1021/acs.jafc.1c05223DOI Listing
October 2021
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