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Article: Evaluation of the Antibacterial Activity of New Dermaseptin Derivatives against

Haddad, Houda / Mejri, Radhia / de Araujo, Alyne Rodrigues / Zaïri, Amira

2024 Volume 17, Issue 2

Abstract: Nosocomial infections represent one of the biggest health problems nowadays. ...

Abstract	Nosocomial infections represent one of the biggest health problems nowadays.
Language	English
Publishing date	2024-01-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph17020171
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Article: DOPE/CHEMS-Based EGFR-Targeted Immunoliposomes for Docetaxel Delivery: Formulation Development, Physicochemical Characterization and Biological Evaluation on Prostate Cancer Cells.

Moreira, Thais da Silva / Silva, Alan Denis Olivindo / Vasconcelos, Bianca Rodrigues Farias / Santos, Elias da Silva / de Sousa, Ana Carolina Cruz / de Freitas, João Vito Barroso / de Oliveira, Yara Santiago / Vidal, Laura Maria Teodorio / Ribeiro, Fábio de Oliveira Silva / de Araújo, Alyne Rodrigues / Vieira Neto, José de Brito / Pessoa, Cláudia do Ó / Petrilli, Raquel / Eloy, Josimar O

Pharmaceutics

2023 Volume 15, Issue 3

Abstract: Docetaxel (DTX) is a non-selective antineoplastic agent with low solubility and a series of side effects. The technology of pH-sensitive and anti-epidermal growth factor receptor (anti-EGFR) immunoliposomes aims to increase the selective delivery of the ... ...

Abstract	Docetaxel (DTX) is a non-selective antineoplastic agent with low solubility and a series of side effects. The technology of pH-sensitive and anti-epidermal growth factor receptor (anti-EGFR) immunoliposomes aims to increase the selective delivery of the drug in the acidic tumor environment to cells with EFGR overexpression. Thus, the study aimed to develop pH-sensitive liposomes based on DOPE (dioleoylphosphatidylethanolamine) and CHEMS (cholesteryl hemisuccinate), using a Box-Behnken factorial design. Furthermore, we aimed to conjugate the monoclonal antibody cetuximab onto liposomal surface, as well as to thoroughly characterize the nanosystems and evaluate them on prostate cancer cells. The liposomes prepared by hydration of the lipid film and optimized by the Box-Behnken factorial design showed a particle size of 107.2 ± 2.9 nm, a PDI of 0.213 ± 0.005, zeta potential of -21.9 ± 1.8 mV and an encapsulation efficiency of 88.65 ± 20.3%. Together, FTIR, DSC and DRX characterization demonstrated that the drug was properly encapsulated, with reduced drug crystallinity. Drug release was higher in acidic pH. The liposome conjugation with the anti-EGFR antibody cetuximab preserved the physicochemical characteristics and was successful. The liposome containing DTX reached an IC
Language	English
Publishing date	2023-03-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15030915
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Article ; Online: Natural cordiaquinones as strategies to inhibit the growth and biofilm formation of methicillin-sensitive and methicillin-resistant Staphylococcus spp.

de Oliveira, Mariana Araújo / Barros, Ayslan Batista / de Araújo, Gisele Santos / de Araújo, Alyne Rodrigues / José Dos Santos Soares, Maria / de Oliveira, Daiane Fernandes / Lima, Filipe Camargo Dalmatti Alves / Batagin-Neto, Augusto / Leite, José Roberto de Souza de Almeida / Cesário, Hozana Patrícia Silva de Freitas / Pessoa, Otília Deusdênia Loiola / Filho, José Delano Barreto Marinho / Araújo, Ana Jérsia

Journal of applied microbiology

2023 Volume 134, Issue 8

Abstract: Aims: The aim of this study was to investigate the antibacterial and antibiofilm potential of cordiaquinones B, E, L, N, and O against different Staphylococci strains, in addition to analyzing in silico the observed effect.: Methods and results: The ... ...

Abstract	Aims: The aim of this study was to investigate the antibacterial and antibiofilm potential of cordiaquinones B, E, L, N, and O against different Staphylococci strains, in addition to analyzing in silico the observed effect. Methods and results: The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined according to CLSI guidelines. The inhibition of biofilm formation was investigated at sub-MICs. Atomic force microscopy (AFM) and density functional theory method were performed. The tested strains of Staphylococcus spp. were susceptible to cordiaquinones B, E, and L, among which cordiaquinone B exerted a bactericidal effect, confirmed by a bacterial growth curve study, against Staphylococcus saprophyticus. Cordiaquinones B and E showed lowest MBC values against S. saprophyticus. AFM revealed that cordiaquinone L reduced the mean cell size of S. saprophyticus. Cordiaquinones B and E inhibited the biofilm formation ability of S. aureus by ∼90%. The in silico analysis suggested that the antimicrobial activity of cordiaquinones is driven by their electron donation capability. Conclusions: Cordiaquinones inhibit the growth and biofilm formation (virulence factor) of both methicillin-sensitive and methicillin-resistant Staphylococci strains, indicating their antimicrobial potential.
MeSH term(s)	Methicillin-Resistant Staphylococcus aureus/drug effects ; Biofilms/drug effects ; Naphthoquinones/pharmacology ; Anti-Bacterial Agents/pharmacology ; Computer Simulation ; Microbial Sensitivity Tests ; Cordia/chemistry ; Plant Extracts/isolation & purification ; Plant Extracts/pharmacology ; Microbial Viability/drug effects
Chemical Substances	Naphthoquinones ; Anti-Bacterial Agents ; Plant Extracts
Language	English
Publishing date	2023-08-08
Publishing country	England
Document type	Journal Article
ZDB-ID	1358023-1
ISSN	1365-2672 ; 1364-5072
ISSN (online)	1365-2672
ISSN	1364-5072
DOI	10.1093/jambio/lxad162
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Article: Human Mesenchymal Stem Cells Seeded on the Natural Membrane to Neurospheres for Cholinergic-like Neurons.

Stricker, Priscila Elias Ferreira / de Souza Dobuchak, Daiany / Irioda, Ana Carolina / Mogharbel, Bassam Felipe / Franco, Celia Regina Cavichiolo / de Souza Almeida Leite, José Roberto / de Araújo, Alyne Rodrigues / Borges, Felipe Azevedo / Herculano, Rondinelli Donizetti / de Oliveira Graeff, Carlos Frederico / Chachques, Juan Carlos / de Carvalho, Katherine Athayde Teixeira

Membranes

2021 Volume 11, Issue 8

Abstract: This study aimed to differentiate human mesenchymal stem cells (hMSCs) from the human umbilical cord in cholinergic-like neurons using a natural membrane. The isolation of hMSCs from Wharton's jelly (WJ) was carried out using "explant" and mononuclear ... ...

Abstract	This study aimed to differentiate human mesenchymal stem cells (hMSCs) from the human umbilical cord in cholinergic-like neurons using a natural membrane. The isolation of hMSCs from Wharton's jelly (WJ) was carried out using "explant" and mononuclear cells by the density gradient from umbilical blood and characterized by flow cytometry. hMSCs were seeded in a natural functional biopolymer membrane to produce neurospheres. RT-PCR was performed on hMSCs and neurospheres derived from the umbilical cord. Neural precursor cells were subjected to a standard cholinergic-like neuron differentiation protocol. Dissociated neurospheres, neural precursor cells, and cholinergic-like neurons were characterized by immunocytochemistry. hMSCs were CD73+, CD90+, CD105+, CD34- and CD45- and demonstrated the trilineage differentiation. Neurospheres and their isolated cells were nestin-positive and expressed NESTIN, MAP2, ßIII-TUBULIN, GFAP genes. Neural precursor cells that were differentiated in cholinergic-like neurons expressed ßIII-TUBULIN protein and choline acetyltransferase enzyme. hMSCs seeded on the natural membrane can differentiate into neurospheres, obtaining neural precursor cells without growth factors or gene transfection before cholinergic phenotype differentiation.
Language	English
Publishing date	2021-08-07
Publishing country	Switzerland
Document type	Journal Article
ISSN	2077-0375
ISSN	2077-0375
DOI	10.3390/membranes11080598
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Article: Nanoemulsion of cashew gum and clove essential oil (Ocimum gratissimum Linn) potentiating antioxidant and antimicrobial activity

Araujo, Thais Danyelle Santos / da Costa, João Marcos Antônio Rodrigues / de Oliveira Silva Ribeiro, Fabio / de Jesus Oliveira, Antonia Carla / do Nascimento Dias, Jhones / de Araujo, Alyne Rodrigues / Barros, Ayslan Batista / da Paixão Brito, Manoel / de Oliveira, Taiane Maria / de Almeida, Miguel Peixoto / de Carvalho Castro, Karina Neoob / dos Santos Fogaça, Fabíola Helena / da Silva, Durcilene Alves / de Souza, Bartolomeu Warlene Silva

International journal of biological macromolecules. 2021 Dec. 15, v. 193

2021

Abstract: In this study, nanoemulsions of essential oil from Ocimumgratissimum (Linn) (EO) were produced using low and high energy techniques using cashew gum (CG) as a co-surfactant. The main constituents of the EO were determined by Gas Chromatography coupled ... ...

Abstract	In this study, nanoemulsions of essential oil from Ocimumgratissimum (Linn) (EO) were produced using low and high energy techniques using cashew gum (CG) as a co-surfactant. The main constituents of the EO were determined by Gas Chromatography coupled with Mass Spectrometry (GC–MS), and their presence in the EO and in the formulations verified by Fourier Transform Infrared Spectroscopy (FTIR) and UV–visible spectrophotometry was observed the encapsulation efficiency (EE%), with colloidal stability. Nuclear magnetic resonance (NMR) was used to study cashew gum. Dynamic light scattering analysis (DLS) determined the nanoemulsion Z means, polydispersity index and the Zeta potential value, nanoparticle tracking analysis (NTA) were determined. The nanostructured EO showed better antibacterial action against the pathogenic gastroenteritis species Staphylococcus aureus, Escherichia coli and Salmonella enterica when compared to free EO. Atomic Force Microscopy (AFM) was used for morphological analysis of the nanoparticle and study of the action of the nanoemulsion through images of the cellular morphology of S. enterica. The antioxidant activity was evaluated against the ABTS radical (2,2′-azino-bis diazonium salt (3-ethylbenzothiazoline-6-sulfonic acid)). The encapsulation of EO in a nanostructured system improved its antibacterial and antioxidant activity, the low energy synthesis showed greater storage stability, remaining stable for 37 days.
Keywords	Escherichia coli ; Fourier transform infrared spectroscopy ; Ocimum gratissimum ; Salmonella enterica ; Staphylococcus aureus ; antibacterial properties ; antioxidant activity ; antioxidants ; atomic force microscopy ; cashew gum ; diazonium compounds ; encapsulation ; energy ; essential oils ; gastroenteritis ; nanoemulsions ; nuclear magnetic resonance spectroscopy ; storage quality ; ultraviolet-visible spectroscopy ; zeta potential
Language	English
Dates of publication	2021-1215
Size	p. 100-108.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2021.09.195
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Antimicrobial and antibiofilm activity of the benzoquinone oncocalyxone A.

da Silva, Raí Emanuel / Ribeiro, Fábio de Oliveira Silva / de Carvalho, Andressa Maria A / Daboit, Tatiane Caroline / Marinho-Filho, José Delano Barreto / Matos, Taynara Simão / Pessoa, Otília Deusdênia Loiola / de Souza de Almeida Leite, José Roberto / de Araújo, Alyne Rodrigues / Dos Santos Soares, Maria José

Microbial pathogenesis

2020 Volume 149, Page(s) 104513

Abstract: Resistance to antimicrobials is a challenging issue that complicates the treatment of infections caused by bacteria and fungi, thus requiring new therapeutic options. Oncocalyxone A, a benzoquinone obtained from Auxemma oncocalyx (Allem) Taub has several ...

Abstract	Resistance to antimicrobials is a challenging issue that complicates the treatment of infections caused by bacteria and fungi, thus requiring new therapeutic options. Oncocalyxone A, a benzoquinone obtained from Auxemma oncocalyx (Allem) Taub has several biological effects; however, there is no data on its antimicrobial action. In this study, its antimicrobial and antibiofilm activities were evaluated against bacteria and fungi of clinical interest. Strains of Gram-positive and Gram-negative bacteria, and filamentous fungi and yeasts were selected to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of oncocalyxone A. The antibacterial effect of oncocalyxone A was studied using survival curves, atomic force microscopy (AFM), and the involvement of oxidative stress. We examined the inhibitory action of the molecule on biofilm formation and its hemolytic activity against human erythrocytes. Our results showed that among the strains tested, Staphylococcus epidermidis was highly sensitive to the action of oncocalyxone A, with an MIC of 9.43 μg/mL. In most bacterial strains analyzed, a bacteriostatic effect was observed, though the molecule showed no antifungal activity. Antibiofilm activity was observed against the methicillin-resistant S. aureus bacteria. Additionally, results from atomic force microscopy imaging showed that oncocalyxone A significantly altered bacterial morphology. Further, oncocalyxone A showed no hemolytic activity at concentrations ≥151 μg/mL. Together, our results demonstrate the antibacterial and antibiofilm potential of oncocalyxone A, indicating its therapeutic potential against bacterial resistance.
MeSH term(s)	Anthraquinones ; Anti-Bacterial Agents/pharmacology ; Benzoquinones/pharmacology ; Biofilms ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Humans ; Methicillin-Resistant Staphylococcus aureus ; Microbial Sensitivity Tests
Chemical Substances	Anthraquinones ; Anti-Bacterial Agents ; Benzoquinones ; oncocalyxone A
Language	English
Publishing date	2020-09-17
Publishing country	England
Document type	Journal Article
ZDB-ID	632772-2
ISSN	1096-1208 ; 0882-4010
ISSN (online)	1096-1208
ISSN	0882-4010
DOI	10.1016/j.micpath.2020.104513
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Article ; Online: Anti-proliferative profile of Anacardium occidentale polysaccharide and characterization by AFM.

de Oliveira Silva Ribeiro, Fábio / de França Dourado, Flaviane / Silva, Maria Francilene Souza / Brito, Lucas Moreira / Pessoa, Claudia / de Lima, Laís Ramos Monteiro / de Paula, Regina Célia Monteiro / de Souza de Almeida Leite, José Roberto / de Araújo, Alyne Rodrigues / da Silva, Durcilene Alves

International journal of biological macromolecules

2020 Volume 156, Page(s) 981–987

Abstract: This paper explores the application of cashew gum (CG) as an in vitro antiproliferative, firstly by isolating and characterizing the gum using elemental analysis, gel-permeation chromatography, nuclear magnetic resonance (NMR) and atomic force microscopy ...

Abstract	This paper explores the application of cashew gum (CG) as an in vitro antiproliferative, firstly by isolating and characterizing the gum using elemental analysis, gel-permeation chromatography, nuclear magnetic resonance (NMR) and atomic force microscopy (AFM). The molar mass of isolated CG was in the order of 10
MeSH term(s)	Anacardium/chemistry ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Biocompatible Materials/chemistry ; Cell Line, Tumor ; Humans ; Magnetic Resonance Spectroscopy ; Microscopy, Atomic Force ; Plant Extracts/chemistry ; Plant Extracts/pharmacology ; Plant Gums/chemistry ; Polysaccharides/chemistry ; Polysaccharides/pharmacology
Chemical Substances	Antineoplastic Agents ; Biocompatible Materials ; Plant Extracts ; Plant Gums ; Polysaccharides
Language	English
Publishing date	2020-03-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2020.03.145
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Article ; Online: Antileishmanial activity of cordiaquinone E towards Leishmania (Leishmania) amazonensis.

Rodrigues, Raiza Raianne Luz / Nunes, Thaís Amanda Lima / de Araújo, Alyne Rodrigues / Marinho Filho, José Delano Barreto / da Silva, Marcos Vinícius / Carvalho, Fernando Aécio de Amorim / Pessoa, Otília Deusdenia Loiola / Freitas, Hozana Patrícia Silva / Rodrigues, Klinger Antonio da Franca / Araújo, Ana Jérsia

International immunopharmacology

2020 Volume 90, Page(s) 107124

Abstract: Leishmaniasis is caused by several protozoan species of Leishmania, and being endemically present in 98 countries around the world, it is also a severe public-health problem. The available antileishmanial drugs are toxic and yet present risks of ... ...

Abstract	Leishmaniasis is caused by several protozoan species of Leishmania, and being endemically present in 98 countries around the world, it is also a severe public-health problem. The available antileishmanial drugs are toxic and yet present risks of recurrent infection. Efforts to find new, effective, and safe oral agents for the treatment of leishmaniasis are continuing throughout the world. This work aimed to evaluate the antileishmania activity of cordiaquinone E (CORe), isolated from the roots of Cordia polycephala (Lam.) I. M. Johnston. Cytotoxicity, and possible mechanisms of action against promastigote and amastigote forms of Leishmania amazonensis were examined. CORe was effective in inhibiting promastigote (IC
MeSH term(s)	Animals ; Apoptosis/drug effects ; Cytokines/metabolism ; Dose-Response Relationship, Drug ; HL-60 Cells ; Host-Parasite Interactions ; Humans ; Leishmania mexicana/drug effects ; Leishmania mexicana/growth & development ; Leishmaniasis, Cutaneous/drug therapy ; Leishmaniasis, Cutaneous/metabolism ; Leishmaniasis, Cutaneous/parasitology ; Macrophages/drug effects ; Macrophages/metabolism ; Macrophages/parasitology ; Mice ; Naphthoquinones/pharmacology ; Naphthoquinones/toxicity ; Nitric Oxide/metabolism ; RAW 264.7 Cells ; Reactive Oxygen Species/metabolism ; Trypanocidal Agents/pharmacology ; Trypanocidal Agents/toxicity
Chemical Substances	Cytokines ; Naphthoquinones ; Reactive Oxygen Species ; Trypanocidal Agents ; Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2020-11-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2020.107124
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Article ; Online: Nanoemulsion of cashew gum and clove essential oil (Ocimum gratissimum Linn) potentiating antioxidant and antimicrobial activity.

Araujo, Thais Danyelle Santos / da Costa, João Marcos Antônio Rodrigues / de Oliveira Silva Ribeiro, Fabio / de Jesus Oliveira, Antonia Carla / do Nascimento Dias, Jhones / de Araujo, Alyne Rodrigues / Barros, Ayslan Batista / da Paixão Brito, Manoel / de Oliveira, Taiane Maria / de Almeida, Miguel Peixoto / de Carvalho Castro, Karina Neoob / Dos Santos Fogaça, Fabíola Helena / da Silva, Durcilene Alves / de Souza, Bartolomeu Warlene Silva

International journal of biological macromolecules

2021 Volume 193, Issue Pt A, Page(s) 100–108

Abstract	In this study, nanoemulsions of essential oil from Ocimumgratissimum (Linn) (EO) were produced using low and high energy techniques using cashew gum (CG) as a co-surfactant. The main constituents of the EO were determined by Gas Chromatography coupled with Mass Spectrometry (GC-MS), and their presence in the EO and in the formulations verified by Fourier Transform Infrared Spectroscopy (FTIR) and UV-visible spectrophotometry was observed the encapsulation efficiency (EE%), with colloidal stability. Nuclear magnetic resonance (NMR) was used to study cashew gum. Dynamic light scattering analysis (DLS) determined the nanoemulsion Z means, polydispersity index and the Zeta potential value, nanoparticle tracking analysis (NTA) were determined. The nanostructured EO showed better antibacterial action against the pathogenic gastroenteritis species Staphylococcus aureus, Escherichia coli and Salmonella enterica when compared to free EO. Atomic Force Microscopy (AFM) was used for morphological analysis of the nanoparticle and study of the action of the nanoemulsion through images of the cellular morphology of S. enterica. The antioxidant activity was evaluated against the ABTS radical (2,2'-azino-bis diazonium salt (3-ethylbenzothiazoline-6-sulfonic acid)). The encapsulation of EO in a nanostructured system improved its antibacterial and antioxidant activity, the low energy synthesis showed greater storage stability, remaining stable for 37 days.
MeSH term(s)	Anti-Bacterial Agents/chemistry ; Emulsions/chemistry ; Ocimum/metabolism ; Oils, Volatile/chemistry ; Plant Gums/chemistry ; Plant Leaves/metabolism
Chemical Substances	Anti-Bacterial Agents ; Emulsions ; Oils, Volatile ; Plant Gums
Language	English
Publishing date	2021-10-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2021.09.195
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Article ; Online: Curzerene antileishmania activity: Effects on Leishmania amazonensis and possible action mechanisms.

Nunes, Thaís Amanda de Lima / Santos, Malu Mateus / de Oliveira, Mariana Silva / de Sousa, Julyanne Maria Saraiva / Rodrigues, Raiza Raianne Luz / Sousa, Paulo Sérgio de Araujo / de Araújo, Alyne Rodrigues / Pereira, Anna Carolina Toledo da Cunha / Ferreira, Gustavo Portela / Rocha, Jefferson Almeida / Rodrigues Junior, Virmondes / da Silva, Marcos Vinicius / Rodrigues, Klinger Antonio da Franca

International immunopharmacology

2021 Volume 100, Page(s) 108130

Abstract: Leishmaniasis is a set of infectious diseases with high rates of morbidity and mortality, it affects millions of people around the world. Treatment, mainly with pentavalent antimonials, presents significant toxicity and many cases of resistance. In ... ...

Abstract	Leishmaniasis is a set of infectious diseases with high rates of morbidity and mortality, it affects millions of people around the world. Treatment, mainly with pentavalent antimonials, presents significant toxicity and many cases of resistance. In previous works we have demonstrated the effective and selective antileishmanial activity of Eugenia uniflora L. essential oil, being constituted (47.3%) by the sesquiterpene curzerene. Considering the high rate of parasite inhibition demonstrated for E. uniflora essential oil, and the significant presence of curzerene in the oil, this study aimed to evaluate its antileishmania activity and possible mechanisms of action. Curzerene was effective in inhibiting the growth of promastigotes (IC
MeSH term(s)	Animals ; Antiprotozoal Agents/pharmacology ; Antiprotozoal Agents/therapeutic use ; Apoptosis/drug effects ; Humans ; Interferon-gamma/metabolism ; Interleukin-10/metabolism ; Interleukin-12/metabolism ; Interleukin-6/metabolism ; Leishmania mexicana/drug effects ; Leishmania mexicana/growth & development ; Macrophages/drug effects ; Mice ; Mice, Transgenic ; Molecular Docking Simulation ; RAW 264.7 Cells ; Sesquiterpenes/pharmacology ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Antiprotozoal Agents ; Interleukin-6 ; Sesquiterpenes ; Tumor Necrosis Factor-alpha ; curzerene ; Interleukin-10 (130068-27-8) ; Interleukin-12 (187348-17-0) ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2021-09-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2021.108130
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