TY  - JOUR
AU  - Bruić, Marija
AU  - Pirković, Andrea
AU  - Borozan, Sunčica
AU  - Nacka-Aleksić, Mirjana
AU  - Jovanović-Krivokuća, Milica
AU  - Spremo-Potparević, Biljana
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5613
AB  - Oxidative stress has been implicated in numerous pregnancy-related disorders. Biologically active plant sec-
ondary metabolites, which are present in everyday diet, could prove effective therapeutic agents in preventing
these disorders. This study evaluated effects of taxifolin (dihydroquercetin) on ROS production, markers of
oxidative damage to lipids and proteins, activity of antioxidant enzymes and production of pro-inflammatory
cytokines in H2O2-induced oxidative stress in trophoblast HTR-8/SVneo cells. Taxifolin in 10 μM and 100 μM
concentrations attenuated oxidative damage to lipids and proteins, as evidenced by a decrease in MDA content,
extracellular LDH activity, carbonyl groups and nitrite contents. A reduction in the activity of antioxidant en-
zymes SOD, CAT and GPx in cells pre-treated with taxifolin, prior to H2O2 exposure, was also observed, along
with a reduction in intracellular ROS production. Both evaluated concentrations of taxifolin showed anti-
inflammatory activity in trophoblast cells, by reducing production of pro-inflammatory cytokines IL-1β and IL-
6. In this model of H2O2-induced oxidative stress, taxifolin showed marked antioxidative and anti-
inflammatory activities in trophoblast cells, adding further evidence of its protective effects and showing po-
tential as a therapeutic agent in preventing adverse pregnancy outcomes.
PB  - Elsevier
T2  - Reproductive Toxicology
T1  - Antioxidative and anti-inflammatory effects of taxifolin in H2O2-induced oxidative stress in HTR-8/SVneo trophoblast cell line
VL  - 126
SP  - 108585
DO  - 10.1016/j.reprotox.2024.108585
ER  - 

@article{
author = "Bruić, Marija and Pirković, Andrea and Borozan, Sunčica and Nacka-Aleksić, Mirjana and Jovanović-Krivokuća, Milica and Spremo-Potparević, Biljana",
year = "2024",
abstract = "Oxidative stress has been implicated in numerous pregnancy-related disorders. Biologically active plant sec-
ondary metabolites, which are present in everyday diet, could prove effective therapeutic agents in preventing
these disorders. This study evaluated effects of taxifolin (dihydroquercetin) on ROS production, markers of
oxidative damage to lipids and proteins, activity of antioxidant enzymes and production of pro-inflammatory
cytokines in H2O2-induced oxidative stress in trophoblast HTR-8/SVneo cells. Taxifolin in 10 μM and 100 μM
concentrations attenuated oxidative damage to lipids and proteins, as evidenced by a decrease in MDA content,
extracellular LDH activity, carbonyl groups and nitrite contents. A reduction in the activity of antioxidant en-
zymes SOD, CAT and GPx in cells pre-treated with taxifolin, prior to H2O2 exposure, was also observed, along
with a reduction in intracellular ROS production. Both evaluated concentrations of taxifolin showed anti-
inflammatory activity in trophoblast cells, by reducing production of pro-inflammatory cytokines IL-1β and IL-
6. In this model of H2O2-induced oxidative stress, taxifolin showed marked antioxidative and anti-
inflammatory activities in trophoblast cells, adding further evidence of its protective effects and showing po-
tential as a therapeutic agent in preventing adverse pregnancy outcomes.",
publisher = "Elsevier",
journal = "Reproductive Toxicology",
title = "Antioxidative and anti-inflammatory effects of taxifolin in H2O2-induced oxidative stress in HTR-8/SVneo trophoblast cell line",
volume = "126",
pages = "108585",
doi = "10.1016/j.reprotox.2024.108585"
}

Bruić, M., Pirković, A., Borozan, S., Nacka-Aleksić, M., Jovanović-Krivokuća, M.,& Spremo-Potparević, B.. (2024). Antioxidative and anti-inflammatory effects of taxifolin in H2O2-induced oxidative stress in HTR-8/SVneo trophoblast cell line. in Reproductive Toxicology
Elsevier., 126, 108585.
https://doi.org/10.1016/j.reprotox.2024.108585

Bruić M, Pirković A, Borozan S, Nacka-Aleksić M, Jovanović-Krivokuća M, Spremo-Potparević B. Antioxidative and anti-inflammatory effects of taxifolin in H2O2-induced oxidative stress in HTR-8/SVneo trophoblast cell line. in Reproductive Toxicology. 2024;126:108585.
doi:10.1016/j.reprotox.2024.108585 .

Bruić, Marija, Pirković, Andrea, Borozan, Sunčica, Nacka-Aleksić, Mirjana, Jovanović-Krivokuća, Milica, Spremo-Potparević, Biljana, "Antioxidative and anti-inflammatory effects of taxifolin in H2O2-induced oxidative stress in HTR-8/SVneo trophoblast cell line" in Reproductive Toxicology, 126 (2024):108585,
https://doi.org/10.1016/j.reprotox.2024.108585 . .

TY  - JOUR
AU  - Rajab Elferjane, Muna
AU  - Jovanović, Aleksandra A.
AU  - Milutinović, Violeta
AU  - Čutović, Natalija
AU  - Jovanović Krivokuća, Milica
AU  - Marinković, Aleksandar
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4956
AB  - In the study, the optimization of the extraction from Aloe vera leaf waste was performed via varying solid-to-solvent ratio, solvent type, extraction time, and technique (maceration, heat-, ultrasound-, and microwave-assisted extractions—HAE, UAE, and MAE, respectively). The optimal extraction conditions for achieving the highest polyphenol content are a 1:30 ratio, 70% ethanol, and 30 min of HAE. Total flavonoid and protein contents were significantly higher in the extract from MAE, while total condensed tannin content was the highest in HAE. LC-MS analysis quantified 13 anthraquinone and chromone compounds. The variations in the FT-IR spectra of the extracts obtained by different extraction procedures are minor. The influence of extraction conditions on the antioxidant ability of the extracts depended on applied antioxidant assays. The extracts possessed medium inhibition properties against Staphylococcus aureus and weak inhibitory activity against Enterococcus feacalis. The extracts had stimulative effect on HaCaT cell viability. Regarding the extraction yield, there was a significant difference between the used extraction techniques (MAE > HAE > maceration and UAE). The presented study is an initial step in the production of polyphenol-rich extracts from A. vera leaf waste aimed to be used for the potential preparation of pharmaceutical and cosmetic formulations for the skin.
PB  - MDPI
T2  - Plants
T1  - From Aloe vera Leaf Waste to the Extracts with Biological Potential: Optimization of the Extractions, Physicochemical Characterization, and Biological Activities
VL  - 12
IS  - 14
DO  - 10.3390/plants12142744
ER  - 

@article{
author = "Rajab Elferjane, Muna and Jovanović, Aleksandra A. and Milutinović, Violeta and Čutović, Natalija and Jovanović Krivokuća, Milica and Marinković, Aleksandar",
year = "2023",
abstract = "In the study, the optimization of the extraction from Aloe vera leaf waste was performed via varying solid-to-solvent ratio, solvent type, extraction time, and technique (maceration, heat-, ultrasound-, and microwave-assisted extractions—HAE, UAE, and MAE, respectively). The optimal extraction conditions for achieving the highest polyphenol content are a 1:30 ratio, 70% ethanol, and 30 min of HAE. Total flavonoid and protein contents were significantly higher in the extract from MAE, while total condensed tannin content was the highest in HAE. LC-MS analysis quantified 13 anthraquinone and chromone compounds. The variations in the FT-IR spectra of the extracts obtained by different extraction procedures are minor. The influence of extraction conditions on the antioxidant ability of the extracts depended on applied antioxidant assays. The extracts possessed medium inhibition properties against Staphylococcus aureus and weak inhibitory activity against Enterococcus feacalis. The extracts had stimulative effect on HaCaT cell viability. Regarding the extraction yield, there was a significant difference between the used extraction techniques (MAE > HAE > maceration and UAE). The presented study is an initial step in the production of polyphenol-rich extracts from A. vera leaf waste aimed to be used for the potential preparation of pharmaceutical and cosmetic formulations for the skin.",
publisher = "MDPI",
journal = "Plants",
title = "From Aloe vera Leaf Waste to the Extracts with Biological Potential: Optimization of the Extractions, Physicochemical Characterization, and Biological Activities",
volume = "12",
number = "14",
doi = "10.3390/plants12142744"
}

Rajab Elferjane, M., Jovanović, A. A., Milutinović, V., Čutović, N., Jovanović Krivokuća, M.,& Marinković, A.. (2023). From Aloe vera Leaf Waste to the Extracts with Biological Potential: Optimization of the Extractions, Physicochemical Characterization, and Biological Activities. in Plants
MDPI., 12(14).
https://doi.org/10.3390/plants12142744

Rajab Elferjane M, Jovanović AA, Milutinović V, Čutović N, Jovanović Krivokuća M, Marinković A. From Aloe vera Leaf Waste to the Extracts with Biological Potential: Optimization of the Extractions, Physicochemical Characterization, and Biological Activities. in Plants. 2023;12(14).
doi:10.3390/plants12142744 .

Rajab Elferjane, Muna, Jovanović, Aleksandra A., Milutinović, Violeta, Čutović, Natalija, Jovanović Krivokuća, Milica, Marinković, Aleksandar, "From Aloe vera Leaf Waste to the Extracts with Biological Potential: Optimization of the Extractions, Physicochemical Characterization, and Biological Activities" in Plants, 12, no. 14 (2023),
https://doi.org/10.3390/plants12142744 . .

TY  - JOUR
AU  - Pirković, Andrea
AU  - Lazić, Vesna
AU  - Spremo-Potparević, Biljana
AU  - Živković, Lada
AU  - Topalović, Dijana
AU  - Kuzman, Sanja
AU  - Antić-Stanković, Jelena
AU  - Božić, Dragana
AU  - Jovanović Krivokuća, Milica
AU  - Nedeljković, Jovan M.
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4919
AB  - Dry olive leaf extract (DOLE) and its active component oleuropein (OLE) were applied as reducing and stabilizing agents to prepare colloidal 20-25 nm silver nanoparticles (Ag NPs). The Ag NPs were characterized using transmission electron microscopy, X-ray diffraction analysis, and absorption spectroscopy. The cytotoxic actions of coated Ag NPs, and their inorganic and organic components, were examined against trophoblast cells and human peripheral blood lymphocytes (PBLs), Gram-positive, Gram-negative bacteria, and yeast. The genotoxic potential was evaluated in PBLs in vitro with the comet assay. Ag/DOLE and Ag/OLE induced cytotoxic effects in both types of cells after 24 h exposure when silver concentrations were 0.025-0.2 mM. However, the most pronounced cytotoxicity exhibits Ag/OLE. Both colloids also caused reduced ROS production in both cell types at 0.1 mM and 0.2 mM, while bare Ag NPs did not alter ROS levels at any of the conditions. Functionalized Ag/DOLE and Ag/OLE did not show genotoxic effects in PBLs, while bare AgNPs increased DNA damage significantly only at 0.2 mM. Regarding the antimicrobial effects, the Ag/OLE had MIC values for all evaluated microorganisms from 0.0625 to less than 0.0312 mM. Also, the antimicrobial effect of Ag/DOLE was significantly higher on Gram-negative bacteria and yeast than on Gram-positive bacteria. Obtained results indicate that Ag/OLE induced the most pronounced biological effects, beneficial for its application as an antimicrobial agent, but with potential risks from exposure to high concentrations that could induce cytotoxicity in healthy human cells.
PB  - Oxford University Press
T2  - Mutagenesis
T1  - Comparative analysis of Ag NPs functionalized with olive leaf extract and oleuropein and toxicity in human trophoblast cells and peripheral blood lymphocytes
VL  - 38
IS  - 3
SP  - 169
EP  - 181
DO  - 10.1093/mutage/gead013
ER  - 

@article{
author = "Pirković, Andrea and Lazić, Vesna and Spremo-Potparević, Biljana and Živković, Lada and Topalović, Dijana and Kuzman, Sanja and Antić-Stanković, Jelena and Božić, Dragana and Jovanović Krivokuća, Milica and Nedeljković, Jovan M.",
year = "2023",
abstract = "Dry olive leaf extract (DOLE) and its active component oleuropein (OLE) were applied as reducing and stabilizing agents to prepare colloidal 20-25 nm silver nanoparticles (Ag NPs). The Ag NPs were characterized using transmission electron microscopy, X-ray diffraction analysis, and absorption spectroscopy. The cytotoxic actions of coated Ag NPs, and their inorganic and organic components, were examined against trophoblast cells and human peripheral blood lymphocytes (PBLs), Gram-positive, Gram-negative bacteria, and yeast. The genotoxic potential was evaluated in PBLs in vitro with the comet assay. Ag/DOLE and Ag/OLE induced cytotoxic effects in both types of cells after 24 h exposure when silver concentrations were 0.025-0.2 mM. However, the most pronounced cytotoxicity exhibits Ag/OLE. Both colloids also caused reduced ROS production in both cell types at 0.1 mM and 0.2 mM, while bare Ag NPs did not alter ROS levels at any of the conditions. Functionalized Ag/DOLE and Ag/OLE did not show genotoxic effects in PBLs, while bare AgNPs increased DNA damage significantly only at 0.2 mM. Regarding the antimicrobial effects, the Ag/OLE had MIC values for all evaluated microorganisms from 0.0625 to less than 0.0312 mM. Also, the antimicrobial effect of Ag/DOLE was significantly higher on Gram-negative bacteria and yeast than on Gram-positive bacteria. Obtained results indicate that Ag/OLE induced the most pronounced biological effects, beneficial for its application as an antimicrobial agent, but with potential risks from exposure to high concentrations that could induce cytotoxicity in healthy human cells.",
publisher = "Oxford University Press",
journal = "Mutagenesis",
title = "Comparative analysis of Ag NPs functionalized with olive leaf extract and oleuropein and toxicity in human trophoblast cells and peripheral blood lymphocytes",
volume = "38",
number = "3",
pages = "169-181",
doi = "10.1093/mutage/gead013"
}

Pirković, A., Lazić, V., Spremo-Potparević, B., Živković, L., Topalović, D., Kuzman, S., Antić-Stanković, J., Božić, D., Jovanović Krivokuća, M.,& Nedeljković, J. M.. (2023). Comparative analysis of Ag NPs functionalized with olive leaf extract and oleuropein and toxicity in human trophoblast cells and peripheral blood lymphocytes. in Mutagenesis
Oxford University Press., 38(3), 169-181.
https://doi.org/10.1093/mutage/gead013

Pirković A, Lazić V, Spremo-Potparević B, Živković L, Topalović D, Kuzman S, Antić-Stanković J, Božić D, Jovanović Krivokuća M, Nedeljković JM. Comparative analysis of Ag NPs functionalized with olive leaf extract and oleuropein and toxicity in human trophoblast cells and peripheral blood lymphocytes. in Mutagenesis. 2023;38(3):169-181.
doi:10.1093/mutage/gead013 .

Pirković, Andrea, Lazić, Vesna, Spremo-Potparević, Biljana, Živković, Lada, Topalović, Dijana, Kuzman, Sanja, Antić-Stanković, Jelena, Božić, Dragana, Jovanović Krivokuća, Milica, Nedeljković, Jovan M., "Comparative analysis of Ag NPs functionalized with olive leaf extract and oleuropein and toxicity in human trophoblast cells and peripheral blood lymphocytes" in Mutagenesis, 38, no. 3 (2023):169-181,
https://doi.org/10.1093/mutage/gead013 . .

TY  - JOUR
AU  - Krstić, Sanja
AU  - Miljić, Milorad
AU  - Antić-Stanković, Jelena
AU  - Božić, Dragana
AU  - Jovanović Krivokuća, Milica
AU  - Pirković, Andrea
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5034
AB  - Methanolic pulp extracts from the four selected Serbian accessions of Cucurbita maxima were evaluated for phenol profile cytotoxic effects and antimicrobial activity. The results revealed that quinic acid and amentoflavone were the most abundant phenols. The extracts increased the viability of HTR-8 SV/Neo, JEG-3, JAR cells, with the most pronounced increase in the treatment with MAX 113 extract. Furthermore, in HeLa cells, the extracts showed a modest cytotoxic effect. The antimicrobial effects evaluation showed that out of four pumpkin extracts, MAX 117 could moderately suppress the growth of Staphylococcus aureus and Staphylococcus epidermidis (MIC=1000 µg/mL). The observed biological effects indicate the potential medicinal properties of these pumpkin extracts and contribute to the varietal selection of the most suitable accessions in national breeding programs as candidates for improving human health.
PB  - Elsevier Ltd
T2  - Food Chemistry Advances
T1  - Pumpkin pulp extracts from a Serbian Cucurbita maxima Breeding Collection: Phenol profile and in vitro bioactivity
VL  - 3
DO  - 10.1016/j.focha.2023.100395
ER  - 

@article{
author = "Krstić, Sanja and Miljić, Milorad and Antić-Stanković, Jelena and Božić, Dragana and Jovanović Krivokuća, Milica and Pirković, Andrea",
year = "2023",
abstract = "Methanolic pulp extracts from the four selected Serbian accessions of Cucurbita maxima were evaluated for phenol profile cytotoxic effects and antimicrobial activity. The results revealed that quinic acid and amentoflavone were the most abundant phenols. The extracts increased the viability of HTR-8 SV/Neo, JEG-3, JAR cells, with the most pronounced increase in the treatment with MAX 113 extract. Furthermore, in HeLa cells, the extracts showed a modest cytotoxic effect. The antimicrobial effects evaluation showed that out of four pumpkin extracts, MAX 117 could moderately suppress the growth of Staphylococcus aureus and Staphylococcus epidermidis (MIC=1000 µg/mL). The observed biological effects indicate the potential medicinal properties of these pumpkin extracts and contribute to the varietal selection of the most suitable accessions in national breeding programs as candidates for improving human health.",
publisher = "Elsevier Ltd",
journal = "Food Chemistry Advances",
title = "Pumpkin pulp extracts from a Serbian Cucurbita maxima Breeding Collection: Phenol profile and in vitro bioactivity",
volume = "3",
doi = "10.1016/j.focha.2023.100395"
}

Krstić, S., Miljić, M., Antić-Stanković, J., Božić, D., Jovanović Krivokuća, M.,& Pirković, A.. (2023). Pumpkin pulp extracts from a Serbian Cucurbita maxima Breeding Collection: Phenol profile and in vitro bioactivity. in Food Chemistry Advances
Elsevier Ltd., 3.
https://doi.org/10.1016/j.focha.2023.100395

Krstić S, Miljić M, Antić-Stanković J, Božić D, Jovanović Krivokuća M, Pirković A. Pumpkin pulp extracts from a Serbian Cucurbita maxima Breeding Collection: Phenol profile and in vitro bioactivity. in Food Chemistry Advances. 2023;3.
doi:10.1016/j.focha.2023.100395 .

Krstić, Sanja, Miljić, Milorad, Antić-Stanković, Jelena, Božić, Dragana, Jovanović Krivokuća, Milica, Pirković, Andrea, "Pumpkin pulp extracts from a Serbian Cucurbita maxima Breeding Collection: Phenol profile and in vitro bioactivity" in Food Chemistry Advances, 3 (2023),
https://doi.org/10.1016/j.focha.2023.100395 . .

TY  - JOUR
AU  - Sredojević, Dušan
AU  - Lazić, Vesna
AU  - Pirković, Andrea
AU  - Periša, Jovana
AU  - Murafa, Natalija
AU  - Spremo-Potparević, Biljana
AU  - Živković, Lada
AU  - Topalović, Dijana
AU  - Zarubica, Aleksandra
AU  - Jovanović Krivokuća, Milica
AU  - Nedeljković, Jovan
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4281
AB  - The antibacterial performance and cytotoxic examination of in situ prepared silver nanoparticles (Ag NPs), on inorganic-organic hybrid nanopowder consisting of zirconium dioxide nanoparticles (ZrO2 NPs) and dihydroquercetin (DHQ), was performed against Gram (−) bacteria Escherichia coli and Gram (+) bacteria Staphylococcus aureus, as well as against human cervical cancer cells HeLa and healthy MRC-5 human cells. The surface modification of ZrO2 NPs, synthesized by the sol-gel method, with DHQ leads to the interfacial charge transfer (ICT) complex formation indicated by the appearance of absorption in the visible spectral range. The prepared samples were thoroughly characterized (TEM, XRD, reflection spectroscopy), and, in addition, the spectroscopic observations are supported by the density functional theory (DFT) calculations using a cluster model. The concentration- and time-dependent antibacterial tests indicated a complete reduction of bacterial species, E. coli and S. aureus, for all investigated concentrations of silver (0.10, 0.25, and 0.50 mg/mL) after 24 h of contact. On the other side, the functionalized ZrO2 NPs with DHQ, before and after deposition of Ag NPs, do not display a significant decrease in the viability of HeLa MRC-5 cells in any of the used concentrations compared to the control
PB  - MDPI
T2  - Nanomaterials
T1  - Toxicity of Silver Nanoparticles Supported by Surface-Modified Zirconium Dioxide with Dihydroquercetin
VL  - 12
IS  - 18
DO  - 10.3390/nano12183195
ER  - 

@article{
author = "Sredojević, Dušan and Lazić, Vesna and Pirković, Andrea and Periša, Jovana and Murafa, Natalija and Spremo-Potparević, Biljana and Živković, Lada and Topalović, Dijana and Zarubica, Aleksandra and Jovanović Krivokuća, Milica and Nedeljković, Jovan",
year = "2022",
abstract = "The antibacterial performance and cytotoxic examination of in situ prepared silver nanoparticles (Ag NPs), on inorganic-organic hybrid nanopowder consisting of zirconium dioxide nanoparticles (ZrO2 NPs) and dihydroquercetin (DHQ), was performed against Gram (−) bacteria Escherichia coli and Gram (+) bacteria Staphylococcus aureus, as well as against human cervical cancer cells HeLa and healthy MRC-5 human cells. The surface modification of ZrO2 NPs, synthesized by the sol-gel method, with DHQ leads to the interfacial charge transfer (ICT) complex formation indicated by the appearance of absorption in the visible spectral range. The prepared samples were thoroughly characterized (TEM, XRD, reflection spectroscopy), and, in addition, the spectroscopic observations are supported by the density functional theory (DFT) calculations using a cluster model. The concentration- and time-dependent antibacterial tests indicated a complete reduction of bacterial species, E. coli and S. aureus, for all investigated concentrations of silver (0.10, 0.25, and 0.50 mg/mL) after 24 h of contact. On the other side, the functionalized ZrO2 NPs with DHQ, before and after deposition of Ag NPs, do not display a significant decrease in the viability of HeLa MRC-5 cells in any of the used concentrations compared to the control",
publisher = "MDPI",
journal = "Nanomaterials",
title = "Toxicity of Silver Nanoparticles Supported by Surface-Modified Zirconium Dioxide with Dihydroquercetin",
volume = "12",
number = "18",
doi = "10.3390/nano12183195"
}

Sredojević, D., Lazić, V., Pirković, A., Periša, J., Murafa, N., Spremo-Potparević, B., Živković, L., Topalović, D., Zarubica, A., Jovanović Krivokuća, M.,& Nedeljković, J.. (2022). Toxicity of Silver Nanoparticles Supported by Surface-Modified Zirconium Dioxide with Dihydroquercetin. in Nanomaterials
MDPI., 12(18).
https://doi.org/10.3390/nano12183195

Sredojević D, Lazić V, Pirković A, Periša J, Murafa N, Spremo-Potparević B, Živković L, Topalović D, Zarubica A, Jovanović Krivokuća M, Nedeljković J. Toxicity of Silver Nanoparticles Supported by Surface-Modified Zirconium Dioxide with Dihydroquercetin. in Nanomaterials. 2022;12(18).
doi:10.3390/nano12183195 .

Sredojević, Dušan, Lazić, Vesna, Pirković, Andrea, Periša, Jovana, Murafa, Natalija, Spremo-Potparević, Biljana, Živković, Lada, Topalović, Dijana, Zarubica, Aleksandra, Jovanović Krivokuća, Milica, Nedeljković, Jovan, "Toxicity of Silver Nanoparticles Supported by Surface-Modified Zirconium Dioxide with Dihydroquercetin" in Nanomaterials, 12, no. 18 (2022),
https://doi.org/10.3390/nano12183195 . .