bluuebunny/crossref_metadata_2025 huggingface dataset:
Stabilization of Natural Pigments in Ethanolic Solutions for Food Applications: The Case Study of Chlorella vulgaris
Authors: Ferreira Andreia S. , Pereira Liliana , Canfora Feliciana , Silva Tiago H. , Coimbra Manuel A. , Nunes Cláudia
Published: January 2023

Chlorella vulgaris is a green microalga with a high chlorophyll content, representing a valuable source of green pigments for food applications. As the application of whole biomass can promote an unpleasant fish-like flavor, the use of chlorophyll extract can overcome this drawback. However, chlorophylls tend to easily degrade when out of the chloroplasts, decreasing their potential as a food ingredient. Thus, to study the suitable conditions for isolated chlorophylls preservation, in this work, the influence of temperature (4 to 60 °C), light (dark or 24 h photoperiod), alkaline conditions (with or without aqueous NaOH addition), and modified atmosphere (air or argon atmosphere) on the stability of the color in ethanolic solutions obtained from C. vulgaris were studied. The loss of green color with temperature followed the first-order kinetics, with an activation energy of 74 kJ/mol. Below 28 °C and dark conditions were suitable to preserve isolated chlorophylls. The addition of NaOH and an inert argon-rich atmosphere did not exhibit a statistically positive effect on color preservation. In the case study, cooked cold rice was colored to be used in sushi. The color remained stable for up to 3 days at 4 °C. Therefore, this work showed that C. vulgaris chlorophylls could be preserved in ethanolic solutions at room or lower temperatures when protected from light, allowing them to obtain a suitable natural food ingredient to color foodstuffs.
Assessment of the Phytochemical Analysis and Antimicrobial Potentials of Zingiber zerumbet
Authors: Ramzan Muhammad , Zeshan Basit
Published: January 2023

Antimicrobial resistance (AMR) has arisen as a global concern in recent decades. Plant extracts used in combination with antibiotics are promising against AMR, synergistically. The purpose of this study was to evaluate the component of the bitter ginger (Zingiber zerumbet) extract in different solvents using high-performance liquid chromatography (HPLC), in addition to evaluate the antibacterial activity of these extracts, in combination with their antibiotic potential against four multi-drug resistant (MDR) bacterial strains (Lactobacillus acidophilus, Streptococcus mutans, Enterococcus faecalis and Staphylococcus aureus). Ethanol and the aqueous extracts of bitter ginger were prepared using a conventional solvent extraction method and were evaluated for their phytochemistry using HPLC, qualitatively and quantitatively. Moreover, the antibiotic susceptibility of the pathogenic isolates was determined. A disc diffusion assay was used to obtain the antimicrobial potential of the extracts alone and with antibiotics. Eight components were identified from the separation of the bitter ginger extract by HPLC. For AMR bacteria, the combination of the antibiotic solution with the bitter ginger crude extracts could improve its susceptibility of these antibiotics. This study indicates that the combination of an antibiotic solution with the bitter ginger crude extract exhibits potent antibacterial activities against MDR bacterial strains. Therefore, they can be used for the treatment of various diseases against the microbial pathogen and can be incorporated into medication for antibacterial therapy.
Targeted Delivery of Sunitinib by MUC-1 Aptamer-Capped Magnetic Mesoporous Silica Nanoparticles
Authors: Torabi Mitra , Aghanejad Ayuob , Savadi Pouria , Barzegari Abolfazl , Omidi Yadollah , Barar Jaleh
Published: January 2023

Magnetic mesoporous silica nanoparticles (MMSNPs) are being widely investigated as multifunctional novel drug delivery systems (DDSs) and play an important role in targeted therapy. Here, magnetic cores were synthesized using the thermal decomposition method. Further, to improve the biocompatibility and pharmacokinetic behavior, mesoporous silica was synthesized using the sol-gel process to coat the magnetic cores. Subsequently, sunitinib (SUN) was loaded into the MMSNPs, and the particles were armed with amine-modified mucin 1 (MUC-1) aptamers. The MMSNPs were characterized using FT-IR, TEM, SEM, electrophoresis gel, DLS, and EDX. MTT assay, flow cytometry analysis, ROS assessment, and mitochondrial membrane potential analysis evaluated the nanoparticles’ biological impacts. The physicochemical analysis revealed that the engineered MMSNPs have a smooth surface and spherical shape with an average size of 97.6 nm. The biological in vitro analysis confirmed the highest impacts of the targeted MMSNPs in MUC-1 overexpressing cells (OVCAR-3) compared to the MUC-1 negative MDA-MB-231 cells. In conclusion, the synthesized MMSNP-SUN-MUC-1 nanosystem serves as a unique multifunctional targeted delivery system to combat the MUC-1 overexpressing ovarian cancer cells.
Extraction of Bioactive Compounds from C. vulgaris Biomass Using Deep Eutectic Solvents
Authors: Dardavila Maria Myrto , Pappou Sofia , Savvidou Maria G. , Louli Vasiliki , Katapodis Petros , Stamatis Haralambos , Magoulas Kostis , Voutsas Epaminondas
Published: January 2023

C. vulgaris microalgae biomass was employed for the extraction of valuable bioactive compounds with deep eutectic-based solvents (DESs). Particularly, the Choline Chloride (ChCl) based DESs, ChCl:1,2 butanediol (1:4), ChCl:ethylene glycol (1:2), and ChCl:glycerol (1:2) mixed with water at 70/30 w/w ratio were used for that purpose. The extracts’ total carotenoid (TCC) and phenolic contents (TPC), as well as their antioxidant activity (IC50), were determined within the process of identification of the most efficient solvent. This screening procedure revealed ChCl:1,2 butanediol (1:4)/H2O 70/30 w/w as the most compelling solvent; thus, it was employed thereafter for the extraction process optimization. Three extraction parameters, i.e., solvent-to-biomass ratio, temperature, and time were studied regarding their impact on the extract’s TCC, TPC, and IC50. For the experimental design and process optimization, the statistical tool Response Surface Methodology was used. The resulting models’ predictive capacity was confirmed experimentally by carrying out two additional extractions under conditions different from the experimental design.
Reductive Deuteration of Acyl Chlorides for the Synthesis of α,α-Dideuterio Alcohols Using SmI2 and D2O
Authors: Li Hengzhao , Hou Yuxia , Peng Mengqi , Wang Lijun , Li Junyu , Ning Lei , Lai Zemin , Li Yixuan , An Jie
Published: January 2023

The synthesis of α,α-dideuterio alcohols has been achieved via single electron transfer reductive deuteration of acyl chlorides using SmI2 and D2O. This method is distinguished by its remarkable functional group tolerance and exquisite deuterium incorporation, which has also been applied to the synthesis of valuable deuterated agrochemicals and their building blocks.
Synthesis, Fungicidal Activity and Plant Protective Properties of 1,2,3-Thiadiazole and Isothiazole-Based N-acyl-N-arylalaninates
Authors: Kalinina Tatiana A. , Balandina Valeriya I. , Obydennov Konstantin L. , Slepukhin Pavel A. , Fan Zhijin , Bakulev Vasiliy A. , Glukhareva Tatiana V.
Published: January 2023

The addition of active groups of known fungicides, or systemic acquired resistance inducers, into novel compound molecules to search for potential antifungal compounds is a popular and effective strategy. In this work, a new series of N-acyl-N-arylalanines was developed and synthesized, in which 1,2,3-thiadiazol-5-ylcarbonyl or 3,4-dichloroisothiazol-5-ylcarbonyl (fragments from synthetic plant resistance activators tiadinil and isotianil, respectively) and a fragment of N-arylalanine, the toxophoric group of acylalanine fungicides. Several new synthesized compounds have shown moderate antifungal activity against fungi in vitro, such as B. cinerea, R. solani and S. sclerotiorum. In vivo tests against A. brassicicola showed that compound 1d was 92% effective at a concentration of 200 µg/mL, similar to level of tiadinil, a known inducer of systemic resistance. Thus, 1d could be considered a new candidate fungicide for further detailed study. The present results will advance research and influence the search for more promising fungicides for disease control in agriculture.
Effects of a Semisynthetic Catechin on Phosphatidylglycerol Membranes: A Mixed Experimental and Simulation Study
Authors: Aranda Elisa , Teruel José A. , Ortiz Antonio , Pérez-Cárceles María Dolores , Rodríguez-López José N. , Aranda Francisco J.
Published: January 2023

Catechins have been shown to display a great variety of biological activities, prominent among them are their chemo preventive and chemotherapeutic properties against several types of cancer. The amphiphilic nature of catechins points to the membrane as a potential target for their actions. 3,4,5-Trimethoxybenzoate of catechin (TMBC) is a modified structural analog of catechin that shows significant antiproliferative activity against melanoma and breast cancer cells. Phosphatidylglycerol is an anionic membrane phospholipid with important physical and biochemical characteristics that make it biologically relevant. In addition, phosphatidylglycerol is a preeminent component of bacterial membranes. Using biomimetic membranes, we examined the effects of TMBC on the structural and dynamic properties of phosphatidylglycerol bilayers by means of biophysical techniques such as differential scanning calorimetry, X-ray diffraction and infrared spectroscopy, together with an analysis through molecular dynamics simulation. We found that TMBC perturbs the thermotropic gel to liquid-crystalline phase transition and promotes immiscibility in both phospholipid phases. The modified catechin decreases the thickness of the bilayer and is able to form hydrogen bonds with the carbonyl groups of the phospholipid. Experimental data support the simulated data that locate TMBC as mostly forming clusters in the middle region of each monolayer approaching the carbonyl moiety of the phospholipid. The presence of TMBC modifies the structural and dynamic properties of the phosphatidylglycerol bilayer. The decrease in membrane thickness and the change of the hydrogen bonding pattern in the interfacial region of the bilayer elicited by the catechin might contribute to the alteration of the events taking place in the membrane and might help to understand the mechanism of action of the diverse effects displayed by catechins.
A Cell-Penetrating Peptide Modified Cu2−xSe/Au Nanohybrid with Enhanced Efficacy for Combined Radio-Photothermal Therapy
Authors: Ran Ruixue , Guo Sinan , Jiang Xiaoyu , Qian Zhanyin , Guo Zhaoyang , Wang Yinsong , Cao Mingxin , Yang Xiaoying
Published: January 2023

Radiotherapy (RT) is one of the main clinical therapeutic strategies against cancer. Currently, multiple radiosensitizers aimed at enhancing X-ray absorption in cancer tissues have been developed, while limitations still exist for their further applications, such as poor cellular uptake, hypoxia-induced radioresistance, and unavoidable damage to adjacent normal body tissues. In order to address these problems, a cell-penetrating TAT peptide (YGRKKRRQRRRC)-modified nanohybrid was constructed by doping high-Z element Au in hollow semiconductor Cu2−xSe nanoparticles for combined RT and photothermal therapy (PTT) against breast cancer. The obtained Cu2−xSe nanoparticles possessed excellent radiosensitizing properties based on their particular band structures, and high photothermal conversion efficiency beneficial for tumor ablation and promoting RT efficacy. Further doping high-Z element Au deposited more high-energy radiation for better radiosensitizing performance. Conjugation of TAT peptides outside the constructed Cu2−xSe/Au nanoparticles facilitated their cellular uptake, thus reducing overdosage-induced side effects. This prepared multifunctional nanohybrid showed powerful suppression effects towards breast cancer, both in vitro and in vivo via integrating enhanced cell penetration and uptake, and combined RT/PTT strategies.
Advanced Fitting Method for the Kinetic Analysis of Thermogravimetric Data
Authors: Bondarchuk Ivan , Bondarchuk Sergey , Vorozhtsov Alexander , Zhukov Alexander
Published: January 2023

The article considered the solution of the inverse problem of chemical kinetics of the analysis of experimental data of a thermogravimetric experiment at a constant sample heating rate. The fitting method for identifying the parameters of a kinetic triplet using the integral method for a model of a solid-state reaction based on the modified Arrhenius equation is described. The effectiveness of the proposed approach was confirmed by solving test cases for low, medium, and high rates of material conversion. Unlike other methods, setting the parameters of the reaction mechanism is not required, as they are determined by the solution. Solutions for real data of TGA studies with high and low sample heating rates were compared with the results obtained by other authors and experimental data. A description of the full cycle of calculations used to identify kinetic parameters from thermogravimetric experimental data is given, from the derivation of calculated relationships to the implementation of a short (three to five formulas) program code for MS Excel spreadsheets. The presented code is easy to verify and reproduce and can be modified to solve various problems.
Branched Linkers for Site-Specific Fluorescent Labeling of Antibodies
Authors: Sapozhnikova Ksenia A. , Gulyak Evgeny L. , Misyurin Vsevolod A. , Simonova Maria A. , Ryabukhina Ekaterina V. , Alexeeva Anastasiya V. , Tikhonova Nataliya A. , Lyzhko Natalia A. , Popova Galina P. , Misyurin Andrey V. , Ustinov Alexey V. , Korshun Vladimir A. , Alferova Vera A. , Ryazantsev Dmitry Yu. , Brylev Vladimir A.
Published: January 2023

Fluorescent antibodies have proved to be an invaluable tool for molecular biology and diagnostics. They are routinely produced by modification of lysine residues, which leads to high heterogeneity. As such, their affinity may be compromised if the antigen-binding site is affected, the probability of which increases along with the degree of labeling. In this work, we propose a methodology for the synthesis of site-specific antibody-dye conjugates with a high degree of labeling. To this end, we synthesized two oxyamine-based branched triazide linkers and coupled them with a periodate-oxidized anti-PRAME antibody 6H8; two oxyamine-based linear monoazide linkers of similar structure were used as controls. The azide-labeled antibodies were subsequently conjugated with fluorescent dyes via SPAAC, a copper-free click reaction. Compared to their counterparts made with linear linkers, the branched conjugates possessed a higher degree of labeling. The utility of the methodology was demonstrated in the detection of the PRAME protein on the surface of the cell by flow cytometry.
Sorption of Organic Contaminants by Stable Organic Matter Fraction in Soil
Authors: Ukalska-Jaruga Aleksandra , Bejger Romualda , Smreczak Bożena , Podlasiński Marek
Published: January 2023

Soil organic matter (SOM) and its heterogeneous nature constitutes the main factor determining the fate and transformation of organic chemicals (OCs). Thus, the aim of thus research was to analyze the influence of the molecular chemodiversity of a stable SOM (S-SOM) on the sorption potential of different groups of OCs (organochloride pesticides—OCPs, and non-chlorinated pesticides—NCPs, polycyclic aromatic hydrocarbons—PAHs). The research was conducted as a batch experiment. For this purpose, a S-SOM was separated from six soils (TOC = 15.0–58.7 gkg−1; TN = 1.4–6.6 gkg−1, pH in KCl = 6.4–7.4 and WRB taxonomy: fluvisols, luviosols, leptosols) by alkaline urea and dimethylsulphoxide with sulfuric acid. Isolated S-SOM fraction was evaluated by UV–VIS, FT-IR and EEM spectroscopy to describe molecular diversity, which allowed the assessment of its potential sorption properties regarding OCs. In order to directly evaluate the sorption affinity of individual OCs to S-SOM, the mixture of the 3 deuterated contaminants: chrysene (PAHs), 4,4′DDT (OCPs) atrazine (NCPs) were applied. The sorption experiment was carried out according to the 106 OECD Guidelines. The OCs concentration was analyzed by gas chromatography triple mass spectrometry (GC-MS/MS). OCs were characterized by different sorption rates to S-SOM fractions according to the overall trend: atrazine (87.5–99.9%) > 4,4′DDT (64–81.6%) > chrysene (35.2–79.8%). Moreover, atrazine exhibited the highest saturation dynamic with fast bounding time amounting to 6 h of contact with S-SOM. Proportionally, the chrysene showed the slowest binding time achieving an average of 55% sorption after 78 h. Therefore, S-SOM isolated from different soils demonstrated varying binding capacity to OCs (CoV = 21%, 27% and 33% for atrazine, DDT and chrysene, respectively). Results indicate that each sample contains S-SOM with different degrees of transformation and sorption properties that affect the OCs availability in soil. Spectroscopic analyses have shown that the main component of S-SOM are biopolymers at various stages of transformation that contain numerous aromatic–aliphatic groups with mostly hydrophilic substituents.
In-Depth Method Investigation for Determination of Boron in Silicate Samples Using an Improved Boron–Mannitol Complex Digestion Method by Inductively Coupled Plasma Mass Spectrometry
Authors: Tan Xijuan , Zhou Ruili , Feng Yonggang , Liang Ting
Published: January 2023

In this paper, a boron–mannitol complex wet acid digestion method proposed for the accurate determination of boron in silicate samples by inductively coupled plasma mass spectrometry (ICP-MS) was investigated in detail for the first time. With the addition of 50 μL of mannitol (2% wt.) into the mixture of 0.6 mL of concentrated HF and 30 μL of concentrated HNO3, the 50 mg of silicate sample was effectively decomposed after being heated overnight with optional pre-ultrasonic treatment. Following fluoride formation prevention by 8% HNO3 (wt.) and fluoride decomposition using 6% HCl (wt.), the samples were fluxed in 2.0 mL of 40% HNO3 (wt.) for 4 h and aged overnight. By diluting 1000-fold using 2% HNO3 (wt.) solution, the samples were directly quantified by an ICP-MS, showing boron recoveries of the standard materials including diabase W-2, basalt JB-2a, and rhyolite JR-2 in the range of 95.5–105.5% (n = 5). For this wet acid method, it was found that the contents of boron had no obvious difference under digestion temperatures of 65, 100, and 140 °C. It was also found that the ICP-MS quantification accuracy deteriorated at the mass of 11B when boron content was about 7250 ng yielding positive bias with average recoveries of 115.5–119.8% (n = 5), while the determination results remained unaffected at the mass of 10B. Furthermore, the digestion efficiency of boron by laboratory high-pressure closed digestion method was assessed. The boron recoveries with samples treated by the high-pressure closed digestion method were found to vary within 49.5–98.0% (n = 5) and even lowered down to 31.1% when skipping pressure relief procedure. The long-term quantification stability study showed that the boron content generally declined in one month for the high-pressure closed digestion method and exhibited no significant changes for the proposed method. By applying such an improved boron–mannitol complex digestion method, the boron concentration in the studied silicate standard materials were accurately determined, providing critical data for further boron isotope analyses and associated geochemical studies. This in-depth method investigation for silicate boron determination demonstrates the feasibility of this boron–mannitol complex strategy under a wide digestion temperature of 65–140 °C, and also sheds light on the extensive applications of boron as a geological tracer.
A Renewable Biosensor Based on LNA-Aptamer Hybridization for the Detection of Salmonella enteritidis in Penaeus vannamei
Authors: Li Zhihua , Zhao Ling , Wu Qian , Zhang Xue , Huang Xiaowei , Shi Jiyong , Zou Xiaobo
Published: January 2023

Salmonella enteritidis (SE) is an important factor causing foodborne disease, and electrochemical sensors have drawn much attention for SE prevention and detection due to their many advantages. A renewable electrochemical sensor using specially designed locked nucleic acids (LNA) as linkers for the detection of SE was proposed to improve the reusability and reproducibility of biosensors. One end of the LNA was designed as an anchor to attach to modified electrodes through the sulfhydryl group; the other end was used to match with a short segment of SE aptamers, which will allow for the convenient renewal of occupied aptamers by raising the temperature. Results revealed that the manufactured biosensor had good stability, reproducibility, and selectivity in addition to a linear range of 6 × 101–6 × 105 CFU/mL and a limit of detection (LOD) of 20.704 CFU/mL. The recovery rate of SE for the real sample varied from 98.84% to 134.82% without exceeding 16.27% in the relative standard deviation (RSD). The proposed biosensor appears to be a promising tool for foodborne pathogen detection.
Variation of Chemical Composition and Antioxidant Properties of Kiwiberry (Actinidia arguta) in a Three-Year Study
Authors: Latocha Piotr , Łata Barbara , Jankowski Paweł
Published: January 2023

The quality of fruit as a source of bioactive ingredients is related to the genetic characteristics of plants, but it can also be modified by growing conditions. Therefore, long-term research can be extremely valuable in evaluating various crop plants, especially novel ones. The aim of the research was to test four popular European kiwiberry (Actinidia arguta) cultivars (‘Geneva’, ‘Bingo’, ‘Weiki’, ‘Anna’) in terms of selected morphological features, yield, and chemical composition as well as their variability over 3 years. It can be concluded that the studied genotypes were very diverse in terms of the biochemical compounds’ concentration in individual seasons. The cultivars ‘Anna’ and ‘Weiki’ were the most similar ones with respect to each other in terms of morphology and chemical composition. The cultivars ‘Bingo’ and ‘Geneva’ were definitely different. ‘Bingo’ was characterized by the largest and most uniform fruits in each season and had the highest concentration of vitamin C but the lowest carotenoid concentration. In turn, ‘Geneva’ produced the smallest fruit in each season with the highest concentration of polyphenols and a high concentration of carotenoids and displayed the highest antioxidant capacity regardless of the determination method. The research was performed with the application of computer-supported statistical analysis.
Bioactive Compounds in Extracts from the Agro-Industrial Waste of Mango
Authors: García-Mahecha Maribel , Soto-Valdez Herlinda , Carvajal-Millan Elizabeth , Madera-Santana Tomás Jesús , Lomelí-Ramírez María Guadalupe , Colín-Chávez Citlali
Published: January 2023

Mango by-products are important sources of bioactive compounds generated by agro-industrial process. During mango processing, 35–60% of the fruit is discarded, in many cases without treatment, generating environmental problems and economic losses. These wastes are constituted by peels and seeds (tegument and kernel). The aim of this review was to describe the extraction, identification, and quantification of bioactive compounds, as well as their potential applications, published in the last ten years. The main bioactive compounds in mango by-products are polyphenols and carotenoids, among others. Polyphenols are known for their high antioxidant and antimicrobial activities. Carotenoids show provitamin A and antioxidant activity. Among the mango by-products, the kernel has been studied more than tegument and peels because of the proportion and composition. The kernel represents 45–85% of the seed. The main bioactive components reported for the kernel are gallic, caffeic, cinnamic, tannic, and chlorogenic acids; methyl and ethyl gallates; mangiferin, rutin, hesperidin, and gallotannins; and penta-O-galloyl-glucoside and rhamnetin-3-[6-2-butenoil-hexoside]. Meanwhile, gallic acid, ferulic acid, and catechin are reported for mango peel. Although most of the reports are at the laboratory level, they include potential applications in the fields of food, active packaging, oil and fat, and pharmaceutics. At the market level, two trends will stimulate the industrial production of bioactive compounds from mango by-products: the increasing demand for industrialized fruit products (that will increase the by-products) and the increase in the consumption of bioactive ingredients.
Hybrid Chlorides with Methylhydrazinium Cation: [CH3NH2NH2]CdCl3 and Jahn-Teller Distorted [CH3NH2NH2]CuCl3
Authors: Zienkiewicz Jan A. , Kowalska Dorota A. , Drozdowski Dawid , Pikul Adam , Ptak Maciej
Published: January 2023

The synthesis, structural, phonon, optical, and magnetic properties of two hybrid organic-inorganic chlorides with monoprotonated methylhydrazinium cations (CH3NH2NH2+, MHy+), [CH3NH2NH2]CdCl3 (MHyCdCl3), and [CH3NH2NH2]CuCl3 (MHyCuCl3), are reported. In contrast to previously reported MHyMIICl3 (MII = Mn2+, Ni2+, and Co2+) analogues, neither compound undergoes phase transitions. The MHyCuCl3 has a crystal structure familiar to previous crystals composed of edge-shared 1D chains of the [CuCl5N] octahedra. MHyCuCl3 crystallizes in monoclinic P21/c symmetry with MHy+ cations directly linked to the Cu2+ ions. The MHyCdCl3 analogue crystallizes in lower triclinic symmetry with zig-zag chains of the edge-shared [CdCl6] octahedra. The absence of phase transitions is investigated and discussed. It is connected with slightly stronger hydrogen bonding between cations and the copper–chloride chains in MHyCuCl3 due to the strong Jahn–Teller effect causing the octahedra to elongate, resulting in a better fit of cations in the accessible space between chains. The absence of structural transformation in MHyCdCl3 is due to intermolecular hydrogen bonding between two neighboring MHy+ cations, which has never been reported for MHy+-based hybrid halides. Optical investigations revealed that the bandgaps in Cu2+ and Cd2+ analogues are 2.62 and 5.57 eV, respectively. Magnetic tests indicated that MHyCuCl3 has smeared antiferromagnetic ordering at 4.8 K.
Structure-Based Identification of Natural-Product-Derived Compounds with Potential to Inhibit HIV-1 Entry
Authors: Ugwu-Korie Nneka , Quaye Osbourne , Wright Edward , Languon Sylvester , Agyapong Odame , Broni Emmanuel , Gupta Yash , Kempaiah Prakasha , Kwofie Samuel K.
Published: January 2023

Broadly neutralizing antibodies (bNAbs) are potent in neutralizing a wide range of HIV strains. VRC01 is a CD4-binding-site (CD4-bs) class of bNAbs that binds to the conserved CD4-binding region of HIV-1 envelope (env) protein. Natural products that mimic VRC01 bNAbs by interacting with the conserved CD4-binding regions may serve as a new generation of HIV-1 entry inhibitors by being broadly reactive and potently neutralizing. This study aimed to identify compounds that mimic VRC01 by interacting with the CD4-bs of HIV-1 gp120 and thereby inhibiting viral entry into target cells. Libraries of purchasable natural products were virtually screened against clade A/E recombinant 93TH057 (PDB: 3NGB) and clade B (PDB ID: 3J70) HIV-1 env protein. Protein–ligand interaction profiling from molecular docking and dynamics simulations showed that the compounds had intermolecular hydrogen and hydrophobic interactions with conserved amino acid residues on the CD4-binding site of recombinant clade A/E and clade B HIV-1 gp120. Four potential lead compounds, NP-005114, NP-008297, NP-007422, and NP-007382, were used for cell-based antiviral infectivity inhibition assay using clade B (HXB2) env pseudotype virus (PV). The four compounds inhibited the entry of HIV HXB2 pseudotype viruses into target cells at 50% inhibitory concentrations (IC50) of 15.2 µM (9.7 µg/mL), 10.1 µM (7.5 µg/mL), 16.2 µM (12.7 µg/mL), and 21.6 µM (12.9 µg/mL), respectively. The interaction of these compounds with critical residues of the CD4-binding site of more than one clade of HIV gp120 and inhibition of HIV-1 entry into the target cell demonstrate the possibility of a new class of HIV entry inhibitors.
Review and Chemoinformatic Analysis of Ferroptosis Modulators with a Focus on Natural Plant Products
Authors: Stepanić Višnja , Kučerová-Chlupáčová Marta
Published: January 2023

Ferroptosis is a regular cell death pathway that has been proposed as a suitable therapeutic target in cancer and neurodegenerative diseases. Since its definition in 2012, a few hundred ferroptosis modulators have been reported. Based on a literature search, we collected a set of diverse ferroptosis modulators and analyzed them in terms of their structural features and physicochemical and drug-likeness properties. Ferroptosis modulators are mostly natural products or semisynthetic derivatives. In this review, we focused on the abundant subgroup of polyphenolic modulators, primarily phenylpropanoids. Many natural polyphenolic antioxidants have antiferroptotic activities acting through at least one of the following effects: ROS scavenging and/or iron chelation activities, increased GPX4 and NRF2 expression, and LOX inhibition. Some polyphenols are described as ferroptosis inducers acting through the generation of ROS, intracellular accumulation of iron (II), or the inhibition of GPX4. However, some molecules have a dual mode of action depending on the cell type (cancer versus neural cells) and the (micro)environment. The latter enables their successful use (e.g., apigenin, resveratrol, curcumin, and EGCG) in rationally designed, multifunctional nanoparticles that selectively target cancer cells through ferroptosis induction.
Promising Role of Polylactic Acid as an Ingenious Biomaterial in Scaffolds, Drug Delivery, Tissue Engineering, and Medical Implants: Research Developments, and Prospective Applications
Authors: Ranakoti Lalit , Gangil Brijesh , Bhandari Prabhakar , Singh Tej , Sharma Shubham , Singh Jujhar , Singh Sunpreet
Published: January 2023

In the present scenario, the research is now being focused on the naturally occurring polymers that can gradually replace the existing synthetic polymers for the development of bio composites having applications in medical surgeries and human implants. With promising mechanical properties and bio compatibility with human tissues, poly lactic acid (PLA) is now being viewed as a future bio material. In order to examine the applicability of PLA in human implants, the current article sheds light on the synthesis of PLA and its various copolymers used to alter its physical and mechanical properties. In the latter half, various processes used for the fabrication of biomaterials are discussed in detail. Finally, biomaterials that are currently in use in the field of biomedical (Scaffolding, drug delivery, tissue engineering, medical implants, derma, cosmetics, medical surgeries, and human implants) are represented with respective advantages in the sphere of biomaterials.
Accuracy of Citrate Anticoagulant Amount, Volume, and Concentration in Evacuated Blood Collection Tubes Evaluated with UV Molecular Absorption Spectrometry on a Purified Water Model
Authors: Gros Nataša , Klobučar Tadej , Gaber Klara
Published: January 2023

Citrate anticoagulant concentration affects the results of coagulation tests. Until now, the end user had no direct insight into the quality of evacuated blood collection tubes. By introducing an easy-to-perform UV spectrometric method for citrate determination on a purified water model, we enabled the evaluation of (1) the accuracy of the anticoagulant amount added into the tubes by a producer, (2) the accuracy of the volume of anticoagulant solution in the tube at the instant of examination, (3) the anticoagulant concentrations at a draw volume. We examined the Vacuette®, Greiner BIO-ONE, Vacutube, LT Burnik d.o.o., and BD Vacutainer® tubes. The anticoagulant amount added into the tubes during production had a relative bias between 3.2 and 23.0%. The anticoagulant volume deficiency at the instant of examination expressed as a relative bias ranged between −11.6 and −91.1%. The anticoagulant concentration relative bias after the addition of purified water in a volume that equalled a nominal draw volume extended from 9.3 to 25.7%. Draw-volume was mostly compliant during shelf life. Only Vacutube lost water over time. Contamination with potassium, magnesium, or both was observed in all the tubes but did not exceed a 0.21 mmol/L level. This study enables medical laboratories to gain insight into the characteristics of the citrate blood collection tubes as one of the preanalytical variables. In situations that require anticoagulant adjustment for accurate results, this can help make the right decisions. The methodology gives producers additional means of controlling the quality of their production process.
Ultrasound-Assisted Extraction of Antioxidants from Melastoma malabathricum Linn.: Modeling and Optimization Using Box–Behnken Design
Authors: Hosni Suzziyana , Gani Siti Salwa Abd , Orsat Valérie , Hassan Masriana , Abdullah Sumaiyah
Published: January 2023

This study presents modeling and optimization of ultrasound-assisted extraction (UAE) of Melastoma malabathricum with the objective of evaluating its phytochemical properties. This one-factor-at-a-time (OFAT) procedure was conducted to screen for optimization variables whose domains included extraction temperature (XET), ultrasonic time (XUT), solvent concentration (XSC), and sample-to-liquid ratio (XSLR). Response surface methodology (RSM) coupled with Box–Behnken design (BBD) was applied to establish optimum conditions for maximum antioxidant extraction. Modeling and optimization conditions of UAE at 37 kHz, XET 32 °C for XUT 16 min and dissolved in an XSC 70% ethanol concentration at a XSLR 1:10 ratio yielded scavenging effects on 2,2-diphenyl-1-picryl-hydrazyl (DPPH) at 96% ± 1.48 and recorded values of total phenolic content (TPC) and total flavonoid content (TFC) at 803.456 ± 32.48 mg GAE (gallic acid equivalents)/g, and 102.972 ± 2.51 mg QE (quercetin equivalents)/g, respectively. The presence of high flavonoid compounds was verified using TWIMS-QTOFMS. Chromatic evaluation of phytochemicals using gas chromatography–mass spectrometry (GC–MS) revealed the presence of 14 phytocompounds widely documented to play significant roles in human health. This study provides a comparative evaluation with other studies and may be used for validation of the species’ potential for its much-acclaimed medicinal and cosmeceutical uses.
A Low Driving-Voltage Hybrid-Electrolyte Electrochromic Window with Only Ferreous Redox Couples
Authors: Song Jisheng , Huang Bingkun , Xu Yinyingjie , Yang Kunjie , Li Yingfan , Mu Yuqi , Du Lingyu , Yun Shan , Kang Litao
Published: January 2023

Even after decades of development, the widespread application of electrochromic windows (ECW) is still seriously restricted by their high price and inadequate performance associated with structural/fabrication complexity and electrochemical instability. Herein, a simple hybrid electrochromic system based on PFSA (perfluorosulfonic acid)-coated Prussian blue (PB, Fe4III [FeII(CN)6]3) film and Ferricyanide–Ferrocyanide ([Fe(CN)6]4−/[Fe(CN)6]3−)-containing hybrid electrolyte is reported. The PB film and the [Fe(CN)6]4−/[Fe(CN)6]3− couple show near redox potentials well inside the electrochemical window of water, resulting in a low driven voltage (0.4 V for coloring and −0.6 V for bleaching) and a relatively long lifespan (300 cycles with 76.9% transmittance contrast retained). The PFSA layer, as a cation-exchange structure, significantly improves the transmittance modulation amplitude (ΔT: 23.3% vs. 71.9% at a wavelength of 633 nm) and optical memory abilities (ΔT retention: 10.1% vs. 67.0% after 300 s open-circuit rest increases) of the device, by means of preventing the direct contact and charge transfer between the PB film and the [Fe(CN)6]4−/[Fe(CN)6]3− couple. This “hybrid electrolyte + electron barrier layer” design provides an effective way for the construction of simple structured electrochromic devices.
Triple-Band Square Split-Ring Resonator Metamaterial Absorber Design with High Effective Medium Ratio for 5G Sub-6 GHz Applications
Authors: Hakim Mohammad Lutful , Islam Mohammad Tariqul , Alam Touhidul , Abdul Rahim Sharul Kamal , Bais Badariah , Islam Md. Shabiul , Soliman Mohamed S.
Published: January 2023

This article proposes a square split-ring resonator (SSRR) metamaterial absorber (MMA) for sub-6 GHz application. The unit cell of the MMA was designed and fabricated on commercially available low-cost FR-4 substrate material with a dielectric constant o 4.3. The higher effective medium ratio (EMR) of the designed unit cell shows the compactness of the MMA. The dimension of the unit cell is 9.5 × 9.5 × 1.6 mm3, which consists of two split rings and two arms with outer SSRR. The proposed MMA operates at 2.5 GHz, 4.9 GHz, and 6 GHz frequency bands with a 90% absorption peak and shows a single negative metamaterial property. The E-field, H-field, and surface current are also explored in support of absorption analysis. Moreover, the equivalent circuit model of the proposed MMA is modelled and simulated to validate the resonance behavior of the MMA structure. Finally, the proposed MMA can be used for the specific frequency bands of 5G applications such as signal absorption, crowdsensing, SAR reduction, etc.
Carbon Dot Emission Enhancement in Covalent Complexes with Plasmonic Metal Nanoparticles
Authors: Arefina Irina A. , Kurshanov Danil A. , Vedernikova Anna A. , Danilov Denis V. , Koroleva Aleksandra V. , Zhizhin Evgeniy V. , Sergeev Aleksandr A. , Fedorov Anatoly V. , Ushakova Elena V. , Rogach Andrey L.
Published: January 2023

Carbon dots can be used for the fabrication of colloidal multi-purpose complexes for sensing and bio-visualization due to their easy and scalable synthesis, control of their spectral responses over a wide spectral range, and possibility of surface functionalization to meet the application task. Here, we developed a chemical protocol of colloidal complex formation via covalent bonding between carbon dots and plasmonic metal nanoparticles in order to influence and improve their fluorescence. We demonstrate how interactions between carbon dots and metal nanoparticles in the formed complexes, and thus their optical responses, depend on the type of bonds between particles, the architecture of the complexes, and the degree of overlapping of absorption and emission of carbon dots with the plasmon resonance of metals. For the most optimized architecture, emission enhancement reaching up to 5.4- and 4.9-fold for complexes with silver and gold nanoparticles has been achieved, respectively. Our study expands the toolkit of functional materials based on carbon dots for applications in photonics and biomedicine to photonics.
Differential Orbitofrontal Cortex Responses to Chocolate Images While Performing an Approach–Avoidance Task in the MRI Environment
Authors: Lender Anja , Wirtz Janina , Kronbichler Martin , Kahveci Sercan , Kühn Simone , Blechert Jens
Published: January 2023

Background: Chocolate is one of the most frequently craved foods, and it often challenges self-regulation. These cravings may be underpinned by a neural facilitation of approach behavior toward chocolate. This preregistered study investigated the behavioral and neural correlates of such a bias using functional magnetic resonance imaging (fMRI) and reaction times (RTs). Methods: A total of n = 30 frequent chocolate eaters performed a relevant-feature approach–avoidance task (AAT) in the MRI scanner using buttons to enlarge (approach) or to shrink (avoid) pictures of chocolate and inedible control objects. We tested (a) whether implicit RT-based approach biases could be measured in a supine position in the scanner, (b) whether those biases were associated with activity in reward-related brain regions such as the insula, amygdala, striatum, and orbitofrontal cortex (OFC), and (c) whether individual RT-based bias-scores correlated with measures of chocolate craving. Results: Behaviorally, we found a highly reliable approach bias toward chocolate, defined by faster RTs in the compatible conditions (approach chocolate, avoid objects) compared to the incompatible conditions (avoid chocolate, approach objects). Neurally, this compatibility effect involved activity in the left medial OFC, a neural response that was positively correlated with individual approach bias scores. Conclusions: This study shows that the relevant feature AAT can be implemented in an fMRI setting in a supine position using buttons. An approach bias toward chocolate seems related to medial OFC activation that might serve to devalue chocolate when it has to be avoided. Our demonstration of neural and behavioral approach biases for chocolate underscores the need for stimulus-specific cognitive trainings to support healthy consumption and successful self-regulation.
Copaiba Oil-Loaded Polymeric Nanocapsules: Production and In Vitro Biosafety Evaluation on Lung Cells as a Pre-Formulation Step to Produce Phytotherapeutic Medicine
Authors: Rodrigues Victor M. , Oliveira Wógenes N. , Pereira Daniel T. , Alencar Éverton N. , Porto Dayanne L. , Aragão Cícero F. S. , Moreira Susana M. G. , Rocha Hugo A. O. , Amaral-Machado Lucas , Egito Eryvaldo S. T.
Published: January 2023

Copaiba oil has been largely used due to its therapeutic properties. Nanocapsules were revealed to be a great nanosystem to carry natural oils due to their ability to improve the bioaccessibility and the bioavailability of lipophilic compounds. The aim of this study was to produce and characterize copaiba oil nanocapsules (CopNc) and to evaluate their hemocompatibility, cytotoxicity, and genotoxicity. Copaiba oil was chemically characterized by GC-MS and FTIR. CopNc was produced using the nanoprecipitation method. The physicochemical stability, toxicity, and biocompatibility of the systems, in vitro, were then evaluated. Β-bisabolene, cis-α-bergamotene, caryophyllene, and caryophyllene oxide were identified as the major copaiba oil components. CopNc showed a particle size of 215 ± 10 nm, a polydispersity index of 0.15 ± 0.01, and a zeta potential of −18 ± 1. These parameters remained unchanged over 30 days at 25 ± 2 °C. The encapsulation efficiency of CopNc was 54 ± 2%. CopNc neither induced hemolysis in erythrocytes, nor cytotoxic and genotoxic in lung cells at the range of concentrations from 50 to 200 μg·mL−1. In conclusion, CopNc showed suitable stability and physicochemical properties. Moreover, this formulation presented a remarkable safety profile on lung cells. These results may pave the way to further use CopNc for the development of phytotherapeutic medicine intended for pulmonary delivery of copaiba oil.
Optimizing Antiviral Dosing for HSV and CMV Treatment in Immunocompromised Patients
Authors: Huntjens Daan W. , Dijkstra Jacob A. , Verwiel Lisanne N. , Slijkhuis Mirjam , Elbers Paul , Welkers Matthijs R. A. , Veldkamp Agnes I. , Kuijvenhoven Marianne A. , de Leeuw David C. , Abdullah-Koolmees Heshu , Kuipers Maria T. , Bartelink Imke H.
Published: January 2023

Herpes simplex virus (HSV) and cytomegalovirus (CMV) are DNA viruses that are common among humans. Severely immunocompromised patients are at increased risk of developing HSV or CMV disease due to a weakened immune system. Antiviral therapy can be challenging because these drugs have a narrow therapeutic window and show significant pharmacokinetic variability. Above that, immunocompromised patients have various comorbidities like impaired renal function and are exposed to polypharmacy. This scoping review discusses the current pharmacokinetic (PK) and pharmacodynamic (PD) knowledge of antiviral drugs for HSV and CMV treatment in immunocompromised patients. HSV and CMV treatment guidelines are discussed, and multiple treatment interventions are proposed: early detection of drug resistance; optimization of dose to target concentration by therapeutic drug monitoring (TDM) of nucleoside analogs; the introduction of new antiviral drugs; alternation between compounds with different toxicity profiles; and combinations of synergistic antiviral drugs. This research will also serve as guidance for future research, which should focus on prospective evaluation of the benefit of each of these interventions in randomized controlled trials.
mRNA in the Context of Protein Replacement Therapy
Authors: Vavilis Theofanis , Stamoula Eleni , Ainatzoglou Alexandra , Sachinidis Athanasios , Lamprinou Malamatenia , Dardalas Ioannis , Vizirianakis Ioannis S.
Published: January 2023

Protein replacement therapy is an umbrella term used for medical treatments that aim to substitute or replenish specific protein deficiencies that result either from the protein being absent or non-functional due to mutations in affected patients. Traditionally, such an approach requires a well characterized but arduous and expensive protein production procedure that employs in vitro expression and translation of the pharmaceutical protein in host cells, followed by extensive purification steps. In the wake of the SARS-CoV-2 pandemic, mRNA-based pharmaceuticals were recruited to achieve rapid in vivo production of antigens, proving that the in vivo translation of exogenously administered mRNA is nowadays a viable therapeutic option. In addition, the urgency of the situation and worldwide demand for mRNA-based medicine has led to an evolution in relevant technologies, such as in vitro transcription and nanolipid carriers. In this review, we present preclinical and clinical applications of mRNA as a tool for protein replacement therapy, alongside with information pertaining to the manufacture of modified mRNA through in vitro transcription, carriers employed for its intracellular delivery and critical quality attributes pertaining to the finished product.
Demonstrating Biological Fate of Nanoparticle-Loaded Dissolving Microneedles with Aggregation-Caused Quenching Probes: Influence of Application Sites
Authors: Fu Yanping , Shi Chaonan , Li Xiaodie , Wen Ting , Wu Qiaoli , Zhang Antian , Hu Ping , Wu Chuanbin , Pan Xin , Huang Zhengwei , Quan Guilan
Published: January 2023

Integrating dissolving microneedles (DMNs) and nanocarriers (NC) holds great potential in transdermal drug delivery because it can simultaneously overcome the stratum corneum barrier and achieve efficient and controlled drug delivery. However, different skin sites with different thicknesses and compositions can affect the transdermal diffusion of NC-loaded DMNs. There are few reports on the biological fate (especially transdermal diffusion) of NC-loaded DMNs, and inaccurate bioimaging information of intact NC limits the accurate understanding of the in vivo fate of NC-loaded DMNs. The aggregation-caused quenching (ACQ) probes P4 emitted intense fluorescence signals in intact NC while quenched after the degradation of NC, had been demonstrated the feasibility of label intact NC. In this study, P4 was loaded in solid lipid nanoparticles (SLNs), and further encapsulated into DMNs, to track the transdermal diffusion of SLNs delivered at different skin sites. The results showed that SLNs had excellent stability after being loaded into DMNs with no significant changes in morphology and fluorescence properties. The in vivo live and ex vivo imaging showed that the transdermal diffusion rate of NC-loaded DMNs was positively correlated with skin thickness, with the order ear > abdomen > back. In conclusion, this study confirmed the site-dependency of transdermal diffusion in NC-loaded DMNs.