bluuebunny/crossref_metadata_2025 huggingface dataset:
Wound Healing Impairment in Type 2 Diabetes Model of Leptin-Deficient Mice—A Mechanistic Systematic Review
Authors: Stachura Albert , Khanna Ishani , Krysiak Piotr , Paskal Wiktor , Włodarski Paweł
Published: August 2022

Type II diabetes mellitus (T2DM) is one of the most prevalent diseases in the world, associated with diabetic foot ulcers and impaired wound healing. There is an ongoing need for interventions effective in treating these two problems. Pre-clinical studies in this field rely on adequate animal models. However, producing such a model is near-impossible given the complex and multifactorial pathogenesis of T2DM. A leptin-deficient murine model was developed in 1959 and relies on either dysfunctional leptin (ob/ob) or a leptin receptor (db/db). Though monogenic, this model has been used in hundreds of studies, including diabetic wound healing research. In this study, we systematically summarize data from over one hundred studies, which described the mechanisms underlying wound healing impairment in this model. We briefly review the wound healing dynamics, growth factors’ dysregulation, angiogenesis, inflammation, the function of leptin and insulin, the role of advanced glycation end-products, extracellular matrix abnormalities, stem cells’ dysregulation, and the role of non-coding RNAs. Some studies investigated novel chronic diabetes wound models, based on a leptin-deficient murine model, which was also described. We also discussed the interventions studied in vivo, which passed into human clinical trials. It is our hope that this review will help plan future research.
Long-Term Alcohol Consumption Caused a Significant Decrease in Serum High-Density Lipoprotein (HDL)-Cholesterol and Apolipoprotein A-I with the Atherogenic Changes of HDL in Middle-Aged Korean Women
Authors: Cho Kyung-Hyun , Nam Hyo-Seon , Kang Dae-Jin , Park Min-Hee , Kim Ju-Hyun
Published: August 2022

Light-to-moderate alcohol drinking is associated with a low incidence of cardiovascular disease (CVD) via an elevation of high-density lipoproteins-cholesterol (HDL-C), particularly with the short-term supplementation of alcohol. However, there is no information on the change in the HDL qualities and functionalities between non-drinkers and mild drinkers in the long-term consumption of alcohol. This study analyzed the lipid and lipoprotein profiles of middle-aged Korean female non-drinkers, mild-drinkers, and binge-drinkers, who consumed alcohol for at least 10 years. Unexpectedly, the serum levels of HDL-C and apolipoprotein A-I (apoA-I) were decreased significantly depending on the alcohol amount; the binge-drinker group showed 18% and 13% lower HDL-C (p = 0.011) and apoA-I levels (p = 0.024), respectively, than the non-drinker group. Triglyceride (TG) and oxidized species, malondialdehyde (MDA), and low-density lipoproteins (LDL) levels were significantly elevated in the drinker groups. Interestingly, the binge-drinker group showed 1.4-fold higher (p = 0.020) cholesterol contents in HDL2 and 1.7-fold higher (p < 0.001) TG contents in HDL3 than those of the non-drinker group. The mild-drinker group also showed higher TG contents in HDL3 (p = 0.032) than the non-drinker group, while cholesterol contents were similar in the HDL3 of all groups. Transmission electron microscopy (TEM) showed that the non-drinker group showed a more distinct and clear particle shape of the LDL and HDL image with a larger particle size than the drinker group. Electrophoresis of LDL showed that the drinker group had faster electromobility with a higher smear band intensity and aggregation in the loading position than the non-drinker group. The HDL level of binge drinkers showed the lowest paraoxonase activity, the highest glycated extent, and the most smear band intensity of HDL and apoA-I, indicating that HDL quality and functionality were impaired by alcohol consumption. In conclusion, long-term alcohol consumption in middle-aged women, even in small amounts, caused a significant decrease in the serum HDL-C and apoA-I with atherogenic changes in LDL and HDL, such as an increase in TG and MDA content with a loss of paraoxonase activity.
Isothiocyanates (ITCs) 1-(Isothiocyanatomethyl)-4-phenylbenzene and 1-Isothiocyanato-3,5-bis(trifluoromethyl)benzene—Aldehyde Dehydrogenase (ALDH) Inhibitors, Decreases Cisplatin Tolerance and Migratory Ability of NSCLC
Authors: Kryczka Jolanta , Kryczka Jakub , Janczewski Łukasz , Gajda Anna , Frączyk Andrzej , Boncela Joanna , Kolesińska Beata , Brzeziańska-Lasota Ewa
Published: August 2022

One of the main treatment modalities for non-small-cell lung cancer (NSCLC) is cisplatin-based chemotherapy. However, the acquisition of cisplatin resistance remains a major problem. Existing chemotherapy regimens are often ineffective against cancer cells expressing aldehyde dehydrogenase (ALDH). As such, there is an urgent need for therapies targeting ALDH-positive cancer cells. The present study compares the anticancer properties of 36 structurally diverse isothiocyanates (ITCs) against NSCLC cells with the ALDH inhibitor disulfiram (DSF). Their potential affinity to ALDH isoforms and ABC proteins was assessed using AutoDockTools, allowing for selection of three compounds presenting the strongest affinity to all tested proteins. The selected ITCs had no impact on NSCLC cell viability (at tested concentrations), but significantly decreased the cisplatin tolerance of cisplatin-resistant variant of A549 (A549CisR) and advanced (stage 4) NSCLC cell line H1581. Furthermore, long-term supplementation with ITC 1-(isothiocyanatomethyl)-4-phenylbenzene reverses the EMT phenotype and migratory potential of A549CisR to the level presented by parental A549 cells, increasing E-Cadherin expression, followed by decreased expression of ABCC1 and ALDH3A1. Our data indicates that the ALDH inhibitors DSF and ITCs are potential adjuvants of cisplatin chemotherapy.
Activation Markers on B and T Cells and Immune Checkpoints in Autoimmune Rheumatic Diseases
Authors: Gerasimova Elena V. , Tabakov Dmitry V. , Gerasimova Daria A. , Popkova Tatiana V.
Published: August 2022

In addition to identifying the major B- and T-cell subpopulations involved in autoimmune rheumatic diseases (ARDs), in recent years special attention has been paid to studying the expression of their activation markers and immune checkpoints (ICPs). The activation markers on B and T cells are a consequence of the immune response, and these molecules are considered as sensitive specific markers of ARD activity and as promising targets for immunotherapy. ICPs regulate the activation of the immune response by preventing the initiation of autoimmune processes, and they modulate it by reducing immune cell-induced organ and tissue damage. The article considers the possible correlation of ICPs with the activity of ARDs, the efficacy of specific ARD treatments, and the prospects for the use of activation molecules and activation/blocking ICPs for the treatment of ARDs.
Improved Carpooling Experience through Improved GPS Trajectory Classification Using Machine Learning Algorithms
Authors: Pandey Manish Kumar , Saini Anu , Subbiah Karthikeyan , Chintalapudi Nalini , Battineni Gopi
Published: August 2022

Globally, smart cities, infrastructure, and transportation have led to a rise in vehicle numbers, resulting in an increasing number of problems. This includes problems such as air pollution, noise pollution, high energy consumption, and people’s health. A viable solution to these problems is carpooling, which involves sharing vehicles between people going to the same location. As carpooling solutions become more popular, they need to be implemented efficiently. Data analytics can help people make informed decisions when selecting a ride (Car or Bus). We applied machine learning algorithms to select the desired ride (Car or Bus) and used feature ranking algorithms to identify the foremost traits for selecting the desired ride. Based on the performance evaluation metric, 11 classifiers were used for the experiment. In terms of selecting the desired ride, Random Forest performs best. Using ten-fold cross-validation, we obtained a sensitivity of 87.4%, a specificity of 73.7%, an accuracy of 81.0%, a sensitivity of 90.8%, a specificity of 77.6%, and an accuracy of 84.7% using leave-one-out cross-validation. To identify the most favorable characteristics of the Ride (Car or Bus), the recursive elimination of features algorithm was applied. By identifying the factors contributing to users’ experience, the service providers will be able to rectify those factors to increase business. It has been determined that the weather can make or break the user experience. This model will be used to quantify and map intrinsic and extrinsic sentiments of the people and their interactions with locality, socio-economic conditions, climate, and environment.
Visualizing Social Media Research in the Age of COVID-19
Authors: Michailidis Panagiotis D.
Published: August 2022

During the last three years, numerous research papers have been reported which use social media data to explore several issues related to the COVID-19 pandemic. Bibliometric methods in this work are used to analyze 1427 peer-reviewed documents from the last three years extracted from the Web of Science database. The results of this study show that there was high growth in publications in open access journals with an annual rate reaching 19.3% and they also identify the top cited journals and research papers. The thematic analysis of papers shows that research topics related to social media for surveillance and monitoring of public attitudes and perceptions, mental health, misinformation, and fake news are important and well-developed, whereas topics related to distance-learning education with social media are emerging. The results also show that the USA, China, and the UK have published many papers and received a high number of citations because of their strong international collaboration.
Phylogenetic Analysis of Mitochondrial Genome of Tabanidae (Diptera: Tabanidae) Reveals the Present Status of Tabanidae Classification
Authors: Liu Mingyue , Wu Tingting , Ju Hao , Ma Xiaoxiao , Fang Zihao , Chang Qiaocheng
Published: August 2022

Tabanidae suck the blood of humans and animals, are important biological vectors for the transmission of diseases, and are of considerable economic and medical significance. However, current knowledge about the mitochondrial genome of this family is limited. More complete mitochondrial genomes of Tabanidae are essential for the identification and phylogeny. Therefore, this study sequenced and analyzed six complete mitochondrial (mt) genome sequences of four genera of Tabanidae for the first time. The complete mt genomes of the six new sequences are circular molecules ranging from 15,851 to 16,107 base pairs (bp) in size, with AT content ranging from 75.64 to 77.91%. The six complete mitochondrial genomes all consist of 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (RRNA), 22 transfer RNA genes (tRNAs), and a control region, making a total of 37 functional subunits. ATT/ATG was the most common start codon, and the stop codon was TAA of all PCGS. All tRNA except tRNA Ser1 had a typical clover structure. Phylogeny was inferred by analyzing the 13 concatenated amino acid sequences of the 22 mt genomes. Bayesian inference, maximum-likelihood trees, and maximum-parsimony inference analyses all showed consistent results. This study supports the concept of monophyly of all genus, ratifies the current taxonomic classification, and provides effective genetic markers for molecular classification, systematics, and genetic studies of Tabanidae.
Ground Beetle (Coleoptera: Carabidae) Responses to Cattle Grazing, Grassland Restoration, and Habitat across a Precipitation Gradient
Authors: Waite Evan S. , Houseman Gregory R. , Jensen William E. , Reichenborn Molly M. , Jameson Mary L.
Published: August 2022

Grasslands in North America have declined by over 70% since industrialization of settlements due to the conversion of natural habitats to cropland and urban centers. In the United States, the federally supported Conservation Reserve Program (CRP) was created to improve water quality, reduce soil erosion, and increase native habitats for wildlife. Within these restored grasslands, ground beetles (Coleoptera: Carabidae) are a keystone invertebrate group that fill several crucial niches and may serve as bioindicators of successful land management strategies. To understand the impact of land management on ground beetles, we examined carabid beetle community responses to a grazing treatment and two plant restoration treatments with low and relatively high initial plant diversity over two field seasons. We used pitfall traps at 108 CRP sites across a 63.5 cm precipitation gradient, encompassing three grassland types. Overall, grazing and restoration treatment did not have detectable effects on carabid abundance, biomass, or diversity. Carabid communities, however, responded differently to grazing within grassland types—all three community measures increased in response to grazing in tallgrass sites only. Our short-term study suggests that moderate levels of cattle grazing do not negatively affect carabid communities and might have positive effects on abundance, biomass, and diversity in tallgrass regions.
Cephalad Migration of Tunneled-Cuffed Catheter: The Importance of Post Procedure Imaging
Authors: Kumar Asheesh , Singh Ram
Published: August 2022

TCC placement is a skilled procedure; one must be aware of possible complications, particularly those related to the positioning of catheters, which are vital for the proper functioning of catheters and hemodialysis procedure. It is also equally important to be familiar with the appropriate management if such complications are encountered.
Modeling of Internal Geometric Variability and Statistical Property Prediction of Braided Composites
Authors: Li Wenli , Zhu Donghui , Shao Wenqi , Jiang Dong
Published: August 2022

Due to the advantages of high specific strength, specific stiffness, and excellent fatigue resistance, carbon fiber reinforced braided composites have been widely applied in engineering. Since the molding process of braided composites is complex and immature, substantial variability of the internal geometry exists in composites, in which the yarn path with uncertainty is a main factor, so it is necessary to establish an uncertainty model to study the influence of randomness of the yarn path on mechanical properties, which is significantly related to the fatigue resistance properties of composite. An uncertain mesoscopic model with uniform distribution of yarn paths is proposed. Assuming the yarn path is spatially varying in interval range, the variability of yarn path is represented geometrically in the unit cell of composite. The three-dimensional coordinates of the yarn trajectory are calculated, the meso-uncertainty models of 2-D and 2.5-D braided composites are established. The equivalent elastic parameters and the thermal expansion coefficients are obtained by applying homogenization method and temperature field boundary conditions to the mesoscopic model. The effect of yarn path uncertainty on the statistical characteristics of elastic and thermal parameters of braided composites was studied by using Monte-Carlo simulation. A simulation method for modeling yarn path uncertainty of braided composites is provided in this paper for predicting the statistical characteristics of the equivalent elastic and thermal parameters.
Growth, Structure and Optical Characterization of Rb3Ti3P5O20 Single Crystal
Authors: Zhao Jianfu , Zhu Pengfei , Wang Zhenyan , Ai Li , Duan Xiulan , Yu Fapeng
Published: August 2022

Phosphate crystals attract much attention on account of their rich crystal structures and excellent physical and chemical properties. Herein, Rb3Ti3P5O20 single crystals were grown by the high temperature solution method using Rb2CO3 and NH4H2PO4 as the fluxes. This crystal, with non-centrosymmetric Pca21 space group, presents a three-dimensional framework structure composed of [TiO6] octahedron, [PO4] tetrahedra, and [P2O7] dimers. The electronic structure was measured via X-ray photoelectron spectroscopy. The measurements found that Rb3Ti3P5O20 has stronger Ti–O ionic bonding properties and weaker P–O covalent bonding properties compared to RbTiOPO4. Optical measurements indicated that Rb3Ti3P5O20 has a 3.54 eV band gap and a wide transmission range (0.33–4.5 μm). Theoretical calculations showed that Rb3Ti3P5O20 crystals have a moderate birefringence of 0.079 at 1064 nm. In addition, the relationship of the structure–property was studied using first-principles method. The results demonstrated that TiO6 octahedron played a significant role for the optical properties.
Genome-Wide Identification, Evolutionary Analysis, and Expression Patterns of Cathepsin Superfamily in Black Rockfish (Sebastes schlegelii) following Aeromonas salmonicida Infection
Authors: Li Yuqing , Li Xingchun , Zhang Pei , Chen Defeng , Tao Xinran , Cao Min , Li Chao , Fu Qiang
Published: August 2022

Cathepsins are lysosomal cysteine proteases belonging to the papain family and play crucial roles in intracellular protein degradation/turnover, hormone maturation, antigen processing, and immune responses. In the present study, 18 cathepsins were systematically identified from the fish S. schlegelii genome. Phylogenetic analysis indicated that cathepsin superfamilies are categorized into eleven major clusters. Synteny and genome organization analysis revealed that whole-genome duplication led to the expansion of S. schlegelii cathepsins. Evolutionary rate analyses indicated that the lowest Ka/Ks ratios were observed in CTSBa (0.13) and CTSBb (0.14), and the highest Ka/Ks ratios were observed in CTSZa (1.97) and CTSZb (1.75). In addition, cathepsins were ubiquitously expressed in all examined tissues, with high expression levels observed in the gill, intestine, head kidney, and spleen. Additionally, most cathepsins were differentially expressed in the head kidney, gill, spleen, and liver following Aeromonas salmonicida infection, and their expression signatures showed tissue-specific and time-dependent patterns. Finally, protein–protein interaction network (PPI) analyses revealed that cathepsins are closely related to a few immune-related genes, such as interleukins, chemokines, and TLR genes. These results are expected to be valuable for comparative immunological studies and provide insights for further functional characterization of cathepsins in fish species.
Treatment Options in Early Stage (Stage I and II) of Oropharyngeal Cancer: A Narrative Review
Authors: Meccariello Giuseppe , Catalano Andrea , Cammaroto Giovanni , Iannella Giannicola , Vicini Claudio , Hao Sheng-Po , De Vito Andrea
Published: August 2022

Objective: to show an overview on the treatments’ options for stage I and II oropharyngeal carcinomasquamous cell carcinoma (OPSCC). Background: The traditional primary treatment modality of OPSCC at early stages is intensity modulated radiation therapy (IMRT). Trans-oral robotic surgery (TORS) has offered as an alternative, less invasive surgical option. Patients with human papilloma virus (HPV)-positive OPSCC have distinct staging with better overall survival in comparison with HPV-negative OPSCC patients. Methods: a comprehensive review of the English language literature was performed using PubMed, EMBASE, the Cochrane Library, and CENTRAL electronic databases. Conclusions: Many trials started examining the role of TORS in de-escalating treatment to optimize functional consequences while maintaining oncologic outcome. The head–neck surgeon has to know the current role of TORS in HPV-positive and negative OPSCC and the ongoing trials that will influence its future implementation. The feasibility of this treatment, the outcomes ensured, and the side effects are key factors to consider for each patient. The variables reported in this narrative review are pieces of a bigger puzzle called tailored, evidence-based driven medicine. Future evidence will help in the construction of robust and adaptive algorithms in order to ensure the adequate treatment for the OPSCC at early stages.
In Situ Generation of Fouling Resistant Ag/Pd Modified PES Membranes for Treatment of Pharmaceutical Wastewater
Authors: Patala Rapelang , Mahlangu Oranso T. , Nyoni Hlengilizwe , Mamba Bhekie B. , Kuvarega Alex T.
Published: August 2022

In this study, Ag and Pd bimetallic nanoparticles were generated in situ in polyethersulfone (PES) dope solutions, and membranes were fabricated through a phase inversion method. The membranes were characterized for various physical and chemical properties using techniques such as FTIR, SEM, AFM, TEM, EDS, and contact angle measurements. The membranes were then evaluated for their efficiency in rejecting EOCs and resistance to protein fouling. TEM micrographs showed uniform distribution of Ag/Pd nanoparticles within the PES matrix, while SEM images showed uniform, fingerlike structures that were not affected by the presence of embedded nanoparticles. The presence of Ag/Pd nanoparticles resulted in rougher membranes. There was an increase in membrane hydrophilicity with increasing nanoparticles loading, which resulted in improved pure water permeability (37–135 Lm2h−1bar−1). The membranes exhibited poor salt rejection (<15%), making them less susceptible to flux decline due to concentration polarization. With a mean pore radius of 2.39–4.70 nm, the membranes effectively removed carbamazepine, caffeine, sulfamethoxazole, ibuprofen, and naproxen (up to 40%), with size exclusion being the major removal mechanism. Modifying the membranes with Ag/Pd nanoparticles improved their antifouling properties, making them a promising innovation for the treatment of pharmaceutical wastewater.
Extreme Alteration of Chevkinite-(Ce) by Pb-CO2-Rich Fluids: Evidence from the White Tundra Pegmatite, Keivy Massif, Kola Peninsula
Authors: Macdonald Ray , Bagiński Bogusław , Stachowicz Marcin , Zozulya Dmitry , Kotowski Jakub , Jokubauskas Petras
Published: August 2022

An unusual hydrothermal alteration scheme was presented for chevkinite-(Ce) from the White Tundra pegmatite (2656 ± 5 Ma), Keivy massif, Kola Peninsula. Pb-CO2-rich fluids initially removed REE and Y from the chevkinite-(Ce), with enrichment in Pb and U. PbO abundances reaching 17.35 wt%. Continued alteration resulted in the altered chevkinite-(Ce) being progressively transformed to a Pb-Ti-Fe-Si phase, which proved, upon EBSD analysis, to be almost totally amorphous. Pb enrichment was accompanied by a loss of LREE, especially La, relative to HREE, and the development of strong positive Ce anomalies. A notably U-rich aeschynite-(Y), with UO2 values ≤7.67 wt%, crystallized along with the chevkinite-(Ce). Aeschynite-(Y) with a lower UO2 value (3.91 wt%) and bastnäsite-(Ce) formed during alteration. The formation of bastnäsite-(Ce) rather than cerussite, which might have been expected in a high Pb-CO2 environment, is ascribed to the fluids being acidic.
Proximate, Elemental, and Functional Properties of Novel Solid Dispersions of Moringa oleifera Leaf Powder
Authors: Tafu Nontsikelelo Noxolo , Jideani Victoria A.
Published: August 2022

Moringa oleifera leaf powder (MOLP) is a rich source of antioxidants, protein, minerals, vitamins, and various phytochemicals and has been used to combat malnutrition in many countries. However, despite its many benefits, MOLP has low a solubility in water, necessitating the development of ways to address this issue. To improve the solubility of MOLP, solid-dispersed Moringa oleifera leaf powders (SDMOLPs) have been developed through freeze-drying, melting, microwave irradiation, and solvent evaporation methods using polyethylene glycols (PEG4000 and PEG6000) (1:1) as hydrophilic carriers. The solid dispersions were evaluated for their proximate composition using standard analytical procedures. Elemental composition was characterized using scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDS). Water absorption capacity (WAC) and water-solubility were further evaluated as functional properties. Proximate composition revealed that MOLP and SDMOLPs were rich in protein, energy, carbohydrate, ash, and fat contents. MOLP solid dispersions are a major source of minerals (Ca, Mg, Cu, and Zn), and can be used to alleviate many mineral deficiencies. All solid dispersions had significantly higher (p < 0.05) solubilities (ranging from 54 to 64%) and WAC (ranging from 468.86 to 686.37%), relative to that of pure MOLP. The increased solubility of SDMOLPs may be attributed to the hydrogen bonds and intermolecular interactions between MOLP and the hydrophilic carriers. The results indicate that the solid dispersion technique can be successfully employed to improve the solubility of MOLP. And the solid-dispersed MOLPs with enhanced functional properties may be useful as functional ingredients in foods and beverages, dietary supplements, or nutraceutical formulations.
Adsorption of Helium and Hydrogen on Triphenylene and 1,3,5-Triphenylbenzene
Authors: Bergmeister Stefan , Kollotzek Siegfried , Calvo Florent , Gruber Elisabeth , Zappa Fabio , Scheier Paul , Echt Olof
Published: August 2022

The adsorption of helium or hydrogen on cationic triphenylene (TPL, C18H12), a planar polycyclic aromatic hydrocarbon (PAH) molecule, and of helium on cationic 1,3,5-triphenylbenzene (TPB, C24H18), a propeller-shaped PAH, is studied by a combination of high-resolution mass spectrometry and classical and quantum computational methods. Mass spectra indicate that HenTPL+ complexes are particularly stable if n = 2 or 6, in good agreement with the quantum calculations that show that for these sizes, the helium atoms are strongly localized on either side of the central carbon ring for n = 2 and on either side of the three outer rings for n = 6. Theory suggests that He14TPL+ is also particularly stable, with the helium atoms strongly localized on either side of the central and outer rings plus the vacancies between the outer rings. For HenTPB+, the mass spectra hint at enhanced stability for n = 2, 4 and, possibly, 11. Here, the agreement with theory is less satisfactory, probably because TPB+ is a highly fluxional molecule. In the global energy minimum, the phenyl groups are rotated in the same direction, but when the zero-point harmonic correction is included, a structure with one phenyl group being rotated opposite to the other two becomes lower in energy. The energy barrier between the two isomers is very small, and TPB+ could be in a mixture of symmetric and antisymmetric states, or possibly even vibrationally delocalized.
Enhancement of TRP Gene Expression and UV Absorption by Bioconverted Chestnut Inner Shell Extracts Using Lactiplantibacillus plantarum
Authors: Kim So-Hee , Yoem Suh-Hee , Kim Jun-Hee , Hong Ji-Woo , Oh Ye-Sol , Kim Jin-Woo
Published: August 2022

In this work, the suppression of tyrosinase-related genes, including an improvement in UV absorption effects of bioconverted CS extracts (BCS), was investigated to improve the skin-whitening effect. Total polyphenols and total flavonoids, which are bioactive components, increased 2.6- and 5.4-times in bioconversion using Lactiplantibacillus plantarum SM4, respectively, as compared to ultrasound-assisted extracts (UCS). The effect of BCS on radical scavenging activity, UV-A absorption, and tyrosinase activity inhibition, contributing to skin-whitening, were 1.3-, 1.2-, and 1.2-times higher than those of UCS, respectively. The main component identified in high-performance liquid chromatography (HPLC) was gallic acid in both UCS and BCS, which increased by 2.9-times following bioconversion. The gene expression of tyrosinase-related proteins, including TRP-1 and TRP-2 genes, was studied to confirm the suppression of melanin synthesis by BCS in order to identify the skin-whitening mechanism, and BCS decreased both genes’ expression by 1.7- and 1.6-times, demonstrating that BCS effectively suppressed melanin synthesis. These findings imply that the chestnut inner shell can be employed as a cosmetic material by simultaneously inhibiting melanogenesis and enhancing UV-A absorption through bioconversion using L. plantarum SM4.
Recent Strategies in Transition-Metal-Catalyzed Sequential C–H Activation/Annulation for One-Step Construction of Functionalized Indazole Derivatives
Authors: Shiri Pezhman , Roosta Atefeh , Dehaen Wim , Amani Ali Mohammad
Published: August 2022

Designing new synthetic strategies for indazoles is a prominent topic in contemporary research. The transition-metal-catalyzed C–H activation/annulation sequence has arisen as a favorable tool to construct functionalized indazole derivatives with improved tolerance in medicinal applications, functional flexibility, and structural complexity. In the current review article, we aim to outline and summarize the most common synthetic protocols to use in the synthesis of target indazoles via a transition-metal-catalyzed C–H activation/annulation sequence for the one-step synthesis of functionalized indazole derivatives. We categorized the text according to the metal salts used in the reactions. Some metal salts were used as catalysts, and others may have been used as oxidants and/or for the activation of precatalysts. The roles of some metal salts in the corresponding reaction mechanisms have not been identified. It can be expected that the current synopsis will provide accessible practical guidance to colleagues interested in the subject.
Effects of High Pressure Processing and Thermal Treatment on the Interaction between α-Lactalbumin and Pelargonium-3-Glucoside
Authors: Tian Xuezhi , Zou Hui , Yang Peiqing , Ma Yan , Li Yuwan , Zhao Liang , Wang Yongtao , Liao Xiaojun
Published: August 2022

In this study, high pressure processing (HPP) and thermal treatment were comparatively evaluated by examining their impacts on the binding behavior and interaction between α-lactalbumin (α-La) and pelargonium-3-glucoside (P3G) under pH values of 6.0, 7.4, and 8.0. The methods of circular dichroism spectroscopy, fluorescence quenching, dynamic light scattering, and molecular simulation were used to characterize the effects of processing-induced changes in protein structure, size distribution, binding site conformation, and residue charges on their binding characteristics between them. The results indicated that the thermal treatments significantly increased the quenching constants of the complex at pH 7.4/8.0 and 60/80 °C, as well as the accessible fraction of protein at pH 8.0/80 °C. Both HPP and thermal treatments increased the random coil content and showed limited effects on the α-helix and β-sheet contents of α-La and caused the aggregation of the complex to varying degrees. Molecular dynamic simulation and docking analyses revealed that the binding site of the complex did not change under different processing conditions, but the solvent-accessible surface area varied under different conditions.
A Comparison of Conventional and Ultrasound-Assisted BCR Sequential Extraction Methods for the Fractionation of Heavy Metals in Sewage Sludge of Different Characteristics
Authors: Tytła Malwina , Widziewicz-Rzońca Kamila , Bernaś Zuzanna
Published: August 2022

The purpose of this study was to determine the heavy metal (HM: Cd, Cr, Cu, Ni, Pb, Zn, and Hg) content in particular chemical fractions (forms) of sewage sludge with different characteristics (primary and dewatered sludge) using conventional (CSE) and ultrasound-assisted (USE) BCR sequential extraction methods (Community Bureau of Reference, now the Standards, Measurements and Testing Programme). The concentrations of HMs were determined using inductively coupled plasma optical spectrometry (ICP-OES). Only mercury was assayed with cold vapor atomic absorption spectrometry (CVAAS). Ultrasound treatment was conducted in the ultrasonic bath (Sonic 5, Polsonic). The optimal sonication time (30 min) was determined using ERM-CC144 (Joint Research Center; JCR) certified reference material. The conducted experiment revealed that the use of ultrasound waves shortened the extraction time to 4 h and 30 min (Stages I to III). The recoveries (RM) of heavy metals ranged from 62.8% to 130.2% (CSE) and from 79.8% to 135.7% (USE) for primary sludge, and from 87.2% to 113.2% (CSE) and from 87.8% to 112.0% (USE) for dewatered sludge. The only exception was Hg in dewatered sludge. The conducted research revealed minor differences in the concentrations and fractionation patterns for Cd, Ni, and Zn extracted from sludge samples by the tested methods. However, it was confirmed that the above findings do not significantly affect the results of a potential ecological risk assessment (with minor exceptions for Cd and Zn in the primary sludge), which is extremely essential for the natural use of sludge, and especially dewatered sludge (the final sludge). The shorter extraction time and lower energy consumption prove that ultrasound-assisted extraction is a fast and simple method for HM fractionation, and that it provides an alternative to the conventional procedure. Therefore, it can be considered a “green method” for the assessment of the bioavailability and mobility of heavy metals in solid samples.
Hybrid Molecules Containing Naphthoquinone and Quinolinedione Scaffolds as Antineoplastic Agents
Authors: Mancini Ines , Vigna Jacopo , Sighel Denise , Defant Andrea
Published: August 2022

In recent decades, molecular hybridization has proven to be an efficient tool for obtaining new synthetic molecules to treat different diseases. Based on the core idea of covalently combining at least two pharmacophore fragments present in different drugs and/or bioactive molecules, the new hybrids have shown advantages when compared with the compounds of origin. Hybridization could be successfully applied to anticancer drug discovery, where efforts are underway to develop novel therapeutics which are safer and more effective than those currently in use. Molecules presenting naphthoquinone moieties are involved in redox processes and in other molecular mechanisms affecting cancer cells. Naphthoquinones have been shown to inhibit cancer cell growth and are considered privileged structures and useful templates in the design of hybrids. The present work aims at summarizing the current knowledge on antitumor hybrids built using 1,4- and 1,2-naphthoquinone (present in natural compounds as lawsone, napabucasin, plumbagin, lapachol, α-lapachone, and β -lapachone), and the related quinolone- and isoquinolinedione scaffolds reported in the literature up to 2021. In detail, the design and synthetic approaches adopted to produce the reported compounds are highlighted, the structural fragments considered in hybridization and their biological activities are described, and the structure–activity relationships and the computational analyses applied are underlined.
Development of a Lateral Flow Strip with a Positive Readout for the On-Site Detection of Aflatoxin B1
Authors: Shen Kemin , Hu Xiaoqin , Sun Linlin , Han Chun , Yang Jianzhou
Published: August 2022

Aflatoxin B1 is one of the contamination indicators for food safety monitoring. The rapid and effective assessment and determination of AFB1 in food is of great importance to dietary safety. The lateral flow assay shows advantages in its simplicity, and rapidity, and provides a visual readout, while the available lateral flow assay for AFB1 requires a competitive format that produces readings inversely proportional to the AFB1 concentration, which is counterintuitive and may lead to a potential misinterpretation of the results. Herein, we developed a positive readout aptamer-based lateral flow strip (Apt-strip) for the detection of AFB1. This Apt-strip relies on the competition between AFB1 and fluorescein-labeled complementary DNA strands (FAM-cDNA) for affinity binding to limited aptamers against AFB1 (AFB1-Apt). In the absence of AFB1, AFB1-Apt hybridizes with FAM-cDNA. No signal at the T-line of the Apt-strip was observed. In contrast, AFB1-Apt binds to AFB1 in the sample, and then a part of the FAM-cDNA is hybridized with the free AFB1-Apt, at which time the other unreacted FAM-cDNA is captured by A35-Apt on the T-line. The signal was observed. This method achieved fast detection of AFB1 with a detection limit (DL) of 0.1 ng/mL, positive readout, and increased sensitivity.
Chemical Approach to the Optimization of Conditions Using HS-SPME/GC–MS for Characterization of Volatile Compounds in Eugenia brasiliensis Fruit
Authors: Ramos Ana Luiza Coeli Cruz , Nogueira Laiza Andrade , Silva Mauro Ramalho , do Carmo Mazzinghy Ana Carolina , Mariano Ana Paula Xavier , de Albuquerque Rodrigues Tássia Nunes , de Paula Ana Cardoso Clemente Filha Ferreira , de Melo Angelita Cristine , Augusti Rodinei , de Araújo Raquel Linhares Bello , Lacerda Inayara Cristina Alves , Melo Júlio Onésio Ferreira
Published: August 2022

Grumixama (Eugenia brasiliensis Lam.) is a native fruit of the Brazilian Atlantic Forest, belonging to the Myrtaceae family, which designatesthe most significant number of species with food potential. It stands out due to its phytochemical characteristics because of the presence of polyphenols and volatile organic compounds. Volatile compounds are substances released by foods that give off an aroma and influence flavor. Solid-phase microextraction is a technique that allows for low-cost, fast, and solvent-free extraction, has an affinity for numerous analytes, and is easily coupled to gas chromatography. The objectives of this work were to evaluate the efficiency of different fibers of SPME (solid-phase microextraction) in the extraction of volatile organic compounds from grumixama pulp; optimize a method for extraction time, temperature, and sample weight; and to determine the characteristic volatile profile of this fruit. For the extraction of volatile compounds, three fibers of different polarities were used: polar polyacrylate (PA) fibers, divinylbenzene/carboxyne/polydimethylsiloxane (DVB/CAR/PDMS) semipolar fibers, and polydimethylsiloxane/divinylbenzene (PDMS/DVB). Fourteen volatile organic compounds (VOCs) were identified by DVB/CAR/PDMS, six by PA, and seven by PDMS/DVB through solid-phase microextraction in the headspace mode (SPME-HS). Considering the total number of compounds identified, regardless of the fiber used, and the optimization of the method, Eugenia brasiliensis presented sesquiterpene fractions (85.7%, 83.3%, and 85.7% of total VOCs) higher than the monoterpene fractions (14.3%, 16.7%, and 14.3%) for DVB/CAR/PDMS, PA, and PDMS/DVB, respectively in its composition. In addition, it was possible to verify that the fiber DVB/CAR/PDMS presented a better efficiency due to the larger chromatographic area observed when the grumixama pulp was subjected to conditions of 75 °C, 2.0 g, and an adsorption time of 20 min.
Antibacterial Properties of Silver Nanoclusters with Carbon Support on Flexible Polymer
Authors: Hurtuková Klaudia , Vašinová Tereza , Kasálková Nikola Slepičková , Fajstavr Dominik , Rimpelová Silvie , Pavlíčková Vladimíra Svobodová , Švorčík Václav , Slepička Petr
Published: August 2022

Here, we aimed at the preparation of an antibacterial surface on a flexible polydimethylsiloxane substrate. The polydimethylsiloxane surface was sputtered with silver, deposited with carbon, heat treated and exposed to excimer laser, and the combinations of these steps were studied. Our main aim was to find the combination of techniques applicable both against Gram-positive and Gram-negative bacteria. The surface morphology of the structures was determined by atomic force microscopy and scanning electron microscopy. Changes in surface chemistry were conducted by application of X-ray photoelectron spectroscopy and energy dispersive spectroscopy. The changes in surface wettability were characterized by surface free energy determination. The heat treatment was also applied to selected samples to study the influence of the process on layer stability and formation of PDMS-Ag or PDMS-C-Ag composite layer. Plasmon resonance effect was determined for as-sputtered and heat-treated Ag on polydimethylsiloxane. The heating of such structures may induce formation of a pattern with a surface plasmon resonance effect, which may also significantly affect the antibacterial activity. We have implemented sputtering of the carbon base layer in combination with excimer laser exposure of PDMS/C/Ag to modify its properties. We have confirmed that deposition of primary carbon layer on PDMS, followed by sputtering of silver combined with subsequent heat treatment and activation of such surface with excimer laser, led to the formation of a surface with strong antibacterial properties against two bacterial strains of S. epidermidis and E. coli.
Biomolecular Corona Stability in Association with Plasma Cholesterol Level
Authors: Trinh Duong N. , Radlinskaite Meda , Cheeseman Jack , Kuhnle Gunter , Osborn Helen M. I. , Meleady Paula , Spencer Daniel I. R. , Monopoli Marco P.
Published: August 2022

Biomolecular corona is spontaneously formed on the surface of nanoparticles (NPs) when they are in contact with biological fluids. It plays an important role in the colloidal stability of NPs, which is of importance for most of their medical applications and toxicity assessment. While typical studies use either blood plasma or serum from a pooled biobank, it is unclear whether differences in the media, such as cholesterol level or protein concentration, might affect the NP colloidal stability and corona composition. In this study, the silica corona was prepared at particularly low plasma concentrations (3%, v/v–1.98 mg/mL) to identify the critical roles of the protein mass/NP surface ratio and the level of plasma cholesterol on the corona protein pattern and particle stability. While depending on the plasma dilution factor, the corona protein composition could be controlled by keeping the protein/NP constant. The NP colloidal stability was found to strongly correlate with the level of cholesterol in human plasma, particularly due to the high enrichment of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) in the corona. A cohort study on plasma samples from individuals with known cholesterol levels was performed to highlight that association, which could be relevant for all corona systems enriched with the LDL.
Dietary Fibre and Organic Acids in Kiwifruit Suppress Glycaemic Response Equally by Delaying Absorption—A Randomised Crossover Human Trial with Parallel Analysis of 13C-Acetate Uptake
Authors: Monro John , Mishra Suman , Stoklosinski Halina , Bentley-Hewitt Kerry , Hedderley Duncan , Dinnan Hannah , Martell Sheridan
Published: August 2022

Non-sugar components of kiwifruit reduce the amplitude of the glycaemic response to co-consumed cereal starch. We determined the relative contribution of different non-sugar kiwifruit components to this anti-glycaemic effect. Healthy participants (n = 9) ingested equal carbohydrate meals containing 20 g starch as wheat biscuit (WB, 30 g), and the sugar equivalent of two kiwifruit (KFsug, 20.4 g), either intrinsic or added as glucose, fructose and sucrose (2:2:1). The meals were WB+KFsug (control, no non-sugar kiwifruit components), WB + whole kiwifruit pulp (WB+KF), WB + neutralised kiwifruit pulp (WB+KFneut), WB + low-fibre kiwifruit juice (WB+KFjuice) and WB+KFsug + kiwifruit organic acids (WB+KFsug+OA). All meals were spiked with 100 mg sodium [1-13C] acetate to measure intestinal absorption. Each participant ingested all meals in random order. Blood glucose and breath 13CO2 were measured at ingestion and at 15 min intervals up to 180 min. Compared with WB+KFsug, whole kiwifruit pulp (WB+KF) almost halved glycaemic response amplitude (p < 0.001), reduced incremental area under the blood glucose response curve (iAUC) at 30 min (peak) by 50% (p < 0.001), and averted late postprandial hypoglycaemia. All other treatments suppressed response amplitude half as much as whole kiwifruit and averted acute hypoglycaemia, with little effect on iAUC. Effects on 13CO2 exhalation paralleled effects on blood glucose (R2 = 0.97). Dietary fibre and organic acids contributed equally to the anti-glycaemic effect of kiwifruit by reducing intestinal absorption rate. Kiwifruit flesh effectively attenuates glycaemic response in carbohydrate exchange, as it contains fructose, dietary fibre and organic acids.
Optimization of Long-Acting Bronchodilator Dose Ratios Using Isolated Guinea Pig Tracheal Rings for Synergistic Combination Therapy in Asthma and COPD
Authors: Menchi Elena , El Khattabi Charaf , Pochet Stéphanie , Denis Olivier , Amighi Karim , Wauthoz Nathalie
Published: August 2022

The co-administration of a long-acting β2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA), has been shown to be beneficial in the management of non-communicable chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). The resulting relaxation of the airways can be synergistically enhanced, reducing symptoms and optimizing lung function. This provides an insight into more effective treatments. In this study, the LABAs formoterol fumarate dihydrate (FOR) and indacaterol maleate (IND) were each associated with tiotropium bromide monohydrate (TIO) to assess their synergistic potential. This was done using an appropriate ex vivo model of isolated perfused guinea pig tracheal rings, and pharmacological models of drug interaction. Among the dose ratios studied for both types of combination, a higher synergistic potential was highlighted for FOR/TIO 2:1 (w/w). This was done through three steps by using multiple additions of drugs to the organ baths based on a non-constant dose ratio and then on a constant dose ratio, and by a single addition to the organ baths of specific amounts of drugs. In this way, the synergistic improvement of the relaxant effect on the airways was confirmed, providing a basis for improving therapeutic approaches in asthma and COPD. The synergy found at this dose ratio should now be confirmed on a preclinical model of asthma and COPD by assessing lung function.
Factors Affecting the Metabolic Conversion of Ciprofloxacin and Exposure to Its Main Active Metabolites in Critically Ill Patients: Population Pharmacokinetic Analysis of Desethylene Ciprofloxacin
Authors: Šíma Martin , Bobek Daniel , Cihlářová Petra , Ryšánek Pavel , Roušarová Jaroslava , Beroušek Jan , Kuchař Martin , Vymazal Tomáš , Slanař Ondřej
Published: August 2022

The objective of this prospective study was to examine the exposure to the main active metabolites of ciprofloxacin in critically ill patients and to examine the factors (demographic, laboratory and genetic) that could potentially affect the drug metabolic conversion of ciprofloxacin. The secondary aim was to develop a population pharmacokinetic model for the metabolite showing the most associations with the abovementioned factors. A total of 29 patients were treated with intravenous infusion of ciprofloxacin and enrolled on this trial. Blood samples for pharmacokinetic analysis were taken at 1, 4, and 11.5 h following the completion of the infusion. Sex, age, body weight, height, serum creatinine and bilirubin levels, and creatinine clearance (CLCR) were recorded, and polymorphisms rs2032582 and rs1045642 in the ABCB1 gene, rs4148977 in the SLCO1A2 gene and rs762551 in the CYP1A2 gene were analyzed. A three-stage parent drug–metabolite population pharmacokinetic model was developed. Median (IQR) metabolite/parent ratios of the desethylene ciprofloxacin, formyl ciprofloxacin and oxociprofloxacin were 5.86 (4.09–9.87)%, 4.08 (3.38–6.92)% and 5.91 (3.42–13.65)%, respectively. The desethylene ciprofloxacin metabolic ratio was positively associated with height (r2 = 0.2277, p = 0.0089) and CLCR (r2 = 0.2023, p = 0.0144) and negatively associated with age (r2 = 0.2227, p = 0.0112). Males had a significantly higher oxociprofloxacin metabolic ratio than females (9.14 vs 3.42%, p = 0.0043). In the desethylene ciprofloxacin population PK model, the volume of distribution decreased with age, the parent drug-metabolite transfer rate constant increased with CLCR, and the metabolite elimination rate constant decreased with age and is increased in CYP1A2 rs762551 variant allele carriers. We therefore hypothesized that the CYP1A2 inhibition by ciprofloxacin is mediated by its metabolite desethylene ciprofloxacin.