bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical Reclamation of Spent Moulding Sand on Chromite Sand Matrix; Removal of Alkali-Phenolic Binder
Authors: Łucarz Mariusz , Garbacz-Klempka Aldona , Drożyński Dariusz , Skrzyński Mateusz , Kostrzewa Krzysztof
Published: April 2023

The foundry industry generates large amounts of waste when casting metal into sand moulds. An important issue is the activities that are related to the re-recovery of the grain matrix (the main component of the moulding sand) for realising subsequent technological cycles. This process is particularly important in the case of the expensive chromite matrix that is necessary for use in manganese steel casting. The effects of the reclamation treatments of spent alkali-phenolic binder sand were evaluated by scanning electron microscopy with EDS, analysing the chemical composition in micro areas and proving the loss of binder on the surfaces of the matrix grains. Tests were also performed using the main criteria for evaluating a reclaimed organic binder: sieve analysis and ignition loss. A thermogravimetric analysis study was performed to assess the change in the chromite character of the grain matrix under the influence of temperature. The effects of the reclamation measures were verified by making moulding compounds on a matrix of reclaimed sand and a mixture of reclaimed and fresh sand. The tests and analyses that were carried out indicated the direction of an effective method for reclaiming used alkali-phenolic binder masses and the extent of the proportion of the regenerate in moulding sand in order to maintain the relevant technological parameters of the moulding sand.
Thermodynamic Analysis of Chemical Hydrogen Storage: Energetics of Liquid Organic Hydrogen Carrier Systems Based on Methyl-Substituted Indoles
Authors: Vostrikov Sergey V. , Samarov Artemiy A. , Turovtsev Vladimir V. , Wasserscheid Peter , Müller Karsten , Verevkin Sergey P.
Published: April 2023

Liquid organic hydrogen carriers can store hydrogen in a safe and dense form through covalent bonds. Hydrogen uptake and release are realized by catalytic hydrogenation and dehydrogenation, respectively. Indoles have been demonstrated to be interesting candidates for this task. The enthalpy of reaction is a crucial parameter in this regard as it determines not only the heat demand for hydrogen release, but also the reaction equilibrium at given conditions. In this work, a combination of experimental measurements, quantum chemical methods and a group-additivity approach has been applied to obtain a consistent dataset on the enthalpies of formation of different methylated indole derivatives and their hydrogenated counterparts. The results show a namable influence of the number and position of methyl groups on the enthalpy of reaction. The enthalpy of reaction of the overall hydrogenation reaction varies in the range of up to 18.2 kJ·mol−1 (corresponding to 4.6 kJ·mol(H2)−1). The widest range of enthalpy of reaction data for different methyl indoles has been observed for the last step (hydrogenation for the last double bond in the five-membered ring). Here a difference of up to 7.3 kJ·mol(H2)−1 between the highest and the lowest value was found.
Predicting the Quality of Grain Refiners from Electrical Resistance Measurements of Aluminum
Authors: Vončina Maja , Paulin Irena , Medved Jožef , Petrič Mitja
Published: April 2023

The objective of grain refining is to reduce the size of the primary solidified crystal grains in aluminum alloys, thereby eliminating large columnar grains. Excellent grain refining results can be achieved only when the grain refining agent is of excellent quality, i.e., the number of Al3Ti and TiB2 particles must be appropriate, the shape and size distribution of the particles must be suitable, the Ti/B ratio must be appropriate, and so on. To evaluate the quality of grain refiners, the electric resistivity was measured on four different grain refiners. The obtained results were supported by differential scanning calorimetry analyses and microstructure analyses. It was found that the quality of a grain refiner can be assessed by measurements of electrical resistance. The lowest electrical resistivity was measured for grain refiner B (Al-3Ti-1B), which had the lowest impurity content and the most suitable number and size distribution of TiB2 and Al3Ti particles, as well as the most optimal Ti/B ratio, namely, 3.6. A larger number and size of TiB2 and Al3Ti particles, as well as elements such as Fe and Si, and also inclusions, which were also confirmed by DSC analyses, cause a higher electrical resistivity due to a stronger scattering of electrons through the matrix.
Oral Exposure to Epoxiconazole Disturbed the Gut Micro-Environment and Metabolic Profiling in Male Mice
Authors: Weng You , Xu Ting , Wang Caihong , Jin Yuanxiang
Published: April 2023

Epoxiconazole (EPX), a triazole fungicide, is widely used in agriculture to control pests and diseases. High residual and occupational exposure to EPX increases health risks, and evidence of potential harm to mammals remains to be added. In the present study, 6-week-old male mice were exposed to 10 and 50 mg/kg bw EPX for 28 days. The results showed that EPX significantly increased the liver weights. EPX also decreased the mucus secretion of the colon and altered intestinal barrier function in mice including a reduced expression of some genes (Muc2, meprinβ, tjp1). Moreover, EPX altered the composition and abundance of gut microbiota in the colon of mice. The alpha diversity indices (Shannon, Simpson) in the gut microbiota increased after exposure to EPX for 28 days. Interestingly, EPX increased the ratio of Firmicutes to Bacteroides and the abundance of other harmful bacteria including Helicobacter and Alistipes. Based on the untargeted metabolomic analysis, it was found that EPX altered the metabolic profiles of the liver in mice. KEGG analysis of differential metabolites revealed that EPX disrupted the pathway related to glycolipid metabolism, and the mRNA levels of related genes were also confirmed. In addition, the correlation analysis showed that the most altered harmful bacteria were associated with some significantly altered metabolites. The findings highlight that EPX exposure changed the micro-environment and lipid metabolism disturbance. These results also suggest that the potential toxicity of triazole fungicides to mammals cannot be ignored.
Urinary Metabolomics for the Prediction of Radiation-Induced Cardiac Dysfunction
Authors: Li Yaoxiang , Bansal Shivani , Sridharan Vijayalakshmi , Bansal Sunil , Jayatilake Meth M. , Fernández Jose A. , Griffin John H. , Boerma Marjan , Cheema Amrita K.
Published: April 2023

Survivors of acute radiation exposure are likely to experience delayed effects that manifest as injury in late-responding organs such as the heart. Non-invasive indicators of radiation-induced cardiac dysfunction are important in the prediction and diagnosis of this disease. In this study, we aimed to identify urinary metabolites indicative of radiation-induced cardiac damage by analyzing previously collected urine samples from a published study. The samples were collected from male and female wild-type (C57BL/6N) and transgenic mice constitutively expressing activated protein C (APCHi), a circulating protein with potential cardiac protective properties, who were exposed to 9.5 Gy of γ-rays. We utilized LC-MS-based metabolomics and lipidomics for the analysis of urine samples collected at 24 h, 1 week, 1 month, 3 months, and 6 months post-irradiation. Radiation caused perturbations in the TCA cycle, glycosphingolipid metabolism, fatty acid oxidation, purine catabolism, and amino acid metabolites, which were more prominent in the wild-type (WT) mice compared to the APCHi mice, suggesting a differential response between the two genotypes. After combining the genotypes and sexes, we identified a multi-analyte urinary panel at early post-irradiation time points that predicted heart dysfunction using a logistic regression model with a discovery validation study design. These studies demonstrate the utility of a molecular phenotyping approach to develop a urinary biomarker panel predictive of the delayed effects of ionizing radia-tion. It is important to note that no live mice were used or assessed in this study; instead, we focused solely on analyzing previously collected urine samples.
Study on the Metabolic Transformation Rule of Enrofloxacin Combined with Tilmicosin in Laying Hens
Authors: Guo Jingchao , Zhang Liyun , Zhao Yongxia , Ihsan Awais , Wang Xu , Tao Yanfei
Published: April 2023

There is often abuse of drugs in livestock and poultry production, and the improper use of drugs leads to the existence of a low level of residues in eggs, which is a potential threat to human safety. Enrofloxacin (EF) and tilmicosin (TIM) are regularly combined for the prevention and treatment of poultry diseases. The current studies on EF or TIM mainly focus on a single drug, and the effects of the combined application of these two antibiotics on EF metabolism in laying hens are rarely reported. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the residual EF and TIM in laying hens and to investigate the effect of TIM on the EF metabolism in laying hens. In this paper, we first establish a method that can detect EF and TIM simultaneously. Secondly, the results showed that the highest concentration of EF in the egg samples was 974.92 ± 441.71 μg/kg on the 5th day of treatment. The highest concentration of EF in the egg samples of the combined administration group was 1256.41 ± 226.10 μg/kg on the 5th day of administration. The results showed that when EF and TIM were used in combination, the residue of EF in the eggs was increased, the elimination rate of EF was decreased, and the half-life of EF was increased. Therefore, the use of EF and TIM in combination should be treated with greater care and supervision should be strengthened to avoid risks to human health.
Petrophysical Acoustic Characterization of Weathered Granite: A Case Study of Mesozoic Granites in the Coastal Area of Fujian Province, China
Authors: Tian Zhiwen , Liu Jinshui , Tang Huafeng , Ma Wenrui , Tao Peng , Dong Zhe , Hu Jingsong
Published: April 2023

In recent years, with the exploration and development of granite buried-hill oil and gas reservoirs, petrophysics research has played an important role in the study of reservoir characteristics and fluid identification. Through analysis of the relationship between the fluid-bearing petrophysical parameters and the reservoir, the seismic response changes caused by reservoir fluid changes can be determined. Mesozoic granites in the coastal area of Fujian Province in eastern China were investigated as the research object of this project. The mineral composition, density, porosity, P-wave velocity, and S-wave velocity of the granite were measured and analyzed by X-ray diffraction, rock density, rock porosity, and rock acoustics methods. Therefore, the granite’s petrophysical properties, fluid response characteristics, and gas sensitivity parameters were analyzed. The result of the study shows that the granite is predominantly monzogranite. According to the type of reservoir space assemblage, the samples can be divided into two types: those containing fracture-dissolution pores and those containing only dissolution pores. All the samples were characterized by medium to high densities and low to extra-low porosity. There was a linear correlation between the P-wave velocity and S-wave velocity under gas and water-saturated conditions. Factors such as P-wave to S-wave velocity ratio, Poisson’s ratio, Lame coefficient, and other parameters of the samples were analyzed, and the threshold values that distinguished the water and gas-saturated states of the samples were measured and determined. In addition, there were negative correlations between the P- and S-wave velocities and porosity. The sensitivities of the petrophysical parameters to the gas capacity from high to low are Ip2 − 2.03 Is2, λ − 0.03 μ, λ, λ/μ, E − 2.03 μ, σ, K/μ, K, Ip, Vp/Vs, Vp, E, μ, Vs, and Is. For granite-buried hill reservoirs, the variation ranges of the parameters, such as the density, porosity, and P-wave velocity, of the fracture-dissolution pore granite samples were larger than those of the dissolution pore samples. The bulk parameters (Ip, Vp, K, λ) and combination parameters (Ip2 − 2.03 Is2, K/μ, λ− 0.03 μ, E − 2.03 μ, λ/μ) of the dissolution pore samples were more sensitive to the gas capacity. The results of this study provide a basis for the geophysical identification of granite-buried hill reservoirs.
Pseudo-Karst Silicification Related to Late Ni Reworking in New Caledonia
Authors: Cathelineau Michel , Boiron Marie-Christine , Grimaud Jean-Louis , Favier Sylvain , Teitler Yoram , Golfier Fabrice
Published: April 2023

Silicification in New Caledonian pseudo-karsts developed on peridotite was assessed using δ18O and δ30Si pairs on quartz cements. The objective was to document the chronology of pseudo-karst development and cementation relative to geomorphic evolution. The latter began at the end of the Eocene with the supergene alteration of peridotites and the subsequent formation of extended lateritic weathering profiles. Neogene uplift favoured the dismantling of these early lateritic profiles and valley deepening. The river incision resulted in (i) the stepping of a series of lateritic paleo-landforms and (ii) the development of a pseudo-karst system with subvertical dissolution pipes preferentially along pre-existing serpentine faults. The local collapse of the pipes formed breccias, which were then cemented by white quartz and Ni-rich talc-like (pimelite). The δ30Si of quartz, ranging between −5‰ and −7‰, are typical of silcretes and close to the minimum values recorded worldwide. The estimated δ18O of −6 to −12‰ for the fluids are lower than those of tropical rainfall typical of present-day and Eocene–Oligocene climates. Evaporation during drier climatic episodes is the main driving force for quartz and pimelite precipitation. The silicification presents similarities with silcretes from Australia, which are considered predominantly middle Miocene in age.
Development of Alkylthiazole-Based Novel Thermoelectric Conjugated Polymers for Facile Organic Doping
Authors: Kim Junho , Suh Eui Hyun , Lee Kyumin , Kim Gyuri , Kim Hansu , Jang Jaeyoung , Jung In Hwan
Published: April 2023

In this study, we developed two novel conjugated polymers that can easily be doped with F4TCNQ organic dopants using a sequential doping method and then studied their organic thermoelectric (OTE) properties. In particular, to promote the intermolecular ordering of OTE polymers in the presence of the F4TCNQ dopant, alkylthiazole-based conjugated building blocks with highly planar backbone structures were synthesized and copolymerized. All polymers showed strong molecular ordering and edge-on orientation in the film state, even in the presence of the F4TCNQ organic dopant. Thus, the sequential doping process barely changed the molecular ordering of the polymer films while making efficient molecular doping. In addition, the doping efficiency was improved in the more π-extended polymer backbones with thienothiophene units due to the emptier space in the polymer lamellar structure to locate ionized F4TCNQ. Moreover, the study of organic thin-film transistors (OTFTs) revealed that higher hole mobility in OTFTs was the key to increasing the electrical conductivity of OTE devices fabricated using the sequential doping method.
Enhanced Responsivity and Optoelectronic Properties of Self-Powered Solar-Blind Ag2O/β-Ga2O3 Heterojunction-Based Photodetector with Ag:AZO Co-Sputtered Electrode
Authors: Yoon Younghwa , Park Sangbin , Park Taejun , Kim Hyungmin , Kim Kyunghwan , Hong Jeongsoo
Published: April 2023

A Ag:AZO electrode was used as an electrode for a self-powered solar-blind ultraviolet photodetector based on a Ag2O/β-Ga2O3 heterojunction. The Ag:AZO electrode was fabricated by co-sputtering Ag and AZO heterogeneous targets using the structural characteristics of a Facing Targets Sputtering (FTS) system with two-facing targets, and the electrical, crystallographic, structural, and optical properties of the fabricated thin film were evaluated. A photodetector was fabricated and evaluated based on the research results that the surface roughness of the electrode can reduce the light energy loss by reducing the scattering and reflectance of incident light energy and improving the trapping phenomenon between interfaces. The thickness of the electrodes was varied from 20 nm to 50 nm depending on the sputtering time. The optoelectronic properties were measured under 254 nm UV-C light, the on/off ratio of the 20 nm Ag:AZO electrode with the lowest surface roughness was 2.01 × 108, and the responsivity and detectivity were 56 mA/W and 6.99 × 1011 Jones, respectively. The Ag2O/β-Ga2O3-based solar-blind photodetector with a newly fabricated top electrode exhibited improved response with self-powered characteristics.
Efficient Charge Transfer in MAPbI3 QDs/TiO2 Heterojunctions for High-Performance Solar Cells
Authors: Li Hua , Ding Chao , Liu Dong , Yajima Shota , Takahashi Kei , Hayase Shuzi , Shen Qing
Published: April 2023

Methylammonium lead iodide (MAPbI3) perovskite quantum dots (QDs) have become one of the most promising materials for optoelectronics. Understanding the dynamics of the charge transfer from MAPbI3 QDs to the charge transport layer (CTL) is critical for improving the performance of MAPbI3 QD photoelectronic devices. However, there is currently less consensus on this. In this study, we used an ultrafast transient absorption (TA) technique to investigate the dynamics of charge transfer from MAPbI3 QDs to CTL titanium dioxide (TiO2), elucidating the dependence of these kinetics on QD size with an injection rate from 1.6 × 1010 to 4.3 × 1010 s−1. A QD solar cell based on MAPbI3/TiO2 junctions with a high-power conversion efficiency (PCE) of 11.03% was fabricated, indicating its great potential for application in high-performance solar cells.
Plasma 25-Hydroxyvitamin D Level and VDR Gene Single Nucleotide Polymorphism rs2228570 Influence on COVID-19 Susceptibility among the Kazakh Ethnic Group—A Pilot Study
Authors: Protas Valeriya V. , Pogossyan Gayane P. , Li Konstantin G. , Zhumina Assel G. , Bisseneva Anar K. , Shaikina Dinara N.
Published: April 2023

Low plasma levels of the vitamin D metabolite 25-hydroxyvitamin D [25(OH)D] and the vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) have been associated with the body’s susceptibility to infectious diseases, including COVID-19. In this pilot retrospective study, representatives of the Kazakh population (central Kazakhstan) were divided into groups based on the test for IgM and IgG for coronavirus infection. We compared the 25(OH)D plasma levels and concluded that the COVID-19-positive group values (25.17 ng/mL ± 16.65) were statistically lower (p = 0.0114) compared to the COVID-19-negative ones (35.58 ng/mL ± 20.67). There was no association between age, gender and 25(OH)D concentration within the groups (p > 0.05). The genotyping of rs2228570 was performed using a TaqMan Real-Time PCR assay. Allele C predominated among the COVID-19-negative participants and significantly reduced the likelihood of coronavirus infection (p < 0.0001; OR = 0.0804; 95% CI 0.02357–0.2798). There were no statistically significant differences in the frequencies of the A, G and T alleles in the studied groups (p > 0.05). The GG genotype of rs2228570 was associated with a 4.131-fold increased likelihood of COVID-19 infection (p = 0.0288; χ2 = 5.364; OR = 4.131; 95% CI 1.223–13.71). Comprehensive studies are required to determine whether low 25(OH)D plasma concentrations and genetic background represent a risk factor for COVID-19 infection.
Damage from Carbonated Soft Drinks on Enamel: A Systematic Review
Authors: Inchingolo Angelo Michele , Malcangi Giuseppina , Ferrante Laura , Del Vecchio Gaetano , Viapiano Fabio , Mancini Antonio , Inchingolo Francesco , Inchingolo Alessio Danilo , Di Venere Daniela , Dipalma Gianna , Patano Assunta
Published: April 2023

The present study was conducted to analyze the erosive potential of the ever-increasing consumption of carbonated drinks on the dental surface. To identify relevant studies, a comprehensive search was conducted on PubMed, Scopus, and Web of Science covering the last 5 years (2018–2023) using the following Boolean keywords: “soft drinks AND tooth”. Finally, a total of 19 studies were included. The initial search provided a total of 407 items. Nineteen records were finally involved in the inclusion phase, seven of which were in vivo and twelve in vitro. An abuse of carbonated acid substances leads to an increase in the possibility of dental erosion with consequent structural disintegration and reduction of the physical and mechanical properties of the enamel. There is thus greater bacterial adhesion on rougher surfaces, determined by the erosive process, and therefore a greater risk of caries. The pH of most commercialized carbonated drinks is lower than the critical pH for the demineralization of the enamel. Carbonated drinks’ pH and duration of exposure have different deleterious effects on enamel.
Shikonin Binds and Represses PPARγ Activity by Releasing Coactivators and Modulating Histone Methylation Codes
Authors: Park Ui-Hyun , Youn HyeSook , Kim Eun-Joo , Um Soo-Jong
Published: April 2023

Shikonin, a natural ingredient produced by Lithospermum erythrorhizon, has anti-inflammatory, anti-cancer, and anti-obesity effects. It also inhibits adipocyte differentiation; however, the underlying molecular and epigenetic mechanisms remain unclear. We performed RNA-sequencing of shikonin-treated 3T3-L1 cells. Gene ontology and gene set enrichment analysis showed that shikonin is significantly associated with genes related to adipogenesis, histone modification, and PPARγ. Shikonin treatment downregulated the mRNA expression of PPARγ-responsive genes and rosiglitazone-induced transcriptional activity of PPARγ. Microscale thermophoresis assays showed a KD value 1.4 ± 0.13 μM for binding between shikonin and PPARγ. Glutathione S-transferase pull-down assays exhibited that shikonin blocked the rosiglitazone-dependent association of PPARγ with its coactivator CBP. In addition, shikonin decreased the enrichment of the active histone code H3K4me3 and increased the repressive code H3K27me3 of PPARγ target promoters. Shikonin is a PPARγ antagonist that suppresses adipogenesis by regulating the enrichment of histone codes during adipogenesis. Therefore, it may be used to treat obesity-related disorders via epigenetic changes.
Influence of RVFV Infection on Olfactory Perception and Behavior in Drosophila melanogaster
Authors: Bergmann Stella , Bohn Maja C. , Dornbusch Susann , Becker Stefanie C. , Stern Michael
Published: April 2023

In blood-feeding dipterans, olfaction plays a role in finding hosts and, hence, in spreading pathogens. Several pathogens are known to alter olfactory responses and behavior in vectors. As a mosquito-borne pathogen, Rift Valley Fever Virus (RVFV) can affect humans and cause great losses in livestock. We test the influence of RVFV infection on sensory perception, olfactory choice behavior and activity on a non-biting insect, Drosophila melanogaster, using electroantennograms (EAG), Y-maze, and locomotor activity monitor. Flies were injected with RVFV MP12 strain. Replication of RVFV and its persistence for at least seven days was confirmed by quantitative reverse transcription-PCR (RT-qPCR). One day post injection, infected flies showed weaker EAG responses towards 1-hexanol, vinegar, and ethyl acetate. In the Y-maze, infected flies showed a significantly lower response for 1-hexanol compared to uninfected flies. At days six or seven post infection, no significant difference between infected and control flies could be found in EAG or Y-maze anymore. Activity of infected flies was reduced at both time points. We found an upregulation of the immune-response gene, nitric oxide synthase, in infected flies. An infection with RVFV is able to transiently reduce olfactory perception and attraction towards food-related odors in Drosophila, while effects on activity and immune effector gene expression persist. A similar effect in blood-feeding insects could affect vector competence in RVFV transmitting dipterans.
Intermediate Cluster Disinfection: Which Disinfection Solution Is Most Effective on Milking Liners? A Comparison of Microorganism Reduction on Liner Inner Surfaces Using Quantitative Swab Sampling Technique
Authors: Scheib Sabrina , Leimbach Stefanie , Avramidis Georg , Bellmann Martin , Nitz Julia , Ochs Christian , Tellen Anne , Wente Nicole , Zhang Yanchao , Viöl Wolfgang , Krömker Volker
Published: April 2023

During machine milking, pathogenic microorganisms can be transmitted from cow to cow through liners. Therefore, in Germany, a spray method for the intermediate disinfection of the milking cluster is often used for prevention. This method of cluster disinfection is easy to perform, requires little time and no extra materials, and the disinfection solution is safe from outside contamination in the spray bottle. Since no data on a systematic efficacy trial are available, the aim of this study was to determine the microbial reduction effect of intermediate disinfection. Therefore, laboratory and field trials were conducted. In both trials, two sprays of 0.85 mL per burst of different disinfectant solutions were sprayed into the contaminated liners. For sampling, a quantitative swabbing method using a modified wet–dry swab (WDS) technique based on DIN 10113-1: 1997-07 was applied. Thus, the effectiveness of disinfectants based on Peracetic Acid, Hydrogen Peroxide and Plasma-Activated Buffered Solution (PABS) was compared. In the laboratory trial, the inner surfaces of liners were contaminated with pure cultures of Escherichia (E.) coli, Staphylococcus (S.) aureus, Streptococcus (Sc.) uberis and Sc. agalactiae. The disinfection of the contaminated liners with the disinfectants resulted in a significant reduction in bacteria with values averaging 1 log for E. coli, 0.7 log for S. aureus, 0.7 log for Sc. uberis and 0.8 log for Sc. agalactiae. The highest reduction was obtained for contamination with E. coli (1.3 log) and Sc. uberis (0.8 log) when PABS was applied and for contamination with S. aureus (1.1 log) and Sc. agalactiae (1 log) when Peracetic Acid Solution (PAS) was used. Treatment with sterile water only led to an average reduction of 0.4 log. In the field trial, after the milking of 575 cows, the liners were disinfected and the total microorganism count from the liner surface was performed. The reduction was measured against an untreated liner within the cluster. Although a reduction in microorganisms was achieved in the field trial, it was not significant. When using PAS, a log reduction of 0.3 was achieved; when using PABS, a log reduction of 0.2 was obtained. The difference between the two disinfection methods was also not significant. Treatment with sterile water only led to a reduction of 0.1 log. The results show that spray disinfection under these circumstances does result in a reduction in the bacteria on the milking liner surface, but for effective disinfection a higher reduction would be preferred.
Technologies for Direct Detection of Covalent Protein–Drug Adducts
Authors: Mons Elma , Kim Robbert Q. , Mulder Monique P. C.
Published: April 2023

In the past two decades, drug candidates with a covalent binding mode have gained the interest of medicinal chemists, as several covalent anticancer drugs have successfully reached the clinic. As a covalent binding mode changes the relevant parameters to rank inhibitor potency and investigate structure-activity relationship (SAR), it is important to gather experimental evidence on the existence of a covalent protein–drug adduct. In this work, we review established methods and technologies for the direct detection of a covalent protein–drug adduct, illustrated with examples from (recent) drug development endeavors. These technologies include subjecting covalent drug candidates to mass spectrometric (MS) analysis, protein crystallography, or monitoring intrinsic spectroscopic properties of the ligand upon covalent adduct formation. Alternatively, chemical modification of the covalent ligand is required to detect covalent adducts by NMR analysis or activity-based protein profiling (ABPP). Some techniques are more informative than others and can also elucidate the modified amino acid residue or bond layout. We will discuss the compatibility of these techniques with reversible covalent binding modes and the possibilities to evaluate reversibility or obtain kinetic parameters. Finally, we expand upon current challenges and future applications. Overall, these analytical techniques present an integral part of covalent drug development in this exciting new era of drug discovery.
Angiotensin II-Related Activation of Scleral Fibroblasts and Their Role on Retinal Ganglion Cell Death in Glaucoma
Authors: Oh Si-Eun , Kim Jie-Hyun , Shin Hee-Jong , Kim Seong-Ah , Park Chan-Kee , Park Hae-Young Lopilly
Published: April 2023

We identify the angiotensin II (AngII)-associated changes in the extracellular matrix (ECM) and the biomechanical properties of the sclera after systemic hypotension. Systemic hypotension was induced by administering oral hydrochlorothiazide. AngII receptor levels and ECM components in the sclera and biomechanical properties were evaluated based on the stress–strain relationship after systemic hypotension. The effect of inhibiting the AngII receptor with losartan was determined in the systemic hypotensive animal model and the cultured scleral fibroblasts from this model. The effect of losartan on retinal ganglion cell (RGC) death was evaluated in the retina. Both AngII receptor type I (AT-1R) and type II (AT-2R) increased in the sclera after systemic hypotension. Proteins related to the activation of fibroblasts (transforming growth factor [TGF]-β1 and TGF-β2) indicated that transformation to myofibroblasts (α smooth muscle actin [SMA]), and the major ECM protein (collagen type I) increased in the sclera after systemic hypotension. These changes were associated with stiffening of the sclera in the biomechanical analysis. Administering losartan in the sub-Tenon tissue significantly decreased the expression of AT-1R, αSMA, TGF-β, and collagen type I in the cultured scleral fibroblasts and the sclera of systemic hypotensive rats. The sclera became less stiff after the losartan treatment. A significant increase in the number of RGCs and decrease in glial cell activation was found in the retina after the losartan treatment. These findings suggest that AngII plays a role in scleral fibrosis after systemic hypotension and that inhibiting AngII could modulate the tissue properties of the sclera, resulting in the protection of RGCs.
Ultrasound-Responsive Biomimetic Superhydrophobic Drug-Loaded Mesoporous Silica Nanoparticles for Treating Prostate Tumor
Authors: Jin Qiaofeng , Chen Dandan , Song Yishu , Liu Tianshu , Li Wenqu , Chen Yihan , Qin Xiaojuan , Zhang Li , Wang Jing , Xie Mingxing
Published: April 2023

Interfacial nanobubbles on a superhydrophobic surface can serve as ultrasound cavitation nuclei for continuously promoting sonodynamic therapy, but their poor dispersibility in blood has limited their biomedical application. In this study, we proposed ultrasound-responsive biomimetic superhydrophobic mesoporous silica nanoparticles, modified with red blood cell membrane and loaded with doxorubicin (DOX) (F-MSN-DOX@RBC), for RM-1 tumor sonodynamic therapy. Their mean size and zeta potentials were 232 ± 78.8 nm and −35.57 ± 0.74 mV, respectively. The F-MSN-DOX@RBC accumulation in a tumor was significantly higher than in the control group, and the spleen uptake of F-MSN-DOX@RBC was significantly reduced in comparison to that of the F-MSN-DOX group. Moreover, the cavitation caused by a single dose of F-MSN-DOX@RBC combined with multiple ultrasounds provided continuous sonodynamic therapy. The tumor inhibition rates in the experimental group were 71.5 8 ± 9.54%, which is significantly better than the control group. DHE and CD31 fluorescence staining was used to assess the reactive oxygen species (ROS) generated and the broken tumor vascular system induced by ultrasound. Finally, we can conclude that the combination of anti-vascular therapy, sonodynamic therapy by ROS, and chemotherapy promoted tumor treatment efficacy. The use of red blood cell membrane-modified superhydrophobic silica nanoparticles is a promising strategy in designing ultrasound-responsive nanoparticles to promote drug-release.
Correction: Youssef et al. Glibenclamide Nanocrystal-Loaded Bioactive Polymeric Scaffolds for Skin Regeneration: In Vitro Characterization and Preclinical Evaluation. Pharmaceutics 2021, 13, 1469
Authors: Youssef Julie R. , Boraie Nabila A. , Ibrahim Heba F. , Ismail Fatma A. , El-Moslemany Riham M.
Published: April 2023

Figure Correction [...]
Cocrystals by Design: A Rational Coformer Selection Approach for Tackling the API Problems
Authors: Singh Maan , Barua Harsh , Jyothi Vaskuri G. S. Sainaga , Dhondale Madhukiran R. , Nambiar Amritha G. , Agrawal Ashish K. , Kumar Pradeep , Shastri Nalini R. , Kumar Dinesh
Published: April 2023

Active pharmaceutical ingredients (API) with unfavorable physicochemical properties and stability present a significant challenge during their processing into final dosage forms. Cocrystallization of such APIs with suitable coformers is an efficient approach to mitigate the solubility and stability concerns. A considerable number of cocrystal-based products are currently being marketed and show an upward trend. However, to improve the API properties by cocrystallization, coformer selection plays a paramount role. Selection of suitable coformers not only improves the drug’s physicochemical properties but also improves the therapeutic effectiveness and reduces side effects. Numerous coformers have been used till date to prepare pharmaceutically acceptable cocrystals. The carboxylic acid-based coformers, such as fumaric acid, oxalic acid, succinic acid, and citric acid, are the most commonly used coformers in the currently marketed cocrystal-based products. Carboxylic acid-based coformers are capable of forming the hydrogen bond and contain smaller carbon chain with the APIs. This review summarizes the role of coformers in improving the physicochemical and pharmaceutical properties of APIs, and deeply explains the utility of afore-mentioned coformers in API cocrystal formation. The review concludes with a brief discussion on the patentability and regulatory issues related to pharmaceutical cocrystals.
Thermosensitive Cationic Magnetic Liposomes for Thermoresponsive Delivery of CPT-11 and SLP2 shRNA in Glioblastoma Treatment
Authors: Lu Yu-Jen , Hsu Hao-Lung , Lan Yu-Hsiang , Chen Jyh-Ping
Published: April 2023

Thermosensitive cationic magnetic liposomes (TCMLs), prepared from dipalmitoylphosphatidylcholine (DPPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]-2000, and didodecyldimethylammonium bromide (DDAB) were used in this study for the controlled release of drug/gene for cancer treatment. After co-entrapping citric-acid-coated magnetic nanoparticles (MNPs) and the chemotherapeutic drug irinotecan (CPT-11) in the core of TCML (TCML@CPT-11), SLP2 shRNA plasmids were complexed with DDAB in the lipid bilayer to prepare TCML@CPT-11/shRNA with a 135.6 ± 2.1 nm diameter. As DPPC has a melting temperature slightly above the physiological temperature, drug release from the liposomes can be triggered by an increase in solution temperature or by magneto-heating induced with an alternating magnetic field (AMF). The MNPs in the liposomes also endow the TCMLs with magnetically targeted drug delivery with guidance by a magnetic field. The successful preparation of drug-loaded liposomes was confirmed by various physical and chemical methods. Enhanced drug release, from 18% to 59%, at pH 7.4 was observed when raising the temperature from 37 to 43 °C, as well as during induction with an AMF. The in vitro cell culture experiments endorse the biocompatibility of TCMLs, whereas TCML@CPT-11 shows some enhancement of cytotoxicity toward U87 human glioblastoma cells when compared with free CPT-11. The U87 cells can be transfected with the SLP2 shRNA plasmids with very high efficiency (~100%), leading to silencing of the SLP2 gene and reducing the migration ability of U87 from 63% to 24% in a wound-healing assay. Finally, an in vivo study, using subcutaneously implanted U87 xenografts in nude mice, demonstrates that the intravenous injection of TCML@CPT11-shRNA, plus magnetic guidance and AMF treatment, can provide a safe and promising therapeutic modality for glioblastoma treatment.
Labellum Features and Chemical Composition of Floral Scent in Bulbophyllum carunculatum Garay, Hamer & Siegrist (Section Lepidorhiza Schltr., Bulbophyllinae Schltr., Orchidaceae Juss.)
Authors: Wiśniewska Natalia , Gołębiowski Marek , Kowalkowska Agnieszka K.
Published: April 2023

The vast majority of fly-pollinated Bulbophyllum species use a combination of visual and olfactory clues to mimic food sources and brood/oviposition sites of pollinators. The aims of the present work were to characterize the floral secretory tissue and the floral scent and compare them with those previously described in B. echinolabium. Based on the histochemical results, the labellar secretion in B. carunculatum is the protein-rich mucilage. The adaxial epidermal cells of the labellum showed typical features of secretory activity. Plastids contained plastoglobuli, which are thought to be the places for scent production in osmophores. Juxtaposed with FeCl3 staining, the presence of dihydroxyphenolic globules in the cytoplasm of the epidermis and sub-epidermis was confirmed. Phenolic derivatives were also described with GC/MS analysis of the floral scent. The number of aromatic compounds and hydrocarbons was indicated in the floral scent of B. carunculatum. Moreover, pregnane-3,20-dione, occurring in the highest percentage in the floral fragrance of B. carunculatum, is a biologically active, 5-alpha-reduced metabolite of plasma progesterone. Progesterone is a mammalian gonadal hormone, but, like other steroid hormones, has been found in plants as intermediates in different biosynthetic pathways. The research on biosynthesis and functions of progesterone and its derivatives in flowers is still lacking.
Essential Oil of Lavandula officinalis: Chemical Composition and Antibacterial Activities
Authors: Diass Khaoula , Merzouki Mohammed , Elfazazi Kaoutar , Azzouzi Hanane , Challioui Allal , Azzaoui Khalil , Hammouti Belkheir , Touzani Rachid , Depeint Flore , Ayerdi Gotor Alicia , Rhazi Larbi
Published: April 2023

The purpose of this study was to determine the chemical composition of the essential oil of Lavandula officinalis from Morocco using the GC-MS technique and assess the antibacterial effects against seven pathogenic bacteria strains isolated from the food origins of Salmonella infantis, Salmonella kentucky, Salmonella newport, three serotypes of Escherichia coli (O114H8K11, O127K88ac, O127H40K11) and Klebsiella. Tests of sensitivity were carried out on a solid surface using the Disc Diffusion Method. Results showed that E. coli and S.newport were sensitive to Lavandula officinalis essential oil. Minimum inhibitory concentrations (MIC) were determined using the method of agar dilution. The antibacterial results showed that four strains (three serotypes of E. coli, and S. newport) were remarkedly sensitive to Lavandula officinalis essential oil, giving MIC values of 88.7 µg/mL and 177.5 µg/mL. The molecular docking of the main oil products with the E. coli target protein 1VLY, showed that eucalyptol and linalyl acetate bind efficiently with the active site of the target protein. In particular, eucalyptol showed a higher activity than gentamicin used as positive control with a binding energy of −5.72 kcal/mol and −5.55 kcal/mol, respectively.
Rosa davurica Inhibited Allergic Mediators by Regulating Calcium and Histamine Signaling Pathways
Authors: Lim Seojun , Oh Sarang , Nguyen Quynh T. N. , Kim Myeongju , Zheng Shengdao , Fang Minzhe , Yi Tae-Hoo
Published: April 2023

Rosa davurica Pall. exhibits antioxidant, antiviral, and anti-inflammatory properties; however, its pharmacological mechanism in allergy is yet to be understood. This study confirmed the effects of R. davurica Pall. leaf extract (RLE) on allergy as a new promising material. To evaluate the therapeutic potential of RLE against allergy, we investigated the effects of RLE on the regulatory β-hexosaminidase, histamine, histidine decarboxylase (HDC), Ca2+ influx, nitric oxide (NO), and cytokines induced by lipopolysaccharide (LPS) and DNP-IgE/BSA in Raw 264.7 and RBL-2H3 cells. Furthermore, we examined the effects of RLE on the signaling pathways of mitogen-activated protein kinase (MAPK) and Ca2+ pathways. After stimulating Raw 264.7 cells with LPS, RLE reduced the release of inflammatory mediators, such as NO, cyclooxygenase (COX)-2, inducible nitric oxygen synthase (iNOS), interleukin (IL)-1β, -6, and tumor necrosis factor (TNF)-α. Also, RLE reduced the β-hexosaminidase, histamine, HDC, Ca2+ influx, Ca2+ pathways, and phosphorylation of MAPK in DNP-IgE/BSA-stimulated RBL-2H3 cells. Our studies indicated that RLE is a valuable ingredient for treating allergic diseases by regulating cytokine release from macrophages and mast cell degranulation. Consequently, these results suggested that RLE may serve as a possible alternative promising material for treating allergies.
Keeping Healthy in Your Skin—Plants and Fungi Used by Indigenous Himalayan Communities to Treat Dermatological Ailments
Authors: Haq Shiekh Marifatul , Khoja Aadil Abdullah , Lone Fayaz A. , Waheed Muhammad , Bussmann Rainer W. , Casini Ryan , Mahmoud Eman A. , Elansary Hosam O.
Published: April 2023

Dermatological ailments are a major health problem, especially when related to human immune deficiency syndrome and acquired immune deficiency. The goal of this study was to identify the medicinal plants used by the indigenous peoples of the Northwestern Himalayas to treat dermatological diseases. Several field trips were conducted in the spring and summer seasons of 2020–2021 to collect the plants of dermatological value and information about their use through open-ended semi-structured interviews (n = 53) and group discussions (n = 33). The current investigation found 64 ethnomedicinal plants belonging to 34 families commonly used to treat a variety of dermatological ailments. The main growth form was herbs (80%), followed by trees (8%) and ferns (6%). It was found that leaves (51%) were the most commonly used plant part, followed by roots and the whole plant. Wound healing was the most dominant application, with 18 plant species used, followed by skin burns cured by 11 plant species and skin boils by eight plant species. Out of the total (18%) of medicinal plants with cosmetic uses, i.e., roots of Jurinea dolomiaea, Rheum webbianum, and Rheum spiciforme were crushed into powder and mixed with turmeric, and the paste is applied topically for glowing skin. Among the various preparation methods, paste (38%) was the most common way of preparation, followed by poultice (29%) and infusion (9%). Between ethnic groups, the maximum homogeneity was between Gujjar and Bakarwal ethnic groups (23 species, 36%), followed by Gujjars and Kashmiri (14 species, 22%). Bakarwals and Gujjar people live in the same geographical location, and they graze their animals in pastures, practice extensive transhumance pastoralism, and pass through different ecological landscapes, thus having sufficient experiences with certain plants and retaining more knowledge. The species identified with the highest utilization based on the number of citations and use value included Ficus carica, Cichorium intybus, Euphorbia wallichii, Pinus wallichiana, Plantago major, Jurinea dolomiaea, and Artemisia absinthium. The findings of this study demonstrate that people who reside in the Northwestern Himalayas region still rely on medicinal plants.
pH-Sensitive Degradable Oxalic Acid Crosslinked Hyperbranched Polyglycerol Hydrogel for Controlled Drug Release
Authors: de Campos Bianca Andrade , da Silva Natalia Cristina Borges , Moda Lucas Szmgel , Vidinha Pedro , Maia-Obi Lígia Passos
Published: April 2023

pH-sensitive degradable hydrogels are smart materials that can cleave covalent bonds upon pH variation, leading to their degradation. Their development led to many applications for drug delivery, where drugs can be released in a pH-dependent manner. Crosslinking hyperbranched polyglycerol (HPG), a biocompatible building block bearing high end-group functionality, using oxalic acid (OA), a diacid that can be synthesized from CO2 and form highly activated ester bonds, can generate this type of smart hydrogel. Aiming to understand the process of developing this novel material and its drug release for oral administration, its formation was studied by varying reactant stoichiometry, concentration and cure procedure and temperature; it was characterized regarding gel percent (%gel), swelling degree (%S), FTIR and thermal behavior; impregnated using ibuprofen, as a model drug, and a release study was carried out at pH 2 and 7. Hydrogel formation was evidenced by its insolubility, FTIR spectra and an increase in Td and Tg; a pre-cure step was shown to be crucial for its formation and an increase in the concentration of the reactants led to higher %gel and lower %S. The impregnation resulted in a matrix-encapsulated system; and the ibuprofen release was negligible at pH 2 but completed at pH 7 due to the hydrolysis of the matrix. A pH-sensitive degradable HPG-OA hydrogel was obtained and it can largely be beneficial in controlled drug release applications.
Immobilization Approach as a Creative Strategy to Remove Reactive Dye Red 195 and Cu2+ Ions from Wastewater Using Environmentally Benign Geopolymer Cement
Authors: Ahmed Doaa A. , El-Apasery Morsy A. , Ragai Shereen M.
Published: April 2023

Water is a resource that is essential to almost all phases of industrial and manufacturing operations globally. It is important to handle the wastewater generated professionally. The textile industry is one of the major global polluters, with textile producers responsible for one-fifth of all industrial water pollution worldwide. In contrast, heavy metal contamination has developed into a critical, expanding global environmental problem. Geopolymer is a cementitious constituent of amorphous aluminosilicates derived from natural or industrial wastes. It is produced using the polymerization of aluminosilicate raw ingredients in an alkaline atmosphere. The aim of this study is to evaluate the application of eco-friendly geopolymer cement in the immobilization technique for the treatment of wastewater including heavy metals and dyes. Geopolymer cement pastes were organized using slag and fly ash as an aluminosilicate source, (1:1) sodium silicate and sodium hydroxide 15 wt.% as an alkali activator in the presence of organic dye pollutant reactive red 195, and Cu2+ ions (700 ppm) at different hydration times for up to 28 days. The physicochemical and mechanical properties of the prepared geopolymer cement mixes were further examined in relation to reactive dye pollutant and Cu2+ ions. The hydration characteristic was examined using the compressive strength and % of total porosity tests, as well as FTIR and XRD studies. Our findings support the 100% immobilization of both Cu2+ ions and organic dye pollutants in prepared geopolymer pastes for up to 28 days of hydration. Additionally, adding both Cu2+ ions and dye pollutants to the prepared geopolymer paste improves its mechanical properties, which is also supported by FTIR data. XRD and FTIR studies showed that the Cu2+ ions and dying bath effluent addition have no influence on the kind of hydration products that are produced. On the other hand, the geopolymerization process is negatively impacted by the presence of Cu2+ ions alone in the geopolymer paste.