bluuebunny/crossref_metadata_2025 huggingface dataset:
Exposure to Heavy Metals and Serum Adiponectin Levels among Workers: A 2-Year Follow-Up Study
Authors: Wu Chen-Jung , Ho A-Chuan , Chen Shih-Ya , Pan Chih-Hong , Chuang Hsiao-Chi , Lai Ching-Huang
Published: January 2023

The workers exposed to metal fumes had an increased risk of metabolic syndrome, which was correlated with decreased serum adiponectin. Thus, we aimed to explore whether heavy metal exposure affects the adiponectin level. There were 96 male workers recruited from a shipyard at baseline. Apart from 82 participants completed the follow-up assessments, new participants were recruited in next year. Finally, there were 100 welding workers in the exposure group and 31 office workers in the control group. Inferential statistics on repeated measures were performed using generalized estimating equations. A weighted quantile sum (WQS) regression model was conducted to examine the joint effect of the multimetal exposure with serum adiponectin. Significantly negative associations of metals with adiponectin were detected in the welding workers, including Cr (β = −0.088; 95% CI: −0.148, −0.027), Mn (β = −0.174; 95% CI: −0.267, −0.081), Co (β = −0.094; 95% CI: −0.158, −0.029), Ni (β = −0.108; 95% CI: −0.208, −0.008), Cd (β = −0.067; 95% CI: −0.115, −0.018), and Pb (β = −0.089; 95% CI: −0.163, −0.015). The WQS regression suggested that Pb was the greatest contributor. In conclusion, our findings highlighted that welding workers exposed to heavy metals would reduce serum adiponectin.
Assessing Metabolic Markers in Glioblastoma Using Machine Learning: A Systematic Review
Authors: Neil Zachery D. , Pierzchajlo Noah , Boyett Candler , Little Olivia , Kuo Cathleen C. , Brown Nolan J. , Gendreau Julian
Published: January 2023

Glioblastoma (GBM) is a common and deadly brain tumor with late diagnoses and poor prognoses. Machine learning (ML) is an emerging tool that can create highly accurate diagnostic and prognostic prediction models. This paper aimed to systematically search the literature on ML for GBM metabolism and assess recent advancements. A literature search was performed using predetermined search terms. Articles describing the use of an ML algorithm for GBM metabolism were included. Ten studies met the inclusion criteria for analysis: diagnostic (n = 3, 30%), prognostic (n = 6, 60%), or both (n = 1, 10%). Most studies analyzed data from multiple databases, while 50% (n = 5) included additional original samples. At least 2536 data samples were run through an ML algorithm. Twenty-seven ML algorithms were recorded with a mean of 2.8 algorithms per study. Algorithms were supervised (n = 24, 89%), unsupervised (n = 3, 11%), continuous (n = 19, 70%), or categorical (n = 8, 30%). The mean reported accuracy and AUC of ROC were 95.63% and 0.779, respectively. One hundred six metabolic markers were identified, but only EMP3 was reported in multiple studies. Many studies have identified potential biomarkers for GBM diagnosis and prognostication. These algorithms show promise; however, a consensus on even a handful of biomarkers has not yet been made.
Molecular and Biological Investigation of Isolated Marine Fungal Metabolites as Anticancer Agents: A Multi-Target Approach
Authors: Bogari Hanin A. , Elhady Sameh S. , Darwish Khaled M. , Refaey Mohamed S. , Mohamed Radi A. , Abdelhameed Reda F. A. , Almalki Ahmad J. , Aldurdunji Mohammed M. , Lashkar Manar O. , Alshehri Samah O. , Malatani Rania T. , Yamada Koji , Khedr Amgad I. M.
Published: January 2023

Cancer is the leading cause of death globally, with an increasing number of cases being annually reported. Nature-derived metabolites have been widely studied for their potential programmed necrosis, cytotoxicity, and anti-proliferation leading to enrichment for the modern medicine, particularly within the last couple of decades. At a more rapid pace, the concept of multi-target agents has evolved from being an innovative approach into a regular drug development procedure for hampering the multi-fashioned pathophysiology and high-resistance nature of cancer cells. With the advent of the Red Sea Penicillium chrysogenum strain S003-isolated indole-based alkaloids, we thoroughly investigated the molecular aspects for three major metabolites: meleagrin (MEL), roquefortine C (ROC), and isoroquefortine C (ISO) against three cancer-associated biological targets Cdc-25A, PTP-1B, and c-Met kinase. The study presented, for the first time, the detailed molecular insights and near-physiological affinity for these marine indole alkaloids against the assign targets through molecular docking-coupled all-atom dynamic simulation analysis. Findings highlighted the superiority of MEL’s binding affinity/stability being quite in concordance with the in vitro anticancer activity profile conducted via sulforhodamine B bioassay on different cancerous cell lines reaching down to low micromolar or even nanomolar potencies. The advent of lengthy structural topologies via the metabolites’ extended tetracyclic cores and aromatic imidazole arm permitted multi-pocket accommodation addressing the selectivity concerns. Additionally, the presence decorating polar functionalities on the core hydrophobic tetracyclic ring contributed compound’s pharmacodynamic preferentiality. Introducing ionizable functionality with more lipophilic characters was highlighted to improve binding affinities which was also in concordance with the conducted drug-likeness/pharmacokinetic profiling for obtaining a balanced pharmacokinetic/dynamic profile. Our study adds to the knowledge regarding drug development and optimization of marine-isolated indole-based alkaloids for future iterative synthesis and pre-clinical investigations as multi-target anticancer agents.
MetaboVariation: Exploring Individual Variation in Metabolite Levels
Authors: Gupta Shubbham , Gormley Isobel Claire , Brennan Lorraine
Published: January 2023

To date, most metabolomics biomarker research has focused on identifying disease biomarkers. However, there is a need for biomarkers of early metabolic dysfunction to identify individuals who would benefit from lifestyle interventions. Concomitantly, there is a need to develop strategies to analyse metabolomics data at an individual level. We propose “MetaboVariation”, a method that models repeated measurements on individuals to explore fluctuations in metabolite levels at an individual level. MetaboVariation employs a Bayesian generalised linear model to flag individuals with intra-individual variations in their metabolite levels across multiple measurements. MetaboVariation models repeated metabolite levels as a function of explanatory variables while accounting for intra-individual variation. The posterior predictive distribution of metabolite levels at the individual level is available, and is used to flag individuals with observed metabolite levels outside the 95% highest posterior density prediction interval at a given time point. MetaboVariation was applied to a dataset containing metabolite levels for 20 metabolites, measured once every four months, in 164 individuals. A total of 28% of individuals with intra-individual variations in three or more metabolites were flagged. An R package for MetaboVariation was developed with an embedded R Shiny web application. To summarize, MetaboVariation has made considerable progress in developing strategies for analysing metabolomics data at the individual level, thus paving the way toward personalised healthcare.
Species of the Genera Neopestalotiopsis and Alternaria as Dominant Pathogen Species Attacking Mastic Trees (Pistacia lentiscus var. Chia)
Authors: Kamou Nathalie N. , Testempasis Stefanos , Lagopodi Anastasia L.
Published: January 2023

Between 2018 and 2021, several mastic trees (Pistacia lentiscus var. Chia) sampled in the field and the nursery of the Chios Mastiha Growers Association (CMGA) were analyzed to determine the cause of dominant diseases. Symptoms included defoliation, leaf, and twig blight, wilting and/or apoplexy of trees and apoplexy of young hardwood cuttings. Moreover, brown discoloration had also been observed on older woody parts of the trees such as branches and tree trunks. Several pathogens have been isolated and identified as the causing agents. Neopestalotiopsis and Alternaria species were isolated consistently from necrotic tissues of mastic trees (branches, twigs, and leaves) in the field and the nursery. All fungal isolates’ pathogenicity was confirmed by applying Koch’s postulates on young mastic trees under glasshouse conditions. Fungal pathogens were identified by sequence analyses of the ITS, β-tubulin, and histone gene regions. Alternaria species were analyzed further by sequencing the endopolygalacturonase (endoPG) and the Alternaria major allergen (Alta1) genes. More specifically, the isolates were identified as Neopestalotiopsis clavispora, Alternaria arborescens, and A. alternata based on morphological features and sequence analyses. This is the first report of N. clavispora, A. arborescens, and A. alternata on P. lentiscus var. Chia.
The Formation of Magnesite Ores by Reactivation of Dunite Channels as a Key to Their Spatial Association to Chromite Ores in Ophiolites: An Example from Northern Evia, Greece
Authors: Grieco Giovanni , Cavallo Alessandro , Marescotti Pietro , Crispini Laura , Tzamos Evangelos , Bussolesi Micol
Published: January 2023

Ophiolite magnesite deposits are among the main sources of magnesite, a raw material critical for the EU. The present work focuses on magnesite occurrences at Kymasi (Evia Island, Greece), in close spatial association with chromitite within the same peridotite massif, and on the relationship between ultramafic rocks and late magnesite veins. Chromitite lenses are hosted within dunite, in contact with a partially serpentinized peridotite cut by magnesite veins. Close to the veins, the peridotite shows evidence of carbonation (forming dolomitized peridotite) and brecciation (forming a serpentinite–magnesite hydraulic breccia, in contact with the magnesite veins). Spinel mineral chemistry proved to be crucial for understanding the relationships between different lithologies. Spinels within partially serpentinized peridotite (Cr# 0.55–0.62) are similar to spinels within dolomitized peridotite (Cr# 0.58–0.66). Spinels within serpentinite–magnesite hydraulic breccia (Cr# 0.83–0.86) are comparable to spinels within dunite and chromitite (Cr# 0.79–0.84). This suggests that older weak zones, such as dunite channels, were reactivated as fluid pathways for the precipitation of magnesite. Magnesite stable isotope composition, moreover, points towards a meteoric origin of the oxygen, and to an organic source of carbon. The acquired data suggest the following evolution of Kymasi ultramafic rocks: (i) percolation of Cr-bearing melts in a supra-subduction mantle wedge within dunite channels; (ii) obduction of the ophiolitic sequence and peridotite serpentinization; (iii) uplift and erosion of mantle rocks to a shallow crustal level; (iv) percolation of carbon-rich meteoric waters rich at shallow depth, reactivating the dunite channels as preferential weak zones; and (v) precipitation of magnesite in veins and partial brecciation and carbonation of the peridotite host rock.
The High-Pressure Methane/Brine/Quartz Contact Angle and Its Influence on Gas Reservoir Capillaries
Authors: Tian Hua , Fan Junjia , Yu Zhichao , Liu Qiang , Lu Xuesong
Published: January 2023

A capillary high-pressure optical cell (HPOC) combined with a confocal Raman system was used in this study of high-pressure methane/brine contact angles on a quartz surface. The contact angle was determined from the shape of the methane/brine/quartz interface; it increased with fluid pressure from 41° to 49° over a pressure range of 5.7–69.4 MPa. A linear relationship between the contact angle and the Raman shift was also observed. The experimentally measured contact angle was more accurately applied in calculations of capillary resistance than the empirically estimated 0°, and it provides an important parameter in the study of gas migration and production processes. For a natural gas reservoir, pore-throat capillary resistance was 33% lower than the traditionally accepted value, and low capillary resistance is conducive to deeply buried tight gas reservoirs becoming more gas saturated. As burial depth increases, capillary resistance initially decreases and passes through a maximum before decreasing again, rather than increasing linearly with depth. Our results provide critical parameters for gas reservoir production, modeling, and resource assessment. This non-destructive method may be useful for predicting contact angles through measurement of the Raman shift of the HPOC and fluid inclusions in the reservoir.
Quercetin: A Functional Food-Flavonoid Incredibly Attenuates Emerging and Re-Emerging Viral Infections through Immunomodulatory Actions
Authors: Shorobi Fauzia Mahanaz , Nisa Fatema Yasmin , Saha Srabonti , Chowdhury Muhammad Abid Hasan , Srisuphanunt Mayuna , Hossain Kazi Helal , Rahman Md. Atiar
Published: January 2023

Many of the medicinally active molecules in the flavonoid class of phytochemicals are being researched for their potential antiviral activity against various DNA and RNA viruses. Quercetin is a flavonoid that can be found in a variety of foods, including fruits and vegetables. It has been reported to be effective against a variety of viruses. This review, therefore, deciphered the mechanistic of how Quercetin works against some of the deadliest viruses, such as influenza A, Hepatitis C, Dengue type 2 and Ebola virus, which cause frequent outbreaks worldwide and result in significant morbidity and mortality in humans through epidemics or pandemics. All those have an alarming impact on both human health and the global and national economies. The review extended computing the Quercetin-contained natural recourse and its modes of action in different experimental approaches leading to antiviral actions. The gap in effective treatment emphasizes the necessity of a search for new effective antiviral compounds. Quercetin shows potential antiviral activity and inhibits it by targeting viral infections at multiple stages. The suppression of viral neuraminidase, proteases and DNA/RNA polymerases and the alteration of many viral proteins as well as their immunomodulation are the main molecular mechanisms of Quercetin’s antiviral activities. Nonetheless, the huge potential of Quercetin and its extensive use is inadequately approached as a therapeutic for emerging and re-emerging viral infections. Therefore, this review enumerated the food-functioned Quercetin source, the modes of action of Quercetin for antiviral effects and made insights on the mechanism-based antiviral action of Quercetin.
Approved Small-Molecule ATP-Competitive Kinases Drugs Containing Indole/Azaindole/Oxindole Scaffolds: R&D and Binding Patterns Profiling
Authors: Zhang Haofan , He Fengming , Gao Guiping , Lu Sheng , Wei Qiaochu , Hu Hongyu , Wu Zhen , Fang Meijuan , Wang Xiumin
Published: January 2023

Kinases are among the most important families of biomolecules and play an essential role in the regulation of cell proliferation, apoptosis, metabolism, and other critical physiological processes. The dysregulation and gene mutation of kinases are linked to the occurrence and development of various human diseases, especially cancer. As a result, a growing number of small-molecule drugs based on kinase targets are being successfully developed and approved for the treatment of many diseases. The indole/azaindole/oxindole moieties are important key pharmacophores of many bioactive compounds and are generally used as excellent scaffolds for drug discovery in medicinal chemistry. To date, 30 ATP-competitive kinase inhibitors bearing the indole/azaindole/oxindole scaffold have been approved for the treatment of diseases. Herein, we summarize their research and development (R&D) process and describe their binding models to the ATP-binding sites of the target kinases. Moreover, we discuss the significant role of the indole/azaindole/oxindole skeletons in the interaction of their parent drug and target kinases, providing new medicinal chemistry inspiration and ideas for the subsequent development and optimization of kinase inhibitors.
Xanthohumol-Enriched Beer Does Not Exert Antitumorigenic Effects on HeLa Cell Line In Vivo
Authors: Éliás Anna Júlia , Balogh Lajos , Brányik Tomáš , Mák Erzsébet , Csajbókné Csobod Éva , Veresné Bálint Márta , Benedek Csilla
Published: January 2023

Xanthohumol is a hop-derived flavonoid that has been widely examined for its health-protecting and antitumorigenic properties, but not yet in a natural beer matrix. The aim of the study was to investigate the antitumorigenic potential of a xanthohumol-enriched beer in vivo. Four groups of 4 × 10 nude mice were formed. Following the injection of HeLa tumorigenic cell lines, the treatment groups were administered a xanthohumol supplementation for 100 days, either dissolved in beer or in an ethanolic solution with the same alcohol strength as beer. The control groups received un-supplemented material. The terminal tumor masses, liver weights, and plasma antioxidant capacities (FRAP and ABTS methods) were measured. For the statistical analysis, a two-way ANOVA test was performed (p < 0.05). There were no statistically significant differences in tumor size between the groups. Xanthohumol did not induce higher levels of plasma antioxidant capacity, neither in beer nor in the water–ethanol matrix. The terminal liver weights were significantly higher in the control group receiving the unsupplemented ethanol solution. Xanthohumol dissolved in beer or in the water–alcohol matrix did not have a protective effect on tumor growth, nor did it have a positive effect on plasma antioxidant capacity either. However, beer with added xanthohumol had a less harmful effect on the liver compared to the supplemented water–ethanol solution. Our results indicate the possible negative countereffect of ethanol; however, further investigations are needed.
Recent Advances in Catalytic and Technology-Driven Radical Addition to N,N-Disubstituted Iminium Species
Authors: Oudeyer Sylvain , Levacher Vincent , Beucher Hélène , Brière Jean-François
Published: January 2023

Recently, radical chemistry has grown exponentially in the toolbox of organic synthetic chemists. Upon the (re)introduction of modern catalytic and technology-driven strategies, the implementation of highly reactive radical species is currently facilitated while expanding the scope of numerous synthetic methodologies. In this context, this review intends to cover the recent advances in radical-based transformations of N,N-disubstituted iminium substrates that encompass unique reactivities with respect to imines or protonated iminium salts. In particular, we have focused on the literature concerning the dipole type substrates, such as nitrones or azomethine imines, together with the chemistry of N+-X− (X = O, NR) azaarenium dipoles, which proved to be very versatile platforms in that field of research. The N-alkylazaarenium salts were been considered, which demonstrated specific reactivity profiles in radical chemistry.
Two Novel Schiff Base Manganese Complexes as Bifunctional Electrocatalysts for CO2 Reduction and Water Oxidation
Authors: Zhao Xin , Li Jingjing , Jian Hengxin , Lu Mengyu , Wang Mei
Published: January 2023

One mononuclear Mn(III) complex [MnIIIL(H2O)(MeCN)](ClO4) (1) and one hetero-binuclear complex [(CuIILMnII(H2O)3)(CuIIL)2](ClO4)2·CH3OH (2) have been synthesized with the Schiff base ligand (H2L = N,N′-bis(3-methoxysalicylidene)-1,2-phenylenediamine). Single crystal X-ray structural analysis manifests that the Mn(III) ion in 1 has an octahedral coordination structure, whereas the Mn(II) ion in 2 possesses a trigonal bipyramidal configuration and the Cu(II) ion in 2 is four-coordinated with a square-planar geometry. Electrochimerical catalytic investigation demonstrates that the two complexes can electrochemically catalyze water oxidation and CO2 reduction simultaneously. The coordination environments of the Mn(III), Mn(II), and Cu(II) ions in 1 and 2 were provided by the Schiff base ligand (L) and labile solvent molecules. The coordinately unsaturated environment of the Cu(II) center in 2 can perfectly facilitate the catalytic performance of 2. Complexes 1 and 2 display that the over potentials for water oxidation are 728 mV and 216 mV, faradaic efficiencies (FEs) are 88% and 92%, respectively, as well as the turnover frequency (TOF) values for the catalytic reduction of CO2 to CO are 0.38 s−1 at −1.65 V and 15.97 s−1 at −1.60 V, respectively. Complex 2 shows much better catalytic performance for both water oxidation and CO2 reduction than that of complex 1, which could be owing to a structural reason which is attributed to the synergistic catalytic action of the neighboring Mn(III) and Cu(II) active sites in 2. Complexes 1 and 2 are the first two compounds coordinated with Schiff base ligand for both water oxidation and CO2 reduction. The finding in this work can offer significant inspiration for the future development of electrocatalysis in this area.
Potential Impact of Prosthetic Biomaterials on the Periodontium: A Comprehensive Review
Authors: Alarcón-Sánchez Mario Alberto , Heboyan Artak , Fernandes Gustavo Vicentis de Oliveira , Castro-Alarcón Natividad , Romero-Castro Norma Samanta
Published: January 2023

The success of a prosthetic treatment is closely related to the periodontal health of the individual. The aim of this article was to review and present the importance of prosthetic restorative materials on the condition of the periodontium, the changes that occur in the composition of the subgingival microbiota and the levels of inflammatory markers in gingival crevicular fluid. Articles on the influence of different prosthetic restorative materials on subgingival microbiota and proinflammatory cytokines were searched for using the keywords “prosthetic biomaterials”, “fixed prosthesis”, “periodontal health”, “subgingival microbiota”, “periodontal biomarkers” and “gingival crevicular fluid” in PubMed/Medline, Science Direct, Scopus and Google Scholar. The type of material used for prosthesis fabrication together with poor marginal and internal fit can result in changes in the composition of the subgingival microbiota, as well as increased accumulation and retention of dentobacterial plaque, thus favoring the development of periodontal disease and prosthetic treatment failure. Biological markers have helped to understand the inflammatory response of different prosthetic materials on periodontal tissues with the main purpose of improving their clinical application in patients who need them. Metal-free ceramic prostheses induce a lower inflammatory response regardless of the fabrication method; however, the use of CAD/CAM systems is recommended for their fabrication. In addition, it is presumed that metal-ceramic prostheses cause changes in the composition of the subgingival microbiota producing a more dysbiotic biofilm with a higher prevalence of periodontopathogenic bacteria, which may further favor periodontal deterioration.
Self-Assembly of Cyclodextrin-Coated Nanoparticles:Fabrication of Functional Nanostructures for Sensing and Delivery
Authors: Cengiz Busra , Gevrek Tugce Nihal , Chambre Laura , Sanyal Amitav
Published: January 2023

In recent years, the bottom-up approach has emerged as a powerful tool in the fabrication of functional nanomaterials through the self-assembly of nanoscale building blocks. The cues embedded at the molecular level provide a handle to control and direct the assembly of nano-objects to construct higher-order structures. Molecular recognition among the building blocks can assist their precise positioning in a predetermined manner to yield nano- and microstructures that may be difficult to obtain otherwise. A well-orchestrated combination of top-down fabrication and directed self-assembly-based bottom-up approach enables the realization of functional nanomaterial-based devices. Among the various available molecular recognition-based “host–guest” combinations, cyclodextrin-mediated interactions possess an attractive attribute that the interaction is driven in aqueous environments, such as in biological systems. Over the past decade, cyclodextrin-based specific host–guest interactions have been exploited to design and construct structural and functional nanomaterials based on cyclodextrin-coated metal nanoparticles. The focus of this review is to highlight recent advances in the self-assembly of cyclodextrin-coated metal nanoparticles driven by the specific host–guest interaction.
A Comprehensive Review on Adsorption, Photocatalytic and Chemical Degradation of Dyes and Nitro-Compounds over Different Kinds of Porous and Composite Materials
Authors: Haleem Abdul , Shafiq Anum , Chen Sheng-Qi , Nazar Mudasir
Published: January 2023

Dye and nitro-compound pollution has become a significant issue worldwide. The adsorption and degradation of dyes and nitro-compounds have recently become important areas of study. Different methods, such as precipitation, flocculation, ultra-filtration, ion exchange, coagulation, and electro-catalytic degradation have been adopted for the adsorption and degradation of these organic pollutants. Apart from these methods, adsorption, photocatalytic degradation, and chemical degradation are considered the most economical and efficient to control water pollution from dyes and nitro-compounds. In this review, different kinds of dyes and nitro-compounds, and their adverse effects on aquatic organisms and human beings, were summarized in depth. This review article covers the comprehensive analysis of the adsorption of dyes over different materials (porous polymer, carbon-based materials, clay-based materials, layer double hydroxides, metal-organic frameworks, and biosorbents). The mechanism and kinetics of dye adsorption were the central parts of this study. The structures of all the materials mentioned above were discussed, along with their main functional groups responsible for dye adsorption. Removal and degradation methods, such as adsorption, photocatalytic degradation, and chemical degradation of dyes and nitro-compounds were also the main aim of this review article, as well as the materials used for such degradation. The mechanisms of photocatalytic and chemical degradation were also explained comprehensively. Different factors responsible for adsorption, photocatalytic degradation, and chemical degradation were also highlighted. Advantages and disadvantages, as well as economic cost, were also discussed briefly. This review will be beneficial for the reader as it covers all aspects of dye adsorption and the degradation of dyes and nitro-compounds. Future aspects and shortcomings were also part of this review article. There are several review articles on all these topics, but such a comprehensive study has not been performed so far in the literature.
Hydrogen and Deuterium Solubility, Diffusivity and Permeability from Sorption Measurements in the Ni33Ti39Nb28 Alloy
Authors: Palumbo Oriele , Trequattrini Francesco , Tosti Silvano , Santucci Alessia , Paolone Annalisa
Published: January 2023

The hydrogen/deuterium sorption properties of Ni33Ti39Nb28 synthesized by the vacuum induction melting technique were measured between 400 and 495 °C for pressure lower than 3 bar. The Sieverts law is valid up to H(D)/M < 0.2 in its ideal form; the absolute values of the hydrogenation/deuteration enthalpy are ΔH(H2) = 85 ± 5 kJ/mol and ΔH(D2) = 84 ± 4 kJ/mol. From the kinetics of absorption, the diffusion coefficient was derived, and an Arrhenius dependence from the temperature was obtained, with Ea,d = 12 ± 1 kJ/mol for both hydrogen isotopes. The values of the alloy permeability, obtained by combining the solubility and the diffusion coefficient, were of the order of 10−9 mol m−1 s−1 Pa−0.5, a value which is one order of magnitude lower than that of Ni41Ti42Nb17, until now the best Ni-Ti-Nb alloy for hydrogen purification. In view of the simplicity of the technique here proposed to calculate the permeability, this method could be used for the preliminary screening of new alloys.
Development and Recent Advances in Lysine and N-Terminal Bioconjugation for Peptides and Proteins
Authors: Tantipanjaporn Ajcharapan , Wong Man-Kin
Published: January 2023

The demand for creation of protein diversity and regulation of protein function through native protein modification and post-translational modification has ignited the development of selective chemical modification methods for peptides and proteins. Chemical bioconjugation offers selective functionalization providing bioconjugates with desired properties and functions for diverse applications in chemical biology, medicine, and biomaterials. The amino group existing at the lysine residue and N-terminus of peptides and proteins has been extensively studied in bioconjugation because of its good nucleophilicity and high surface exposure. Herein, we review the development of chemical methods for modification of the amino groups on lysine residue and N-terminus featuring excellent selectivity, mild reaction conditions, short reaction time, high conversion, biocompatibility, and preservation of protein integrity. This review is organized based on the chemoselectivity and site-selectivity of the chemical bioconjugation reagents to the amino acid residues aiming to provide guidance for the selection of appropriate bioconjugation methods.
Developed and Validated Capillary Isotachophoresis Method for the Rapid Determining Organic Acids in Children’s Saliva
Authors: Dobrowolska-Iwanek Justyna , Jamka-Kasprzyk Małgorzata , Rusin Marcelina , Paśko Paweł , Grekh Sviatoslav , Jurczak Anna
Published: January 2023

One of the current challenges facing researchers is the search for alternative biological material, as opposed to routinely and invasively collected (such as blood), as the analysis of the former would provide information about the state of human health, allowing for the diagnosis of diseases in their early stages. With the search for disease biomarkers in alternative materials, the development of newer analytical solutions has been observed. This study aims to develop a reliable analytical method using the capillary isotachophoresis technique for the determination of organic acids in children’s saliva, the presence/elevation of which can be used in the future for diagnostic purposes. Organic acids such as formic, lactic, acetic, propionic, and butyric acid, were determined in the saliva of healthy children without carious lesions. The limit of quantification determined in the validation process was found to vary from 0.05 to 1.56 mg/L, the recoveries at the two levels were determined to vary between 90% and 110% for level I, while for level II the corresponding values of 75% and 106% were found; the presentation, expressed as relative standard deviation values (RSD), did not exceed 5%. The parameters determined while validating the results method indicated that the obtained are reliable. The Red–Green–Blue (RGB) additive color model was used for the evaluation of the method. This comparative analysis allowed us to define the color of the method, which expresses whether it meets the given assumptions and requirements. According to the RGB model, the isotachophoresis method developed requires less reagent input, shorter sample preparation times, and results with lower energy consumption. Thus, the subject procedure may provide an alternative, routine tool for determining organic acids in human saliva, to be applied in the diagnosing of diseases of various etiological origins.
Antioxidant Activity and GC-MS Profile of Cardamom (Elettaria cardamomum) Essential Oil Obtained by a Combined Extraction Method—Instant Controlled Pressure Drop Technology Coupled with Sonication
Authors: Castillo Nora E. Torres , Teresa-Martínez Giselle D. , Alonzo-Macías Maritza , Téllez-Pérez Carmen , Rodríguez-Rodríguez José , Sosa-Hernández Juan Eduardo , Parra-Saldívar Roberto , Melchor-Martínez Elda M. , Cardador-Martínez Anaberta
Published: January 2023

Cardamom Essential oils are highly demanded because of their antimicrobial, anti-inflammatory, and antioxidant activities. Nonetheless, retrieving quality extracts quickly with efficient energy savings has been challenging. Therefore, green technologies are emerging as possible alternatives. Thus, this study evaluates the yield and quality of the instant controlled pressure drop (DIC) process coupled with ultrasound-assisted extraction (UAE) of cardamom essential oil (CEO). Likewise, the antioxidant activity, chemical profile of CEO, and microstructure of seeds were analyzed. This study analyzed 13 different treatments with varying saturated steam processing temperatures (SSPT), thermal processing times (TPT), and 1 control. The results showed that CEO yield increased significantly by DIC (140 °C and 30 s) and UAE compared to the control (22.53% vs. 15.6%). DIC 2 (165 °C, 30 s) showed the highest DPPH inhibition (79.48%) and the best Trolox equivalent antioxidant capacity (TEAC) by the control with 0.60 uMTE/g. The GC/MS analysis showed 28 volatile constituents, withα-Terpinyl acetate, geranyl oleate, and oleic acid being the most abundant. DIC (140 °C and 30 s) and UAE showed the best yield and chemical profile. The SEM microscopy of untreated seeds revealed collapsed structures before the oil cell layer, which reduced the extraction yield, contrary to DIC-treated seeds, with more porous structures. Therefore, combining innovative extraction methods could solve the drawbacks of traditional extraction methods.
Tuning Photochemical and Photophysical Properties of P(V) Phthalocyanines
Authors: Safonova Evgeniya A. , Kolomeychuk Filipp M. , Gvozdev Daniil A. , Tsivadze Aslan Yu. , Gorbunova Yulia G.
Published: January 2023

The ability of P(V) phthalocyanines (Pcs) for efficient singlet oxygen (SO) generation was demonstrated for the first time by the example of unsubstituted and α- and β-octabutoxy-substituted P(V)Pcs with hydroxy, methoxy and phenoxy ligands in the apical positions of the octahedral P centre. Variation of substituents in Pc ring and P(V) axial ligands allows careful tuning of photophysical and photochemical properties. Indeed, a combination of BuO groups in the β-positions of the Pc ring and PhO groups as axial ligands provides significant SO generation quantum yields up to 90%; meanwhile, the values of SO generation quantum yields for others investigated compounds vary from 27 to 55%. All the complexes, except α-substituted P(V)Pc, demonstrate fluorescence with moderate quantum yields (10–16%). The introduction of electron-donating butoxy groups, especially in the α-position, increases the photostability of P(V)Pcs. Moreover, it has been shown in the example of β-BuO-substituted P(V) that the photostability depends on the nature of axial ligands and increases in the next row: OPh < OMe < OH. The presence of oxy/hydroxy axial ligands on the P(V) atom makes it possible to switch the photochemical and photophysical properties of P(V)Pcs by changing the acidity of the media.
eEF2K Inhibitor Design: The Progression of Exemplary Structure-Based Drug Design
Authors: Klupt Kody A. , Jia Zongchao
Published: January 2023

The α-kinase, eEF2K, phosphorylates the threonine 56 residue of eEF2 to inhibit global peptide elongation (protein translation). As a master regulator of protein synthesis, in combination with its unique atypical kinase active site, investigations into the targeting of eEF2K represents a case of intense structure-based drug design that includes the use of modern computational techniques. The role of eEF2K is incredibly diverse and has been scrutinized in several different diseases including cancer and neurological disorders—with numerous studies inhibiting eEF2K as a potential treatment option, as described in this paper. Using available crystal structures of related α-kinases, particularly MHCKA, we report how homology modeling has been used to improve inhibitor design and efficacy. This review presents an overview of eEF2K related drug discovery efforts predating from the 1990’s, to more recent in vivo studies in rat models. We also provide the reader with a basic introduction to several approaches and software programs used to undertake such drug discovery campaigns. With the recent exciting publication of an eEF2K crystal structure, we present our view regarding the future of eEF2K drug discovery.
Evolution of the Composition and Melting Behavior of Spinnable Pitch during Incubation
Authors: Li Qian , Zuo Pingping , Qu Shijie , Shen Wenzhong
Published: January 2023

The physical and chemical properties of spinnable pitch showed a huge impact on the performance of resultant pitch carbon fiber even if its physical and chemical properties were slightly changed. Various polycyclic aromatic compounds and abundant free radicals existed in spinnable pitch, and there are many interactions among molecules and free radicals. The molecular structure and composition of spinnable pitch were investigated during incubation, and the effect of molecular evaluation on rheological properties of spinnable pitch was illustrated using various characterization methods in this work. It indicated that n-hexane soluble fraction mainly occurred condensation or cleavage, and a small number of heavy components were generated after a long period. The fraction of n-hexane insoluble/toluene soluble underwent molecular condensation and cross-linking in the presence of oxygen-containing radicals and aromatic hydrocarbon radicals, while toluene insoluble/tetrahydrofuran soluble fraction tended to change in large molecules of polycyclic aromatic hydrocarbons. Lastly, tetrahydrofuran insoluble fraction was condensed due to its high aromaticity during the incubation process, and the content of aromatic carbon increased. These changes of composition and structure of spinnable pitch led to its softening point, increase in viscosity and flow activation energy, and deterioration of the rheological property.
Tautomeric Equilibrium in 1-Benzamidoisoquinoline Derivatives
Authors: Rybczyński Patryk , Kaczmarek-Kędziera Anna , Iglesias-Reguant Alex , Plażuk Damian , Ośmiałowski Borys
Published: January 2023

In this study, the tautomeric equilibrium of a sequence of 1-benzamidoisoquinoline derivatives was investigated with the tools of NMR spectroscopy and computational chemistry. The equilibrium between different tautomers in these systems could be controlled via the substitution effect, and the relative content of the amide form varied from 74% for the strong electron-donating NMe2 substituent to 38% for the strong electron-accepting NO2 group in the phenyl ring. In contrast to the previously investigated 2-phenacylquinoline derivatives, the most stable and thus most abundant tautomer in the 1-benzamidoisoquinoline series except the two most electron-accepting substituents was an amide. The intramolecular hydrogen bond present in the enol tautomer competed with the intermolecular hydrogen bonds created with the solvent molecules and thus was not a sufficient factor to favor this tautomer in the mixture. Although routinely computational studies of tautomeric equilibrium are performed within the continuum solvent models, it is proven here that the inclusion of the explicit solvent is mandatory in order to reproduce the experimental tendencies observed for this type of system, facilitating strong intermolecular hydrogen bonds.
The Tumorigenic Effect of the High Expression of Ladinin-1 in Lung Adenocarcinoma and Its Potential as a Therapeutic Target
Authors: Hu Lei , Liu Yu , Fu Changfang , Zhao Jiarong , Cui Qianwen , Sun Qiuyan , Wang Hongqiang , Lu Li , Dai Haiming , Xu Xiaohui , Yang Wulin
Published: January 2023

The oncogenic role of Ladinin-1 (LAD1), an anchoring filament protein, is largely unknown. In this study, we conducted a series of studies on the oncogenic role of LAD1 in lung adenocarcinoma (LUAD). Firstly, we analyzed the aberrant expression of LAD1 in LUAD and its correlation with patient survival, tumor immune infiltration, and the activation of cancer signaling pathways. Furthermore, the relationship between LAD1 expression and K-Ras and EGF signaling activation, tumor cell proliferation, migration, and colony formation was studied by gene knockout/knockout methods. We found that LAD1 was frequently overexpressed in LUAD, and high LAD1 expression predicts a poor prognosis. LAD1 exhibits promoter hypomethylation in LUAD, which may contribute to its mRNA upregulation. Single-sample gene set enrichment analysis (ssGSEA) showed that acquired immunity was negatively correlated with LAD1 expression, which was verified by the downregulated GO terms of “Immunoglobulin receptor binding” and “Immunoglobulin complex circulating” in the LAD1 high-expression group through Gene Set Variation Analysis (GSVA). Notably, the Ras-dependent signature was the most activated signaling in the LAD1 high-expression group, and the phosphorylation of downstream effectors, such as ERK and c-jun, was strongly inhibited by LAD1 deficiency. Moreover, we demonstrated that LAD1 depletion significantly inhibited the proliferation, migration, and cell-cycle progression of LUAD cells and promoted sensitivity to Gefitinib, K-Ras inhibitor, and paclitaxel treatments. We also confirmed that LAD1 deficiency remarkably retarded tumor growth in the xenograft model. Conclusively, LAD1 is a critical prognostic biomarker for LUAD and has potential as an intervention target.
New Triazine Derivatives as Serotonin 5-HT6 Receptor Ligands
Authors: Łażewska Dorota , Więcek Małgorzata , Satała Grzegorz , Chałupnik Paulina , Żesławska Ewa , Honkisz-Orzechowska Ewelina , Tarasek Monika , Latacz Gniewomir , Nitek Wojciech , Szymańska Ewa , Handzlik Jadwiga
Published: January 2023

Since the number of people with Alzheimer’s disease (AD) continues to rise, new and effective drugs are urgently needed to not only slow down the progression of the disease, but to stop or even prevent its development. Serotonin 5-HT6 receptor (5-HT6R) ligands are still a promising therapeutic target for the treatment of AD. 1,3,5-Triazine derivatives, as novel structures lacking an indole or a sulfone moiety, have proven to be potent ligands for this receptor. In present work, new derivatives of the compound MST4 (4-((2-isopropyl-5-methylphenoxy)methyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine), the potent 5-HT6R antagonist (Ki = 11 nM) with promising ADMET and in vivo properties, were designed. The synthesized compounds were tested for their affinity towards 5-HT6R and other receptor (off)targets (serotonin 5-HT2A, 5-HT7 and dopamine D2). Based on the new results, 4-(2-tert-butylphenoxy)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (3) was selected for extended in vitro studies as a potent and selective 5-HT6R ligand (Ki = 13 nM). Its ability to permeate the blood–brain barrier (BBB) and its hepatotoxicity were evaluated. In addition, X-ray crystallography and solubility studies were also performed. The results obtained confirm that 6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine derivatives, especially compound 3, are promising structures for further pharmacological studies as 5-HT6R ligands.
The Kurtz–Perry Powder Technique Revisited: A Study of the Effect of Reference Selection on Powder Second-Harmonic Generation Response
Authors: Sun Mengran , Wang Guili , Yao Jiyong
Published: January 2023

The accurate evaluation of nonlinear optical (NLO) coefficient, the main parameter affecting light conversion efficiency, plays a crucial role in the development of NLO materials. The Kurtz–Perry powder technique can evaluate second-harmonic generation (SHG) intensity in pristine powder form, saving a significant amount of time and energy in the preliminary screening of materials. However, the Kurtz–Perry method has recently been subject to some controversy due to the limitations of the Kurtz–Perry theory and the oversimplified experimental operation. Therefore, it is very meaningful to revisit and develop the Kurtz–Perry technique. In this work, on the basis of introducing the light scattering effect into the original Kurtz–Perry theory, the theoretical expression of second-harmonic generation intensity with respect to band gap and refractive index are analyzed. In addition, the reference-dependent SHG measurements were carried out on polycrystalline LiB3O5 (LBO), AgGaQ2 (Q = S, Se), BaGa4Q7 (Q = S, Se), and ZnGeP2 (ZGP), and the results of SHG response emphasize the importance of using appropriate references to the Kurtz–Perry method. In order to obtain reliable values of nonlinear coefficients, two criteria for selecting a reference compound were proposed: (1) it should possess a band gap close to that of the sample to be measured and (2) it should possess a refractive index close to that of the sample to be measured. This work might shed light on improvements in accuracy that can be made for effective NLO coefficients obtained using the Kurtz–Perry method.
Mannitol Is a Good Anticaking Agent for Spray-Dried Hydroxypropyl-Beta-Cyclodextrin Microcapsules
Authors: Kou Xingran , Zhang Xinping , Cheng Ying , Yu Miao , Meng Qingran , Ke Qinfei
Published: January 2023

Agglomeration is an undesirable phenomenon that often occurs in spray-dried microcapsules powder. The objective of this work is to determine the best solution for spray-dried hydroxypropyl-β-cyclodextrin (HP-β-CD) microcapsules from four anticaking agents, namely calcium stearate (CaSt), magnesium stearate (MgSt), silicon dioxide (SiO2), and mannitol (MAN), and to explore their anticaking mechanisms. Our results showed that MAN was found to be the superior anticaking agent among those tested. When the MAN ratio is 12%, the microcapsules with a special Xanthium-type shape had higher powder flowability and lower hygroscopicity and exhibited good anticaking properties. Mechanism research revealed that CaSt, MgSt, and SiO2 reduce hygroscopicity and caking by increasing the glass transition temperature of the microcapsules, while MAN prevents the hydroxyl group of HP-β-CD from combining with water molecules in the air by a crystal outer-layer on the microcapsule surface.
Synthesis of Sulfoximines and Sulfonimidamides Using Hypervalent Iodine Mediated NH Transfer
Authors: Luisi Renzo , Bull James A.
Published: January 2023

The development of NH transfer reactions using hypervalent iodine and simple sources of ammonia has facilitated the synthesis of sulfoximines and sulfonimidamides for applications across the chemical sciences. Perhaps most notably, the methods have been widely applied in medicinal chemistry and in the preparation of biologically active compounds, including in the large-scale preparation of an API intermediate. This review provides an overview of the development of these synthetic methods involving an intermediate iodonitrene since our initial report in 2016 on the conversion of sulfoxides into sulfoximines. This review covers the NH transfer to sulfoxides and sulfinamides, and the simultaneous NH/O transfer to sulfides and sulfenamides to form sulfoximines and sulfonimidamides, respectively. The mechanism of the reactions and the identification of key intermediates are discussed. Developments in the choice of reagents, and in the reaction conditions and setups used are described.