bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation on the Cause-Effect Relationships between the Process Parameters and the Resulting Geometric Properties for Wire-Based Coaxial Laser Metal Deposition
Authors: Zapata Avelino , Bernauer Christian , Stadter Christian , Kolb Cara G. , Zaeh Michael F.
Published: March 2022

Coaxial Laser Metal Deposition with wire (LMD-w) is a valuable complement to the already established Additive Manufacturing processes in production because it allows a direction-independent process with high deposition rates and high deposition accuracy. However, there is a lack of knowledge regarding the adjustment of the process parameters during process development to build defect-free parts. Therefore, in this work, a process development for coaxial LMD-w was conducted using an aluminum wire AlMg4,5MnZr and a stainless steel wire AISI 316L. At first, the boundaries for parameter combinations that led to a defect-free process were identified. The proportion between the process parameters energy per unit length and speed ratio proved crucial for a defect-free process. Then, the influence of the process parameters on the height and width of single beads for both materials was analyzed using a regression analysis. It was shown that linear models are suitable for describing the correlation between the process parameters and the dimensions of the beads. Lastly, a material-independent formula is presented to calculate the height increment per layer needed for an additive process. For future studies, the results of this work will be an aid for process development with different materials.
Machine Learning Approaches to Identify Discriminative Signatures of Volatile Organic Compounds (VOCs) from Bacteria and Fungi Using SPME-DART-MS
Authors: Arora Mehak , Zambrzycki Stephen C. , Levy Joshua M. , Esper Annette , Frediani Jennifer K. , Quave Cassandra L. , Fernández Facundo M. , Kamaleswaran Rishikesan
Published: March 2022

Point-of-care screening tools are essential to expedite patient care and decrease reliance on slow diagnostic tools (e.g., microbial cultures) to identify pathogens and their associated antibiotic resistance. Analysis of volatile organic compounds (VOC) emitted from biological media has seen increased attention in recent years as a potential non-invasive diagnostic procedure. This work explores the use of solid phase micro-extraction (SPME) and ambient plasma ionization mass spectrometry (MS) to rapidly acquire VOC signatures of bacteria and fungi. The MS spectrum of each pathogen goes through a preprocessing and feature extraction pipeline. Various supervised and unsupervised machine learning (ML) classification algorithms are trained and evaluated on the extracted feature set. These are able to classify the type of pathogen as bacteria or fungi with high accuracy, while marked progress is also made in identifying specific strains of bacteria. This study presents a new approach for the identification of pathogens from VOC signatures collected using SPME and ambient ionization MS by training classifiers on just a few samples of data. This ambient plasma ionization and ML approach is robust, rapid, precise, and can potentially be used as a non-invasive clinical diagnostic tool for point-of-care applications.
Effect of Quadrature Control Mode on ZRO Drift of MEMS Gyroscope and Online Compensation Method
Authors: Bu Feng , Guo Shuwen , Fan Bo , Wang Yiwang
Published: March 2022

The quadrature coupling error is an important factor that affects the detection output of microelectromechanical system (MEMS) gyroscopes. In this study, two quadrature error control methods, quadrature force-to-rebalance control (Mode I) and quadrature stiffness control (Mode II) were analyzed. We obtained the main factors affecting the zero-rate output (ZRO) under force-to-rebalance (FTR) closed-loop detection. The analysis results showed that the circuit phase delay in Mode I caused the quadrature channel to leak into the in-phase channel. However, in Mode II, the quadrature coupling stiffness was corrected in real time, which effectively improved the stability of the ZRO. The changes in the vibration displacement and Q-factor were the main factors for the ZRO drift in Mode II. Therefore, we propose an online compensation method for ZRO drift based on multiparameter fusion. The experimental results on a cobweb-like disk resonator gyroscope (CDRG) with a 340 k Q-factor showed that the bias instability (BI) of Mode II was significantly better than that of Mode I. After online compensation, the BI reached 0.23°/h, and the bias repeatability reached 3.15°/h at room temperature.
Isometric Double-Layer Staggered Chain Teeth Triboelectric Nanogenerator
Authors: Ding Shuai , Zhai Hua , Shao Yaomin , Lei Rui
Published: March 2022

The sliding freestanding layer triboelectric nanogenerator (SF-TENG) is a sustainable power source that can convert mechanical energy from linear or rotating mechanical motion to electrical energy. This paper proposes a double-layer staggered chain teeth TENG. Comparing the staggered electrode TENG and the double-layer staggered electrode TENG, the output voltage difference is relatively small. The electrode of the TENG is designed to the shape of chain teeth, which proves that TENG can be combined with a zipper, and the best distance among chain teeth in the TENG is determined through experiments. Compared with traditional zippers, the double-layer staggered chain teeth TENG can generate electrical energy during the continuous pulling of the zipper. The double-layer staggered chain teeth TENG has good performance. When the external load is 20 MΩ, the maximum output power reaches 20.18 µW. After the rectification and transformation, the generated electricity can light up 30 LED lights or more, and can also supply power to electronic devices. Through the chain teeth array, the open circuit voltage and transfer charge generated by the zipper during the continuous pulling process are improved. The double-layer staggered chain teeth TENG has a good usage environment in life, and this work will provide valuable insights for the development of SF-TENG technology.
Surface Quality Optimization in Micromachining with Cutting Tool Having Regular Constructive Geometry
Authors: Dumitras Catalin Gabriel , Chitariu Dragos Florin , Chifan Florin , Lates Cristina Georgiana , Horodinca Mihaita
Published: March 2022

In this paper we studied the influence of micromachining parameters on processed surface quality. Usually in discussions about micro-cutting or micromachining, the grinding or diamond turning processes are considered. Cutting tools used in the mentioned processes do not have regular constructive geometry and, in this case, it is difficult to use constructive geometric parameters such as clearance angle α or rake angle γ to optimize the quality of the machined surface. In order to determine the influence of the cutting tool’s constructive geometry on the hardness of the machined material, we used a fractional factorial design of a centered and rotatable type 26−1. A mathematical model based on five independent cutting parameters was created that allowed optimization of surface quality based on obtained roughness. The results can be applied in micromilling or microturning.
Raman Spectroscopic Studies of Pyrite at High Pressure and High Temperature
Authors: Chen Juan , Li Heping , Yuan Yi , Zhang Mengxue , Shuai Shuhang , Wan Jingjing
Published: March 2022

Variations in the Raman spectra of pyrite were studied from 113 to 853 K at room pressure with a Linkam heating and freezing stage, and for 297–513 K and pressures up to 1.9 GPa with a hydrothermal diamond anvil cell. All observed frequencies decreased continuously with an increase in temperatures up to 653 K at ambient pressure. Hematite began to form at 653 K, all pyrite had transformed to hematite (H) at 688 K, and the hematite melted at 853 K. An increase in temperature at every initial pressure (group 1: 0.5 GPa, group 2: 1.1 GPa, group 3: 1.7 GPa, group 4: 1.9 GPa), showed no evidence for chemical reaction or pyrite decomposition. Two or three Raman modes were observed because of crystal orientation or temperature-induced fluorescence effects. The pressure groups showed a decreasing trend of frequency with gradual heating. The interaction of pressure and temperature led to a gradual decrease in Ag and Eg mode at a lower pressure (0.5 GPa and 1.1 GPa) than other pressure groups. Pressure and temperature effects are evident for groups 1 and 2; however, for groups 3 and 4, the temperature shows a larger effect than pressure and leads to a sharp decrease in Ag and Eg modes.
The Grouping and Segregation Error in the Rice Experiment
Authors: Minnitt Richard
Published: March 2022

The grouping and segregation error, one of the seven sampling errors defined by Pierre Gy, is related to the combined effects of gravity and characteristics of the target analyte such as particle size, density, shape, and moisture content of the particulate materials being sampled. Kinetic energy acting on particulate materials that are moved, flow, transported, or stockpiled causes the spatial distribution of fragments relative to one another to change. The grouping and segregation error is identified, quantified, and measured in relative sampling variance terms by comparing the sampling variability due to fractional shovelling (scooping) with that using a Jones riffle splitter. The relative sampling variance of low concentrations, approximately 0.01%, of steel balls, lead balls, and flakes of tungsten carbide in the host substrate indicates that, in this specific sampling space, the grouping and segregation error is primarily a function of particle density. Conclusions from the experiments are that components of the grouping and segregation error, namely the grouping factor and segregation factor, can be identified, measured, and mitigated. Whereas the grouping and segregation error has historically been considered to be less than the fundamental sampling error, these experiments suggest that it can be up to four times the fundamental sampling error depending on the density of the segregated materials.
Effect of Different Mineralogical Proportions on the Electrical Conductivity of Dry Hot-Pressed Sintering Gabbro at High Temperatures and Pressures
Authors: Wang Mengqi , Dai Lidong , Hu Haiying , Sun Wenqing , Hu Ziming , Jing Chenxin
Published: March 2022

Electrical conductivities of the dry hot-pressed sintering gabbro with various mineralogical proportions (CpxXPl100−X, X = 0, 10, 20, 30, 40, 50, 60, 70, 80, 90 and 100 vol% (the signals of Cpx and Pl denote clinopyroxene and plagioclase, respectively) were measured in the YJ-3000t multi-anvil pressure and Solartron-1260 impedance spectroscopy analyzer at temperatures of 773–1073 K and pressures of 1.0–3.0 GPa. At the given pressure conditions, the electrical conductivity and temperature conformed to an Arrhenius relation. For the fixed mineralogical composition of Cpx50Pl50, the electrical conductivities of the samples significantly increased with the rise of temperature, but slightly decreased with increasing pressure. Furthermore, the activation energy and activation volume were determined as 1.06 ± 0.12 eV and 6.00 ± 2.00 cm3/mole, respectively. As for the various mineralogical compositions of dry gabbro, the electrical conductivities of the samples increased with the rise of volume percentage of clinopyroxene (Cpx) at 1.0 GPa. It is proposed that the main conduction mechanism is the small polaron, owing to the positive relation between the electrical conductivity and the iron content in samples. On the basis of these obtained conductivity results, laboratory-based electrical conductivity–depth profiles for the hot-pressed sintering gabbro with various mineralogical proportions and temperature gradients were successfully established. In conclusion, although the present acquired electrical conductivity results on the dry hot-pressed sintering gabbro with various mineralogical proportions cannot explain the high conductivity anomaly in the oceanic crust and West African craton, it can provide one reasonable constraint on the mineralogical composition in these representative gabbro-rich regions.
Characterization of Cabernet Sauvignon Wines by Untargeted HS-SPME GC-QTOF-MS
Authors: Chávez-Márquez Alejandra , Gardea Alfonso A. , González-Rios Humberto , Vazquez-Moreno Luz
Published: March 2022

Untargeted metabolomics approaches are emerging as powerful tools for the quality evaluation and authenticity of food and beverages and have been applied to wine science. However, most fail to report the method validation, quality assurance and/or quality control applied, as well as the assessment through the metabolomics-methodology pipeline. Knowledge of Mexican viticulture, enology and wine science remains scarce, thus untargeted metabolomics approaches arise as a suitable tool. The aim of this study is to validate an untargeted HS-SPME-GC-qTOF/MS method, with attention to data processing to characterize Cabernet Sauvignon wines from two vineyards and two vintages. Validation parameters for targeted methods are applied in conjunction with the development of a recursive analysis of data. The combination of some parameters for targeted studies (repeatability and reproducibility < 20% RSD; linearity > 0.99; retention-time reproducibility < 0.5% RSD; match-identification factor < 2.0% RSD) with recursive analysis of data (101 entities detected) warrants that both chromatographic and spectrometry-processing data were under control and provided high-quality results, which in turn differentiate wine samples according to site and vintage. It also shows potential biomarkers that can be identified. This is a step forward in the pursuit of Mexican wine characterization that could be used as an authentication tool.
Stability Studies of UV Laser Irradiated Promethazine and Thioridazine after Exposure to Hypergravity Conditions
Authors: Simon Ágota , Tozar Tatiana , Smarandache Adriana , Boni Mihai , Stoicu Alexandru , Dowson Alan , van Loon Jack J. W. A. , Pascu Mihail Lucian
Published: March 2022

Pharmaceuticals carried into space are subjected to different gravitational conditions. Hypergravity is encountered in the first stage, during spacecraft launching. The stability of medicines represents a critical element of space missions, especially long-duration ones. Therefore, stability studies should be envisaged before the implementation of drugs for future deep space travel, where the available pharmaceuticals would be limited and restocking from Earth would be impossible. Multipurpose drugs should be proposed for this reason, such as phenothiazine derivatives that can be transformed by optical methods into antimicrobial agents. Within this preliminary study, promethazine and thioridazine aqueous solutions were exposed to UV laser radiation that modified their structures and generated a mixture of photoproducts efficient against particular bacteria. Subsequently, they were subjected to 20 g in the European Space Agency’s Large Diameter Centrifuge. The aim was to evaluate the impact of hypergravity on the physico-chemical and spectral properties of unirradiated and laser-irradiated medicine solutions through pH assay, UV-Vis/FTIR absorption spectroscopy, and thin-layer chromatography. The results revealed no substantial alterations in centrifuged samples when compared to uncentrifuged ones. Due to their stability after high-g episodes, laser-exposed phenothiazines could be considered for future space missions.
Nonlinear Finite Element Analysis of γ-Graphyne Structures under Shearing
Authors: Siampanis Sotirios G. , Giannopoulos Georgios I. , Lagaros Nikos D. , Hatziefremidis Antonios , Georgantzinos Stelios K.
Published: March 2022

In this study, a nonlinear, spring-based finite element approach is employed in order to predict the nonlinear mechanical response of graphyne structures under shear loading. Based on Morse potential functions, suitable nonlinear spring finite elements are formulated simulating the interatomic interactions of different graphyne types. Specifically, the four well-known types of γ-graphyne, i.e., graphyne-1 also known as graphyne, graphyne-2 also known as graphdiyne, graphyne-3, and graphyne-4 rectangular sheets are numerically investigated applying appropriate boundary conditions representing shear load. The obtained finite element analysis results are employed to calculate the in-plane shear stress–strain behaviour, as well as the corresponding mechanical properties as shear modulus and shear strength. Comparisons of the present graphyne shearing response predictions with other corresponding estimations are performed to validate the present research results.
Exploring Peptaibol’s Profile, Antifungal, and Antitumor Activity of Emericellipsin A of Emericellopsis Species from Soda and Saline Soils
Authors: Kuvarina Anastasia E. , Gavryushina Irina A. , Sykonnikov Maxim A. , Efimenko Tatiana A. , Markelova Natalia N. , Bilanenko Elena N. , Bondarenko Sofiya A. , Kokaeva Lyudmila Y. , Timofeeva Alla V. , Serebryakova Marina V. , Barashkova Anna S. , Rogozhin Eugene A. , Georgieva Marina L. , Sadykova Vera S.
Published: March 2022

Features of the biochemical adaptations of alkaliphilic fungi to exist in extreme environments could promote the production of active antibiotic compounds with the potential to control microorganisms, causing infections associated with health care. Thirty-eight alkaliphilic and alkalitolerant Emericellopsis strains (E. alkalina, E. cf. maritima, E. cf. terricola, Emericellopsis sp.) isolated from different saline soda soils and belonging to marine, terrestrial, and soda soil ecological clades were investigated for emericellipsin A (EmiA) biosynthesis, an antifungal peptaibol previously described for Emericellopsis alkalina. The analysis of the Emericellopsis sp. strains belonging to marine and terrestrial clades from chloride soils revealed another novel form with a mass of 1032.7 Da, defined by MALDI-TOF Ms/Ms spectrometers, as the EmiA lacked a hydroxyl (dEmiA). EmiA displayed strong inhibitory effects on cell proliferation and viability of HCT 116 cells in a dose- and time-dependent manners and induced apoptosis.
Long-Term Stability of Redox Mediators in Carbonate Solvents
Authors: Weber Felix M. , Kohlhaas Ina , Figgemeier Egbert
Published: March 2022

Scanning electrochemical microscopy (SECM) used in the feedback mode is one of the most powerful versatile analytical tools used in the field of battery research. However, the application of SECM in the field of lithium-ion batteries (LIBs) faces challenges associated with the selection of a suitable redox mediator due to its high reactivity at low potentials at lithium metal or lithiated graphite electrodes. In this regard, the electrochemical/chemical stability of 2,5-di-tert-butyl-1,4-dimethoxybenzene (DBDMB) is evaluated and benchmarked with ferrocene. This investigation is systematically carried out in both linear and cyclic carbonates of the electrolyte recipe. Measurements of the bulk current with a microelectrode prove that while DBDMB decomposes in ethyl methyl carbonate (EMC)-containing electrolyte, bulk current remains stable in cyclic carbonates, ethylene carbonate (EC) and propylene carbonate (PC). Ferrocene was studied as an alternative redox mediator, showing superior electrochemical performance in ethyl methyl carbonate-containing electrolytes in terms of degradation. The resulting robustness of ferrocene with SECM is essential for a quantitative analysis of battery materials over extended periods. SECM approach curves depict practical problems when using the decomposing DBDMB for data acquisition and interpretation. This study sheds light towards the use of SECM as a probing tool enabled by redox mediators.
Screening of Natural Products Inhibitors of SARS-CoV-2 Entry
Authors: González-Maldonado Pamela , Alvarenga Nelson , Burgos-Edwards Alberto , Flores-Giubi Ma. Eugenia , Barúa Javier E. , Romero-Rodríguez Ma. Cristina , Soto-Rifo Ricardo , Valiente-Echeverría Fernando , Langjahr Patricia , Cantero-González Guadalupe , Sotelo Pablo H.
Published: March 2022

The COVID-19 pandemic has led to the search for new molecules with antiviral activity against SARS-CoV-2. The entry of the virus into the cell is one of the main targets for inhibiting SARS-CoV-2 infection. Natural products are an important source of new therapeutic alternatives against diseases. Pseudotyped viruses allow the study of SARS-CoV-2 viral entry inhibitors, and due to their simplicity, they allow the screening of a large number of antiviral candidates in Biosafety Level 2 facilities. We used pseudotyped HIV-1 with the D614G SARS-CoV-2 spike glycoprotein to test its ability to infect ACE2-expressing HEK 293T cells in the presence of diverse natural products, including 21 plant extracts, 7 essential oils, and 13 compounds from plants and fungi. The 50% cytotoxic concentration (CC50) was evaluated using the resazurin method. From these analyses, we determined the inhibitory activity of the extract of Stachytarpheta cayennensis, which had a half-maximal inhibitory concentration (IC50) of 91.65 µg/mL, a CC50 of 693.5 µg/mL, and a selectivity index (SI) of 7.57, indicating its potential use as an inhibitor of SARS-CoV-2 entry. Moreover, our work indicates the usefulness of the pseudotyped-virus system in the screening of SARS-CoV-2 entry inhibitors.
An Orthogonal Synthetic Approach to Nonsymmetrical Bisazolyl 2,4,6-Trisubstituted Pyridines
Authors: Gamonal Ruiz-Crespo Arturo , Galán-Fernández Laura , Martínez-Martín Paloma , Rodríguez-Ubis Juan Carlos
Published: March 2022

A three-step synthetic route giving access to nonsymmetrical bisazolyl 2,4,6-trisubstituted pyridines with different substituents on the pyrazole, indazole, and pyridine heterocycles is described. From the readily available 4-bromo-2,6-difluoropyridine, both fluorine atoms allow for easy selective stepwise substitution, and the bromine atom provides easy access to additional functionalities through both Suzuki and Sonogashira Pd(0) cross-coupling reactions. These synthons represent optimal structures as building blocks in complexation and metalloorganic structures for the tuning of their chelating and photophysical properties.
Investigating the Effects of Amino Acid Variations in Human Menin
Authors: Biancaniello Carmen , D’Argenio Antonia , Giordano Deborah , Dotolo Serena , Scafuri Bernardina , Marabotti Anna , d’Acierno Antonio , Tagliaferri Roberto , Facchiano Angelo
Published: March 2022

Human menin is a nuclear protein that participates in many cellular processes, as transcriptional regulation, DNA damage repair, cell signaling, cell division, proliferation, and migration, by interacting with many other proteins. Mutations of the gene encoding menin cause multiple endocrine neoplasia type 1 (MEN1), a rare autosomal dominant disorder associated with tumors of the endocrine glands. In order to characterize the structural and functional effects at protein level of the hundreds of missense variations, we investigated by computational methods the wild-type menin and more than 200 variants, predicting the amino acid variations that change secondary structure, solvent accessibility, salt-bridge and H-bond interactions, protein thermostability, and altering the capability to bind known protein interactors. The structural analyses are freely accessible online by means of a web interface that integrates also a 3D visualization of the structure of the wild-type and variant proteins. The results of the study offer insight into the effects of the amino acid variations in view of a more complete understanding of their pathological role.
Greener Synthesis of Antiproliferative Furoxans via Multicomponent Reactions
Authors: Ingold Mariana , de la Sovera Victoria , Dapueto Rosina , Hernández Paola , Porcal Williams , López Gloria V.
Published: March 2022

Prostate and bladder cancers are commonly diagnosed malignancies in men. Several nitric oxide donor compounds with strong antitumor activity have been reported. Thus, continuing with our efforts to explore the chemical space around bioactive furoxan moiety, multicomponent reactions were employed for the rapid generation of molecular diversity and complexity. We herein report the use of Ugi and Groebke–Blackburn–Bienaymé multicomponent reactions under efficient, safe, and environmentally friendly conditions to synthesize a small collection of nitric-oxide-releasing molecules. The in vitro antiproliferative activity of the synthesized compounds was measured against two different human cancer cell lines, LNCaP (prostate) and T24 (bladder). Almost all compounds displayed antiproliferative activity against both cancer cell lines, providing lead compounds with nanomolar GI50 values against the cancer bladder cell line with selectivity indices higher than 10.
Development and Optimization of CRISPR Prime Editing System in Photoautotrophic Cells
Authors: Jiang Zhengzheng , Abdullah  , Zhang Shun , Jiang Yuli , Liu Rui , Xiao Yi
Published: March 2022

Prime editor (PE), a versatile editor that allows the insertion and deletion of arbitrary sequences, and all 12-point mutations without double-strand breaks (DSB) and a donor template, dramatically enhances research capabilities. PE combines nickase Cas9(H840A) and reverse transcriptase (RT), along with prime editing guide RNA (pegRNA). It has been reported in several plant species, but a weak editing efficiency has led to a decrease in applications. This study reports an optimized-prime editor (O-PE) for endogenous gene editing in Arabidopsis thaliana cells, with an average 1.15% editing efficiency, which is 16.4-fold higher than previously reported. Meanwhile, we observed an increase in indels when testing alternative reverse transcriptase and found out that nCas9(H840A) fused to non-functional reverse transcriptase was responsible for the increase. This work develops an efficient prime editor for plant cells and provides a blueprint for applying PE in other photoautotrophic cells, such as microalgae, that have a high industrial value.
A New and Sensitive HPLC-UV Method for Rapid and Simultaneous Quantification of Curcumin and D-Panthenol: Application to In Vitro Release Studies of Wound Dressings
Authors: Anjani Qonita Kurnia , Utomo Emilia , Domínguez-Robles Juan , Detamornrat Usanee , Donnelly Ryan F. , Larrañeta Eneko
Published: March 2022

Curcumin (CUR) and D-panthenol (DPA) have been widely investigated for wound-healing treatment. In order to analyse these two compounds from a dosage form, such as polymer-based wound dressings or creams, an analytical method that allows the quantification of both drugs simultaneously should be developed. Here, we report for the first time a validated high-performance liquid chromatographic (HPLC) method coupled with UV detection to quantify CUR and DPA based on the standards set by the International Council on Harmonization (ICH) guidelines. The separation of the analytes was performed using a C18 column that utilised a mobile phase consisting of 0.001% v/v phosphoric acid and methanol using a gradient method with a run time of 15 min. The method is linear for drug concentrations within the range of 0.39–12.5 μg mL−1 (R2 = 0.9999) for CUR and 0.39–25 μg mL−1 for DPA (R2 = 1). The validated method was found to be precise and accurate. Moreover, the CUR and DPA solution was found to be stable under specific storage conditions. We, therefore, suggest that the HPLC-UV method developed in this study may be very useful in screening formulations for CUR and DPA within a preclinical setting through in vitro release studies.
Cembranolides and Related Constituents from the Soft Coral Sarcophyton cinereum
Authors: Chao Chih-Hua , Chen Yi-Ju , Huang Chiung-Yao , Chang Fang-Rong , Dai Chang-Feng , Sheu Jyh-Horng
Published: March 2022

In an attempt to explore the bioactive metabolites of the soft coral Sarcophyton cinereum, three new cembranolides, cinerenolides A–C (1–3), and 16 known compounds were isolated and identified from the EtOAc extract. The structures of the new cembranolides were elucidated on the basis of spectroscopic analysis, and the NOE analysis of cinerenolide A (1) was performed with the assistance of the calculated lowest-energy molecular model. The relative configuration of cinerenolide C (3) was determined by the quantum chemical NMR calculation, followed by applying DP4+ analysis. In addition, the cytotoxic assays disclosed that some compounds exhibited moderate to potent activities in the proliferation of P388, DLD-1, HuCCT-1, and CCD966SK cell lines.
Electrochemistry of Cobalta Bis(dicarbollide) Ions Substituted at Carbon Atoms with Hydrophilic Alkylhydroxy and Carboxy Groups
Authors: Fojt Lukáš , Grüner Bohumír , Nekvinda Jan , Tűzűn Ece Zeynep , Havran Luděk , Fojta Miroslav
Published: March 2022

In this study we explore the effect on the electrochemical signals in aqueous buffers of the presence of hydrophilic alkylhydroxy and carboxy groups on the carbon atoms of cobalta bis(dicarbollide) ions. The oxygen-containing exo-skeletal substituents of cobalta bis(dicarbollide) ions belong to the perspective building blocks that are considered for bioconjugation. Carbon substitution provides wider versatility and applicability in terms of the flexibility of possible chemical pathways. However, until recently, the electrochemistry of compounds substituted only on boron atoms could be studied, due to the unavailability of carbon-substituted congeners. In the present study, electrochemistry in aqueous phosphate buffers is considered along with the dependence of electrochemical response on pH and concentration. The compounds used show electrochemical signals around −1.3 and +1.1 V of similar or slightly higher intensities than in the parent cobalta bis(dicarbollide) ion. The signals at positive electrochemical potential correspond to irreversible oxidation of the boron cage (the C2B9 building block) and at negative potential correspond to the reversible redox process of (CoIII/CoII) at the central atom. Although the first signal is typically sharp and its potential can be altered by a number of substituents, the second signal is complex and is composed of three overlapping peaks. This signal shows sigmoidal character at higher concentrations and may be used as a diagnostic tool for aggregation in solution. Surprisingly enough, the observed effects of the site of substitution (boron or carbon) and between individual groups on the electrochemical response were insignificant. Therefore, the substitutions would preserve promising properties of the parent cage for redox labelling, but would not allow for the further tuning of signal position in the electrochemical window.
Discovery of Proteins Responsible for Resistance to Three Chemotherapy Drugs in Breast Cancer Cells Using Proteomics and Bioinformatics Analysis
Authors: Cha Hyo Kyeong , Cheon Seongmin , Kim Hyeyoon , Lee Kyung-Min , Ryu Han Suk , Han Dohyun
Published: March 2022

Chemoresistance is a daunting obstacle to the effective treatment of breast cancer patients receiving chemotherapy. Although the mechanism of chemotherapy drug resistance has been explored broadly, the precise mechanism at the proteome level remains unclear. Especially, comparative studies between widely used anticancer drugs in breast cancer are very limited. In this study, we employed proteomics and bioinformatics approaches on chemoresistant breast cancer cell lines to understand the underlying resistance mechanisms that resulted from doxorubicin (DR), paclitaxel (PR), and tamoxifen (TAR). In total, 10,385 proteins were identified and quantified from three TMT 6-plex and one TMT 10-plex experiments. Bioinformatics analysis showed that Notch signaling, immune response, and protein re-localization processes were uniquely associated with DR, PR, and TAR resistance, respectively. In addition, proteomic signatures related to drug resistance were identified as potential targets of many FDA-approved drugs. Furthermore, we identified potential prognostic proteins with significant effects on overall survival. Representatively, PLXNB2 expression was associated with a highly significant increase in risk, and downregulation of ACOX3 was correlated with a worse overall survival rate. Consequently, our study provides new insights into the proteomic aspects of the distinct mechanisms underlying chemoresistance in breast cancer.
Synthesis and Reactivity of Martin’s Spirosilane-Derived Chloromethylsilicate
Authors: Deis Thomas , Forte Jérémy , Fensterbank Louis , Lemière Gilles
Published: March 2022

Pentacoordinate silicon derivatives with a chloromethyl ligand are versatile compounds that are usually obtained from the corresponding tetravalent trialkoxy- or trihalogeno(chloromethyl)silane. We describe herein the synthesis of a chloromethylsilicate bearing two Martin’s ligands readily obtained by addition of in situ generated chloromethyllithium to a spirosilane. The reactivity of this new species was evaluated and it has been established that the chloride is displaced by strong nucleophiles such as alkyllithiums and (hetero)aryllithiums. In Lewis acidic conditions, the pentacoordinate silicon species rearranges through a formal insertion of a methylene into one Si–C bond, to form a new tetravalent spirosilane with a six-membered ring. The same kind of rearrangement can be triggered also by addition of a Lewis base. The mechanism of the rearrangement in both conditions has been studied by means of DFT calculations.
A Sub-Micromolar MraYAA Inhibitor with an Aminoribosyl Uridine Structure and a (S,S)-Tartaric Diamide: Synthesis, Biological Evaluation and Molecular Modeling
Authors: Oliver Martin , Le Corre Laurent , Poinsot Mélanie , Bosco Michaël , Wan Hongwei , Amoroso Ana , Joris Bernard , Bouhss Ahmed , Calvet-Vitale Sandrine , Gravier-Pelletier Christine
Published: March 2022

New inhibitors of the bacterial tranferase MraY are described. Their structure is based on an aminoribosyl uridine scaffold, which is known to be important for the biological activity of natural MraY inhibitors. A decyl alkyl chain was introduced onto this scaffold through various linkers. The synthesized compounds were tested against the MraYAA transferase activity, and the most active compound with an original (S,S)-tartaric diamide linker inhibits MraY activity with an IC50 equal to 0.37 µM. Their antibacterial activity was also evaluated on a panel of Gram-positive and Gram-negative strains; however, the compounds showed no antibacterial activity. Docking and molecular dynamics studies revealed that this new linker established two stabilizing key interactions with N190 and H325, as observed for the highly potent inhibitors carbacaprazamycin, muraymycin D2 and tunicamycin.
N-Glycosylation Patterns across the Age-Related Macular Degeneration Spectrum
Authors: Bućan Ivona , Škunca Herman Jelena , Jerončić Tomić Iris , Gornik Olga , Vatavuk Zoran , Bućan Kajo , Lauc Gordan , Polašek Ozren
Published: March 2022

The pathogenesis of age-related macular degeneration (AMD) remains elusive, despite numerous research studies. Therefore, we aimed to investigate the changes of plasma and IgG-specific N-glycosylation across the disease severity spectrum. We examined 2835 subjects from the 10.001 Dalmatians project, originating from the isolated Croatian islands of Vis and Korčula. All subjects were classified into four groups, namely (i) bilateral AMD, (ii) unilateral AMD, (iii) early-onset drusen, and (iv) controls. We analysed plasma and IgG N-glycans measured by HPLC and their association with retinal fundus photographs. There were 106 (3.7%) detected cases of AMD; 66 of them were bilateral. In addition, 45 (0.9%) subjects were recorded as having early-onset retinal drusen. We detected several interesting differences across the analysed groups, suggesting that N-glycans can be used as a biomarker for AMD. Multivariate analysis suggested a significant decrease in the immunomodulatory bi-antennary glycan structures in unilateral AMD (adjusted odds ratio 0.43 (95% confidence interval 0.22–0.79)). We also detected a substantial increase in the pro-inflammatory tetra-antennary plasma glycans in bilateral AMD (7.90 (2.94–20.95)). Notably, some of these associations were not identified in the aggregated analysis, where all three disease stages were collapsed into a single category, suggesting the need for better-refined phenotypes and the use of disease severity stages in the analysis of more complex diseases. Age-related macular degeneration progression is characterised by the complex interplay of various mechanisms, some of which can be detected by measuring plasma and IgG N-glycans. As opposed to a simple case-control study, more advanced and refined study designs are needed to understand the pathogenesis of complex diseases.
Recent Advances in Glycyrrhetinic Acid-Functionalized Biomaterials for Liver Cancer-Targeting Therapy
Authors: Speciale Antonio , Muscarà Claudia , Molonia Maria Sofia , Cristani Mariateresa , Cimino Francesco , Saija Antonella
Published: March 2022

Liver cancer is one of the most common causes of cancer mortality worldwide. Chemotherapy and radiotherapy are the conventional therapies generally employed in patients with liver tumors. The major issue associated with the administration of chemotherapeutics is their high toxicity and lack of selectivity, leading to systemic toxicity that can be detrimental to the patient’s quality of life. An important approach to the development of original liver-targeted therapeutic products takes advantage of the employment of biologically active ligands able to bind specific receptors on the cytoplasmatic membranes of liver cells. In this perspective, glycyrrhetinic acid (GA), a pentacyclic triterpenoid present in roots and rhizomes of licorice, has been used as a ligand for targeting the liver due to the expression of GA receptors on the sinusoidal surface of mammalian hepatocytes, so it may be employed to modify drug delivery systems (DDSs) and obtain better liver or hepatocyte drug uptake and efficacy. In the current review, we focus on the most recent and interesting research advances in the development of GA-based hybrid compounds and DDSs developed for potential employment as efficacious therapeutic options for the treatment of hepatic cancer.
Natural Product-Derived Phosphonic Acids as Corrosion Inhibitors for Iron and Steel
Authors: Ruf Erik , Naundorf Tim , Seddig Tom , Kipphardt Helmut , Maison Wolfgang
Published: March 2022

Organic acids, typically derived from an oil-based value chain, are frequently used as corrosion inhibitors in industrial metal working fluids. The criteria for selection of these corrosion inhibitors have changed in the last decades, and are today not only performance-driven, but influenced by ecological considerations, toxicity and regulatory standards. We present scalable semisynthetic approaches to organic corrosion inhibitors based on phosphonic acids from renewable resources. They have been evaluated by chip filter assay, potentiodynamic polarization measurements, electrochemical impedance measurements and gravimetry for corrosion protection of iron and steel in an aqueous environment at slightly alkaline pH. The efficacy of several phosphonic acids tested was found to be strongly dependent on structural features influencing molecular self-assembly of protective layers, and the solubility of salts formed with di- and trivalent cations from the media or formed during corrosion. A carboxyphosphonic acid (derived from castor oil) was found to have remarkable anticorrosive effects in all media tested. We attribute the anticorrosion properties of this carboxyphosphonic acid to the formation of particularly stable protective layers on the metal surface. It might thus serve as a commercially attractive substitute for current acidic corrosion inhibitors, derived from renewable resources.
Preparation of Active Peptides from Camellia vietnamensis and Their Metabolic Effects in Alcohol-Induced Liver Injury Cells
Authors: Feng Lu , Chen Jian , Yan Wuping , Ye Zhouchen , Yu Jing , Yao Guanglong , Wu Yougen , Zhang Junfeng , Yang Dongmei
Published: March 2022

Liver damage seriously affects human health. Over 35% of cases of acute liver damage are caused by alcohol damage. Thus, finding drugs that can inhibit and effectively treat this disease is necessary. This article mainly focuses on the effect of the metabolome physical activity of active peptides in Camellia vietnamensis active peptide (CMAP) and improving liver protection. DEAE Sepharose FF ion-exchange column chromatography was used in separating and purifying crude peptides from Camellia vietnamensis Two components, A1 and A2, were obtained, and the most active A1 was selected. Sephadex G-100 gel column chromatography was used in A1 separation and purification. Three components, Al-1, Al-2, and Al-3, were obtained. Through antioxidant activity in vitro as an index of inspection, the relatively active component A1-2 was removed. Reverse-phase high-performance liquid chromatography showed that the purity of component A1-2 was 93.45%. The extracted CMAPs acted on alcoholic liver injury cells. Metabolomics studies revealed that the up-regulated metabolites were ribothymidine and xanthine; the down-regulated metabolites were hydroxyphenyllactic acid, creatinine, stearoylcarnitine, and inosine. This study provides an effective theoretical support for subsequent research.
Effect of Intersection Angle of Input Channels in Droplet Generators
Authors: Kim Gi-Beum , Park Young-Ran , Kim Seong-Jong , Park Kwang-Hyun
Published: March 2022

In this paper, we studied the effects of the intersection angle between the inlet channels on the droplet diameter using a COMSOL Multiphysics® simulation. We employed the level-set method to study the droplet generation process inside a microfluidic flow device. A flow-focusing geometry was integrated into a microfluidics device and used to study droplet formation in liquid–liquid systems. Droplets formed by this flow-focusing technique are typically smaller than the upstream capillary tube and vary in size with the flow rates. Different intersection angles were modeled with a fixed width of continuous and dispersed channels, orifices, and expansion channels. Numerical simulations were performed using the incompressible Navier–Stokes equations for single-phase flow in various flow-focusing geometries. As a result of modeling, when the dispersed flow rate and the continuous flow rate were increased, the flow of the continuous flow fluid interfered with the flow of the dispersed flow fluid, which resulted in a decrease in the droplet diameter. Variations in the droplet diameter can be used to change the intersection angle and fluid flow rate. In addition, it was predicted that the smallest diameter droplet would be generated when the intersection angle was 90°.
Scalable Synthesis and Cancer Cell Cytotoxicity of Rooperol and Analogues
Authors: Schwartz Zachary , Theisen Peter , Bjornstal Olaf , Rodebaugh Mary , Jemal Mauricio , Lee Dallas , Shelton Spencer , Zhao Zhenze , Du Liqin , Kerwin Sean
Published: March 2022

Plant polyphenols, such as the African potato (Hypoxis hemerocallidea)-derived bis-catechol rooperol, can display promising anticancer activity yet suffer from rapid metabolism. Embarking upon a program to systematically examine potentially more metabolically stable replacements for the catechol rings in rooperol, we report here a general, scalable synthesis of rooperol and analogues that builds on our previous synthetic approach incorporating a key Pd-catalyzed decarboxylative coupling strategy. Using this approach, we have prepared and evaluated the cancer cell cytotoxicity of rooperol and a series of analogues. While none of the analogues examined here were superior to rooperol in preventing the growth of cancer cells, analogues containing phenol or methylenedioxyphenyl replacements for one or both catechol rings were nearly as effective as rooperol.
Genesis and Mechanism of Some Cancer Types and an Overview on the Role of Diet and Nutrition in Cancer Prevention
Authors: Kamal Nurkhalida , Ilowefah Muna Abdulsalam , Hilles Ayah Rebhi , Anua Nurul Adlina , Awin Tahani , Alshwyeh Hussah Abdullah , Aldosary Sahar Khamees , Jambocus Najla Gooda Sahib , Alosaimi Areej A. , Rahman Azizur , Mahmood Syed , Mediani Ahmed
Published: March 2022

Cancer is a major disease with a high mortality rate worldwide. In many countries, cancer is considered to be the second most common cause of death after cardiovascular disease. The clinical management of cancer continues to be a challenge as conventional treatments, such as chemotherapy and radiation therapy, have limitations due to their toxicity profiles. Unhealthy lifestyle and poor dietary habits are the key risk factors for cancer; having a healthy diet and lifestyle may minimize the risk. Epidemiological studies have shown that a high fruit and vegetable intake in our regular diet can effectively reduce the risk of developing certain types of cancers due to the high contents of antioxidants and phytochemicals. In vitro and in vivo studies have shown that phytochemicals exert significant anticancer effects due to their free radical scavenging capacity potential. There has been extensive research on the protective effects of phytochemicals in different types of cancers. This review attempts to give an overview of the etiology of different types of cancers and assesses the role of phytonutrients in the prevention of cancers, which makes the present review distinct from the others available.
Coupling Reactions of Anhydro-Aldose Tosylhydrazones with Boronic Acids
Authors: Kaszás Tímea , Baráth Balázs Áron , Balázs Bernadett , Blága Tekla , Juhász László , Somsák László , Tóth Marietta
Published: March 2022

A catalyst-free coupling reaction between O-peracetylated, O-perbenzoylated, O-permethylated, and O-permethoxymethylated 2,6-anhydro-aldose tosylhydrazones (C-(β-d-glycopyranosyl)formaldehyde tosylhydrazones) and aromatic boronic acids is reported. The base-promoted reaction is operationally simple and exhibits a broad substrate scope. The main products in most of the transformations were open-chain 1-C-aryl-hept-1-enitol type compounds while the expected β-d-glycopyranosylmethyl arenes (benzyl C-glycosides) were formed in subordinate yields only. A mechanistic rationale is provided to explain how a complex substrate may change the well-established course of the reaction.
Synthesis of Polysubstituted Ferrocenesulfoxides
Authors: Wen Min , Erb William , Mongin Florence , Halauko Yury S. , Ivashkevich Oleg A. , Matulis Vadim E. , Roisnel Thierry
Published: March 2022

The purpose of the study is to design synthetic methodologies, especially directed deprotometalation using polar organometallic reagents, to access polysubstituted ferrocenesulfoxides. From enantiopure 2-substituted (SiMe3, PPh2) S-tert-butylferrocenesulfoxides, a third substituent was first introduced at the 5 position (SiMe3, I, D, C(OH)Ph2, Me, PPh2, CH2NMe2, F) and removal of the trimethylsilyl group then afforded 2-substituted ferrocenesulfoxides unreachable otherwise. Attempts to apply the “halogen dance” reaction to the ferrocenesulfoxide series led to unexpected results although rationalized in light of calculated pKa values. Further functionalizations were also possible. Thus, new enantiopure, planar chiral di- and trisubstituted ferrocenes have been obtained, in addition to several original 2-substituted, 2,3- and 2,5-disubstituted, 2,3,5-trisubstituted and even 2,3,4,5-tetrasubstituted ferrocenesulfoxides, also enantiopure.