bluuebunny/crossref_metadata_2025 huggingface dataset:
Gram-Scale Synthesis of Carbon-Supported Sub-5 nm PtNi Nanocrystals for Efficient Oxygen Reduction
Authors: Wang Minli , Chen Xu , Xu Wenwen , Wang Zhongfeng , He Peilei , Lu Zhiyi
Published: June 2022

The preparation of a high performance and durability with low-platinum (Pt) loading oxygen reduction catalysts remains a challenge for the practical application of fuel cells. Alloying Pt with a transition metal can greatly improve the activity and durability for oxygen reduction reaction (ORR). In this work, we present a one-pot wet-chemical strategy to controllably synthesize carbon supported sub-5 nm PtNi nanocrystals with a ~3% Pt loading. The as-prepared PtNi/C-200 catalyst with a Pt/Ni atomic ratio of 2:3 shows a high oxygen reduction activity of 0.66 A mgpt−1 and outstanding durability over 10,000 potential cycles in 0.1 M KOH in a half-cell condition. The PtNi/C-200 catalyst exhibits the highest ORR activity, with an onset potential (Eonset) of 0.98 V and a half-wave potential (E1/2) of 0.84 V. The mass activity and specific activity are 3.89 times and 9.16 times those of 5% commercial Pt/C. More importantly, this strategy can be applied to the gram-scale synthesis of high-efficiency electrocatalysts. As a result, this effective synthesis strategy has a significant meaning in practical applications of full cells.
A Current Encyclopedia of Bioinformatics Tools, Data Formats and Resources for Mass Spectrometry Lipidomics
Authors: Hoffmann Nils , Mayer Gerhard , Has Canan , Kopczynski Dominik , Al Machot Fadi , Schwudke Dominik , Ahrends Robert , Marcus Katrin , Eisenacher Martin , Turewicz Michael
Published: June 2022

Mass spectrometry is a widely used technology to identify and quantify biomolecules such as lipids, metabolites and proteins necessary for biomedical research. In this study, we catalogued freely available software tools, libraries, databases, repositories and resources that support lipidomics data analysis and determined the scope of currently used analytical technologies. Because of the tremendous importance of data interoperability, we assessed the support of standardized data formats in mass spectrometric (MS)-based lipidomics workflows. We included tools in our comparison that support targeted as well as untargeted analysis using direct infusion/shotgun (DI-MS), liquid chromatography−mass spectrometry, ion mobility or MS imaging approaches on MS1 and potentially higher MS levels. As a result, we determined that the Human Proteome Organization-Proteomics Standards Initiative standard data formats, mzML and mzTab-M, are already supported by a substantial number of recent software tools. We further discuss how mzTab-M can serve as a bridge between data acquisition and lipid bioinformatics tools for interpretation, capturing their output and transmitting rich annotated data for downstream processing. However, we identified several challenges of currently available tools and standards. Potential areas for improvement were: adaptation of common nomenclature and standardized reporting to enable high throughput lipidomics and improve its data handling. Finally, we suggest specific areas where tools and repositories need to improve to become FAIRer.
Accurate Micromanipulation of Optically Induced Dielectrophoresis Based on a Data-Driven Kinematic Model
Authors: Li Gongxin , Ding Zhanqiao , Wang Mindong , Zhao Zhonggai , Xie Shuangxi , Liu Fei
Published: June 2022

The precise control method plays a crucial role in improving the accuracy and efficiency of the micromanipulation of optically induced dielectrophoresis (ODEP). However, the unmeasurable nature of the ODEP force is a great challenge for the precise automatic manipulation of ODEP. Here, we propose a data-driven kinematic model to build an automatic control system for the precise manipulation of ODEP. The kinematic model is established by collecting the input displacement of the optical pattern and the output displacements of the manipulated object. Then, the control system based on the model was designed, and its feasibility and control precise were validated by numerical simulations and actual experiments on microsphere manipulation. In addition, the applications of ODEP manipulation in two typical scenarios further demonstrated the feasibility of the designed control system. This work proposes a new method to realize the precise manipulation of ODEP technology by establishing a kinematic model and a control system for micromanipulation, and it also provides a general approach for the improvement of the manipulation accuracy of other optoelectronic tweezers.
Effects of Spore-Displayed p75 Protein from Lacticaseibacillus rhamnosus GG on the Transcriptional Response of HT-29 Cells
Authors: Kang Soo-Ji , Kim Min-Joo , Son Do-Yeong , Kang Seok-Seong , Hong Kwang-Won
Published: June 2022

A Lacticaseibacillus rhamnosus GG-derived protein, p75, is one of the key molecules exhibiting probiotic activity. However, the molecular mechanism and transcriptional response of p75 in human intestinal epithelial cells are not completely understood. To gain a deeper understanding of its potential probiotic action, this study investigated genome-wide responses of HT-29 cells to stimulation by spore-displayed p75 (CotG-p75) through a transcriptome analysis based on RNA sequencing. Analysis of RNA-seq data showed significant changes of gene expression in HT-29 cells stimulated by CotG-p75 compared to the control. A total of 189 up-regulated and 314 down-regulated genes was found as differentially expressed genes. Gene ontology enrichment analysis revealed that a large number of activated genes was involved in biological processes, such as epithelial cell differentiation, development, and regulation of cell proliferation. A gene–gene interaction network analysis showed that several DEGs, including AREG, EREG, HBEGF, EPGN, FASLG, GLI2, CDKN1A, FOSL1, MYC, SERPINE1, TNFSF10, BCL6, FLG, IVL, SPRR1A, SPRR1B, SPRR3, and MUC5AC, might play a critical role in these biological processes. RNA-seq results for selected genes were verified by reverse transcription-quantitative polymerase chain reaction. Overall, these results provide extensive knowledge about the transcriptional responses of HT-29 cells to stimulation by CotG-p75. This study showed that CotG-p75 can contribute to cell survival and epithelial development in human intestinal epithelial cells.
Probiotics Enhance Cereal Yield and Quality and Modify Agrochemical Soil Properties
Authors: Gavelienė Virgilija , Jurkonienė Sigita
Published: June 2022

The aim of this study was to determine the influence of microbial biostimulants on wheat and oat growth, grain yield, and grain quality and to evaluate the influence of these probiotics on some soil agrochemical traits in the open field. Active concentrations of ProbioHumus and NaturGel and their mixtures were selected under laboratory conditions using winter wheat as a reference plant. Probiotics had a biostimulating effect on the development of the underground and aboveground part of winter wheat when 2 µL/g was used for seed priming and 2 mL/100 mL for seedling spraying. Under field conditions, after treatment of soil (2 L/ha), wheat and oat seeds (2 L/t), and plants (2 L/ha) with ProbioHumus and NaturGel, it was found that the yield of the studied cereals increased, on average, by 0.50 t/ha to 1.09 t/ha. ProbioHumus promoted protein accumulation in the investigated cereal grains. The level of microelements in wheat and oat grains increased after treatment of plants with NaturGel. Probiotics improved soil agrochemical properties, such as total and nitrate nitrogen, total and available phosphorus, organic carbon, humic acid, and humus content. In conclusion, plant probiotics can be used as an ecological alternative for growing cereals and improving the agrochemical properties of the soil.
Protective Effect of Resveratrol against Hexavalent Chromium-Induced Genotoxic Damage in Hsd:ICR Male Mice
Authors: Nicolás-Méndez Tonancy , Kacew Sam , Ortiz-Muñiz Alda Rocío , Mendoza-Núñez Víctor Manuel , García-Rodríguez María del Carmen
Published: June 2022

The aim of this study is to examine the ability of resveratrol to counteract hexavalent chromium [Cr(VI)]-induced genetic damage, as well as the possible pathways associated with this protection. Hsd:ICR male mice are divided into groups of the following five individuals each: (a) control 1, distilled water; (b) control 2, ethanol 30%; (c) resveratrol, 50 mg/kg by gavage; (d) CrO3, 20 mg/kg intraperitoneally; (e) resveratrol + CrO3, resveratrol administered 4 h prior to CrO3. The assessment is performed on peripheral blood. Micronuclei (MN) kinetics are measured from 0 to 72 h, while 8-hydroxydeoxyguanosine (8-OHdG) adduct repair levels, endogenous antioxidant system biomarkers, and apoptosis frequency were quantified after 48 h. Resveratrol reduces the frequency of Cr(VI)-induced MN and shows significant effects on the 8-OHdG adduct levels, suggesting that cell repair could be enhanced by this polyphenol. Concomitant administration of resveratrol and Cr(VI) results in a return of the activities of glutathione peroxidase and catalase to control levels, accompanied by modifications of superoxide dismutase activity and glutathione levels. Thus, antioxidant properties might play an important role in resveratrol-mediated inhibition of Cr(VI)-induced oxidant genotoxicity. The increase in apoptotic cells and the decrease in necrosis further confirmed that resveratrol effectively blocks the actions of Cr(VI).
Applications of Innovative Non-Thermal Pulsed Electric Field Technology in Developing Safer and Healthier Fruit Juices
Authors: Roobab Ume , Abida Afeera , Chacha James S. , Athar Aiman , Madni Ghulam Muhammad , Ranjha Muhammad Modassar Ali Nawaz , Rusu Alexandru Vasile , Zeng Xin-An , Aadil Rana Muhammad , Trif Monica
Published: June 2022

The deactivation of degrading and pectinolytic enzymes is crucial in the fruit juice industry. In commercial fruit juice production, a variety of approaches are applied to inactivate degradative enzymes. One of the most extensively utilized traditional procedures for improving the general acceptability of juice is thermal heat treatment. The utilization of a non-thermal pulsed electric field (PEF) as a promising technology for retaining the fresh-like qualities of juice by efficiently inactivating enzymes and bacteria will be discussed in this review. Induced structural alteration provides for energy savings, reduced raw material waste, and the development of new products. PEF alters the α-helix conformation and changes the active site of enzymes. Furthermore, PEF-treated juices restore enzymatic activity during storage due to either partial enzyme inactivation or the presence of PEF-resistant isozymes. The increase in activity sites caused by structural changes causes the enzymes to be hyperactivated. PEF pretreatments or their combination with other nonthermal techniques improve enzyme activation. For endogenous enzyme inactivation, a clean-label hurdle technology based on PEF and mild temperature could be utilized instead of harsh heat treatments. Furthermore, by substituting or combining conventional pasteurization with PEF technology for improved preservation of both fruit and vegetable juices, PEF technology has enormous economic potential. PEF treatment has advantages not only in terms of product quality but also in terms of manufacturing. Extending the shelf life simplifies production planning and broadens the product range significantly. Supermarkets can be served from the warehouse by increasing storage stability. As storage stability improves, set-up and cleaning durations decrease, and flexibility increases, with only minor product adjustments required throughout the manufacturing process.
Synthesis of 4,5-Dihydro-1H-[1,2]dithiolo[3,4-c]quinoline-1-thione Derivatives and Their Application as Protein Kinase Inhibitors
Authors: Medvedeva Svetlana M. , Shikhaliev Khidmet S.
Published: June 2022

This study represents the design and synthesis of a new set of hybrid and chimeric derivatives of 4,5-dihydro-4,4-dimethyl-1H-[1,2]dithiolo[3,4-c]quinoline-1-thiones, the structure of which the tricyclic fragment linearly bound or/and condensed with another heterocyclic fragment. Using the PASS Online software, among the previously synthesized and new derivatives of 1,2-dithiolo[3,4-c]quinoline-1-thione we identified 12 substances with pleiotropic activity, including chemoprotective and antitumor activity. All the synthesized derivatives were screened for their inhibitory assessment against a number of kinases. Compounds which exhibited prominent inhibition percentage in cells (>85%) were also examined for their inhibitory efficiency on human kinases via ELISA utilizing sorafenib as a reference standard to estimate their IC50 values. It was revealed that compounds 2a, 2b, 2c, and 2q displayed a significant inhibition JAK3 (IC50 = 0.36 μM, 0.38 μM, 0.41 μM, and 0.46 μM, respectively); moreover, compounds 2a and 2b displayed excellent activities against NPM1-ALK (IC50 = 0.54 μM, 0.25 μM, respectively), against cRAF[Y340D][Y341D], compound 2c showed excellent activity, and compound 2q showed weak activity (IC50 = 0.78 μM, 5.34 μM, respectively) (sorafenib IC50 = 0.78 μM, 0.43 μM, 1.95 μM, respectively). Thus, new promising preferred structures for the creation of drugs for the treatment of cancer and other multifactorial diseases in the future have been found.
Endometriosis: A Disease with Few Direct Treatment Options
Authors: França Patricia Ribeiro de Carvalho , Lontra Anna Carolina Pereira , Fernandes Patricia Dias
Published: June 2022

Endometriosis is a gynecological condition characterized by the growth of endometrium-like tissues inside and outside the pelvic cavity. The evolution of the disease can lead to infertility in addition to high treatment costs. Currently, available medications are only effective in treating endometriosis-related pain; however, it is not a targeted treatment. The objective of this work is to review the characteristics of the disease, the diagnostic means and treatments available, as well as to discuss new therapeutic options.
Human Remains Identification Using Micro-CT, Chemometric and AI Methods in Forensic Experimental Reconstruction of Dental Patterns after Concentrated Sulphuric Acid Significant Impact
Authors: Thurzo Andrej , Jančovičová Viera , Hain Miroslav , Thurzo Milan , Novák Bohuslav , Kosnáčová Helena , Lehotská Viera , Varga Ivan , Kováč Peter , Moravanský Norbert
Published: June 2022

(1) Teeth, in humans, represent the most resilient tissues. However, exposure to concentrated acids might lead to their dissolving, thus making human identification difficult. Teeth often contain dental restorations from materials that are even more resilient to acid impact. This paper aims to introduce a novel method for the 3D reconstruction of dental patterns as a crucial step for the digital identification of dental records. (2) With a combination of modern methods, including micro-computed tomography, cone-beam computer tomography, and attenuated total reflection, in conjunction with Fourier transform infrared spectroscopy and artificial intelligence convolutional neural network algorithms, this paper presents a method for 3D-dental-pattern reconstruction, and human remains identification. Our research studies the morphology of teeth, bone, and dental materials (amalgam, composite, glass-ionomer cement) under different periods of exposure to 75% sulfuric acid. (3) Our results reveal a significant volume loss in bone, enamel, dentine, as well as glass-ionomer cement. The results also reveal a significant resistance by the composite and amalgam dental materials to the impact of sulfuric acid, thus serving as strong parts in the dental-pattern mosaic. This paper also probably introduces the first successful artificial intelligence application in automated-forensic-CBCT segmentation. (4) Interdisciplinary cooperation, utilizing the mentioned technologies, can solve the problem of human remains identification with a 3D reconstruction of dental patterns and their 2D projections over existing ante-mortem records.
Molecular Analysis and Conformational Dynamics of Human MC4R Disease-Causing Mutations
Authors: Fatima Munazza Tamkeen , Islam Zeyaul , Kolatkar Prasanna R. , Al-Shabeeb Akil Ammira Sarah
Published: June 2022

Obesity is a chronic disease with increasing cases among children and adolescents. Melanocortin 4 receptor (MC4R) is a G protein-coupled transporter involved in solute transport, enabling it to maintain cellular homeostasis. MC4R mutations are associated with early-onset severe obesity, and the identification of potential pathological variants is crucial for the clinical management of patients with obesity. A number of mutations have been reported in MC4R that are responsible for causing obesity and related complications. Delineating these mutations and analyzing their effect on MC4R’s structure will help in the clinical intervention of the disease condition as well as designing potential drugs against it. Sequence-based pathogenicity and structure-based protein stability analyses were conducted on naturally occurring variants. We used computational tools to analyze the conservation of these mutations on MC4R’s structure to map the structural variations. Detailed structural analyses were carried out for the active site mutations (i.e., D122N, D126Y, and S188L) and their influence on the binding of calcium and the agonist or antagonist. We performed molecular dynamics (MD) simulations of the wild-type and selected mutations to delineate the conformational changes, which provided us with possible reasons for MC4R’s instability in these mutations. This study provides insight into the potential direction toward understanding the molecular basis of MC4R dysfunction in disease progression and obesity.
Rapid Identification of Constituents in Cephalanthus tetrandrus (Roxb.) Ridsd. et Badh. F. Using UHPLC-Q-Exactive Orbitrap Mass Spectrometry
Authors: Tang Su-Nv , Yang Jian-Bo , E Shuai , He Shuo , Li Jia-Xin , Yu Kai-Quan , Zhang Min , Li Qing , Sun Lei , Li Hui
Published: June 2022

Cephalanthus tetrandrus (Roxb.) Ridsd. et Badh. F. (CT) belongs to the Rubiaceae family. Its dried leaves are widely used in traditional Chinese medicine to treat enteritis, dysentery, toothache, furuncles, swelling, traumatic injury, fracture, bleeding, and scalding. In order to further clarify the unknown chemical composition of CT, a rapid strategy based on UHPLC-Q-exactive orbitrap was established for this analysis using a Thermo Scientific Hypersil GOLDTM aQ (100 mm × 2.1 mm, 1.9 µm) chromatographic column. The mobile phase was 0.1% formic acid water–acetonitrile, with a flow rate of 0.3 mL/min and injection volume of 2 µL; for mass spectrometry, an ESI ion source in positive and negative ion monitoring modes was adopted. A total of 135 chemicals comprising 67 chlorogenic acid derivatives, 48 flavonoids, and 20 anthocyanin derivatives were identified by comparing the mass spectrum information with standard substances, public databases, and the literature, which were all discovered for the first time in this plant. This result broadly expands the chemical composition of CT, which will contribute to understanding of its effectiveness and enable quality control.
Design, Synthesis, and Biological Evaluation of N14-Amino Acid-Substituted Tetrandrine Derivatives as Potential Antitumor Agents against Human Colorectal Cancer
Authors: Wang Yu-Chan , Zhang Rong-Hong , Hu Sheng-Cao , Zhang Hong , Yang Dan , Zhang Wen-Li , Zhao Yong-Long , Cui Dong-Bing , Li Yong-Jun , Pan Wei-Dong , Liao Shang-Gao , Zhou Meng
Published: June 2022

As a typical dibenzylisoquinoline alkaloid, tetrandrine (TET) is clinically used for the treatment of silicosis, inflammatory pulmonary, and cardiovascular diseases in China. Recent investigations have demonstrated the outstanding anticancer activity of this structure, but its poor aqueous solubility severely restricts its further development. Herein, a series of its 14-N-amino acid-substituted derivatives with improved anticancer effects and aqueous solubility were designed and synthesized. Among them, compound 16 displayed the best antiproliferative activity against human colorectal cancer (HCT-15) cells, with an IC50 value of 0.57 μM. Compared with TET, 16 was markedly improved in terms of aqueous solubility (by 5-fold). Compound 16 significantly suppressed the colony formation, migration, and invasion of HCT-15 cells in a concentration-dependent manner, with it being more potent in this respect than TET. Additionally, compound 16 markedly impaired the morphology and motility of HCT-15 cells and induced the death of colorectal cancer cells in double-staining and flow cytometry assays. Western blot results revealed that 16 could induce the autophagy of HCT-15 cells by significantly decreasing the content of p62/SQSTM1 and enhancing the Beclin-1 level and the ratio of LC3-II to LC3-I. Further study showed that 16 effectively inhibited the proliferation, migration, and tube formation of umbilical vein endothelial cells, manifesting in a potent anti-angiogenesis effect. Overall, these results revealed the potential of 16 as a promising candidate for further preclinical studies.
Unveiling Chemical Cues of Insect-Tree and Insect-Insect Interactions for the Eucalyptus Weevil and Its Egg Parasitoid by Multidimensional Gas Chromatographic Methods
Authors: Mendes Davide , Branco Sofia , Paiva Maria Rosa , Schütz Stefan , Mateus Eduardo P. , Gomes da Silva Marco
Published: June 2022

Multidimensional gas chromatography is, presently, an established and powerful analytical tool, due to higher resolving power than the classical 1D chromatographic approaches. Applied to multiple areas, it allows to isolate, detect and identify a larger number of compounds present in complex matrices, even in trace amounts. Research was conducted to determine which compounds, emitted by host plants of the eucalyptus weevil, Gonipterus platensis, might mediate host selection behavior. The identification of a pheromone blend of G. platensis is presented, revealing to be more attractive to weevils of both sexes, than the individual compounds. The volatile organic compounds (VOCs) were collected by headspace solid phase microextraction (HS-SPME), MonoTrapTM disks, and simultaneous distillation-extraction (SDE). Combining one dimensional (1D) and two-dimensional (2D) chromatographic systems—comprehensive and heart-cut two-dimensional gas chromatography (GC×GC and H/C-MD-GC, respectively) with mass spectrometry (MS) and electroantennographic (EAD) detection, enabled the selection and identification of pertinent semiochemicals which were detected by the insect antennal olfactory system. The behavioral effect of a selected blend of compounds was assessed in a two-arm olfactometer with ten parallel walking chambers, coupled to video tracking and data analysis software. An active blend, composed by cis and trans-verbenol, verbenene, myrtenol and trans-pinocarveol was achieved.
Solubility and Thermodynamic Data of Febuxostat in Various Mono Solvents at Different Temperatures
Authors: Haq Nazrul , Alghaith Adel F. , Alshehri Sultan , Shakeel Faiyaz
Published: June 2022

This study examines the solubility and thermodynamics of febuxostat (FBX) in a variety of mono solvents, including “water, methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO)” at 298.2–318.2 K and 101.1 kPa. The solubility of FBX was determined using a shake flask method and correlated with “van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models”. The overall error values for van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models was recorded to be 1.60, 2.86, and 1.14%, respectively. The maximum mole fraction solubility of FBX was 3.06 × 10−2 in PEG-400 at 318.2 K, however the least one was 1.97 × 10−7 in water at 298.2 K. The FBX solubility increased with temperature and the order followed in different mono solvents was PEG-400 (3.06 × 10−2) > THP (1.70 × 10−2) > 2-BuOH (1.38 × 10−2) > 1-BuOH (1.37 × 10−2) > IPA (1.10 × 10−2) > EtOH (8.37 × 10−3) > EA (8.31 × 10−3) > DMSO (7.35 × 10−3) > MeOH (3.26 × 10−3) > PG (1.88 × 10−3) > EG (1.31 × 10−3) > water (1.14 × 10−6) at 318.2 K. Compared to the other combinations of FBX and mono solvents, FBX-PEG-400 had the strongest solute-solvent interactions. The apparent thermodynamic analysis revealed that FBX dissolution was “endothermic and entropy-driven” in all mono solvents investigated. Based on these findings, PEG-400 appears to be the optimal co-solvent for FBX solubility.
Porphyrins and Metalloporphyrins Combined with N-Heterocyclic Carbene (NHC) Gold(I) Complexes for Photodynamic Therapy Application: What Is the Weight of the Heavy Atom Effect?
Authors: Scoditti Stefano , Chiodo Francesco , Mazzone Gloria , Richeter Sébastien , Sicilia Emilia
Published: June 2022

The photophysical properties of two classes of porphyrins and metalloporphyrins linked to N-heterocyclic carbene (NHC) Au(I) complexes have been investigated by means of density functional theory and its time-dependent extension for their potential application in photodynamic therapy. For this purpose, the absorption spectra, the singlet–triplet energy gaps, and the spin–orbit coupling (SOC) constants have been determined. The obtained results show that all the studied compounds possess the appropriate properties to generate cytotoxic singlet molecular oxygen, and consequently, they can be employed as photosensitizers in photodynamic therapy. Nevertheless, on the basis of the computed SOCs and the analysis of the metal contribution to the involved molecular orbitals, a different influence in terms of the heavy atom effect in promoting the intersystem crossing process has been found as a function of the identity of the metal center and its position in the center of the porphyrin core or linked to the peripheral NHC.
Pharmacological Inhibition of Endogenous Hydrogen Sulfide Attenuates Breast Cancer Progression
Authors: Khan Nazeer Hussain , Wang Di , Wang Wenkang , Shahid Muhammad , Khattak Saadullah , Ngowi Ebenezeri Erasto , Sarfraz Muhammad , Ji Xin-Ying , Zhang Chun-Yang , Wu Dong-Dong
Published: June 2022

Hydrogen sulfide (H2S), a gaseous signaling molecule, is associated with the development of various malignancies via modulating various cellular signaling cascades. Published research has established the fact that inhibition of endogenous H2S production or exposure of H2S donors is an effective approach against cancer progression. However, the effect of pharmacological inhibition of endogenous H2S-producing enzymes (cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MPST)) on the growth of breast cancer (BC) remains unknown. In the present study, DL-propargylglycine (PAG, inhibitor of CSE), aminooxyacetic acid (AOAA, inhibitor of CBS), and L-aspartic acid (L-Asp, inhibitor of 3-MPST) were used to determine the role of endogenous H2S in the growth of BC by in vitro and in vivo experiments. An in silico study was also performed to confirm the results. Corresponding to each enzyme in separate groups, we treated BC cells (MCF-7 and MDA-MB-231) with 10 mM of PAG, AOAA, and L-Asp for 24 h. Findings reveal that the combined dose (PAG + AOAA + L-Asp) group showed exclusive inhibitory effects on BC cells’ viability, proliferation, migration, and invasion compared to the control group. Further, treated cells exhibited increased apoptosis and a reduced level of phospho (p)-extracellular signal-regulated protein kinases such as p-AKT, p-PI3K, and p-mTOR. Moreover, the combined group exhibited potent inhibitory effects on the growth of BC xenograft tumors in nude mice, without obvious toxicity. The molecular docking results were consistent with the wet lab experiments and enhanced the reliability of the drugs. In conclusion, our results demonstrate that the inhibition of endogenous H2S production can significantly inhibit the growth of human breast cancer cells via the AKT/PI3K/mTOR pathway and suggest that endogenous H2S may act as a promising therapeutic target in human BC cells. Our study also empowers the rationale to design novel H2S-based anti-tumor drugs to cure BC.
Repair of Iron Center Proteins—A Different Class of Hemerythrin-like Proteins
Authors: Silva Liliana S. O. , Matias Pedro M. , Romão Célia V. , Saraiva Lígia M.
Published: June 2022

Repair of Iron Center proteins (RIC) form a family of di-iron proteins that are widely spread in the microbial world. RICs contain a binuclear nonheme iron site in a four-helix bundle fold, two basic features of hemerythrin-like proteins. In this work, we review the data on microbial RICs including how their genes are regulated and contribute to the survival of pathogenic bacteria. We gathered the currently available biochemical, spectroscopic and structural data on RICs with a particular focus on Escherichia coli RIC (also known as YtfE), which remains the best-studied protein with extensive biochemical characterization. Additionally, we present novel structural data for Escherichia coli YtfE harboring a di-manganese site and the protein’s affinity for this metal. The networking of protein interactions involving YtfE is also described and integrated into the proposed physiological role as an iron donor for reassembling of stress-damaged iron-sulfur centers.
Naphthalene Diimides Carrying Two β-Cyclodextrins Prefer Telomere RNA G-Quadruplex Recognition
Authors: Zou Tingting , Sato Yuka , Kaneyoshi Shuma , Mano Kota , Yasukawa Rui , Nakano Yoshifumi , Fujii Satoshi , Sato Shinobu , Takenaka Shigeori
Published: June 2022

Newly synthesized naphthalene diimide carrying two β-cyclodextrins (NDI-β-CyDs) showed improved specificity for the parallel G-quadruplex structure alongside the hybrid G-quadruplex structure. Specifically, the highest binding affinity of NDI-β-CyDs for the telomere RNA G-quadruplex was observed. The binding simulation indicated that β-cyclodextrins might be available for loop nucleobase inclusion under its complex.
Coumarin Derivatives Inhibit ADP-Induced Platelet Activation and Aggregation
Authors: Lu Ping-Hsun , Liao Tzu-Hsien , Chen Yau-Hung , Hsu Yeng-Ling , Kuo Chan-Yen , Chan Chuan-Chi , Wang Lu-Kai , Chern Ching-Yuh , Tsai Fu-Ming
Published: June 2022

Coumarin was first discovered in Tonka bean and then widely in other plants. Coumarin has an anticoagulant effect, and its derivative, warfarin, is a vitamin K analogue that inhibits the synthesis of clotting factors and is more widely used in the clinical treatment of endovascular embolism. At present, many artificial chemical synthesis methods can be used to modify the structure of coumarin to develop many effective drugs with low toxicity. In this study, we investigated the effects of six coumarin derivatives on the platelet aggregation induced by adenosine diphosphate (ADP). We found that the six coumarin derivatives inhibited the active form of GPIIb/IIIa on platelets and hence inhibit platelet aggregation. We found that 7-hydroxy-3-phenyl 4H-chromen-4-one (7-hydroxyflavone) had the most severe effect. In addition, we further analyzed the downstream signal transduction of the ADP receptor, including the release of calcium ions and the regulation of cAMP, which were inhibited by the six coumarin derivatives selected in this study. These results suggest that coumarin derivatives inhibit coagulation by inhibiting the synthesis of coagulation factors and they may also inhibit platelet aggregation.
Molecular Networking, Network Pharmacology, and Molecular Docking Approaches Employed to Investigate the Changes in Ephedrae Herba before and after Honey-Processing
Authors: Li Hengyang , Guo Long , Ding Xiaoying , An Qi , Wang Lei , Hao Shenghui , Li Wenjie , Wang Tao , Gao Zetong , Zheng Yuguang , Zhang Dan
Published: June 2022

Raw Ephedrae herba (REH) and honey-processed Ephedrae herba (HEH) were the different decoction pieces of Ephedrae herba (EH). Honey-processing that changes REH into HEH has been shown to relieve cough and asthma to a synergistic extent. However, the chemical markers and the synergistic mechanism of HEH need to be further studied. In this study, the ultra-high performance liquid chromatography coupled with hybrid quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) and molecular networking (MN) were used to investigate the chemical composition of REH and HEH, which led to the identification of 92 compounds. A total of 38 differential chemical markers for REH and HEH were identified using principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Network pharmacology suggests that the synergistic effect of HEH in relieving cough and asthma may be due to 31 differential chemical markers acting through 111 biological targets. Among them, four compounds and two targets probably played an important role based on the results of molecular docking. This study enriched our knowledge about the chemical composition of REH and HEH, as well as the synergistic mechanism of HEH.
DisiMiR: Predicting Pathogenic miRNAs Using Network Influence and miRNA Conservation
Authors: Wang Kevin R. , McGeachie Michael J.
Published: June 2022

MiRNAs have been shown to play a powerful regulatory role in the progression of serious diseases, including cancer, Alzheimer’s, and others, raising the possibility of new miRNA-based therapies for these conditions. Current experimental methods, such as differential expression analysis, can discover disease-associated miRNAs, yet many of these miRNAs play no functional role in disease progression. Interventional experiments used to discover disease causal miRNAs can be time consuming and costly. We present DisiMiR: a novel computational method that predicts pathogenic miRNAs by inferring biological characteristics of pathogenicity, including network influence and evolutionary conservation. DisiMiR separates disease causal miRNAs from merely disease-associated miRNAs, and was accurate in four diseases: breast cancer (0.826 AUC), Alzheimer’s (0.794 AUC), gastric cancer (0.853 AUC), and hepatocellular cancer (0.957 AUC). Additionally, DisiMiR can generate hypotheses effectively: 78.4% of its false positives that are mentioned in the literature have been confirmed to be causal through recently published research. In this work, we show that DisiMiR is a powerful tool that can be used to efficiently and flexibly to predict pathogenic miRNAs in an expression dataset, for the further elucidation of disease mechanisms, and the potential identification of novel drug targets.
Nutritional Outcomes One Year after One Anastomosis Gastric Bypass Compared to Sleeve Gastrectomy
Authors: Shirazi Naama , Beglaibter Nahum , Grinbaum Ronit , Ahmad Wiessam Abu , Aronis Anna
Published: June 2022

One Anastomosis Gastric Bypass (OAGB) and Sleeve Gastrectomy (SG) are the most common bariatric procedures performed worldwide. SG is a restrictive procedure whereas OAGB involves malabsorption as well, supposing a risk of deficiency development post OAGB. The aim of the study was to compare nutritional deficiencies and metabolic markers one year after the procedures, while adhering to the current protocols. Retrospective analysis was performed for data on 60 adults undergoing primary OAGB, compared to 60 undergoing primary SG. Mean pre-surgery BMI for SG was 42.7 kg/m2 and 43.3 kg/m2 for OAGB. A multidisciplinary team followed up with the patients at least 3 times during the first year. Mean weight loss was 39.0 kg for SG and 44.1 kg for OAGB. The OAGB group presented a significantly sharper decline in T.Chol and a trend for sharper LDL decrease; a higher increase in folate and a trend for a greater decrease in albumin and hemoglobin were observed in OAGB. For vitamin B12, D, iron and ferritin, no difference was observed between the treatment groups, although there were some in-group differences. Nutritional recommendations and adopted supplement plans minimize the risk of deficiencies and result in improvement in metabolic biomarkers one year after OAGB, which was comparable to SG.
TRPV1-Mediated Sensing of Sodium and Osmotic Pressure in POMC Neurons in the Arcuate Nucleus of the Hypothalamus
Authors: Zhang Boyang , Kario Kazuomi , Yada Toshihiko , Nakata Masanori
Published: June 2022

The central melanocortin system conducted by anorexigenic pro-opiomelanocortin (POMC) neurons and orexigenic agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus (ARC) not only regulates feeding behavior but also blood pressure. Excessive salt intake raises the Na+ concentration ([Na+]) in the cerebrospinal fluid (CSF) and worsens hypertension. The blood–brain barrier is immature in the ARC. Therefore, both AgRP and POMC neurons in the ARC have easy access to the electrolytes in the blood and can sense changes in their concentrations. However, the sensitivity of AgRP and POMC neurons to Na+ remains unclear. This study aimed to explore how the changes in the extracellular Na+ concentration ([Na+]) influence these neurons by measuring the cytosolic Ca2+ concentration ([Ca2+]i) in the single neurons isolated from the ARC that were subsequently immunocytochemically identified as AgRP or POMC neurons. Both AgRP and POMC neurons responded to increases in both [Na+] and osmolarity in C57BL/6 mice. In contrast, in transient receptor potential vanilloid 1 (TRPV1) knockout (KO) mice, POMC neurons failed to respond to increases in both [Na+] and osmolarity, while they responded to high glucose and angiotensin II levels with increases in [Ca2+]i. Moreover, in KO mice fed a high-salt diet, the expression of POMC was lower than that in wild-type mice. These results demonstrate that changes in [Na+] and osmolarity are sensed by the ARC POMC neurons via the TRPV1-dependent mechanism.
Methodological Rigor and Transparency in Clinical Practice Guidelines for Nutrition Care in Critically Ill Adults: A Systematic Review Using the AGREE II and AGREE-REX Tools
Authors: Noyahr John K. , Tatucu-Babet Oana A. , Chapple Lee-anne S. , Barlow Christopher Jake , Chapman Marianne J. , Deane Adam M. , Fetterplace Kate , Hodgson Carol L. , Winderlich Jacinta , Udy Andrew A. , Marshall Andrea P. , Ridley Emma J.
Published: June 2022

Background: To evaluate the methodological quality of (1) clinical practice guidelines (CPGs) that inform nutrition care in critically ill adults using the AGREE II tool and (2) CPG recommendations for determining energy expenditure using the AGREE-REX tool. Methods: CPGs by a professional society or academic group, intended to guide nutrition care in critically ill adults, that used a systematic literature search and rated the evidence were included. Four databases and grey literature were searched from January 2011 to 19 January 2022. Five investigators assessed the methodological quality of CPGs and recommendations specific to energy expenditure determination. Scaled domain scores were calculated for AGREE II and a scaled total score for AGREE-REX. Data are presented as medians (interquartile range). Results: Eleven CPGs were included. Highest scoring domains for AGREE II were clarity of presentation (82% [76–87%]) and scope and purpose (78% [66–83%]). Lowest scoring domains were applicability (37% [32–42%]) and stakeholder involvement (46% [33–51%]). Eight (73%) CPGs provided recommendations relating to energy expenditure determination; scores were low overall (37% [36–40%]) and across individual domains. Conclusions: Nutrition CPGs for critically ill patients are developed using systematic methods but lack engagement with key stakeholders and guidance to support application. The quality of energy expenditure determination recommendations is low.
Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review
Authors: Kubina Robert , Krzykawski Kamil , Kabała-Dzik Agata , Wojtyczka Robert D. , Chodurek Ewa , Dziedzic Arkadiusz
Published: June 2022

Diet plays a crucial role in homeostasis maintenance. Plants and spices containing flavonoids have been widely used in traditional medicine for thousands of years. Flavonols present in our diet may prevent cancer initiation, promotion and progression by modulating important enzymes and receptors in signal transduction pathways related to proliferation, differentiation, apoptosis, inflammation, angiogenesis, metastasis and reversal of multidrug resistance. The anticancer activity of fisetin has been widely documented in numerous in vitro and in vivo studies. This review summarizes the worldwide, evidence-based research on the activity of fisetin toward various types of cancerous conditions, while describing the chemopreventive and therapeutic effects, molecular targets and mechanisms that contribute to the observed anticancer activity of fisetin. In addition, this review synthesized the results from preclinical studies on the use of fisetin as an anticancer agent. Based on the available literature, it might be suggested that fisetin has a bioactive potential to become a complementary drug in the prevention and treatment of cancerous conditions. However, more in-depth research is required to validate current data, so that this compound or its derivatives can enter the clinical trial phase.
Temporal and Spatial Evaluation of Mono(2-ethylhexyl) Phthalate (MEHP) Detection in Common Bottlenose Dolphins (Tursiops truncatus) from Sarasota Bay, Florida, USA
Authors: Dziobak Miranda K. , Balmer Brian C. , Wells Randall S. , Pisarski Emily C. , Wirth Ed F. , Hart Leslie B.
Published: June 2022

Phthalates are endocrine-disrupting chemicals added to plastics, personal care products, cleaning solutions, and pesticides. Extensive use has led to its exposure to wildlife, including common bottlenose dolphins (Tursiops truncatus) from Sarasota Bay, Florida, USA; however, there are gaps in knowledge regarding whether sample timing or geographic location influence exposure. Dolphins were evaluated for temporal and spatial variability in urinary mono(2-ethylhexyl) phthalate (MEHP) detection (2010–2019). Significant fluctuations in detectable MEHP concentrations were found across the dataset. All samples from 2014 and 2015 (n = 12) had detectable MEHP concentrations; thus, data were classified into cohorts to explore the significance of prevalent MEHP detection (“Cohort 1” (n = 10; 2010–2013), “Cohort 2” (2014–2015), and “Cohort 3” (n = 29; 2016–2019)). Compared to Cohorts 1 and 3, Cohort 2 had higher detectable MEHP concentrations (Dunn’s; p = 0.0065 and p = 0.0012, respectively) and a greater proportion of detectable MEHP concentrations (pairwise comparisons using Benjamini–Hochberg adjustments: p = 0.0016 and p = 0.0059, respectively). MEHP detection also varied across spatial scales. Dolphins with detectable MEHP concentrations had ranges primarily within enclosed embayments, while dolphins with nondetectable MEHP concentrations extended into open waters, potentially indicating geographically linked exposure risk. This study suggests that researchers and management agencies should consider a population’s ranging pattern, geographic habitat characteristics, and sample timing when assessing small cetacean health in relation to contaminant exposure.
Biologics in COVID-19 So Far: Systematic Review
Authors: Arias Milton , Oliveros Henry , Lechtig Sharon , Bustos Rosa-Helena
Published: June 2022

This systematic review aimed to reevaluate the available evidence of the use of biologics as treatment candidates for the treatment of severe and advanced COVID-19 disease; what are the rationale for their use, which are the most studied, and what kind of efficacy measures are described? A search through Cochrane, Embase, Pubmed, Medline, medrxiv.org, and Google scholar was performed on the use of biologic interventions in COVID-19/SARS-CoV-2 infection, viral pneumonia, and sepsis, until 11 January 2022. Throughout the research, we identified 4821 records, of which 90 were selected for qualitative analysis. Amongst the results, we identified five popular targets of use: IL6 and IL1 inhibitors, interferons, mesenchymal stem cells treatment, and anti-spike antibodies. None of them offered conclusive evidence of their efficacy with consistency and statistical significance except for some studies with anti-spike antibodies; however, Il6 and IL1 inhibitors as well as interferons show encouraging data in terms of increased survival and favorable clinical course that require further studies with better methodology standardization.
Theory of Knowledge Based on the Idea of the Discursive Space
Authors: Maciag Rafal
Published: June 2022

This paper discusses the theory of knowledge based on the idea of dynamical space. The goal of this effort is to comprehend the knowledge that remains beyond the human domain, e.g., of the artificial cognitive systems. This theory occurs in two versions, weak and strong. The weak version is limited to knowledge in which retention and articulation are performed through the discourse. The strong version is general and is not limited in any way. In the weak version, knowledge is represented by the trajectories of discourses in time, in a dynamical space called the discursive space, which has an arbitrary number of dimensions. Given space is used to represent a given part of knowledge. A manifold is introduced to represent knowledge with a wider scope (all knowledge). The strong version is an extrapolation of the weak version to cover all forms of knowledge, not necessarily human or manifesting in language. The use of dynamical space construction allows one to formalize knowledge as such. Such an effort requires us to initially consider knowledge as mainly a social and linguistic phenomenon, which also could be presented as a result of the evolution of the understanding of knowledge that took place in the 20th century.
A Comparative Analysis of the Anatomy, Phenolic Profile, and Antioxidant Capacity of Tussilago farfara L. Vegetative Organs
Authors: Bota Viviane Beatrice , Neamtu Andreea-Adriana , Olah Neli-Kinga , Chișe Elisabeta , Burtescu Ramona Flavia , Pripon Furtuna Flavia Roxana , Nicula Alexandru-Sabin , Neamtu Carmen , Maghiar Adrian-Marius , Ivănescu Lăcrămioara-Carmen , Zamfirache Maria-Magdalena , Mathe Endre , Turcuș Violeta
Published: June 2022

Tussilago farfara L., a perennial species, is a medicinal herb used in traditional medicine, mainly for the treatment of respiratory tract-related pathology. In traditional Chinese medicine, flower buds are preferred; in Europe, the leaves are used; and in some parts of India, the whole plant is utilized. This preferential usage of the plant organs might be based on differences in the chemical composition due to environmental conditions, along with preferred traditional and cultural approaches. In this article, the impact of pedoclimatic growth conditions on the morpho-anatomical development and phytochemical profile of the plant were studied on T. farfara in the vegetative state, collected from two different locations in the Romanian spontaneous flora, revealing significant variations. Furthermore, the antioxidant profile of the specific extracts from the aerial and subterranean plant parts is also in accordance with these discrepancies. The plant anatomy was assessed histologically by optical microscopy, while the analytical chemistry evaluation was based on LC/MS and spectral methods for the evaluation of the antioxidant and enzyme inhibitory activity. To our knowledge, this is the first comparative analysis contextually reporting on the histology, phenolic profile, antioxidant capacity, and geographical location of the vegetative form of T. farfara.