bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiosynthesis and In Vitro Evaluation of [11C]tozadenant as Adenosine A2A Receptor Radioligand
Authors: Humpert Swen , Schneider Daniela , Lang Markus , Schulze Annette , Neumaier Felix , Holschbach Marcus , Bier Dirk , Neumaier Bernd
Published: March 2024

Tozadenant (4-hydroxy-N-(4-methoxy-7-morpholinobenzo[d]thiazol-2-yl)-4-methylpiperidine-1-carboxamide) is a highly selective adenosine A2A receptor (A2AR) antagonist and a promising lead structure for the development of A2AR-selective positron emission tomography (PET) probes. Although several 18F-labelled tozadenant derivatives showed favorable in vitro properties, recent in vivo PET studies observed poor brain penetration and lower specific binding than anticipated from the in vitro data. While these findings might be attributable to the structural modification associated with 18F-labelling, they could also reflect inherent properties of the parent compound. However, PET studies with radioisotopologues of tozadenant to evaluate its cerebral pharmacokinetics and brain distribution are still lacking. In the present work, we applied N-Boc-O-desmethyltozadenant as a suitable precursor for the preparation of [O-methyl-11C]tozadenant ([11C]tozadenant) by O-methylation with [11C]methyl iodide followed by acidic deprotection. This approach afforded [11C]tozadenant in radiochemical yields of 18 ± 2%, with molar activities of 50–60 GBq/µmol (1300–1600 mCi/µmol) and radiochemical purities of 95 ± 3%. In addition, in vitro autoradiography in pig and rat brain slices demonstrated the expected striatal accumulation pattern and confirmed the A2AR specificity of the radioligand, making it a promising tool for in vivo PET studies on the cerebral pharmacokinetics and brain distribution of tozadenant.
Determination of Methamphetamine by High-Performance Liquid Chromatography in Odor-Adsorbent Material Used for Training Drug-Detection Animals
Authors: Sun Ning , Chao Jingjing , Liu Xiaochang , Li Hao , Jia Dongshun , Zhang Dajun , Xie Liuwei , Zhou Yuanting , Lang Wenxuan , Shui Yingyi , Zhu Qiwen
Published: March 2024

The objective of the present report was to develop and validate a simple, sensitive, and selective analytical method for the determination of methamphetamine in an odor-adsorbent material (gauze) which was used to improve and standardize the training method used for drug-detection animals. High-performance liquid chromatography (HPLC) was performed using a Spherisorb ODS2 C18 column (200 mm × 4.6 mm, 5 μm), with a mobile phase consisting of a 0.25% methanol/triethylamine aqueous solution (V:V = 20:80), the pH of which was adjusted to 3.1 using glacial acetic acid, at a flow rate of 1.0 mL/min. The column temperature was 25 °C, and the detection of the analytes was performed at a wavelength of 260 nm. Methamphetamine showed good linearity (R2 = 0.9999) in the range of 4.2~83.2 mg/mL. The stability of the test material was good over 24 h. The precision of the method was good, with an average spiked recovery of 86.2% and an RSD of 2.9%. The methamphetamine content in the gauze sample was determined to be 7.8 ± 2.2 μg/sample. A high-performance liquid chromatography (HPLC) method was optimized and validated for the determination of methamphetamine in adsorbent materials (gauze). Validation data in terms of specificity, linearity, the limit of detection and the limit of quantification, reproducibility, precision, stability, and recovery indicated that the method is suitable for the routine analysis of methamphetamine in adsorbent materials (gauze) and provided a basis for training drug-detection animals.
Effects and Mechanisms of Luteolin, a Plant-Based Flavonoid, in the Prevention of Cancers via Modulation of Inflammation and Cell Signaling Molecules
Authors: Almatroodi Saleh A. , Almatroudi Ahmad , Alharbi Hajed Obaid A. , Khan Amjad Ali , Rahmani Arshad Husain
Published: March 2024

Luteolin, a flavonoid, is mainly found in various vegetables and fruits, including carrots, cabbages, onions, parsley, apples, broccoli, and peppers. Extensive research in vivo and in vitro has been performed to explore its role in disease prevention and treatment. Moreover, this compound possesses the ability to combat cancer by modulating cell-signaling pathways across various types of cancer. The studies have confirmed that luteolin can inhibit cancer-cell survival and proliferation, angiogenesis, invasion, metastasis, mTOR/PI3K/Akt, STAT3, Wnt/β-catenin, and cell-cycle arrest, and induce apoptosis. Further, scientific evidence describes that this compound plays a vital role in the up/down-regulation of microRNAs (miRNAs) in cancer therapy. This review aims to outline the anti-cancer mechanisms of this compound and its molecular targets. However, a knowledge gap remains regarding the studies on its safety and efficacy and clinical trials. Therefore, it is essential to conduct more research based on safety, efficacy, and clinical trials to explore the beneficial role of this compound in disease management, including cancer.
Zn-Doped MnCO3/CS Composite Photocatalyst for Visible-Light-Driven Decomposition of Organic Pollutants
Authors: Liang Hui , Zhao Yongxin , Liu Tongjin , Li Ruijuan , Li Rumei , Zhu Yuxiao , Fang Feng
Published: March 2024

Zn-doped MnCO3/carbon sphere (Zn-doped MnCO3/CS) composites were synthesized using a simple hydrothermal procedure. Among various samples (ZM-50, ZM-05, and ZMC-0), the ternary Zn-doped MnCO3/CS (ZMC-2) catalyst demonstrated excellent visible light-induced photocatalytic activity. This improvement comes from the Zn addition and the conductive CS, which facilitate electron movement and charge transport. The catalyst exhibited efficient degradation of methylene blue (MB) over a wide pH range, achieving a removal efficiency of 99.6% under visible light. Radical trapping experiments suggested that •OH and •O2− played essential roles in the mechanism of organic pollutant degradation. Moreover, the catalyst maintained good degradation performance after five cycles. This study offers valuable perspectives into the fabrication of carbon-based composites with promising photocatalytic activity.
Spectrophotometric and Chromatographic Assessment of Total Polyphenol and Flavonoid Content in Rhododendron tomentosum Extracts and Their Antioxidant and Antimicrobial Activity
Authors: Kukhtenko Halyna , Bevz Nataliia , Konechnyi Yulian , Kukhtenko Oleksandr , Jasicka-Misiak Izabela
Published: March 2024

In the literature, the chemical composition of Rhododendron tomentosum is mainly represented by the study of isoprenoid compounds of essential oil. In contrast, the study of the content of flavonoids will contribute to the expansion of pharmacological action and the use of the medicinal plant for medical purposes. The paper deals with the technology of extracts from Rh. tomentosum shoots using ethanol of various concentrations and purified water as an extractant. Extracts from Rh. tomentosum were obtained by a modified method that combined the effects of ultrasound and temperature to maximize the extraction of biologically active substances from the raw material. Using the method of high-performance thin-layer chromatography in a system with solvents ethyl acetate/formic acid/water (15:1:1), the following substances have been separated and identified in all the extracts obtained: rutin, hyperoside, quercetin, and chlorogenic acid. The total polyphenol content (TPC) and total flavonoid content (TFC) were estimated using spectrophotometric methods involving the Folin-Ciocalteu (F-C) reagent and the complexation reaction with aluminum chloride, respectively. A correlation analysis was conducted between antioxidant activity and the polyphenolic substance content. Following the DPPH assay, regression analysis shows that phenolic compounds contribute to about 80% (r2 = 0.8028, p < 0.05) of radical scavenging properties in the extract of Rh. tomentosum. The extract of Rh. tomentosum obtained by ethanol 30% inhibits the growth of test cultures of microorganisms in 1:1 and 1:2 dilutions of the clinical strains #211 Staphylococcus aureus and #222 Enterococcus spp. and the reference strain Pseudomonas aeruginosa ATCC 10145.
Discovery of Novel Metalloenzyme Inhibitors Based on Property Characterization: Strategy and Application for HDAC1 Inhibitors
Authors: Zhang Lu , Yang Yajun , Yang Ying , Xiao Zhiyan
Published: March 2024

Metalloenzymes are ubiquitously present in the human body and are relevant to a variety of diseases. However, the development of metalloenzyme inhibitors is limited by low specificity and poor drug-likeness associated with metal-binding fragments (MBFs). A generalized drug discovery strategy was established, which is characterized by the property characterization of zinc-dependent metalloenzyme inhibitors (ZnMIs). Fifteen potential Zn2+-binding fragments (ZnBFs) were identified, and a customized pharmacophore feature was defined based on these ZnBFs. The customized feature was set as a required feature and applied to a search for novel inhibitors for histone deacetylase 1 (HDAC1). Ten potential HDAC1 inhibitors were recognized, and one of them (compound 9) was a known potent HDAC1 inhibitor. The results demonstrated the effectiveness of our strategy to identify novel inhibitors for zinc-dependent metalloenzymes.
Functionalized Linear Conjugated Polymer/TiO2 Heterojunctions for Significantly Enhancing Photocatalytic H2 Evolution
Authors: Gong Hao , Xing Yuqin , Li Jinhua , Liu Shiyong
Published: March 2024

Conjugated polymers (CPs) have attracted much attention in recent years due to their structural abundance and tunable energy bands. Compared with CP-based materials, the inorganic semiconductor TiO2 has the advantages of low cost, non-toxicity and high photocatalytic hydrogen production (PHP) performance. However, studies on polymeric-inorganic heterojunctions, composed of D-A type CPs and TiO2, for boosting the PHP efficiency are still rare. Herein, an elucidation that the photocatalytic hydrogen evolution activity can actually be improved by forming polymeric-inorganic heterojunctions TFl@TiO2, TS@TiO2 and TSO2@TiO2, facilely synthesized through efficient in situ direct C–H arylation polymerization, is given. The compatible energy levels between virgin TiO2 and polymeric semiconductors enable the resulting functionalized CP@TiO2 heterojunctions to exhibit a considerable photocatalytic hydrogen evolution rate (HER). Especially, the HER of TSO2@TiO2 heterojunction reaches up to 11,220 μmol g−1 h−1, approximately 5.47 and 1260 times higher than that of pristine TSO2 and TiO2 photocatalysts. The intrinsic merits of a donor-acceptor conjugated polymer and the interfacial interaction between CP and TiO2 account for the excellent PHP activity, facilitating the separation of photo-generated excitons. Considering the outstanding PHP behavior, our work discloses that the coupling of inorganic semiconductors and suitable D-A conjugated CPs would play significant roles in the photocatalysis community.
Levan Production by Suhomyces kilbournensis Using Sugarcane Molasses as a Carbon Source in Submerged Fermentation
Authors: González-Torres Mariana , Hernández-Rosas Francisco , Pacheco Neith , Salinas-Ruiz Josafhat , Herrera-Corredor José A. , Hernández-Martínez Ricardo
Published: March 2024

The valorization of byproducts from the sugarcane industry represents a potential alternative method with a low energy cost for the production of metabolites that are of commercial and industrial interest. The production of exopolysaccharides (EPSs) was carried out using the yeast Suhomyces kilbournensis isolated from agro-industrial sugarcane, and the products and byproducts of this agro-industrial sugarcane were used as carbon sources for their recovery. The effect of pH, temperature, and carbon and nitrogen sources and their concentration in EPS production by submerged fermentation (SmF) was studied in 170 mL glass containers of uniform geometry at 30 °C with an initial pH of 6.5. The resulting EPSs were characterized with Fourier-transform infrared spectroscopy (FT-IR). The results showed that the highest EPS production yields were 4.26 and 44.33 g/L after 6 h of fermentation using sucrose and molasses as carbon sources, respectively. Finally, an FT-IR analysis of the EPSs produced by S. kilbournensis corresponded to levan, corroborating its origin. It is important to mention that this is the first work that reports the production of levan using this yeast. This is relevant because, currently, most studies are focused on the use of recombinant and genetically modified microorganisms; in this scenario, Suhomyces kilbournensis is a native yeast isolated from the sugar production process, giving it a great advantage in the incorporation of carbon sources into their metabolic processes in order to produce levan sucrose, which uses fructose to polymerize levan.
Ginsenoside Rb1, Compound K and 20(S)-Protopanaxadiol Attenuate High-Fat Diet-Induced Hyperlipidemia in Rats via Modulation of Gut Microbiota and Bile Acid Metabolism
Authors: Zhang Kang-Xi , Zhu Yue , Song Shu-Xia , Bu Qing-Yun , You Xiao-Yan , Zou Hong , Zhao Guo-Ping
Published: March 2024

Hyperlipidemia, characterized by elevated serum lipid concentrations resulting from lipid metabolism dysfunction, represents a prevalent global health concern. Ginsenoside Rb1, compound K (CK), and 20(S)-protopanaxadiol (PPD), bioactive constituents derived from Panax ginseng, have shown promise in mitigating lipid metabolism disorders. However, the comparative efficacy and underlying mechanisms of these compounds in hyperlipidemia prevention remain inadequately explored. This study investigates the impact of ginsenoside Rb1, CK, and PPD supplementation on hyperlipidemia in rats induced by a high-fat diet. Our findings demonstrate that ginsenoside Rb1 significantly decreased body weight and body weight gain, ameliorated hepatic steatosis, and improved dyslipidemia in HFD-fed rats, outperforming CK and PPD. Moreover, ginsenoside Rb1, CK, and PPD distinctly modified gut microbiota composition and function. Ginsenoside Rb1 increased the relative abundance of Blautia and Eubacterium, while PPD elevated Akkermansia levels. Both CK and PPD increased Prevotella and Bacteroides, whereas Clostridium-sensu-stricto and Lactobacillus were reduced following treatment with all three compounds. Notably, only ginsenoside Rb1 enhanced lipid metabolism by modulating the PPARγ/ACC/FAS signaling pathway and promoting fatty acid β-oxidation. Additionally, all three ginsenosides markedly improved bile acid enterohepatic circulation via the FXR/CYP7A1 pathway, reducing hepatic and serum total bile acids and modulating bile acid pool composition by decreasing primary/unconjugated bile acids (CA, CDCA, and β-MCA) and increasing conjugated bile acids (TCDCA, GCDCA, GDCA, and TUDCA), correlated with gut microbiota changes. In conclusion, our results suggest that ginsenoside Rb1, CK, and PPD supplementation offer promising prebiotic interventions for managing HFD-induced hyperlipidemia in rats, with ginsenoside Rb1 demonstrating superior efficacy.
NMR Analysis of Extra Virgin Olive Oil of the Epirus Region of Greece with Emphasis on Selected Phenolic Compounds
Authors: Tsolis Theodoros , Kyriakou Dimitra , Sifnaiou Evangelia , Thomos Dimitrios , Glykos Dimitrios , Tsiafoulis Constantinos G. , Garoufis Achilleas
Published: March 2024

Extra virgin olive oil (EVOO) is recognized for its numerous health benefits, attributed to its rich phenolic components. NMR has emerged as a prevalent technique for precisely identifying these compounds. Among Mediterranean countries, Greece stands as the third-largest producer of olives, with the Epirus region notably advancing in olive cultivation, contributing significantly to the dynamic growth of the region. In this study, an NMR method was employed based on the acquisition of a 1H NMR spectrum along with multiple resonant suppression in order to increase the sensitivity. Using the above method, 198 samples of extra virgin olive oil, primarily sourced from the Epirus region, were analyzed, and both the qualitative and quantitative aspects of the phenolic compounds were obtained. In addition, we examined the effects of various factors such as variety, harvest month, and region origin on the phenolic compounds’ concentration. The results revealed an average total phenolic content of 246 mg/kg, closely approaching the EU health claim limit of 250 mg/kg. Approximately 15% of the samples were confidently characterized as high-phenolic olive oil. The highest concentrations were observed in the Thesprotia samples, with several Lianolia varieties exceeding the total phenolic content of 400 mg/kg. Statistical tests demonstrated a significant influence of the olive variety and the month of fruit harvest on phenolic component concentration, followed by the region of origin. A very strong correlation was noted between the total phenolics content and the levels of oleocanthal and oleacein, with a correlation coefficient (r) of 0.924. Upon optimization of all factors affecting olive oil quality, the majority of the EVOOs from the Epirus region have the potential to be characterized as high in phenolic content.
Study on the Effects of Wettability and Pressure in Shale Matrix Nanopore Imbibition during Shut-in Process by Molecular Dynamics Simulations
Authors: Jiang Wen , Lv Weifeng , Jia Ninghong , Lu Xiaoqing , Wang Lu , Wang Kai , Mei Yuhao
Published: March 2024

Shut-in after fracturing is generally adopted for wells in shale oil reservoirs, and imbibition occurring in matrix nanopores has been proven as an effective way to improve recovery. In this research, a molecular dynamics (MD) simulation was used to investigate the effects of wettability and pressure on nanopore imbibition during shut-in for a typical shale reservoir, Jimsar. The results indicate that the microscopic advancement mechanism of the imbibition front is the competitive adsorption between “interfacial water molecules” at the imbibition front and “adsorbed oil molecules” on the pore wall. The essence of spontaneous imbibition involves the adsorption and aggregation of water molecules onto the hydroxyl groups on the pore wall. The flow characteristics of shale oil suggest that the overall push of the injected water to the oil phase is the main reason for the displacement of adsorbed oil molecules. Thus, shale oil, especially the heavy hydrocarbon component in the adsorbed layer, tends to slip on the walls. However, the weak slip ability of heavy components on the wall surface is an important reason that restricts the displacement efficiency of shale oil during spontaneous imbibition. The effectiveness of spontaneous imbibition is strongly dependent on the hydrophilicity of the matrix pore’s wall. The better hydrophilicity of the matrix pore wall facilitates higher levels of adsorption and accumulation of water molecules on the pore wall and requires less time for “interfacial water molecules” to compete with adsorbed oil molecules. During the forced imbibition process, the pressure difference acts on both the bulk oil and the boundary adsorption oil, but mainly on the bulk oil, which leads to the occurrence of wetting hysteresis. Meanwhile, shale oil still existing in the pore always maintains a good, stratified adsorption structure. Because of the wetting hysteresis phenomenon, as the pressure difference increases, the imbibition effect gradually increases, but the actual capillary pressure gradually decreases and there is a loss in the imbibition velocity relative to the theoretical value. Simultaneously, the decline in hydrophilicity further weakens the synergistic effect on the imbibition of the pressure difference because of the more pronounced wetting hysteresis. Thus, selecting an appropriate well pressure enables cost savings and maximizes the utilization of the formation’s natural power for enhanced oil recovery (EOR).
Characterization of the Sideritis scardica Extract SidTea+TM and Its Effect on Physiological Profile, Metabolic Health and Redox Biomarkers in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Study
Authors: Papanikolaou Konstantinos , Kouloridas Konstantinos , Rosvoglou Anastasia , Gatsas Athanasios , Georgakouli Kalliopi , Deli Chariklia K. , Draganidis Dimitrios , Argyropoulou Aikaterini , Michailidis Dimitris , Fatouros Ioannis G. , Jamurtas Athanasios Z.
Published: March 2024

This study aimed to characterize a Sideritis scardica extract (SidTea+TM) and investigate its effect on the physiological profile, metabolic health and redox status in healthy individuals. The chemical profile and antioxidant potential of the SidTea+TM extract were evaluated by UPLC-HRMS analysis and in vitro cell-free methods. Twenty-eight healthy adults participated in this randomized, double-blind, placebo-controlled study. Participants consumed 1500 mg/day of SidTea+TM or a placebo for 4 weeks. At baseline and post-supplementation, participants were assessed for their anthropometric and physiological profile and provided a resting blood sample. SidTea+TM decreased (p < 0.05) systolic blood pressure (−10.8 mmHg), mean arterial pressure (−4.5 mmHg), resting heart rate (−3.1 bpm) and handgrip strength of the non-dominant limb (−0.8 kg) whereas the placebo decreased (p < 0.05) handgrip strength of the dominant (−5.8 kg) and non-dominant (−3.2 kg) limb. SidTea+TM also resulted in an increase (p < 0.05) in estimated VO2max (+1.1 mL/kg/min) and a reduction (p < 0.05) in γ-GT and SGPT enzymatic activity in serum (−3.7 and −3.3 U/L, respectively). Finally, SidTea+TM increased (p < 0.001) total antioxidant capacity and decreased (p < 0.05) lipid peroxidation levels in plasma. These results indicate that SidTea+TM is a potent and safe to use antioxidant that can elicit positive changes in indices of blood pressure, cardiorespiratory capacity, liver metabolism, and redox status in healthy adults over a 4-week supplementation period.
[Tc(NO)(Cp)(PPh3)Cl] and [Tc(NO)(Cp)(PPh3)(NCCH3)](PF6), and Their Reactions with Pyridine and Chalcogen Donors
Authors: Ernst Moritz Johannes , Abdulkader Abdullah , Hagenbach Adelheid , Claude Guilhem , Roca Jungfer Maximilian , Abram Ulrich
Published: March 2024

Reactions of the technetium(I) nitrosyl complex [Tc(NO)(Cp)(PPh3)Cl] with triphenylphosphine chalcogenides EPPh3 (E = O, S, Se), and Ag(PF6) in a CH2Cl2/MeOH mixture (v/v, 2/1) result in an exchange of the chlorido ligand and the formation of [Tc(NO)(Cp)(PPh3)(EPPh3)](PF6) compounds. The cationic acetonitrile complex [Tc(NO)(Cp)(PPh3)(NCCH3)]+ is formed when the reaction is conducted in NCCH3 without additional ligands. During the isolation of the corresponding PF6− salt a gradual decomposition of the anion was detected in the solvent mixture applied. The yields and the purity of the product increase when the BF4− salt is used instead. The acetonitrile ligand is bound remarkably strongly to technetium and exchange reactions readily proceed only with strong donors, such as pyridine or ligands with ‘soft’ donor atoms, such as the thioether thioxane. Substitutions on the cyclopentadienyl ring do not significantly influence the ligand exchange behavior of the starting material. 99Tc NMR spectroscopy is a valuable tool for the evaluation of reactions of the complexes of the present study. The extremely large chemical shift range of this method allows the ready detection of corresponding ligand exchange reactions. The observed 99Tc chemical shifts depend on the donor properties of the ligands. DFT calculations support the discussions about the experimental results and provide explanations for some of the unusual findings.
Facile One-Pot Synthesis and Anti-Microbial Activity of Novel 1,4-Dihydropyridine Derivatives in Aqueous Micellar Solution under Microwave Irradiation
Authors: Goswami Asmita , Kaur Navneet , Kaur Manvinder , Singh Kishanpal , Sohal Harvinder Singh , Han Haesook , Bhowmik Pradip K.
Published: March 2024

The current study describes a novel and eco-conscious method to synthesize 1,4-dihydropyridine derivatives utilizing an aqueous micellar solution containing aluminum dodecyl sulfate, Al(DS)3, using readily available starting material. The final products were synthesized with excellent yields within remarkably quick reaction durations, promoting remarkable atom economy and minimizing environmental impacts. The present protocol has several advantages over other methodologies in terms of high yield (up to 97%) with excellent purity. Further, the synthesized 1,4-DHPs exhibit favorable to excellent resistance against examined bacterial and fungal species. Intriguingly, polar groups on the phenyl ring (5b, 5c, 5i and 5j) make the 1,4-DHPs equally potent against the microbes as compared to the standard drugs.
Full Characterisation of Heroin Samples Using Infrared Spectroscopy and Multivariate Calibration
Authors: Deconinck Eric , Lievens Sybrien , Canfyn Michael , Van Campenhout Peter , Debehault Loic , Gremaux Lies , Balcaen Margot
Published: March 2024

The analysis of heroin samples, before use in the protected environment of user centra, could be a supplementary service in the context of harm reduction. Infrared spectroscopy hyphenated with multivariate calibration could be a valuable asset in this context, and therefore 125 heroin samples were collected directly from users and analysed with classical chromatographic techniques. Further, Mid-Infrared spectra were collected for all samples, to be used in Partial Least Squares (PLS) modelling, in order to obtain qualitative and quantitative models based on real live samples. The approach showed that it was possible to identify and quantify heroin in the samples based on the collected spectral data and PLS modelling. These models were able to identify heroin correctly for 96% of the samples of the external test set with precision, specificity and sensitivity values of 100.0, 75.0 and 95.5%, respectively. For regression, a root mean squared error of prediction (RMSEP) of 0.04 was obtained, pointing at good predictive properties. Furthermore, during mass spectrometric screening, 10 different adulterants and impurities were encountered. Using the spectral data to model the presence of each of these resulted in performant models for seven of them. All models showed promising correct-classification rates (between 92 and 96%) and good values for sensitivity, specificity and precision. For codeine and morphine, the models were not satisfactory, probably due to the low concentration of these impurities as a consequence of acetylation. For methacetin, the approach failed.
Targeted Library of Phosphonic-Type Inhibitors of Human Neutrophil Elastase
Authors: Torzyk-Jurowska Karolina , Ciekot Jaroslaw , Winiarski Lukasz
Published: March 2024

Despite many years of research, human neutrophil elastase (HNE) still remains an area of interest for many researchers. This multifunctional representative of neutrophil serine proteases is one of the most destructive enzymes found in the human body which can degrade most of the extracellular matrix. Overexpression or dysregulation of HNE may lead to the development of several inflammatory diseases. Previously, we presented the HNE inhibitor with kinact/KI value over 2,000,000 [M−1s−1]. In order to optimize its structure, over 100 novel tripeptidyl derivatives of α-aminoalkylphosphonate diaryl esters were synthesized, and their activity toward HNE was checked. To confirm the selectivity of the resultant compounds, several of the most active were additionally checked against the two other neutrophil proteases: proteinase 3 and cathepsin G. The developed modifications allowed us to obtain a compound with significantly increased inhibitory activity against human neutrophil elastase with high selectivity toward cathepsin G, but none toward proteinase 3.
Synthetic Modifications of a Pb2+-Sensor Acridono-Crown Ether for Covalent Attachment and Their Effects on Selectivity
Authors: Vezse Panna , Gede Martin , Golcs Ádám , Huszthy Péter , Tóth Tünde
Published: March 2024

Because of environmental impact, there is a great need for chemosensors, especially for toxic heavy metals such as lead. The conventional instrumental analytical techniques rarely provide an available real-time sensing platform, thus the development of highly selective and stable synthetic chemosensor molecules is of great importance. Acridono-18-crown-6 ethers have such properties, and much research has proven their outstanding applicability in various supramolecular devices. In this present work, we aimed to enable their covalent immobilization capability by synthesizing functionalized derivatives while preserving the favored molecular recognition ability. Several new macrocycle analogues were synthesized, while synthetization difficulties and design aspects were also dealt with. The selectivity of the macrocycle analogues was studied using UV–Vis spectroscopy and compared with that of the parent compounds. The ultimate crown ether derivative showed high Pb2+-selectivity, reversibility (decomplexation by extraction with water) and stability.
The Effect of Ultrasound on the Extraction and Functionality of Proteins from Duckweed (Lemna minor)
Authors: Mirón-Mérida Vicente Antonio , Soria-Hernández Cintya , Richards-Chávez Alejandro , Ochoa-García Juan Carlos , Rodríguez-López Jorge Luis , Chuck-Hernández Cristina
Published: March 2024

The inclusion of protein in the regular human diet is important for the prevention of several chronic diseases. In the search for novel alternative protein sources, plant-based proteins are widely explored from a sustainable and ecological point of view. Duckweed (Lemna minor), also known as water lentil, is an aquatic plant with potential applications for human consumption due to its protein content and carbohydrate contents. Among all the conventional and novel protein extraction methods, the utilization of ultrasound has attracted the attention of scientists because of its effects on improving protein extraction and its functionalities. In this work, a Box–Behnken experimental design was proposed to optimize the alkaline extraction of protein from duckweed. In addition, an exploration of the effects of ultrasound on the morphological, structural, and functional properties of the extracted protein was also addressed. The optimal extraction parameters were a pH of 11.5 and an ultrasound amplitude and processing time of 60% and 20 min, respectively. These process conditions doubled the protein content extracted in comparison to the value from the initial duckweed sample. Furthermore, the application of ultrasound during the extraction of protein generated changes in the FTIR spectra, color, and structure of the duckweed protein, which resulted in improvements in its solubility, emulsifying properties, and foaming capacity.
Acceptability, Feasibility, and Effectiveness of a Worksite Intervention to Lower Cardiometabolic Risk in South Africa: Protocol
Authors: Singh Evonne Shanita , Naicker Ashika , Singh Shivneta
Published: March 2024

As an important way to translate cardiovascular disease prevention efforts, worksite intervention programs can be used to effectively facilitate healthy food choices, health education, and social support among employees, in a targeted approach to improve health outcomes and physical activity levels of employees. In this study, the effectiveness of a canteen and a behavioral intervention on cardiometabolic risk among prediabetic and prehypertensive employees at two multinational worksites in South Africa will be measured. This two-arm randomized controlled trial (RCT) will be structured to provide a six-week intervention at two multinational companies spread across eight worksites and will include a canteen and behavioral arm (CB) and a canteen only (CO) arm. Participants who are either prediabetic or prehypertensive will complete the baseline assessments, which will include anthropometry, a demographic and lifestyle survey, the global physical activity questionnaire (GPAQ) and the 24 h food recall. Participants will be randomized into the CO and the canteen and CB intervention groups. The CO group will receive six weeks of canteen intervention [changes to enable a healthy food environment], while the CB group will receive six weeks of canteen intervention along with a behavioral intervention. The behavioral intervention will include an intense six-week lifestyle program aligned to the Diabetes Prevention Program (DPP). This study will assess the added benefit of environmental-level changes aimed at lowering cardiometabolic risk in a low–middle-income country (LMIC) and has the potential for scale-up to other worksites in South Africa and globally.
Keep the Human in the Loop: Arguments for Human Assistance in the Synthesis of Simulation Data for Robot Training
Authors: Liebers Carina , Megarajan Pranav , Auda Jonas , Stratmann Tim C. , Pfingsthorn Max , Gruenefeld Uwe , Schneegass Stefan
Published: March 2024

Robot training often takes place in simulated environments, particularly with reinforcement learning. Therefore, multiple training environments are generated using domain randomization to ensure transferability to real-world applications and compensate for unknown real-world states. We propose improving domain randomization by involving human application experts in various stages of the training process. Experts can provide valuable judgments on simulation realism, identify missing properties, and verify robot execution. Our human-in-the-loop workflow describes how they can enhance the process in five stages: validating and improving real-world scans, correcting virtual representations, specifying application-specific object properties, verifying and influencing simulation environment generation, and verifying robot training. We outline examples and highlight research opportunities. Furthermore, we present a case study in which we implemented different prototypes, demonstrating the potential of human experts in the given stages. Our early insights indicate that human input can benefit robot training at different stages.
A Photochemically Active Cu2O Nanoparticle Endows Scaffolds with Good Antibacterial Performance by Efficiently Generating Reactive Oxygen Species
Authors: He Yushan , Zan Jun , He Zihui , Bai Xinna , Shuai Cijun , Pan Hao
Published: March 2024

Cuprous oxide (Cu2O) has great potential in photodynamic therapy for implant-associated infections due to its good biocompatibility and photoelectric properties. Nevertheless, the rapid recombination of electrons and holes weakens its photodynamic antibacterial effect. In this work, a new nanosystem (Cu2O@rGO) with excellent photodynamic performance was designed via the in situ growth of Cu2O on reduced graphene oxide (rGO). Specifically, rGO with lower Fermi levels served as an electron trap to capture photoexcited electrons from Cu2O, thereby promoting electron-hole separation. More importantly, the surface of rGO could quickly transfer electrons from Cu2O owing to its excellent conductivity, thus efficiently suppressing the recombination of electron-hole pairs. Subsequently, the Cu2O@rGO nanoparticle was introduced into poly-L-lactic acid (PLLA) powder to prepare PLLA/Cu2O@rGO porous scaffolds through selective laser sintering. Photochemical analysis showed that the photocurrent of Cu2O@rGO increased by about two times after the incorporation of GO nanosheets, thus enhancing the efficiency of photogenerated charge carriers and promoting electron-hole separation. Moreover, the ROS production of the PLLA/Cu2O@rGO scaffold was significantly increased by about two times as compared with that of the PLLA/Cu2O scaffold. The antibacterial results showed that PLLA/Cu2O@rGO possessed antibacterial rates of 83.7% and 81.3% against Escherichia coli and Staphylococcus aureus, respectively. In summary, this work provides an effective strategy for combating implant-related infections.
RNA Sequencing Reveals the Inhibitory Effect of High Levels of Arachidonic Acid and Linoleic Acid on C2C12 Differentiation and Myogenic Biomarkers
Authors: Wang Wei , Abdelrahman Mohamed , Yang Ying , Lv Haimiao , Yang Liguo
Published: March 2024

Over the past three decades, studies have shown that consuming polyunsaturated fatty acids (PUFAs) can enhance animal and human health and welfare through biological, biochemical, pathological, and pharmacological impacts. Furthermore, omega-6 plays key roles in the cardiopulmonary system, including promoting airway relaxation and inhibiting atherosclerosis and hypertension. However, findings from investigations of the effects of omega-6 fatty acids on molecular and cellular activity and discussions on their influence on biomarkers are still unclear. Therefore, the present study aimed to evaluate omega-6 fatty acids, the arachidonic acid (AA), and linoleic acid (LA) effects on C2C12 proliferation, myogenesis morphology, and relative myogenic biomarker expression through the Wnt pathway. C2C12 cells were cultured with and without 25, 50, 100, and 150 µM of LA and AA and then subjected to CCK8, Giemsa staining, RT qPCR, Western blotting, and RNA Sequencing. The CCK8 Assay results showed that 25, 50, 100, and 150 µM LA significantly decreased the viability after 72 h for 25, 50, 100, and 150 µM concentrations. Also, AA supplementation decreased cell viability after 24 h for 150 µM, 48 h for 150 µM, and 72 h for 50, 100, and 150 µM concentrations. Moreover, the LA and AA inhibitory effects noticed through Gimesa staining were morphological changes during myoblast differentiation. Both LA and AA showed inhibiting IGF1, Cola1, Col6a2, Col6a1, Itga10, Itga11, SFRP2, DAAM2, and NKD2 effects; however, the depressing effect was higher for AA compared to LA. The previous results were confirmed through Western blotting, which showed that 50 µM LA and AA significantly reduced DAAM2 and SFRP2 protein levels compared to the control. Regarding RNA sequencing results, LA and AA increased the number of differentially expressed (DE) Mt-rRNA and snoRNA; however, the numbers of lncRNA detected decreased compared to the control. Our findings demonstrate that high and moderate LA and AA concentrations reduce primary myoblast proliferation and differentiation. Also, they highlight novel biomarkers and regulatory factors to improve our understanding of how the nutrition of fatty acids can control and modulate the myogenesis and differentiation process through different biomarker families.
Gut Microbiome and Metabolome Modulation by High-Hydrostatic-Pressure-Processed Tomato Juice
Authors: Wang Xuehua , Li Daotong , Ma Chen , Hu Xiaosong , Chen Fang
Published: March 2024

High hydrostatic pressure (HHP) is a non-thermal pasteurization technology for the enhancement of food products’ safety and quality. The components of tomato juice can be affected by HHP processing. Little is known about the effects of HHP-processed tomato juice on the gut microbiome and metabolism. Here, we performed high-throughput sequencing and metabolomics profiling to determine the critical differences in gut microbiota structure and metabolic profiles in mice administered with HHP-processed tomato juice. Tomato juice administration significantly increased the gut bacterial alpha diversity and the relative abundance of Bacteroides. The mice administered with HHP-processed tomato juice were characterized by the enrichment of Bacteroidetes, Alistieps, and Faecalibaculum compared with those administered with HTST-processed tomato juice. Moreover, HHP-processed tomato juice promoted SCFA levels, which were positively correlated with the enriched Alistieps. Our results show that HHP-processed tomato juice may drive healthy gut microbes and metabolites.
Continuous Zonal Gradients Characterize Epipelagic Plankton Assemblages and Hydrography in the Subtropical North Atlantic
Authors: Bode Antonio , Louro María , Rey Elena , Lamas Angel
Published: March 2024

The subtropical North Atlantic is a key region for understanding climate impact in the ocean. Plankton studies in this region have been generally framed in biogeographic provinces or focused on latitudinal gradients. In this study, we demonstrate the benefits of using empirically constructed continuous gradients versus the use of average values for biogeographical provinces to characterize plankton assemblages along a longitudinal transect at 24.5° N using an unprecedented array of stations including hydrographic observations, abundance of phytoplankton and zooplankton, and plankton size spectra in the epipelagic layer (0–200 m). In addition, the variability of zooplankton assemblages was analyzed using detailed taxonomic identification at selected stations. We found significant gradients in most hydrographic and plankton variables. The former, including surface temperature and salinity, the depth of the upper mixing layer, and the depth of the chlorophyll maximum, displayed non-linear gradients with maximum or minimum values near the center of the transect. In contrast, most plankton variables showed linear zonal gradients. Phytoplankton, microzooplankton (<100 µm), and the slope and the intercept of the size spectra increased (and Trichodesmium decreased) to the west. Total mesozooplankton (>200 µm) did not show any significant zonal pattern, but the taxonomic assemblages were characterized by a gradual replacement of large Calanoids by small-bodied Cyclopoid copepods from east to west. The use of continuous gradients provides more detailed information on the zonal structure of subtropical plankton than the classical approach using discrete areas.
Influence of Amitraz-Based Product Characteristics on Varroa Mite Population Control
Authors: Almecija Gabrielle , Poirot Benjamin , Mielgo Paulo , Watkins Max , Suppo Christelle
Published: March 2024

The presence of the Varroa destructor mite requires the use of acaricide treatments for honeybee colonies. Amitraz is one of the most common acaricide-active ingredients used by beekeepers. Certain Varroa mite populations have developed resistance to amitraz, thereby leading to a loss in the efficacy of amitraz-based treatments. Two products, Apivar and Supatraz, were applied in the same apiary in France to evaluate their efficacy. Both treatments are amitraz-based but have different galenics. Thanks to field data, a dynamic model was used to simulate the actions of Apivar and Supatraz on the mite population. We considered two parameters to compare the products as follows: the daily mortality rate and the treatment duration. In the field, the percentage of the efficacy of the two products was not significantly different, but Supatraz kills mites faster and decreases 90% of the mite infestation in 28.4 days compared with 50.9 days when using Apivar. Through modeling, we showed the daily impact of the two different products on mite population. Supatraz has a higher daily mortality rate during the first two weeks than Apivar. Supatraz requires a lower efficacy (% of varroa mites killed during all the treatment) to stabilize the varroa mite population due to its faster release of active ingredients than Apivar, thereby needing a shorter period to achieve the same result. Depending on the model, Supatraz conserves effective efficacy when used against moderately resistant mites (with mite mortality being 40–70% at the LC90) but not against highly resistant mites (with mite mortality being <40% at the LC90). These results show that the comparison of the efficacy of the two products with different characteristics (duration of treatment and daily mortality rate) should be analyzed with caution.
Circadian Rhythms of Body Temperature and Locomotor Activity in Spontaneously Hypertensive Rats under Frequent Changes in Light Conditions
Authors: Ryabinina Anna Yu. , Bryk Anna A. , Blagonravov Mikhail L. , Goryachev Vyacheslav A. , Mozhaev Andrey A. , Ovechkina Vera S.
Published: March 2024

Changes in lighting accompany modern urbanization trends and can lead to various pathologies based on circadian disturbances. In this study, we assessed the changes in the circadian rhythm of core body temperature (Tcore) and locomotor activity of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) following exposure to different lighting conditions: extended light phase of the day (16 h–8 h, 20 h–4 h, 24 h–0 h), light pollution, monochromatic light, and bright light therapy. The telemetry data was collected after experimental lighting conditions during periods with standard lighting (12 h of light and 12 h of darkness) and was processed using linear and cosinor analysis. The daily rhythms of rats’ parameters persisted in accordance with the standard lighting regime. Tcore changes were observed in both groups compared to the initial period: in WKY, a decrease in Tcore during the darkness and an increase during the light; in SHR, the opposite trend, with Tcore increased during the darkness and decreased during the light phase of the day. A relationship between Tcore and activity was observed with weak correlation. WKY exhibited more pronounced signs of adaptive variation and desynchronization compared to SHR, which could be associated with a wider range of functional capabilities of the organism without cardiovascular pathology.
Marine-Derived Bioactive Metabolites as a Potential Therapeutic Intervention in Managing Viral Diseases: Insights from the SARS-CoV-2 In Silico and Pre-Clinical Studies
Authors: Okechukwu Queency , Adepoju Feyisayo , Kanwugu Osman , Adadi Parise , Serrano-Aroca Ángel , Uversky Vladimir , Okpala Charles
Published: March 2024

Worldwide urbanization and subsequent migration have accelerated the emergence and spread of diverse novel human diseases. Among them, diseases caused by viruses could result in epidemics, typified by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which hit the globe towards the end of December 2019. The global battle against SARS-CoV-2 has reignited interest in finding alternative treatments for viral infections. The marine world offers a large repository of diverse and unique bioactive compounds. Over the years, many antiviral compounds from marine organisms have been isolated and tested in vitro and in vivo. However, given the increasing need for alternative treatment, in silico analysis appears to provide a time- and cost-effective approach to identifying the potential antiviral compounds from the vast pool of natural metabolites isolated from marine organisms. In this perspective review, we discuss marine-derived bioactive metabolites as potential therapeutics for all known disease-causing viruses including the SARS-CoV-2. We demonstrate the efficacy of marine-derived bioactive metabolites in the context of various antiviral activities and their in silico, in vitro, and in vivo capacities.