bluuebunny/crossref_metadata_2025 huggingface dataset:
Agarose-Degrading Characteristics of a Deep-Sea Bacterium Vibrio Natriegens WPAGA4 and Its Cold-Adapted GH50 Agarase Aga3420
Authors: Zhang Mengyuan , Wang Jianxin , Zeng Runying , Wang Dingquan , Wang Wenxin , Tong Xiufang , Qu Wu
Published: November 2022

Up until now, the characterizations of GH50 agarases from Vibrio species have rarely been reported compared to GH16 agarases. In this study, a deep-sea strain, WPAGA4, was isolated and identified as Vibrio natriegens due to the maximum similarity of its 16S rRNA gene sequence, the values of its average nucleotide identity, and through digital DNA–DNA hybridization. Two circular chromosomes in V. natriegens WPAGA4 were assembled. A total of 4561 coding genes, 37 rRNA, 131 tRNA, and 59 other non-coding RNA genes were predicted in the genome of V. natriegens WPAGA4. An agarase gene belonging to the GH50 family was annotated in the genome sequence and expressed in E. coli cells. The optimum temperature and pH of the recombinant Aga3420 (rAga3420) were 40 °C and 7.0, respectively. Neoagarobiose (NA2) was the only product during the degradation process of agarose by rAga3420. rAga3420 had a favorable stability following incubation at 10–30 °C for 50 min. The Km, Vmax, and kcat values of rAga3420 were 2.8 mg/mL, 78.1 U/mg, and 376.9 s−1, respectively. rAga3420 displayed cold-adapted properties as 59.7% and 41.2% of the relative activity remained at 10 3 °C and 0 °C, respectively. This property ensured V. natriegens WPAGA4 could degrade and metabolize the agarose in cold deep-sea environments and enables rAga3420 to be an appropriate industrial enzyme for NA2 production, with industrial potential in medical and cosmetic fields.
Dostarlimab an Inhibitor of PD-1/PD-L1: A New Paradigm for the Treatment of Cancer
Authors: Alkholifi Faisal K. , Alsaffar Rana M.
Published: November 2022

Immunomodulation checkpoints usually adopted by healthy cells by tumors might cause an imbalance between host surveillance and tumor progression. Several tumors are incredibly resistant to standard treatment. The dynamic and long-lasting tumor regressions caused by antibodies targeting the PD-1/PD-L1 checkpoint have suggested a rebalancing of the host–tumor relationship. Checkpoint antibody inhibitors, like anti-PD-1/PD-L1, are unique inhibitors that reduce tumor growth by modulating the interaction between immune cells and tumor cells. These checkpoint inhibitors are swiftly emerging as a highly promising strategy for treating cancer because they produce impressive antitumor responses while having a limited number of adverse effects. Over the past several years, numerous checkpoint antibody inhibitors pointing to PD-1, PDL-1, and CTLA-4 have been available on the market. Despite its enormous success and usefulness, the anti-PD treatment response is restricted to certain kinds of cancer. This restriction can be attributed to the inadequate and diverse PD-1 expression in the tumor (MET) micro-environment. Dostarlimab (TSR-042), a drug that interferes with the PD-1/PD-L1 pathway, eliminates a crucial inhibitory response of an immune system and, as a result, has the potential to cause severe or deadly immune-mediated adverse effects. As cancer immunotherapy, dostarlimab enhances the antitumor immune response of the body.
Public Leadership Challenges in a Complex Context
Authors: Fialho Elisabete , Sousa Maria José , Moreira Ana
Published: November 2022

The objectives of this study are to identify the importance of teleworking during the COVID-19 pandemic and, evaluate the future development of this working form, characterize the process, identify its benefits and challenges, and present some solutions to deal with telework. To this end, the following research questions were formulated: (1) What areas of telework had the most significant impact during the COVID-19 pandemic? (2) What is the impact of telework on productivity? (3) What are the positive and negative aspects of teleworking? (4) What solutions do leaders propose for telework to intensify in the future? The sample for this study consists of 159 participants holding managerial positions. The data analyses were completed and allowed us to study the challenges of leadership in teleworking in direct public administrations. The results indicate that productivity is maintained, although productivity has decreased in the education sector. The positive aspects found were flexibility, better time management, that communication became simpler, and greater motivation. As negative aspects, we found changes in leadership, communication, and lack of material. To minimise the negative aspects of teleworking, the leaders essentially mentioned mixed-work (face-to-face and teleworking), distribution of appropriate material, training, teleworking regulation, and productivity control.
Comparing Psychological Wellbeing and Work-Related Quality of Life between Professional Groups within Health and Social Care during the COVID-19 Pandemic in the UK
Authors: Neill Ruth D. , Gillen Patricia , Moriarty John , Manthorpe Jill , Mallett John , Schroder Heike , Currie Denise , Nicholl Patricia , Ravalier Jermaine , McGrory Susan , McFadden Paula
Published: November 2022

This paper shared the compared results on the psychological wellbeing and work-related quality of life amongst health and social care workers during the COVID-19 pandemic in the UK. Health and social care professionals within nursing, midwifery, allied health professions, social care and social work occupations working in the United Kingdom (UK) during the pandemic were recruited. Repeated cross-sectional online surveys were conducted during two time periods of the pandemic (May–July 2020 and May−July 2021). A total of 4803 respondents completed the survey. The findings revealed that over the pandemic, psychological wellbeing (SWEWBS measure) and work-related quality of life (WRQoL scale) scores significantly decreased in all five occupations (p < 0.001) with midwives having the lowest scores on both scales at all time points. Respondents were found to significantly (p < 0.001) use of negative coping strategies such as behavioural disengagement and substance usage. Analysis of variance revealed a statistical difference between occupations and wellbeing across 2020 and 2021, while work-related quality of life was only statistically significantly different in 2021. The findings revealed that due to this decrease, there is a distinct need for more support services and flexible working conditions within health and social care services, to improve wellbeing and work-related quality of life.
Heat Dissipation Behavior of a Low-Strength-Steel Welded Joint in Ultrasonic Fatigue
Authors: Hu Jiang-Tao , Chen Rong , Zhu Gang , Wang Chong , Zhu Ming-Liang , Xuan Fu-Zhen
Published: November 2022

The coupled effects of heat and frequency in very-high-cycle fatigue are known under ultrasonic testing, while the heat dissipation behavior of welded joints is less investigated. In this work, the specimen surface temperature of a low-strength-steel welded joint and its base metal were monitored by infrared thermal imaging technique under ultrasonic fatigue loading. Results showed that the surface temperature distribution of both welded and base metal exhibited a parabola shape, and the temperature evolved with three stages. The location of the highest temperature within the weld metal correlated well with fatigue failure location. The inhomogeneity and asymmetry of temperature distribution implied a dominant role for heat transfer mode and insignificant influence of microstructure heterogeneity or specimen type. The nature of heat dissipation in low-strength steel in ultrasonic fatigue was thermal–mechanical coupling effect, which should be paid close attention in the standardization of ultrasonic fatigue testing.
A Flexible Thermocouple Film Sensor for Respiratory Monitoring
Authors: Miao Xiaodan , Gao Xiang , Su Kaiming , Li Yahui , Yang Zhuoqing
Published: November 2022

A novel flexible thermocouple film sensor on a polyimide substrate is proposed that is simple and flexible for monitoring the respiratory signal. Several thermocouples were connected in series and patterned on the polyimide substrate, and each one is formed by copper and a constant line connected to each other at two nodes. The respiratory signal was measured by the output voltage, which resulted from the temperature difference between the hot and cold junctions. The sensors were fabricated with surface-microfabrication technology with three sputtering steps. The measurement results showed that the peak voltage decreased by 90% in the case of apnea compared with normal breathing. The sensor has potential application for wearable detection of sleep apnea hypopnea syndrome (OSAHS).
Virulence Potential and Antibiotic Susceptibility of S. aureus Strains Isolated from Food Handlers
Authors: Fernandes Adriana , Ramos Carla , Monteiro Victor , Santos Joana , Fernandes Paulo
Published: November 2022

Staphylococcus spp. are common members of the normal human flora. However, some Staphylococcus species are recognised as human pathogens due to the production of several virulence factors and enterotoxins that are particularly worrisome in food poisoning. Since many of Staphylococcal food poisoning outbreaks are typically associated with cross-contamination, the detection of S. aureus on food handlers was performed. Hand swabs from 167 food handlers were analysed for the presence of S. aureus. More than 11% of the samples were positive for S. aureus. All S. aureus strains were isolated and analysed for the presence of virulence and enterotoxin genes, namely, sea, seb, sec, sed, seg, sei, tsst-1 and pvl. The same strains were phenotypically characterised in terms of antibiotic susceptibility using the disc diffusion method and antimicrobial agents from 12 different classes. A low prevalence of antibiotic-resistant strains was found, with 55.6% of the strains being sensitive to all of the antimicrobial agents tested. However, a high prevalence of resistance to macrolides was found, with 44.4% of the strains showing resistance to erythromycin. At least one of the virulence or toxin genes was detected in 61.1% of the strains, and seg was the most prevalent toxin gene, being detected in 44.4% of the strains.
Myo-D-inositol Trisphosphate Signalling in Oomycetes
Authors: Nair Indu Muraleedharan , Condon Emma , Prestwich Barbara Doyle , Mackrill John James
Published: November 2022

Oomycetes are pathogens of plants and animals, which cause billions of dollars of global losses to the agriculture, aquaculture and forestry sectors each year. These organisms superficially resemble fungi, with an archetype being Phytophthora infestans, the cause of late blight of tomatoes and potatoes. Comparison of the physiology of oomycetes with that of other organisms, such as plants and animals, may provide new routes to selectively combat these pathogens. In most eukaryotes, myo-inositol 1,4,5 trisphosphate is a key second messenger that links extracellular stimuli to increases in cytoplasmic Ca2+, to regulate cellular activities. In the work presented in this study, investigation of the molecular components of myo-inositol 1,4,5 trisphosphate signaling in oomycetes has unveiled similarities and differences with that in other eukaryotes. Most striking is that several oomycete species lack detectable phosphoinositide-selective phospholipase C homologues, the enzyme family that generates this second messenger, but still possess relatives of myo-inositol 1,4,5 trisphosphate-gated Ca2+-channels.
Functionalized Noble Metal Nanoparticles for the Treatment of Herpesvirus Infection
Authors: Janicka Martyna , Ranoszek-Soliwoda Katarzyna , Chodaczek Grzegorz , Antos-Bielska Małgorzata , Brytan Marek , Tomaszewska Emilia , Celichowski Grzegorz , Grobelny Jarosław , Cymerys Joanna , Krzyżowska Małgorzata , Chodkowski Marcin
Published: November 2022

Neuroinfections caused by herpesviruses, mainly by HHV-1, represent a significant problem for modern medicine due to the small number of therapeutic substances available in the pharmaceutical sector. Furthermore, HHV-1 infection has been linked to neurodegenerative processes such as Alzheimer’s disease, which justifies the search for new effective therapies. The development of nanotechnology opens up new possibilities for the treatment of neuroinflammation. Gold and silver nanoparticles are gaining popularity, and the number of clinical trials involving metallic nanoparticles is constantly increasing. This paper reviews the research on gold and silver nanoparticles and their potential use in the treatment of herpesvirus neuroinfection.
Complex Resistivity Anisotropy Response Characteristics of Wufeng-Longmaxi Formation Shale in Southern Sichuan
Authors: Xiang Kui , Yan Liangjun , Tan Gongxian , Luo Yuanyuan , Yu Gang
Published: November 2022

Electrical exploration has become an important means of shale gas reservoir exploration and evaluation, and is expected to play a key role in the later stages of reservoir fracturing and development. At present, the research on the electrical response characteristics of shale gas reservoirs and their relationship with reservoir parameters is extensive and in-depth, but there is little research on their complex resistivity anisotropy characteristics and influencing factors, which restricts petrophysical modeling and reservoir parameter prediction, and reduces the reliability of shale gas exploration and reservoir evaluation by electromagnetic methods. In this paper, shale samples from the Longmaxi Formation and the Wufeng Formation of shale gas wells in southern Sichuan were collected, the complex resistivity of 34 shales in bedding direction and vertical bedding direction were measured, and the induced polarization (IP) parameters of shales were extracted by inversion. The electrical anisotropy response characteristics under different temperature and pressure conditions were analyzed, and the influencing factors and laws of complex resistivity anisotropy of shales were revealed. Combined with the test results of shale porosity and permeability, the evaluation model of resistivity, polarizability and porosity and permeability parameters was established. The research results have formed a set of testing methods and analysis techniques for electrical anisotropy of shale reservoirs, which are mainly based on complex resistivity parameter testing. It is helpful to understand the electrical anisotropy characteristics of shale gas reservoirs in southern Sichuan; this will provide the theoretical and physical basis for shale gas reservoir evaluation and fracturing monitoring by electrical exploration.
Crosstalk between Depression and Breast Cancer via Hepatic Epoxide Metabolism: A Central Comorbidity Mechanism
Authors: Ye Zhen , Ganesan Kumar , Wu Mingquan , Hu Yu , She Yingqi , Tian Qianqian , Ye Qiaobo , Chen Jianping
Published: November 2022

Breast cancer (BC) is a serious global challenge, and depression is one of the risk factors and comorbidities of BC. Recently, the research on the comorbidity of BC and depression has focused on the dysfunction of the hypothalamic–pituitary–adrenal axis and the persistent stimulation of the inflammatory response. However, the further mechanisms for comorbidity remain unclear. Epoxide metabolism has been shown to have a regulatory function in the comorbid mechanism with scattered reports. Hence, this article reviews the role of epoxide metabolism in depression and BC. The comprehensive review discloses the imbalance in epoxide metabolism and its downstream effect shared by BC and depression, including overexpression of inflammation, upregulation of toxic diols, and disturbed lipid metabolism. These downstream effects are mainly involved in the construction of the breast malignancy microenvironment through liver regulation. This finding provides new clues on the mechanism of BC and depression comorbidity, suggesting in particular a potential relationship between the liver and BC, and provides potential evidence of comorbidity for subsequent studies on the pathological mechanism.
Use of Pineapple Waste as Fuel in Microbial Fuel Cell for the Generation of Bioelectricity
Authors: Rojas-Flores Segundo , Nazario-Naveda Renny , Benites Santiago M. , Gallozzo-Cardenas Moisés , Delfín-Narciso Daniel , Díaz Félix
Published: November 2022

The excessive use of fossil sources for the generation of electrical energy and the increase in different organic wastes have caused great damage to the environment; these problems have promoted new ways of generating electricity in an eco-friendly manner using organic waste. In this sense, this research uses single-chamber microbial fuel cells with zinc and copper as electrodes and pineapple waste as fuel (substrate). Current and voltage peaks of 4.95667 ± 0.54775 mA and 0.99 ± 0.03 V were generated on days 16 and 20, respectively, with the substrate operating at an acid pH of 5.21 ± 0.18 and an electrical conductivity of 145.16 ± 9.86 mS/cm at two degrees Brix. Thus, it was also found that the internal resistance of the cells was 865.845 ± 4.726 Ω, and a maximum power density of 513.99 ± 6.54 mW/m2 was generated at a current density of 6.123 A/m2, and the final FTIR spectrum showed a clear decrease in the initial transmittance peaks. Finally, from the biofilm formed on the anodic electrode, it was possible to molecularly identify the yeast Wickerhamomyces anomalus with 99.82% accuracy. In this way, this research provides a method that companies exporting and importing this fruit may use to generate electrical energy from its waste.
Phenylethanoid and Phenylmethanoid Glycosides from the Leaves of Ligustrum robustum and Their Bioactivities
Authors: Lu Shi-Hui , Zuo Hao-Jiang , Huang Jing , Chen Ran , Pan Jia-Ping , Li Xiu-Xia
Published: November 2022

The phytochemical study on the leaves of Ligustrum robustum, which have been used as Ku-Ding-Cha, led to the isolation and identification of three new phenylethanoid glycosides and three new phenylmethanoid glycosides, named ligurobustosides R1 (1b), R2–3 (2), R4 (3), S1 (4b), S2 (5), and S3 (6), and five reported phenylethanoid glycosides (7–11). In the bioactivity test, (Z)-osmanthuside B6 (11) displayed strong fatty acid synthase (FAS) inhibitory activity (IC50: 4.55 ± 0.35 μM) as the positive control orlistat (IC50: 4.46 ± 0.13 μM), while ligurobustosides R4 (3) and S2 (5), ligupurpuroside B (7), cis-ligupurpuroside B (8), ligurobustoside N (9), osmanthuside D (10), and (Z)-osmanthuside B6 (11) showed stronger ABTS radical scavenging activity (IC50: 2.68 ± 0.05~4.86 ± 0.06 μM) than the positive control L-(+)-ascorbic acid (IC50: 10.06 ± 0.19 μM). This research provided a theoretical basis for the leaves of L. robustum as a tea with function in treating obesity and diabetes.
Comparative Analysis of Coumarin Profiles in Different Parts of Peucedanum japonicum and Their Aldo–Keto Reductase Inhibitory Activities
Authors: Park Jisu , Paudel Sunil Babu , Jin Chang Hyun , Lee Gileung , Choi Hong-Il , Ryoo Ga-Hee , Kil Yun-Seo , Nam Joo-Won , Jung Chan-Hun , Kim Bo-Ram , Na Min Kyun , Han Ah-Reum
Published: November 2022

Peucedanum japonicum (Umbelliferae) is widely distributed throughout Southeast Asian countries. The root of this plant is used in traditional medicine to treat colds and pain, whereas the young leaves are considered an edible vegetable. In this study, the differences in coumarin profiles for different parts of P. japonicum including the flowers, roots, leaves, and stems were compared using ultra-performance liquid chromatography time-of-flight mass spectrometry. Twenty-eight compounds were tentatively identified, including three compounds found in the genus Peucedanum for the first time. Principal component analysis using the data set of the measured mass values and intensities of the compounds exhibited distinct clustering of the flower, leaf, stem, and root samples. In addition, their anticancer activities were screened using an Aldo–keto reductase (AKR)1C1 assay on A549 human non-small-cell lung cancer cells and the flower extract inhibited AKR1C1 activity. Based on these results, seven compounds were selected as potential markers to distinguish between the flower part versus the root, stem, and leaf parts using an orthogonal partial least-squares discriminant analysis. This study is the first to provide information on the comparison of coumarin profiles from different parts of P. japonicum as well as their AKR1C1 inhibitory activities. Taken together, the flowers of P. japonicum offer a new use related to the efficacy of overcoming anticancer drug resistance, and may be a promising source for the isolation of active lead compounds.
Gastric Enteric Glial Cells: A New Contributor to the Synucleinopathies in the MPTP-Induced Parkinsonism Mouse
Authors: Heng Yang , Li Yan-Yan , Wen Lu , Yan Jia-Qing , Chen Nai-Hong , Yuan Yu-He
Published: November 2022

Accumulating evidence has shown that Parkinson’s disease (PD) is a systemic disease other than a mere central nervous system (CNS) disorder. One of the most important peripheral symptoms is gastrointestinal dysfunction. The enteric nervous system (ENS) is regarded as an essential gateway to the environment. The discovery of the prion-like behavior of α-synuclein makes it possible for the neurodegenerative process to start in the ENS and spread via the gut-brain axis to the CNS. We first confirmed that synucleinopathies existed in the stomachs of chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid (MPTP/p)-induced PD mice, as indicated by the significant increase in abnormal aggregated and nitrated α-synuclein in the TH-positive neurons and enteric glial cells (EGCs) of the gastric myenteric plexus. Next, we attempted to clarify the mechanisms in single MPTP-injected mice. The stomach naturally possesses high monoamine oxidase-B (MAO-B) activity and low superoxide dismutase (SOD) activity, making the stomach susceptible to MPTP-induced oxidative stress, as indicated by the significant increase in reactive oxygen species (ROS) in the stomach and elevated 4-hydroxynonenal (4-HNE) in the EGCs after MPTP exposure for 3 h. Additionally, stomach synucleinopathies appear before those of the nigrostriatal system, as determined by Western blotting 12 h after MPTP injection. Notably, nitrated α-synuclein was considerably increased in the EGCs after 3 h and 12 h of MPTP exposure. Taken together, our work demonstrated that the EGCs could be new contributors to synucleinopathies in the stomach. The early-initiated synucleinopathies might further influence neighboring neurons in the myenteric plexus and the CNS. Our results offer a new experimental clue for interpreting the etiology of PD.
Targeted and Non-Targeted HPLC Analysis of Coffee-Based Products as Effective Tools for Evaluating the Coffee Authenticity
Authors: Klikarová Jitka , Česlová Lenka
Published: November 2022

Coffee is a very popular beverage worldwide. However, its composition and characteristics are affected by a number of factors, such as geographical and botanical origin, harvesting and roasting conditions, and brewing method used. As coffee consumption rises, the demands on its high quality and authenticity naturally grows as well. Unfortunately, at the same time, various tricks of coffee adulteration occur more frequently, with the intention of quick economic profit. Many analytical methods have already been developed to verify the coffee authenticity, in which the high-performance liquid chromatography (HPLC) plays a crucial role, especially thanks to its high selectivity and sensitivity. Thus, this review summarizes the results of targeted and non-targeted HPLC analysis of coffee-based products over the last 10 years as an effective tool for determining coffee composition, which can help to reveal potential forgeries and non-compliance with good manufacturing practice, and subsequently protects consumers from buying overpriced low-quality product. The advantages and drawbacks of the targeted analysis are specified and contrasted with those of the non-targeted HPLC fingerprints, which simply consider the chemical profile of the sample, regardless of the determination of individual compounds present.
Effect of Sex Steroids and PGF2α on the Expression of Their Receptors and Decorin in Bovine Caruncular Epithelial Cells in Early–Mid Pregnancy
Authors: Jamioł Monika , Sozoniuk Magdalena , Wawrzykowski Jacek , Kankofer Marta
Published: November 2022

Changes in the expression of various genes, including pregnancy-associated hormone receptors and extracellular matrix proteins, have been suggested to play a significant role in bovine placental development. This study aimed to examine the influence of sex steroids and PGF2α on decorin (DCN) expression in the epithelial cells of bovine caruncle in early–mid pregnancy in cows. The expression patterns of DCN, PTGFR, PGR and ESR1 were analyzed by RT-qPCR and Western blotting in primary caruncular epithelial cell cultures (PCECC) and placental tissue homogenates derived from the 2nd and 4th months of pregnancy. PCECC were found to express DCN, PTGFR, PGR and ESR1. The intensity of PGR staining was higher in cells derived from the 4th month of pregnancy (p < 0.05). The 17β-estradiol, progesterone and PGF2α have not been shown to affect DCN expression. PGF2α decreased PTGFR expression in cells derived from the 4th month of gestation (p < 0.05). In conclusion, the results of the present preliminary study showed that the expression of the PTGFR, ESR1, PGR and DCN in PCECC does not vary throughout early–mid pregnancy. Further studies should be carried out to observe the relationship between hormonal status and cellular adhesion to determine their importance for properly developing placentation and pregnancy in cows.
Supramolecular Protein-Polyelectrolyte Assembly at Near Physiological Conditions—Water Proton NMR, ITC, and DLS Study
Authors: Marin Alexander , Taraban Marc B. , Patel Vanshika , Yu Y. Bruce , Andrianov Alexander K.
Published: November 2022

The in vivo potency of polyphosphazene immunoadjuvants is inherently linked to the ability of these ionic macromolecules to assemble with antigenic proteins in aqueous solutions and form physiologically stable supramolecular complexes. Therefore, in-depth knowledge of interactions in this biologically relevant system is a prerequisite for a better understanding of mechanism of immunoadjuvant activity. Present study explores a self-assembly of polyphosphazene immunoadjuvant—PCPP and a model antigen—lysozyme in a physiologically relevant environment—saline solution and neutral pH. Three analytical techniques were employed to characterize reaction thermodynamics, water-solute structural organization, and supramolecular dimensions: isothermal titration calorimetry (ITC), water proton nuclear magnetic resonance (wNMR), and dynamic light scattering (DLS). The formation of lysozyme–PCPP complexes at near physiological conditions was detected by all methods and the avidity was modulated by a physical state and dimensions of the assemblies. Thermodynamic analysis revealed the dissociation constant in micromolar range and the dominance of enthalpy factor in interactions, which is in line with previously suggested model of protein charge anisotropy and small persistence length of the polymer favoring the formation of high affinity complexes. The paper reports advantageous use of wNMR method for studying protein-polymer interactions, especially for low protein-load complexes.
Ionic Liquids Effect on the Stability of 17-Electron Cation Product of the Electrochemical Oxidation of Cymantrene
Authors: Torriero Angel A. J.
Published: November 2022

The oxidative electrochemistry of cymantrene, CpMn(CO)3 (1; Cp = [η5-C5H5]–), was examined in ionic liquids (ILs) composed of anions of varying Lewis base properties. It was observed that the cyclic voltammetric responses strongly depended on the nucleophilic properties of the IL anion. Still, all observations are consistent with the initial formation of 1+ followed by an attack from the IL anion. In bis(trifluoromethylsulfonyl)amide [NTf2]-based ILs, the process shows close to ideal electrochemical reversibility as the reaction between 1+ and [NTf2] anion is very slow. On the other hand, in tetrafluoroborate and trifluoromethanesulfonate-based IL, the oxidation of 1 shows different levels of electrochemical reversibility with a marked sign of anion attack to 1+. In contrast, 1 exhibits an irreversible oxidation process in hexafluorophosphate-based IL. The reaction rate constants for the interaction of 1+ with the different IL anions were estimated by fitting the experimental data to digital simulations of the proposed mechanism. Besides, the use of [NTf2]-based ILs as a supporting electrolyte in CH2Cl2 was also examined. The oxidation process of 1 shows a close to ideal electrochemical reversibility but low to non-chemical reversibility. This study illustrates the wide range of electrochemical environments available with ILs and demonstrates their limited utility for investigating the redox properties of metal carbonyl compounds. It also intends to warn the reader on how the IL media may influence an electrochemical study if care is not exercised.
Chemical Composition and Biological Activities of Prangos ferulacea Essential Oils
Authors: Badalamenti Natale , Maresca Viviana , Di Napoli Michela , Bruno Maurizio , Basile Adriana , Zanfardino Anna
Published: November 2022

Prangos ferulacea (L.) Lindl, which belongs to the Apiaceae family, is a species that mainly grows in the eastern Mediterranean region and in western Asia. It has been largely used in traditional medicine in several countries and it has been shown to possess several interesting biological properties. With the aim to provide new insights into the phytochemistry and pharmacology of this species, the essential oils of flowers and leaves from a local accession that grows in Sicily (Italy) and has not yet been previously studied were investigated. The chemical composition of both oils, obtained by hydrodistillation from the leaves and flowers, was evaluated by GC-MS. This analysis allowed us to identify a new chemotype, characterized by a large amount of (Z)-β-ocimene. Furthermore, these essential oils have been tested for their possible antimicrobial and antioxidant activity. P. ferulacea essential oils exhibit moderate antimicrobial activity; in particular, the flower essential oil is harmful at low and wide spectrum concentrations. They also exhibit good antioxidant activity in vitro and in particular, it has been shown that the essential oils of the flowers and leaves of P. ferulacea caused a decrease in ROS and an increase in the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) in OZ-stimulated PMNs. Therefore, these essential oils could be considered as promising candidates for pharmaceutical and nutraceutical preparations.
Anti-Inflammatory, Antioxidative, and Nitric Oxide-Scavenging Activities of a Quercetin Nanosuspension with Polyethylene Glycol in LPS-Induced RAW 264.7 Macrophages
Authors: Kang Sang Gu , Lee Gi Baek , Vinayagam Ramachandran , Do Geum Sook , Oh Se Yong , Yang Su Jin , Kwon Jun Bum , Singh Mahendra
Published: November 2022

Quercetin (Qu) is a dietary antioxidant and a member of flavonoids in the plant polyphenol family. Qu has a high ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) molecules; hence, exhibiting beneficial effects in preventing obesity, diabetes, cancer, cardiovascular diseases, and inflammation. However, quercetin has low bioavailability due to poor water solubility, low absorption, and rapid excretion from the body. To address these issues, the usage of Qu nanosuspensions can improve physical stability, solubility, and pharmacokinetics. Therefore, we developed a Qu and polyethylene glycol nanosuspension (Qu-PEG NS) and confirmed its interaction by Fourier transform infrared analysis. Qu-PEG NS did not show cytotoxicity to HaCaT and RAW 264.7 cells. Furthermore, Qu-PEG NS effectively reduced the nitrogen oxide (NO) production in lipopolysaccharide (LPS)-induced inflammatory RAW 264.7 cells. Additionally, Qu-PEG NS effectively lowered the levels of COX-2, NF-κB p65, and IL-1β in the LPS-induced inflammatory RAW 264.7 cells. Specifically, Qu-PEG NS exhibited anti-inflammatory properties by scavenging the ROS and RNS and mediated the inhibition of NF-κB signaling pathways. In addition, Qu-PEG NS had a high antioxidant effect and antibacterial activity against Escherichia coli and Bacillus cereus. Therefore, the developed novel nanosuspension showed comparable antioxidant, anti-inflammatory, and antibacterial functions and may also improve solubility and physical stability compared to raw quercetin.
Dissipative Particle Dynamics Simulation of the Sensitive Anchoring Behavior of Smectic Liquid Crystals at Aqueous Phase
Authors: Chen Shiwei , Zhang Jinliang , Liu Huilong , Qiu Tongyue , Tang Haoxiang , Zhang Zunmin
Published: November 2022

Rational design of thermotropic liquid crystal (LC)-based sensors utilizing different mesophases holds great promise to open up novel detection modalities for various chemical and biological applications. In this context, we present a dissipative particle dynamics study to explore the unique anchoring behavior of nematic and smectic LCs at amphiphile-laden aqueous-LC interface. By increasing the surface coverage of amphiphiles, two distinct anchoring sequences, a continuous planar-tilted-homeotropic transition and a discontinuous planar-to-homeotropic transition, can be observed for the nematic and smectic LCs, respectively. More importantly, the latter occurs at a much lower surface coverage of amphiphiles, demonstrating an outstanding sensitivity for the smectic-based sensors. The dynamics of reorientation further reveals that the formation of homeotropic smectic anchoring is mainly governed by the synchronous growth of smectic layers through the LCs, which is significantly different from the mechanism of interface-to-bulk ordering propagation in nematic anchoring. Furthermore, the smectic LCs have also been proven to possess a potential selectivity in response to a subtle change in the chain rigidity of amphiphiles. These simulation findings are promising and would be valuable for the development of novel smectic-based sensors.
Pain Management and Analgesics Used in Small Mammals during Post-Operative Period with an Emphasis on Metamizole (Dipyrone) as an Alternative Medication
Authors: Lupu Georgiana , Bel Lucia , Andrei Sanda
Published: November 2022

Metamizole (dipyrone) is a widely used non-opioid analgesic in both human and animal medicine. Metamizole’s safety has been the topic of numerous opposing debates, given the fact that in certain countries metamizole is frequently used as an over-the-counter (OTC) medicine, while in others it is banned due to the risk of agranulocytosis. Further, small mammals such as rabbits, ferrets, rodents, and hedgehogs have become some of the most common pets present in veterinary practice, and each of these species has specific analgesic needs due to their anatomy and physiology. The key to providing appropriate medical care is in finding a substance that has minimal negative effects. In small mammals, analgesia is an important factor and, it happens frequently that, pain in these patients is not well managed. Post-operative pain management is an important topic in the welfare of animals. The objectives of this review, thus, were to provide a concise overview of analgesics that are used in the treatment of postoperative pain in small mammals (e.g., rabbits and rodents) and to highlight the importance of this product, metamizole, in veterinary medicine, as well as the potential of this substance as an alternative analgesic for the treatment of postoperative pain in small mammals.
Structure-Based Discovery and Biological Assays of a Novel PRMT5 Inhibitor for Non-Small Cell Lung Cancer
Authors: Chen Yingqing , Zhang Mingyu , Wu Anxin , Yao Xiaojun , Wang Qianqian
Published: November 2022

Protein arginine methyltransferase 5 (PRMT5) is a popular anticancer target that regulates histone or nonhistone methylation and is linked to the development and poor prognosis of non-small cell lung cancer. PRMT5 inhibitors have shown great promise in clinical trials as a cancer therapy. However, most inhibitors reported recently act in a SAM-competitive mode and lack structural diversity. In this paper, a novel non-SAM inhibitor, 3039-0164, was discovered by the structure-based virtual screening method. The binding mechanism of 3039-0164 to PRMT5 was revealed via molecular docking and molecular dynamics simulations. 3039-0164 inhibited PRMT5 enzymatic activity, downregulated the expression of PRMT5 downstream target genes (FGFR3 and eIF4E), and blocked the activation of the PI3K/AKT/mTOR and ERK signaling pathways. The discovery of 3039-0164 provides precise and creative hit compounds for the design optimization of PRMT5 lead compounds in non-small cell lung cancer.
N-Hydroxy-N-Propargylamide Derivatives of Ferulic Acid: Inhibitors of Cholinesterases and Monoamine Oxidases
Authors: Bautista-Aguilera Óscar M. , Alonso José M. , Catto Marco , Iriepa Isabel , Knez Damijan , Gobec Stanislav , Marco-Contelles José
Published: November 2022

Alzheimer’s disease (AD) is a complex disorder characterized by impaired neurotransmission in cholinergic and monoaminergic neurons, which, in combination with the accumulation of misfolded proteins and increased oxidative stress, leads to the typical features of the disease at the biomolecular level. Given the limited therapeutic success of approved drugs, it is imperative to explore rationally supported therapeutic approaches to combat this disease. The search for novel scaffolds that bind to different receptors and inhibit AD disease-related enzymes could lead to new therapeutic solutions. Here, we describe N-hydroxy-N-propargylamide hybrids 1–6, which were designed by combining the structures of Contilisant—a multifunctional anti-AD ligand—and ferulic acid, a natural antioxidant with various other biological activities. Among the synthesized compounds, we identified compound 4 as a micromolar inhibitor of hAChE with a potent radical-scavenging capacity comparable to resveratrol and Trolox. In addition, compound 4 chelated copper(II) ions associated with amyloid β pathology, mitochondrial dysfunction, and oxidative stress. The promising in vitro activity combined with favorable drug-like properties and predicted blood-brain barrier permeability make compound 4 a multifunctional ligand that merits further studies at the biochemical and cellular levels.
Design and Preparation of NiFe2O4@FeOOH Composite Electrocatalyst for Highly Efficient and Stable Oxygen Evolution Reaction
Authors: Li Tian-Tian , Shi Bu-Yan , Jiang Li-Wen , Zheng Jin-Fan , Wang Jian-Jun
Published: November 2022

Rational design and constructing earth-abundant electrocatalysts for efficient electrocatalytic water splitting is a crucial challenge. Herein, we report a simple and efficient one-step electrochemical synthetic route of the NiFe2O4@FeOOH composite electrocatalyst for the oxygen evolution reaction. The unique morphology of the NiFe2O4 nanoflowers loaded on FeOOH nanosheets allows more active sites to be exposed and promote charge transfer as well as gas release, and the resulting electrode enables a current density of 10 mA cm−2 at a low overpotential of 255 mV with outstanding stability at a current density of 100 mA cm−2 for 300 h.
Development of a GC/Q-ToF-MS Method Coupled with Headspace Solid-Phase Microextraction to Evaluate the In Vitro Metabolism of β-Caryophyllene
Authors: Lee Joseph , Wang Mei , Mondal Goutam , Khan Ikhlas A. , Yates Charles R.
Published: November 2022

Sample preparation remains both a challenging and time-consuming process in the field of bioanalytical chemistry. Many traditional techniques often require multi-step processes, which can introduce additional errors to the analytical method. Given the complexity of many biological matrices, thorough analyte extraction presents a major challenge to researchers. In the present study, a headspace solid-phase microextraction (HS-SPME) coupled with a GC/Q-ToF-MS method, was developed to quantify in vitro metabolism of β-caryophyllene by both human liver microsome (HLM) and S9 liver fractions. Validation of the method was demonstrated both in terms of linearity (R2 = 0.9948) and sensitivity with a limit of detection of 3 ng/mL and a limit of quantitation of 10 ng/mL. In addition, the method also demonstrated both inter- and intra-day precision with the relative standard deviation (RSD) being less than 10% with four concentrations ranging from 50–500 ng/mL. Since this method requires no solvents and minimal sample preparation, it provides a rapid and economical alternative to traditional extraction techniques. The method also eliminates the need to remove salts or buffers, which are commonly present in biological matrices. Although this method was developed to quantify in vitro metabolism of one analyte, it could easily be adapted to detect or quantify numerous volatiles and/or semi-volatiles found in biological matrices.
Endogenous Synthesis of Tetrahydroisoquinoline Derivatives from Dietary Factors: Neurotoxicity Assessment on a 3D Neurosphere Culture
Authors: Aro Rania , Nachtergael Amandine , Palmieri Claudio , Ris Laurence , Duez Pierre
Published: November 2022

Tetrahydroisoquinoline (THIQ) alkaloids and their derivatives have a structural similarity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a well-known neurotoxin. THIQs seem to present a broad range of actions in the brain, critically dependent on their catechol moieties and metabolism. These properties make it reasonable to assume that an acute or chronic exposure to some THIQs might lead to neurodegenerative diseases including essential tremor (ET). We developed a method to search for precursor carbonyl compounds produced during the Maillard reaction in overcooked meats to study their reactivity with endogenous amines and identify the reaction products. Then, we predicted in silico their pharmacokinetic and toxicological properties toward the central nervous system. Finally, their possible neurological effects on a novel in vitro 3D neurosphere model were assessed. The obtained data indicate that meat is an alkaloid precursor, and we identified the alkaloid 1-benzyl-1,2,3,4-tetrahydroisoquinoline-6,7-diol (1-benz-6,7-diol THIQ) as the condensation product of phenylacetaldehyde with dopamine; in silico study of 1-benz-6,7-diol-THIQ reveals modulation of dopamine receptor D1 and D2; and in vitro study of 1-benz-6,7-diol-THIQ for cytotoxicity and oxidative stress induction does not show any difference after 24 h contact for all tested concentrations. To conclude, our in vitro data do not support an eventual neurotoxic effect for 1-benz-6,7-diol-THIQ.
A Review on Data Fusion of Multidimensional Medical and Biomedical Data
Authors: Azam Kazi Sultana Farhana , Ryabchykov Oleg , Bocklitz Thomas
Published: November 2022

Data fusion aims to provide a more accurate description of a sample than any one source of data alone. At the same time, data fusion minimizes the uncertainty of the results by combining data from multiple sources. Both aim to improve the characterization of samples and might improve clinical diagnosis and prognosis. In this paper, we present an overview of the advances achieved over the last decades in data fusion approaches in the context of the medical and biomedical fields. We collected approaches for interpreting multiple sources of data in different combinations: image to image, image to biomarker, spectra to image, spectra to spectra, spectra to biomarker, and others. We found that the most prevalent combination is the image-to-image fusion and that most data fusion approaches were applied together with deep learning or machine learning methods.
Revisiting Non-Conventional Crystallinity-Induced Effects on Molecular Mobility in Sustainable Diblock Copolymers of Poly(propylene adipate) and Polylactide
Authors: Klonos Panagiotis A. , Evangelopoulou Alexandra , Terzopoulou Zoi , Zamboulis Alexandra , Valera Miguel Ángel , Mangas Ana , Kyritsis Apostolos , Bikiaris Dimitrios N.
Published: November 2022

This work deals with molecular mobility in renewable block copolymers based on polylactide (PLA) and poly(propylene adipate) (PPAd). In particular, we assess non-trivial effects on the mobility arising from the implementation of crystallization. Differential scanning calorimetry, polarized light microscopy and broadband dielectric spectroscopy were employed in combination for this study. The materials were subjected to various thermal treatments aiming at the manipulation of crystallization, namely, fast and slow cooling, isothermal melt- and cold-crystallization. Subsequently, we evaluated the changes recorded in the overall thermal behavior, semicrystalline morphology and molecular mobility (segmental and local). The molecular dynamics map for neat PPAd is presented here for the first time. Unexpectedly, the glass transition temperature, Tg, in the amorphous state drops upon crystallization by 8–50 K. The drop becomes stronger with the increase in the PPAd fraction. Compared to the amorphous state, crystallization leads to significantly faster segmental dynamics with severely suppressed cooperativity. For the PLA/PPAd copolymers, the effects are systematically stronger in the cold- as compared to the melt-crystallization, whereas the opposite happens for neat PLA. The local βPLA relaxation of PLA was, interestingly, recorded to almost vanish upon crystallization. This suggests that the corresponding molecular groups (carbonyl) are strongly involved and immobilized within the semicrystalline regions. The overall results suggest the involvement of either spatial nanoconfinement imposed on the mobile chains within the inter-crystal amorphous areas and/or a crystallization-driven effect of nanophase separation. The latter phase separation seems to be at the origins of the significant discrepancy recorded between the calorimetric and dielectric recordings on Tg in the copolymers. Once again, compared to more conventional techniques such as calorimetry, dielectric spectroscopy was proved a powerful and quite sensitive tool in recording such effects as well as in providing indirect indications for the polymer chains’ topology.
Janus-Type AIE Fluorophores: Synthesis and Properties of π-Extended Coumarin-Bearing Triskelions
Authors: Ueda Masafumi , Kokubun Mirai , Yanagi Nao , Yamamoto Norifumi , Mazaki Yasuhiro
Published: November 2022

Janus-type triskelion-shaped fluorophores comprising coumarins bearing various electron-donating substituents (1aad, 1add, 1ccd, and 1cdd) were successfully synthesized via an intramolecular Ullmann coupling. Density functional theory (DFT) calculations indicated that all the compounds presented two different molecular surfaces, similar to Janus-type molecules. The absorption and fluorescence spectra of asymmetrical derivatives 1aad, 1add, 1ccd, and 1cdd exhibited a bathochromic shift due to their narrow highest occupied molecular orbital (HOMO) –lowest unoccupied molecular orbital (LUMO) gap. Natural transition orbital (NTO) analysis indicated that the excited state orbital overlaps differ among the C3 symmetrical and asymmetrical dyes. These triskelion-shaped fluorophores were found to form molecular nanoaggregates in THF/H2O mixtures and demonstrated aggregation-induced emission (AIE) enhancement characteristics as a result of restricting their molecular inversion. These results indicate that Janus-type AIE fluorophores are potentially applicable as solid-state fluorescent chiral materials, which can be optimized by controlling their molecular rearrangement in the solid state.